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Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic study


  • Presented in part at the 49th annual meeting of the New Clinical Drug Evaluation Unit, Hollywood, Fla., June 29, 2009–July 02, 2009. The authors wish to thank the many collaborators who made this study possible: Drexel University College of Medicine, Department of Psychiatry, Philadelphia, PA, USA; Friends Hospital, Philadelphia, PA, USA; Montgomery County Community College, Blue Bell, PA, USA; Montgomery County Emergency Services, Norristown PA, USA; and NAMI – Montgomery County Chapter. Address correspondence and reprint requests to Dr Josiassen, Translational Neuroscience, LLC, 180 Barren Hill Road, Conshohocken, PA 19428; (e-mail). This study was funded by BristolMyers Squibb.

Professor Richard C. Josiassen, Drexel University College of Medicine, Philadelphia, PA 19102-1192, USA. Email:


Objective: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis.

Method: In a naturalistic, ‘single-blind’ design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly.

Results: The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged.

Conclusions: Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms.