Opioid receptor antagonists in psychiatry : Beyond drug addiction

The central role of the opioid system and its multiple connections to other neurotransmitter and neuroendocrine systems favours its involvement in many physiological functions and behaviours and, as a consequence, in many disorders, including psychiatric disorders. In addition to substance abuse or addiction, the efficacy of opioid receptor antagonist (ORA) treatment has been assessed in various disorders such as eating disorders, schizophrenia, self-injurious behaviour, autism, tics, obsessive-compulsive disorders and trichotillomania, and post- traumatic stress disorder, as opioids may play an important or prominent role in the pathophysiology of these disorders. Although the efficacy of ORA treatment remains controversial for most of these pathologies, the data are encouraging and an improvement of symptoms was mostly found when long-acting ORAs were used, given for several weeks and used as adjuncts to more classical medications. Moreover, in most of these pathologies, ORAs seemed to act by reducing the intensity and frequency of a specific pathological behaviour, which can be characterised as compulsive, repetitive, stereotyped and `uncontrollable, and which can be linked to a reward-seeking or an addictive dimension. Our global impression is that a dimensional approach would be of great value in investigating mental disorders, and of great help in defining the targets that can be expected to be reached by a specific medication. In this dimensional perspective opioid antagonists alone are not believed to have a decisive global therapeutic effect on any of the diseases reviewed in this article, and should not be prescribed alone as first line treatments. ORAs should be directed against more specific behavioural targets and their primary usefulness may be as adjuncts to other medications and/or to cognitive and behavioural therapy.