Few patients achieved a favorable outcome in the year after a first hospitalization for an affective psychosis. Low socioeconomic status, poor premorbid function, treatment noncompliance, and substance abuse were associated with lower rates or delayed onset of recovery.

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Evidence from earlier studies indicates that the antimanic action of valproate becomes most apparent within 1-4 days of achieving serum concentrations 50 µg/ml, that valproate can be orally loaded with achievement of therapeutic serum concentrations within the first several days of treatment, there is a rapid onset of response, and minimal side effects. To provide further data on the safety and efficacy of valproate oral loading in the treatment of acute mania, we evaluated 13 consecutive patients with acute manic syndromes who received valproate initiated at a dosage of 20 mg/kg/day. In most cases, valproate was added to other psychotropics. All 13 patients received at least 5 full days of valproate maintained at or above 20 mg/kg/day, and valproate serum concentrations were 50 µg/ml (mean ± SD = 88 + 25) by the second or third day of treatment. Ten (77%) patients displayed a moderate or marked response. Side effects were infrequent and minor. Consistent with our earlier study, these findings suggest that valproate can be safely administered via a loading dose of 20 mg/kg/day to patients with acute mania, including those on other psychotropics, and that it may produce a rapid response with minimal side effects.

The relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder was studied. Sixty-two patients (29 depressed type; 33 bipolar type) entered a three-site, randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). Trained raters assessed baseline, weekly, and end-of-study levels of psychopathology with the Positive and Negative Syndrome Scale (PANSS), the 24-item Hamilton Rating Scale for Depression (HAM-D-24) and the Clinician-Administered Rating Scale for Mania (CARS-M). The authors were unable to statistically distinguish between risperidone and haloperidol in the amelioration of psychotic and manic symptoms. In addition, there was no difference in worsening of mania between the two agents in either subgroup (i.e., depressed or bipolar subgroups). For the total PANSS, risperidone produced a mean decrease of 16 points from baseline compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively, and for the CARS-M Mania subscale, 3 and 7 points, respectively. Additionally, risperidone produced a mean decrease of 13 points from the baseline 24-item HAM-D, compared with an 8-point decrease with haloperidol. In those patients who had more severe depressive symptoms (i.e., HAM-D baseline score >20), risperidone produced at least a 50% mean improvement in 12 (75%) of 16 patients in comparison to 8 (38%) of 21 patients receiving haloperidol. Haloperidol produced significantly more extrapyramidal side effects and resulted in more dropouts caused by any side effect. There was no difference between risperidone and haloperidol in reducing both psychotic and manic symptoms in this group of patients with schizoaffective disorder. Risperidone did not demonstrate a propensity to precipitate mania and was better tolerated than haloperidol. In those subjects with higher baseline HAM-D scores (i.e., >20), risperidone produced a greater improvement in depressive symptoms than haloperidol.