METHYLENE-BLUE ADJUVANT THERAPY OF SCHIZOPHRENIA

There is growing interest in the role of the nitric oxide (NO) pathway in idiopathic psychotic disorders such as schizophrenia. In this prel iminary study, we examined the therapeutic efficacy of methylene blue (MB), a ''downstream'' inhibitor of one of NO's actions, administered orally as an adjuvant to conventional neuroleptic medications. Specifi cally, MB blocks NO's activation of soluble guanylyl cyclase. MB has p reviously been reported to have therapeutic effects in the treatment o f psychosis and mania. Preclinical data also suggest that MB might pos sess antipsychotic potential. Participants in the current study were e ight patients with schizophrenia who had incomplete responses to conve ntional antipsychotics (as evidenced by a Brief Psychiatric Rating Sca le [BPRS] total score of 35 or more). These patients completed a 4-wee k open-label study with a 1 week ''off'', 2 week ''on'', and one final week ''off'' design. Measures of treatment efficacy were the BPRS, Sc hedule for the Assessment of Negative Symptoms, and Clinical Global Im provement Scale administered weekly. Final scores for each outcome mea sure item were based on the consensus of at least two trained raters p resent during each rating interview. A statistically significant, albe it modest, decrease in the severity of psychopathology was observed wh ile the subjects were taking MB, and psychopathology significantly wor sened when MB was discontinued. The results suggest a need for further study with MB or perhaps other NO-dependent guanylyl cyclase-inhibiti ng medications.