Adjunctive Armodafinil in Schizophrenia

John M. Kane, MD; Richard S. E. Keefe, PhD; Deepak C. D’Souza, MD, MBBS; Ashwin A. Patkar, MD; James M. Youakim, MD; Jane Tiller, FRCPsych; and Ronghua Yang, PhD
The Zucker Hillside Hospital, Glen Oaks, New York (Dr Kane); Duke University, Durham, North Carolina (Drs Keefe and Patkar); Yale University School of Medicine, New Haven, Connecticut (Dr D’Souza); and Cephalon Inc, Frazer, Pennsylvania (Drs Tiller, Yang, and Youakim)

This poster presentation was supported by Cephalon, Inc.

Background: Armodafinil, the R- and longer lasting isomer of modafinil, improves wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea, shift-work disorder, and narcolepsy.¹ In patients with schizophrenia, modafinil may improve cognition and other symptoms.² This 4-week, double-blind, proof-of-concept study evaluated the efficacy and tolerability of armodafinil as adjunctive therapy in adults with schizophrenia.

Methods: Enrolled patients had stable schizophrenia for ≥8 weeks, were receiving oral risperidone, olanzapine, or paliperidone for ≥6 weeks (stable dose for ≥4 weeks), and were randomized to once-daily placebo or armodafinil 50, 100, or 200 mg (initiated at 50 mg and titrated on days 2, 4, and 6). The primary outcome measure was the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery composite score. Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS).

Results: Sixty patients were randomized (15 per treatment group). Mean (SD) age was 43.2 (9.6) years and 73% were men. There were no apparent differences between groups in the MATRICS composite score at final visit: effect sizes (95% confidence intervals [CI]) with armodafinil 50, 100, and 200 mg versus placebo were -0.04 (-0.81, 0.73), 0.09 (-0.68, 0.86), and 0.15 (-0.66, 0.95), respectively. There were numerically greater reductions with armodafinil 200 mg versus placebo at final visit in mean PANSS total score (effect size [95% CI] 0.73 [-0.08, 1.54]) and PANSS negative symptoms score (effect size 1.69 [0.78, 2.60]). There was no evidence of worsening of positive symptoms in patients in the armodafinil group compared with the placebo group (PANSS positive symptoms score). Armodafinil was generally well tolerated. The most common adverse events reported with armodafinil (all doses) versus placebo, respectively, were: diarrhea (n=5 versus 1), headache (4 versus 1), and restlessness (3 versus 0). One serious adverse event was reported in a patient receiving placebo.

Conclusions: Adjunctive armodafinil 200 mg/day may improve negative symptoms of schizophrenia, without worsening positive symptoms. There was no apparent improvement in cognition. Armodafinil was generally well tolerated. Further investigation in larger studies is warranted.

References

1. Nishino S, Okuro M. Armodafinil for excessive daytime sleepiness. Drugs Today. 2008;44(6):395–414.
2. Saavedra-Velez C, Yusim A, Ambarasan D, et al. Modafinil as an adjunctive treatment of sedation, negative symptoms, and cognition in schizophrenia: a critical review [published online ahead of print November 24, 2008]. J Clin Psychiatry. 2009;70(1):104–112. doi: 10.4088/JCP.07r03982.

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