Article

Efficacy and Cost-Effectiveness of Intensive Short-Term Dynamic Psychotherapy for Treatment Resistant Depression: 18-Month Follow-Up of The Halifax Depression Trial

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Abstract

Background : Depressed patients with chronic and complex health issues commonly relapse; therefore, examining longer-term outcomes is an important consideration. For treatment resistant depression (TRD), the post-treatment efficacy of time-limited Intensive Short-Term Dynamic Psychotherapy (ISTDP) has been demonstrated but longer-term outcomes and cost-effectiveness are unclear. Method : In this superiority trial, 60 patients referred to Community Mental Health Teams (CMHT) were randomised to 2 groups (ISTDP=30 and CMHT=30). The primary outcome was Hamilton Depression Rating scale (HAM-D) scores at 18 months. Secondary outcomes included Patient Health Questionnaire (PHQ-9) depression scores and dichotomous measure remission. A health economic evaluation examined mental health costs with quality-adjusted life years (QALYs). Results : Statistically significant treatment differences in depression previously found at 6 months favouring ISTDP were maintained at 18-month follow-up. Group differences in depression were in the moderate to large range on both the observer rated (Cohen's d = .64) and self-report measures (Cohen's d = .70). At 18 months follow-up the remission rate in ISTDP patients was 40.0%, and 23.4% had discontinued antidepressants. Health economic analysis suggests that ISTDP was more cost-effective than CMHT at 18 months. Probabilistic analysis suggests that there is a 64.5% probability of ISTDP being cost-effective at a willingness to pay for a QALY of $25,000 compared to CMHT at 18 months. Limitations : Replication of these findings is necessary in larger samples and future cost analyses should also consider indirect costs. Conclusions : ISTDP demonstrates long-term efficacy and cost-effectiveness in TRD.

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... It has also developed an award-winning service using ISTDP to treat emergency department patients with recurrent visits for somatic symptoms (Abbass et al., 2009). This method has also been shown to be efficacious for complex and refractory populations (Abbass, 2016;Town et al., 2017Town et al., , 2020, and cost effective (Abbass & Katzman, 2013;Abbass et al., 2015;Town et al., 2020). Despite these successes and large clinical demand from both mental health and medical services, this specialty service is chronically under-resourced while the province focuses on CBT training. ...
... It has also developed an award-winning service using ISTDP to treat emergency department patients with recurrent visits for somatic symptoms (Abbass et al., 2009). This method has also been shown to be efficacious for complex and refractory populations (Abbass, 2016;Town et al., 2017Town et al., , 2020, and cost effective (Abbass & Katzman, 2013;Abbass et al., 2015;Town et al., 2020). Despite these successes and large clinical demand from both mental health and medical services, this specialty service is chronically under-resourced while the province focuses on CBT training. ...
... There is no strategy to assess who is already treatment refractory on initial assessment. In a randomized controlled trial in the province for treatment resistant depression, only 3.7% and 28% of mental health team patients were able to achieve remission on the HAM-D in the first six and 12 months respectively, while providing medication increases for most and an average 16 sessions of mainly CBT: in comparison ISTDP yielded 36% and 40% HAM-D remissions even while reducing medications after an average of 16 sessions (Town et al., 2017(Town et al., , 2020. This finding adds to evidence that PDT methods can be effective for complex and refractory populations (Abbass, 2016;Leichsenring & Rabung, 2011) and should be considered in treatment guidelines (McPherson et al., 2018). ...
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In this article, Canadian psychotherapy researchers and teachers review the state of psychodynamic therapy (PDT) in Canada. We review the ways in which PDT has been implemented, developed and researched within the public and private sector, and how psychoanalytic and psychodynamic practitioners regionally have responded to the challenges of evidence-based practice and the emphasis on empirically supported treatments (EST) as it is defined today. We note that neglect and misrepresentation of the scientific evidence behind PDT has resulted in its marginalization. There is also a dearth of evidence collected to measure the effectiveness of implementing EST. Based on its empirical standing, we propose a model of care that incorporates PDT as an effective, evidence-based model for first line treatment, and also as an alternative for those patients who do not respond to other treatments or who express a preference for PDT or insight-oriented therapy.
... Meta-analytic studies on psychodynamic psychotherapy have shown that patients maintained their therapeutic gains in both general symptoms and interpersonal functioning (Abbass et al., 2012;Town et al., 2020). Ellison et al. (2009) reported 6-and 18-months follow-up of experiential therapies, both emotion-focused and client-centered, for depression. ...
... Overall, present findings support the long-term effectiveness of AEDP at 6-and 12-month follow-up. These results showing the long-term effectiveness of AEDP are consistent with the long-term effectiveness of other experiential and psychodynamic psychotherapies, such as emotion focused therapy (EFT) for depression (Ellison et al., 2009), and short-and long-term psychodynamic psychotherapy for a variety of psychological issues (Abbass et al., 2012;Town et al., 2022), including treatment-resistant depression (Town et al., 2020). The results are also comparable with the long-term effectiveness of cognitive behavioral therapy (CBT; Karyotaki et al., 2016). ...
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Accelerated experiential dynamic psychotherapy (AEDP; Fosha, 2000, 2021b) is an integrative, healing-oriented, mind-body, affect-focused therapy. A posttreatment outcome study demonstrated AEDP's effectiveness (Iwakabe et al., 2020) on a variety of measures of psychological functioning. This study sought to address AEDP's long-term effectiveness. As previously reported, 63 adult patients completed a 16-session AEDP treatment with qualified therapists in private practice in the United States, Canada, Israel, Japan, and Sweden. Forty patients responded to 6-month follow-up and 52 responded to 12-month follow-up. Results indicate that patients maintained their posttreatment therapeutic gains, both 6 and 12 months later. Large effect sizes (d = 0.74 to d = 1.60) both for reductions on measures of psychopathology (e.g., depression, negative automatic thoughts, experiential avoidance) and improvements on measures of positive mental health (e.g., well-being, self-compassion) were obtained. Patients with more pervasive and severe problems tended to have larger effect sizes (all ds > 1.0) and a larger proportion of them achieved clinically significant change over 6 and 12 months than patients with subclinical symptomatology. Piecewise growth modeling was used to confirm these results, with attrition over the follow-up period taken into account. Consistent with the above findings, piecewise growth modeling similarly showed that patients significantly improved from pre- to posttreatment and maintained gains from posttreatment through the 6- and 12-month follow-up. These results provide empirical support for the long-term effectiveness of AEDP for alleviating a variety of psychological problems and enhancing positive functioning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
... When the attachment system and associated affects are triggered in later relationships, the individual may resort to a type of maladaptive coping leading to symptom formation (i.e., depression) and relational difficulties (Lilliengren et al., 2016). There are clear indications that psychodynamic psychotherapy is effective in treating depression in general (Driessen, Cuijpers, de Maat, et al., 2010;Driessen et al., 2013;Leichsenring et al., 2015), and CD sin particular (Town et al., 2020;Town, Abbass, Stride, & Bernier, 2017). Although more high standard trials are needed, psychodynamic treatments are recommended as a viable option in treating CD (Jobst et al., 2016). ...
... Our finding may provide indirect support of this assertion in the sense that since our treatment provided more relief for the severely distressed, it seems to have been effective in addressing the specific problems of the disorders in our sample. Moreover, that severely depressed patients benefitted more than moderately depressed patients also supports prior findings that psychodynamic treatment may be especially suited to address chronic depression (Town et al., 2020;Town et al., 2017). ...
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Research indicates combination of psychotherapy and antidepressant medication (ADM) provide cumulative effects and thus outperforms monotherapy in treating chronic depression. In this quasi‐experimental study, we explored symptom change for patients with chronic depression treated with ADM when presenting for a 12‐week psychotherapeutic inpatient treatment program. We compared outcomes through treatment and follow‐up of patients who continued medication with those who discontinued. We also tested possible moderator effects of initial depression severity on change between the groups. Based on prior research, we hypothesized that combination treatment would yield better results (i.e., more reduction in depression). Patients (N=112) were referred from general practitioners or local secondary health care. Outcome was measured by Beck Depression Inventory‐II (BDI‐II) and comparisons were carried out using multi‐level modelling. While 35 patients discontinued ADM during treatment, 77 continued. Both continuers and discontinuers had a significant treatment effect that was maintained at one‐year follow up. There was no difference in outcome between continuers and discontinuers of ADM. Patients with severe depression had significantly more symptom improvement than patients with moderate depression, but depression severity did not affect outcomes across continuers and discontinuers of ADM differently. The results could indicate that patients had developed resistance and/or tolerance to the prophylactic effects of medication and that ADM did not contribute to the reduction of depressive symptoms. The findings may also indicate psychotherapy alone in some instances can be a viable alternative to continued combined treatment. Clinicians should carefully assess benefits of patients´ ongoing use of antidepressant medication when entering psychotherapy.
... Davanloo's STPP model has an explicit focus on handling resistance in treatment through emotional mobilisation in the transference. Emerging evidence shows that this particular therapeutic modality appears as an effective option for 'treatment resistant' patients who have showed little or no response to other forms of treatment (Abbass, 2016;Town et al., 2017;Town et al., 2020). ...
... Overall, several studies have reported positive outcomes employing this therapeutic modality on treatment resistant samples (Abbass, 2006;Cornelissen & Verhuel, 2002;Hajkowski & Buller, 2012;Town et al., 2017;Town et al., 2020;Solbakken & Abbass, 2013). This case series adds to this evidence by reporting outcomes of patients from a naturalistic NHS secondary care setting with complex and chronic difficulties, who have showed limited response to previous mental health treatments. ...
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... Time-limited Intensive Short-Term Dynamic Psychotherapy (ISTDP; Abbass, 2015;Davanloo, 2000) for MDD is a 20-session treatment that is efficacious and cost-effective for treatment resistant depression in one study conducted in Canada (Town, Abbass, et al., 2017;Town et al., 2020). ISTDP focuses on mobilizing and experiencing complex emotional states, including unacknowledged anger toward attachment figures. ...
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Objective: A central tenet of psychodynamic theory of depression is the role of avoided anger. However empirical research has not yet addressed the question of for which patients and via hat pathways experiencing anger in sessions can help. The therapeutic alliance and acquisition of patient insight are important change processes in dynamic therapy and may mediate the anger-depression association. Methods: This study was embedded into a randomised trial testing the efficacy of Intensive Short-Term Dynamic Psychotherapy (ISTDP) for treatment resistant depression. In-session patient affect experiencing (AE) was coded for every available session (475/481) by blinded observers in 27 patients randomized to ISTDP. Dynamic Structural Equation Modelling was used to examine within-person associations between variation in depression scores session-by-session and both patient ratings (alliance) and observer ratings (AE and insight) of the treatment process. Results: Alliance and insight were independent mediators of the effect of anger on next-session depression. However, the relative importance of these two indirect effects of anger on depression was conditional on pre-treatment patient personality pathology (PP). In patients with higher PP, in-session anger was negatively related to depressive symptoms next-session, with this effect operating through higher alliance. In patients with low PP, in-session anger was negatively related to depressive symptoms next-session, with this effect operating through enhanced patient insight. Discussion: These findings highlight an anger-depression mechanism of change in dynamic therapy. Depending upon patient personality, either an ‘insight pathway’ or a ‘relational pathway’ may promote the effectiveness of facilitating arousal and expression of patients’ in-session feelings.
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First, meditation therapy is to urge patients to address their issues and feelings instead of dismissing them, but in the dispassionate and unbiased manner that defines the attentive state. Both the patient and the treating professional may benefit from this treatment method, since it appears to be a very effective therapeutic strategy. After colorectal cancer treatment, in studies, it has been demonstrated that ACT improves mental health, and Internet search engines such as Web of Science and Google Scholar as well as Dialnet were utilized to conduct a systematic literature There were 19 articles that fit the criteria. This includes a discussion of the ACT’s philosophical and theoretical basis, as well as the treatment itself. On the other hand, the study on ACT for enhancing mental health and quality of life is examined. Several of the available trials had serious flaws, making it impossible to establish reliable conclusions about the effectiveness of ACT for improving mental health and quality of life. The study determined that there is only a small amount of data supporting the use of ACT for improving mental health. The aim of this study is the application of the nursing model on improving the mental health of the colorectal patients. In addition, the limits of the current empirical state of ACT are acknowledged, and the importance of further research is highlighted. 1. Introduction Cancer is a major cause of death [1]. Cancer was diagnosed in one out of every fourteen persons in 2012. Eight out of ten cancer victims died within 5 years after diagnosis [2, 3]. As a result of cancer diagnosis and treatment, there is an increase in psychotic disorders. 16.3% and 10.3% of cancer patients in oncological and haematological settings matched the criteria for clinical anxiety and depression, correspondingly, according to a new meta-analysis of 70 studies from 14 countries. There are currently many institutions and experts that agree with Bultz and Carlson’s suggestion that cancer patients’ anguish be identified as the sixth [4]. Salmon Clark McGrath Fisher released the book in 2015 and also found that distress was associated to reduce immune function and higher mortality as well as poorer quality of life [5, 6]. A cancer diagnosis is followed by five years of physical symptoms and psychological suffering, interpersonal strain, and sexual issues for 20–30% of patients [7]. On the whole, cancer patients report feeling pain in the range of 35–96%. So, it is no surprise that it was among the most often reported symptoms of diagnosis and treatment, and it is also a major. Psychiatry can improve the quality of life for cancer patients by decreasing feelings of depression. Treatment efficacy is varied and typically viewed as low [8], which leaves opportunity for therapeutic improvements to improve the effectiveness of psychological oncology therapies. As a relatively recent psychotherapy method in psychosocial oncology, acceptance and commitment therapy (ACT) may be particularly useful in the treatment of cancer-related pain and discomfort. The theoretical foundation for accept theory is examined in this narrative review. This is followed by an evaluation and discussion of the current evidence on ACT in cancer patients, as well as suggestions for further study. 2. Colorectal Cancer and Mental Health Large intestinal cancer called malignancy of the colon starts in the colon (colon). This final section of the digestive system is called the colon. In general, colon cancer affects the elderly most, although it may affect anyone at any age. Typically, colon cancer begins with polyps, which are benign (noncancerous) cell groupings that develop on the colon’s inner wall. A small percentage of these polyps may develop into colon cancer in the long run. It is possible to have little polyps that do not create any problems. Identifying and eliminating polyps before they turn malignant helps prevent colon cancer; therefore, physicians prescribe frequent screening tests as a strategy to avoid the disease colon cancer that can be treated with a combination of surgical procedures and pharmacological therapies including chemotherapy and targeted therapy. Colorectal cancer occurs when colon and rectal cancer merge. Factors that may increase your risk of colon cancer include the following:(i)Older age people: despite the fact that colon cancer affects people of all ages, the majority of patients are over 50 years old. Children have a greater risk of colon cancer than adults, but physicians are unsure.(ii)African American race: in comparison to other races, African Americans have a higher risk of colon cancer(iii)A personal history of colorectal cancer or polyps: the risk of colon cancer in the future is higher for people who have had colon cancer or noncancerous polyps in the past.(iv)Inflammatory intestinal conditions: there are a number of illnesses, such as ulcerative colitis and Crohn’s disease that may raise the risk.(v)Inherited syndromes risk: inheritable mutations in some genes can significantly raise the risk of colon cancer. Occasionally, colon cancer can be traced back to hereditary genes. Family members with familial adenomatous polyposis are more likely to get colorectal cancer due to hereditary nonpolyposis or Lynch syndrome.(vi)History of colon: having a blood relative with colon cancer doubles your chance of getting it.(vii)Diet: colon and rectal cancer may be linked to a normal Western diet heavy in fats and calories but poor in fiber. Researchers have come up with a variety of outcomes. According to several studies, those who consume red and processed meat have a higher chance of developing colon cancer.(viii)A sedentary lifestyle: exercise can reduce the risk of colon cancer in those with sedentary lifestyles.(ix)Diabetes: there is a higher risk of colon cancer in those who have diabetes.(x)Obesity: comparatively, obese persons have a higher chance of developing colon cancer and dying from colon cancer than people who are deemed normal weight(xi)Smoking: tobacco users may have a higher chance of developing colon cancer(xii)Alcohol: drinking too much alcohol might raise your risk of developing colon cancer(xiii)Radiation therapy for cancer: radiation therapy given to the abdomen to treat previous cancers increases the chance of colon cancer 2.1. Treatment Patients’ preferences and general health are taken into consideration while deciding on treatment choices and suggestions, which are based on a variety of criteria, including the kind keep an open mind and ask questions if anything is not obvious. Have a discussion with the doctor about the purpose of each therapy and what to expect during the course of the “Shared decision-making” refers to these sorts of discussion. Together, the patient and your doctor decide on therapies that will help to achieve their health objectives. There are a variety of therapy options for colorectal cancer, which need better treatment decisions by learning more about the studies. Studies have demonstrated that no matter how old the patient is, these different therapy techniques give equivalent advantages. Older individuals, on the other hand, may face distinct; see what effects surgery, chemotherapy, and radiation therapy have on older individuals. All treatment decisions should take these characteristics into account in order to customize the treatment for each patient. There are a number of factors to consider.(i)The patient’s various medical issues(ii)The patient’s general health(iii)Possible adverse effects of the treatment plan(iv)Other drugs that the patient already takes 2.2. Physical, Emotional, and Social Effects of Cancer When it comes to cancer treatment, there are not only physical symptoms and side effects to worry about, but also emotional, palliative care, also known as supportive care, is the process of managing all along with therapies to delay, halt, or eradicate cancer; it is an important element of the care plan. The goal of palliative care is to improve the patient’s quality of life throughout treatment by controlling symptoms and providing nonmedical assistance to the patient. Such care is available to anybody, regardless of age or cancer kind and stage. It is most effective when it was started as soon as possible, following a cancer patient who received palliative care in addition to their cancer therapy that report less severe symptoms, a higher quality of life, and a higher level of satisfaction with their treatment. Palliative treatments come in a variety of forms, including medication, dietary modifications, relaxation methods, emotional and spiritual support, and palliative therapies including chemotherapy, surgery, and radiation therapy. After treatment, we may be asked to explain the symptoms and side effects, as well as to answer questions regarding them. Be careful to let their healthcare provider know if you are having any problems with their treatment. Healthcare providers can treat symptoms and side effects more promptly if they know about them in advance to keep their self from becoming more significant (Table 1). Reference Sample demographics at baseline Cancer site and stage Study design Theoretical framework Mental health measures Results [9] N = 542, 57% male, mean age = 71 years, France 63% colon cancer, 37% rectal cancer, 41% stage I, 26% stage II, 19% stage III, 2% stage IV, and 12% unknown Cross-sectional, population-based, case-controlled (N = 1,181 controls), surveyed at 5-, 10-, and 15-year postdiagnosis None SF-36 : MCS, EORTC QLQ-C30: emotional functioning scale, STAI Mental health and anxiety were not significantly different between cancer survivors and noncancer controls [10] N = 1,703, 60% male, 71% aged between 60 and 80 years, Australia Type of CRC not reported, 55% stage 0, I, or II, 35% stage III or IV, and 11% unknown Longitudinal, surveyed at 5, 12, 24, 36, 48, and 60 months postdiagnosis, population-based None BSI During the 5-year research period, 32–44% of participants reported significant levels of psychological discomfort. According to the study’s findings, three distinct distress trajectories were found, including continuous low distress (19%), medium discomfort that varied between time points (30%), medium distress that rose progressively over time (39%), and (13%). Distress was mentioned more frequently by males than when it came to males in distress, they tended to be younger, with less education, a weak social network, and advanced [11] N = 339, 55% male, mean age = 71 years, Israel Type of CRC not reported, 18% stage 0 or I, 62% stage II, and 20% stage III Cross-sectional, surveyed between 2- and 6-year posttreatment None BSI, IES, MAC Survivors who were single and unmarried reported the highest levels of anxiety and help married and unmarried survivors have similar levels of family support, but higher family support was exclusively associated with decreased suffering among married survivors [12] N = 439, 57% male, mean age = 65 years, Germany 59% colon cancer, 41% rectal cancer, 51% local, 31% regional, 17% distal, and 1% unknown Longitudinal, surveyed at 1-, 3-, 5-, and 10-year postdiagnosis, population-based, case-controlled (N = 2,028 controls) None EORTC QLQ-C30: emotional functioning scale Patients who had been diagnosed with cancer had significantly poorer emotional functioning at 1-, 3-, and 10-year postdiagnosis compared to controls; however, the differences were not clinically significant (>10 points). Comparing younger survivors (age 60) to older survivors (age 70 at diagnosis), younger survivors (age 60) reported substantially poorer emotional functioning 1 and 3 years after diagnosis. [13] N = 491, 62% male, mean age = 72 years, 76% non-Hispanic White, USA 100% rectal cancer, 53% local, 41% regional, 1% distal, and 5% unknown Cross-sectional, surveyed at least 5 years postdiagnosis, case-controlled: ostomies (n = 246 cases) vs. anastomoses (n = 245 controls) None Modified COH-QOL-ostomy, SF-36 version 2: MCS As a result of their ostomies, ladies with anastomoses reported a worse psychological well-being; there was also a higher rate of depression among male and female survivors who had ostomies compared to those who did not. [14] N = 1,419, 53% male, mean age = 70 years, Netherlands 59% colon cancer, 41% rectal, 33% stage I, 38% stage II, 26% stage III, 2% stage IV, and 1% unknown Cross-sectional, surveyed at an average of 8 years postdiagnosis (minimum of 5 years postdiagnosis), population-based, case-controlled (N = 338 normative population controls) None HADS Anxiety symptoms were recorded by 20% of survivors, whereas depression symptoms were reported by 18%. Anxiety levels in survivors were higher than those in the normative group when using a stricter cutoff point of less than 11. Depressive symptoms were higher in survivors than in the normative population when using a stricter cutoff of less than 11
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In this chapter reported use of psychotropic medication and psychological therapy are examined, as well as the extent of use of health care services for a mental health reason (GP, inpatient and outpatient health care) and day and community service use. It should be noted that rates presented are based on participant self-reports, not health records. Misclassifications of type of treatment or service are possible, and which was the providing organisation was not established.
Article
Background It is unclear what session frequency is most effective in cognitive–behavioural therapy (CBT) and interpersonal psychotherapy (IPT) for depression. Aims Compare the effects of once weekly and twice weekly sessions of CBT and IPT for depression. Method We conducted a multicentre randomised trial from November 2014 through December 2017. We recruited 200 adults with depression across nine specialised mental health centres in the Netherlands. This study used a 2 × 2 factorial design, randomising patients to once or twice weekly sessions of CBT or IPT over 16–24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II at baseline, before session 1, and 2 weeks, 1, 2, 3, 4, 5 and 6 months after start of the intervention. Intention-to-treat analyses were conducted. Results Compared with patients who received weekly sessions, patients who received twice weekly sessions showed a statistically significant decrease in depressive symptoms (estimated mean difference between weekly and twice weekly sessions at month 6: 3.85 points, difference in effect size d = 0.55), lower attrition rates ( n = 16 compared with n = 32) and an increased rate of response (hazard ratio 1.48, 95% CI 1.00–2.18). Conclusions In clinical practice settings, delivery of twice weekly sessions of CBT and IPT for depression is a way to improve depression treatment outcomes.
Article
Background: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. Methods: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. Findings: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. Interpretation: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. Funding: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
Article
Background: Patients with treatment-resistant depression (TRD) suffer very significant morbidity and are at a disadvantage concerning optimal clinical management. There are high associated societal costs. Aims: A detailed analysis of health economic costs in the United Kingdom in a group manifesting a severe form of TRD in the 12 months before their participation in a major randomized controlled treatment trial. Methods: The sample consisted of 118 participants from the Tavistock Adult Depression Study. Recruitment was from primary care on the basis of current major depression disorder of at least 2 years’ duration and two failed treatment attempts. Service utilization was assessed based on self-report and general practitioner (GP) medical records. Generalized linear models were used to identify predictors of cost. Results: All participants used GP services. Use of other doctors and practice nurses was also high. The mean total societal cost was £22 124, 80% of which was due to lost work and care required of families. Level of general functioning was found to be the most consistent predictor of costs. Conclusions: Severe forms of TRD are associated with high costs in which unpaid care and lost work predominate. Treatments that improve functioning may reduce the large degree of burden.
Article
Background: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD. Methods: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission. Results: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes. Conclusions: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.
Article
This pragmatic randomized controlled trial tested the effectiveness of long-term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment-as-usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long-standing major depression who had failed at least two different treatments and were considered to have treatment-resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6-monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow-up. The primary outcome measure was the 17-item version of the Hamilton Depression Rating Scale (HDRS-17), with complete remission defined as a HDRS-17 score ≤8, and partial remission defined as a HDRS-17 score ≤12. Secondary outcome measures included self-reported depression as assessed by the Beck Depression Inventory - II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation - Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42-month follow-up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow-up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer-based and self-reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long-term outcome of treatment-resistant depression. End-of-treatment evaluations or short follow-ups may miss the emergence of delayed therapeutic benefit.
Article
The nine-item Patient Health Questionnaire depression scale is a dual-purpose instrument that can establish provisional depressive disorder diagnoses as well as grade depression severity.
Article
Een gestandaardiseerde methode voor het meten van directe medische kosten en indirecte kosten vergoot de vergelijkbaarheid van de resultaten van economische evaluaties. Het instituut voor Medische Technology Assessment (iMTA) heeft in samenwerking met het Trimbos instituut een vragenlijst ontwikkeld voor het meten directe medische kosten en indirecte kosten die samenhangen met psychische aandoeningen. Deel I van de vragenlijst heeft betrekking op de directe medische kosten. Deel II is een verkorte versie van de Health and Labour Questionnaire (HLQ) voor meten van de indirecte kosten (SF-HLQ). Deel II is niet ziekte-specifiek en is daarom ook van toepassing op andere indicaties. In de handleiding wordt een beschrijving gegeven van de items en de scoring daarvan.
Article
Background: Major depressive disorder (MDD) is a leading cause of disability, morbidity, and mortality worldwide. The lifetime prevalence in the United States is estimated at 17%. Treatment-resistant depression (TRD) is generally defined as failure to achieve remissions despite adequate treatment. About 30% of patients do not achieve remission after 4 different antidepressant treatment trials. A few studies have examined the economic burden of TRD, but none has investigated the cost associated with more chronic and extensive forms of TRD characterized by nonresponse to ≥4 treatment trials. Objective: The objective of this study was to compare the health care utilization (HCU) and direct medical expenditures of TRD patients with those of chronic MDD patients. Methods: Patients with chronic MDD (defined as ≥2 years of continuous treatment) and patients with TRD (defined as undergoing at least 4 different qualifying antidepressant therapy trials) were identified in the PharMetrics Patient-centric Database. The association between TRD and medical expenditures was measured by using multivariate regression analysis. Results: The classification of TRD had a clinically meaningful and statistically significant association with increased medical expenditures. Holding all else equal, the classification of TRD was associated with a 29.3% higher costs (P < 0.001) in medical expenditures compared with patients not meeting the study definition of TRD. Conclusions: These results demonstrate that TRD is associated with significantly higher per-patient medical costs due to higher HCU. The findings suggest that the development of treatment alternatives for TRD is warranted. Limitations related to the use of secondary administrative data are noted.
Article
This report examines a possible distortion in the results of comparative treatment studies due to the association of the researcher's treatment allegiances with outcomes of those treatments. In eight past reviews a trend appeared for significant associations between the researcher's allegiance and outcomes of treatments compared. In a new review of 29 studies of treatment comparisons, a similar trend appeared. Allegiance ratings were based not only on the usual reprint method, but also on two new methods: ratings by colleagues who knew the researcher well, and self-ratings by the researchers themselves. The two new allegiance methods Interco related only moderately, but each allegiance measure correlated significantly with outcomes of the treatments compared, and when combined, the three measures explained 69% of the variance in outcomes Such an association can distort comparative treatment results. Our report concludes with how the researcher's allegiance may become associated with treatment outcomes and how studies should deal with these associations.
Book
Linear Mixed-Effects * Theory and Computational Methods for LME Models * Structure of Grouped Data * Fitting LME Models * Extending the Basic LME Model * Nonlinear Mixed-Effects * Theory and Computational Methods for NLME Models * Fitting NLME Models
Article
Treatment-Resistant Depression (TRD) affects 60 to 70% of patients with Major Depressive Disorder (MDD). The economic impact of depression in general, and of TRD specifically, was found to be relatively high. As the course of depression can be defined both by the severity of the disease and by the resistance to treatment, the question of the unique contribution of MDD severity vs. resistance to the economic burden of depression is being raised. One hundred and seven unipolar MDD patients, all treated for at least 4weeks, were enrolled in the study. Patients were assessed for their current MDD severity using the Hamilton Depression Rating Scale (HDRS) and past treatments, and for medical-related costs (number of blood and imaging tests, visits paid to physicians, psychiatric hospitalizations) and incapacity-related costs (number of working days lost) during the last episode. TRD and non-TRD patients were, respectively, 39.3% and 60.7% of the patients recruited for the study. TRD patients had more severe depression, and higher costs for imaging tests, physician visits, psychiatric hospitalizations, and number of working days lost. In addition, higher MDD severity was found to be associated with higher costs. Finally, when controlling for the shared variance of TRD and MDD severity, by using residual scores, TRD was associated with higher costs, but MDD severity was no longer related to costs. While both resistance and severity are associated with higher direct and indirect costs, our findings suggest that TRD may be the main factor in determining the economic burden of depression. http://www.ariel.ac.il/research/apl/publications
Article
In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included Levels of Evidence and expert clinical support. This section on "Pharmacotherapy" is one of 5 guideline articles. Despite emerging data on efficacy and tolerability differences amongst newer antidepressants, variability in patient response precludes identification of specific first choice medications for all patients. All second-generation antidepressants have Level 1 evidence to support efficacy and tolerability and most are considered first-line treatments for MDD. First-generation tricyclic and monoamine oxidase inhibitor antidepressants are not the focus of these guidelines but generally are considered second- or third-line treatments. For inadequate or incomplete response, there is Level 1 evidence for switching strategies and for add-on strategies including lithium and atypical antipsychotics. Most of the evidence is based on trials for registration and may not reflect real-world effectiveness. Second-generation antidepressants are safe, effective and well tolerated treatments for MDD in adults. Evidence-based switching and add-on strategies can be used to optimize response in MDD that is inadequately responsive to monotherapy.
Article
Antidepressants have recently become the most commonly prescribed class of medications in the United States. To compare sociodemographic and clinical patterns of antidepressant medication treatment in the United States between 1996 and 2005. Analysis of antidepressant use data from the 1996 (n = 18 993) and 2005 (n = 28 445) Medical Expenditure Panel Surveys. Households in the United States. Respondents aged 6 years or older who reported receiving at least 1 antidepressant prescription during that calendar year. Rate of antidepressant use and adjusted rate ratios (ARRs) of year effect on rate of antidepressant use adjusted for age, sex, race/ethnicity, annual family income, self-perceived mental health, and insurance status. The rate of antidepressant treatment increased from 5.84% (95% confidence interval [CI], 5.47-6.23) in 1996 to 10.12% (9.58-10.69) in 2005 (ARR, 1.68; 95% CI, 1.55-1.81), or from 13.3 to 27.0 million persons. Significant increases in antidepressant use were evident across all sociodemographic groups examined, except African Americans (ARR, 1.13; 95% CI, 0.89-1.44), who had comparatively low rates of use in both years (1996, 3.61%; 2005, 4.51%). Although antidepressant treatment increased for Hispanics (ARR, 1.75; 95% CI, 1.60-1.90), it remained comparatively low (1996, 3.72%; 2005, 5.21%). Among antidepressant users, the percentage of patients treated for depression did not significantly change (1996, 26.25% vs 2005, 26.85%; ARR, 0.95; 95% CI, 0.83-1.07), although the percentage of patients receiving antipsychotic medications (5.46% vs 8.86%; ARR, 1.77; 95% CI, 1.31-2.38) increased and those undergoing psychotherapy declined (31.50% vs 19.87%; ARR, 0.65; 95% CI, 0.56-0.72). From 1996 to 2005, there was a marked and broad expansion in antidepressant treatment in the United States, with persisting low rates of treatment among racial/ethnic minorities. During this period, individuals treated with antidepressants became more likely to also receive treatment with antipsychotic medications and less likely to undergo psychotherapy.
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
Somatization is prevalent in primary care and is associated with substantial functional impairment and healthcare utilization. However, instruments for identifying and monitoring somatic symptoms are few in number and not widely used. Therefore, we examined the validity of a brief measure of the severity of somatic symptoms. The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-15 comprises 15 somatic symptoms from the PHQ, each symptom scored from 0 ("not bothered at all") to 2 ("bothered a lot"). The PHQ-15 was administered to 6000 patients in eight general internal medicine and family practice clinics and seven obstetrics-gynecology clinics. Outcomes included functional status as assessed by the 20-item Short-Form General Health Survey (SF-20), self-reported sick days and clinic visits, and symptom-related difficulty. As PHQ-15 somatic symptom severity increased, there was a substantial stepwise decrement in functional status on all six SF-20 subscales. Also, symptom-related difficulty, sick days, and healthcare utilization increased. PHQ-15 scores of 5, 10, 15, represented cutoff points for low, medium, and high somatic symptom severity, respectively. Somatic and depressive symptom severity had differential effects on outcomes. Results were similar in the primary care and obstetrics-gynecology samples. The PHQ-15 is a brief, self-administered questionnaire that may be useful in screening for somatization and in monitoring somatic symptom severity in clinical practice and research.
Article
Treatment-resistant depression (TRD) typically refers to inadequate response to at least one antidepressant trial of adequate doses and duration. TRD is a relatively common occurrence in clinical practice, with up to 50% to 60% of the patients not achieving adequate response following antidepressant treatment. A diagnostic re-evaluation is essential to the proper management of these patients. In particular, the potential role of several contributing factors, such as medical and psychiatric comorbidity, needs to be taken into account. An accurate and systematic assessment of TRD is a challenge to both clinicians and researchers, with the use of clinician-rated or self-rated instruments being perhaps quite helpful. It is apparent that there may be varying degrees of treatment resistance. Some staging methods to assess levels of treatment resistance in depression are being developed, but need to be tested empirically.
Reaching through Resistance
  • A Abbass
Abbass, A., 2015. Reaching through Resistance. Seven Leaves Press, Kansas City.
GRID-HAM-17 GRID-HAM-21 Structured Interview Guide International Society for CNS Drug Development
  • P Bech
  • N Engelhardt
  • K Evans
  • A Kalali
  • K Kobak
  • J Lipsitz
  • J Olin
  • J Pearson
  • M Rothman
  • J B W Williams
Bech, P., Engelhardt, N., Evans, K., Kalali, A., Kobak, K., Lipsitz, J., Olin, J., Pearson, J., Rothman, M., Williams, J.B.W., 2003. GRID-HAM-17 GRID-HAM-21 Structured Interview Guide International Society for CNS Drug Development, San Diego, CA, USA.
Estimated fixed effects coefficients (B) and 95% Confidence Intervals (CI) from exponential decay growth models with random initial value and change parameters, and study group as a predictor of variation in initial value and change Outcome
  • Ham-D Outcome
Table 2: Estimated fixed effects coefficients (B) and 95% Confidence Intervals (CI) from exponential decay growth models with random initial value and change parameters, and study group as a predictor of variation in initial value and change Outcome: HAM-D Outcome: PHQ-9