A study with low statistical power has a reduced chance of detecting a true effect, but it is less well appreciated that low power also reduces the likelihood that a statistically significant result reflects a true effect. Here, we show that the average statistical power of studies in the neurosciences is very low. The consequences of this include overestimates of effect size and low reproducibility of results. There are also ethical dimensions to this problem, as unreliable research is inefficient and wasteful. Improving reproducibility in neuroscience is a key priority and requires attention to well-established but often ignored methodological principles.

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Power failure: why small sample size undermines the reliability of neuroscience

A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

A rating scale for drug-induced akathisia

The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

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Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013.

Placebo

4. Modelling Survival Data in Medical Research

OBJECTIVE: The objective of this study was to evaluate the relationship between compliance with an antipsychotic medication regimen and risk of hospitalization in a cohort of California Medicaid patients with schizophrenia. METHODS: Compliance behavior was estimated by using a retrospective review of California Medicaid pharmacy refill and medical claims for 4,325 outpatients for whom antipsychotics were prescribed for treatment of schizophrenia from 1999 to 2001. Compliance behavior was estimated by using four different definitions: gaps in medication therapy, medication consistency and persistence, and a medication possession ratio. Patients were followed for one year and had an average of 19.1 dispensing events. Logistic regression models using each compliance estimate were used to determine the odds of hospitalization. RESULTS: Risk of hospitalization was significantly correlated with compliance. With all definitions, lower compliance was associated with a greater risk of hospitalization over and abov...

https://ps.psychiatryonline.org/doi/pdf/10.1176/appi.ps.55.8.886

Partial Compliance and Risk of Rehospitalization Among California Medicaid Patients With Schizophrenia

Bipolar disorder is recognized as a major mental health issue, and its economic impact has been examined in the United States. However, there exists a general scarcity of published studies and lack of standardized data on the burden of the illness across European countries. In this systematic literature review, we highlight the epidemiological, clinical, and economic outcomes of bipolar disorder in Europe. A systematic review of publications from the last 10 years relating to the burden of bipolar disorder was conducted, including studies on epidemiology, patient-related issues, and costs. Data from the UK, Germany, and Italy indicated a prevalence of bipolar disorder of ~1%, and a misdiagnosis rate of 70% from Spain. In one study, up to 75% of patients had at least one DSM-IV comorbidity, commonly anxiety disorders and substance/alcohol abuse. Attempted suicide rates varied between 21%–54%. In the UK, the estimated rate of premature mortality of patients with bipolar I disorder was 18%. The chronicity of bipolar disorder exerted a profound and debilitating effect on the patient. In Germany, 70% of patients were underemployed, and 72% received disability payments. In Italy, 63%–67% of patients were unemployed. In the UK, the annual costs of unemployment and suicide were £1510 million and £179 million, respectively, at 1999/2000 prices. The estimated UK national cost of bipolar disorder was £4.59 billion, with hospitalization during acute episodes representing the largest component. Bipolar disorder is a major and underestimated health problem in Europe. A number of issues impact on the economic burden of the disease, such as comorbidities, suicide, early death, unemployment or underemployment. Direct costs of bipolar disorder are mainly associated with hospitalization during acute episodes. Indirect costs are a major contributor to the overall economic burden but are not always recognized in research studies.

/pdf/a-systematic-review-of-the-evidence-of-the-burden-of-bipolar-5372pu7wq5.pdf

A systematic review of the evidence of the burden of bipolar disorder in Europe.

This meta-analysis examined the effectiveness of treatments of bipolar depression. Trials were identified using the MEDLINE, EMBASE, http://www.clinicaltrials.gov, and Cochrane databases (1993 to July 2008). The outcome measures included mean change in Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D) total scores, and rates of response and remission. Overall, 19 publications were included. Medications included quetiapine, lamotrigine, paroxetine, lithium, olanzapine, aripiprazole, phenelzine, and divalproex. The most trials were identified for quetiapine (5) and lamotrigine (6). Not all medications were associated with symptomatic improvement (significant reduction in MADRS/HAM-D total scores vs placebo), with lamotrigine, paroxetine, aripiprazole, and lithium not being different from placebo. Highest reductions in MADRS scores versus placebo were reported for the olanzapine-fluoxetine combination (1 trial: -6.6; 95% confidence interval [CI], -9.59 to -3.61; P = 0.000) and quetiapine monotherapy (5 trials: for 300 mg/d, -4.8; 95% CI, -6.18 to -3.49; P = 0.000; for 600 mg/d, -4.8; 95% CI, -6.22 to -3.28; P = 0.000), with quetiapine monotherapy also showing the highest reduction in HAM-D scores (4 trials: -4.0; 95% CI, -5.0 to -2.9; P = 0.000). All medications except paroxetine, lithium, aripiprazole, and phenelzine significantly improved the ratio of probabilities of response (overall rate, 1.31; 95% CI, 1.22-1.40) and remission (1.32; 95% CI, 1.20-1.45) versus placebo. Variability in efficacy exists between treatments of bipolar depression. Quetiapine and the olanzapine-fluoxetine combination showed the greatest symptomatic improvement. Efficacy considerations will need to be balanced against safety and tolerability of the individual agents.

Treatment options for bipolar depression: a systematic review of randomized, controlled trials.

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of o6 months' dur- ation with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combi- nation treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of re- lapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical anti- psychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

/pdf/effectiveness-of-psychotropic-medications-in-the-maintenance-l6w5y1jx4p.pdf

Julie C. Locklear

Papers

Partial Compliance and Risk of Rehospitalization Among California Medicaid Patients With Schizophrenia

A systematic review of the evidence of the burden of bipolar disorder in Europe.

Treatment options for bipolar depression: a systematic review of randomized, controlled trials.

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder : a meta-analysis of randomized controlled trials

Humanistic and economic burden of generalized anxiety disorder in North America and Europe