Treating Bipolar Depression

On average people with Bipolar I Disorder spend three times more in a depressive episode than in a manic or hypomanic state; those with Bipolar II Disorder suffer 40 times more in a depressive episode than in a manic or hypomanic state. According to DSM-5 a bipolar depressive episode and a unipolar depressive episode have the same diagnostic criteria marked by five of the following nine symptoms for two weeks:

• Depressed mood
• Loss of pleasure
• Weight or appetite change
• Change in sleep
• Psychomotor agitation or retardation
• Fatigue
• Feelings of worthlessness or guilt
• Indecisiveness or trouble concentrating
• Suicidal ideation

Bipolar I patients have had at least one manic episode lasting at least one week during which time the person feels euphoric and overly optimistic or is extremely irritable marked by three of the following symptoms:

•  Unrealistic, grandiose beliefs about one’s abilities or powers
•  Rapid speech that makes it difficult for others to keep up
• Acting recklessly without thinking about the consequences
• Racing thoughts, jumping quickly from one idea to the next
•  Distractibility marked by poor concentration and attention
•  Impulsiveness, poor judgment, agitation or excessive goal pursuit
•  Sleeping very little but without loss of energy

Bipolar II patients have had at least one hypomanic episode that differs from mania by intensity and duration. A hypomanic episode is only required to persist for four days instead of seven. Those in a hypomanic state can make bad decisions that harm relationships, careers, and reputations, but they are able to perform without losing touch with reality.

Three medications have been approved by the FDA for the treatment of acute bipolar depressive episodes:

1.  Seroquel (quetiapine)
2.  Symbyax (a combination of fluoxetine and olanzapine)
3.  Latuda (lurasidone)

Seroquel can contribute to significant weight gain and metabolic syndrome as can Symbyax. Both Latuda and Symbyax are expensive.

Lithium listed as first-line treatment for acute bipolar depression in the APA practice guidelines also has the following advantages:

• FDA approval for acute manic episodes
• FDA approval for maintenance treatment for those bipolar patients with a history of mania. 
• Frequently used to augment antidepressants in treatment resistant major depression. 
• Works rapidly (1-3 weeks)
• Is inexpensive
• Substantially decreases suicide risk
• May be useful for episodic rage, anger or violence unassociated with bipolar illness 
• May be useful for self-destructive behavior found in personality disorders

Lithium is underutilized. Because lithium is a generic medication pharmaceutical companies have little incentive to seek FDA approval for Bipolar II depression.

In most cases the benefits of lithium supersede the risks with the following precautions:

• Regular blood levels are necessary because toxic levels characterized by nausea, vomiting, diarrhea, slurred speech, gross tremor and staggering  occur close to therapeutic effects. With proper dosing and monitoring these side effects rarely occur.
• Should be avoided in patients with severe kidney disease, dehydration or sodium depletion
• Category D in pregnancy with positive evidence of risk to human fetus 

The initial dose can be begun at 300 mg 2-3 times daily. Alternatively the cautious clinician can prescribe 300 mg lithium at night. After one week the dose can be increased to 600 mg. Following another week the dose can be increased to 900 mg. Baseline labs and a lithium level can be drawn within a week of starting lithium. Gradually titration slows the time to response.