ARIPIPRAZOLE (Abilify):

Emerging as Next Great Hope for Schizophrenia

Editor's note:  My son was diagnosed with schizophrenia in 1999 at the age of eighteen.  We tried respirdal, zyprexa, seroquel, navane and clozaril without success or reduction of voices and symptoms, in fact, things just got worse.  In December, 2002, he switched to Aripiprazole (Abilify).  Almost immediately there was a dramatic improvement which has continued until today. Now he is more independent, has a renewed interest in life, has returned to college, and has an active social life.  Things that previously were beyond our wildest hopes, are now routine for him.  Do not give up the search for something that works, every patient is unique! (June, 2004)

Aripiprazole (Abilitat) is being touted as the first member of the new generation of atypical antipsychotic drugs. This once-daily novel antipsychotic has undergone a number of studies, revealing that aripiprazole is significantly better at controlling both the positive and negative symptoms of schizophrenia than placebo and has equaled haloperidol and risperidone in its ability to control these symptoms.

On October 31, 2001, Bristol-Myers Squibb and Otsuka Pharmaceutical Co. filed a New Drug Application (NDA) with the FDA and the two companies anticipate the launch of aripiprazole late in the third quarter of 2002.

Stephen M. Stahl, M.D., Ph.D., Professor of Psychiatry at the University of California at San Diego, places aripiprazole in the class of antipsychotics called dopamine system stabilizers (DSSs). Stahl dubs these new therapeutic agents “Goldilocks” because of their ability to strike a balance between too much and too little dopamine. With “just right” result, negative and cognitive symptoms are reduced and motor side effects or prolactin elevation is absent. Previous atypical drugs block dopamine D2 receptors resulting in motor side effects such as pseudo-parkinsonism, and ultimately tardive dyskinesia.

Robert McQuade, Ph.D., director of Global Medical Marketing for Bristol-Myers Squibb, cites the evolution of antipsychotic medications and how their mechanisms of action have changed over time. “The big disadvantage was the side effects,” he says. “The atypicals were designed to address symptoms such as EPS, but brought about different side effects.” Each drug within the atypical category elicited its own particular adverse event, according to McQuade. Literature suggests, he says, that olanzapine causes weight gain, ziprasidone increases the QTc interval and risperidone increases plasma prolactin. “These drugs solved some problems, but created others.” “From a psychopharmacologic viewpoint, aripiprazole is bringing new science to the field,” he says. Unlike the older atypical antipsychotics that reduce positive symptoms of psychosis, such as delusions and hallucinations, by blocking D2 receptors, aripiprazole stabilizes or modulates them. McQuade underscores the multi-faceted benefits of aripiprazole based on the results of several controlled trials, some of which lasted up to 52 weeks in duration, involving more than 3,400 patients with schizophrenia. Aripiprazole was statistically superior to placebo on positive and negative symptoms and superior to haloperidol for negative symptoms, according to McQuade. “Aripiprazole delivers a package of tolerability that enhances the benefit to the patient and thus enhances compliance,” he concludes.

Potential problem with akathisia

According to Larry Ereshefsky, Pharm.D., professor of pharmacy, pharmacology and psychiatry at the University of Texas Health Science Center at San Antonio, the novel partial dopamine agonist mechanism of action augments the 5-Htla and 5-HT2 effects of aripiprazole. “These effects should lead to greater dopaminergic throughput and cortical activity which is good for thinking,” says Ereshefsky. “But it also might possibly explain the increased rates of akathisia at the middle doses (15 mg/d) in some studies. There is clearly a greater effect on the Barnes akathisia scale than from risperidone, and about half the effect of haloperidol.” Ereshefsy adds, “Akathisia is a potential side effect which bares further evaluation in long-term studies to see whether it abates.”

(Akathisia is having a feeling of inner restlessness and the urge to move, rocking while standing or sitting, lifting of the feet as if marching on the spot, and crossing and uncrossing of the legs while sitting.)

Article from Psychopharmacology Update published February 2002.

Update on recent clinical trials.

Full article from Medscape. (Note: free registration required)

Bristol-Myers Squib study on long term effects of aripiprazole in treatment of schizophrenia.

Other Articles on Aripiprazole

Journal Article Abstract for Overview of New Atypical Antipsychotics

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