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).

Baclofen for Alcohol Dependency with Liver Cirrhosis

May 2008

In 2004, "chronic liver disease and cirrhosis" was the 12th leading cause of death in the United States, accounting for over 26,000 fatalities.1 When alcohol is the cause, reducing or stopping drinking can improve survival. But, as so many patients have experienced, abstinence is difficult to achieve.

For decades, there were two interventions to help achieve abstinence: behavioral approaches and the original anti-alcohol medication, disulfiram (Antabuse and others). Recently we described two new treatments: oral and long-acting intramuscular naltrexone (Depade and others) and acamprosate (Campral) (BTP 2006;29:49). However, investigators have excluded patients with cirrhosis from trials of these new agents due to fear of drug-induced hepatotoxicity or a more general concern about medical stability. Naltrexone is contraindicated in people with liver disease because of its hepatic metabolism and reports of drug-related hepatic injury. By contrast, there is preliminary evidence that acamprosate may be more tolerable. Topiramate (Topamax) is being studied for alcoholism (BTP 2003;26:33–34), but it has been associated with hyperammonemia and changes in hepatic function.

Preliminary evidence suggests that baclofen (Lioresal and others), a γ-aminobutyric acid (GABA) B receptor agonist, can reduce alcohol craving and intake and enhance abstinence in alcohol-dependent patients. Only about 15% of baclofen is metabolized in the liver; it is mainly eliminated unmodified by the kidneys. No hepatic effects have been reported in alcohol-dependent patients. This led Addolorato and collaborators to conduct a randomized, double-blind study of oral baclofen in alcohol-dependent patients with cirrhosis of the liver.2 Subjects were treated with baclofen, 5 mg tid for 3 days and then 10 mg tid, or placebo for 12 weeks, with 4 additional weeks of follow-up.

Of 42 patients who took baclofen, 30 (71%) achieved and maintained abstinence versus only 12 (29%) of 42 who took placebo (P = .0001). Baclofen patients had a mean of 63 nondrinking days versus 31 in the placebo group, and only 19% had relapsed to heavy drinking by 60 days versus 45% among placebo subjects. Nearly three-quarters of patients taking baclofen maintained sobriety compared with about one-quarter of the placebo controls. More patients assigned to placebo dropped out (31%) compared with the group taking baclofen (14%). No adverse hepatic effects occurred.

An accompanying comment by Garbutt and Flannery called the results of Dr Addolorato's group "surprisingly robust."1 Slowly, treatments for alcohol dependence are improving. These findings for patients who have already suffered liver impairment are particularly encouraging.

1Garbutt JC, Flannery B: Baclofen for alcoholism. Lancet 2007:370:1884–1885.

2Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, Abenavoli L, D'Angelo C, Caputo F, Zambon A, Haber PS, Gasbarrini G: Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: Randomised, double-blind controlled study. Lancet 2007;370:1915–1922.