Antidepressant efficacy in HIV-seropositive outpatients with major depressive disorder: an open trial of nefazodone.

BACKGROUND: Treatment studies of major depression in patients who are seropositive for the human immunodeficiency virus (HIV) have shown comparable efficacy for both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Nefazodone appears to be more tolerable than TCAs and similar to SSRIs. This study examined the efficacy and tolerability of nefazodone in an open 12-week trial of HIV-seropositive outpatients with major depressive disorder. METHOD: Fifteen HIV-seropositive patients with DSM-IV major depressive disorder and a 21-item Hamilton Rating Scale for Depression (HAM-D) score of > or =18 were treated with open-label nefazodone for 12 weeks. Hamilton Rating Scale for Anxiety, HAM-D, Clinical Global Impressions scale, and Systematic Assessment for Treatment Emergent Events general inquiry (for safety and tolerability) scores were obtained at weeks 2, 4, 6, 8, and 12. RESULTS: Of 15 patients receiving nefazodone, 4 discontinued treatment (1 for adverse effects). Of 11 patients who completed the trial, 8 (73%) were classified as full responders with a 50% reduction in HAM-D scores and final CGI score of 1 or 2, and 10 (91%) were classified as partial responders (only 50% reduction in HAM-D scores). Nefazodone-treated subjects experienced few total adverse effects (mean = 1.5), no sexual side effects, and low rates of adverse-effect-related dropout (1 subject, 7%). CONCLUSION: Depressed HIV-seropositive outpatients respond to nefazodone comparably to other outpatient populations and have few adverse effects, suggesting that nefazodone may have a role in the treatment of depression in HIV-seropositive patients. Potential drug interactions with protease inhibitors indicate that it is essential to evaluate for appropriate dosing to avoid adverse effects and increase overall antidepressant efficacy.

Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients.

OBJECTIVE: This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection. METHOD: Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12. RESULTS: Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%). CONCLUSIONS: Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.

Cognitive functions and complaints in HIV-1 individuals treated for depression.

Progressive neuropsychological dysfunction and complaints of cognitive difficulty frequently accompany HIV-1 infection. Providing appropriate treatment to HIV-1 patients requires determination of the extent to which the presentation of cognitive complaints reflects HIV-1-associated neuropsychological abnormalities or represents expression of depressive symptomatology. We prospectively treated 75 HIV-1 patients who were not demented but met criteria for major mood disorder with antidepressants for 12 weeks and compared pretreatment and posttreatment measures of depression, cognitive complaints, and neuropsychological performance. Complaints of difficulty with memory and attention were found to be independent of neuropsychological impairment, whereas memory complaints were highly correlated with severity of depression. Cognitive complaints declined significantly across the course of treatment for those patients who responded to antidepressant treatment. All patients, regardless of antidepressant treatment response, exhibited parallel improvement on 12-week follow- up neuropsychological examination. These findings suggest that treatment of depression affects cognitive complaints in HIV-1 individuals and that cognitive complaints of patients in asymptomatic or early symptomatic stages of HIV-1 infection may signal the need for evaluation of depression. In patients with more advanced HIV-1 infection, investigation into the basis of cognitive complaints may require a dual assessment of mood disturbance and neuropsychological status.