Medications for Treatment of Bipolar Disorders

Choice of pharmacologic agents to treat bipolar disorders can be difficult because all medications can potentially have significant adverse effects, drug interactions are common, and no medication is universally effective. Selection should be based on what has previously been effective and well-tolerated in a given patient. If there is no prior experience (or it is unknown), choice is based on the patient’s medical history (in relation to the adverse effects of the specific mood stabilizer) and the severity of symptoms.

(See also Bipolar Disorders.)

For severe manic psychosis, in which immediate patient safety and management is compromised, urgent behavioral control usually requires a sedating second-generation antipsychoticBenzodiazepines).

For less severe acute episodes

For bipolar depression,1, 2).

Once remission is achieved, preventive treatment with mood stabilizers is indicated for all patients with bipolar I disorder (bipolar I is defined by the presence of at least one full-fledged manic episode). If episodes recur during maintenance treatment, clinicians should determine whether adherence is poor and, if so, whether nonadherence preceded or followed recurrence. Reasons for nonadherence should be explored to determine whether a change in mood stabilizer type or dosing would render treatment more acceptable.

lithium.

Whether lithium or another mood stabilizer is being used, breakthroughs are more likely in patients who have mixed states, rapid-cycling forms of bipolar disorder (usually defined as ≥ 4 episodes/year), comorbid anxiety, substance use disorder, or a neurologic disorder.

Lithium carbonate is typically titrated based on blood levels, tolerance, and response. Higher maintenance levels are more protective against manic (but not depressive) episodes but have more adverse effects. Adolescents, whose glomerular function is excellent, need higher doses; older patients need lower doses.

Lithium can cause sedation and cognitive impairment directly or indirectly (by causing hypothyroidism) and often exacerbates acne and psoriasis

is manifested initially by gross tremor, increased deep tendon reflexes, persistent headache, vomiting, and confusion and may progress to stupor, seizures, and arrhythmias. Toxicity is more likely to occur in the following:

• Older patients

• Patients with decreased creatinine clearance

• Those with sodium loss (eg, due to fever, vomiting, diarrhea, or use of diuretics)

Lithium blood levels should be measured every 6 months and whenever the dose is changed.

Long-term adverse effects of lithium include

• Hypothyroidism, particularly when there is a family history of hypothyroidism

• Hypercalcemia and hyperparathyroidism

• Renal damage involving the distal tubule that appears after ≥

hypothyroidism1, 2, 3).

For valproate, the initial dose and route of administration may vary, but it requires adjustment based on target serum levels. A loading-dose protocol based on weight may result in earlier symptom improvement. Adverse effects include nausea, headache, sedation, dizziness, and weight gain; rare serious effects include hepatotoxicity and pancreatitis.

should not be loaded; it should be increased gradually to achieve a target serum level. Adverse effects include nausea, dizziness, sedation, and unsteadiness. Very severe effects include aplastic anemia and agranulocytosis.

Stevens-Johnson syndrome

Acute manic psychosis is being increasingly managed with second-generation antipsychotics, such as

In addition, evidence suggests that some of these medications may enhance the effects of mood stabilizers after the acute phase (1).

metabolic syndrome (including weight gain, excess abdominal fat, insulin

Specific antidepressants (eg, selective serotonin reuptake inhibitors12).

use during pregnancy has been associated with an increased risk of cardiovascular malformations (particularly Ebstein anomaly). However, the absolute risk of this particular malformation is quite low (1

With valproate, risk of neural tube defects and other congenital malformations appears to be 2 to 7 times higher than that with other commonly used antiseizure medications and should not be used during pregnancy (2). Valproate increases the risk of neural tube defects, congenital heart defects, genitourinary anomalies, musculoskeletal abnormalities, and cleft lip or palate. Also, cognitive outcomes (eg, IQ scores) in children of women who took valproate during pregnancy are worse than those with other antiseizure medications; risk appears to be dose-related. Valproate also appears to increase risk of attention-deficit/hyperactivity disorder and autism spectrum disorders (3).

4). The risk of teratogenicity also appears to be low for selective serotonin reuptake inhibitors (SSRIs) (56), but the data are inconsistent. Data about the risks of second-generation antipsychotics to the fetus are sparse as yet, even though these medications are being more widely used for all phases of bipolar disorder.

Treatment decisions are complicated by the fact that with unplanned pregnancy, teratogenic effects may already have taken place by the time clinicians become aware of the issue. Consultation with a perinatal psychiatrist should be considered. In all cases, discussing the risks and benefits of treatment with patients is important. (See also Antidepressants During Pregnancy.)