Opportunities to improve the efficiency of naltrexone for the stabilization of remission in opiate dependence: combination therapy and pharmacogenetic stratification on the basis of the pathogenetic approach
It seems promising to study the opportunities to improve efficiency of remission stabilization in opiate dependence using complex pathogenetic approach with the combination pharmacotherapy and pharmacogenetic analysis. The combination of guanfacine, agonist of alpha-adrenoreceptors with naltrexone, competitive antagonist of opioid receptors, may be more effective than monotherapy with naltrexone by reducing the symptoms of craving for opioids in post abstinence period: depression, anhedonia, high impulsivity and low resistance to stressors. Disturbances in dopamine neuromediation in brain reinforcement system underlie both etiology and pathogenesis of opiate dependence, and most post abstinence disorders. Pharmacogenetic analysis based on key genes of dopamine system and genes of the direct targets of naltrexone (opioid receptors) and guanfacine (adrenoceptors) in one genetic panel can be useful for genetic stratification of patients in terms of efficacy of combined therapy for stabilization of remission in opiate dependence.