A Double-Blind Randomized Comparison of Nortriptyline Plus Perphenazine Versus Nortriptyline Plus Placebo in the Treatment of Psychotic Depression in Late Life
J Clin Psychiatry 2001;62(8):597-604
© Copyright 2015 Physicians Postgraduate Press, Inc.
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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 plus perphenazine was compared
in 36 patients aged 50 years or older presenting with a major
depressive episode with psychotic features (DSM-III-R criteria).
Patients were started openly on nortriptyline treatment titrated
to therapeutic levels. They were then randomly assigned under
double-blind conditions to addition of perphenazine or placebo.
Outcomes were compared in the 2 treatment groups using measures
including the Hamilton Rating Scale for Depression (HAM-D) and
the Brief Psychiatric Rating Scale (BPRS); side effects were
assessed with the Geriatric Movement Disorder Assessment.
Results: Both treatments were well tolerated. Of
the 36 randomly assigned patients, 2 (1 in each group) dropped
out due to treatment-related adverse effects. Four additional
patients dropped out for administrative reasons. Thirty patients
received nortriptyline for at least 4 weeks combined with either
perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks
(median = 9 weeks). There was no significant difference between
the completers in the 2 treatment groups when comparing their
scores on the HAM-D, the BPRS, its psychoticism subscale, or any
side effects measure. Rates of response (defined as resolution of
both depression and psychosis) did not differ significantly in
the 2 groups (nortriptyline-plus-perphenazine group, 50% vs.
nortriptyline-plus-placebo group, 44%).
Conclusion: When treating older patients
with psychotic depression, the addition of a moderate dose of a
traditional neuroleptic to a tricyclic antidepressant was well
tolerated but did not improve efficacy. This finding supports
existing data suggesting that the pathophysiology (and thus the
required treatment) of psychotic depression may be different
early and late in life.