A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode nonaffective psychosis.
OBJECTIVE
Randomized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis. However, these results may not be generalizable to routine clinical practice. We evaluated the effectiveness, tolerability, and safety of olanza-pine, risperidone, and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical settings.


METHODS
172 patients participated in a practical clinical trial and were randomly assigned to haloperidol (N = 56), risperidone (N = 61), and olanzapine (N = 55). The mean modal daily doses were 5.4 mg/day for halo-peridol, 4 mg/day for risperidone, and 15.3 mg/day for olanzapine; 98.3% of subjects were drug naive at baseline. Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal (February 2001 to February 2005) intervention program of first-episode psychosis (schizophrenia spectrum disorders, DSM-IV criteria) are reported.


RESULTS
All 3 treatments showed similar effectiveness in reducing the severity of general, negative, and positive symptomatology after 6 weeks of treatment, as reported by mean change in total Clinical Global Impressions-Severity of Illness scale, Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks. The proportion of study subjects responding, defined as 40% or greater BPRS total score improvement from baseline, was 57.1% (N = 32 of 56) haloperidol, 52.5% (N = 32 of 61) risperidone, and 63.6% (N = 35 of 55) olanzapine, with no statistical differences among groups. The frequency of extrapyramidal symptoms (chi(2) = 24.519; p < .001) and concomitant anticholinergic medication use (chi(2) = 57.842; p < .0001) was greater with haloperidol than olanzapine or risperidone. Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups (p < .001).


CONCLUSIONS
Relatively low doses of haloperidol, risperidone, and olanzapine are equally effective for the acute treatment of first-episode nonaffective psychosis under usual conditions of real clinical practice.
Crespo-Facorro
Benedicto
B
University Hospital Marqués de Valdecilla, Department of Psychiatry, Santander, Spain. bcfacorro@humv.es
Pérez-Iglesias
Rocío
R
Ramirez-Bonilla
Mariluz
M
Martínez-García
Obdulia
O
Llorca
Javier
J
Luis Vázquez-Barquero
José
J
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004334:Drug Administration Schedule; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine