Pharmacotherapy of impaired affect in recovering schizophrenic patients.
BACKGROUND
Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their 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 defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned 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 supplemental 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 affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.


CONCLUSIONS
Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.
Hogarty
G E
GE
Western Psychiatric Institute and Clinic, University of Pittsburgh, School of Medicine, PA.
McEvoy
J P
JP
Ulrich
R F
RF
DiBarry
A L
AL
Bartone
P
P
Cooley
S
S
Hammill
K
K
Carter
M
M
Munetz
M R
MR
Perel
J
J
D000293:Adolescent; D000328:Adult; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000009:adverse effects; D001008:Anxiety Disorders / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D001590:Benztropine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003866:Depressive Disorder / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D003891:Desipramine / Q000627:therapeutic use; D003937:Diagnosis, Differential; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005476:Fluphenazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006024:Glycopyrrolate / Q000627:therapeutic use; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012737:Sex Factors
D014150:Antipsychotic Agents; D010919:Placebos; D001590:Benztropine; D016651:Lithium Carbonate; C011825:fluphenazine depot; D005476:Fluphenazine; D003891:Desipramine; D006024:Glycopyrrolate