May 2008

Three IM Antipsychotics
New intramuscular (IM) formulations of second-generation antipsychotics appear comparable and possibly superior in efficacy and safety to older agents, but are more expensive.

Baclofen for Alcohol Dependency with Liver Cirrhosis
Baclofen (Lioresal and others) shows efficacy in treating alcohol dependency with no adverse hepatic effects.

Antipsychotics to Treat Aggression in Patients with Intellectual Disability
A double-blind study finds little evidence to support the use of antipsychotics to treat aggression in patients with intellectual disability.

In Brief
Desvenlafaxine Approved for Depression; Olanzapine LAI Not Approved for Schizophrenia

Depression Infrequently Treated
Many patients with depression worldwide do not receive effective care.

Clozapine Plus Aripiprazole
Aripiprazole (Abilify) may be beneficial for patients with schizophrenia who respond only partially to clozapine (Clozaril and others).

Clozapine Plus Aripiprazole

May 2008

Today's treatments for schizophrenia fall far short of ideal (BTP 2008;31:5, 2007;30:43–44). Sometimes antipsychotic monotherapy fails to bring about even modest improvement, despite sequential trials of modern drugs. Simultaneous use of multiple antipsychotics is common practice, although little science supports this strategy. Karunakaran and colleagues added aripiprazole (Abilify) for 26 schizophrenia patients who had responded only partially to clozapine (Clozaril and others).

Aripiprazole was discontinued in two patients due to severe dyskinesia or neuroleptic malignant syndrome. The remaining 24 had been in treatment for 1.5 to 38 years and were taking an average clozapine dose of almost 400 mg daily.

Adding aripiprazole, 5 to 30 mg daily, led to a mean 22% reduction in the clozapine dose. Seventy-five percent of the patients lost weight, and there was an upward trend of high density lipoprotein (the "good cholesterol"). Hallucinations, delusions, and social function also improved with aripiprazole.

Clozapine is the ultimate "go to" medication for psychosis when other treatments have failed. When patients don't experience reasonable benefits from clozapine, clinicians, patients, and family members are left to seek less-established remedies. With its partial dopamine agonist properties, aripiprazole is a novel antipsychotic. This case series with aripiprazole combined with clozapine is encouraging, although far from conclusive. Further study is warranted and, in the meantime, clinicians might experiment cautiously with the combination when more established approaches fail to achieve sufficient results.

1Karunakaran K, Tungaraza TE, Harborne GC: Is clozapine-aripiprazole combination a useful regime in the management of treatment-resistant schizophrenia? J Psychopharmacol 2007;21:453–456.