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If one atypical antipsychotic fails, try another.

SAN DIEGO -- Figuring out which atypical antipsychotic will work in a patient with schizophrenia or bipolar disorder requires more art than science, Dr. Stephen M. Stahl said.

Five atypical antipsychotics are approved as monotherapy for the treatment of schizophrenia and are approved or on track for approval for the treatment of bipolar disorder: risperidone (Risperdal); olanzapine (Zyprexa); quetiapine (Seroquel); ziprasidone (Geodon), and aripiprazole (Abilify). Although the drugs share mechanisms of action, such as antagonism to serotonin 2A receptors and dopamine [D.sub.2] receptors, differences among them in other receptor actions make it difficult to predict response, he noted at a psychopharmacology congress sponsored by the Neuroscience Education Institute.

A patient who responds to one atypical antipsychotic may not respond to another. A patient who gets side effects on one atypical antipsychotic may not get those side effects on another. "We don't have any way to know" yet which will happen in a particular patient, so physicians have to be willing to try them serially if necessary, said Dr. Stahl of the University of California, San Diego, and chairman of the institute.

"Knowing that these drugs are different [from one another] means that you should have the faith to go through them iteratively until you find the right action," he said.

Secondary receptor properties shared by some of these drugs may be sedating and may interfere with the drugs' procognitive actions Muscarinic cholinergic receptor antagonism seen with olanzapine and quetiapine may interfere with procholinergic actions on acetylcholine release related to improved cognition. Antihistamine receptor antagonism, also seen with olanzapine and quetiapine, again may interfere with pro-cognitive actions and may contribute to weight gain. An [[alpha].sub.1]-adrenergic receptor antagonism, seen especially with quetiapine or risperidone (and with the other atypical antipsychotics if dosed high enough), may interfere with procognitive actions and mood actions or cause hypotension. All three pharmacologic actions may be sedating.

Rather than combine two atypical antipsychotics for combination therapy, it makes more sense to choose a second drug with a different mechanism of action, such as an anticonvulsant, he added. The additive effects of combining these two classes of drugs for schizophrenia or bipolar disorder now are well documented, particularly for the combination of olanzapine plus the anticonvulsant divalproex (Depakote).

Not all anticonvulsants are the same for this purpose, however, probably because of different mechanisms of action on ion channels, Dr. Stahl said.

The only two anticonvulsants with good evidence of effectiveness in treating schizophrenia or bipolar disorder both act on voltage-gated sodium channels--divalproex and lamotrigine. Divalproex is proved to be helpful in treating bipolar mania. There's compelling evidence of its utility in augmenting schizophrenia therapy, and it looks promising for bipolar maintenance therapy or treatment of bipolar depression, he said. Lamotrigine (Lamictal) has been proved effective in maintenance therapy for bipolar disorder, has compelling evidence of utility in treating bipolar depression, and may help augment schizophrenia therapy.

Among other anticonvulsants that act on sodium channels, there's less robust evidence that carbamazepine may help treat schizophrenia or bipolar disorder, and toxicities make it less attractive. Oxcarbazepine, which acts like carbamazepine, may have these same properties, but there's no evidence to support that, he said.

Dr. Stahl has been a consultant for, or received funding from, companies that manufacture all the drugs mentioned in this article except risperidone, topiramate, and carbamazepine.

BY SHERRY BOSCHERT

San Francisco Bureau
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Title Annotation:Adult Psychiatry
Author:Boschert, Sherry
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Jun 1, 2004
Words:560
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