Abstract
Background: Antidepressants, opioids for non-cancer pain, gabapentinoids (gabapentin and pregabalin), benzodiazepines, and Z-drugs (zopiclone, zaleplon, and zolpidem) are commonly prescribed medicine classes associated with a risk of dependence or withdrawal. We aimed to review the evidence for these harms and estimate the prevalence of dispensed prescriptions, their geographical distribution, and duration of continuous receipt using all patient-linked prescription data in England. Methods: This was a mixed-methods public health review, comprising a rapid evidence assessment of articles (Jan 1, 2008, to Oct 3, 2018; with searches of MEDLINE, Embase, and PsycINFO, and the Cochrane and King's Fund libraries), an open call-for-evidence on patient experience and service evaluations, and a retrospective, patient-linked analysis of the National Health Service (NHS) Business Services Authority prescription database (April 1, 2015, to March 30, 2018) for all adults aged 18 years and over. Indirectly (sex and age) standardised rates (ISRs) were computed for all 195 NHS Clinical Commissioning Groups in England, containing 7821 general practices for the geographical analysis. We used publicly available mid-year (June 30) data on the resident adult population and investigated deprivation using the English Indices of Multiple Deprivation (IMD) quintiles (quintile 1 least deprived, quintile 5 most deprived), with each patient assigned to the IMD quintile score of their general practitioner's practice for each year. Statistical modelling (adjusted incident rate ratios [IRRs]) of the number of patients who had a prescription dispensed for each medicine class, and the number of patients in receipt of a prescription for at least 12 months, was done by sex, age group, and IMD quintile. Findings: 77 articles on the five medicine classes were identified from the literature search and call-for-evidence. 17 randomised placebo-controlled trials (6729 participants) reported antidepressant-associated withdrawal symptoms. Almost all studies were rated of very low, low, or moderate quality. The focus of qualitative and other reports was on patients' experiences of long-term antidepressant use, and typically sudden onset, severe, and protracted withdrawal symptoms when medication was stopped. Between April 1, 2017, and March 31, 2018, 11·53 million individuals (26·3% of residents in England) had a prescription dispensed for at least one medicine class: antidepressants (7·26 million [16·6%]), opioids (5·61 million [12·8%]), gabapentinoids (1·46 million [3·3%]), benzodiazepines (1·35 million [3·1%]), and Z-drugs (0·99 million [2·3%]). For three of these medicine classes, more people had a prescription dispensed in areas of higher deprivation, with adjusted IRRs (referenced to quintile 1) ranging from 1·10 to 1·24 for antidepressants, 1·20 to 1·85 for opioids, and 1·21 to 1·85 for gabapentinoids across quintiles, and higher ISRs generally concentrated in the north and east of England. In contrast, the highest ISRs for benzodiazepines and Z-drugs were generally in the southwest, southeast, and east of England, with low ISRs in the north. Z-drugs were associated with increased deprivation, but only at the highest quintile (adjusted IRR 1·11 [95% CI 1·01–1·22]). For benzodiazepines, prescribing was reduced for people in quintiles 4 (0·90 [0·85–0·96]) and 5 (0·89 [0·82–0·97]). In March, 2018, for each of medicine class, about 50% of patients who had a prescription dispensed had done so continuously for at least 12 months, with the highest ISRs in the north and east. Long-term prescribing was associated with a gradient of increased deprivation. Interpretation: In 1 year over a quarter of the adult population in England had a prescription dispensed for antidepressants, opioids (for non-cancer pain), gabapentinoids, benzodiazepines, or Z-drugs. Long-term (>12 months) prescribing is common, despite being either not recommended by clinical guidelines or of doubtful efficacy in many cases. Enhanced national and local monitoring, better guidance for personalised care, and better doctor–patient decision making are needed. Funding: Public Health England.
| Original language | English |
|---|---|
| Pages (from-to) | 935-950 |
| Number of pages | 16 |
| Journal | The Lancet Psychiatry |
| Volume | 6 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2019 |
Bibliographical note
Funding Information:In the past 3 years, JM has received research grants from the National Institute for Health Research (NIHR) for a randomised controlled trial of depot naltrexone for opioid use disorder, and a randomised controlled trial of acamprosate for alcohol use disorder; and research grants from the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service (NHS) Mental Health Foundation Trust (SLaM) for a randomised controlled trial of novel cognitive therapy for cocaine use disorder. JM has worked part-time as the Senior Academic Advisor for the Alcohol, Drugs, Tobacco and Justice Division, of the Public Health England (PHE) Health and Wellbeing Directorate, and is a clinical academic consultant for the US National Institute on Drug Abuse, Centre for Clinical Trials Network. JM also declares an unrestricted research grant at the King's College London Institute of Psychiatry, Psychology & Neuroscience (IoPPN) and SLaM from Indivior via Action on Addiction for a completed randomised controlled trial of personalised psychosocial intervention in opioid agonist medication for opioid use disorder; unrestricted research grant funding at IoPPN and SLaM from Indivior for a 3-year, multicentre, randomised controlled trial of injectable depot buprenorphine for opioid use disorder (2019–21); and honoraria and travel support from Reckitt-Benckiser (2016; treatment of opioid use disorder) and PCM Scientific and Martindale for the Improving Outcomes in Treatment of Opioid Dependence conference (2018; contribution and chairing). MK has received a research grant from NIHR (for a randomised controlled trial of depot naltrexone); is the site principal investigator for a randomised controlled trial of extended-release buprenorphine for the treatment of opioid use disorder funded by Camurus and Braeburn Pharmaceuticals; is a research collaborator for a study of treatment for hepatitis C virus (HCV) for people who inject drugs, funded by Merck; has received support from Cepheid for a finger prick testing unit for HCV and HIV; has received an unrestricted research grant at IoPPN and SLaM from Indivior via Action on Addiction for a completed randomised controlled trial of personalised psychosocial intervention in opioid agonist medication for opioid use disorder and unrestricted research grant funding at IoPPN and SLaM from Indivior for a 3-year, multicentre, randomised controlled trial of injectable depot buprenorphine for opioid use disorder (2019–21). MK also declares honoraria and travel support from Mundipharma (2016; expert panel discussion on novel pharmacotherapies for opioid use disorder) and Abbvie and Gilead (2017 and 2018; discussion with hepatology specialists on HCV treatment for people who inject drugs). FG is a clinical senior lecturer at Imperial College London and has received funding from the National Institute for Health Research (NIHR), in particular the Collaboration for Leadership in Applied Health Research and Care programme and the Applied Research Collaboration for Northwest London. All other authors declare no competing interests. No author received support from the US National Institutes for Health for their contribution to this study.
