Treating Bipolar Depression

Medically Reviewed by Smitha Bhandari, MD on August 14, 2022
4 min read

Treatment for bipolar  depression has come a long way from the days (not so long ago) when patients were given sedatives and medications with numerous side effects. Today, mood stabilizing drugs are a mainstay treatment for bipolar disorder. Doctors may prescribe lithium, an antimanic drug, or an antipsychotic drug -- or a combination of both -- in order to alleviate symptoms of depression without triggering a manic episode.

While depression episodes are far more common than manias and have a tremendous effect on the lives of patients, there are only a few established treatments for bipolar  depression.

Lithium and the anticonvulsants lamotrigine and valproate are mood stabilizers that are sometimes used "off label" as treatments for bipolar depression, although none of these has been established as an FDA-approved first-line treatment for bipolar depression. For many years, psychiatrists have traditionally added an antidepressant to a mood stabilizer if a mood stabilizer alone is ineffective; however, research shows that antidepressants are often not effective for bipolar depression.

A mood-stabilizing medication works on improving social interactions, mood, and behavior and is recommended for both treatment and prevention of bipolar mood states that swing from the lows of depression to the highs of hypomania or mania. According to the American Psychiatric Association (APA), lithium, lamotrigine, valproate, carbamazepine, and most atypical antipsychotic medications are approved by the FDA for treating one (or more) phases of bipolar disorder.

In some patients with bipolar disorder, a mood stabilizer may be all that's needed to modulate the depressed mood. However, in bipolar patients who do not respond to one mood stabilizer, another mood stabilizer or an atypical antipsychotic is sometimes added to the treatment regimen.

While antidepressants are effective treatment for people with major depressive (unipolar) disorder, they are not always as effective for bipolar depression, and generally should not be given alone (monotherapy) in people with bipolar I disorder. When antidepressants are given alone to someone with bipolar disorder, there's a risk the drug might ignite a manic episode in some patients. Knowing this, most doctors may avoid using antidepressants as monotherapy for bipolar depression.

A very large randomized study sponsored by the National Institute of Mental Health (NIMH) called the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) showed that mood stabilizers alone produced a stable improvement only in about 1 in 4 people with bipolar depression, and surprisingly, adding an antidepressant to the mood stabilizer did not boost improvement further. The STEP-BD study underscored the need to find treatments other than mood stabilizers or antidepressants for bipolar depression.

Studies have shown that some antipsychotic drugs can also treat bipolar depression.

Lumateperone (Caplyta) and Quetiapine (Seroquel, Seroquel XR) is used for the short-term treatment of bipolar depression. Another option is olanzapine (Zyprexa) with fluoxetine (Prozac).

The atypical antipsychotic lurasidone (Latuda) can be taken alone or with lithium or valproate for treating bipolar depression. Cariprazine (Vraylar), a treatment for bipolar disorder, may also be an off-label option.

These medications work by affecting receptors (called neurotransmitters) for chemicals in the brain that help regulate mood and behavior.

Your doctor will weigh the pros and cons of the available medications to help you get relief from the bipolar depression without the risk of mania or drug interactions.

Central nervous system (CNS) depressants, which include the benzodiazepines, act on neurotransmitters to slow down normal brain function. CNS depressants are commonly used to treat anxiety and sleep disorders and may be an effective alternative or adjunctive therapy in some bipolar patients with acute mania.

Some commonly used benzodiazepines include clonazepam (Klonopin), lorazepam (Ativan), alprazolam (Xanax), and diazepam (Valium). These drugs all can be addictive and can cause sluggish thinking. They generally should be used only to treat agitation or sleep problems during the acute phase of the illness and not as long-term medications. They typically should be tapered off rather than stopped abruptly, in order to minimize the risk of drug withdrawal.

Guidelines from the American Psychiatric Association suggest that ECT is an appropriate and sometimes preferred treatment for depressed bipolar patients who have psychotic symptoms or a very high risk for suicidal behavior. In addition, ECT may benefit women who are pregnant and suffer with severe bipolar depression or mania.

Along with medications for bipolar depression, patients may benefit from ongoing psychotherapy. This one-on-one therapy combines interpersonal psychotherapy with behavioral techniques to help patients learn how to more effectively manage interpersonal problems, stay on their medications, and normalize their lifestyle habits. The STEP-BD study mentioned earlier found that in addition to medications, adding a structured psychotherapy -- such as cognitive behavioral therapy, interpersonal/social rhythm therapy, or family-focused therapy -- can speed up treatment response in bipolar depression by as much as 150%.