PHOENIX – To continue second-generation antipsychotics in adolescents with bipolar disorder after their psychosis or aggression has stabilized may not be helpful beyond 6 months of therapy, preliminary data from a randomized, controlled trial suggest.
Details on 21 of 68 patients who were randomized to continue combination treatment with a second-generation antipsychotic plus mood stabilizers or to replace the antipsychotic with placebo showed that a slightly greater proportion (4 of 12, or 33%) in the combination group maintained remission at 48 weeks, compared with the placebo group (2 of 9, or 22%). But the difference between groups was not statistically significant, Dr. Vivian Kafantaris and her associates reported.
Patients gained a “shocking” amount of weight because of the antipsychotics–two pounds per week during 6 months of open treatment, followed by more weight gain in those randomized to stay on an antipsychotic rather than placebo for maintenance therapy, she said at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institutes for Mental Health.
“There does not appear to be a very large protective effect of continuing antipsychotic medications for an additional 48 weeks, once remission is achieved and functional recovery is underway,” said Dr. Kafantaris, director of research in child and adolescent psychiatry at the Zucker Hillside Hospital, Glen Oaks, N.Y.
The single-center study was funded by the National Institutes of Mental Health. Pharmaceutical companies donated the medications and matching placebos used in the trial. Dr. Kafantaris reported no other potential conflicts of interest.
The addition of a second-generation antipsychotic to treatment with a mood stabilizer has been shown to rapidly stabilize mania in children and adults, but it's unclear how long to continue this adjunctive use of antipsychotics once initial symptoms have resolved, she said.
Earlier case series in which patients were tapered off a second-generation antipsychotic after achieving therapeutic serum levels of lithium showed that reducing the antipsychotic dose after only a week or a month of lithium therapy led to high relapse rates, she said. In the current study, patients with bipolar disorder and psychotic features or severe aggression started with 6 months of open treatment using lithium (and valproic acid if needed) for mood stabilization and a second-generation antipsychotic–initially olanzapine (Zyprexa), with switches permitted to risperidone (Risperdal) or quetiapine (Seroquel).
Weight gain was a problem during this open-treatment phase. “We had a very difficult time. We would switch from one atypical to a different one, and we really didn't see much benefit” in weight, she said.
At the end of the 6-month open treatment, patients could be randomized to blinded maintenance therapy if they'd had 8 weeks free of psychosis, physical aggression, mania, depression, and mixed mania-depressive episodes, if they had been in school for 8 weeks, and if they'd had consistent therapeutic levels of a mood stabilizer on blood tests.
Twelve patients continued their combined treatment regimen as maintenance therapy for 48 weeks. Nine patients tapered off the antipsychotic over a 4-week period, replacing it with placebo, and continued on placebo plus mood stabilizers for 44 more weeks.
Compared with their prerandomization weights (after 6 months on open treatment), patients who continued the drug combination gained 4% in weight, and those on placebo and mood stabilizers lost 4% in weight after 48 weeks of maintenance therapy.
The investigators had hypothesized that remission would be maintained in 90% of the patients who continued the combination therapy and in 60% of the patients on placebo and mood stabilizers, but neither group came close to those expectations.
“There is a critical need for effective and well-tolerated maintenance medication strategies for this population,” Dr. Kafantaris said. “They will likely have a high recurrence rate and require intensive mental health care for life.”