Management of Bipolar Disorder: Guidelines From the VA/DoD

Bipolar disorder has a lifetime prevalence of 1% in adults in the United States, and its onset peaks at three different ages—19, 26, and 29 years. The onset of bipolar disorder may be associated with asthma, migraines, multiple sclerosis, traumatic brain injury, and irritable bowel syndrome. More than 90% of patients with bipolar disorder report another mental health disorder, most commonly impulse control disorders, substance use disorders, and generalized anxiety disorder. The U.S. Department of Veterans Affairs and U.S. Department of Defense (VA/DoD) published new recommendations for diagnosing and managing bipolar disorder. These guidelines recommend management options when there is strong evidence of a benefit and suggest options when the evidence is not strong.

Routine screening for bipolar disorder is not suggested because of the high rates of false-positive results with most screening tools. Use of screening tools is suggested in specialty care when bipolar disorder is suspected; however, sensitivities can be less than 50% with limited specificity. Tools such as the Mood Disorder Questionnaire (https://ibpf.org/wp-content/uploads/2016/11/MDQ.pdf) are suggested for patients taking antidepressant medications who demonstrate signs of hypomania or mania. Scores have not been studied to guide care.

Pharmacotherapy should focus on treating patients in each phase of bipolar disorder—acute mania, acute depression, and maintenance therapy. Most medications have different effectiveness over the phases. Table 1 summarizes pharmacotherapy recommendations for each phase of bipolar disorder.

Monotherapy with lithium or quetiapine should be considered for acute mania because they are effective and useful for all phases of bipolar disorder. The stigma of taking lithium and the need for monitoring reduce the acceptability for some patients. Both medications can cause weight gain. Quetiapine can cause sedation, and lithium can cause tremors. Although olanzapine (Zyprexa) is similarly effective as lithium and quetiapine, the metabolic adverse effects are more severe with olanzapine. Paliperidone (Invega) and risperidone are effective for acute mania but do not prevent depression. Aripiprazole, asenapine, carbamazepine, cariprazine (Vraylar), haloperidol, valproate, and ziprasidone can be effective for acute mania with small effect sizes but do not prevent mania or depression. Brexpiprazole (Rexulti), topiramate, and lamotrigine are not suggested for the treatment of acute mania.

Lithium or valproate with quetiapine, olanzapine, or risperidone should be considered in patients with acute mania that does not respond to monotherapy or who have breakthrough symptoms despite monotherapy. Adding aripiprazole, paliperidone, or ziprasidone to lithium or valproate monotherapy should be avoided due to a lack of added benefit.

Quetiapine is the recommended monotherapy for acute depression in patients with bipolar disorder. Quetiapine demonstrates a moderate effect on depressive symptoms for up to 36 weeks and may also improve anxiety symptoms.

Although olanzapine is more effective, the guidelines recommend quetiapine because of the metabolic effects of weight gain and hyperlipidemia. Cariprazine, lurasidone (Latuda), and lumateperone (Caplyta) are similarly effective as olanzapine and are recommended as second-line options due to adverse effects, including metabolic and neurologic effects. Although limited evidence suggests that some anti-depressants are effective for bipolar depression, the rate of conversion to mania is unknown. Ketamine infusions may have short-term benefits, but the long-term effects are unknown.

Adding lamotrigine to lithium or quetiapine maintenance therapy is beneficial; however, lamotrigine monotherapy does not appear to be effective for bipolar depression. Augmenting mood stabilizer treatment with antidepressants has insufficient evidence for improving depressive symptoms.

Lithium and quetiapine are recommended as the most effective medications to prevent the recurrence of mania. Evidence reviews, including observational studies, suggest that lithium has an antisuicide effect on patients, whereas reviews limited to randomized trials do not. Quetiapine has more global benefits because lithium is not useful for treating bipolar depression. The adverse effects of lithium and quetiapine are similar.

Olanzapine is similarly effective as lithium and quetiapine in preventing mania but is associated with more severe metabolic adverse effects. Oral paliperidone and long-acting injectable risperidone are effective in preventing mania but do not prevent or treat depression. Lamotrigine effectively prevents depressive episodes but not mania.

When patients require combination therapy because monotherapy is ineffective, lithium or valproate with aripiprazole, quetiapine, olanzapine, or ziprasidone should be considered to prevent mania.

Lamotrigine is recommended as the most effective monotherapy to prevent the recurrence of bipolar depression, although it does not prevent mania. Quetiapine, lithium, and olanzapine are also effective as monotherapy to prevent depression in patients with bipolar disorder.

When patients require combination therapy because monotherapy is ineffective, lithium or valproate with olanzapine, lurasidone, or quetiapine is recommended to prevent depressive episodes.

Lithium is the safest bipolar medication in pregnancy despite a small increased risk of congenital malformations. Lithium should be continued at the lowest effective dose during pregnancy and discontinued 48 to 72 hours before delivery. Valproate, carbamazepine, and topiramate have higher teratogenicity risks and are not recommended in patients with childbearing potential.

For severe acute mania, weak evidence suggests electroconvulsive therapy with pharmacotherapy can lead to rapid control of symptoms despite a risk of cognitive and memory impairment.

Short-term light therapy can be considered for bipolar depression when added to pharmacotherapy. In patients with a limited response to medication for depressive symptoms, repetitive transcranial magnetic stimulation may improve symptoms.

No nutritional supplements improve depressive or manic symptoms based on limited evidence.

In patients without acute mania, cognitive behavior therapy, family therapy, interpersonal and social therapy, and psychoeducation can be beneficial when added to pharmacotherapy. Evidence for meditation is limited. Individual placement support can provide effective vocation and education guidance. Support programs for caregivers can improve mental health outcomes for caregivers.

Editor's Note: As delays to mental health referrals increase, I found this guideline beneficial in providing a simple guide to the treatment of bipolar disorder that can allow my patient to start a medication while waiting for a referral.—Michael J. Arnold, MD, Assistant Medical Editor

The views expressed are those of the author and do not necessarily reflect the official policy or position of the Naval Undersea Medical Institute, Uniformed Services University of the Health Sciences, U.S. Navy, U.S. Department of Defense, or U.S. government.

Guideline source: U.S. Department of Veterans Affairs and U.S. Department of Defense

Available at: https://www.healthquality.va.gov/guidelines/MH/bd/VA-DoD-CPG-BD-Full-CPGFinal508.pdf