Statistical power of multiplicity adjustment strategies for correlated binary endpoints.

There are numerous alternatives to the so-called Bonferroni adjustment to control for familywise Type I error among multiple tests. Yet, for the most part, these approaches disregard the correlation among endpoints. This can prove to be a conservative hypothesis testing strategy if the null hypothesis is false. The James procedure was proposed to account for the correlation structure among multiple continuous endpoints. Here, a simulation study evaluates the statistical power of the Hochberg and James adjustment strategies relative to that of the Bonferroni approach when used for multiple correlated binary variables. The simulations demonstrate that relative to the Bonferroni approach, neither alternative sacrifices power. The Hochberg approach has more statistical power for rho

Bias reduction in effectiveness analyses of longitudinal ordinal doses with a mixed-effects propensity adjustment.

A mixed-effects propensity adjustment is described that can reduce bias in longitudinal studies involving non-equivalent comparison groups. There are two stages in this data analytic strategy. First, a model of propensity for treatment intensity examines variables that distinguish among subjects who receive various ordered doses of treatment across time using mixed-effects ordinal logistic regression. Second, the effectiveness model examines multiple times until recurrence to compare the ordered doses using a mixed-effects grouped-time survival model. Effectiveness analyses are initially stratified by propensity quintile. Then the quintile-specific results are pooled, assuming that there is not a propensity x treatment interaction. A Monte Carlo simulation study compares bias reduction in fully specified propensity model relative to misspecified models. In addition, type I error rate and statistical power are examined. The approach is illustrated by applying it to a longitudinal, observational study of maintenance treatment of major depression.

Antidepressant treatment patterns in a novel methadone maintenance clinic targeting young adults an observational study.

This observational study examined the antidepressant treatment patterns of a novel New York City methadone maintenance treatment program (MMTP), founded for the treatment of adolescents and now targeting young adults and older patients with special problems. The goal of the study was to investigate demographic or clinical characteristics that were associated with prescribing patterns, as well as whether antidepressant use was associated with sobriety. The method of data collection was a thorough chart review. Antidepressant treatment was significantly associated with gender, education, marital status, and relapse. However, after controlling for demographic and clinical characteristics, antidepressant treatment was not significantly associated with a reduction in relapse risk. Further research is needed to explore these relationships, as well as their generalizability to adult methadone clinics, and to examine the underlying factors that lead to similarities and distinctions in antidepressant prescribing practices between various types of clinics (i.e., general outpatient vs. methadone maintenance).

Distinguishing bipolar major depression from unipolar major depression with the screening assessment of depression-polarity (SAD-P).

BACKGROUND: Patients with bipolar I or II major depression are often misdiagnosed with unipolar major depression. The goal of this study was to develop and validate a brief instrument to screen for bipolar disorder in patients actively ill with major depression. METHOD: The sample consisted of subjects who enrolled in the National Institute of Mental Health-Collaborative Program on the Psychobiology of Depression-Clinical Studies from 1978 to 1981 during an episode of major depression and included 91 subjects with bipolar I major depression, 52 with bipolar II major depression, and 338 with unipolar major depression diagnosed according to Research Diagnostic Criteria. Most of the subjects were inpatients at the time of enrollment, and subjects were prospectively followed for up to 20 years. In order to create, test, and cross-validate the screening instrument, a split-sample data analytic procedure was performed. This procedure yielded 3 groups of subjects: the bipolar I index sample, the bipolar I cross-validation sample, and the bipolar II cross-validation sample. Each group included subjects with bipolar major depression and subjects with unipolar major depression. Within the bipolar I index sample, subjects with bipolar I major depression at study intake were compared with subjects with unipolar major depression at study intake on a pool of 59 sociodemographic and clinical candidate variables. The 3 variables showing the greatest disparity between bipolar I subjects and unipolar subjects were selected for the screen, the Screening Assessment of Depression-Polarity (SAD-P). The operating characteristics of the SAD-P were then examined within the bipolar I index sample, bipolar I cross-validation sample, and bipolar II cross-validation sample. RESULTS: The items selected for the screening instrument were (1) presence of delusions during the current episode of major depression, (2) number of prior episodes of major depression, and (3) family history of major depression or mania. The screen identified bipolar major depression with a sensitivity of 0.82 in the bipolar I index sample, 0.72 in the bipolar I cross-validation sample, and 0.58 in the bipolar II cross-validation sample. With regard to misclassifying subjects with unipolar major depression, the screen provided a positive predictive value of 0.36 in the bipolar I index sample, 0.29 in the bipolar I cross-validation sample, and 0.27 in the bipolar II cross-validation sample. CONCLUSION: We suggest using the 3-item SAD-P as a preliminary screen for bipolar disorder in patients who present with an active episode of major depression.

Tachyphylaxis in unipolar major depressive disorder.

BACKGROUND: Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis. METHOD: The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders. Subjects diagnosed with unipolar major depressive disorder according to Research Diagnostic Criteria were enrolled from 1978-1981 and prospectively followed for up to 20 years. As an observational study, treatment was recorded but not controlled by anyone connected with the study. Subjects were selected for the present study if at some point during follow-up they received antidepressant medication for treatment of an episode of major depressive disorder, recovered from this episode, and subsequently received maintenance pharmacotherapy. Some subjects were successfully treated for multiple episodes of major depressive disorder and then received maintenance medication after each of these episodes, resulting in multiple maintenance treatment intervals. Data were collected using the Longitudinal Interval Follow-Up Evaluation, and mixed-effects logistic regression was used to test the association of sociodemographic and clinical variables with tachyphylaxis. RESULTS: For the 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder. The median duration of maintenance treatment was 20 weeks. Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals. The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval. CONCLUSIONS: Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence.

Paroxetine, other antidepressants, and youth suicide in New York City: 1993 through 1998.

BACKGROUND: Regulatory agencies in the United Kingdom and the United States have recently issued warnings about a possible link between suicidal ideation and attempts and the use of paroxetine in a pediatric patient population. The objective of this study was to determine the proportion of youth suicides that tested positive for paroxetine or other antidepressants in medical examiner toxicologic testing in New York City from 1993 through 1998, the first 6 years that paroxetine was available in the United States. METHOD: Subjects in this medical examiner surveillance study were suicides less than 18 years of age. Serum toxicology was examined for paroxetine and other antidepressants. RESULTS: There were 66 suicides among persons under 18 years of age in the years 1993 through 1998. Toxicology was tested in 58 (87.9%) of the 66 suicides, and 54 (81.8%) had injury-death intervals of 3 days or less. None of the victims had paroxetine detected in their blood obtained at the time of autopsy. Imipramine was detected in 2 victims and fluoxetine in another 2. CONCLUSION: Despite regulatory concerns, none of the autopsies of youth suicides in New York City detected paroxetine in the victims, although other antidepressants were detected in 4 victims. However, in the vast majority of the youth suicides, there was no evidence of anti-depressant use immediately prior to death.

Inexpensive ethography using digital video.

We describe an inexpensive method for digital video recording of behavioral experiments and present a simple, freely-redistributable software tool enabling ethographic analysis of these recordings via classification of video frames into user-defined categories. While high-end commercial solutions already exist for these purposes, we focus on minimizing equipment expenses and complexity for research projects or undergraduate laboratory courses employing compatible behavioral paradigms.