Impaired reproduction after exposure to ADHD drugs: Systematic review of animal studies

BACKGROUND: Few studies have reported on long-term harms caused by ADHD drugs but they are known to impair growth. OBJECTIVE: To assess whether ADHD drugs impair reproduction in mammals. METHODS: Systematic review of reproduction in studies of animals treated with ADHD drugs. DATA SOURCES: PubMed, Biosis and EMBASE. RESULTS: We included 17 studies. The studies were generally of poor quality or poorly reported. Two studies reported the use of one of three advised randomisation methods. Fifteen studies used placebo which suggested blinding. On clonidine, the ability to produce offspring was reduced for male rats, which approached two females each. In one study, 10 treated rats produced no offspring while all four controls did. In another study, 10 treated rats impregnated nine females while 10 controls impregnated 16. On methylphenidate, vaginal opening was delayed in two studies (in one, the mean difference was 4.0 days, 95% CI 2.5 to 5.6, and number of estrous cycles was halved; in the other, the minimum delay was 6 days), while in two other studies no difference occurred. Generally, the impairments improved after a drug-free period and were less pronounced when treatment started later in life. CONCLUSION: ADHD drugs impair the reproduction in animals.