Over-the-counter Psychosis: A Systematic Review of the Misuse of Antihistamines, Cough Medicines, and Decongestants and the Risk of Developing Psychosis

Background: The widespread availability and accessibility of over-the-counter (OTC) medicines play a vital role in modern healthcare systems, enabling individuals to manage minor health concerns independently. However, certain OTC medications possess pharmacological properties that render them susceptible to misuse and abuse, including stimulants, laxatives, sedatives, and opiate-containing products. Misuse involves improper dosage, duration, or indication, while abuse entails non-therapeutic use to achieve psychoactive effects or other illicit purposes, potentially leading to dependence and addiction. This review explores the risk of developing psychotic symptoms associated with OTC drug misuse. Synthesizing existing literature, it comprehensively examines the relationship between antihistamines, cough medicines, and decongestants misuse, and the onset of psychotic symptoms. Methods: A systematic literature review was carried out using Pubmed, Scopus and Web of Science databases through the following search strategy: (“diphenhydramine” OR “promethazine” OR “chlorpheniramine” OR “dimenhydrinate” OR “dextromethorphan” OR “pseudoephedrine” OR codeine- based cough medicines) AND (“abuse” OR “misuse” OR “craving” OR “addiction”) NOT review NOT (animal OR rat OR mouse). For data gathering purposes, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Research methods were registered on PROSPERO (CRD42024527558). Results: We analysed 46 relevant studies out of an initial pool of 2,677 articles. Key findings indicate that antihistamines, dextromethorphan, and other OTC drugs can induce psychotic symptoms, such as paranoia, hallucinations, and thought disorders when abused. Dextromethorphan is particularly associated with a chronic tendency towards psychosis, whereas other substances more commonly result in acute substance-induced psychosis. Conclusion: The study underscores the necessity for increased awareness and specific interventions to address the misuse of OTC drugs and their potential to cause significant psychiatric disorders, emphasizing the broader public health implications of such misuse.