The Dose Reduction in Schizophrenia (DORIS) Study: a final report

Twenty-one medication-free chronic schizophrenics were randomly assigned to three treatment groups: 50% blockade of the bromocriptine growth hormone (GH) response, 100% blockade or 10 ng/ml haloperidol. Only seven of the 21 patients showed a significant improvement after 6 weeks in positive psychotic symptoms; six of the seven responders came from the 50 and 100% blockade groups, suggesting greater efficacy at lower doses. Fifty percent blockade was associated with an average daily haloperidol dose of 3.2 mg and plasma haloperidol levels below the limit of detection (< 1 ng/ml). 100% blockade was associated with a daily dose of 6.5 mg and a plasma haloperidol level of 1 ng/ml. Negative symptoms significantly improved in only four of the 21 patients, and three of these patients were from the 100% blockade group. Twenty-nine patients currently receiving 20 mg/day haloperidol were randomly assigned to three treatment groups: placebo, 100% blockade of the GH response and 10 ng/ml. Patients in the placebo group showed significant deterioration along both the positive and negative symptom dimensions. There were no significant symptom differences between the 100% blockade and the 10 ng/ml groups. The patients in the 100% blockade group had on average a daily dose reduction from 20 to 11 mg/day and a 65% reduction in the plasma haloperidol level. There was a 70% difference in the average daily dose for 100% blockade between the two study arms. The higher daily dose in the dose-reduction arm may reflect receptor up-regulation and/or other "tolerance'-like mechanisms associated with chronic neuroleptic administration.