PHARMACOTHERAPY OF IMPAIRED AFFECT IN RECOVERING SCHIZOPHRENIC-PATIENTS

Background: Prominent and persistent anxiety, depression, and/or negat ive features characterize a substantial minority of recovered or resid ually psychotic schizophrenic outpatients and contribute to poor outco me. Because extrapyramidal side effects of typical neuroleptic medicat ions often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and the ir treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken. Methods: In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a de fect state (patients with negative symptoms) participated in a double- blind, intramuscular challenge that compared centrally acting benztrop ine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 d istressed patients and 22 patients in a defect state were randomly ass igned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a suppl emental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks. Results: For patients who were already maintained on antiparkinsonian medication, impaired affe ct was not resolved by additional benztropine. Only distressed patient s with a family history of severe mental disorder (often affective) sh owed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neurole ptic medication dose, but negative symptoms persisted. Desipramine imp roved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improve d in women only. Lithium positively affected multiple indexes of anxie ty and anxious depression. Conclusion: Most often, persistent affectiv e impairments are neither resistant extrapyramidal side effects nor ch aracterological traits. Thymoleptics improve the non-phasic, chronic t ypes of anxiety and depression in contrast to the acute, episodic form s, for which little support can be found in the literature.