Buprenorphine induces ceiling in respiratory depression but not in analgesia

Dahan, Albert; Yassen, Ashraf; Romberg, Raymonda; Sarton, Elise; Teppema, Luc J.; Olofsen, Erik; Danhof, Meindert

doi:10.1093/bja/ael051

Cited by 304 publications

(215 citation statements)

References 20 publications

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“…Contrary to earlier concerns, there was a ceiling effect found for respiratory depression but not for analgesia (Dahan et al, 2005 Level III-2; Dahan et al, 2006 Level III-2). The risk of respiratory depression is low compared with morphine, methadone, hydromorphone and fentanyl, even in the doses used for the treatment of opioid addiction, as long as concurrent sedative medications are not given (Kress, 2009).…”

Section: Chaptercontrasting

confidence: 96%

Safety of opioid patch initiation in Australian residential aged care

Gadzhanova

Roughead

Pont

2015

Medical Journal of Australia

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Objective: To explore opioid use by aged care facility residents before and after initiation of transdermal opioid patches. Design: A cross‐sectional cohort study, analysing pharmacy data on individual patient supply between 1 July 2008 and 30 September 2013. Setting: Sixty residential aged care facilities in New South Wales. Participants: Residents receiving an initial opioid patch during the study period. Main outcome measure: The proportion of residents who were opioid‐naive in the 4 weeks prior to patch initiation was determined. In addition, the patch strength at initiation and the daily dose of transdermal patches and of additional opioids 1 month after initiation were determined. Results: An opioid patch was initiated in 596 of 5297 residents (11.3%: 2.6% fentanyl, 8.7% buprenorphine) in the 60 residential aged care facilities. The mean age at initiation was 87 years, and 74% of the recipients were women. The proportion of recipients who were opioid‐naive before patch initiation was 34% for fentanyl and 49% for buprenorphine. Most were initiated at the lowest available patch strength, and the dose was up‐titrated after initiation. Around 15% of fentanyl users and 10% of buprenorphine users needed additional regular opioids after patch initiation. Conclusions: The results suggest some inappropriate initiation of opioid patches in Australian residential aged care facilities. Contrary to best practice, a third of residents initiated on fentanyl patches were opioid‐naive in the 4 weeks before initiation.

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Section: Chaptercontrasting

confidence: 96%

Safety of opioid patch initiation in Australian residential aged care

Gadzhanova

Roughead

Pont

2015

Medical Journal of Australia

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“…Buprenorphine is a partial m-opioid receptor agonist. At clinical doses, it exhibits full-dose-dependent analgesia but a plateau in respiratory depression (11,13,14). Neuropathic pain is associated with loss of pertussis toxin-sensitive G-protein activity (15) on which the analgesic action of pure m-opioids, such as morphine, depends.…”

mentioning

confidence: 99%

Transdermal Buprenorphine Relieves Neuropathic Pain: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial in Diabetic Peripheral Neuropathic Pain

Simpson

Wlodarczyk

2016

Diabetes Care

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OBJECTIVETo evaluate the efficacy and safety of transdermal buprenorphine in patients with diabetic peripheral neuropathic pain (DPNP). RESEARCH DESIGN AND METHODSThis multicenter, randomized, double-blind, placebo-controlled, parallel-group trial enrolled patients with type 1 or type 2 diabetes and stable glycemic control who had been experiencing moderate to severe DPNP for at least 6 months on maximal tolerated conventional therapy. Patients were randomly assigned to receive buprenorphine (5 mg/h) or placebo patches. The dose was titrated to effect to a maximum of 40 mg/h. Paracetamol was available as rescue analgesia. The severity of pain and other symptoms of DPNP were assessed daily in a patient diary and at clinic visits. RESULTSOne hundred eight-six patients were enrolled, with 93 randomized to either buprenorphine or placebo. A high proportion of patients did not complete the study (buprenorphine 37 of 93, placebo 24 of 93). The main reason for premature withdrawal in the buprenorphine group was adverse events commonly due to untreated nausea and/or vomiting. Among the per-protocol population, more patients in the buprenorphine group (86.3%) experienced a 30% reduction in average versus baseline pain at week 12 than those in the placebo group (56.6%, P < 0.001). A nonsignificant trend favored the buprenorphine group within the intention-to-treat analysis of the same end point (51.7% vs. 41.3%, P = 0.175). CONCLUSIONSTransdermal buprenorphine, when tolerated, is an effective therapy for DPNP and provides another option to manage this challenging painful condition. Nausea and constipation need to be managed proactively to optimize treatment outcomes.

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“…In fact, there is no ceiling for buprenorphine analgesia, and it has been used to good effect even in severe cancer and non-cancer pain lasting many months. [10][11][12] This apparent paradox, i.e., unlimited analgesic potential combined with a ceiling on adverse effects, sounds almost too good to be true. The explanation may lie in the observation that buprenorphine has a differential effect, which results in its being more potent at spinal receptor sites than at cerebral opioid receptor sites, the latter obviously being where centrally-mediated adverse effects would be generated.…”

Section: Buprenorphinementioning

confidence: 99%

“…En fait, il n'y a pas de plafond pour l'analgésie avec la buprénorphine, et ce médicament a été utilisé de façon concluante dans des cas de douleur cancéreuse et non cancéreuse grave durant plusieurs mois. [10][11][12] Ce paradoxe apparent, soit un potentiel analgésique illimité combiné à un plafond des effets indésirables, a l'air trop beau pour être vrai. L'explication pourrait se trouver dans le fait que la buprénorphine a un effet différentiel, d'où sa puissance supérieure aux sites de récepteurs rachidiens qu'aux sites de récepteurs opioïdes cérébraux, ces derniers étant évidemment le site de génération des effets indésirables médiés par le système nerveux central.…”

Section: La Buprénorphineunclassified