Magazine article Clinical Psychiatry News

Practical Psychopharmacology: Lithium Remains Key in Bipolar Treatment. (Psychopharmacology)

Magazine article Clinical Psychiatry News

Practical Psychopharmacology: Lithium Remains Key in Bipolar Treatment. (Psychopharmacology)

Article excerpt

The use of lithium as a psychotropic agent dates back more than a half-century, and it remains the only agent approved by the Food and Drug Administration for maintenance treatment of bipolar disorder. But U.S. prescriptions for lithium have declined in recent years. That decline is largely tied to the belief that the drug is less effective than alternatives such as anticonvulsants and more difficult to use because of its side effect profile and the need for blood tests to measure serum lithium levels.

Expert opinion runs counter to the conventional wisdom on lithium. A review of the data finds that lithium's efficacy has not declined in well-selected patients (Harvard Rev. Psychiatry 1O[2]: 59-75, 2002). In fact, the data suggest that at appropriate doses and with intelligent side effect management, lithium is often the mood stabilizer of choice.

The best candidates for lithium monotherapy are bipolar patients who show "a clear episodic pattern, with symptom-free intervals and a normal psychological profile during remission," said Dr. Bruno Muller-Oerlinghausen, professor emeritus of clinical psychopharmacology at Freie Universitat, Berlin.

Dr. Frederick K. Goodwin, research professor of psychopharmacology at George Washington University, Washington, D.C., said lithium is his maintenance drug of choice for the 35%-40% of bipolar patients whose presentation includes classic mania.

"For those who have been hospitalized with episodes of euphoria, grandiosity, and hyperactivity without depression, [the data clearly show] it is better than vaiproate," he said.

While he may start patients with mixed episodes or rapid cycling on an anticonvulsant, lithium is usually added to the regimen, Dr. Goodwin said.

Its inclusion is particularly important for patients who have a history of suicide attempts. "The evidence for a specific antisuicidal effect is very strong," Dr. MullerOerlinghausen said. Because the antisuicidal effect of lithium is not coupled with the drug's overall efficacy, he advocates adding, rather than switching to, another mood stabilizer in patients for whom lithium fails to prevent bipolar episodes.

Close attention to dosing is key to effective, well-tolerated therapy. The blood level range for maintenance, as defined by package inserts and the Physicians' Desk Reference, goes as high as 1.2 mEq/L. But a metaanalysis of the literature concluded that there is rarely much gain above 0.8. "The best benefit-side effect ratio is between 0.6 and 0.8," Dr. Goodwin said.

Some patients, particularly older ones who have been on lithium for many years, may do well at even lower levels, such as 0.5. This might reflect changes in tissue sensitivity.

When lithium is combined with other mood stabilizers, apparent synergy often makes it possible to maintain blood levels in the area of 03 or lower, he said.

Lower blood levels translate into a lower side effect burden and better compliance. Difficulties such as cognitive impairment, in fact, can sometimes be resolved by fine-tuning the dosage, Dr. Muller-Oerlinghausen said.

Bedtime dosing can also minimize cognitive difficulties, and supplementing with folic acid at a dosage of 400 [micro]g/day--the amount found in many multivitamins-is useful as well, Dr. …

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