Investigating Outcomes, Efficacy at ACNP

(This is the third in a series of new research highlights from the 1999 American College of Neuropsychopharmacology Annual Meeting. The second part ran in November Psychiatric Times, p16 -Ed.)

Impact of Fluoxetine on Individual PTSD Symptoms

Samantha Meltzer-Brody, M.D., et al. provided data suggesting that fluoxetine (Prozac) exerts a broad-spectrum effect in reducing all symptom clusters in a sample of 53 patients with posttraumatic stress disorder (PTSD). Their results indicated that fluoxetine was most effective in treating the individual symptoms of intrusive recollections and having a sense of failure.

The double-blind study of fluoxetine therapy in civilians with PTSD from varied trauma assessed subjects using the Structured Clinical Interview for PTSD and the Davidson Trauma Scale. At the end of the study, all Davidson Trauma Scale clusters were found to have statistical significance. Two individual items from this scale, intrusive recollections and having a sense of a foreshortened future, were the most responsive to the effects of fluoxetine treatment. All Structured Clinical Interviews for PTSD clusters were statistically significant; however, individual symptoms in this instrument were not found to have statistical significance.

Sertraline Versus Bupropion SR Treatment of Major Depression: Sexual Functions

Alan Metz, M.D., and other Glaxo-Wellcome investigators presented data comparing the sexual functioning effects as well as the safety and efficacy of bupropion sustained release (BuSpar SR), sertraline (Zoloft) and placebo. A total of 364 outpatients with moderate to severe recurrent major depression with normal sexual functioning were randomized to receive bupropion SR (150 mg/day to 400 mg/day) (n=122), sertraline (50 mg/day to 200 mg/day) (n=118) or placebo (n=124) for eight weeks in this double-blind, multicenter study. Efficacy was evaluated by the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression (CGI) Scales for Severity of Illness and Improvement. Sexual functioning was evaluated at each clinic visit by structured interviews. Vital signs, weight and adverse effects were also collected at each clinic visit.

Analyses showed that sertraline was associated with a significantly greater incidence of orgasm dysfunction than bupropion SR or placebo, and it had more of a negative impact on satisfaction with sexual functioning than bupropion SR or placebo. ANOVA analyses of the efficacy measures showed comparable efficacy between bupropion SR and sertraline; bupropion SR showed significant improvement compared to placebo at day 56. Both active drugs were well-tolerated with a low rate of discontinuation for adverse events. Thus, at comparably effective doses, sertraline was associated with a significantly greater incidence of orgasm dysfunction and had more of a negative impact on satisfaction with sexual functioning than bupropion SR.

Suicide in the Elderly and Alzheimer's Disease

University of Rochester investigator Ana Rubio, M.D., Ph.D., studied suicide to determine if elderly patients with Alzheimer's disease (AD) were overrepresented in elderly patients committing suicide. Rubio compared subjects older than 60 years who committed suicide with matched controls who died of natural causes. Data were analyzed by multiple logistic regression to determine whether there was an association between AD stage and suicide, with a higher AD stage predicting a greater likelihood of suicide. Rubio's findings led her to conclude that patients with late stages of AD pathology are able to commit suicide, and that moderate to severe AD pathology is overrepresented in a sample of elderly patients who complete suicide.

Acute and Continuation Fluoxetine Therapy of Minor Depression

The results of a four-week, single-blind placebo and fluoxetine treatment trial and a continuation (over six months) fluoxetine treatment trial for minor depression were reported. These trials tested the hypothesis that minor depression is not evanescent and would respond to both acute and continuation treatment with fluoxetine. Seventy-two percent of patients who met entrance criteria were randomized into the study.

Patients randomized to active treatment with fluoxetine had statistically significant decreases in HAM-D-17 scores. During continuation treatment, 52% of fluoxetine-treated patients had complete symptomatic response (no depression symptoms and restoration of functioning to normal range) compared to 27% of placebo-treated patients.

This study was headed by Lewis Judd, M.D., chair of the department of psychiatry at the University of California at San Diego School of Medicine. His team concluded that minor depression is a clinically significant subtype of the depressive disorders and can be treated successfully.

Continuation Combination Pharmacotherapy for Delusional Depression in Elderly Patients

Barnett S. Meyers, M.D., and investigators at New York-Presbyterian Hospital, Weill Medical College of Cornell University presented the results of a study of the efficacy of combination pharmacotherapy for delusional depression in older patients. The trial included 29 remitted older patients (age=72.28.5 years) with DSM-IV unipolar depression. They were randomized to double-blind, placebo-controlled continuation treatment with nortriptyline (Pamelor, Aventyl) plus perphenazine (Etrafon, Triavil) or nortriptyline monotherapy following electroconvulsive therapy. Target nortriptyline concentration was 80 ng/ml to 120 ng/ml, and perphenazine doses were 8 mg/day to 16 mg/day. Baseline and prerandomization HAM-D-17 scores were 27.47 and 3.24, respectively.

Relapse rates did not differ significantly during the five months of treatment (13.3% versus 15.4%). Combination subjects had significantly greater EPS scores, incidence of falling and treatment-emergent dyskinesia (42% versus 0%). These findings indicate that continuation treatment using moderate doses of a conventional antipsychotic does not decrease relapse rates, but it is associated with significant untoward adverse events in older people with delusional depression.

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