Antipsychotics and the Treatment of Bipolar Disorder

By Candida Fink, Joe Kraynak

Atypical antipsychotics (atypical neuroleptics or second-generation antipsychotics) were originally formulated to treat psychosis in schizophrenia, but this class of medications has also proven effective in reducing mania and augmenting antidepressant treatment.

The atypical or second-generation moniker stems from the fact that this newer breed of antipsychotics works differently than the older standard or first-generation neuroleptics, such as chlorpromazine (Thorazine) and haloperidol (Haldol). The following table lists the most common atypical antipsychotics used to treat bipolar and their benefits and potential side effects.

Potential Benefits and Side Effects of Atypical Antipsychotics
Generic Name Brand Name Average Adult Dose Potential Benefits Some Possible Side Effects*
Aripiprazole Abilify (also available in quick-dissolving tablets and
long-lasting injectable)
15 to 30 mg/day Antimanic; may prevent or reduce recurrent episodes;
antipsychotic.
Akathisia (severe restlessness); weight gain; increased blood
sugar and cholesterol levels; increased risk of diabetes and heart
disease; reversible movement disorders; sedation or insomnia;
headache.
Asenapine Saphris 10 to 20 mg/day Antimanic; antipsychotic. Weight gain; increased blood sugar and cholesterol levels;
increased risk of diabetes and heart disease; reversible movement
disorders; sedation or insomnia; nausea.
Lurasidone Latuda 20 to 80 mg/day Approved to treat bipolar depression; unknown as to whether it
has benefits in mania or preventing/reducing recurrent episodes;
antipsychotic.
Weight gain; increased blood sugar and cholesterol levels;
akathisia; nausea; reversible movement disorders.
Olanzapine Zyprexa
Relprevv (injectable)
Zydis (oral disintegrating tablet)
Symbyax (a combination of olanzapine and fluoxetine); see the later
discussion on antidepressants
5 to 20 mg/day Antimanic (FDA labeled); may prevent or reduce recurrent
episodes; antipsychotic.
Used in combination with fluoxetine as Symbyax to treat bipolar
depression.
Weight gain, increased blood sugar and cholesterol levels;
increased risk of diabetes and heart disease; elevated prolactin
levels; reversible movement disorders; akathisia; sedation or
insomnia.
Quetiapine Seroquel 50 to 800 mg/day Antimanic; may prevent or reduce recurrent episodes;
antipsychotic; treats bipolar depression; augmentation of
antidepressants in unipolar depression.
Sedation; weight gain; increased blood sugar and cholesterol
levels; increased risk of diabetes and heart disease; dry mouth;
constipation.
Risperidone Risperdal (also available in quick-dissolving tablets and
long-lasting injectable)
2 to 6 mg/day for mania Antimanic; may prevent or reduce recurrent episodes;
antipsychotic.
Weight gain; increased blood sugar and cholesterol levels;
increased risk of diabetes and heart disease; elevated prolactin
levels; reversible movement disorders; akathisia; sedation or
insomnia.
Ziprasidone Geodon 40 to 160 mg/day split into two doses and always given with
food
Antimanic; may prevent or reduce recurrent episodes;
antipsychotic.
Heart rhythm changes; may need EKGs before starting and during
treatment; minimal risk of weight gain; increased blood sugar and
cholesterol levels; increased risk of diabetes and heart disease;
reversible movement disorders; sedation.

mg/day = milligrams per day.

* Other side effects may occur that are not listed.

Paliperidone (Invega) and iloperidone (Fanapt) are two additional antipsychotics that don’t have indications for use in bipolar disorder. Invega is indicated for use in treating schizophrenia and schizoaffective disorder, and iloperdione is indicated only for use in schizophrenia. Given that they’re in the same family, some prescribers may use these medications in bipolar disorder. They carry the same overall side effect risks as other atypical antipsychotics presented in the table.

Second-generation antipsychotics share the following possible side effects:

  • Sugar metabolism problems and increased risk of developing type 2 diabetes (The FDA requires atypical antipsychotic medications to include a label warning for people at risk for hyperglycemia and diabetes.)

  • Weight gain and increases in cholesterol and other fats

  • Reversible movement problems, similar to those associated with Parkinson’s disease (tremors and stiffness), which go away when the dose is decreased or the medicine is stopped

  • Irreversible uncontrolled movements called tardive dyskinesia (facial twitches or uncontrolled movements of the tongue, lips, arms, and so on), which usually don’t go away when the medicine is stopped

  • Akathisia, a feeling of extreme restlessness, commonly described as the overwhelming desire to jump out of your skin

  • Changes in cardiac rhythms

  • Some can increase levels of the hormone prolactin, which sometimes causes breast enlargement in men and lactation or menstrual problems in women

  • Impaired sexual function

  • Other general side effects, including sedation, dizziness, constipation, and headaches

Clozapine (Clozaril)

Clozapine (Clozaril) is an atypical antipsychotic that psychiatrists often consider to be a medication of last resort due to its severe negative side effects. Clozapine is most commonly used for treatment-resistant schizophrenia, but it’s used off-label for severe bipolar mania or psychosis that isn’t responding to other treatments. Clozapine also has an indication (that is, licensed approval for a particular use in the United States by the FDA or in Europe by the EMA) as a treatment for “recurrent suicidal behavior,” regardless of diagnosis.

Clozapine has a high risk of causing a severe reduction in white blood cells, a condition called agranulocytosis. People taking this medication must get their blood drawn every week for the first six months of treatment and every other week after that. Clozapine also tends to cause significant weight gain.

Typical, first-generation antipsychotics

First-generation antipsychotics include haloperidol (Haldol), perphenazine (Trilafon), molindone (Moban), and thiothixene (Navane). These medications were developed to treat schizophrenia and then expanded into use for other conditions, including bipolar disorder and agitation. The first-generation antipsychotics have fallen out of use now that newer ones are available.

One reason for the reduced use of the older antipsychotics is the higher risks they carry for triggering movement disorders, including tardive dyskinesia (often irreversible, involuntary muscle movements especially around the face and jaw). But one of the benefits that these medications have over their second-generation counterparts is that they carry a lower risk of metabolic changes associated with weight gain and diabetes.

Some large studies suggest that the older medicines are just as effective in treating schizophrenia at lower cost and without significantly more side effects than the second-generation antipsychotics. However, no systematic large studies compare the first- and second-generation antipsychotics in treating bipolar disorder. Therefore, first-generation antipsychotics are used only as a second choice for treating bipolar when the newer antipsychotics or other alternatives are ineffective or not tolerated by an individual.