New study indicates reduction in potential risks of widespread opioid and antidepressant co-prescribing

The research, funded by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration (ARC) East Midlands, analysed primary care data from 4.3 million people between 2010 and 2019. It found that 304,029 individuals were co-prescribed both an opioid and an antidepressant during that time.

The study was led by Dr Ruth Jack, Senior Research Fellow at the Centre for Academic Primary Care, School of Medicine, University of Nottingham. The research team also included colleagues from the University’s Schools of Medicine and Pharmacy, as well as public contributors.

Importantly, the study found that co-prescribing rates rose from 35.8 per 1,000 person-years in 2010 to 44.1 in 2015, before declining to 39.2 in 2019, following increased awareness and clinical guidance around the risks.

Opioids are powerful medications used to relieve pain, while antidepressants are used to treat depression, anxiety, other mental health conditions, and in some cases, pain. Certain antidepressants inhibit an enzyme called CYP2D6, which is necessary for metabolising opioid medications. When taken together, these drugs can interact in dangerous ways.

Respiratory depression occurs when breathing becomes too slow or shallow to allow proper gas exchange in the lungs. Serotonin syndrome, meanwhile, is a potentially life-threatening condition caused by too much serotonin in the body.

Researchers found that co-prescribing was more common among women, older adults, people living in more deprived areas, and individuals from White communities. The most frequently co-prescribed drug combinations were codeine with amitriptyline, followed by codeine with citalopram.

Professor Richard Morriss, Mental Health and Well-being Theme Lead at NIHR ARC East Midlands and Professor of Psychiatry at the University of Nottingham, said: “These findings highlight a previous pattern of concern in co-prescribing, but the recent decline in rates is encouraging and suggests that national warnings and prescriber education may be having a positive effect.

“While opioids and antidepressants both play important roles in treatment, their combined use requires close monitoring due to the risk of serious side effects.”

He added: “This reduction in co-prescribing should motivate clinicians to continue reviewing medication regimens and to consider alternative, safer options wherever possible.”

Professor Kamlesh Khunti, Director of NIHR ARC East Midlands and Professor of Primary Care Diabetes and Vascular Medicine at the University of Leicester, said: “The drop in co-prescribing rates is a step in the right direction. It highlights the impact of improved prescribing practices and the importance of regular medication reviews — especially for people with multiple long-term conditions.

“This research supports a move towards safer, more personalised care in primary settings.”

Read the study in full here.