Naltrexone and Transdiagnostic Modulation of Reward Salience in “Instinctopathies”: A Narrative Review and Clinical Hypothesis
Abstract
Ester Borges, Giovanna Azevedo Rodrigues, Luiz Costa and Marcelo Caixeta
Introduction: Naltrexone is an opioid antagonist with established indications for alcohol dependence and opioid blockade and has been investigated in behaviors characterized by craving and repetitive reward seeking. Objective: To examine whether the literature supports a transdiagnostic reward-salience hypothesis and to define the clinical limits of the proposed “instinctopathy” construct.
Methods: A narrative review of PubMed/MEDLINE, Scopus, and Google Scholar was conducted through September 20, 2026, including regulatory, mechanistic, preclinical, and clinical studies.
Synthesis: Evidence is strongest for approved indications. Gambling disorder and kleptomania show signals of benefit with limited certainty, whereas findings in compulsive sexual behavior disorder are mixed. Animal studies, experiments in healthy volunteers, case reports, and combination treatments do not demonstrate broad transdiagnostic efficacy or establish effects of naltrexone monotherapy.
Conclusion: “Instinctopathy,” “motivational depotentiation,” and “anti-drive” are heuristic constructs. Their validity and intermittent-dosing hypotheses require prospective testing and do not constitute clinical indications or dosing recommendations.