Treatment Options for Bipolar Disorder

Treatment of the Acute Phase of Bipolar Disorder

During the acute phase of any episode in bipolar disorder, regardless of whether it is mania or depression, the goals of treatment include:

• Stabilizing the episode
• Achieving remission
• Returning the patient to a baseline level of functioning with no symptoms

Though mania and depression are treated with the same medications, some of which have been approved by the U.S. Food and Drug Administration (FDA) for mania, to date there are no FDA approved drugs for the treatment of bipolar depression.

Mania

In 2002, the American Psychiatric Association (APA) issued a Practice Guideline for the treatment of bipolar disorder. In it they recommend that the following drugs be considered in combination for the first line of treatment for acute severe mania:

• Mood stabilizers (lithium and/or divalproex sodium)
• Antipsychotics (e.g., olanzapine)

For less severe episodes, any of these medications may be used as monotherapy (single drug therapies). During the manic episode, use of antidepressants is usually tapered and discontinued. Benzodiazapines are recommended in the short term if the patient is agitated. Lithium, divalproex and olanzapine are approved by the US Food and Drug Administration for treatment of mania.

The second-line of therapy for acute mania is either optimizing the first-line medications by raising their levels in the blood to therapeutic levels, adding medication to the first-line drugs, or switching to a different antipsychotic medication. Electroconvulsive therapy should remain an option for people with mixed mania episodes and pregnant women.

Lithium and divalproex are both effective for pure mania. Divalproex is also effective for mixed and rapid cycling and also has the advantage that it can be given initially in high doses for rapid relief.

Carbamazepine may be used in mixed and rapid cycling bipolar. It can be combined with lithium but not with divalproex. Carbamazepine may also be used if lithium and divalproex are contraindicated.

Newer anticonvulsants (e.g., lamotrigine, gabapentin, topiramate) may be used in combination with other first line drugs or as first line drugs if side effects of lithium and divalproex are intolerable.

Since mood stabilizers may take a few weeks to have an effect, they may be combined with other medications that provide short-term, rapid relief from anxiety, insomnia, and agitation in an acute episode. These include antipsychotics and benzodiazepine sedatives such as lorazepam (Ativan), clonazepam (Klonopin) and diazepam (Valium). The dosages of these medications can be reduced as the patient recovers.

Sometimes, patients experience a "breakthrough" episode that occurs when there is a manic or mixed episode recurrence despite receiving medications. Treatment consists of optimizing their medication and ensuring that blood levels of the drugs remain at a therapeutic level as determined by the physician.

To read more about the 2002 Practice Guidelines of the APA for treatment of bipolar disorder, please click on the following link:

http://www.psych.org/psychpract/treatg/pg/Bipolar2ePG05-15-06.pdf

In 2005, the American Psychiatric Association (APA) issued a Guideline Watch which summarizes significant developments in clinical practice since the last Practice Guidelines were published in 2002. Several medications are discussed in the Guideline Watch and are recommended by the APA to be considered as "options" for treatment of acute mania and mixed episodes (as monotherapy or adjunct therapy) including:

• Olanzapine
• Risperidone
• Ziprasidone
• Aripiprazole
• Quetiapine
• Carbamazepine (extended release formulation)

A significant concern that is raised by the APA regarding second generation antipsychotics is their metabolic effects. Clozapine and olanzapine increase the risk of diabetes and dyslipidemia. Clozapine and olanzatine are also associated with more weight gain than other medications. Risperidone and quetiapine are associated with moderate weight gain, while ziprasidone and aripiprazole are associated with minimal weight gain.

As a result, the APA advises clinicians to monitor their patients who are taking any of these medications for weight, waist circumference, blood pressure, and glucose/lipids at baseline and monthly thereafter.

To read more about the 2005 Guideline Watch published by the APA, please click on the following link:

http://www.psych.org/psych_pract/treatg/pg/Bipolar.watch.pdf

Depression

The primary goal of treatment for acute bipolar depression is to minimize or eliminate the symptoms and return the patient to normal functioning levels.

There is relatively little research that has been done regarding depression in bipolar disorder even though depression often is the dominant symptom and is associated with functional impairment, suicide, and other aspects of suffering. It may be considered even worse than manic episodes in terms of the duration of depressive episodes and impact on quality of life. Unfortunately, to date, no medications have been approved by the U.S. Food and Drug Administration for bipolar depression.

First-line therapy for severe depression, according to the American Psychiatric Association, is lithium or lamotrigine as monotherapy, and lithium combined with antidepressants as a second line therapy. Electroconvulsive therapy (ECT) is recommended for treatment of severe depression, pregnant women with severe symptoms, or those with psychotic symptoms. If a breakthrough episode occurs, first line medications need to be optimized. Antidepressants must be combined with mood stabilizers since, if taken alone, they may cause an increase in cycling and/or may overshoot the depression and result in mania.

Bipolar patients may take antidepressants for several weeks before they feel the therapeutic effect. It is common for the doctor to have to prescribe 2 or 3 different drugs before finding one that is most effective and does not cause bothersome side effects. A sedative may be added to relieve insomnia, anxiety, or agitation.

Psychotherapy may be helpful in an acute bipolar depression but it should always be combined with a regimen of medication.

The Guideline Watch published by the APA in 2005 notes that the following drugs have shown the strongest evidence of efficacy for acute depression in Bipolar I:

• Combination of fluoxetine and olanzapine
• Quetiapine
• Lamotrigine

There is "suggestive evidence" that pramipexole, a dopamine agonist, may be helpful as an adjunct medication. Antidepressants in combination with mood stabilizers offer only modest efficacy.

Rapid Cycling

It is important to evaluate and address any medical issue that could be the source of rapid cycling, (e.g. hypothyroidism, use of drugs or alcohol, or prior use of antidepressants).

First line medications used for rapid cycling include lithium, divalproex, and/or lamotrigine. In many cases, combinations of medications are required.

When a bipolar patient is experiencing a severe attack of either mania or depression, or a mixed episode, treatment may have to be supplemented with ECT. Electroconvulsive therapy can be life-saving for the following conditions:

• If the person is suicidal
• If the person is severely ill and cannot wait for medication to work
• If there is a history of unsuccessful response to medication in the past
• If psychosis is present