Long-term Changes in Observed Behaviour after Exposure to Psychiatric Drugs A Systematic Review of Animal Studies

Many patients are taking psychiatric drugs for years despite little knowledge about their long-term harms. Here, we summarise the findings of whether psychiatric drug exposure causes long-term harms in mammals after a drug-free period. We searched PubMed, Biosis and Embase for controlled animal studies (no behavioural priming; behavioural assessments performed after a 90 day drug-free period). Data was extracted by two assessors for animal characteristics, study design, funding and behavioural outcomes: sleep, addiction, pain, anxiety, depression, locomotion, cognition and social (sexual) behaviour. Meta-analysis was performed when two or more studies were eligible. We included 33 studies in mice, rats, hamsters, cats and monkeys. The quality of the studies was poor or poorly reported and heterogeneity was high. Antidepressants caused impaired sexual behaviour; benzodiazepines, antidepressants and methylphenidate caused statistically significant but variable effects on anxiety. Cognition was unaffected by haloperidol, olanzapine decreased learning in one test and diazepam impaired cognition on all cognitive outcomes. Antipsychotics increased vacuous chewing movements. Animal research on long-term outcomes is sparse and dominated by poor methodology. Still, impaired sexual behaviour, cognition and locomotion were seen. Action should be taken to improve reporting and reduce bias. We suggest that psychiatric drug research follow the animals after end of the intervention to assess long-term harms.