Expert guidelines developed for medication treatment of bipolar disorder. What bipolar medications work best? Natural treatments for bipolar. And how to handle weight gain from mood stabilizers and atypical antipsychotics.

The joke is, "If you have two psychiatrists, you will get three conclusions," says Gary Sachs, M.D. Such is not the case with the recently published Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000.

The level of consensus among the experts is extraordinary, said Sachs, who is director of Partners Bipolar Treatment Center at Massachusetts General Hospital and one of the guidelines' editors. On 89% of the issues, he explained, there is consensus about what the first-line treatments are. Additionally, consensus exists about how to handle a manic patient and what to do if someone has rapid cycling or bipolar depression.

"That really is heartening, because it means we can speak to our patients, their family members and the general public with greater confidence," he said, adding that people familiar with the literature are "speaking with one voice."

The 2000 medication guidelines-an update of the first guidelines (Kahn et al., 1996)-were based on reviews of the medical literature and a survey of experts. Funding for the project was provided through unrestricted educational grants from several pharmaceutical companies. The guidelines were assembled under the direction of the editors: Sachs of Harvard Medical School; David J. Printz, M.D., and David A. Kahn, M.D., of Columbia University; and Daniel Carpenter, Ph.D., and John P. Docherty, M.D., of Comprehensive NeuroScience Inc.

"Years of experience are behind the guidelines, and physicians can rely on this tool to provide up-to-date information," said Docherty in a press statement. Docherty is also adjunct professor of psychiatry at Weill Medical College of Cornell University.

The survey asked about 1,276 options for psychopharmacologic interventions in 48 specific clinical situations. Fifty-eight experts on bipolar treatment and clinical research completed the two-hour survey. Questions focused on broad strategies, such as classes of medication, and then delved into tactics, such as specific medication selection and dosing. A modified RAND Corporation format was used to ascertain consensus.

Major Recommendations

The experts favor proven treatments-the mood stabilizers. "In every phase of the illness, the expert consensus speaks very strongly to the fact that you treat bipolar patients with mood stabilizers," said Sachs, assistant professor of psychiatry at Harvard Medical School. "We are seeing fewer physicians who say, 'Yeah, if this was a depressed bipolar patient, I would give them the antidepressant alone.'"

Divalproex (Depakote) (especially for mixed or dysphoric subtypes) and lithium are the cornerstone choices among the mood stabilizers for both acute and preventive treatment of mania.

"Regardless of which is selected first, if monotherapy fails, the next recommended intervention is to use these agents in combination," the experts agree. "The combination can then serve as the foundation on which other medications are added, if needed. Carbamazepine [Tegretol] is the leading alternative mood stabilizer for mania. Expert opinion regards other new anticonvulsants as second-line options (e.g., if the previously mentioned mood stabilizers fail or are contraindicated)."

For milder depression, the experts agree:

A mood stabilizer, especially lithium, may be used as monotherapy. Divalproex and lamotrigine [Lamictal] are other first-line choices. For more severe depression, a standard antidepressant should be combined with lithium or divalproex. Bupropion [Wellbutrin], selective serotonin reuptake inhibitors (SSRIs), and venlafaxine [Effexor] are preferred antidepressants and should be tapered 2 to 6 months after remission. Divalproex monotherapy is recommended for initial treatment of either depression or mania with rapid cycling.

According to Sachs, the experts also agree that bipolar disorder should be treated as a chronic illness.

"It looks like the percentage that would start patients on prophylactic treatment and leave them on that treatment long-term is increasing," he said.

Adjunctive use of antipsychotics is recommended for mania or depression with psychosis and possibly in nonpsychotic episodes. "It is very clear that we have moved away from conventional antipsychotics and on to the atypical antipsychotics," Sachs said.

Atypical antipsychotics such as olanzapine (Zyprexa) and risperidone (Risperdal) are rated as first-line agents for adjunctive treatment of mania. Atypical antipsychotics are also rated as first-line agents for combined treatment of psychotic depression. The experts noted, however, that in more severe cases of mania another first-line option is to change the antipsychotic to clozapine [Clozaril].

Electroconvulsive therapy (ECT), according to Sachs, is regarded by the experts as an appropriate treatment in some instances. "The desire is to reserve ECT for treatment failures, even though it is clearly an acceptable choice under certain clinical circumstances, like when the patient is acutely suicidal or has multiple medical complications," he said.

The experts were also asked about their preferred first-line medications when comorbidity is present. The most frequent conditions comorbid with bipolar disorder, Sachs explained, are anxiety disorders, such as panic disorder or obsessive-compulsive disorder; substance abuse; so-called disruptive behavior disorders, such as attention-deficit/hyperactivity disorder and oppositional defiant disorder; and, among women, posttraumatic stress disorder (PTSD) and eating disorders.

Some preferred first-line treatments are divalproex or gabapentin (Neurontin) for comorbid panic disorder; divalproex for comorbid PTSD; divalproex or lithium for alcohol abuse; and divalproex for other substance abuse.

Handling Weight Gain Associated with Mood Stabilizers and Atypical Antipsychotic Medications

While there was consensus on most of the major clinical decisions in the guidelines, there was not a clear-cut consensus on some issues, including how frequently to monitor labs and what to do in situations where patients have gained a lot of weight, Sachs said.

For weight gain associated with mood stabilizers, the experts prefer to continue the present medication and attempt weight loss through diet or exercise. Adding topiramate (Topamax) or switching to a different mood stabilizer are second-line options. No consensus exists on whether dose reduction is helpful.