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Abstract

Little is known about the clinical relevance of the Hamilton Rating Scale for Depression (HAMD-17) total scores. It is unclear how total scores translate into clinical severity, or what commonly used measures for response (reduction from baseline of ≥50% in the total score) and remission (total HAMD-17 score ≤7) mean from a clinical perspective. We therefore compared: (a) the percentage and absolute change in the HAMD-17 total scores with Clinical Global Impression-Improvement (CGI-I); (b) the absolute and percentage change in the HAMD-17 total scores with Clinical Global Impression-Severity (CGI-S) absolute change; and (c) the percentage and absolute change in the HAMD-17 total scores with CGI-I in the subgroups of patients with≤median and>median HAMD-17 total scores at baseline. The method used was equipercentile linking of HAMD-17 and CGI ratings from 43 drug trials in patients with Major Depressive Disorder (MDD) (n=7131). Our results confirm the validity of the commonly used measures for remission and response in MDD trials: a CGI-I score of 2 ('much improved') corresponded to a reduction from baseline of >50% and <60%, and a CGI-I score of 1 ('very much improved') to a reduction of >75% and <85%. The CGI-S score of 1 ('normal., not at all ill') corresponded to the HAMD-17 total score of <5 and the CGI-S score of 2 ('borderline mentally ill') to the score between 6 and 8. An effect of baseline illness severity was observed.

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... e total score is 0-56. It was divided into an absence of anxiety (0-6), possible anxiety (7-13), mild anxiety (14)(15)(16)(17)(18)(19)(20), moderate anxiety (21)(22)(23)(24)(25)(26)(27)(28), and severe anxiety [22]. e HAMA score has good reliability and acceptable validity to measure the severity of participants' anxiety [23,24]. ...
... e scale's seven-factor structure includes anxiety and somatization, weight, cognitive disorders, diurnal variation, block, sleep disorder, and hopelessness. [25] It has a high overall reliability as depressive outcome measure [26]. e CGI scale was used to assess the clinical efficacy of treatment. ...
... e TCM Syndrome Scale was developed by the Chinese medical team of experts. It contained over 90 items, assessing (n): mental symptoms (11), the head and face (7), the heart and chest (10), gastrointestinal symptoms (25), urologic symptoms (14), the reproduction system (10), and limb symptoms (11). In addition, two other TCM syndrome characteristics (i.e., tongue coating and pulse) are recorded as part of the scale. ...
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Objective: To systematically assess the clinical efficacy of the Jie Yu Wan (JYW) formula in treating generalized anxiety disorder (GAD). Methods: A multicenter, prospective, double-blind, double-dummy, randomized controlled trial (RCT) was conducted at four hospitals in China. A total of one hundred thirty-three patients with GAD were enrolled from 2017 to 2019. This study aimed to evaluate the effects of a Traditional Chinese Medicine (TCM) JYW formula on GAD at eight weeks, with the use of Buspirone as the comparator. A stepwise dosing protocol was used (JYW: high dose 24 g/day, low dose 12 g/day; Buspirone: high dose 30 mg/day, low dose 15 mg/day) and the dose was adjusted depending on whether the treatment response of Hamilton Anxiety Scale (HAMA) score was less than or equal to 25% after one week. The primary outcome was a change in total score on the HAMA. The secondary outcomes included the Hamilton Depression Scale (HAMD), Clinical Global Impression (CGI) scale, and TCM Syndrome Scale. Adverse events were recorded using the Treatment Emergent Symptom Scale (TESS). Assessments were conducted at the baseline and 1, 2, 4, and 8 weeks. Results: A total of one hundred thirty-three participants were randomly assigned to the JYW group (n = 66) and the Buspirone group (n = 67). One hundred twenty-one patients (91%) completed at least one follow-up session. There were no significant differences between the two groups in terms of gender, age, disease course, HAMA, HAMD, CGI, and TCM Syndrome Scale scores at baseline (all P > 0.05). Repeated-measures analysis of variance revealed statistically significant time effects for the HAMA (P=0.002), HAMD (P = 0.018), and CGI (P=0.001) in both groups. Sensitivity analyses supported the credibility of the main results (P > 0.05). The group effect was not significant for the HAMA (P=0.43), HAMD (P=0.27), CGI (P=0.37), and TCM Syndrome Scale (P=0.86). Furthermore, there were no significant interaction effects between time and group in terms of the HAMA (P=0.47), HAMD (P=0.79), CGI (P=0.67), and TCM Syndrome Scale (P=0.69). After one week, 53 patients (80%) of the JYW group and 52 patients (78%) of the Buspirone group were adjusted to high doses. The interaction effect between time, group, and the dose was determined by repeated measures ANOVA test, and the HAMA score served as the outcome measure. The interaction effect between time and dose was statistically significant (P=0.04), which shows that high-dose JYW (24 g/day) was more effective in decreasing patients' HAMA scores than low-dose JYW (12 g/day), and Buspirone had the same effect, which means that high-dose Buspirone (30 mg/day) was more effective than low dose. (15 mg/day). Conclusions: The conclusion of this study supports that JYW and Buspirone can effectively alleviate the anxiety symptoms of GAD patients, which are both effective and safe for treatment of mild to moderate GAD. Besides, high-dose JYW or Buspirone are more effective than low-dose, which is of great importance in assisting clinical medication choice.
... Most articles about the clinical significance of antidepressants in patients with moderate-tosevere depression have exclusively cited a MID estimate derived from a study by Leucht et al. 18 using a sample of mirtazapine trials. However, we are aware of three more studies applying a clinical anchor-based method in antidepressant trials for depression. ...
... The method was first applied by Rush et al. 19 using data from a nefazodone-psychotherapy trial and then by Furukawa et al. 20 using a sample of imipramine, amitriptyline, trazodone, fluoxetine, paroxetine, and fluvoxamine trials. After Leucht et al., 18 Bobo et al. 21 Table 1. ...
... The four studies have consistently demonstrated that for a clinician to detect a minimal improvement according to CGI rating (the clinical anchor), about 5-8 points change on the HDRS-17 are necessary, depending on depression severity at baseline. [18][19][20][21] The MID estimates are thus considerably higher than the meta-analytically established average treatment effect of about 2 points. 16 17 22 - Table 1-The psychometric and clinimetric properties of the HDRS-17 are subject to longstanding controversy. ...
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The efficacy of antidepressants in the acute treatment of moderate-to-severe depression remains a controversial issue. The minimal important difference (MID) is relevant to judge the clinical significance of treatment effects. In this analysis paper, we discuss estimates of the MID for common depression outcome measures. For the Hamilton Depression Rating Scale 17-item Version (HDRS-17), according to both anchor-based and distribution-based approaches, MID estimates range from 3 to 8 points, and the most accurate values are likely between 3 and 5 points. For the 6-item version (HDRS-6), MID estimates range between 2 and 4 points. For both the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory II (BDI-II), MID estimates range between 3 and 9 points, with estimates of 3–6 points likely being the most accurate. Quality of life appears to be more important to patients than core depression symptoms. We thus also evaluated the Short-Form 36 (SF-36) mental component score, a popular mental-health-related quality of life measure. Its MID estimate is likely about 5 points. By contrast, the average treatment effects of antidepressants on the HDRS-17, HDRS-6, MADRS, BDI-II and SF-36 are 2 points, 1.5 points, 3 points, 2 points and 3–5 points, respectively. In conclusion, the efficacy of antidepressants in the acute treatment of moderate-to-severe depression consistently fails to exceed the lower bound of the MID estimates for common depression outcome measures. The clinical significance of antidepressants thus remains uncertain and we call for more research on quality of life measures, which are the patients’ most valued outcome domains.
... The antidepressant trials mentioned routinely show a drug-placebo difference of less than 2 points on the 52-point Hamilton Depression Rating scale, 9 a difference thought to be clinically unimportant. 10 ...
... The antidepressant trials mentioned routinely show a drug-placebo difference of less than 2 points on the 52-point Hamilton Depression Rating scale, 9 a difference thought to be clinically unimportant. 10 The US Food and Drug Administration's recent modelling exercise was exploratory and probabilistic and does not exclude mental alterations or amplified placebo effects as an explanation for the slightly different, although substantially overlapping, distributions of antidepressant and placebo response. 11 Understanding that antidepressants produce mental and physical alterations that might account for their effects has quite different implications from the idea that they work by reversing an underlying abnormality, which makes the use of drugs seem necessary and reassuring. ...
... Maternal depressive symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D) (68), a 17-item clinicianrated questionnaire administered by trained research staff, blinded to SRI exposure-status. Mothers were considered to be symptomatically depressed with a total HAM-D score > 8 (69). In this study, SRI antidepressants included any selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). ...
... While this approach identified appropriate exposure groups, the impact of maternal depressive illness severity, or variations in symptoms across pregnancy, could not be addressed. Moreover, women scoring close to the depressed/non-depressed cut-off may not differ in a clinically meaningful manner, even though a HAM-D score > 8 (as used here) has been clinically validated as a cut-off between symptomatic and asymptomatic depression (69). However, our findings suggest a differential fetal sensitivity may exist in the context of maternal response to SRI treatment, highlighting the importance of making such distinctions in future studies. ...
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Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants increases risk for adverse neurodevelopmental outcomes, yet little is known about whether effects are present before birth. In relation to maternal SRI pharmacokinetics, this study investigated chronic and acute effects of prenatal SRI exposure on third-trimester fetal heart rate variability (HRV), while evaluating confounding effects of maternal depressed mood. Methods: At 36-weeks' gestation, cardiotocograph measures of fetal HR and HRV were obtained from 148 pregnant women [four groups: SRI-Depressed ( n = 31), SRI-Non-Depressed ( n = 18), Depressed (unmedicated; n = 42), and Control ( n = 57)] before, and ~5-h after, typical SRI dose. Maternal plasma drug concentrations were quantified at baseline (pre-dose) and four time-points post-dose. Mixed effects modeling investigated group differences between baseline/pre-dose and post-dose fetal HR outcomes. Post hoc analyses investigated sex differences and dose-dependent SRI effects. Results: Maternal SRI plasma concentrations were lowest during the baseline/pre-dose fetal assessment (trough) and increased to a peak at the post-dose assessment; concentration-time curves varied widely between individuals. No group differences in fetal HR or HRV were observed at baseline/pre-dose; however, following maternal SRI dose, short-term HRV decreased in both SRI-exposed fetal groups. In the SRI-Depressed group, these post-dose decreases were displayed by male fetuses, but not females. Further, episodes of high HRV decreased post-dose relative to baseline, but only among SRI-Non-Depressed group fetuses. Higher maternal SRI doses also predicted a greater number of fetal HR decelerations. Fetuses exposed to unmedicated maternal depressed mood did not differ from Controls. Conclusions: Prenatal SRI exposure had acute post-dose effects on fetal HRV in late gestation, which differed depending on maternal mood response to SRI pharmacotherapy. Importantly, fetal SRI effects were sex-specific among mothers with persistent depressive symptoms, as only male fetuses displayed acute HRV decreases. At trough (pre-dose), chronic fetal SRI effects were not identified; however, concurrent changes in maternal SRI plasma levels suggest that fetal drug exposure is inconsistent. Acute SRI-related changes in fetal HRV may reflect a pharmacologic mechanism, a transient impairment in autonomic functioning, or an early adaption to altered serotonergic signaling, which may differ between males and females. Replication is needed to determine significance with postnatal development.
... A reduction of 2 points on the HAMD scale is probably not detectable by the treating physician and of questionable clinical relevance. According to Leucht et al. [7], a reduction of up to 3 points on the HAMD corresponds to "no change" in the Clinical Global Impressions-Improvement Scale (CGI-I) and the assumed threshold of clinical significance is between 3 and 7 points [8,9]. ...
... Despite their widespread use, it remains unclear how many and which patients benefit from this medication. In a recent re-analysis [6] of a highly cited network meta-analysis [4], the average treatment effect of antidepressants was found to be about 2 points on the HAMD-17 scale, which is almost undetectable by clinicians [7] and lies below the assumed minimally clinically relevant effect [8,9]. While this does not exclude the possibility of subgroups of patients that have a meaningful benefit, substantial differences in the individual treatment effect of antidepressants have not been shown to exist yet. ...
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Background The average treatment effect of antidepressants in major depression was found to be about 2 points on the 17-item Hamilton Depression Rating Scale, which lies below clinical relevance. Here, we searched for evidence of a relevant treatment effect heterogeneity that could justify the usage of antidepressants despite their low average treatment effect. Methods Bayesian meta-analysis of 169 randomized, controlled trials including 58,687 patients. We considered the effect sizes log variability ratio (lnVR) and log coefficient of variation ratio (lnCVR) to analyze the difference in variability of active and placebo response. We used Bayesian random-effects meta-analyses (REMA) for lnVR and lnCVR and fitted a random-effects meta-regression (REMR) model to estimate the treatment effect variability between antidepressants and placebo. Results The variability ratio was found to be very close to 1 in the best fitting models (REMR: 95% highest density interval (HDI) [0.98, 1.02], REMA: 95% HDI [1.00, 1.02]). The between-study standard deviation τ under the REMA with respect to lnVR was found to be low (95% HDI [0.00, 0.02]). Simulations showed that a large treatment effect heterogeneity is only compatible with the data if a strong correlation between placebo response and individual treatment effect is assumed. Conclusions The published data from RCTs on antidepressants for the treatment of major depression is compatible with a near-constant treatment effect. Although it is impossible to rule out a substantial treatment effect heterogeneity, its existence seems rather unlikely. Since the average treatment effect of antidepressants falls short of clinical relevance, the current prescribing practice should be re-evaluated.
... Differentiating one step further, absolute changes in HAMD-17 and CGI-I scores have been compared in patients with higher or lower depression severity at baseline. Patients with higher depression severity needed a decrease of 13-14 points to be considered "much improved," while the lower severity group only needed a nine-point decrease [40,41]. This effect disappeared when the relative change on HAMD scores was considered. ...
... This effect disappeared when the relative change on HAMD scores was considered. The more severe the depression severity, the larger should be the improvement before the clinician decides on a "much improved" status [41]. ...
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Background Standard depression rating scales like the Hamilton Depression Rating Scale and the Montgomery–Åsberg Depression Rating Scale were developed more than 40 years ago. They are mandatory in clinical trials but are for a variety of reasons seldom used in clinical practice. Moreover, most clinicians are less familiar with more recent trends or with some dilemmas in assessment tools for major depression. Methods Narrative review. Results Asssessment tools can be observer-rating or self-rating scales, disease-specific or non–disease-specific scales, subjective scales or objective lab assessments, standard questionnaires or experience sampling methods. An overarching question is to what degree current assessment methods really address the individual patient’s needs and treatment expectations. Conclusions The present paper aims to offer a framework for understanding the current trends in assessment tools that can orientate and guide the clinician.
... The sociodemographic variables and clinical variables were collected at pre-rTMS treatment (baseline) and post-rTMS treatment (six weeks), using the 17-item Hamilton Depression Scale (HAMD) [52], which is used to quantify depression symptom severity in patients diagnosed with MDD; the Columbia Suicide Severity Rating Scale (CSSRS), which is used to screen and evaluate a person's level of suicidal ideations [53]; the self-reported 16 items Quick Inventory Depression Scale (QIDS-SR16), which is used to evaluate the nine diagnostic symptoms domain of the DSM-IV [54]; and the EQ-5D-5L, which is used to assess the quality of overall health status [55]. The HAMD has strong psychometric properties [56], including internal reliability evaluated by Cronbach's alpha statistic [57] of ≥0.70, which is deemed sufficient reliability [58]. Ratings on the HAMD are determined on a semi-structured clinical interview, producing the highest score of 52. ...
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Background: Treatment-resistant depression (TRD) is considered one of the major clinical challenges in the field of psychiatry. An estimated 44% of patients with major depressive disorder (MDD) do not respond to two consecutive antidepressant therapies, and 33% do not respond to up to four antidepressants. Over 15% of all patients with MDD remain refractory to any treatment intervention. rTMS is considered a treatment option for patients with TRD. Likewise, iCBT is evidence-based, symptom-focused psychotherapy recommended for the treatment of TRD. Objective: This study aimed to evaluate the initial comparative clinical effectiveness of rTMS treatment with and without iCBT as an innovative intervention for the treatment of participants diagnosed with TRD. Methods: This study is a prospective two-arm randomized controlled trial. Overall, 78 participants diagnosed with TRD were randomized to one of two treatment interventions: rTMS sessions alone and rTMS sessions plus iCBT. Participants in each group were made to complete evaluation measures at baseline, and 6 weeks (discharge) from treatment. The primary outcome measure was baseline to six weeks change in mean score for the 17-item Hamilton depression rating scale (HAMD-17). Secondary outcomes included mean baseline to six-week changes in the Columbia suicide severity rating scale (CSSRS) for the rate of suicidal ideations, the QIDS-SR16 for subjective depression, and the EQ-5D-5L to assess the quality of health in participants. Results: A majority of the participants were females 50 (64.1%), aged ≥ 40 39 (50.0%), and had college/university education 54 (73.0%). After adjusting for the baseline scores, the study failed to find a significant difference in the changes in mean scores for participants from baseline to six weeks between the two interventions under study on the HAMD-17 scale: F (1, 53) = 0.15, p = 0.70, partial eta squared = 0.003, CSSRS; F (1, 56) = 0.04 p = 0.85, partial eta squared = 0.001, QIDS-SR16 scale; F (1, 53) = 0.04 p = 0.61, partial eta squared = 0.005, and EQ-5D-VAS; F (1, 51) = 0.46 p = 0.50, and partial eta squared = 0.009. However, there was a significant reduction in means scores at week six compared to baseline scores for the combined study population on the HAMD-17 scale (42%), CSSRS (41%), QIDS-SR16 scale (35%), and EQ-VAS scale (62%). Conclusion: This study did not find that combined treatment of TRD with rTMS + iCBT (unguided) was superior to treatment with rTMS alone. Our findings do not support the use of combined treatment of rTMS + iCBT for the management of TRD disorders.
... Variables used for the propensity score were age, sex, education status, presence of personality or anxiety disorders, history of MDE, history lifetime of suicide attempt, and duration of current MDE. A 4 point change in HAMD-17 (corresponding to 15% improvement) is minimal value to detect clinically meaningful improvement (Leucht et al., 2013;Rush et al., 2021). A priori power calculations showed that our sample had 81% statistical power to detect a 15% higher HAMD-17 score percentage improvement in South/East facing rooms (65 (±18.5)% ...
... The HAMD is a 17-item clinical assessment instrument used to quantify the severity of depression in subjects who have been diagnosed with depression (Hamilton, 1967). It became one of the most widely used prognostic indicators in depression and was used in many trials of new antidepressant drugs submitted to the Food and Drug Administration (FDA) (Leucht et al., 2013). We studied here only the amount of HAMD change at the 4th and 8th week end, and the percentage of patients with 50% improvement in HAMD, with the intention of analyzing which treatment modality is the most efficacious now. ...
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Introduction: Post-stroke depression (PSD) is a common mental health problem after cerebrovascular accidents. There are several treatments that have been shown to be effective in treating post-stroke depression. However, it is not clear which treatment is more effective. Methods: In this meta-analysis, an appropriate search strategy was used to search eligible randomized controlled trials (RCTs) on different treatments to treat patients with Post-stroke depression published up to December 2021 from the CNKI, PubMed, and Cochrane Library. We assessed the mean difference or odds ratio between each treatment and placebo and summarized them as the average and 95% confidence interval (CI) by conducting Bayesian network meta-analyses. Results: By constructing a Bayesian network meta-analysis, we found that acupuncture combined with fluoxetine (vs placebo MD, −8.9; 95% CI, [−15, −2.9]) or paroxetine (vs placebo MD,—8.5; 95% CI, [−15, −2.5]) was the most effective for change in Hamilton depression scale (HAMD) at the end of the 4th week. For change in Hamilton depression scale at the end of the 8th week, rTMS combined with paroxetine (vs placebo MD, −13; 95% CI, [−17, −7.9]) had the greatest amount of change. The efficacy of medication combined with adjuvant therapy was also superior for the percentage of patients with Hamilton depression scale change over 50%. Discussion: The combination of antidepressants with adjuvant therapy may enhance the efficacy of antidepressants and achieve better results than antidepressant monotherapy in both Hamilton depression scale changes at the end of week 4 or 8 and 50% Hamilton depression scale improvement rate. Acupuncture combined with fluoxetine treatment was more effective in the treatment of post-stroke depression at week 4, while rTMS combined with paroxetine was more effective at week 8. Further research is needed to determine whether acupuncture combined with fluoxetine is better than rTMS combined with paroxetine for post-stroke depression at week 8.
... Patients with a CGI-I score of 1 or 2 were considered to have responded to treatment; a score of 1 indicated "very much improved" and a score of 2 indicated "much improved." Remission based on the clinical rating was defined as a score of 1 or 2 on the Clinical Global Impression-Severity scale (CGI-S) [22]. The CGI-S is a well-established standard measurement tool for the global assessment of patients with psychiatric illnesses, a reliable and valid measure rating the severity of a subject's condition on a 7-point scale ranging from 1 (not at all ill), 2 (borderline ill) to 7 (among the most extremely ill) [23,24]. ...
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Electroconvulsive therapy (ECT) is effective and safe for adults with severe depression, but less studied in adolescents. Here, we examined the indications, prevalence, practice, response and remission rates, and side effects in young people treated with ECT in Sweden. We also examined the usage of ECT in the transition to adult psychiatry. Using data from national patient registers and the Swedish National Quality Register for ECT (Q-ECT), we identified patients aged up to 19 years treated with ECT over a 5-year study period. Response and remission rates were analysed using the Clinical Global Impression (7-point scale)-Improvement (CGI-I) and Severity (CGI-S). A total of 118 individuals were identified, of which 105 were also enrolled in the Q-ECT. The most common indication for ECT was depression (68%; n = 80). Adolescents aged < 18 years were more severely ill before treatment than those aged 18 years ( P < 0.01). Three of the hospitals in Sweden treated the majority of adolescents < 18 years old. The median number of sessions in each ECT series was seven. Unilateral placement of the electrodes was the most common (88%; n = 99). Fifty-seven percent ( n = 54) of the patients responded (CGI-I, 1–2) to the treatment; remission (CGI-S, 1–2) was achieved by 32% ( n = 30). Psychotic symptoms were associated with a higher response rate in patients with depression ( P = 0.038). A deterioration of memory compared to pre-treatment was reported in six patients. ECT was associated with high response and remission rates in adolescents with severe psychiatric disorders after non-response to medication.
... We used the validated Brazilian-Portuguese version (Fleck et al., 2004) with 17 items, which was completed at baseline and 4 weeks later by a trained psychiatrist. Participants were categorized in R and NR to the antidepressant treatment (Leucht et al., 2013) based on a reduction of HAM-D score by 50 % in the second assessment compared to the baseline. ...
Article
Background Alterations in circadian system organization have been related to major depressive disorder manifestations. This study aimed to evaluate chronobiological parameters, such as sleep, levels of 6-sulfatoxymelatonin, and others derived from actimetry as potential predictors of adequate treatment response in MDD. Methods 98 adult women with confirmed diagnosis of MDD were included. Participants completed standard questionnaires (Hamilton Depression Rating Scale – HAM-D; Munich Chronotype Questionnaire - MCTQ) at baseline and after 4 weeks of treatment. Urinary samples for assessing 6-sulfatoxymelatonin were collected on the day before and immediately after pharmacological treatment administration, and 28 continuous days of actigraphy data were collected during the protocol. Participants were classified into Responder (R) or Non-responder (NR) to antidepressant treatment in 4 weeks (early responder), which was characterized by a ≥50 % decrease in the HAM-D score. Results The following biological rhythms variables significantly predicted a better treatment response in a model controlling for age, sex, and previous treatments: higher levels of activity (M10 - average activity in the 10 most active hours within the 24 h-day) and an earlier center of the 10 most active hours (M10c), as well as lower intradaily variability (IV) of light exposure. Sleep parameters and 6-sulfatoxymelatonin levels did not associate with treatment response prediction. Limitation Actimetry data were not assessed before changing in the treatment plan. Conclusion Different patterns in activity and light exposure might be linked to early antidepressant response.
... HAMD-17 78% change from baseline, after averaging values from several citations [14][15][16][17] ; and MADRS 82% change from baseline. 18 Finally, for BDI-1A, a 75% change from baseline was considered ''very much improved,'' following the benchmarks used for the other measures, since benchmark values of ''very much improved'' were not readily available in the literature for this scale. ...
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Background: A trial of psilocybin (COMP360) versus escitalopram for major depressive disorder (MDD) was reported as negative, as there was no significant difference in the primary outcome, mean change in the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16). However, analyses using three other depression scales (17-item Hamilton Depression Rating Scale [HAMD-17], Montgomery and Åsberg Depression Rating Scale [MADRS], and Beck Depression Inventory 1A [BDI-1A]) all significantly favored psilocybin, although without a prespecified plan for multiple comparisons correction. Methods: Bayesian reanalysis of a trial of two doses of psilocybin (25 mg) versus 6 weeks of escitalopram (20 mg) was done in 59 patients with MDD. We used skeptical priors, which bias estimates toward zero, and Bayes factors, which quantify evidence for or against a hypothesis. We report posterior estimates for the difference between psilocybin and escitalopram for four different depression scales. Results: Using Bayes factors and ''skeptical priors'' that bias estimates toward zero, for the hypothesis that psi-locybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a ''clinically meaningful amount'' (using literature-defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. For all scales, we found extremely strong evidence for psilocybin's noninferiority versus escitalopram. Findings were robust to prior sensitivity analysis. Conclusions: The overall pattern of evidence provided by this Bayesian reanalysis supports the following inferences: (1) psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful and (2) psilocybin is almost certainly noninferior to escitalopram. These results provide a more precise and nuanced interpretation to previously reported results from this trial and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.
... Depression severity was measured using the 17-item Hamilton Rating Scale for Depression (HAMD-17), which is a clinician-rated instrument developed to quantify the severity of depression in subjects already diagnosed with this disorder (Cronbach's alpha = 0.70 in this study) [34]. The seventeen items' total score ranges from 0 to 53, with the higher scores indicating more severe depression symptomatology [35]. ...
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Background Suboptimal medication adherence is a major reason for failure in the management of major depressive disorder (MDD), childhood trauma might be an essential risk factor of suboptimal medication adherence. This study aimed to comprehensively explore the associations between different types of childhood trauma and medication adherence among patients with MDD, and to test whether resilience has moderating effects on the foregoing associations. Methods Participants were from the Depression Cohort in China (ChiCTR registry number 1900022145), 282 MDD patients with completed both baseline and 12-weeks follow-up investigations were included in this study. The diagnosis of MDD was assessed by trained psychiatrists using the Mini-International Neuropsychiatric Interview (M.I.N.I.). Childhood trauma was evaluated using the Childhood Trauma Questionnaire-28 item Short Form (CTQ-SF), and resilience was evaluated using the Connor-Davidson Resilience Scale (CD-RISC). Demographic characteristics, depression symptoms, anxiety symptoms, suicidal ideation, suicidal attempt, insomnia symptoms, and painful somatic symptoms were also investigated. Participants were divided into groups of optimal and suboptimal adherence based on their Medication Adherence Rating Scale scores. Logistic regression and stratified analyses were performed. Results A total of 234 participants (83%) reported suboptimal medication adherence. After adjusting for covariates, CTQ total scores (AOR = 1.03, 95%CI = 1.01–1.06), CTQ measures of sexual abuse (AOR = 1.17, 95%CI = 1.01–1.37), and CTQ measures of physical neglect (AOR = 1.12, 95%CI = 1.02–1.23) were all associated with an increased likelihood of suboptimal adherence. There were significant moderating effects of resilience on the associations of childhood trauma (P = 0.039) and physical neglect (P = 0.034) with medication adherence. The stratification analyses showed that CTQ total scores and CTQ measures of physical neglect were independently associated with an increased risk of suboptimal adherence among patients with MDD with low-resilience or moderate-resilience, while not significantly associated with suboptimal adherence in those with high-resilience. Conclusion Childhood trauma was a significant risk factor of suboptimal adherence among patients with MDD, and resilience moderated the foregoing association. Obtaining a history of childhood trauma and assessing resilience may help identify patients with suboptimal adherence when providing MDD pharmacotherapy. Psychiatrists may consider enhancing resilience to cope with the adverse effects of childhood trauma on medication adherence.
... Subjects will be administered questionnaires before the intervention, at week 3 of the intervention and at week 6 of the intervention to compare changes in social self-efficacy. { Hamilton depression scale (HAMD-17) scale: Developed by Hamilton in 1960, it is the most commonly used questionnaire for assessing depression in hospitals (54). Most of the HAMD-17 entries are scored on a five-point scale from 0 to 4. The scale is applied to adult patients with depressive symptoms, and the patient's condition is assessed over a period of nearly one week. ...
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Introduction Depression is a common psychiatric disorder characterized by persistent low mood, reduced interest, and slowed thinking. Young adults are the main first-onset group for depression in all categories of the population. Program for education and enrichment of relational skills (PEERS) training, a program for the Education and Enrichment of Relational Skills, has been used in Europe and America for people with various types of social disorders with good results. A Chinese adaptation of the PEERS training program may be a new approach to help youth with depression return to society as soon as possible. This study aimed to construct and optimize a social skills training program for Chinese young adults with depression and to validate the impact of the program. Materials and methods and analysis The aim of this trial protocol is to evaluate the efficacy of the localized PEERS training program on social competence, depressed mood in a Chinese young adult population with depression. The primary outcome will be a change in self-reported depressive symptoms from baseline to week 3 post-randomization to week 6 post-randomization measured using the Liebowitz social anxiety scale (LSAS). Secondary outcomes include the rate of decline in severe social anxiety, the Social Avoidance and Distress Scale (SAD), the Social Self-Efficacy Scale (PSSE), and the Hamilton Depression Scale (HAMD-17). Data for each assessment will be collected at baseline, week 3 of the trial, and week 6 of the trial. Ethics and dissemination Ethics approval was obtained from the Hospital Ethics Committee. Findings will be disseminated through scientific journals, conferences, and university courses. Trial registration number [ http://www.chictr.org.cn/ ], identifier [ChiCTR2100046050].
... All our patients and healthy controls were assessed by two senior clinicians who were present at the same time and did not dispute the assessment results. The Hamilton Rating Scale for Depression (51) is a 17-item clinician-rated tool that measures the severity of depression in patients and is one of the most widely used outcome measures in depression (52). The Cronbach's alpha coefficient of the HAMD scale in this experiment was 0.86, with good internal consistency. ...
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Abnormal cognitive conflict resolution has been considered as a critical element of executive dysfunctions inpatient with major depression (MD). Further clarifying whether there was a deficit at perceptual encoding stage or the early response-execution stage in conflict control function by event-related potential (ERP) technique in MD would be helpful in understanding the neural mechanism of MD. Participants included twenty-six depressed patients and twenty-six healthy controls (HCs). All participants measured with Hamilton Depression Scale (17-item edition, HAMD) and a Simon task. Electroencephalograms were synchronously recorded when performing the Simon task. The method of residue iteration decomposition was used to analyze the lateralized readiness potential (LRP) and P300 components, which contributed to divides ERP components into a stimulus-locked component (S-cluster), a response-locked component (R-cluster) and an intermediate component cluster (C-cluster) by using latency variability and time markers. Results showed that reactive times (RTs) for both groups were fastest in congruent trials, and slowest in incongruent trials; however, there is no difference in RTs under the three conditions between two groups. Accuracy Rate (ACC) for both groups were the highest in neutral trials, and the lowest in incongruent trials; ACC in MD group were all lower than that of HC group under three conditions. ERP data analyses showed that depressed patients had a deficit in activating the correct response, as reflected by reduced amplitudes of R-LRP, but no abnormality in LRP-S and P300-C. In conclusion, patients with MD present conflict control dysfunction (i.e., abnormal cognitive conflict resolution) at the early response-execution stage, not at perceptual encoding stage, which may be reflected by the reduced R-LRP amplitudes. The abnormal cognitive conflict resolution in activating the correct response might constitute an interesting treatment target.
... The mood of each patient was evaluated using the HDRS and the 11-item Young Mania Rating Scale (YMRS) at baseline and 12 weeks after the initiation of treatment. Predefined cutoffs for remission were a HAMD or YMRS score ≤ 7 [52,53], and those for response were the percentage change in HAMD score (defined as ∆HAMD score %) or percentage change in YMRS score (defined as ∆YMRS score %) ≤ −50%. ...
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Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether LEPR polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between LEPR polymorphisms and VPA treatment response in BD patients who were drug naïve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of LEPR (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the LEPR polymorphism frequencies of alleles and genotypes were not significantly different between the controls (n = 77) and BD patients (n = 130). In addition, after the 12-week course of VPA treatment in BD patients, the LEPR polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the LEPR haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, p = 0.016), and the LEPR CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, LEPR polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment.
... For constructing the skeptical priors, the following benchmark values for "very much improved" were used. These criteria are based on values previously identified in the literature: QIDS 75% change from baseline (Rush et al. 2003); HAMD-17 78% change from baseline, after averaging values from several citations (Rush et al. 2003;Furukawa et al. 2007;Leucht et al. 2013;Bobo et al. 2016); MADRS 82% change from baseline (Leucht et al. 2017). Finally, for BDI-1A a 75% change from baseline was considered "very much improved", following the benchmarks used for the other measures, since benchmark values of "very much improved" were not readily available in the literature for this scale. ...
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Objectives: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis.Design: Reanalysis of a two-arm double-blind placebo controlled trial.Participants: Fifty-nine patients with MDD.Interventions: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups.Outcome measures: Quick Inventory of Depressive Symptomatology–Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A.Results: Using Bayes factors and ‘skeptical priors’ which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a ‘clinically meaningful amount’ (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin’s non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis.Conclusions: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful—-and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.
... Assessments were done at every visit with the exception of CGI-I score at V0. Percent-changes from baseline in HAMD and BDI-IA scores were calculated with formula: and used as final outcomes in order to control for inter-individual differences in baseline scores. Response incidence, defined as the proportion of patients with ≥50% HAMD score reduction (Leucht et al., 2013), was also used as a qualitative measure of the treatment efficacy. As of CGI-S and CGI-I scores, their absolute values at V1 and V2 were compared across the groups. ...
Article
The inter-individual variability in CYP2C19-mediated metabolism may affect the antidepressant treatment. The aim of this study is to evaluate differences in antidepressant efficacy and tolerability between different CYP2C19 metabolizer categories in inpatients suffering from major depressive disorder. The cohort was divided into experimental groups based on CYP2C19 genotype and it contained 24 slow (SMs), 41 normal (NMs), and 37 fast metabolizers (FMs). Efficacy and tolerability were assessed at baseline, and after two and four weeks as a follow-up. The primary efficacy measurement was the change from baseline in Hamilton's Depression Rating Scale (HAMD), while the primary tolerability measurement was the Toronto Side-Effects Scale (TSES) intensity scores at the last visit. The reduction in HAMD score was 36% less pronounced and response rate was exceedingly less prevalent (75% lower) in SMs, compared with NMs. The TSES intensity score was increased in SMs, compared with NMs, by 43% for central nervous system and by 22% for gastrointestinal adverse drug reactions. No significant differences in measured parameters were observed between NMs and FMs. Compared with NM and RM, lower antidepressant efficacy and tolerability was observed in SMs; this association is likely connected with the lower SM capacity to metabolize antidepressant drugs.
... It consists of 17 items. The higher the score, the more severe the depression (49). The classification is as follows: normal (< 7), possible depression (7-17), diagnosed depression (18)(19)(20)(21)(22)(23)(24) and severe depression (> 24). ...
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Background Post-stroke depression (PSD), a common neuropsychiatric comorbidity after stroke, has a negative impact on the functional recovery and quality of life of survivors. It lacks effective therapeutic drugs with good curative effects and few adverse reactions. Preliminary experiments have shown that the optimized acupuncture and moxibustion treatment (OAMT), including acupuncture, moxibustion, and auricular intradermal acupuncture, improved depressive symptoms and neurological deficits in patients with PSD. However, the evidence for its effectiveness is still insufficient. Hence, we designed this study to evaluate the efficacy and safety of the OAMT in the treatment of PSD and to explore its possible mechanism from the perspective of executive functions. Methods/Design This is a randomized controlled trial, which comprises a total of 134 patients with PSD. Participants are randomized into intervention group and control group at a 1:1 ratio. All treatments are given five times per week for 4 weeks. The primary outcome is the severity of depression, which is evaluated by the Hamilton Depression Scale-17 (HAMD-17) and the Beck Depression Rating Scale (BDI). Secondary outcomes are executive abilities, which are measured by several neuropsychological tests, including the Stroop Color and Word Test (SCWT), the Trial Making Test (TMT), the Digit Symbol Substitution Test (DSST), and the Matrix Reasoning Test (MRT). All outcomes have been evaluated at baseline and weeks 4, 8, 12, and 20. At the same time, functional MRI (fMRI) is used to measure the functional connectivity in the cognitive control network (CCN) at baseline and 4 weeks after intervention. Discussion This study aims to provide high-quality evidence for the efficacy and safety of the OAMT for treating PSD. In addition, this trial is the first trial to explore if the improvement condition of depression in the OAMT group is related to the improvement of executive functions and the favorable changes in the structure. Clinical Trial Registration Chinese Clinical Trial Registry, identifier: ChiCTR2100048431.
... Secondary outcomes included change in PCL-5, PHQ-9, GAD-7 and CGI scores. Clinical response was defined as >= 50% reduction of baseline scores on the HAMD-17, PCL-5, PHQ-9 and GAD-7, whereas remission was defined by HAMD-17 score of <=7 [19]. We opted to define remission for the remaining scales when scores fell below the normative cut-offs: PCL-5 score of <31-33 [20], PHQ-9 score of <5 [21] and GAD-7 score of <5 [22]. ...
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Background Depression comorbid with posttraumatic stress disorder (PTSD) can be disabling and treatment resistant. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS), may have a role in helping these patients. There are only few published studies using different rTMS paradigms including bilateral intermittent theta burst (iTBS) and low frequency rTMS. Methods In this small cohort observation study, we examined the efficacy of bilateral sequential theta-burst stimulation (bsTBS) in 8 treatment resistant depression (TRD) military veterans with PTSD comorbidity stemming from military service experience. Results bsTBS was generally well tolerated and resulted in 25% and 38% remission and response rates on Depression scores respectively; 25% remission and response rate on PTSD scores. Discussion This study demonstrates preliminary feasibility and safety of bsTBS in TRD with comorbid military service related PTSD. We concluded that this paradigm might hold promise as a therapeutic tool to help patients with TRD co-morbid with military service related PTSD. Further adequately powered studies to compare rTMS treatment paradigms in this patient group are warranted.
... 4 published and unpublished studies suggests an effect size of around 0.3 across different metaanalyses, which translates into a difference of around 2.0 points on the commonly used Hamilton Depression rating scale (HAM-D) (Hamilton, 1960), which has a maximum score of 54 points. This has not been shown to be a clinically relevant difference (Leucht et al., 2013;Moncrieff & Kirsch, 2015). Matching HAM-D scores against Clinical Global Impression scale scores (Guy, 1976) suggests a difference of 8 points is required to indicate 'mild clinical improvement' and that a difference of 3 points and below does not register as indicating any change. ...
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The dominant view within mental health services and research suggests that feeling depressed is a kind of medical illness, partially caused by various biological deficits which are somehow corrected by physical interventions. This article critically appraises evidence for the effectiveness and value of antidepressant drugs and electroconvulsive therapy (ECT), the two principle physical treatments recommended for depression. It also describes the negative effects of these interventions and raises concerns about how they impact the brain. We propose an alternative understanding that recognises depression as an emotional and meaningful response to unwanted life events and circumstances. This perspective demands that we address the social conditions that make depression likely and suggests that a combination of politics and common sense needs to guide us in providing help for one another when we are suffering in this way. This alternative view is increasingly endorsed around the world, including by the United Nations, the World Health Organization and service users who have suffered negative consequences of physical treatments that modify brain functions in ways that are not well-understood.
... The clinical benefit of an intervention needs to be determined by comparison with a benchmark such as the minimal clinically important difference (MCID) 146 . For the HAM-D, for example, a minimal clinically relevant improvement has been claimed by some authors to correspond to a 7-point difference 147 or to an SMD of 0.88 148 . If this is correct, in psychotherapies or pharmacotherapies for depression, effect sizes of 0.30, 0.40 or even 0.50 correspond to a difference on the HAM-D of 2 or 4 points (i.e. ...
Article
Mental disorders represent a worldwide public health concern. Psychotherapies and pharmacotherapies are recommended as first line treatments. However, evidence has emerged that their efficacy may be overestimated, due to a variety of shortcomings in clinical trials (e.g., publication bias, weak control conditions such as waiting list). We performed an umbrella review of recent meta-analyses of randomized controlled trials (RCTs) of psychotherapies and pharmacotherapies for the main mental disorders in adults. We selected meta-analyses that formally assessed risk of bias or quality of studies, excluded weak comparators, and used effect sizes for target symptoms as primary outcome. We searched PubMed and PsycINFO and individual records of the Cochrane Library for meta-analyses published between January 2014 and March 2021 comparing psychotherapies or pharmacotherapies with placebo or treatment-as-usual (TAU), or psychotherapies vs. pharmacotherapies head-to-head, or the combination of psychotherapy with pharmacotherapy to either monotherapy. One hundred and two meta-analyses, encompassing 3,782 RCTs and 650,514 patients, were included, covering depressive disorders, anxiety disorders, post-traumatic stress disorder, obsessive-compulsive disorder, somatoform disorders, eating disorders, attention-deficit/hyperactivity disorder, substance use disorders, insomnia, schizophrenia spectrum disorders, and bipolar disorder. Across disorders and treatments, the majority of effect sizes for target symptoms were small. A random effect meta-analytic evaluation of the effect sizes reported by the largest meta-analyses per disorder yielded a standardized mean difference (SMD) of 0.34 (95% CI: 0.26-0.42) for psychotherapies and 0.36 (95% CI: 0.32-0.41) for pharmacotherapies compared with placebo or TAU. The SMD for head-to-head comparisons of psychotherapies vs. pharmacotherapies was 0.11 (95% CI: –0.05 to 0.26). The SMD for the combined treatment compared with either monotherapy was 0.31 (95% CI: 0.19-0.44). Risk of bias was often high. After more than half a century of research, thousands of RCTs and millions of invested funds, the effect sizes of psychotherapies and pharmacotherapies for mental disorders are limited, suggesting a ceiling effect for treatment research as presently conducted. A paradigm shift in research seems to be required to achieve further progress.
... As mentioned earlier, a reduction of ≥25% in the HAMD score will be used to indicate that the treatment is effective. [14] 2.2.4.2. Secondary outcomes. ...
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Background: Post-stroke depression (PSD) refers to a series of affective disorder syndromes that occur after stroke and are often accompanied by physical symptoms. PSD presents with low mood and lack of interest as the main characteristics along with the symptoms of stroke. The physical symptoms of PSD include sleep disorder, loss of appetite, and reluctance to communicate. Although Wendan decoction has been suggested to be effective in the treatment of PSD, there is no meta-analysis providing evidence for the usefulness of Wendan decoction for treating PSD. Methods: The following electronic databases will be searched: the Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure, Wan Fang databases, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. Each database will be searched from its inception to November 2021. Two independent researchers will conduct study selection, data extraction, and risk bias assessment. Any discrepancies will be resolved through consultation with a third researcher. If the included data are suitable, we will conduct a meta-analysis using RevMan v5.4 software. Results: In this systematic review, the effectiveness and safety of Wendan decoction in the treatment of PSD will be evaluated. Conclusion: The findings of this meta-analysis will provide evidence-based data for the application of Wendan decoction in the treatment of PSD. Ethics and dissemination: Individual patient data and privacy will not be involved in this research,so ethics approval is not required. Inplasy registration number: INPLASY2021110018.
... 14 One analysis of 5000 patients has suggested that NICE's threshold was too liberal and that more than a 6point change on the HAM-D was required for 'minimal improvement' to be detected by a clinician, whereas a change on the HAM-D of 3 points or less corresponded to 'no change'. 15 16 A comprehensive recent analysis has confirmed that a minimal clinically important difference on the HAM-D ranges between 3 and 5 points. 17 Nevertheless, some authors have argued that the small differences in rating scales scores produced by SSRI antidepressants constitute a worthwhile effect, postulating a sub-group with greater than average response. ...
Article
In England, the prescribing of antidepressants, primarily the newer generation antidepressant classes, has steadily increased over recent years. There is ongoing debate about how the efficacy of these drugs is viewed, their place in therapy and the harms associated with stopping them. Much of the evidence of their efficacy comes from short-term placebo-controlled trials which tend not to include outcomes that are of greatest relevance to patients, such as social functioning or quality of life, but rather restrict outcomes narrowly to symptom measures. On such measures these studies do not demonstrate clinically significant differences from placebo for depression. A range of adverse effects are also recognised, often greater in naturalistic studies of long-term antidepressants users than those measured in short-term efficacy studies, including emotional numbing, sexual difficulties, fatigue and weight gain. There is increasing recognition that withdrawal symptoms from antidepressants are common and that these symptoms can be severe and long-lasting in some patients. Recent guidance on how to stop antidepressants in a tolerable way has been presented by the Royal College of Psychiatrists. We believe that increasing awareness about the difficulty that some patients have in stopping antidepressants should lead to more cautious prescribing practice, with antidepressants given to fewer patients and for shorter periods of time. This article discusses the perceived benefits and harms of antidepressant use.
... HAMD is a scale used to assess depression. The version used in this study consists of 17 items, with a total score ranged from 0 to 53 points: 0-7 points without depression, 8-17 is mild depression, 17-24 is moderate depression, and > 24 is severe depression [32]. ...
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Background Insomnia is a common sleeping disorder which affects the quality of life which can bring harms to physical and mental health of human beings and even economic development. Traditional Chinese medicine (TCM) plays an outstanding role in treating chronic diseases and alleviating their symptoms. Therefore, the purpose of this study is to assess the treatment efficacy in patients with insomnia treated with abdomen-rubbing qigong exercise (ARQE). In addition, the brain function changes of patients will be explored by resting state functional magnetic resonance imaging (rs-fMRI). Method/design This trial is a randomized, single-blind, controlled study planned to transpire between July 1, 2020, and July 31, 2021. A sample size of 114 participants (57 per group) with chronic insomnia will be randomly assigned to receive ARQE or CBTI for 8 weeks. The study duration will be 13 weeks, including a 1-week screening period, 8 weeks of intervention, and another 4 weeks of follow-up. The primary outcome is the Pittsburgh sleep quality index scores. Secondary outcomes include insomnia severity index, gastrointestinal symptom rating scale, the Hamilton Depression Scale, and rs-fMRI scan. The adverse events will be in control. Discussion The results of this study will help to clarify the efficacy of ARQE in the treatment of insomnia and try to use rs-fMRI technology to explore the brain function changes of ARQE in improving sleep quality in patients with insomnia disorder. If the results are as expected, this study will provide high-quality evidence for the treatment of insomnia with ARQE. Trial registration China Clinical Registration Agency ChiCTR1900028009 . Registered on 19 December 2019.
... This major finding of this study is that acupuncture combined with antidepressants compared to the sole use of antidepressants had a more significant reduction in depressive symptoms and a significantly stronger resting-state functional connectivity (rsFC) in the DLPFC after 3 weeks of treatment. HAMD-17 is a golden standard commonly used by clinicians to assess the remission and response in MDD patients [26], where PHQ-9 as a self-assessment tool is commonly used in the initial screening and follow-ups to monitor treatment responses [27]. In our study, both HAMD-17 and PHQ-9 scores reduced significantly, with a medium effect size of −0.4 to −0.6, indicating a reduction in depression severity. ...
Article
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Depression is a common psychiatric illness affecting over 300 million people globally. Acupuncture has been reported to be a safe complementary treatment for depression. This study is aimed to investigate the efficacy and mechanism of combining acupuncture with antidepressants in treating depression compared to the sole use of antidepressants. Seventy depression patients were randomly assigned to the treatment group (n = 50) and control group (n = 20). The treatment group received acupuncture combined antidepressants treatment for 3 weeks, while the control group took antidepressants monotherapy for 3 weeks. Among the 70 patients, 40 participants (20 control; 20 treatment) were randomized for studying functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) measured by the functional near-infrared spectroscopy. The primary outcome was HAMD-17 and secondary outcomes were PHQ-9, and the relationships of resting-state FC (rsFC) with the depression severity. PHQ-9 and HAMD-17 scores in the treatment group were significantly lower than those in the control group at Week 3 (p = 0.01) with effect sizes of −0.4 and −0.61 respectively. The rsFC in F1, F3, AF3, AF7, FC3, FC5 (left DLPFC, 10–20 system), AF8, and F6 (right DLPFC) in the treatment group had significant temporal correlation (p < 0.05, FDR corrected) in DLPFC compared to the channels in the control group. No significant correlation was found between the changes of rsFC and depression severity. In conclusion, depressed patients receiving acupuncture combined with antidepressants have improvement of depressive symptoms and the stronger rsFC in the DLPFC compared to those using antidepressants alone.
... Hamilton depression rating scale, [1] Patient Health Questionnaire-9 (PHQ-9), [2] Generalized Anxiety Disorder-7, [3] and Medical Outcomes Survey Short Form-36 (SF-36) [4] were used to evaluate his psychological distress level. The results showed that he had mild level of depression. ...
... 0-7 points without depression, 8-17 is mild depression, 17-24 is moderate depression,> 24 is severe depression. (32) Neuroimaging: ...
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Background Insomnia is a common sleeping disorder which affects the quality of life which can bring harms to physical and mental health of human beings and even economic development. Traditional Chinese medicine (TCM) plays an outstanding role in treating chronic diseases and alleviating their symptoms. Therefore, the purpose of this study is to assess the treatment efficacy in patients with insomnia treated with abdomen-rubbing qigong exercise (ARQE). In addition, the brain function changes of patients will be explored by resting state functional magnetic resonance imaging(rs-fMRI).Method/designThis trial is a randomized, single-blind, controlled study planned to transpire between July 1, 2020, and July 31, 2021. A sample size of 114 participants (57 per group) with chronic insomnia will be randomly assigned to receive ARQE or CBTI for 8 weeks. The study duration will be 13 weeks, including a 1-week screening period, 8 weeks of intervention, and another 4 weeks of follow-up. The primary outcome is the Pittsburgh sleep quality index scores. Secondary outcomes include insomnia severity index, gastrointestinal symptom rating scale, the Hamilton depression scale, and rs-fMRI scan. The adverse events will be in control. DiscussionThe results of this study will help to clarify the efficacy of ARQE in the treatment of insomnia, and try to use rs-fMRI technology to explore the brain function changes of ARQE in improving sleep quality in patients with insomnia disorder. If the results are as expected, this study will provide high-quality evidence for the treatment of insomnia with ARQE. Trial registrationChina Clinical Registration Agency (registration number: ChiCTR1900028009). Registered on 19 December 2019. http://www.chictr.org.cn/showproj.aspx?proj=46679
... CGI-I is rated between 1 (very much improved since initiation of treatment) to 7 (very much worse since initiation of treatment). CGI-I scores of 1 or 2 correspond to a reduction of 50% or more on the Hamilton Rating Scale for Depression (HRSD), which is an established response criterion (Leucht et al., 2013). ...
Article
Background Response rates after and tolerability of electroconvulsive therapy (ECT) in depressive disorders with psychiatric comorbidity are uncertain. Methods Data on patients with a depressive episode were collected from the Swedish National Quality Register for ECT. Logistic regression analyses, adjusted for gender, age, and depressive episode severity, were used to compare patients with and without comorbidity. The clinical response assessment Clinical Global Impression - Improvement Scale was used in 4,413 patients and the memory item from the Comprehensive Psychiatric Rating Scale was used for subjective memory impairment rating after ECT in 3,497 patients. Results In patients with depressive disorder and comorbid personality disorder or anxiety disorder, 62.7% and 73.5%, respectively, responded after ECT compared with 84.9% in patients without comorbidity [adjusted odds ratio (aOR) 0.43, 95% confidence interval (CI) 0.34–0.55, and aOR 0.61, 95% CI 0.51–0.73, respectively]. The proportion of responding patients with comorbid alcohol use disorder was 77.1%, which was not significantly different from that in patients without comorbidity (aOR 0.75, 95% CI 0.57–1.01). The impact of comorbidity decreased with higher age and depressive episode severity. Subjective ratings of memory impairment did not differ between patients with and without comorbidity. Limitations Observational non-validated clinical data. Conclusions The response rate after ECT in depression may be lower with concurrent personality disorder and anxiety disorder; however, the majority still respond to ECT. This implies that psychiatric comorbidity should not exclude patients from ECT.
... All the participants also had an identical assessment protocol, including the review of medical history and week. According to the reduction of HAMD (Leucht et al., 2013) (HAMD baseline À HAMD week-2 )/HAMD baseline ), the MDD patients were classified into nonresponsive depression (NRD, n = 40) (HAMD score reduction ≤50%) and responsive depression (RD, n = 42) (HAMD score reduction >50%). In total, there were 132 samples, consisting of 50 HCs, 42 RDs, and 40 NRDs. ...
Article
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The pathophysiology of major depressive disorder (MDD) has been explored to be highly associated with the dysfunctional integration of brain networks. It is therefore imperative to explore neuroimaging biomarkers to aid diagnosis and treatment. In this study, we developed a spatiotemporal graph convolutional network (STGCN) framework to learn discriminative features from functional connectivity for automatic diagnosis and treatment response prediction of MDD. Briefly, dynamic functional networks were first obtained from the resting‐state fMRI with the sliding temporal window method. Secondly, a novel STGCN approach was proposed by introducing the modules of spatial graph attention convolution (SGAC) and temporal fusion. A novel SGAC was proposed to improve the feature learning ability and special anatomy prior guided pooling was developed to enable the feature dimension reduction. A temporal fusion module was proposed to capture the dynamic features of functional connectivity between adjacent sliding windows. Finally, the STGCN proposed approach was utilized to the tasks of diagnosis and antidepressant treatment response prediction for MDD. Performances of the framework were comprehensively examined with large cohorts of clinical data, which demonstrated its effectiveness in classifying MDD patients and predicting the treatment response. The sound performance suggests the potential of the STGCN for the clinical use in diagnosis and treatment prediction. In this study, we developed a spatiotemporal graph convolutional network framework to learn discriminative features from functional connectivity for automatic diagnosis and treatment response prediction of major depressive disorder. Performances of the framework were comprehensively examined with large cohorts of clinical data, which demonstrated its effectiveness in classifying major depressive disorder patients and predicting the treatment response.
... Accordingly, the current suicidal risk and its degree were evaluated based on the HAM-D item 3 focusing on suicidality. Being aw are that suicidality might be more appropriately explored using specific scales as the Columbia-Suicide Severity Rating Scale (Posner, Brown et al. 2011), we are confident that the abovementioned approach, that wa s introduced in our previous work (Dold, Ba rtova et al. 2018), is not too fa r-fetched, since the HAMD represents an objective, valid and reliable measure that wa s numerously employed in clinical trials on depression and that is internationally acknowledged for the assessment of depressive symptoms and their extent (Leucht, Fennema et al. 2013). ...
Article
Background : While the association between relationship status and the development of depressive symptoms in the general population were reported previously, its relation to the severity and the course of major depressive disorder (MDD) as well as the treatment patterns and response rates needs to be elucidated. Methods : The present international multicenter cross-sectional study performed by the European Group for the Study of Resistant Depression (GSRD) investigated socio-demographic and clinical patterns of relationship status in a real-world sample of 1410 adult in- and outpatients with MDD as primary diagnosis. Results : While 49.9% of all MDD patients were partnered, 25.4% were separated, and 24.8% were single. Single relationship status was linked to younger mean age, earlier mean age of onset, and current suicidal risk. Being separated was related to older mean age, unemployment, greater symptom severity, current suicidal risk, and add-on treatment strategies. Partnered relationship status was associated with less frequent current suicidal risk. Limitations : The retrospective assessment of treatment response that was exclusively based on psychopharmacotherapeutic strategies should be critically considered and weighed while interpreting the present results providing novel insights into the complex interaction of relationship status with the clinical phenotype of MDD. Conclusions : Although MDD patients living in relationships do not seem to be omitted from the evolution of MDD, they may be spared from chronicity and suicidality. Hence, being aware of the current relationship status might support clinicians in the diagnostic and therapeutic process towards optimized management of such challenging clinical phenomena and their negative consequences.
... omawiania pacjentów, a ich oceny były zgodne poza 2 przypadkami, gdy występowała niewielka rozbieżność i ocenę uśredniono. Jako remisję definiowano ustąpienie objawów depresyjnych lub ustąpienie objawów wytwórczych odpowiadające wynikowi na skali CGI-S 1 (zdrowy) lub 2 (niemal zdrowy) [50][51][52], jako reakcję na leczenie (istotna poprawa) -zmniejszenie nasilenia objawów chorobowych odpowiadające wynikowi na skali CGI-S ≤ 3 [53], niepełną poprawę -CGI-S ≥ 4, a jako pogorszenie nasilenie objawów depresji lub objawów psychotycznych (wynik na skali CGI-S w ocenie po zabiegach EW wyższy niż w ocenie bazowej). ...
Article
Cel pracy Celem badania była ocena skuteczności i bezpieczeństwa leczenia elektrowstrząsowego w populacji pacjentów ≥ 65 lat Metoda Omawiane badanie miało charakter naturalistyczny, retrospektywny. Do badania włączono 65 pacjentów, kobiety i mężczyzn hospitalizowanych w oddziałach Instytutu Psychiatrii i Neurologii i poddawanych terapii EW. Analizowano przebieg 615 zabiegów przeprowadzonych w latach 2015-2019. Skuteczność EW oceniano z wykorzystaniem skali CGI-S. Bezpieczeństwo oceniano analizując działania niepożądane terapii, uwzględniając obciążenia somatyczne grupy badanych. Wyniki Aż 94 % pacjentów wyjściowo spełniało kryteria lekooporności. W badanej grupie nie odnotowano poważnych powikłań takich jak zgon, stan zagrożenia życia, konieczność hospitalizacji na innym oddziale czy trwały uszczerbek na zdrowiu. Łącznie w całej grupie działania niepożądane odnotowano u 47,7% starszych pacjentów, w większości przypadków (88%) miały one niewielkie nasilenie i ustępowały bez stosowania żadnego specyficznego postępowania. Najczęściej obserwowanym działaniem niepożądanym EW były wzrosty ciśnienia tętniczego (55,4%). Czterech pacjentów nie ukończyło terapii EW z powodu działań niepożądanych. U większości badanych (86,2%) wykonano co najmniej 8 zabiegów w serii. Zabiegi EW okazały się być skuteczną metodą leczenia w populacji pacjentów po 65 roku życia - reakcję na leczenie stwierdzono u 76,92% chorych, a remisję u 49, 23% leczonych osób. Wyjściowe nasilenie choroby w skali CGI-S wyniosło średnio 5,54, po leczeniu EW 2,67. Wnioski Tolerancja zabiegów jest po 65 r.ż gorsza niż u młodszych pacjentów, większość działań niepożądanych jest związana z wyjściowymi obciążeniami somatycznymi, głównie dotyczącymi układu sercowo-naczyniowego. Nie zmienia to faktu, że terapia EW jest w tej populacji wysoce skuteczna i może stanowić bardzo dobrą alternatywę dla często nieskutecznej lub powodującej uboczne działania farmakoterapii.
... Any significant positive change of outcome measure within group (pre-vs. posttreatment) was accepted as matching "demonstrates efficacy" criterion (level 1) without necessarily having to meet minimal clinically important values for depression (HAM-D < 5 for full remission, HAM-D < 9 for partial remission, and 25-35% or 5-6 points' reduction for minimal clinically relevant changes [12]). ...
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This article is aimed at showing the current level of evidence for the usage of biofeedback and neurofeedback to treat depression along with a detailed review of the studies in the field and a discussion of rationale for utilizing each protocol. La Vaque et al. criteria endorsed by the Association for Applied Psychophysiology and Biofeedback and International Society for Neuroregulation & Research were accepted as a means of study evaluation. Heart rate variability (HRV) biofeedback was found to be moderately supportable as a treatment of MDD while outcome measure was a subjective questionnaire like Beck Depression Inventory (level 3/5, “probably efficacious”). Electroencephalographic (EEG) neurofeedback protocols, namely, alpha-theta, alpha, and sensorimotor rhythm upregulation, all qualify for level 2/5, “possibly efficacious.” Frontal alpha asymmetry protocol also received limited evidence of effect in depression (level 2/5, “possibly efficacious”). Finally, the two most influential real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback protocols targeting the amygdala and the frontal cortices both demonstrate some effectiveness, though lack replications (level 2/5, “possibly efficacious”). Thus, neurofeedback specifically targeting depression is moderately supported by existing studies (all fit level 2/5, “possibly efficacious”). The greatest complication preventing certain protocols from reaching higher evidence levels is a relatively high number of uncontrolled studies and an absence of accurate replications arising from the heterogeneity in protocol details, course lengths, measures of improvement, control conditions, and sample characteristics.
... Type of outcome measures. Primary outcomes: The total scores of the Hamilton rating scale for depression, [16] and the efficacy rate of reducing those. Secondary outcomes: adverse reactions and quality of life assessed using standard quality of life instruments. ...
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Background: Cancer-related depression (CRD) is the most common mood disorder in patients with malignant tumors, negatively influencing the patient's daily life. Traditional Chinese medicine, as an alternative CRD therapy, has shown good treatment performance in recently years. Soothing liver-qi stagnation, as a classic therapy for depression, is based on traditional Chinese medicine theory. However, there is no evidence-based medical confirmation for the soothing liver-qi stagnation method for CRD treatment. Methods: We will systematically search relevant articles from their inception to July 1, 2019 in the following electronic databases: the Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, Chinese Science and Technique Journals Database, and the Wan-fang Database. The primary outcome is the total scores of the Hamilton rating scale for depression and, the efficacy rate of reducing Hamilton rating scale for depression scores. The secondary outcomes are adverse reactions and quality of life as assessed by standard instruments. Two researchers will independently perform study selection, data extraction, and quality assessment. If there is any disagreement, it will be settled through third-party negotiations. We will assess the risk of bias and data synthesis using Review Manager (the Cochrane Collaboration) software, Version 5.3.0. Results: This work will evaluate the clinical effectiveness and safety of the soothing liver-qi stagnation method for CRD. Conclusion: This study may provide evidence-based medical corroboration for clinical application of the soothing liver-qi stagnation method for CRD treatment. Prospero registration number: CRD42019145678.
... HC subjects had to have not had any current or lifetime Axis I Disorders, nor could they have had any first-degree relatives with a history of an Axis I disorder. All of the participants were assessed using the Hamilton Depression Rating Scale (HAMD) for symptoms of depression [22], and the Young Mania Rating Scale (YMRS) for manic symptoms [23]. Exclusion criteria for the study were as follows: (1) must not have had a history of major physical disorders, particularly those that may be associated with brain tissue changes, such as hypertension, diabetes, or metastatic disease; (2) must not have had unstable diseases such as heavy asthma; neurological abnormalities, including major head trauma (loss of consciousness lasting more than 5 min), epilepsy, cerebrovascular disease, brain tumors, or neurodegenerative diseases; somatic diseases that may cause mood disorders, such as multiple sclerosis, thyroid disease, etc.; (3) no MRI contraindications; and (4) no lifetime or current substance dependence or abuse. ...
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Background Mood disorders are severe mental disorders related to increased suicidal behavior. Finding neural features for suicidal behavior, including suicide attempts (SAs) and suicidal ideation (SI), in mood disorders may be helpful in preventing suicidal behavior. Methods Subjects consisted of 70 patients with mood disorders and suicidal behavior, 128 patients with mood disorders without suicidal behavior (mood disorders control, MC), and 145 health control (HC) individuals. All participants underwent structural magnetic resonance imaging (MRI). We used voxel-based morphometry (VBM) techniques to examine gray matter volumes (GMVs). Results Significant differences were found in GMVs of the left and right middle frontal gyrus among the patients with mood disorders and suicidal behavior, MC, and HC. Post hoc comparisons showed significant differences in the GMVs of the above regions across all three groups (P < 0.01): HC > MC > mood disorders with suicidal behavior. However, there were no significant differences in the GMVs of the left and right middle frontal gyrus between the mood disorders with SI and mood disorders with SAs groups. Conclusions These findings provide evidence that abnormal regional GMV in the middle frontal gyrus is associated with suicidal behavior in mood disorders. Further investigation is warranted to determine whether the GMV alterations in mood disorders with SI are different from these in mood disorders with SAs.
... Partial response was defined as a decrease in HDRS score of > 25%, a cutoff which has been used to define partial response in prior reports (Nierenberg and DeCecco, 2001) and has been found to correspond to improvement ["minimally improved"] on the Clinical Global Impressions-Improvement (CGI-I) scale (Masson and Tejani, 2013). We defined worsening dysphoria as an increase in HDRS score of more than 3 points, which has been found to correspond to significant worsening ["much worse"] on the CGI-I scale in one report (Leucht et al., 2013). Subjects who did not participate in follow-up assessment were given 0 points on the treatment response subscale (87% of participants had 3-month follow-up data available, see limitations section for more detail). ...
Article
Background: It has been argued that unipolar major depressive disorder (MDD) and bipolar disorder (BD) exist on a continuous spectrum, given their overlapping symptomatology and genetic diatheses. The Bipolarity Index (BI) is a scale that considers bipolarity as a continuous construct and was developed to assess confidence in bipolar diagnosis. Here we investigated whether BI scores correlate with gray matter volume (GMV) in a sample of unmedicated unipolar and bipolar depressed individuals. Methods: 158 subjects (139 with MDD, 19 with BD) in a major depressive episode at time of scan were assigned BI scores. T1-weighted Magnetic Resonance Imaging scans were obtained and processed with Voxel-Based Morphometry using SPM12 (CAT12 toolbox) to assess GMV. Regression was performed at the voxel level to identify clusters of voxels whose GMV was associated with BI score, (p<0.001, family-wise error-corrected cluster-level p<0.05), with age, sex and total intracranial volume as covariates. Results: GMV was inversely correlated with BI score in four clusters located in left lateral occipital cortex, bilateral angular gyri and right frontal pole. Clusters were no longer significant after controlling for diagnosis. GMV was not correlated with BI score within the MDD cohort alone. Limitations: Incomplete clinical data required use of a modified BI scale. Conclusion: BI scores were inversely correlated with GMV in unmedicated subjects with MDD and BD, but these correlations appeared driven by categorical diagnosis. Future work will examine other imaging modalities and focus on elements of the BI scale most likely to be related to brain structure and function.
... Others have used approaches that rely upon the error of measurement of the scales. Clinician ratings of improvement have also been frequently used in depression research but none of these approaches incorporates the patient's perspective (Leucht et al., 2013). ...
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Background The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists. Methods A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a ‘global rating of change’ scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R). Results For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) −26.7 to −14.9) on the PHQ-9; 23% (95% CI −27.8 to −18.0) on the BDI-II and 26.8% (95% CI −33.5 to −20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were −1.7, −3.5 and −1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement. Conclusions An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit. Funding Funding. National Institute for Health Research.
Article
Background: Depression and pain are highly comorbid and share biological mechanisms. Acupuncture is commonly used to manage both pain and depression, but the choice of acupoints for specific disorders differs. This study aimed to investigate whether specific acupuncture intervention on pain- and depression-acupoints would have specific efficacy and immune effects in patients with comorbid chronic pain and major depressive disorder (MDD). Methods: We performed a subject- and assessor-blinded, crossover, and randomized controlled clinical trial of depression- and pain-specific acupuncture intervention and measured clinical responses and proinflammatory cytokines in patients with comorbid chronic pain and MDD. Specific acupoints for pain and depression were used in random order with a washout interval. Forty-seven patients were enrolled and randomly assigned to two groups: (1) the depression-pain group (23 patients who were treated with depression-specific acupoints and then the pain-specific acupoints after the washout) and (2) pain-depression group (24 patients with the reverse order). Results: The pain-specific acupoints for pain did not reduce Brief Pain Inventory scores to a significantly greater degree (-0.97 ± 1.69) than the depression-specific acupoints (-0.28 ± 1.88); likewise, the depression-specific acupoints did not significantly ameliorate Hamilton Depression Rating Scale (-4.59 ± 6.02) than the pain-specific acupoints (-6.69 ± 6.61). The pain-specific acupoints improved Beck Depression Inventory-Second Edition (-6.74 ± 9.76) even better than the depression-specific acupoints (-1.92 ± 10.74). The depression-specific acupoints did not significantly decrease the depression-related interleukin (IL)-6 level (-1.24 ± 6.67) than the pain-specific acupoints (-0.60 ± 4.36). The changed levels of IL-1β, tumor necrosis factor (TNF)-α between the depression-specific acupoints (-37.41 ± 194.49; -12.53 ± 54.68) and the pain-specific acupoints (-15.46 ± 87.56; -7.28 ± 27.86) could not reach significantly different, too. Conclusion: This study rejected our hypothesis that the pain-specific acupoints might produce superior analgesic effects than the depression-specific acupoints and vice versa. The cytokine results might imply that pain and depression share common biological mechanisms. (trial registration: https://www. Clinicaltrials: gov: NCT03328819).
Article
When it comes to antidepressant medications - popular, backbone drugs of modern psychiatry - even learned scholars and savvy clinicians find it difficult to separate honest, rigorous research from that which thrives on hidden agendas and ulterior motives. Fortunately, a mounting corpus of data-based studies, mostly meta-analyses, casts new and critical light on the clinical efficacy, side effects, and therapeutic outcomes of antidepressants. Spearheading these efforts over the past few decades, Irving Kirsch and colleagues have challenged the hegemonic view of antidepressants as an effective therapeutic intervention. Notably, Kirsch illuminates the small difference between antidepressants and placebos in mitigating depression-a difference that may be statistically significant yet fails to reach clinical significance. This piece sketches the important contributions Kirsch has made to the scientific understanding of antidepressant medications.
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Background Early prediction of high depressive symptoms is crucial for selective intervention and the minimization of functional impairment. Recent cross-sectional studies indicated decision-making deficits in depression, which may be an important contributor to the disorder. Our goal was to test whether description- and experience-based decision making, two major neuroeconomic paradigms of decision-making under uncertainty, predict future depressive symptoms in young adults. Methods One hundred young adults performed two decision-making tasks, one description-based, in which subjects chose between two gambling options given explicitly stated rewards and their probabilities, and the other experience-based, in which subjects were shown rewards but had to learn the probability of those rewards (or cue-outcome contingencies) via trial-and-error experience. We evaluated subjects' depressive symptoms with BDI-II at baseline (T1) and half a year later (T2). Results Comparing subjects with low versus high levels of depressive symptoms at T2 showed that the latter performed worse on the experience- but not description-based task at T1. Computational modeling of the decision-making process suggested that subjects with high levels of depressive symptoms had a more concave utility function, indicating enhanced risk aversion. Furthermore, a more concave utility function at T1 increased the odds of high depressive symptoms at T2, even after controlling depressive symptoms at T1, perceived stress at T2, and several covariates (OR = 0.251, 95% CI [0.085, 0.741]). Conclusions This is the first study to demonstrate a prospective link between experience-based decision-making and depressive symptoms. Our results suggest that enhanced risk aversion in experience-based decision-making may be an important contributor to the development of depressive symptoms.
Article
Background: Fluoxetine was approved for depression in children and adolescents based on two placebo-controlled trials, X065 and HCJE, with 96 and 219 participants, respectively. Objective: To review these trials, which appear to have been misreported. Methods: Systematic review of the clinical study reports and publications. The primary outcomes were the efficacy variables in the trial protocols, suicidal events, and precursors to suicidality or violence. Results: Essential information was missing and there were unexplained numerical inconsistencies. (1) The efficacy outcomes were biased in favour of fluoxetine by differential dropouts and missing data. The efficacy on the Children's Depression Rating Scale-Revised was 4% of the baseline score, which is not clinically relevant. Patient ratings did not find fluoxetine effective. (2) Suicidal events were missing in the publications and the study reports. Precursors to suicidality or violence occurred more often on fluoxetine than on placebo. For trial HCJE, the number needed to harm was 6 for nervous system events, 7 for moderate or severe harm, and 10 for severe harm. Fluoxetine reduced height and weight over 19 weeks by 1.0 cm and 1.1 kg, respectively, and prolonged the QT interval. Conclusions: Our reanalysis of the two pivotal trials showed that fluoxetine is unsafe and ineffective.
Article
Background: Antidepressant medications are suggested as the first-line treatment in patients with major depressive disorder (MDD). However, the drug therapy outcomes vary from person to person. The functional activity of the brain and DNA methylation levels correlate with the antidepressant efficacy. To predict the early antidepressant responses in MDD and establish the prediction framework, we aimed to apply multidimensional data based on the resting-state activity of the brain and HTR1A/1B methylation. Methods: The values of Amplitude of Low-Frequency Fluctuations (ALFF) and regional homogeneity (ReHo) were measured as variables in 116 brain regions along with 181 CpG sites in the promoter region of HTR1A/1B and 11 clinical characteristics. After performing the feature reduction step using the least absolute shrinkage and selection operator (LASSO) method, the selected variables were put into Support Vector Machines (SVM), Random Forest (RF), Naïve Bayes (NB), and logistic regression (LR), consecutively, to construct the prediction models. The models' performance was evaluated by the Leave-One-Out Cross-Validation. Results: The LR model composed of the selected multidimensional features reached a maximum performance of 78.57% accuracy and 0.8340 area under the ROC curve (AUC). The prediction accuracies based on multidimensional datasets were found to be higher than those obtained from the data based only on fMRI or methylation. Limitations: A relatively small sample size potentially restricted the usage of our prediction framework in clinical applications. Conclusion: Our study revealed that combining the data of brain imaging and DNA methylation could provide a complementary effect in predicting early-stage antidepressant outcomes.
Article
Objective: To explore the effect of cognitive behavior oriented psychological intervention on the psychological status of depressed facial acne scar patients receiving fractional photothermolysis. Methods: The study enrolled 48 depressed facial acne scar patients who received treatment at our hospital between May 2018 and May 2021. They were randomized to the control group and the fractional photothermolysis group with 24 patients in each group using the random number table method. They received nursing intervention and cognitive behavior-oriented psychological intervention, respectively. Results: The Hamilton Anxiety and Hamilton Depression scores were lower after intervention than before intervention in both groups, and the fractional photothermolysis group had lower Hamilton Anxiety and Hamilton Depression scores than the control group (P < 0.05). The interpersonal sensitivity had hostility and phobic anxiety scores were lower after 12 weeks of treatment than before intervention in both groups, and the fractional photothermolysis group had lower interpersonal sensitivity hostility and phobic anxiety scores than the control group (P < 0.05). The H, M, V, and P scores after 12 weeks of intervention were both lower in the 2 groups than those before intervention. The humanistic care quality of service nursing care and health education scores were lower after intervention before intervention in both groups and the fractional photothermolysis group had significantly lower humanistic care quality of service nursing care and health education scores than the control group (P < 0.05). Conclusions: Cognitive behavior-oriented psychological intervention can effectively improve the psychological status and psychological health of depressed facial acne scar patients receiving fractional photothermolysis.
Article
Background Exploratory eye movements (EEMs) and P300 are often used to facilitate the clinical diagnosis of depression. However, There were few studies using the combination of EEMs and P300 to build a model for detecting depression and predicting a curative effect. Methods Sixty patients were recruited for 2 groups: high frequency repetitive transcranial magnetic stimulation(rTMS) combined with paroxetine group and simple paroxetine group. Clinical efficacy was evaluated by the Hamilton Depression scale-24(HAMD-24), EEMs and P300. The classification model of the auxiliary diagnosis of depression and the prediction model of the two treatments were developed based on a machine learning algorithm. Results The classification model with the greatest accuracy for patients with depression and healthy controls was 95.24% (AUC = 0.75, recall = 1.00, precision = 0.95, F1-score = 0.97). The root mean square error (RMSE) of the model for predicting the efficacy of high frequency rTMS combined with paroxetine was 3.54 (MAE [mean absolute error] = 2.56, R² = -0.53). The RMSE of the model for predicting the efficacy of paroxetine was 4.97 (MAE = 4.00, R² = -0.91). Conclusion Based on the machine learning algorithm, P300 and EEMs data was suitable for modeling to distinguish depression patients and healthy individuals. However, it was not suitable for predicting the efficacy of high frequency rTMS combined with paroxetine or to predict the efficacy of paroxetine.
Article
Background Acupuncture is considered as an effective alternative treatment for post-stroke depression because of its low side effects and easy availability. However, it usually depends on the skills and experience of doctors to choose which acupuncture methods for specific parts. This study compared the effectiveness of different frequently-used acupuncture methods for specific parts in treating post-stroke depression patients by using network meta-analysis. Methods We searched eight databases including China National Knowledge Infrastructure (CNKI) database, Wanfang database, Chinese Biomedical Database (CBM), VIP Chinese Science, the Cochrane Library, Embase, PubMed and Web of Science from the date of database inception to November 29, 2020 to identify eligible RCTs. The trial registers in ClinicalTrials.gov, World Health Organization, and Cochrane trials were searched as a supplement. The effective rate was extracted from the included RCTs as primary outcomes after screening. The network meta-analysis was performed by Review Manager 5.3, Stata14.0, and R 3.6.3. Results 51 studies were included, which contained 3966 participants among 12 interventions. Based on the ranking probability, scalp acupuncture plus conventional acupuncture was considered to be the most effective method, followed by auricular acupuncture, eye acupuncture, eye acupuncture plus drug, auricular acupuncture plus drug, auricular acupuncture plus conventional acupuncture, scalp acupuncture, scalp acupuncture plus drug, abdominal acupuncture, conventional acupuncture plus drug, drug, conventional acupuncture. Conclusions 12 acupuncture methods may be effective and safe in improving the condition of patients with PSD. Higher quality randomized controlled trials need sufficient evidence because the overall quality of included trials can only be classified as low quality. This study is registered with PROSPERO (CRD42020177099).
Article
Background: Four ablative neurosurgical procedures are used in the treatment of refractory psychiatric illness. The long-term effects of these procedures on psychiatric symptoms across disorders has never been synthesised and meta-analysed. Methods: A preregistered systematic review was performed on studies reporting clinical results following ablative psychiatric neurosurgery. Four possible outcome measures were extracted for each study: depression, obsessive-compulsive symptoms, anxiety and clinical global impression. Effect sizes were calculated using Hedge's g. Equipercentile linking was used to convert symptom scores to a common metric. The main outcome measures were the magnitude of improvement in depression, obsessive compulsive symptoms, anxiety and clinical global impression. The secondary outcome was a subgroup analysis comparing the magnitude of symptom changes between the four procedures. Results: Of 943 articles, 43 studies reporting data from 1414 unique patients, were included for pooled effects estimates with a random-effects meta-analysis. Results showed that there was a large effect size for improvements in depression (g=1.27; p<0.0001), obsessive-compulsive symptoms (g=2.25; p<0.0001) and anxiety (g=1.76; p<0.0001). The pooled clinical global impression improvement score was 2.36 (p<0.0001). On subgroup analysis, there was only a significant degree of heterogeneity in effect sizes between procedure types for anxiety symptoms, with capsulotomy resulting in a greater reduction in anxiety than cingulotomy. Conclusions: Contemporary ablative neurosurgical procedures were significantly associated with improvements in depression, obsessive-compulsive symptoms, anxiety and clinical global impression. Prospero registration number: CRD42020164784.
Article
Electroconvulsive Therapy's (ECT) use and place in treatment guidelines varies worldwide with a primary indication of depression in Western countries and acute psychosis in Asian countries. There is sparse evidence about the relative effectiveness of ECT among different indications that may account for this discrepancy. We aimed to compare the clinical global impression of disease severity, cognitive change, subjective quality of life (QoL) and global functioning after ECT given for treatment of the indications of acute psychosis, mania, depression, psychotic depression and catatonia. We conducted a retrospective naturalistic cohort study with post-hoc analyses of patients’ ECT registry data from 2017 to 2019. 691 patients were assessed before and after 6 sessions of ECT treatment, using the Clinical Global Impression-Improvement and Severity (CGI-I and CGI-S) scale, Montreal Cognitive Assessment (MoCA), Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), EQ-5D utility score and Global Assessment of Functioning (GAF) scale. The pre-ECT vs post-ECT clinical assessment change scores were compared within and across the five indications. For each indication, there were large improvements in clinical global impression of disease severity, QoL and global functioning. There were no significant changes in MoCA score for most indications except for an improvement in patients with schizophrenia. ECT is a rapidly acting and effective acute treatment across several severe mental illnesses with large improvements in symptoms, QoL and global functioning.
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Objective: To provide additional understanding of the clinical significance of Attention-Deficit/Hyperactivity Disorder Rating Scale, Version IV (ADHD-RS-IV) total and change scores in relation to Clinical Global Impressions-Severity or -Improvement (CGI-S/-I) levels. Methods: Using two similarly designed pivotal trials of lisdexamfetamine dimesylate (Vyvanse, Shire US Inc), equipercentile linking was used to identify scores on the ADHD-RS-IV and CGI that have the same percentile rank. Results: As assessed by CGI-S levels, moderately, markedly, severely, and extremely ill adults had mean (SD) baseline ADHD-RS-IV scores of 36.2 (4.9), 42.1 (6.1), 45.4 (5.1), and 53.0, respectively. A similar relationship was observed in children. At endpoint, children categorized as minimally, much, or very much improved by CGI-I demonstrated mean (SD) ADHD-RS-IV changes from baseline of -9.9 (6.8), -25.5 (7.2), and -33.2 (9.3), respectively. Adults demonstrated a similar relationship between ADHD-RS-IV change scores and CGI-I ratings. Based on equipercentile link function, a change from baseline in ADHD-RS-IV total score of ∼10-15 points or 25% to 30% corresponded to a change of 1 level in CGI-I score. Conclusion: This analysis makes possible the establishment of a clinical impression of severity of illness from total ADHD-RS-IV scores and may facilitate the clinical interpretation of improvement of ADHD-RS-IV change scores.
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This article presents a SAS program that uses equipercentile equating to derive equated scores on two test forms. The program uses the SAS MACRO language to process multiple iterations of equatiing for multiple tests in an automated manner. The output consists of equated forms for X and Y for any two tests.
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The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inner-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
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The Hamilton Depression Rating Scale has been the gold standard for the assessment of depression for more than 40 years. Criticism of the instrument has been increasing. The authors review studies published since the last major review of this instrument in 1979 that explicitly examine the psychometric properties of the Hamilton depression scale. The authors' goal is to determine whether continued use of the Hamilton depression scale as a measure of treatment outcome is justified. MEDLINE was searched for studies published since 1979 that examine psychometric properties of the Hamilton depression scale. Seventy studies were identified and selected, and then grouped into three categories on the basis of the major psychometric properties examined-reliability, item-response characteristics, and validity. The Hamilton depression scale's internal reliability is adequate, but many scale items are poor contributors to the measurement of depression severity; others have poor interrater and retest reliability. For many items, the format for response options is not optimal. Content validity is poor; convergent validity and discriminant validity are adequate. The factor structure of the Hamilton depression scale is multidimensional but with poor replication across samples. Evidence suggests that the Hamilton depression scale is psychometrically and conceptually flawed. The breadth and severity of the problems militate against efforts to revise the current instrument. After more than 40 years, it is time to embrace a new gold standard for assessment of depression.
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To understand what given scores of the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) mean from a clinical point of view is important for the translation of research results into practice. We therefore (a) compared the absolute change of the BPRS/PANSS with the Clinical Global Impressions Ratings (CGI) -improvement score and the change of the CGI severity score, (b) analyzed whether the severity of illness at baseline had an impact on the latter association, and (c) attempted to replicate previous BPRS findings using a completely different data set based upon the PANSS-derived BPRS. The method used was equipercentile linking of BPRS and CGI ratings from 14 drug trials in acutely ill patients with schizophrenia (n=5970). An absolute reduction of the BPRS/PANSS by approximately 10/15 points corresponded to a CGI change of 'minimally improved' and to a change of the CGI severity score by one severity step. However, the latter associations depended on the severity of symptoms at baseline. Less severely ill patients required less BPRS/PANSS total score reduction to achieve the same CGI-improvement score than more severely ill patients. This effect of initial severity was attenuated using percentage rather than absolute BPRS/PANSS reduction scores. The linking analysis between the absolute BPRS/PANSS reduction and the CGI may have an implication for the interpretation of efficacy differences found in clinical trials, and for sample size estimations. Clinicians seem to base CGI ratings on relative change rather than on absolute change of symptoms.
Article
Background: The potential inclusion of cognitive assessments in the DSM-V and large time-consuming assessments drive a need for short tests of cognitive impairments. We examined the reliability and validity of a brief, 15-minute, version of the Wechsler Adult Intelligence Scale-III (WAIS-III). Methods: The sample consisted of patients diagnosed with schizophrenia (n=75), their siblings without schizophrenia (n=74) and unrelated healthy controls (n=84). A short WAIS-III consists of the Digit Symbol Coding subtest, and every second (or third) item of Block Design, Information, and Arithmetic. Psychometric analyses were implemented using item-response theory (IRT) to determine the best minimal item short version, while maintaining the sensitivity and reliability of the IQ score. Results: The proposed 15-minute WAIS-III gave reliable estimates of the Full Scale IQ (FSIQ) in all three groups in the sample. The 15-minute (select-item) version yielded an overall R of.95 (R(2)=.92) and IRT yielded an R of .96 (R(2)=.92). All four subtests performed well in differentiating patients, relatives, and healthy controls. Multivariate analysis showed a significant difference in FSIQ-estimate between patients, relatives, and healthy controls, F(2, 202) = 19.00, p < .0001. Regression modelling showed that the three versions of the WAIS had similar associations with functional outcome after a 3-year follow-up. Conclusions: Our proposed 15-minute version of the WAIS may serve as a useful screening device for general intellectual ability in research or clinical settings, and is recommended when a quick and accurate IQ estimate is desired.
Article
The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inter-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
Article
There is concern over the methods used to evaluate antipsychotic drugs. To assess the clinical relevance of findings in the literature. A systematic review identified studies of antipsychotics that used the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS). A published method of translating these into Clinical Global Impression - Change scale (CGI-C) scores was used to measure clinical relevance. In total 98 data-sets were included in the BPRS analysis and 202 data-sets in the PANSS analysis. When aggregated scores were translated into notional CGI-C scores, most drugs reached 'minimal improvement' on the BPRS, but few reached that level for PANSS. This was true of both first- and second-generation drugs, including clozapine. Amisulpride and olanzapine had better than average CGI-C scores. Our findings show improvements of limited clinical relevance. The CGI-C scores were better for the BPRS than for the PANSS.
Article
Assessment of depression severity is of key importance, since several clinical guidelines recommend choice of treatment dependent on the depression severity grade. Using different tools to assess baseline severity may result in different outcomes. This paper describes the results of a multicentre, naturalistic study investigating the relationship between depression symptom severity (using 4 different measures of symptom severity) and clinical outcome among patients hospitalised for depression (N=1 014). Moreover, the impact of differences between methods of measuring depression severity has been investigated. Statistical analyses (univariate measurements, logistic regression models) were conducted to detect coherences and differences between the various methods of severity categorisation. Results revealed different associations between outcome and classification methods. Response or remission rates varied if baseline severity was assessed by different instruments. Moreover, the number of responders increased with higher baseline severity grades of depression, whereas the number of remitters decreased. Additional analyses dependent on outcome criteria using continuous instead of categorical data revealed similar results. Baseline severity may be only one of many other important clinical variables that mediate clinical outcome, but it is surely an important one deserving further research and consideration.
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Incl. bibliographical references, index
Article
Remission and response were suggested as the most relevant outcome criteria for the treatment of depression. There is still marked uncertainty as to what cut-offs should be used on current depression rating scales. The goal of the present study was to compare the validity of different HAMD, MADRS and BDI cut-offs for response and remission. The naturalistic prospective study was performed in 12 psychiatric hospitals in Germany. All evaluable patients (n=846) were hospitalized and had to meet DSM-IV criteria for major depressive disorder. Biweekly ratings were assessed using HAMD-21, MADRS and BDI. A CGI-S score of 1 and a CGI-I score of at least 2 was used as the primary comparative measure of remission and response, respectively. A HAMD-21 cut-off ≤7 (AUC: 0.92), HAMD-17 cut-of ≤6 (AUC: 0.90), MADRS cut-off ≤7 (AUC: 0.94) and BDI cut-off ≤12 (AUC: 0.83) were associated with a maximum of specificity and sensitivity for defining remission. A minimum decrease of 47% of the HAMD-21 (AUC: 0.90), ≤57% for HAMD-17 (AUC: 0.89), ≤ 46% for MADRS (0.91) and a decrease of 47% for the BDI baseline score (AUC: 0.78) best corresponded CGI response criteria. Our data largely confirmed currently used remission and response criteria in naturalistically treated patients.
Article
To review and make recommendations for the definition and presentation of the terms 'response' and 'remission' in schizophrenia. Selective review of publications on definitions of response and remission in schizophrenia. When the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) are used for definitions of response, a cut-off of at least 50% reduction of the baseline score should be used for acutely ill, non-refractory patients and a cut-off of at least 25% reduction for refractory patients. When percentage BPRS/PANSS reduction is calculated, the 18/30 points minimum scores meaning 'no symptoms' on the should be subtracted. In addition, responder rates from 0-100% could be presented in a table in steps of 25%. For large and simple practical trials, the Clinical Global Impression scale with suggested improvements could be used 1-7 scale. To show how many patients are still symptomatic at the end of study and to show the overall amount of change in both remission and responder criteria should be presented.
Article
The Panic Disorder Severity Scale (PDSS) is promising to be a standard global rating scale for panic disorder. In order for a clinical scale to be useful, we need a guideline for interpreting its scores and their changes, and for defining clinical change points such as response and remission. We used individual patient data from two large randomized controlled trials of panic disorder (total n=568). Study participants were administered the PDSS and the Clinical Global Impression (CGI)--Severity and --Improvement. We applied equipercentile linking technique to draw correspondences between PDSS and CGI-Severity, numeric changes in PDSS and CGI-Improvement, and percent changes in PDSS and CGI-Improvement. The interpretation of the PDSS total score differed according to the presence or absence of agoraphobia. When the patients were not agoraphobic, score ranges 0-1 corresponded with "Normal," 2-5 with "Borderline," 6-9 with "Slightly ill," 10-13 with "Moderately ill," and 14 and above with "Markedly ill." When the patients were agoraphobic, score ranges 3-7 meant "Borderline ill," 8-10 "Slightly ill," 11-15 "Moderately ill," and 16 and above "Markedly ill." The relationship between PDSS change and CGI-Improvement was more linear when measured as percentile change than as numeric changes, and was indistinguishable for those with or without agoraphobia. The decrease by 75-100% was considered "Very much improved," that by 40-74% "Much improved," and that by 10-39% "Minimally improved." We propose that "remission" of panic disorder be defined by PDSS scores of five or less and its "response" by 40% or greater reduction.
Article
The Global Assessment Scale (GAS) is a rating scale for evaluating the overall functioning of a subject during a specified time period on a continuum from psychological or psychiatric sickness to health. In five studies encompassing the range of population to which measures of overall severity of illness are likely to be applied, the GAS was found to have good reliability. GAS ratings were found to have a greater sensitivity to change over time than did other ratings of overall severity or specific symptom dimensions. Former inpatients in the community with a GAS rating below 40 had a higher probability of readmission to the hospital than did patients with higher GAS scores. The relative simplicity, reliability, and validity of the GAS suggests that it would be useful in a wide variety of clinical and research settings.
Article
In 1988, the MacArthur Foundation Research Network on the Psychobiology of Depression convened a task force to examine the ways in which change points in the course of depressive illness had been described and the extent to which inconsistency in these descriptions might be impeding research on this disorder. We found considerable inconsistency across and even within research reports and concluded that research on depressive illness would be well served by greater consistency in the definition change points in the course of illness. We propose an internally consistent, empirically defined conceptual scheme for the terms remission, recovery, relapse, and recurrence. In addition, we propose tentative operational criteria for each term. Finally, we discuss ways to assess the usefulness of such operational criteria through reanalysis of existing data and the design and conduct of new experiments.
Article
This is an account of further work on a rating scale for depressive states, including a detailed discussion on the general problems of comparing successive samples from a ‘population’, the meaning of factor scores, and the other results obtained. The intercorrelation matrix of the items of the scale has been factor-analysed by the method of principal components, which were then given a Varimax rotation. Weights are given for calculating factor scores, both for rotated as well as unrotated factors. The data for 152 men and 120 women having been kept separate, it is possible to compare the two sets of results. The method of using the rating scale is described in detail in relation to the individual items.
Article
Multiple definitions have been used to characterize the outcome of treatments for depression. Beyond the simple criterion of a statistically significant improvement in depression rating scale scores, researchers have had to use more clinically relevant categorical outcomes: response (without remission), remission, nonresponse, partial response, relapse, recurrence, recovery, and, more recently, depressive breakthrough. This article reviews the definitions of these terms and their relevance for the study of treatment-resistant depression.
Article
To compare the effects and side effects of low dosage tricyclic antidepressants with placebo and with standard dosage tricyclics in acute phase treatment of depression. Systematic review of randomised trials comparing low dosage tricyclics (< or =100 mg/day) with placebo or with standard dosage tricyclics in adults with depression. Relative risk of response in depression (random effects model), according to the original authors' definition but usually defined as 50% or greater reduction in severity of depression. Relative risks of overall dropouts and dropouts due to side effects. 35 studies (2013 participants) compared low dosage tricyclics with placebo, and six studies (551 participants) compared low dosage tricyclics with standard dosage tricyclics. Low dosage tricyclics, mostly between 75 and 100 mg/day, were 1.65 (95% confidence interval 1.36 to 2.0) and 1.47 (1.12 to 1.94) times more likely than placebo to bring about response at 4 weeks and 6-8 weeks, respectively. Standard dosage tricyclics failed, however, to bring about more response but produced more dropouts due to side effects than low dosage tricyclics. Treatment of depression in adults with low dose tricyclics is justified. However, more rigorous studies are needed to definitively establish the relative benefits and harms of various dosages.
Article
Despite the frequent use of the Positive and Negative Syndrome Scale (PANSS) for rating the symptoms of schizophrenia, the clinical meaning of its total score and of the cut-offs that are used to define treatment response (e.g. at least 20% or 50% reduction of the baseline score) are as yet unclear. We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions (CGI). PANSS and CGI ratings at baseline (n = 4091), and after one, two, four and six weeks of treatment taken from a pooled database of seven pivotal, multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking. Being considered "mildly ill" according to the CGI approximately corresponded to a PANSS total score of 58, "moderately ill" to a PANSS of 75, "markedly ill" to a PANSS of 95 and severely ill to a PANSS of 116. To be "minimally improved" according to the CGI score was associated with a mean percentage PANSS reduction of 19%, 23%, 26% and 28% at weeks 1, 2, 4 and 6, respectively. The corresponding figures for a CGI rating "much improved" were 40%, 45%, 51% and 53%. The results provide a better framework for understanding the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations. Such studies may ideally use at least a 50% reduction from baseline cut-off to define response rather than lower thresholds. In treatment resistant populations, however, even a small improvement can be important, so that a 25% cut-off might be appropriate.
Article
Two scales of the Clinical Global Impressions (CGI) Scale are frequently used in antidepressant trials. No research has systematically addressed how CGI change compares to change on established measures such as the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale, or Beck Depression Inventory. The current meta-analysis examined 75 antidepressant trials in which the CGI was used along with at least one other popular depression measure. The CGI-Severity scale was significantly more conservative than the HAM-D in rating change in double-blind trials, but not in open trials. The Beck Depression Inventory was significantly more conservative than the CGI-Severity. The CGI-Improvement scale was significantly more liberal than the HAM-D or Montgomery-Asberg Depression Rating Scale. Rater bias or scale content may explain differences between measures. Given the often substantial differences between instruments, researchers should use a variety of measures rather than relying on any single tool in assessing treatment response.
Article
Scale-derived cutoff points are frequently used to define 'response' in antipsychotic drug trials. This procedure is useful, because responder rates can be understood more intuitively than a difference in means of rating scales. As various definitions of response have been used, we examined original participant data to assess whether the choice of the Brief Psychiatric Rating Scale-based response cutoff had an impact on the results of seven (n=1870) antipsychotic drug trials in schizophrenia. We also analyzed whether the chronicity of the illness has an impact on the question of which cutoff is most sensitive in detecting differences between drugs. The results in terms of p-values and response rate differences varied substantially in dependence on the cutoff chosen. The use of response rate ratios attenuated the variability. In contrast to a widely held belief, low response cutoffs were not more sensitive in detecting differences between drugs than higher cutoffs. In more chronic, less responsive participants, there was a trend for higher cutoffs to be less sensitive in detecting differences between drugs than lower ones. The results of clinical trials depend considerably on the response cutoff chosen. Therefore, the cutoff should never be chosen post hoc, a large range of cutoffs should be presented and the a priori choice of the primary cutoff should be based on clinical relevance. The use of ratios rather than differences attenuates the variability. Cutoffs need to be calculated on the basis of 0-6 rather than on 1-7 scoring systems. We suggest a table presenting responder rates in 25 percent steps covering the whole range up to 100% reduction from baseline, which could be displayed together with recently presented criteria for remission.
Article
Research based on pooling data from clinical trials suggests that it is possible to extrapolate from a CGI-S to a PANSS severity score and from the CGI-I to a PANSS percentage change score. This research has not been replicated nor examined in individual trials. This study aims to examine the feasibility of extrapolation from the CGI to the PANSS across and within 4 large clinical trials of antipsychotic medication. Equipercentile linking is used to examine extrapolation (a) from CGI-S to PANSS severity ratings and (b) from CGI-I to PANSS percentage change (n=2698). Linking is conducted at baseline and after 2, 4, 6 and 8 weeks of treatment from ITT clinical trial participants with schizophrenia. Across weeks 2, 4, 6 and 8, being considered 'not ill' according to the CGI-S corresponded to PANSS scores of 31-2. The relationship between the CGI-S and the PANSS followed an increasing trend, such that 'very mild' corresponded with 41-7, 'mild' corresponded with 55-62, 'moderate' corresponded with 71-7, 'marked' corresponded with 88-94, 'severe' corresponded with 105-110, and 'extremely severe' corresponded with 126-134. The relationship between CGI-I ratings and percentage change followed a linear trend, such that 'very much improved' corresponded to PANSS percentage change scores from 79 to 75, 'much improved' corresponded with 45 to 49, 'minimally improved' corresponded with 21 to 23, 'unchanged' corresponded with 2 to 3, 'minimally worse' corresponded with -15 to -20, 'much worse' corresponded with -44 to -51. Generally, within the trials the cut-off ranges identified overlapped within around 10 points of those found in the pooled analysis. Despite trial heterogeneity, the results support the extrapolation from the CGI-I to PANSS percentage change. Extrapolation of the CGI-S to the PANSS is observed, except in the case of severe symptomatology which is rare. Collectively, the results support the extrapolation between the PANSS and CGI.
QUIPERCENT: A SAS program for calculating equivalent scores using the quipercentile method Concordance between measures of functioning, symptoms, and change examining the
  • L R Price
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Price, L.R., Lurie, A., Wilkins, C., 2001. QUIPERCENT: A SAS program for calculating equivalent scores using the quipercentile method. Applied Psychological Measurement 25, 332. Rabinowitz, J., Levine, S., Martinez, G., 2010. Concordance between measures of functioning, symptoms, and change examining the GAF, CGI-S, CGI-C, and PANSS. Journal of Clinical Psychopharmacology 30, 478–480.
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Washington, DC, APA. American Psychiatric Association, 1987. Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-III-R).
A total of 7131 patients participated in the examined studies (2733/38.4% males; 4393/61.6% females; mean age
  • ( Dsm
  • Dsm Iii-R Iii
  • Dsm Iv
(DSM) III, DSM III-R or DSM IV criteria (American Psychiatric Association, 1980, 1987, 1994). A total of 7131 patients participated in the examined studies (2733/38.4% males; 4393/61.6% females; mean age (standard deviation (SD)): 45.4 (14.7) years; mean weight (SD):