Olanzapine Long-Acting Injection: A 24-Week, Randomized, Double-Blind Trial of Maintenance Treatment in Patients With Schizophrenia

• Published in: The American journal of psychiatry Vol. 167; no. 2; pp. 181 - 189
• Main Authors: Kane, John M., Detke, Holland C., Naber, Dieter, Sethuraman, Gopalan, Lin, Daniel Y., Bergstrom, Richard F., McDonnell, David
• Format: Journal Article
• Language: English
• Published: Arlington, VA American Psychiatric Association 01.02.2010
• Subjects: Administration, Oral; Adolescent; Adult; Adult and adolescent clinical studies; Aged; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Benzodiazepines - administration & dosage; Benzodiazepines - adverse effects; Benzodiazepines - therapeutic use; Biological and medical sciences; Delayed-Action Preparations - adverse effects; Double-Blind Method; Drug therapy; Female; Humans; Injections, Intramuscular; Male; Medical sciences; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Psychiatric Status Rating Scales; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Psychotropic drugs; Risk factors; Schizophrenia; Schizophrenia - drug therapy; Young Adult; Human; Dibenzodiazepine derivatives; Atypical antipsychotic; Olanzapine; Controlled release form; Neuroleptic; Psychotropic; Dopamine antagonist; Serotonin antagonist; Schizophrenia; Serotonine receptor; Thienobenzodiazepine derivatives; Psychosis; D2 Dopamine receptor; Maintenance treatment; Double blind study; Dosage form
• ISSN: 0002-953X; 1535-7228; 1535-7228
• DOI: 10.1176/appi.ajp.2009.07081221

ObjectiveThe purpose of the present study was to evaluate the efficacy and tolerability of olanzapine long-acting injection for maintenance treatment of schizophrenia. MethodOutpatients with schizophrenia who had maintained stability on an oral regimen of olanzapine (10, 15, or 20 mg/day) for 4 to 8 weeks were randomly assigned to 24 weeks of double-blind treatment with "low" (150 mg every 2 weeks; N=140), "medium" (405 mg every 4 weeks; N=318), or "high" (300 mg every 2 weeks; N=141) doses of olanzapine long-acting injection; a very low reference dose of olanzapine long-acting injection (45 mg every 4 weeks; N=144); or their stabilized dose of oral olanzapine (N=322). Rates of and time to psychotic exacerbation were estimated using Kaplan-Meier methodology. ResultsAt 24 weeks, the majority of oral olanzapine-treated patients (93%), as well as most olanzapine long-acting injection-treated patients receiving high (95%), medium (90%), low (84%), and very low doses (69%), remained exacerbation free, with the therapeutic 4-week regimen (medium dose) and pooled 2-week regimen (low and high doses) demonstrating efficacy similar to that of oral olanzapine as well as to each other. The three standard long-acting doses were superior to the very low reference dose based on time to exacerbation. Incidence of weight gain ≥7% of baseline was 21% for oral olanza­pine compared with 21%, 15%, 16%, and 8% for the high, medium, low, and very low olanzapine long-acting treatment groups, respectively. No clinically significant differences were observed between the long-acting injection and oral olanzapine groups in general safety parameters. Few injection-site reactions occurred (3%). Two patients experienced sedation and delirium consistent with olanzapine overdose following possible accidental intravascular injection. ConclusionsOlanzapine long-acting injection was efficacious in maintenance treatment of schizophrenia for up to 24 weeks, with a safety profile similar to oral olanzapine except for injection-related adverse events.