The FDA has cleared ziprasidone (Geodon) for maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate.
It joins several other antipsychotic drugs -- including quetiapine (Seroquel), aripiprazole (Abilify), and olanzapine (Zyprexa) -- approved for this indication.
Ziprasidone is also approved for acute manic and mixed episodes associated with bipolar disorder, with or without psychotic features, and for schizophrenia.
The approval as bipolar maintenance therapy follows a a six-month, double-blind, randomized, placebo-controlled trial in adult patients with bipolar I disorder, according to the drug's manufacturer, Pfizer.
After an open-label stabilization period of 10 to 16 weeks, 240 patients were randomized to continue on ziprasidone plus lithium or valproate, or to have ziprasidone replaced by placebo.
The primary endpoint in this study was time to recurrence of a mood episode requiring intervention.
The patients who stayed on ziprasidone showed increased time to recurrence of a mood episode, compared with those who switched to placebo.
During six months of treatment, 19.7% of those in the ziprasidone arm required intervention for a mood episode, compared with 32.4% of the placebo group, Pfizer reported.
Ziprasidone comes with a long list of precautions and contraindications:
- It should not be used in patients with a known history of QT prolongation, recent acute myocardial infarction, or uncompensated heart failure, and should not be used with other QT-prolonging drugs.
- It should also be avoided in elderly patients with dementia-related psychosis, as studies have shown that ziprasidone increases the risk of death in such patients.
- Discontinuation should be considered in patients showing signs of tardive dyskinesia.
- Treatment should be stopped immediately in patients with symptoms of neuroleptic malignant syndrome, which include hyperpyrexia, muscle rigidity, diaphoresis, tachycardia, irregular pulse or blood pressure, cardiac dysrhythmia, and altered mental status.
- Patients and clinicians should be alert for hyperglycemia, rash, seizures, and orthostatic hypotension with ziprasidone.
Somnolence was the most common side effect. Other adverse effects seen in trials of bipolar patients included extrapyramidal symptoms, dizziness, akathisia, and abnormal vision.
In the maintenance therapy trial, discontinuations due to adverse effects were slightly more common in the placebo group than in those taking ziprasidone (13% versus 9%).