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ABSTRACT: Background: Elevated prolactin (hyperprolactinemia) has been commonly reported during treatment with some antipsychotic drugs. A decrease in bone mineral density (BMD) may be related to elevated prolactin. The objective of this study was to determine the prevalence of low BMD in patients with schizophrenia treated with conventional antipsychotics or risperidone and to evaluate any potential relationship with treatment.Methods: A large-scale, cross-sectional secondaryanalysis was performed to determine low BMD in schizophrenia patients (N=402) treated with conventional antipsychotics or risperidone for at least 3 months prior to study entry. BMD was determined by ultrasonography of the calcaneus. The potential effect of age, elevated prolactin, and duration of antipsychotic drug treatment on BMD was evaluated. Bone metabolism measures were determined and the potential effect of elevated prolactin and sex hormones on bone metabolism measures was also evaluated. Regression analysis was used for all the above analyses.Results: Low BMD was observed in about 1 in 4 female patients and 1 in 3 male patients. A negative correlation between T-score (BMD measure) and prolactin levels was found in male patients after controlling for age (p=0.05) and this correlation was not observed in female patients. Controlling for age, elevated prolactin was associated with elevated bone formation marker (osteocalcin) in both genders (female: p=0.03; male: p=0.05) and there was no significant correlation between change in T-scores and duration of antipsychotic drug for either gender. Total testosterone levels were negatively correlated with bone resorption marker (N-telopeptide) in men (p=0.04).Conclusion: Contrary to the trend in the general population with osteopenia, hyperprolactinemia during treatment with antipsychotic drugs may be associated with a greater prevalence of low bone mass in men compared to women. Elevated prolactin may have a direct effect on the bone, increasing bone turnover in patients of both genders, while hypogonadism may be associated with elevated prolactin in male patients only. Decreased testosterone levels due to hypogonadism in men may lead to increased bone resorption and subsequent low BMD.
Clinical Schizophrenia & Related Psychoses 02/2013;
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ABSTRACT: BACKGROUND: Little is known about the long-term outcomes for patients with schizophrenia who fail to achieve symptomatic remission. This post-hoc analysis of a 3-year study compared the costs of mental health services and functional outcomes between individuals with schizophrenia who met or did not meet cross-sectional symptom remission at study enrollment. METHODS: This post-hoc analysis used data from a large, 3-year prospective, non-interventional observational study of individuals treated for schizophrenia in the United States conducted between July 1997 and September 2003. At study enrollment, individuals were classified as non-remitted or remitted using the Schizophrenia Working Group Definition of symptom remission (8 core symptoms rated as mild or less). Mental health service use was measured using medical records. Costs were based on the sites' medical information systems. Functional outcomes were measured with multiple patient-reported measures and the clinician-rated Quality of Life Scale (QLS). Symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Outcomes for non-remitted and remitted patients were compared over time using mixed effects models for repeated measures or generalized estimating equations after adjusting for multiple baseline characteristics. RESULTS: At enrollment, most of the 2,284 study participants (76.1%) did not meet remission criteria. Non-remitted patients had significantly higher PANSS total scores at baseline, a lower likelihood of being Caucasian, a higher likelihood of hospitalization in the previous year, and a greater likelihood of a substance use diagnosis (all p < 0.05). Total mental health costs were significantly higher for non-remitted patients over the 3-year study (p = 0.008). Non-remitted patients were significantly more likely to be victims of crime, exhibit violent behavior, require emergency services, and lack paid employment during the 3-year study (all p < 0.05). Non-remitted patients also had significantly lower scores on the QLS, SF-12 Mental Component Summary Score, and Global Assessment of Functioning during the 3-year study. CONCLUSIONS: In this post-hoc analysis of a 3-year prospective observational study, the failure to achieve symptomatic remission at enrollment was associated with higher subsequent healthcare costs and worse functional outcomes. Further examination of outcomes for schizophrenia patients who fail to achieve remission at initial assessment by their subsequent clinical status is warranted.
BMC Psychiatry 12/2012; 12(1):222. · 2.55 Impact Factor
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ABSTRACT: BACKGROUND: Little is known about the specific reasons for antipsychotic discontinuation or continuation from patients or clinicians perspectives. This study aimed to assess the construct validity of 2 new measures of the Reasons for Antipsychotic Discontinuation/Continuation (RAD): RAD-I (a structured interview assessing the patients perspective) and RAD-Q (a questionnaire assessing the clinicians perspective). METHODS: Data were used from a 12-week antipsychotic trial of schizophrenia patients in which the RAD was administered at study entry and at study completion (or discontinuation). Construct validity was assessed through comparisons of RAD responses, clinicians responses to a standard patient disposition form identifying reasons for patients study discontinuation, and several standard psychiatric measures. Percent agreement quantified the correspondence between patient and clinician scores. RESULTS: Patients indicating lack of improvement/worsening of positive symptoms as a somewhat to primary reason for medication discontinuation had statistically significantly less improvement in Positive and Negative Syndrome Scale positive score than patients not reporting these as a reason (concurrent validity). Similar results were observed for the RAD negative symptom, functional, social support, and adherence items, whereas the mood and cognitive items were not significantly associated with change scores on standard psychiatric measures. Responses to the RAD were also weakly associated with variables that theoretically should not be related to them (divergent validity). Level of agreement between the clinician- and patient-rated RAD scores was high (60%-100%). CONCLUSIONS: Initial validation of the RAD suggests that the instruments are valid tools for gathering detailed information regarding reasons for antipsychotic discontinuation and continuation from patients and clinicians perspectives.
BMC Medical Research Methodology 09/2012; 12(1):142. · 2.67 Impact Factor
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Louis S Matza,
Glenn A Phillips,
Dennis A Revicki,
Haya Ascher-Svanum,
Karen G Malley,
Andrew C Palsgrove,
Douglas E Faries,
Virginia Stauffer, Bruce J Kinon,
A George Awad,
Richard S E Keefe,
Dieter Naber
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ABSTRACT: The Reasons for Antipsychotic Discontinuation Questionnaire (RAD-Q) was designed to assess clinicians' perceptions of reasons for antipsychotic discontinuation or continuation. The current study examined psychometric properties of this instrument and patterns of antipsychotic discontinuation. The sample of 121 patients (81 discontinuation, 40 continuation) with schizophrenia or schizoaffective disorder was 66.9% male, with a mean age of 41.6 years. Treating clinicians reported a mean of 4.1 reasons for discontinuation and 7.5 reasons for continuation. RAD-Q domain scores were derived to quantify the impact of three factors on the decision to discontinue or continue: treatment benefits, adverse events, and distal reasons other than direct effects of the medication. Analysis of inter-rater reliability indicated an acceptable degree of agreement between clinicians (weighted Kappa for discontinuation scores=0.70-0.78). Correlations with symptom measures (Clinical Global Impression-Schizophrenia Scale (CGI-SCH), Positive and Negative Syndrome Scale (PANSS)) supported convergent validity of the benefits domain score (r=0.28-0.47; all p<0.05). Domain scores discriminated among groups of patients differing in clinician and patient-reported clinical variables. Results suggest that the RAD-Q is a useful detailed measure of reasons for antipsychotic discontinuation and continuation. Findings indicate that clinicians usually report multiple reasons for discontinuation, rather than a single reason for each patient.
Psychiatry Research 07/2012; · 2.52 Impact Factor
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Journal of clinical psychopharmacology 06/2012; 32(3):420-2. · 5.09 Impact Factor
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The Journal of Clinical Psychiatry 04/2012; 73(4):504-5. · 5.80 Impact Factor
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Bruce J Kinon
Journal of clinical psychopharmacology 04/2012; 32(2):292-3. · 5.09 Impact Factor
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ABSTRACT: Patients with schizophrenia who have predominant negative symptoms are often considered less responsive to treatment. This analysis of patients with schizophrenia or schizoaffective disorder compares changes in symptom severity between those with predominant versus merely prominent negative symptoms. Prominent negative symptoms were defined by a baseline score of ≥4 on at least 3, or ≥5 on at least 2, of the 7 Positive and Negative Syndrome Scale (PANSS) negative subscale items. Predominant negative symptoms were defined by the foregoing plus a PANSS positive score of <19, a Barnes Akathisia score of <2, a Simpson-Angus score of <4, and a Calgary Depressive Scale score of <9. Adult patients with schizophrenia (n=227) or schizoaffective disorder (n=116) received either olanzapine (10-20mg/day, n=169) or quetiapine (300-700mg/day, n=174) for up to 24weeks. Data for both medications were pooled. Of the 343 patients enrolled in the study, 34.7% met the criteria for predominant negative symptoms, the remaining 65.3% being characterized only by their prominent negative symptoms. Changes in the severity of negative symptoms in both patient types largely followed similar trajectories during treatment, as reflected both in Marder PANSS negative subscale scores and in the Scale for Assessment of Negative Symptoms total and domain scores. Patients with either predominant or prominent negative symptoms therefore appear to respond similarly to atypical antipsychotic treatment. This distinction, incorporating an evaluation of the presence of positive, affective, and extrapyramidal symptoms, may therefore not have prognostic implications for the responsiveness of patients' negative symptoms to treatment.
Biological Psychiatry 02/2012; 134(2-3):195-201. · 8.28 Impact Factor
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ABSTRACT: It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients' clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0-14 days prior) and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%). Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions-Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient's worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians' stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research.
Neuropsychiatric Disease and Treatment 01/2012; 8:113-8. · 1.81 Impact Factor
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Louis S Matza,
Glenn A Phillips,
Dennis A Revicki,
Haya Ascher-Svanum,
Karen G Malley,
Andrew C Palsgrove,
Douglas E Faries,
Virginia Stauffer, Bruce J Kinon,
A George Awad,
Richard Se Keefe,
Dieter Naber
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ABSTRACT: The Reasons for Antipsychotic Discontinuation Interview (RAD-I) was developed to assess patients' perceptions of reasons for discontinuing or continuing an antipsychotic. The current study examined reliability and validity of domain scores representing three factors contributing to these treatment decisions: treatment benefits, adverse events, and distal reasons other than direct effects of the medication.
Data were collected from patients with schizophrenia or schizoaffective disorder and their treating clinicians. For approximately 25% of patients, a second rater completed the RAD-I for assessment of inter-rater reliability.
All patients (n = 121; 81 discontinuation, 40 continuation) reported at least one reason for discontinuation or continuation (mean = 2.8 reasons for discontinuation; 3.4 for continuation). Inter-rater reliability was supported (kappas = 0.63-1.0). Validity of the discontinuation domain scores was supported by associations with symptom measures (the Positive and Negative Syndrome Scale for Schizophrenia, the Clinical Global Impression - Schizophrenia Scale; r = 0.30 to 0.51; all P < 0.01), patients' primary reasons for discontinuation, and adverse events. However, the continuation domain scores were not significantly associated with these other indicators.
Results support the reliability, convergent validity, and known-groups validity of the RAD-I for assessing patients' reasons for antipsychotic discontinuation. Further research is needed to examine validity of the RAD-I continuation section.
Patient Preference and Adherence 01/2012; 6:521-32. · 1.14 Impact Factor
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ABSTRACT: To fully assess the various dimensions affected by schizophrenia, clinical trials often include multiple scales measuring various symptom profiles, cognition, quality of life, subjective well-being, and functional impairment. In this exploratory study, we characterized the relationships among six clinical, functional, cognitive, and quality-of-life measures, identifying a parsimonious set of measurements.
We used baseline data from a randomized, multicenter study of patients diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder who were experiencing an acute symptom exacerbation (n = 628) to examine the relationship among several outcome measures. These measures included the Positive and Negative Syndrome Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Assessment of Cognition in Schizophrenia Symbol Coding Test, Subjective Well-being Under Neuroleptics Scale Short Form (SWN-K), Schizophrenia Objective Functioning Instrument (SOFI), and Quality of Life Scale (QLS). Three analytic approaches were used: 1) path analysis; 2) factor analysis; and 3) categorical latent variable analysis. In the optimal path model, the SWN-K was selected as the final outcome, while the SOFI mediated the effect of the exogenous variables (PANSS, MADRS) on the QLS.
The overall model explained 47% of variance in QLS and 17% of the variance in SOFI, but only 15% in SWN-K. Factor analysis suggested four factors: "Functioning," "Daily Living," "Depression," and "Psychopathology." A strong positive correlation was observed between the SOFI and QLS (r = 0.669), and both the QLS and SOFI loaded on the "Functioning" factor, suggesting redundancy between these scales. The measurement profiles from the categorical latent variable analysis showed significant variation in functioning and quality of life despite similar levels of psychopathology.
Researchers should consider collecting PANSS, SOFI, and SWN-K in their trials. This would allow a broad spectrum of assessments that would have the ability to capture a wide range of treatment outcomes and allow for a rich characterization of the subgroups involved. Additional research is needed to identify the critical cognitive measures.
Clinical trials registration: Predicting Response to Risperidone Treatment Through Identification of Early-onset of Antipsychotic Drug Action in SchizophreniaClinicalTrials.gov identifier: NCT00337662; http://www.clinicaltrials.gov/
BMC Psychiatry 12/2011; 11:203. · 2.55 Impact Factor
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ABSTRACT: We examined 6 single nucleotide polymorphisms (SNPs) previously reported to be associated with response to iloperidone therapy for association with response to risperidone therapy.
Patients with schizophrenia (DSM-IV) were assessed during 2006 and 2007 for response/nonresponse (defined as ≥ 20%/<20% improvement in Positive and Negative Syndrome Scale [PANSS] total score) after 2 weeks of risperidone treatment (2 to 6 mg/d). Responders continued risperidone treatment; nonresponders were randomly assigned to either risperidone or olanzapine treatment (10 to 20 mg/d) for an additional 10 weeks. Associations between change in PANSS total (primary outcome measure), positive, and negative scores and the 6 SNPs were examined in risperidone-treated patients (N = 145). Genotype frequencies and improvement in PANSS total scores were analyzed for those SNPs significantly associated with change in PANSS total score.
The SNPs XKR4 rs9643483 and GRIA4 rs2513265 were significantly associated with change in PANSS total response (adjusted P < .05 for both), with the same direction of effect as reported for iloperidone. For patients with nonresponsive genotypes for these SNPs, mean improvement in PANSS total score for African Americans was two-thirds that seen for whites (XKR4: -13.9 versus -21.4; GRIA4: -12.5 versus -20.9).
In this retrospective pharmacogenomic analysis, we found that 2 SNPs previously linked to iloperidone response were also associated with response to risperidone.
clinicaltrials.gov Identifier: NCT00337662.
The Journal of Clinical Psychiatry 07/2011; 73(3):367-71. · 5.80 Impact Factor
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ABSTRACT: Time to treatment discontinuation and rates of discontinuation are commonly used when evaluating effectiveness of antipsychotic medication. However, less is known about reasons for discontinuation. The purpose of this study was to develop two measures of reasons for discontinuation or continuation of antipsychotics for the treatment of schizophrenia. Based on literature review, a patient interview pilot study, and expert panel input, two measures were drafted: the clinician-reported Reasons for Antipsychotic Discontinuation/Continuation Questionnaire (RAD-Q) and the patient-reported Reasons for Antipsychotic Discontinuation/Continuation Interview (RAD-I). Patients and clinicians completed the draft measures and structured cognitive debriefing interviews. For the draft instruments, reasons for discontinuation/continuation were divided into 3 categories: therapeutic benefits (positive symptoms, negative symptoms, mood, cognition, functional status), adverse events, and reasons other than direct effects of the medication (e.g., cost, inadequate social support). In cognitive debriefings, 10 clinicians and 15 patients indicated that the RAD-Q and RAD-I were clear, easy to complete, and comprehensive. Clinicians and patients suggested minor revisions, and the instruments were revised accordingly. The RAD-Q and RAD-I appear to be useful instruments for assessing reasons for antipsychotic discontinuation and continuation. The next step is a psychometric evaluation of the measures in a larger sample.
Psychiatry Research 06/2011; 189(3):463-8. · 2.52 Impact Factor
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ABSTRACT: The primary objective of this study was to test the hypothesis that 1 or more dose levels of LY2140023 monohydrate, an oral prodrug of the potent metabotropic glutamate (mGlu) 2/3 receptor agonist LY404039, given to patients with schizophrenia for 4 weeks would demonstrate significantly greater efficacy than placebo. The HBBI study was a multicenter, randomized, double-blind, parallel, placebo- and active-controlled trial. Male and female patients aged 18 to 65 years who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia were randomized in a 2:2:2:2:2:1 ratio to receive 5-, 20-, 40-, or 80-mg LY2140023 monohydrate twice daily, placebo twice daily, or placebo (am) and 15 mg of olanzapine (pm) daily. Efficacy was defined as the change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score assessed at 4 weeks. The primary analysis did not show that any of the 4 LY2140023 monohydrate doses were more efficacious than placebo as measured by the PANSS total score. Similarly, olanzapine did not significantly separate from placebo. A higher-than-anticipated treatment effect (14.6-point improvement) in the placebo group was observed on PANSS total score. LY2140023 monohydrate was generally well tolerated, although 4 patients reported the serious adverse event of convulsion. LY2140023 monohydrate-treated patients showed little change in dopamine-related adverse events and weight. The results of the HBBI study are considered to be inconclusive because LY2140023 monohydrate and the active control olanzapine did not separate from placebo in the treatment of patients with acutely exacerbated schizophrenia. Additional efficacy, safety, and tolerability testing are needed.
Journal of clinical psychopharmacology 06/2011; 31(3):349-55. · 5.09 Impact Factor
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ABSTRACT: Research has identified distinct trajectories of antipsychotic response in patients with chronic schizophrenia in short-duration trials (~12 weeks). This post-hoc analysis identified trajectories in patients with chronic schizophrenia treated for ≤24 weeks. We pooled data from 1990 patients with chronic schizophrenia from 6 randomized, double-blind, olanzapine-comparator trials of atypical antipsychotics. Trajectory analysis identified homogeneous subpopulations within the larger heterogeneous population. Baseline demographics were compared between the identified latent classes. Five distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) Total score were identified: Dramatic Responders (n=47/1990, 2.4%), severely-ill patients (PANSS=124) with rapid and sustained improvement (51%) by Week 3; Partial Responders (n=1802/1990, 90.6%), moderately-ill (PANSS=90) with minimal improvement (21%) by Week 4, and little further improvement; Partial Responders-Unsustained (Late) (n=32/1990, 1.6%), markedly-ill (PANSS=95) with minimal initial improvement followed by worsening after Week 12; Partial Responders-Unsustained (Early) (n=28/1990, 1.4%), markedly-ill (PANSS=102) with minimal initial improvement followed by worsening after Week 8; and Delayed Responders (n=81/1990, 4.1%), markedly-to-severely-ill (PANSS=113) with minimal (11%) improvement at Week 8, but noticeable improvement thereafter (49%). Significant differences were noted for several baseline characteristics (p<.05) and discontinuation rates (46%-72%). Dramatic Responders were younger and more likely to be female and Hispanic with higher baseline illness severity. Analysis of antipsychotic response over 24 weeks in a large, pooled, heterogeneous population treated for schizophrenia revealed 5 distinct trajectories. Most patients had modest and sustained improvements during atypical antipsychotic treatment, regardless of their baseline illness severity, representing a partial response to currently available treatments.
Biological Psychiatry 04/2011; 130(1-3):11-9. · 8.28 Impact Factor
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ABSTRACT: The magnitude of placebo response is an important factor in the outcome of clinical trials, in that excessive placebo response can obscure true drug-placebo differences. There is ample evidence of the impact of elevated placebo response in trials of major depression, but less intensive research has been done in the area of schizophrenia. We present a current review of placebo response in clinical trials of schizophrenia.
The existing evidence suggests that placebo response in schizophrenia trials may be similar in magnitude, quality, and impact to that observed in depression trials, and has similarly increased over the past several years. We discuss factors influencing excessive placebo response during the conduct of clinical trials and how they may be managed to help minimize placebo response.
There does not appear to be any single major factor contributing to the high levels of placebo response in schizophrenia clinical trials; therefore, a multipronged approach to minimizing excessive placebo response or its impact is recommended.
Current opinion in psychiatry 03/2011; 24(2):107-13. · 3.57 Impact Factor
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ABSTRACT: To identify a simple decision tree using early symptom change to predict response to atypical antipsychotic therapy in patients with (Diagnostic and Statistical Manual, Fourth Edition, Text Revised) chronic schizophrenia.
Data were pooled from moderately to severely ill patients (n = 1494) from 6 randomized, double-blind trials (N = 2543). Response was defined as a ≥ 30% reduction in Positive and Negative Syndrome Scale (PANSS) Total score by Week 8 of treatment. Analyzed predictors were change in individual PANSS items at Weeks 1 and 2. A decision tree was constructed using classification and regression tree (CART) analysis to identify predictors that most effectively differentiated responders from non-responders.
A 2-branch, 6-item decision tree was created, producing 3 distinct groups. First branch criterion was a 2-point score decrease in at least 2 of 5 PANSS positive items (Week 2). Second branch criterion was a 2-point score decrease in the PANSS excitement item (Week 2). "Likely responders" met the first branch criteria; "likely non-responders" did not meet first or second criterion; "not predictable" patients did not meet the first but did meet the second criterion. Using this approach, response to treatment could be predicted in most patients (92%) with high positive predictive value (79%) and high negative predictive value (75%). Predictive findings were confirmed through analysis of data from 2 independent trials.
Using a data-driven approach, we identified decision rules using early change in the scores of selected PANSS items to accurately predict longer-term treatment response or non-response to atypical antipsychotic therapy. This could lead to development of a simple quantitative evaluation tool to help guide early treatment decisions.
This is a retrospective, non-intervention study in which pooled results from 6 previously published reports were analyzed; thus, clinical trial registration is not required.
BMC Psychiatry 02/2011; 11:23. · 2.55 Impact Factor
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ABSTRACT: To compare the cost-effectiveness of treating early responders versus early nonresponders to an atypical antipsychotic (risperidone) and the cost-effectiveness of treating early nonresponders maintained on risperidone versus those switched to olanzapine.
This post hoc analysis used data from a randomized, double-blind, 12-week schizophrenia study (Study Code: HGMN, n = 628). Participants were initially assigned to risperidone therapy. Early response was defined as a ≥ 20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score from baseline to two weeks. Early responders continued on risperidone, whereas early nonresponders were randomized in a double-blind manner to continue on risperidone or switch to olanzapine for 10 additional weeks. Early responders and early nonresponders maintained on risperidone were compared for health-state utilities (benefits) and total cost over the 12-week study; early nonresponders maintained on risperidone or switched to olanzapine were compared from randomization (10-week period). Utilities were derived from the PANSS and adverse events. Mixed models were used to assess group differences in utilities. Treatment costs were calculated based on health states. Incremental cost-effectiveness ratios were then utilized to compare treatment groups.
Early responders to risperidone had significantly greater total utility and lower total treatment costs than early nonresponders to risperidone. Compared with early nonresponders who continued on risperidone, those who were switched to olanzapine had significantly higher total utility scores at endpoint and numerically lower total treatment costs, reflecting significantly lower nonmedication treatment costs, even though medication costs were significantly higher compared with generic risperidone.
Treatment of early responders was more cost-effective than treatment of early nonresponders to atypical antipsychotic therapy. Switching early nonresponders to olanzapine resulted in improved treatment effectiveness, met the criteria for some dominance, and appeared modestly more cost-effective than maintaining treatment with generic risperidone.
ClinicoEconomics and Outcomes Research 01/2011; 3:79-87.
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ABSTRACT: Early response to antipsychotic medication has been shown to accurately predict later response to continued use of the same treatment in patients with chronic schizophrenia. This study examines whether this predictive pattern exists for patients with first-episode psychosis. We used a data-driven threshold for early response of ≥ 26.2% improvement from baseline on the Positive and Negative Syndrome Scale (PANSS(0-6)) Total score to determine whether response at Week 2 of treatment may predict response at Week 12 in a randomized, double-blind trial of olanzapine versus haloperidol for treatment of patients with first-episode psychosis (N=225). Later response was defined as a ≥ 40% and ≥ 50% improvement in PANSS Total(0-6) score and as remission. At Week 2, 43% (97/225) of patients were identified as early responders. At a threshold for later response of ≥ 50% improvement in PANSS(0-6) Total score, early non-response most strongly predicted later non-response, demonstrating high specificity (74%) and high negative predictive value (80%). As had been seen in the treatment of patients with chronic schizophrenia, early non-response was a robust predictor of subsequent non-response in the treatment of patients with first-episode psychosis.
Psychiatry Research 12/2010; 187(1-2):42-8. · 2.52 Impact Factor
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ABSTRACT: To identify reasons for discontinuation and continuation of antipsychotic medications in the treatment of schizophrenia from the patients' and their clinicians' perspectives.
Two measures were previously developed to assess the Reasons for Antipsychotic Discontinuation/Continuation (RAD), one from the patient's perspective and another from the clinician's perspective. These measures were administered to acutely ill schizophrenia patients enrolled in a 12-week study of antipsychotic medications (N = 596) and to their clinicians. The RAD was assessed at baseline and at endpoint. Reasons were rated on a 5-point scale from 'primary reason' to 'not a reason.' The single most important reason was also identified. The 'single most important reason' and the 'primary reasons' for discontinuing the drug used prior to enrollment, and for discontinuing or continuing the study drug were identified. Levels of concordance between patients' and clinicians' reasons were assessed.
The data source for this study is a clinical trial registered at www.clinicaltrials.gov (NCT00337662).
Reasons for Antipsychotic Discontinuation/Continuation (RAD).
Patients and clinicians identified several reasons for medication discontinuation and continuation (2.3 to 6.3 reasons, on average). The top 'single most important' reason for discontinuing the drug used prior to enrollment and for discontinuing the study drug was 'positive symptoms not sufficiently improved or made worse,' followed by 'medication-related adverse events.' The most frequent 'single most important' reason for medication continuation was 'improved positive symptoms,' followed by 'patient's perception of improvement,' and 'functional improvement.' A high level of concordance was observed between patients' and clinicians' ratings.
Medication efficacy appears to be the core driver of medication discontinuation and continuation, especially with regard to positive symptoms. There was a high level of concordance between patients' and clinicians' perspectives. Limitations include the study requirement that patients be at least moderately ill and experiencing acute psychotic exacerbation, a potential selection bias in the readiness to respond to measures, and small sample sizes for some analyses. Further research is needed to replicate findings in patients who are not acutely ill.
Current Medical Research and Opinion 10/2010; 26(10):2403-10. · 2.38 Impact Factor
