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For decades, the only drug for bipolar patients--and one that is still an important part of the pharmacological arsenal--was lithium. It works by regulating a number of neurotransmitters, including dopamine and norepinephrine, as well as protein kinase C, a family of chemicals that help determine the neurotransmitter amounts that nerve cells release. With its hands on so many of the brain's chemical levers, lithium can help bring bipolars back to equilibrium. For 30% of sufferers, however, it has no effect at all; for others, the side effects are intolerable. "It's still a miraculous drug," says Keck. "But some people simply don't respond to it enough."
New drugs are stepping into the breach. Rather than rely on the imprecise relief that a single drug like lithium provides, contemporary chemists are investigating a battery of other medications. Depakote, an anticonvulsant developed to calm the storms of epilepsy, was found to have a similarly soothing effect on bipolar cycling, and it was approved in 1995 to treat that condition too. The success of one anticonvulsant prompted researchers to look at others, and in the past five years, several--including Lamictal, Tegretol, Trileptal and Topamax--have been put to use.
Anticonvulsants are not the only drugs being reformulated. Also showing promise are the atypical antipsychotics. The best-known antipsychotic, Thorazine, is a comparatively crude preparation that controls delusions by blocking dopamine receptors. In the process, it also causes weight gain, mood flattening and other side effects. Atypical antipsychotics work more precisely, manipulating both dopamine and serotonin and suppressing symptoms without causing so many associated problems. There are numerous atypical antipsychotics out there, including Zyprexa, Risperdal and Haldol, and many are being used to good effect on bipolar patients.
For any bipolar, the sheer number of drug options is a real boon, as what works for one patient will not necessarily work for another. When Brandon Kent, the 9-year-old Texas boy, started taking Depakote and Risperdal, his body began to swell. Then he switched to Topamax, which made him lethargic. Eventually he was put on a mix of Tegretol and Risperdal, which have stabilized him with few side effects. Kyle Broman in Los Angeles is having a harder time but has grown calmer on a combination of Risperdal and Celexa, an antidepressant that for now at least does not appear to be flipping him into mania.
But drugs go only so far. Just as important is what comes after medication: therapies and home regimens designed to help patients and their families cope with the disorder. Early last year the National Institute of Mental Health launched a five-year, $22 million study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) to refine bipolar therapies. Some 2,300 volunteers are participating in the program, and enrollment is expected to reach 5,000. Of all the treatments the STEP-BD doctors are studying, the most basic and perhaps the most important one for children and teens involves lifestyle management.
