Treatment of Anxiety Symptoms/Disorders

Treatment of Anxiety Symptoms/Disorders

A number of studies have shown chlordiazepoxide to be effective in the maintenance of alcoholics in long-term outpatient treatment. However, the potential for additive CNS depression produced by the concurrent use of alcohol and benzodiazepines is well recognized.

Furthermore, the use of benzodiazepines may itself result in tolerance and dependence and may increase depressive symptoms. Although this concern may be exaggerated and all benzodiazepines may not be equal in their capacity to produce dependence in al-coholics the use of benzodiazepines in alcoholics is probably best limited to detoxification. Buspirone, a nonbenzodiazepine anxi-olytic that is less sedating than diazepam or clorazepate, does not interact with alcohol to impair psychomotor skills, and has a low potential for abuse. When combined with appropriate psychosocial treatment, buspirone appears useful in the treatment of alcoholics with persistent anxiety. Currently, antipsychotics are indicated only in alcoholics with a coexistent psychotic disorder or for the treat-ment of alcoholic hallucinosis. Several placebo-controlled studies have found no advantage in the use of phenothiazines for treatment of anxiety, tension and depression following detoxification (Jaffe et al., 1992). Because of their capacity to lower seizure threshold, antipsychotics should be used with caution in this population.

Drugs that May Directly Reduce Alcohol Consumption

A number of specific neurotransmitter systems have been impli-cated in the control of alcohol consumption, including endogenous opioids, catecholamines, especially dopamine and serotonin. Al-though these systems appear to function interactively in their effects on drinking behavior, efforts to use medications to treat excessive drinking have increasingly focused on agents that have selective effects on specific neurotransmitter systems.

Opioid Antagonists

An extensive literature supports the role of opioidergic neurotrans-mission in the pathophysiology of alcohol consumption and related phenomena. For example, small doses of morphine increase alcohol intake in experimental animals. In contrast, opioid antagonists, such as naltrexone, decrease ethanol consumption and self-administra-tion. Effects similar to those in animals have been reported in some, but not all, studies of naltrexone for the treatment of alcohol depend-ence (Kranzler and Van Kirk, 2001). The considerable variability in findings concerning the efficacy of naltrexone underscores the need to identify the circumstances under which the medication exerts its therapeutic effects. Naltrexone appears to produce a modest effect on drinking behavior among alcoholics. However, given the compar-atively small overall effect of the medication, a variety of other fac-tors, including medication compliance, the severity and chronicity of alcohol dependence, and the choice of concomitant psychotherapy, may determine whether an effect of the medication is observed.

Serotonergic Medications

5-HT has been shown consistently to exert an influence over al-cohol consumption in preclinical models of drinking behavior. In contrast to this preclinical literature, data on the effects of sero-tonergic medications on human drinking behavior are more lim-ited, and the results are less consistent. One explanation for the variable findings in studies of whether SSRIs reduce drinking is the diversity of study samples. The initial studies were conducted in nontreatment-seeking heavy drinkers. Subsequent studies, which have shown differential effects based on severity, suggest that SSRIs are efficacious only in subgroups of alcoholics.

Acamprosate

Acamprosate, an amino acid derivative, affects both gamma-aminobutyric acid (GABA) and excitatory amino acid (i.e., glutamate) neurotransmission (the latter effect most likely being the one that is important for its therapeutic effects in alcohol-ism. Together, studies involving more than 4000 patients provide consistent evidence of the efficacy of acamprosate in alcoholism rehabilitation (Kranzler and Van Kirk, 2001). Based on these findings, and the benign side-effect profile of the medication, it appears to hold considerable value for the treatment of alcohol dependence.

Summary

Considerable additional research is required before medica-tions are likely to play a meaningful role in the postwithdrawal treatment of alcohol dependence. One currently useful strategy is the identification of comorbid psychopathology in alcoholics, with pharmacotherapy directed toward reducing both psychiatric symptoms and alcohol consumption. In addition, the opioid an-tagonist naltrexone, which is capable of yielding a modest effect overall in reducing drinking behavior, appears to be of consider able value in some individuals. Further research is required with naltrexone to determine the optimal dosage, duration of treatment and psychosocial treatment strategies with which to use the medication. The question of whether the medication is most effi cacious for alcoholics with high levels of craving for alcohol remains an important one. The SSRIs fl uoxetine, citalopram and sertraline may be of value in subgroups of heavy drinkers, particularly those with a later onset of problem drinking. In contrast, ondansetron may be useful in alcoholics with an early onset of problem drinking. Prospective replication of this serotonergic matching strategy is required, however, before it can be recommended for general clinical use. A camprosate could assume a prominent role in the pharmacological management of alcohol dependence in the USA.