Armodafinil as adjunctive therapy in adults with cognitive deficits associated with schizophrenia: a 4-week, double-blind, placebo-controlled study.

OBJECTIVE

To evaluate the efficacy and tolerability of armodafinil, the longer-lasting isomer of modafinil, as adjunctive therapy in patients with schizophrenia.

METHOD

This 4-week, randomized, double-blind, placebo-controlled, proof-of-concept study was conducted between July and December 2007. Patients had a history of stable schizophrenia (DSM-IV-TR criteria) for ≥ 8 weeks and were treated with oral risperidone, olanzapine, or paliperidone for ≥ 6 weeks at stable doses for ≥ 4 weeks. Patients were randomly assigned to once-daily placebo or armodafinil 50, 100, or 200 mg. The primary efficacy measure was the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery. Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS).

RESULTS

Sixty patients were randomly assigned (15 in each group). No apparent differences between groups in the MATRICS composite score were observed (mean ± SD change from baseline to final visit: armodafinil 50 mg, 1.9 ± 6.22; 100 mg, 2.8 ± 7.98; 200 mg, 2.9 ± 4.72; placebo, 2.2 ± 5.06). The mean ± SD changes in PANSS total scores were -6.3 ± 7.25 for armodafinil 200 mg and -1.7 ± 4.89 for placebo at final visit (effect size=0.73; 95% CI, -0.08 to 1.54) and PANSS negative symptoms scores were -3.4 ± 2.07 and 0.1 ± 1.93 (effect size=1.69; 95% CI, 0.78 to 2.60), respectively. Although reductions in SANS total score were observed with both armodafinil and placebo at final visit, no between-group difference was shown. Armodafinil was generally well tolerated, with diarrhea and headache the most commonly reported adverse events. There was no evidence of worsening of psychosis with adjunctive armodafinil.

CONCLUSIONS

In this 4-week study, adjunctive armodafinil was not associated with an improvement in cognitive measures, but armodafinil 200 mg/d appeared to mitigate the negative symptoms of schizophrenia. Treatment was generally well tolerated.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00487942.