Negative Signs and Symptoms Secondary to Antipsychotics: A Double-Blind, Randomized Trial of a Single Dose of Placebo, Haloperidol, and Risperidone in Healthy Volunteers

• Published in: The American journal of psychiatry Vol. 163; no. 3; pp. 488 - 493
• Main Authors: Artaloytia, Juan Francisco, Arango, Celso, Lahti, Adrienne, Sanz, Javier, Pascual, Ana, Cubero, Pedro, Prieto, David, Palomo, Tomás
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01.03.2006; American Psychiatric Association
• Subjects: Adolescent; Adult; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Basal Ganglia Diseases - chemically induced; Basal Ganglia Diseases - diagnosis; Basal Ganglia Diseases - epidemiology; Behavioral Symptoms - chemically induced; Behavioral Symptoms - diagnosis; Behavioral Symptoms - epidemiology; Biological and medical sciences; Brief Psychiatric Rating Scale; Clinical trials; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug therapy; Female; Haloperidol - adverse effects; Haloperidol - therapeutic use; Health Status; Hospitals; Humans; Male; Medical sciences; Middle Aged; Neuropharmacology; Patients; Pharmaceutical industry; Pharmacology. Drug treatments; Placebos; Psychiatric Status Rating Scales - statistics & numerical data; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Risperidone - adverse effects; Risperidone - therapeutic use; Schizophrenia; Schizophrenia - diagnosis; Schizophrenia - drug therapy; Schizophrenic Psychology; Sleep Stages - drug effects; Surveys and Questionnaires; Atypical antipsychotic; Healthy subject; Neuroleptic; Psychotropic; Dopamine antagonist; Serotonin antagonist; Butyrophenone derivatives; Serotonine receptor; Haloperidol; Psychosis; Chemotherapy; D2 Dopamine receptor; Treatment; Negative symptom; Placebo; Double blind study; Risperidone
• DOI: 10.1176/appi.ajp.163.3.488
• ISSN: 0002-953X

OBJECTIVE: Despite the clinical observation that antipsychotics can produce negative symptoms, no previous controlled study, to our knowledge, has evaluated this action in healthy subjects. The present study assessed observer-rated and self-rated negative symptoms produced by conventional and second-generation antipsychotics in healthy volunteers. METHOD: The authors used a double-blind, placebo-controlled trial of single doses of haloperidol (5 mg) and risperidone (2.5 mg) in normal subjects. Thirty-two subjects were administered haloperidol, risperidone, and placebo in a random order. Motor variables and observer-rated negative symptoms were assessed after 3-4 hours and subjective negative symptoms and drowsiness after 24 hours. RESULTS: Neither of the active drugs caused significant motor extrapyramidal symptoms after administration. Haloperidol caused significantly more negative signs and symptoms than placebo on the Scale for the Assessment of Negative Symptoms (SANS) and two self-rated negative symptom scales: the Subjective Deficit Syndrome Scale total score and an analog scale that evaluates subjective negative symptoms. Risperidone caused significantly more negative signs and symptoms than placebo on the Brief Psychiatric Rating Scale (BPRS), the SANS, the Subjective Deficit Syndrome Scale total score, and the analog scale for subjective negative symptoms. After control for drowsiness, risperidone but not haloperidol produced more negative symptoms than placebo on the BPRS and the SANS. Significance was lost for the subjective negative symptoms with both drugs. CONCLUSIONS: Single doses of both haloperidol and risperidone produce negative symptoms in normal individuals. Drowsiness may be an important confounding factor in the assessment of negative symptoms in antipsychotic trials.