Early relapse in alcohol dependence may result from late withdrawal symptoms

Alcohol dependence has two distinct clinical features: (1) Physiological Dependence (PD), which characterizes the pharmacological tolerance that alcohol progressively induces in the brain and (2) Alcohol Addiction (AA), which is the behavioral conditioning of alcohol drinking resulting from the chronic activation of the reward system. PD results from a progressive imbalance between excitatory and inhibitory neurotransmission systems and leads to the occurrence of Alcohol Withdrawal Syndrome (AWS), which is prevented by benzodiazepines in cases of alcohol cessation. AA is considered to persist much longer and results from a disruption of the dopaminergic mesolimbic pathway, which is treated by anticraving drugs. Relapse in alcohol dependence is usually considered to be the result of AA. However, 50% of the relapses in alcohol occur within the first month after alcohol cessation. During this period, it has been shown that many patients experience anxious symptoms that have been neurobiologically related to withdrawal symptoms and PD. Thus, we hypothesize that early relapses are more the consequence of late symptoms of PD than AA. From this standpoint, we propose that prolonged treatment with benzodiazepines may reduce the first-month relapse rate.