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Medications for Bipolar Disorder: Antidepressants

The use of antidepressants in bipolar disorder is highly controversial. On one side, research shows that the use of antidepressants can induce mania or hypomania both in those with established bipolar disorder and those with previously undiagnosed or misdiagnosed bipolar disorder. On the other side, the use of antidepressants in treatment-resistant depression may help alleviate symptoms. Since more than half of patients with bipolar disorder are prescribed antidepressants, it is important to remain educated about any effectiveness as well as inherent risks.

The term “antidepressant” is a blanket term used to describe several different classes of medications. Antidepressants are not only used to treat depression. They are also used to treat sleep problems, chronic pain, premenstrual dysphoric disorder, addiction and anxiety disorders. The most common antidepressants prescribed for use in treating bipolar disorder are selective serotonin reuptake inhibitors (SSRI’s) and serotonin and norepinephrine reuptake inhibitors (SNRI’s).

Common SSRI’s:

  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Fluoxetine (Prozac)
  • Paroxetine (Paxil, Pexeva)
  • Sertraline (Zoloft)
  • Vilazodone (Viibryd)

Common SNRI’s:

  • Duloxetine (Cymbalta)
  • Desvenlafaxine (Pristiq)
  • Levomilnacipran (Fetzima)
  • Milnacipran (Savella)
  • Venlafaxine (Effexor)

How they work:

Selective serotonin reuptake inhibitors work by increasing levels of serotonin available in the brain. Serotonin is a neurotransmitter not only found in the brain, but in the gut and blood platelets as well. Its role is to transport nerve impulses between cells. When serotonin is blocked from entering the subsequent nerve ending, it essentially free floats in the brain to remain available when the channel is no longer blocked. It is this increased level of available serotonin that is thought to be how antidepressants work.

Serotonin and norepinephrine reuptake inhibitors work in a similar way only they block the reuptake of norepinephrine in addition to serotonin. Serotonin can affect mood, social behavior, digestion, sleep, memory and sexual function. Norepinephrine is a stress hormone that triggers the “fight or flight” response.

Effectiveness in treating bipolar disorder:

  • Adding an antidepressant to a mood stabilizer may not be any more effective than adding a placebo to a mood stabilizer.
  • Antidepressants may lower the chance of new depressive episodes by 27% but may also increase the chance of new manic episodes by 75%.
  • Up to 30% of patients receiving antidepressant treatment switch from depressive to manic or hypomanic states.
  • Approximately 50% of people taking antidepressants short-term for acute depression see results or remission within 12 weeks.
  • Antidepressants may be more effective in bipolar II versus bipolar I for acute treatment.
  • Use of antidepressants can induce or worsen rapid cycling in some patients.

Common side effects:

  • Increased agitation
  • Digestive distress
  • Changes in appetite
  • Weight gain
  • Fatigue
  • Dizziness
  • Trouble sleeping
  • Sexual dysfunction
  • Suicidal ideation

Withdrawal symptoms:

  • Insomnia
  • Vivid dreams
  • Headaches
  • Dizziness
  • Fatigue
  • Irritability
  • Flu-like symptoms
  • Nausea
  • Depression


There is limited data to suggest that antidepressants are more effective at treating bipolar depression than mood stabilizers. Since there is a significantly increased risk in switching moods from depression to mania with the use of antidepressants, they should be used with caution, if at all. Dosage titration should be slow and use should be discontinued after the episode has subsided. Antidepressants should also only be used in combination therapy with a mood stabilizer.

Always consult a physician before adding, discontinuing or changing any medication regimen. If you experience any side effects or signs of withdrawal, contact your doctor immediately.

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Image credit: Kim Siever


Medications for Bipolar Disorder: Antidepressants

LaRae LaBouff

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APA Reference
LaBouff, L. (2017). Medications for Bipolar Disorder: Antidepressants. Psych Central. Retrieved on April 3, 2020, from


Last updated: 4 Mar 2017
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