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Modafinil: A Candidate for Pharmacotherapy of Negative Symptoms in Schizophrenia

Published online by Cambridge University Press:  28 November 2007

John H. Peloian  and
Joseph M. Pierre
John H. Peloian
Affiliation:
Department of Psychiatry, VA Greater Los Angeles Healthcare System; Email: jpeloian@ucla.edu
Joseph M. Pierre
Affiliation:
Department of Psychiatry, VA Greater Los Angeles Healthcare System Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, USA; Email: joseph.pierre2@va.gov
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Extract

ABSTRACT

Background: Although historically neglected in clinical research, negative symptoms of schizophrenia are now considered distinct targets of pharmacotherapy. While second-generation antipsychotic treatments were heralded as having a greater therapeutic impact on negative symptoms than their conventional antipsychotic counterparts, the size of this effect is modest. Adjunctive medications such as antidepressants offer limited efficacy, while stimulants have a poor risk–benefit profile. More recently, promising results have been demonstrated with pro-glutamatergic agents such as glycine or D-cycloserine, although a larger trial found no advantage with either agent compared with placebo. Modafinil, a novel wakefulness-promoting agent, is an intriguing candidate for adjunctive pharmacotherapy to treat negative symptoms in schizophrenia. We explored this therapeutic potential through a placebo-controlled trial of patients with prominent negative symptoms. Methods: We randomly assigned patients with schizophrenia or schizoaffective disorder to treatment with either modafinil or placebo for 8 weeks. Double-blind assessments of clinical symptoms and neurocognition were administered at baseline and every 2 weeks thereafter. Results: Twenty subjects were enrolled (N = 10 modafinil, N = 10 placebo). There were no significant differences between modafinil and placebo for changes in negative symptom ratings, the primary study endpoint. However, modafinil treatment was associated with a greater rate and degree of global improvement at study endpoint compared with placebo. No significant worsening of psychopathology was observed and modafinil was well-tolerated. Interpretation: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms. These findings support additional research into a potential role for modafinil in the treatment of negative symptoms in schizophrenia.

Keywords

cognitiondeficit syndromemodafinilnegative symptomsschizophrenia.
Type
Research Article
Information
Progress in Neurotherapeutics and Neuropsychopharmacology , Volume 3 , Issue 1 , January 2008 , pp. 259 - 274
Copyright
© 2008 Cambridge University Press

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