A PLACEBO-CONTROLLED TRIAL OF FLUOXETINE ADDED TO NEUROLEPTIC IN PATIENTS WITH SCHIZOPHRENIA

Following a 2-week placebo lead-in, schizophrenic patients were random ly assigned to fluoxetine 20 mg/day or placebo added to depot neurolep tic for a 6-week, double blind trial. All patients had received a stab le dose of depot neuroleptic for at least 6 months and did not meet cr iteria for depression, Serum samples were obtained at baseline and at weeks 4 and 6. Scores on the negative symptom subscale of the Brief Ps ychiatric Rating Scale (BPRS) were significantly lower at week 6, cont rolling for baseline scores, in patients receiving fluoxetine (n = 20) compared to patients receiving placebo (n = 21). Measures of psychosi s, depression, global functioning and extrapyramidal symptoms (EPS) di d not differ between groups at week 6. Fluoxetine administration was a ssociated with a mean 65% increase in serum fluphenazine concentration s in 15 patients and a mean 20% increase in serum haloperidol concentr ations in three patients. The change in negative symptoms at week 6 di d not correlate with serum concentrations of fluoxetine or norfluoxeti ne, but did inversely correlate with S-norfluoxetine, an active stereo isomer of fluoxetine. For these chronically ill patients, fluoxetine s ignificantly improved negative symptoms and did not worsen EPS, despit e causing substantial elevation in serum concentrations of neuroleptic s.