Alcohol Abuse and Dependence

A substantial amount of evidence supports a 5-HT dysfunction in alcohol abuse and dependence. Animal studies have shown that increased 5-HT levels reduce alcohol consumption (Farren 1995). For example, Murphy et al. (1988) reported beneficial effects with fluoxetine and fluvoxamine in reducing alcohol intake in a rat model.

Although results are not consistent, some clinical trials with SSRIs have reported reduced alcohol consumption in patients with and without depression, in contrast to patients treated with TCAs, which have less robust efficacy (Cornelius et al. 1997; Lejoyeux 1996). A precise mechanism for the role of SSRIs in the treatment of alcohol dependence is not understood. To date, the beneficial effect, if any, appears to be independent of antidepressant activity (Naranjo et al. 1986, 1990). More work is needed to determine the specific patient subpopulations that might benefit most from SSRIs (see Gorelick 1989).

From a risk-benefit assessment, it is reassuring that fluoxetine does not appear to potentiate the effects of ethanol (Lemberger et al. 1985) and does not carry a high risk of fatal poisoning when taken in combination with alcohol (Koski et al. 2005). SSRIs may help selected patients with alcohol dependence in recovery when these drugs are used as part of a multifaceted treatment program.

Obesity

SSRIs have been extensively investigated for an effect on food consumption. This interest stems from evidence that perturbation of 5-HT receptors modifies animal feeding behavior (Garattini et al. 1986). This modification appears to be independent of a local gastrointestinal effect (e.g., the perception of nausea). 5-HT innervation to the hypothalamus influences satiety and may selectively affect carbohydrate consumption (Wurtman et al. 1981). In one large trial, 458 patients were treated for 52 weeks with fluoxetine (60 mg/day) or placebo (Goldstein et al. 1994). Weight loss was significantly greater in the fluoxetine-treated group at 28 weeks, but not at 52 weeks. Long-term benefits may be better sustained when fluoxetine is combined with behavior modification (Marcus et al. 1990).

The broad involvement of the serotonergic system in modulating behavior and cognition supports the wide potential utility of SSRIs.

Other Medical Conditions

Fluoxetine has been evaluated and observed to be efficacious in a variety of medical conditions, including poststroke depression, fibromyalgia, chronic pain, and depression in cancer patients. It has also proved useful in some patients with chronic fatigue syndrome.

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