An Overview of Atypical Antipsychotics for Bipolar Depression

An Overview of Atypical Antipsychotics for Bipolar Depression

Bipolar disorder is composed of emotional highs (mania or hypomania) and lows (depression). For many, those emotional lows may take up the bulk of their days, which is why many doctors may prescribe atypical antipsychotics for bipolar depression.

Atypical antipsychotics are complex drugs. They are considered “atypical” (as opposed to “typical” or “conventional” antipsychotics) based on their clinical profile. They tend to have fewer side effects including extrapyramidal symptoms, which may involve tremors, involuntary movements, and muscle contractions. In addition to being used for treatment of schizophrenia, atypical antipsychotics have become a popular treatment option for Bipolar Disorder.  So far, the FDA has approved four atypical antipsychotics for bipolar depression. 

Atypical Antipsychotics for Bipolar Depression

Cariprazine (Vraylar®)

Cariprazine, which is sold in the US under the brand name Vraylar®, is FDA-approved for both manic and depressive episodes in bipolar disorder. It is believed to work by affecting the activity of neurotransmitters such as dopamine and serotonin. However, the exact way the Cariprazine works is still unknown.

The most common side effects include akathisia, a movement disorder characterized by the inability to sit still, similar to restless leg syndrome, and extrapyramidal symptoms. Additionally, the dosage needed for treatment is higher than other atypical antipsychotics for bipolar depression. Despite this, Cariprazine is rated favorably for rates of weight gain and fatigue, especially in lower doses. In order to minimize the akathisia, it is usually started at a low dosage of 1.5mg daily. 

Lurasidone (Latuda®)

Patients with bipolar depression as young as 12 years old are approved by the FDA to take Lurasidone. It is sold in the United States under the brand name Latuda® and has favorable rates of weight gain and fatigue in patients. Notably, it is the only atypical antipsychotic for bipolar depression with evidence to improve cognition in bipolar disorder, based on a small, controlled trial.

Side effects of Lurasidone include nausea and akathisia. Additionally, the drug must be taken with a meal of more than 350 calories, and grapefruit should be avoided, as it can affect the drug’s absorption rate.

The ideal dose of Lurasidone is still unknown as it has been dosed flexibly in trials for atypical antipsychotics for bipolar depression. Data suggests that higher doses are more effective, with a dose-response relationship between 20 and 120mg.

Olanzapine-fluoxetine combo (OFC) (Symbyax)

OFC is a combination of two psychotropic agents: Olanzapine and Fluoxetine (the active ingredient in Prozac). Olanzapine does not treat depression on its own, so it requires the fluoxetine component, which works by increasing the activity of serotonin in the brain, in order to work. The prescription for OFC may be written as a single combo pill, or as two separate medications. 

There are some significant risks associated with the Olanzapine-fluoxetine combination, most notably weight gain and metabolic adverse effects. Those metabolic effects may be mitigated by taking metformin, an anti-diabetic agent.

Quetiapine (Seroquel)

Quetiapine is sold under the name Seroquel and is FDA-approved for treatment of both manic and depressed episodes in bipolar disorder. It works by rebalancing dopamine and serotonin to improve thinking, mood, and behavior.

There are two formats of quetiapine that may be prescribed, extended release (XR) and instant release (IR). Both of these are approved atypical antipsychotics for bipolar depression, yet only the XR is approved to treat unipolar depression. Quetiapine IR can be dosed all-at-night, which typically results in lessened daytime fatigue as opposed to the XR version.

Quetiapine has favorable rates of akathisia and extrapyramidal effects, and may work to improve sleep quality and comorbid anxiety in patients. However, there are a few adverse effects of this drug, namely extreme sedation and hypotension, which are common causes of drug discontinuation and emergency room visits. Hypotension may be lessened by taking Quetiapine XR as opposed to the IR format, particularly when using doses greater than 300 mg.

Additionally, significant longterm issues may include weight gain and metabolic effects. Some patients on quetiapine are at risk for tardive dyskinesia, a disorder that may develop as a result of taking atypical antipsychotics for bipolar depression that appears as repetitive, jerking movements in the face, neck, and tongue.


Of the atypical antipsychotics for bipolar depression approved by the FDA, none really stands out as the best option for treatment. Quetiapine and OFC are not as well-tolerated by patients; OFC is the most likely to work and quetiapine may help with sleep and anxiety. The two brand name drugs, Latuda® and Vraylar®, tend to be better tolerated by patients but may lend themselves to difficulties with akathisia and costliness.

Contact Mid City TMS

If you’re struggling with depression or bipolar depression, Mid City TMS can help. Mid City TMS is a New York TMS center that provides transcranial magnetic stimulation as a part of our comprehensive depression treatments, including those with bipolar depression. TMS is often an excellent treatment choice for those with bipolar depression, especially for those who wish to avoid side effects of medications.  Learn more about what TMS treatment feels like here, and please contact us with any questions. If you’re interested in starting treatment, make an appointment today!

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