Atypical antipsychotics such as Zyprexa are less intense in their side effect profiles than that of typical antipsychotics. although persistent side effects do remain an issue. Some have come under fire for contributing to weight gain, diabetes, and subsequent deaths.

Atypical Antipsychotics are powerful mood-altering drugs

Not all atypical antipsychotics have the same side effects. Atypical antipsychotics, however, still need to be considered powerful mood altering drugs. Like all psychiatric drugs, atypical antipsychotics address or alleviate symptoms rather than the underlying illness or brain disorder.

Introduction to Atypical Antipsychotic Drugs

The atypical antipsychotics (also known as second generation antipsychotics) are a group of antipsychotic drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia. Some carry FDA approved indications for acute mania, bipolar mania, psychotic agitation, bipolar maintenance, and other indications.

Atypicals are a group of unrelated drugs united by the fact that they work differently from typical antipsychotics. Most share a common attribute of working on serotonin receptors as well as dopamine receptors. One drug, amisulpride, does not have serotonergic activity, instead it has some partial dopamine agonism. Another drug, aripiprazole, also displays some partial dopamine agonism, 5-HT1A partial agonism and 5-HT2A antagonism.

The first atypical anti-psychotic medication, clozapine, was discovered in the 1950s, and introduced in clinical practice in the 1970s.

Clozapine fell out of favor due to concerns over drug-induced agranulocytosis. With research indicating its effectiveness in treatment-resistant schizophrenia and the development of an adverse event monitoring system, clozapine reemerged as a viable antipsychotic.

Despite the effectiveness of clozapine for treatment-resistant schizophrenia, agents with a more favorable side effect profile were sought after for widespread use. During the 1990s, olanzapine, risperidone, and quetiapine were introduced, with ziprasidone and aripiprazole following in the early 2000s. The newest atypical anti-psychotic, paliperidone, was approved by the FDA in late 2006.

Atypical Antipsychotics: Types

Clozapine Clozaril (FDA-approval: 1990) Available in oral tablets and dissolving tablets (FazaClo).

Risperidone Risperdal (FDA-approval: 1993) Available in oral tablets, dissolving tablets, liquid form, and extended release intramusclar injection.

Olanzapine Zyprexa (FDA-approval: 1996) Available in oral tablets, dissolving tablets, and intramuscular injection.

Quetiapine Seroquel (FDA-approval: 1997) Available only in oral tablets.

Ziprasidone Geodon (FDA-approval: 2001) Available in oral capsules and intramuscular injection.

Aripiprazole Abilify (FDA)-approval: 2002) Available in oral tablets and dissolving tablets.

Paliperidone Invega (FDA)-approval: 2006) Available in extended-release oral tablets.

Asenapine FDA has accepted NDA as of November 26, 2007.

Iloperidone (Fanapta or Zomaril) FDA has accepted NDA as of November 27, 2007.

Antipsychotics not approved for use in the United States

Sertindole (Serlect) (Not approved by the FDA for use in the USA).

Zotepine (Not approved by the FDA for use in the USA).

Amisulpride (Not approved by the FDA for use in the USA).

Bifeprunox (Not approved by the FDA for use in the USA).

Melperone Approved in Europe. Currently in clinical trial in the USA.

Atypical Antipsychotics Side Effects

The side effects reportedly associated with the various atypical antipsychotics vary and are medication-specific. Generally speaking, atypical antipsychotics are hoped to have a lower likelihood for the development of tardive dyskinesia than the typical antipsychotics.

However, tardive dyskinesia typically develops after long term (possibly decades) use of antipsychotics. It is not clear, then, if atypical antipsychotics, having been in use for a relatively short time, produce a lower incidence of tardive dyskinesia.

There have been, as of the date of this article's research, 1328 reports of serious, and sometimes life threatening, side effects. These include tardive dyskinesia (involuntary jerking and facial grimacing) and dystonia (involuntary muscle contractions that can interfere with talking and eating).

Akathisia is more likely to be less intense with these drugs then the typical antipsychotics[citation needed] although many patients would dispute this claim. In 2004, the Committee for the Safety of Medicines (CSM) in the UK issued a warning that olanzapine and risperidone should not be given to elderly patients with dementia, because of an increased risk of stroke. Sometimes atypical antipsychotics can cause abnormal shifts in sleep patterns, and extreme tiredness and weakness.

Tardive Dyskinesia All the atypical antipsychotics warn about the possibility of tardive dyskinesia in their package inserts and in the PDR. It is not possible to truly know the risks of tardive dyskinesia when taking atypicals, because tardive dyskinesia can take many decades to develop and the atypical antipsychotics are not old enough to have been tested over a long enough period of time to determine all of the long-term risks.

Metabolic side effects
Metabolic side effects with atypical antipsychotics have been of grave concern to clinicians, patients and the FDA. In 2003, the Food and Drug Administration (FDA) required all manufacturers of atypical antipsychotics to change their labeling to include a warning about the risks of hyperglycemia and diabetes with atypical antipsychotics.

It must also be pointed out that although all atypicals must carry the warning on their labeling, some evidence shows that all atypicals are not equal in their effects of weight and insulin sensitivity.

The general consensus is that clozapine and olanzapine are associated with the greatest effects on weight gain and decreased insulin sensitivity, followed by risperidone and quetiapine. Ziprasidone and aripiprazole are thought to have the smallest effects on weight and insulin resistance, but clinical experience with these newer agents is not as developed as that with the older agents.

Children and atypical antipsychotics

In 2006, USA Today published an article about the effects of antipsychotic medication in children. None of the atypicals (Clozaril, Risperdal, Zyprexa, Seroquel, Abilify and Geodon) have been approved for children, and there is little research on their effects on children. (Abilify is the only atypical antipsychotic approved for use in teens 15 to 17 years old).

From 2000-2004, there were 45 reported deaths in which an atypical antipsychotic was listed as the "primary suspect." They are still being used and prescribed for children, however, despite not being approved by the FDA.

References for Atypical Antipsychotics

1. Cause Of Antipsychotic Drug Weight Gain, (February 15, 2007). Medical News Today.

2. Mental Health Medications. (June 24, 2009). NIMH. https://www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.shtml

3. New antipsychotic drugs carry risks for children, (May 2, 2006). Marilyn Elias. USA Today

4. The risks of prescribing antipsychotics to kids, (February 5, 2012. Carly. The Globe and Mail.

5. Weight Gain Associated With Antipsychotic Drugs, (October 27, 2009). Duff Wilson. New York Times.

Pages Related to Atypical Antipsychotics

Psychiatric Drugs - Types

Typical Antipsychotics - Major Tranquilizers, Neurolyptics

Opium and Brief History of Psychiatric Drugs

Drugging Our Children: How Profiteers Are Pushing Antipsychotics on Our Youngest, and What We Can Do to Stop It (Childhood in America), by Sharna Olfman (Editor), Brent Dean Robbins

The prescription rate for toddlers, preschoolers, and middle-class children has doubled, while the prescribing rate for low-income children covered by Medicaid has quadrupled. In a majority of cases, these drugs are neither FDA-approved nor justified by research for the children's conditions. This book examines the reasons behind the explosion of antipsychotic drug prescriptions for children. (from the publisher)

A History of Psychiatry: From the Era of the Asylum to the Age of Prozac by Edward Shorter

Psychiatry has gone through many twists and turns from the days of oppressive and abusive insane asylums, through various movements within the field, into the modern day of psychopharmacology. This book details the history of psychiatry through the centuries.