Background:

Sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have significantly increased over the past decade in the United States. Doxycycline as chemoprophylaxis (i.e., post-exposure prophylaxis [PEP]) offers promise for addressing bacterial STIs. The goal of the current study was to evaluate the safety of longer-term doxycycline use (defined as eight or more weeks) in the context of potential use as STI chemoprophylaxis through a systematic literature review and meta-analysis.

Methods:

This review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search MEDLINE/PubMed for clinical studies published from August 2003 through January 2023 that reported on adverse events with doxycycline use with a focus on side-effects and metabolic effects of long-term use.

Results:

A total of 67 studies were included in the systematic review. Overall, studies on longer-term doxycycline use reported 0% to over 50% adverse events ranging from mild to severe. Most common adverse events included gastrointestinal symptoms (i.e., nausea, vomiting, and abdominal pain), dermatologic (i.e., rash), and neurological (i.e., headache and dizziness) symptoms. Discontinuation of doxycycline due to adverse events was relatively uncommon in most studies. A meta-analysis of placebo controlled clinical trials (N=18) revealed gastrointestinal and dermatological adverse events were more likely to occur in the doxycycline group.

Conclusion:

Longer-term (8+ weeks) doxycycline use is generally safe and may be associated with minor side-effects. Further research is needed on the potential metabolic impact of longer-term doxycycline use.