Patients were randomized to paroxetine (n=80), PST-PC (n=80), and placebo (n=81). Sociodemographic and clinical characteristics were similar for the 3 treatment groups Table 1. Comorbid anxiety disorders assessed by the PRIME-MD at baseline were present in approximately 25% of the patients but with no significant difference in prevalence across the 3 treatment groups. Depression severity was mild to moderate as reflected by a mean HDRS of 14.2 (standard deviation [SD]=3.33) and mean HSCL-D-20 of 1.6 (SD=0.65). On the SF-36, mental health functioning was more impaired (MHC mean=33.7; SD=10.2) than physical health functioning (PHC mean=47.1; SD=12.1). At baseline, there were no significant differences between patients with dysthymia and those with minor depression on any of these 4 outcome measure scales.
Treatment Received and Follow-Up
Of the 241 patients randomized, 197 (81.7%) attended at least 4 treatment sessions Figure 1; 191 (79.3%) completed all scheduled treatment sessions. Twenty patients (8.3%) did not attend any treatment sessions; they dropped out after randomization. Of these 20 patients, 16 (80%) were assigned to paroxetine or placebo; 4 (20%) were assigned to PST-PC. Subsequently, 6 patients (2.4%) discontinued treatment for adverse effects; all of these were in the paroxetine group. One patient also in the paroxetine group discontinued because of medical illness. Twenty-three patients (9.5%) with at least 1 treatment visit discontinued for a variety of other reasons, such as relocation, self-medication, or because they felt they were not getting better.
Adherence to paroxetine and placebo was high. By the second treatment visit, 85% of patients initiating treatment achieved the target dose of 20 mg (2 pills) per day (81% of those receiving paroxetine, 89% receiving placebo). By study end, 94% had achieved the target dose or higher. Of patients who came for at least 1 visit, more patients randomized to placebo were increased to 40 mg per day (21/72, 29.2%) than those randomized to paroxetine (10/73, 13.7%; P=.023). For patients randomized to PST-PC, treatment attendance was high. Of those beginning treatment, 84.2% (64/76) completed all 6 treatment sessions.
Outcomes
HSCL-D-20
One principal outcome measure was change in depression level on the HSCL-D-20 scale. In the intention-to-treat analysis, all treatment groups showed significant improvement over the 11-weeks Figure 2. The average mean change was 0.88 (SE=0.08) for paroxetine, 0.79 (0.09) for PST-PC, and 0.85 (0.09) for placebo. For paroxetine and for placebo, the rate of symptom resolution was similar and rapid during the first 2 weeks of treatment: 0.60 (.06) and 0.56 (.06), respectively; from week 2 to week 11 it slowed and remained similar: paroxetine, 0.28 (.06); placebo, 0.29 (.07). For PST-PC in the first 2 weeks, the rate of symptom resolution was slower 0.36 (.06) compared with paroxetine or placebo, but it was more rapid from week 2 through week 11; 0.43 (.07).
In this overall analysis, from baseline to 2 weeks there were significant differences in outcome by site (P=.006) and by treatment group (P=.007) but not by diagnosis (P=.497). For this time period the site by treatment group interaction was marginal (P=.101). Lebanon accounted for the majority of these treatment differences. At that site, from baseline to week 2 the improvement was significantly more rapid for paroxetine (P=.003) and for placebo (P=.016) compared with PST-PC. When outcome was examined from week 2 to week 11, there were no significant differences at the .05 level, although there was a trend toward the earlier pattern of differences by site (P=.104) and by treatment group (P=.190), with PST-PC marginally better than paroxetine (P=.090) and placebo Figure 2. On this measure diagnostic group again showed no relationship to outcome (P=.718). When the overall outcome (baseline to week 11) was examined, there were no significant differences between the 3 intervention groups.
When these analyses were repeated on the adequate treatment exposure group of patients, the results were essentially similar. There was significant reduction in symptomatology for all 3 treatment groups, but from baseline to week 11 there were essentially no differences in the amount of this reduction between the 3 treatment groups.
Remission over 11 Weeks as Measured by HDRS
The proportion of patients achieving remission status (HDRS score 6) was examined using the 197 patients with adequate treatment exposure (4 or more visits). This group was compared with the 44 patients with less than 4 visits on baseline variables. There were no significant differences except for education: 54.5% of those with fewer than 4 visits had 13 or more years of education compared with 75.6% of those with 4 or more visits (P=.005).
In the generalized linear model used to analyze the HDRS remission data, diagnostic group, treatment group, site, and all the interactions (diagnosis by treatment, site by treatment, site by diagnosis, and site by diagnosis by treatment) were entered into the analysis. There was a significant site by treatment group interaction (P=.001) and a significant diagnostic group by treatment group interaction (P=.005). To understand these interaction terms, results were examined separated by diagnosis and by site. For dysthymia at the Lebanon site, there were 2 significant effects: paroxetine had a better outcome than placebo (P <.001) or PST-PC (P<.001). For dysthymia at the Seattle site, both paroxetine and PST-PC had marginally better outcomes than placebo (P=.093 and P=.073, respectively). To display these findings, bivariate analyses were carried out for each diagnosis by site Table 2. Table 2 also shows the remission rates when patients with each diagnosis were combined across sites. For dysthymia, the remission rates were 80% for paroxetine, 56.8% for PST-PC, and 44.4% for placebo (P=.008). For minor depression, the overall remission rate was high (64.0%), and it was similar for each treatment group: 60.7% for paroxetine, 65.5% for PST-PC, and 65.6% for placebo (P=.906).