A double-blind randomized comparison of nortriptyline plus perphenazine versus nortriptyline plus placebo in the treatment of psychotic depression inlate life

Objective: To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression, Method: The efficacy of nortriptyline plus placebo versus nortriptyline plu s perphenazine was compared in 36 patients aged 50 years or older presentin g with a major depressive episode with psychotic features (DSM-III-R criter ia). Patients wt re started openly on nortriptyline treatment titrated to t herapeutic levels. They were then randomly assigned under double-blind cond itions to addition of perphenazine or placebo, Outcomes were compared in th e 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side eff ects were assessed with the Geriatric Movement Disorder Assessment. Results: Both treatments were well tolerated. Of the 36 randomly assigned p atients. 2 (1 in each group) dropped out due to treatment-related adverse e ffects. Four additional patients dropped out for administrative reasons. Th irty patients received nortriptyline for at least 4 weeks combined with eit her perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in t he 2 treatment groups when comparing their scores on the HAM-D, the BPRS, i ts psychoticism subscale, or any side effects measure. Rates of response (d efined as resolution of both depression and psychosis) did not differ signi ficantly in the 2 groups (nortriptyline-plus-perphenazine group, 50% vs. no rtriptyline-plus-placebo group. 44%,). Conclusion: When treating older patients with psychotic depression, the add ition of a moderate dose of a traditional neuroleptic to a tricyclic antide pressant was well tolerated but did not improve efficacy. This finding supp orts existing data suggesting that the pathophysiology (and thus the requir ed treatment) of psychotic depression may be different early and late in li fe.