Search results
Of the 52 papers included in at least 1 of the reviews, 9 papers, reporting on 7 studies,91,92,110,111,112,113,116 reported on AEs because of an intervention used for the tapering of opioids in people with chronic non-cancer pain. Five of those studies110,111,112,113,116 also reported on the effectiveness of the intervention and have been reported in Chapter 5. Of the 52 papers included in at least 1 of the reviews, 9 papers, reporting on 7 studies,90,91,109,110,111,112,115 reported on AEs because of an intervention used for the tapering of opioids in people with chronic non-cancer pain. Five of those studies109,110,111,112,115 also reported on the effectiveness of the intervention and have been reported in Effectiveness of interventions to reduce opioid use.
Study characteristics
The two publications not included in the effectiveness review were both case reports.91,92 Four studies were RCTs111,112,113,116 and one was a non-comparative prospective cohort study.110 The study characteristics of all seven studies are shown in Table 18.
Four studies were conducted in the USA,91,110,111,113 two in Australia112,116 and one in France.92 The length of follow-up was reported by five studies91,110,112,113,116 and varied from 8110 to 34 weeks.113 The number of participants in the studies were generally small (N = 1,91 N = 1,92 N = 15,111 N = 35113) though two studies reported ~100 participants (N = 97110 and N = 108116). Most studies had more female participants, though all but the case studies included some male participants. The mean age of participants ranged from 3692 to 58.4 years.116 The type and duration of chronic pain that participants were experiencing was poorly reported by the studies as were details on the types and the duration of use of opioids. The baseline levels of opioid use were reported but ranged greatly from 112111 to 871.41 mg/daily.116
| Study | DesignNumber of arms | CountrySetting | Timing of assessments | N | Arm | NFemalesMales | Age (years), mean (SD) | Type of chronic pain | Duration (years) of chronic pain, mean (SD) | Types of opioids | Duration (years) of opioid use, mean (SD) | Level of opioid use (mg/daily), mean (SD) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Jackson 2021111 | RCT2 | USAOutpatient | BaselineNR | 15 | I and C | N = 15F = 7M = 8 | 56.5 (17.3) | NR | NR | NR | NR | I = 112 (71) |
| C = 191 (121) | ||||||||||||
| Sullivan2017113 | RCT2 | USAOutpatientMultidisciplinary pain centre | BaselineEnd of treatment period34 weeks follow-up | 35 | I | N = 18F = 12M = 6 | 54.4 (10.1) | NR | NR | NR | 10.2 (4.3) | 207.2 (269.3) |
| C | N = 17F = 13M = 4 | 245.2 (347.3) | ||||||||||
| Zheng2008112 | RCT2 | AustraliaOutpatientPain management clinic | BaselineEnd of treatment periodEvery 4 weeks until 20 weeks follow-up | 35 | I | N = 17F = 8M = 9 | 51.1 (13) | NR | 19.8 (24.5) | Codeine 10Methadone = 1Oxycodone 4Morphine 4Tramadol 6 | NR | 461.6 (462.6) |
| C | N = 18F = 9M = 9 | 48.4 (10.5) | 13 (1.1) | Codeine 14Methadone 0Oxycodone 5Morphine 3Tramadol 4 | 295.5 (288) | |||||||
| Zheng2019116 | RCT3 | AustraliaOutpatientThree pain clinics and from the public | BaselineEnd of the treatment periodEvery 4 weeks for 12 weeks follow-up | 108 | I | N = 48F = 28M = 20 | 55.9 (11.3) | NR | 10.8 (9.4) | NR | NR | 463.3 (438.6) |
| C | N = 29F = 18M = 11 | 58.4 (12.8) | 13.3 (9.6) | 620.8 (792.4) | ||||||||
| C2 | N = 31F = 16M = 15 | 58.4 (12.8) | 16.3 (12.5) | 871.41 (1772.3) | ||||||||
| Capano 2020110 | Prospective cohort1 | USAPrivate pain management centre | Baseline4 and 8 weeks | 97 | N/A | N = 97F = 66M = 31 | 56.1 (NR), 39–70 | NR | NR | NR | NR | NR |
| Caldera 202091 | Case report | USAOutpatientUniversity hospital | BaselineSix months follow-up | 1 | N/A | 1F = 1 | 43 | Right-sided headaches and neck and shoulder pain | 14 years | Morphine | 14 years | 150 |
| Lalanne 201692 | Case report | FranceInpatientUniversity Hospital | BaselineNR | 1 | N/A | 1F = 1 | 36 | Lumbar pain | NR | Diazepam 10 mg three times per day, hydroxyzine 100 mg twice daily, venlafaxine 150 mg in the morning, oxycontin® extended-release 60 mg twice daily, oxycodone 10 mg every 4 hours, and acetaminophen/codeine 300 mg/25 mg six times per day | 1 year | NR |
Intervention characteristics
The intervention characteristics of the included studies are shown in Table 19.
| Study | Aim of intervention | Type of intervention | Brief intervention description | Type of comparator | Brief comparator description | Mode(s) of deliveryGroup/individual | Duration/intensity |
|---|---|---|---|---|---|---|---|
| Jackson 2021111 | Reduction | Acupuncture + standard of care | Participants received standard of care in addition to the National Acupuncture Detoxification Association protocol (standard of care consists of medication management with opioid weaning, and also received acupuncture sessions with each visit). | Standard of care | Standard of care (consists of medication management with opioid weaning). | Face to faceIndividual | Monthly for 12 months |
| Sullivan 2017113,114 | Reduction | Sequential opioid dose reduction and behavioural intervention | 10% reduction of the original dose per week until 30% of the original dose was reached. At that point, the 10% was recalculated on the basis of this dose and the taper then proceeded by 10% of this new dose per week.MI and CBT | TAU | Usual care | TelephoneGroup and individual | 30 minutes/week for 18 weeks |
| Zheng 2008112 | Reduction | Acupuncture | Electroacupuncture | Sham | Sham electroacupuncture | Face to faceIndividual | 20 minutes, twice/week for 6 weeks |
| Zheng 2019115,116 | Reduction | Acupuncture | Electroacupuncture | C1 = ShamC2 = Education only | Sham electroacupunctureEducation only | Face to faceIndividual | 20 minutes, twice/week for 4 weeks, then 20 minutes, once/week for 2 weeks then 20 minutes/fortnightly for 4 weeks.Total, 12 sessions within 10 weeks.Pain specialists provided pain and medication education to each participant once in the whole trial. |
| Capano 2020110 | Reduction | Pharmacological | CBD hemp extractParticipants self-titrated their dose of CBD. | N/A | N/A | Face to faceIndividual | N/A |
| Caldera 202091 | Discontinuation | Pharmacological | 15 mg per week weaning protocol for daily morphine conducted over 1 month.Then a weaning protocol for the immediate relief morphineMedical cannabis | N/A | N/A | Face to faceIndividual | Medical cannabis 500 mg which had a 2 : 1 CBD to THC ratio in vape form.It had 26.3% CBD and 17% THC. These were divided into 2.5 mg doses per inhalation. |
| Lalanne 201692 | Reduction | Pharmacological | Ketamine oral solution for 2 days, then gradual reduction of opioid treatment over 2 days | N/A | N/A | Face to faceIndividual | Ketamine oral solution (5 mg/ml, magistral formulae) 1 mg/kg, and 2 days after ketamine initiation her opioid treatment was gradually reduced (10% reduction in the initial dosage each 2 days). |
All but one study aimed to reduce the dose of opioids, whereas one study aimed for the participant to discontinue use of opioids.
Three studies assessed the use of acupuncture,111,112,116 three used pharmacological interventions (CBD91,110 and ketamine92) and one used a combination of a sequential opioid dose reduction with MI and CBT.113 For four comparative studies, the comparator was usual care in two studies111,113 and sham acupuncture in two studies.112,116 For all but one study,113 the intervention was delivered individually and face to face. The duration of the intervention varied; for the two studies using CBD to taper opioid use participants continued to use CBD,91,110 for the participant in Lalanne et al.,92 ketamine was used for 4 days and then withdrawn (there are no details on length of time). The three studies using acupuncture varied in their duration from 8 weeks112 to 12 months.111
Quality assessment
The quality assessment for the four RCTs111,112,113,116 and the comparative study110 are shown in Tables 13 and 15. The overall rating in the Risk of Bias 236 showed that there were some concerns; no study had a rating of high risk in any of the domains. For the comparator study, the CASP cohort checklist38 showed that the study was of good quality.110 Single case reports were not quality assessed.
Outcomes
The AEs reported in each of the studies is shown in Table 20. No study reported serious AEs. Five studies did report some AEs with two of the acupuncture studies reporting incidence rates of between 15% and 21%. No study reported that an AE resulted in withdrawal from the study.
| Study | Intervention | AE data |
|---|---|---|
| Jackson 2021111 | Acupuncture + standard of care | ‘There were no adverse outcomes such as skin irritation, inflammation, or vagal responses throughout this study’. |
| Sullivan 2017113,114 | Sequential opioid dose reduction and behavioural intervention | One AE in the taper support group; was classified as severe and study-related. A patient prescribed nortriptyline developed an allergic reaction 2 days later (including difficulty breathing, a swollen uvula, redness in neck and flushed face); primary care physician discontinued the medication and the symptoms resolved. |
| Zheng 2008112 | Electroacupuncture | No serious AEs were reported. Overall incidence rate of AEs was 52/345 = 15%. Intervention = 33; comparator = 19. |
| Zheng 2019115,116 | Electroacupuncture | No serious AEs were reported. The most common AEs were pain at the site of needling, lethargy and bruising. No group differences.Intervention = 86, 17% incidence rate, 1.8 (3.1) per personComparator = 70, 21% incidence rate, 2.4 (5.1) per person |
| Capano 2020110 | CBD hemp extract | One participant reported that CBD ‘made her heart race’ and combined twice-daily dosing into one dose to manage the side effect. One participant reported nausea from CBD but continued using the product. One participant reported ‘heart burn and dry mouth’ after initiating CBD. One participant reported CBD increased her night-time anxiety and disturbed sleep. No significant AEs were reported. |
| Caldera 202091 | Medical cannabis | Reported no side effects from the medical cannabis. |
| Lalanne 201692 | Ketamine oral solution | ‘She complained of no side effects of ketamine other than an unusual weakness’. |
Summary
Nine papers, reporting on seven studies,91,92,110,111,112,113,116 reported on AEs. All but one study aimed to reduce the dose of opioids, whereas one study aimed for the participant to discontinue use of opioids. Three studies assessed the use of acupuncture, three used pharmacological interventions (CBD and ketamine) and one used a combination of a sequential opioid dose reduction with MI and CBT. No study reported serious AEs.