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Atypical antipsychotics are antipsychotics that are less likely than traditional antipsychotics to cause certain side effects, such as extrapyramidal symptoms (EPS). EPS are drug-induced movement disorders and include tremor, Parkinson's-like symptoms (walking with a shuffle, mask-like facial features) and tardive dyskinesia (this describes abnormal, repetitive facial movements such as lip smacking or poking the tongue out).

Most atypical antipsychotics were discovered recently; however, clozapine is often referred to as atypical antipsychotic even though it was discovered more than 60 years ago. Atypical antipsychotics are also known as second generation antipsychotics.

Experts aren’t exactly sure how atypical antipsychotics work but they appear block certain chemical receptors in the brain, affecting levels of various neurotransmitters such as dopamine, acetylcholine, noradrenaline, or serotonin. Atypical antipsychotics appear to have a higher affinity for serotonin receptors and a lower affinity for dopamine receptors than typical antipsychotics.

What are atypical antipsychotics used for?

Atypical antipsychotics are used to relieve symptoms such as delusions (mistaken beliefs), hearing voices, seeing things that aren’t there (hallucinations), or paranoid or confused thoughts typically associated with some mental illnesses.

They may be used to treat the symptoms of schizophrenia or a psychotic episode; in the treatment of severe depression; severe agitation or anxiety; or for stabilizing episodes of mania in people with Bipolar Disorder. Some are FDA-approved in children to treat irritability associated with Autistic disorder.

What are the differences between atypical antipsychotics?

Atypical antipsychotics differ in the way that they are absorbed into the body, how they are metabolized, the length of their effect, and how they are excreted. There are also differences between them with regards to:

• Weight gain: Clozapine appears to have the highest risk followed by olanzapine and quetiapine
• Reduction in the risk of suicidal events and behavior: Clozapine appears superior to olanzapine
• Discontinuation because of adverse effects: Clozapine has the highest rate of discontinuation in the short-term but the lowest rate out of any antipsychotic in the long-term (two years or more)
• Risperidone appears to have higher rates of EPS than olanzapine
• Risperidone may have higher rates of sexual dysfunction compared with quetiapine, but similar rates when compared with ziprasidone
• Women may be more responsive to clozapine and olanzapine than men.

With regards to the difference between atypical antipsychotics and typical antipsychotics, atypical antipsychotics are less likely to produce EPS but more likely to cause weight gain. Recently, no difference in effectiveness regarding symptom improvement between atypical antipsychotics and typical antipsychotics has been shown.

Common Atypical Antipsychotics Available in the U.S.

Are atypical antipsychotics safe?

All medicines have their risks and benefits and atypical antipsychotics are no exception. When taken as prescribed by a doctor in people with no contraindications for their use, atypical antipsychotics are considered safe; however, some, such as clozapine, require ongoing monitoring.

About 1 in 10 people who take clozapine develop neutropenia, which is a loss in the capacity to produce white blood cells needed to fight infection. This could result in a serious infection and potentially, death. Anybody taking clozapine requires regular blood tests to check their blood cell counts. Clozapine may also cause changes in heart rate or blood pressure, constipation, excessive salivation, sedation, or weight gain. However, it does not tend to cause movement-related symptoms such as EPS.

All antipsychotics are associated with an increased risk of death when used in elderly people, especially those with dementia, and they are not approved for this use. In addition, atypical antipsychotics may cause changes in metabolism and increase the risk for diabetes and high cholesterol.

What are the side effects of atypical antipsychotics?

Atypical antipsychotics are more likely than typical antipsychotics to cause weight gain and metabolic disturbances including an increase in the incidence of type 2 diabetes and high cholesterol.

Other common side effects include:

• difficulty concentrating or speaking
• changes in blood pressure
• constipation
• difficulty sleeping
• drooling
• drowsiness
• mask-like face
• restlessness or need to keep moving
• sexual dysfunction
• shuffling walk
• tremor
• vision problems (blurred or double vision).

All antipsychotics can cause drowsiness. Most antipsychotics are associated with high rates of discontinuation either because of side effects or a lack of effect.