Medication treatment of different types of alcoholism

Abstract

Alcoholism remains a serious cause of morbidity and mortality despite progress through neurobiological research in identifying new pharmacological strategies for its treatment. Drugs that affect neural pathways that modulate the activity of the cortico-mesolimbic dopamine system have been shown to alter drinking behavior, presumably because this dopaminergic system is closely associated with rewarding behavior. Ondansetron, naltrexone, topiramate, and baclofen are examples. Subtyping alcoholism in adults into an early-onset type, with chronic symptoms and a strong biological predisposition to the disease, and a late-onset type, typically brought on by psychosocial triggers and associated with mood symptoms, may help in the selection of optimal therapy. Emerging adults with binge drinking patterns also might be aided by selective treatments. Although preliminary work on the pharmacogenetics of alcoholism and its treatment has been promising, the assignment to treatment still depends on clinical assessment. Brief behavioral interventions that encourage the patient to set goals for a reduction in heavy drinking or abstinence also are part of optimal therapy.

Figure 1

Neuronal pathways involved with the reinforcing effects of alcohol and other drugs of abuse. Cholinergic inputs arising from the caudal part of the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) can stimulate ventral tegmental area dopamine neurons. The ventral tegmental area dopamine neuron projection to the nucleus accumbens and cortex, the critical substrate for the reinforcing effects of drugs of abuse (including alcohol), is modulated by a variety of inhibitory [gamma-aminobutyric acid (GABA) and opioid] and excitatory [nicotinic (NIC-R), glutamate (GLU), and cannabinoid-1 receptor (CB1-R)] inputs. The glutamate pathways include those that express alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptors. Serotonin-3 receptors (5-HT3-R) also modulate dopamine release in the nucleus accumbens. The glycine system, orexins, and corticotropin-releasing factor also are shown. CRF-R1, CRF-R2=corticotropin-releasing factor receptors 1 and 2; DRD1, DRD2, DRD3=dopamine receptors D1, D2, and D3; GlyR=glycine receptor; LH/PFA=perifornical region of the lateral hypothalamus; OXR1, OXR2=orexin receptor types 1 and 2; PVN=paraventricular nucleus. Adapted and embellished from Johnson (46) (copyright © 2006 American Medical Association; all rights reserved).