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I'm a paranoid schizophrenic and have been in treatment for about 10 years. So, I know where Dr. Nash is coming from. Question: What new schizophrenia medications are in the pipeline at this time? Will these new drugs be more specific in their effect? That is, what about undesirable side effects like TD and akathesia? Believe me, the side effects I mention can be so severe for some people that they decide to quit taking their medications! Answers please!! Thank you so much.

L. Ryan
El Cajon, CA

Answered by John Hsiao, M.D.:
There are a number of new compounds being developed by the pharmaceutical industry to treat schizophrenia. Two in particular, iloperidone and aripiprazole, are rumored to be on the verge of a New Drug Application: a request by the sponsoring pharmaceutical company to the Food and Drug Administration (FDA) to review all the safety and efficacy data the company has gathered, and to approve marketing of the new drug. There are multiple other compounds at earlier stages in the testing and approval process. When the drug manufacturer files for FDA approval, what, if anything is special about these new antipsychotic drugs will become public. Until then, the information is closely guarded by the manufacturer. Keep in mind that as far as motor side effects like tardive dyskinesia (TD), akathisia, and dystonia are concerned, previously approved atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, and ziprasidone) already appear to be quite a bit better than the older antipsychotics.

What may be more interesting than new drugs from the pharmaceutical industry are some new approaches to drug development, particularly identification of medications with fundamentally new mechanisms of action (all currently available antipsychotic medications act on the dopamine neurotransmitter system). For example, there have been a number of preliminary studies demonstrating that modulation of the glutamate neurotransmitter system may have beneficial effects on "negative" symptoms (withdrawal, apathy, amotivation).

There is also considerable interest in drugs that might improve cognitive function in people with schizophrenia. The NIMH has undertaken a new initiative to identify aspects of cognitive impairment that may respond favorably to pharmacological interventions and to collaborate with industry to develop new drugs for this purpose.

A nonpharmacological approach to treatment is being tried out in preliminary studies supported by NIMH. Transcranial magnetic stimulation is being used to transiently and noninvasively suppress electrical activity in selected brain regions, hoping to suppress auditory hallucinations in people with schizophrenia.

Finally, one should keep in mind that as well as looking for new drugs and treatments, it's important for us to learn how to use existing treatments better. It may be a long time before we find the "magic bullet" that cures schizophrenia, but in the meantime, we have a number of pharmacological and psychosocial interventions already proven to be helpful. An analogy here might be made to cancer treatment. There are many antineoplastic drugs that have modest effects when given alone, but that are much more effective when given in combination. Similarly, in schizophrenia, there may be great benefit to combining different pharmacological and psychological treatments to optimize long term outcome and function for people with this devastating illness.

John Hsiao, M.D.

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