• Home
  • Store
    • Newsletter Subscriptions
    • Multimedia
    • Books
    • eBooks
    • ABPN SA Courses
    • Social Work Courses
  • CME Center
  • Multimedia
    • Podcast
    • Webinars
    • Blog
    • Psychiatry News Videos
    • Medication Guide Videos
  • Newsletters
    • General Psychiatry
    • Child Psychiatry
    • Addiction Treatment
    • Hospital Psychiatry
    • Geriatric Psychiatry
    • Psychotherapy and Social Work
  • FAQs
  • Med Fact Book App
  • Log In
  • Register
  • Welcome
  • Sign Out
  • Subscribe
Home » Abilify: The Perfect Antipsychotic?

Abilify: The Perfect Antipsychotic?

February 1, 2003
Daniel Carlat, MD
From The Carlat Psychiatry Report
Issue Links: Learning Objectives | Editorial Information | PDF of Issue
Daniel Carlat, MD Dr. Carlat has disclosed that he has no significant relationships with or financial interests in any commercial companies pertaining to this educational activity.

Abilify (aripiprazole) is out! But you probably already know this, if your mailbox and fax machine have become as saturated with BMS-funded missives from CME, Inc. as mine have been. The hired guns are out in force once again, and so we front-line clinicians are faced with the task of separating the authentic wheat from the hyped-up chaff.

The buzz is about its mechanism of action, which is unique among currently approved antipsychotics. Rather than being a dopamine blocker, it is a “dopamine system stabilizer”. What does this fancy moniker actually mean?

Let’s go back to the basics of antipsychotics. Conventional agents are dopamine antagonists throughout the brain, not distinguishing between the mesolimbic regions (where too much dopamine causes psychosis, we hypothesize) and the nigrostriatal region (where dopamine normally modulates fluidity of movement). Thus, far from “stabilizing” dopamine, conventional neuroleptics shut down on dopamine indiscriminately, leading to the movement disorders for which they are infamous.

So, along came the atypicals, first Clozaril, and subsequently the “first-line atypicals” (Risperdal, Zyprexa, Seroquel, and Geodon). Like conventionals, atypicals block dopamine receptors, but they also do something to modulate this effect: they block serotonin 2A receptors, especially in the nigrostriatal cortex. Since decreasing serotonin tends to increase dopamine, blocking 5HT 2A has the effect of releasing more dopamine where it is needed to prevent movement problems. Thus, atypicals tend not to cause EPS or TD. In a very real sense, then, current atypicals already are dopamine system stabilizers. So why the hullabaloo over Abilify?

It is not entirely clear. It may be because Abilify’s mechanism of stabilizing the dopamine system is more elegant. Rather than blocking dopamine in one area, then relying on also blocking serotonin to normalize levels, Abilify is a “partial agonist” of D2 in the first place, meaning that it sits on the dopamine receptor strongly enough to bat away the excess dopamine that causes psychosis, while at the same time exerting enough mild dopamine-like activity to prevent movement disorders. So its dopamine stabilizing mechanism is more direct. But does that make it a better antipsychotic? Probably not.
“Currently available atypicals do a pretty good job of ‘stabilizing’ the dopamine system already. Abilify is just more elegant in its mechanism.”

In fact, the clinical trials very clearly show that Abilify is no more effective than either Haldol or Risperdal. The most widely read study, by Kane and colleagues, randomized 414 acutely relapsed schizophrenic patients to one of four groups: Abilify 15 mg, Abilify 30 mg, Haldol 10 mg, and Placebo. All three active treatments improved both positive and negative symptoms equivalently. The only significant benefit of Abilify was in its better side effect profile.

In terms of side effects, Abilify may very well be the most perfect antipsychotic yet developed. No EPS, no weight gain, no hyperprolactinemia, less sedation than any of its competitors (but watch out for insomnia, which is common). Abilify is Geodon without QT prolongation, and for this reason TCR predicts that it will become very popular, very quickly.

Dose it like this: Start at 15 mg Q AM, aim for 15 mg to 30 mg for best therapeutic effect. Try to stay at 15 mg though, because at 30 mg there is more sedation. It’s a very easy drug to use.

If only the Abilify-boosters would stop harping on its pseudo-unique mechanism of action and emphasize what makes it truly unique—the best side effect profile in its class.

TCR VERDICT: The most perfect atypical—but enough about its mechanism!

1. Kane JM, Carson WH, Saha AR: Efficacy and safety of aripiprazole and haloperidal versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002;63:763-771.
General Psychiatry
    Carlat 150x150
    Daniel Carlat, MD

    Medication Fact Book for Psychiatric Practice, Seventh Edition (2024)

    More from this author
    www.thecarlatreport.com
    Issue Date: June 1, 2008
    SUBSCRIBE NOW
    Table Of Contents
    Abilify
    Dr. Michael Jibson on Choosing Among Atypicals
    Atypicals: Do they work for Depression?
    Abilify: The Perfect Antipsychotic?
    The Trouble with Zyprexa
    The First Antipsychotic
    DOWNLOAD NOW
    Featured Book
    • MFB7e_Print_App_Access.png

      Medication Fact Book for Psychiatric Practice, Seventh Edition (2024) - Regular Bound Book

      The updated 2024 reference guide covering the most commonly prescribed medications in psychiatry.
      READ MORE
    Featured Video
    • KarXT (Cobenfy)_ The Breakthrough Antipsychotic That Could Change Everything.jpg
      General Psychiatry

      KarXT (Cobenfy): The Breakthrough Antipsychotic That Could Change Everything

      Read More
    Featured Podcast
    • shutterstock_2622607431.jpg
      General Psychiatry

      Should You Test MTHFR?

      MTHFR is a...
      Listen now
    Recommended
    • Join Our Writing Team

      July 18, 2024
      WriteForUs.png
    • Insights About a Rare Transmissible Form of Alzheimer's Disease

      February 9, 2024
      shutterstock_2417738561_PeopleImages.com_Yuri A.png
    • How to Fulfill the DEA's One Time, 8-Hour Training Requirement for Registered Practitioners

      May 24, 2024
      DEA_Checkbox.png
    • Join Our Writing Team

      July 18, 2024
      WriteForUs.png
    • Insights About a Rare Transmissible Form of Alzheimer's Disease

      February 9, 2024
      shutterstock_2417738561_PeopleImages.com_Yuri A.png
    • How to Fulfill the DEA's One Time, 8-Hour Training Requirement for Registered Practitioners

      May 24, 2024
      DEA_Checkbox.png
    • Join Our Writing Team

      July 18, 2024
      WriteForUs.png
    • Insights About a Rare Transmissible Form of Alzheimer's Disease

      February 9, 2024
      shutterstock_2417738561_PeopleImages.com_Yuri A.png
    • How to Fulfill the DEA's One Time, 8-Hour Training Requirement for Registered Practitioners

      May 24, 2024
      DEA_Checkbox.png

    About

    • About Us
    • CME Center
    • FAQ
    • Contact Us

    Shop Online

    • Newsletters
    • Multimedia Subscriptions
    • Books
    • eBooks
    • ABPN Self-Assessment Courses

    Newsletters

    • The Carlat Psychiatry Report
    • The Carlat Child Psychiatry Report
    • The Carlat Addiction Treatment Report
    • The Carlat Hospital Psychiatry Report
    • The Carlat Geriatric Psychiatry Report
    • The Carlat Psychotherapy Report

    Contact

    carlat@thecarlatreport.com

    866-348-9279

    PO Box 626, Newburyport MA 01950

    Follow Us

    Please see our Terms and Conditions, Privacy Policy, Subscription Agreement, Use of Cookies, and Hardware/Software Requirements to view our website.

    © 2025 Carlat Publishing, LLC and Affiliates, All Rights Reserved.