Background: Prescription opioids are the leading cause of injury deaths and considerable morbidity in the US and other developed countries. In large part this began because of unsupported claims of effectiveness and lack of adverse effects. However, regulatory approval documents and many guidelines still do not balance known adverse effects with evidence of effectiveness. Both patients and clinicians often underestimate the risk of adverse effects. Further, informed consent discussions are hampered by lack of synthesised data to support risk vs. benefit discussions.

Objectives: To review and summarise the adverse personal and population effects of acute and chronic opioids to compare to benefits.
To support clinician, patient and policy maker informed decision making, considering risks vs. benefits

Methods: We used the Cochrane Adverse Effects Review methodology to search, critically assess and synthesise the literature about the adverse effects of acute and chronic opioid use.

Results: Opioids affect most organ systems, posing risks to the respiratory, neuropsychiatric, gastrointestinal, endocrine, cardiovascular, vestibular, musculoskeletal, genitourinary/reproductive and other systems. These effects appear to be related to dose, age, gender, comorbidity, and concurrent use of multiple opioids and sedative/hypnotic and psychiatric medication. We noted increased incidence of falls, fractures, endocrine suppression, overdose, mortality, vehicle crashes, birth defects, cardiorespiratory events, effects on CNS structure and function, and adverse interactions with psychiatric disorders and medications. Review of observational studies is an important part of comprehensive adverse-effects reviews. 

Conclusions: Clinicians, patients, medical organisations and policy makers have not explicitly considered the many effects of opioid use on personal and public safety, quality of life, function and avoidable adverse health effects. Guideline developers, and all other stakeholders, need full information about benefits, risks, and adverse effects and risks to inform recommendation development and decision making about the use of opioids.