Matic et al. 2017 [12] | Advanced cancer | 238 advanced cancer patients referred to a pain consultation service due to inadequate analgesia, Netherlands | Opioids (fentanyl 73.3%, oxycodone 43%, hydromorphone 11%, morphine 5%, buprenorphine 5%) with 9% requiring ketamine as an adjuvant analgesic | GG (n = 10) GA (n = 81) AA (n = 147) | No association was found between genotypes and morphine equivalent dose (MED) or relative change in MED from baseline. No association was found for use of ketamine as an adjuvant analgesic. |
Oosten et al. 2016 [13] | Advanced cancer | 335 moderate-to-severe cancer-related pain, Netherlands | Opioids (oxycodone, morphine, fentanyl, hydromorphone) | GG (n = 215) GA + AA (n = 120) | No association between genotypes and opioid failure, defined as rotation to another opioid or treatment with intrathecal opioids due to insufficient pain control and/or side effects, or the use of palliative sedation because of refractory symptoms associated with opioid treatment in the dying phase. |
Lotsch et al. 2010 [11] | Chronic pain | 352 chronic pain patients treated for pain of various reasons in tertiary outpatient care, Germany | Opioids (morphine, fentanyl, buprenorphine, oxycodone, tilidine, tramadol, hydromorphone, dihydrocodeine, levomethadone, piritramide) | AA (n = 17) MAF = 0.2 | AA genotype associated with a significantly higher oral MED than combined AG and GG genotypes, with no significant difference in AA genotype distribution for pain diagnoses or opioid used, and no significant difference in pain score. |
Margarit et al. 2019 [20] | Chronic pain | 222 patients with chronic lower back pain referred for opioid prescription, Spain | Opioids (fentanyl, tramadol, oxycodone, morphine, tapentadol, buprenorphine) | AA (n = 63) AG (n = 33) GG (= 5) MAF = 0.21 | Carriers of the A allele (AA and AG) were associated with a significantly higher pain intensity at the final visit and at the follow up visit (2–4 years later) than the GG genotype. |
Bruehl et al. 2013 [5] | Post-operative pain | 311 white patients receiving opioids after total knee arthroplasty (TKA), United States | Opioids (96.4% of orders were for oral immediate release oxycodone) | MAF = 0.229 | No association between genotypes and total number of oral opioid analgesic medication orders for patients undergoing TKA. It was not possible in the study to examine the number of individual analgesic medication doses actually administered or directly assess their efficacy. |
Nishizawa et al. 2009 [10] | Post-operative pain | 129 undergoing major open abdominal surgery (mostly gastrectomy for gastric cancer and colectomy for colorectal cancer), Japan | Continuous epidural fentanyl or morphine diluted with bupivacaine. Opioids (morphine, buprenorphine, pentazocine, pethidine) and/or NSAIDS used for rescue analgesia. | AA (n = 11) AG (n = 62) GG (n = 56) MAF = 0.344 | AA genotype required rescue pain medication more frequently than AG and GG genotypes, with no associations for postsurgical pain ratings observed. A trending increase in oral MED was seen for AA genotypes, which was significant for female patients. |
Lotsch et al. 2010 [11] | Opioid substitution therapy | 85 patients on methadone substitution therapy for heroin addiction, Germany | Methadone | AA (n = 4) AG (n = 12) GG (n = 69) MAF = 0.22 | AA genotype had significantly higher average and maximum daily methadone doses during the first year of substitution therapy than combined AG and GG genotypes, and AA carriers lacked opioid withdrawal symptoms. |