Acute Treatment of Manic Episode

The following drugs may be used to treat manic episodes:

In August 2009, the U.S. Food and Drug Administration (FDA) approved the atypical antipsychotic drug asenapine (Saphris) to treat bipolar I disorder and schizophrenia in adults. Cariprazine (Vraylar) was approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder and to treat schizophrenia in September 2015. Asenapine side effects include decreased sensitivity in the mouth, drowsiness, and an inability to remain still or motionless. Cariprazine can cause tremor, slurred speech, involuntary muscle movements, indigestion, vomiting, drowsiness, and restlessness.

These medications control mood swings and acute symptoms, manage recurrences, reduce the risk of suicide, and restore a sense of well-being. Atypical antidepressants carry a Boxed Warning about an increased risk of death in older people with dementia-related psychoses and should not be used in these patients.

Lithium revolutionized psychiatry when first introduced as a drug of treatment in the 1950s. The use of a simple salt to effectively treat mental illness supported the theory that chemical imbalances caused the disorders and dispelled beliefs that bad parenting or neglect were the only causes. Lithium is the mainstay of bipolar treatment, and the condition can often be controlled with lithium alone. It effectively treats both manic and depressive episodes and prevents devastating relapses. It typically takes 1 to 2 weeks for lithium to be effective.

There is a high rate of suicide among people with untreated bipolar disorder, and studies show that lithium treatment significantly reduces this risk. Conversely, patients who discontinue lithium treatment are 20 times as likely to commit suicide during the first 6 months following discontinuation.

Common side effects of lithium treatment include the following:

  • Blurred vision
  • Dry mouth
  • Fine hand tremor
  • Frequent urination
  • Mild nausea, occasional vomiting

Long-term effects include weight gain, possible hypothyroidism, and kidney dysfunction. Patients who have kidney disease should not take lithium. Levels of lithium in the blood are monitored regularly to ensure that the proper concentration is maintained.

Lithium may cause birth defects and pregnant women should discuss the risks of taking the drug during pregnancy with their health care providers.

Valproate, which was initially used to treat seizures, is also approved to treat bipolar disorder. This drug is more effective than lithium in treating rapid-cycling bipolar disorder. Blood levels of valproate must be monitored regularly because high levels can be toxic. Common side effects of valproate include the following:

  • Dizziness
  • Drowsiness
  • Nausea
  • Tremor

Long-term effects include weight gain and possible liver dysfunction. Patients with liver disease should not take this medication.

Carbamazapine is also an antiseizure drug. Although not approved by the FDA for the treatment of bipolar disorder, it is sometimes used to control mania and depression in patients with the disorder. Common side effects include the following:

  • Dizziness
  • Drowsiness
  • Nausea and occasional vomiting
  • Rash

Long-term effects include reduced white blood cell count (leukopenia) and liver dysfunction. Patients who have liver disease should not take this drug. Blood levels of carbamazapine are monitored regularly.

Carbamazepine may cause birth defects and pregnant women should discuss the risks of taking the drug during pregnancy with their health care providers. Carbamazepine may cause oral contraceptive (i.e., birth control pill) failure. To avoid becoming pregnant, another form of birth control should be used while taking the drug.

Antipsychotic medications (e.g., olanzapine [Zyprexa]) can be used to treat psychosis when it occurs in a manic episode. Symbyax combines olanzapine with fluoxetine hydrochloride (the active ingredient in Prozac) to treat bipolar disorder. Antipsychotic medications may cause serious long-term side effects (e.g., tardive dyskinesia) and should be used at the lowest effective dose and discontinued as soon as symptoms resolve.

Patients taking antipsychotic medications should be evaluated periodically to assess the need for maintenance therapy (see treatment of schizophrenia). Side effects include the following:

  • Blurred vision
  • Drowsiness
  • Dry mouth
  • Weight gain

Ziprasidone (Geodon) is an antipsychotic medication approved by the FDA to treat manic episodes. This medication, which also is used to treat schizophrenia, is prescribed at higher doses to treat bipolar disorder. Side effects include the following:

  • Constipation
  • Cough
  • Diarrhea
  • Difficulty swallowing
  • Extreme tiredness
  • Increased or decreased body temperature
  • Low blood pressure (dizziness, increased heart rate, fainting)
  • Muscle spasms
  • Nausea
  • Seizures

Studies indicate that ziprasidone may cause fewer side effects (e.g., weight gain, movement disorders) than other medications. In December 2014, the FDA warned that this medication may be associated with a rare, but serious skin reaction that may affect other areas of the body. This reaction, which is called drug reaction with eosinophilia and systemic symptoms (DRESS), causes high levels of certain white blood cells (eosinophils) and can be fatal. Symptoms include rash that spreads, fever, swollen lymph nodes, and organ inflammation.

Benzodiazepines are used to treat anxiety or agitation during a manic episode.

Risperidone (Risperda) has been approved by the Food and Drug Administration (FDA) as short-term treatment for acute mania associated with bipolar I disorder. This drug, which also is used to treat schizophrenia, may be used alone (called monotherapy) or in combination with lithium or valproate.

Side effects include the following:

  • Agitation
  • Anxiety
  • Dizziness
  • Excessive sleepiness (somnolence)
  • Headache

Aripiprazole (Abilify) is a dopamine partial agonist that was approved by the FDA in 2002 to treat acute mania or mixed episodes in adults who have bipolar I disorder. In February 2008, this drug was also approved for use in pediatric patients between the ages of 10 and 17.

Patients who are taking aripiprazole should be monitored closely for unusual changes in behavior, worsening of symptoms, and suicidal tendencies. Side effects include nausea and vomiting, constipation, headache, dizziness, and insomnia. In children, common side effects include excessive sleepiness (somnolence) and headache. Elderly patients with dementia disorders are at higher risk for severe side effects and death.

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 31 Jan 2001

Last Modified: 18 Sep 2015