Antipsychotic Side Effects More Common in Patients with Bipolar Disorder

Patients with bipolar disorder were roughly twice as likely to suffer movement-related side effects from antipsychotic drugs as those with schizophrenia, a researcher said here.

That was the result of a meta-analysis looking at the frequency of extrapyramidal symptoms with haloperidol (Haldol) and five atypical antipsychotics reported by Keming Gao, M.D., of Case Western University in Cleveland, at the American Psychiatric Association meeting and in the April issue of the Journal of Clinical Psychopharmacology.

Only olanzapine (Zyprexa) was no different from placebo in causing extrapyramidal symptoms in either bipolar or schizophrenic patients, Dr. Gao said.

The researchers pooled data from 24 randomized, double-blind, placebo-controlled, monotherapy trials of various antipsychotic agents in bipolar disorder, mania, and schizophrenia.

They calculated risks as the number of patients needed to treat to cause harm (NNTH) to one patient. Thus, an NNTH value of 10 indicates that for every 10 patients treated, one would develop extrapyramidal symptoms.

Dr. Gao and colleagues calculated NNTH values for overall extrapyramidal symptoms, akathisia, and anti-cholinergic drug use for ziprasidone (Geodon), risperidone (Risperdal), quetiapine (Seroquel), and aripiprazole (Abilify), in addition to haloperidol and olanzapine.

The studies included a total of nearly 6,400 patients.

Drug doses used in the studies were:

  * Haloperidol, 10 to 12 mg/day
  * Ariprazole, 15 to 30 mg/day
  * Olanzapine, 12 to 16.4 mg/day
  * Quetiapine, 600 mg/day
  * Risperidone, 4.1 to 6 mg/day
  * Ziprasidone, 112 to 160 mg/day

Doses did not differ markedly between conditions, Dr. Gao said.

After olanzapine, it appeared the safest drug was quetiapine, which was not significantly different from placebo in causing extrapyramidal symptoms in patients with schizophrenia.

Among bipolar patients, quetiapine had an NNTH value of 19 for overall extrapyramidal symptoms. For akathisia and anticholinergic use, it was not different from placebo.

NNTH values for risperidone were 5 for overall symptoms and anticholinergic use in bipolar mania, whereas it was not significantly different from placebo in schizophrenic patients.

Aripiprazole was significantly more likely to cause akathisia in bipolar manic and bipolar depressed patients relative to those with schizophrenia. It had NNTH values of 5 in depression and 4 in mania, but was not different from placebo among schizophrenics.

Ziprasidone was the only atypical drug included in the study that showed a significant risk of extrapyramidal effects in schizophrenia. It had an NNTH value of 19 for anticholinergic usage in those patients.

Like most of the other drugs, it also was more likely to cause extrapyramidal symptoms in bipolar patients, with an NNTH value of 11.

NNTH values for haloperidol were lower than for the other drugs, reflecting its increased propensity to induce extrapyramidal symptoms relative to atypical antipsychotics.

For overall symptoms, akathisia, and anticholinergic usage among schizophrenics, haloperidol showed pooled NNTH values of 5 to 7 compared with 3 to 4 in bipolar patients.

David Baron, D.O., of Temple University in Philadelphia and program chair of the meeting, said most clinicians recognize that antipsychotic drugs have different side-effect profiles in different conditions.

“The issue here is that these are powerful drugs and they are going to have side effects,” he said.

Dr. Baron said future research should concentrate on determining why drugs have different side-effect rates in patients with different disorders.

No external funding was reported. No potential conflicts of interest were reported.

Primary source: Journal of Clinical Psychopharmacology
Source reference:
Gao K, et al “Antipsychotic-induced extrapyramidal side effects in bipolar disorder and schizophrenia: a systematic review” Journal of Clinical Psychopharmacology 2008; 28: 203-209.