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The Ups and Downs of Antipsychotics for Bipolar Disorder

The Ups and Downs of Antipsychotics for Bipolar DisorderAntipsychotics have become one of the most popular treatments for bipolar disorder. Ten years ago they were mostly prescribed acutely when a patient was in the midst of a manic episode. Even then they were only prescribed to 37% of patients. Now antipsychotics, especially newer, atypical-antipsychotics, are being used for maintenance therapy- taken regularly to prevent manic or depressive episodes- at a rate of over 60%.

These are powerful drugs, especially at higher doses. Think along the lines of tranquilizers. Sometimes that’s what it takes to save you from your own mind.

Some examples of atypical antipsychotics include:

  • Aripiprazole (brand name: Abilify)
  • Lurasidone (Latuda)
  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel)
  • Risperidone (Risperdal)

They work by manipulating the levels of dopamine in the brain. During mania, dopamine levels soar, producing effects similar to taking amphetamines. In depression, dopamine levels tend to be significantly lower than average.  Newer antipsychotics affect the production and distribution of dopamine in the brain, acting as a mood stabilizer and reducing the severity of symptoms.

That’s the simple version. The production and actions of dopamine depend on several factors. Some of these factors depend on the person’s environment. Others depend on genetics and how those genes signal the body to produce or breakdown dopamine.

One such gene is catechol-O-methyltransferase (COMT), which breaks down dopamine in the prefrontal cortex. The prefrontal cortex is where “executive functioning” happens in the brain. That’s where functions like memory, personality, learning, inhibition decision making and attention all take place. It’s possible that variants of the COMT gene are partially responsible for susceptibility to bipolar disorder.

So let’s say you have a variant of the COMT gene that prevents dopamine levels from normalizing; antipsychotics can actually manipulate how genes express themselves in order to balance dopamine levels. Excellent.

Well, not so fast. That one gene is not responsible for the whole of bipolar disorder. There are more genes under investigation and other physical factors like brain structure and environmental factors like abuse, alcoholism or hormone imbalances that go into a person’s experience of bipolar disorder. So evening out dopamine levels isn’t a quick-fix.

As with all drugs, there are also side-effects to consider, and antipsychotics have their fair share. Here are some of the most common:

  • Drowsiness
  • Dizziness
  • Restlessness
  • Weight gain (the risk is higher with some atypical antipsychotic medicines)
  • Dry mouth
  • Constipation
  • Nausea
  • Vomiting
  • Blurred vision
  • Low blood pressure
  • Uncontrollable movements, such as tics and tremors (the risk is higher with typical antipsychotic medicines)
  • Seizures
  • A low number of white blood cells, which fight infections

Not listed among these are possible cognitive side effects. People with bipolar disorder are prone to cognitive functioning issues even between episodes, affecting the same prefrontal cortex operations previously mentioned: memory, learning, attention and thought speed. While antipsychotics seemingly improve these symptoms in schizophrenic patients, they may worsen them in bipolar disorder.

One reason for this may lie in the same COMT gene responsible for breaking down dopamine. Patients with a specific variant of the gene (the GG genotype of COMT rs5993883 or COMT Val108/158Met) tend to have more problems with learning, memory and attention when treated with antipsychotics.

These types of variables and complications all contribute to the fact that it can take years to find the most effective combination of medications to treat bipolar disorder, even if antipsychotics are not among them.



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Photo credit: Hiroh Satoh

The Ups and Downs of Antipsychotics for Bipolar Disorder

LaRae LaBouff

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APA Reference
LaBouff, L. (2016). The Ups and Downs of Antipsychotics for Bipolar Disorder. Psych Central. Retrieved on October 21, 2020, from


Last updated: 4 Apr 2016
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