Treatment of Dysthymia and Minor Depression in Primary Care A Randomized Trial in Patients Aged 18 to 59 Years

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Original Research

Treatment of Dysthymia and Minor Depression in Primary Care A Randomized Trial in Patients Aged 18 to 59 Years

J Fam Pract. 2001 May;50(5):405-412

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Design

Patients who met the entrance criteria and consented to the study were randomly assigned to paroxetine, placebo, or PST-PC using a computer-generated random allocation table. Randomization was blocked and stratified by site and by diagnosis. Treatment assignments were held by a local pharmacist and were available to study personnel only in the event of a medical emergency.

Treatment

Patients were scheduled for 6 treatment sessions occurring over 11 weeks. The treatment sessions took place in the general medical setting. Medication visits were 10 to 15 minutes each, were conducted by psychiatrists or psychiatric residents, and consisted of medication dose titration, symptom assessment, a review of adverse effects, and general support. Specific psychologic treatments or counseling were prohibited. Paroxetine and placebo were given in a double-blind fashion. Paroxetine was initiated at 10 mg per day and increased at week 2 to the target dose of 20 mg. At week 4 or 6, the dose could be further increased to 30 mg per day and at week 6 or 8 to 40 mg if there had been limited clinical improvement. Placebo was titrated in an identical fashion.

The PST-PC therapists were PhD psychologists. All therapists received training in PST-PC. The patients received 6 PST-PC sessions, lasting approximately 1 hour for the first visit and 30 minutes for each subsequent visit. Antidepressant medication was prohibited for the PST-PC group.

Assessments

Sociodemographic and clinical information was collected at baseline. Coexisting medical illness was evaluated by chart review using the Duke Severity of Illness Checklist.²⁵ Outcome measurements included self-report and interviewer rated instruments; the latter were completed blind to the patient’s treatment assignment. There were 3 principal outcome measures. One was the 20-item Hopkins Depression self-report scale²⁶ (HSCL-D-20) consisting of the 13-item depression scale and 7 additional depression-related items added to increase responsiveness.²⁷ The HSCL-D-20 score was obtained at baseline and at each treatment visit. The other principal outcome measures were a 17-item Hamilton Depression Rating Scale (HDRS), used to determine remission status, and the 36-item Medical Outcomes Study Short Form (SF-36), that provided 2 functional status measures—a mental health component (MHC) and a physical health component (PHC).^28,29 Both these measures were obtained at baseline and at 6 and 11 weeks.

Data Analysis

For continuous demographic and clinical data, we used parametric and nonparametric analysis of variance to analyze baseline differences across site, diagnostic group, and treatment assignment. Stratified contingency table analyses were used to analyze baseline differences in categorical patient variables. For all analyses, design variables (specified in advance) included diagnosis, treatment provided, and site.

We analyzed the HSCL-D-20 using a nonlinear piece-wise random coefficient model with 2 random intercepts and a random slope fit to the individual patient data.³⁰ Random intercepts were defined at baseline and at week 2. The random intercept at week 2 enabled us to model a nonlinear response to treatment. Treatment effects were evaluated by comparing the slopes of the fitted function from week 2 through week 11. Restricted maximum likelihood estimation was used to fit the random coefficient model to the data.³¹ The Tukey-Kramer multiple comparison procedure³² was used to adjust P values for multiple comparisons. For the HSCL-D-20, analyses were performed both on an intention-to-treat group (full sample) and on an adequate treatment exposure subgroup defined as patients who completed at least 4 treatment sessions.

For the HDRS data, patients were classified as remitted (HDRS≤6) or as nonremitters³³ at week 11 on the basis of previously reported normative data. The analytic method we used was a generalized linear model with binomial response and logit link function; adjustment of P values for multiple comparisons was by the Sidak procedure.³² Six-week assessment scores were carried forward for patients for whom HDRS data were unavailable at the 11-week follow-up. The analysis reported was based on the adequate treatment exposure patient sample. This analysis gives clinicians an estimate of treatment effects for patients who actually received the treatment.

For the SF-36 data, analyses were performed both on the intention-to-treat group and the adequate exposure subgroup. The analytic method used was a mixed model analysis of covariance. Baseline SF-36 MHC and PHC component scores served as covariates in each respective analysis.

Results

Patient Enrollment and Characteristics

Of the 407 patients who received a study assessment, 241 (59%) were eligible and were randomized. Of those patients assessed but not randomized, 22 were eligible but refused participation, and 144 were ineligible Figure 1.The most common reasons for ineligibility were major depression (n=77), depression with an HDRS score of less than 10 (n=26), and no depression diagnosis (n=21).