Neurobehavioural basis for the pharmacotherapy of alcoholism: current and future directions

Results from studies of pharmacotherapies for primary alcoholism are reviewed, including selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (e.g. fluoxetine), opiate antagonists (e.g. naltrexone) and dopamine agonists (e.g. bromocriptine). Because there is considerable comorbidity between alcohol dependence, anxiety, and affective disorders, results from studies of medications used to treat these psychiatric disorders are also reviewed, including the 5-HT agonist buspirone and the noradrenergic agent desipramine. The neurobehavioural model of alcohol dependence implies that combinations of medications may lead to more effective treatment; thus, identifying subtypes of alcoholic patients will be important in determining which therapies or combinations of therapy will be most effective in treating alcohol dependence. For example, in an ongoing study, we are attempting to subtype an alcoholic population for treatment selection by measuring endogenous opioid activity. Because endogenous opioids are involved in analgesia, we exposed male and female subjects with alcoholism [some of whom had post-traumatic stress disorder (PTSD)] to cold-induced pain and measured their response before and after administration of naloxone or placebo. The naloxone injection reduced pain response. In addition, women who have PTSD are much more sensitive to stress, which may be related to levels of brain opioid activity.