Negative signs and symptoms secondary to antipsychotics: a double-blind, randomized trial of a single dose of placebo, haloperidol, and risperidone in healthy volunteers.
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.


METHODS
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.
Artaloytia
Juan Francisco
JF
Hospital Universitario 12 de Octobre, Madrid, Spain.
Arango
Celso
C
Lahti
Adrienne
A
Sanz
Javier
J
Pascual
Ana
A
Cubero
Pedro
P
Prieto
David
D
Palomo
Tomás
T
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D001526:Behavioral Symptoms / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D010054:Brief Psychiatric Rating Scale; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006220:Haloperidol / Q000009:adverse effects* / Q000627:therapeutic use; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data*; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012894:Sleep Stages / Q000187:drug effects; D011795:Surveys and Questionnaires
D014150:Antipsychotic Agents; D010919:Placebos; D006220:Haloperidol; D018967:Risperidone