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Off-Label Anticonvulsants Useful in Schizophrenia.

One of the drugs most often prescribed for schizophrenia-valproate--has never been approved by the Food and Drug Administration for that indication. In fact, it hasn't even been subjected to randomized controlled trials.

A survey of New York state mental health facilities reported that in 1998, 35% of schizophrenic inpatients were given the anticonvulsant adjunctively during their stay. This represents a near tripling in the use of the drug since 1994, noted Dr. Leslie Citrome, director of the clinical research and evaluation facility at Nathan S. Kline Institute for Psychiatric Research, Orangeburg, N.Y. The use of other anticonvulsants for schizophrenia also appear to be on the rise.

"There's very little literature to back up this use," Dr. Citrome said. "But psychiatrists are pretty desperate to help patients any way they can." He sees the rise in anticonvulsant prescribing as part of a more global trend toward coprescription--for which the data are generally "quite sparse."

The increased use of drugs such as anticonvulsants also reflects a greater awareness of diverse symptoms in schizophrenia (including negative symptoms, cognitive dysfunction, depression, and aggression) that can be approached through specific therapy, he suggested.

"I use these drugs even though there's a lack of data [supporting their use]," Dr. Citrome said. "I follow patients longitudinally, using rating scales rather than depending on general impression. If they don't show evidence of improvement, I discontinue [the drugs]."

Aggression, a fairly well-accepted indication for anticonvulsants across diagnostic categories, is perhaps the most common reason for the use of these drugs in schizophrenia. Dr. Jean Pierre Lindenmeyer, director of psychopharmacology research at Manhattan Psychiatric Center, New York, is likely to prescribe valproate for "intermittent violence, aggression, hostility, and irritability," he said. In a retrospective chart review of 72 patients with schizophrenia treated with the drug for these indications displayed a significant decrease verbal and physical aggression.

But he also adds valproate as adjunctive therapy for patients who do not respond adequately to an antipsychotic--particularly when residual symptoms are positive.

"Valproate is our next most frequently used concomitant agent [in schizophrenia], after a second antipsychotic," he said. He would consider prescribing the drug for a patient with a vague history of brain injury or accident or with soft neurologic signs that are not necessarily documented on an EEG. Positive symptoms that involve agitation, irritability, excitement, or mood swings that suggest possible schizotypal disorder also warrant use of the drug.

"If someone were simply to be quietly hallucinatory or delusional, on the other hand, [valproate] wouldn't be a first choice," Dr. Lindenmeyer said.

Dr. Guy Chouinard likely has prescribed as many anticonvulsants for schizophrenia as anyone: In nearly 15 years, he has treated 4,000 patients with the drugs.

Any patient who shows drug tolerance to antipsychotics, who needs an increasingly high dose, or who needs dual or triple therapy is a candidate for adjunctive therapy with anticonvulsants, he said.

Dr. Chouinard, professor of psychiatry at the University of Montreal and McGill University, Montreal, considers using anticonvulsants when a patient fails to respond adequately to 6 mg of risperidone, 20 mg of olanzapine, or 200 mg of dozapine.

He is particularly impressed by the apparent value of anticonvulsants in first-episode patients. In one series, 80% remained healthy 2-3 years after combined treatment, far better than the usual course.

Like others, Dr. Chouinard most often prescribes valproate because it has a longer track record than other anticonvulsants. But he also has had good experience with gabapentin and lamotrigine, and he is starting to use topiramate as well.

Side effects often guide the choice: Gabapentin has advantages over the sedating valproate for patients who are working full time and for those with high levels of anxiety. He favors lamotrigine for patients who are particularly high functioning. He considers using lamotrigine or topiramate when weight gain (an issue with most antiepileptic drugs as well as with antipsychotics) is problematic.
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Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Aug 1, 2001
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