Background:
Opioid-induced hyperalgesia (OIH) is a recognised but underdiagnosed complication of prolonged opioid therapy in patients with advanced cancer. It presents as paradoxical pain amplification despite opioid dose escalation and may be mistaken for disease progression or opioid tolerance, resulting in further increases in opioid exposure and associated toxicity. Although opioid rotation remains a cornerstone of management, evidence supporting adjuvant therapies is limited. Clonidine, an α₂-adrenergic agonist, has been proposed as an opioid-sparing agent that may attenuate central sensitisation and improve symptoms of OIH. Current literature review and pharmacologic mechanisms will be presented.
Case Report:
A 32-year-old woman with metastatic cervical cancer and a history of opioid use disorder was admitted with severe uncontrolled pain despite escalating opioid therapy. Methadone (180 mg/day) had previously been discontinued because of QT interval prolongation, and she was receiving oral morphine 400 mg three times daily on presentation. In addition to worsening pain, she developed agitation, restlessness, insomnia, and dysaesthesia, raising clinical suspicion of OIH. Following multidisciplinary assessment, morphine was rotated to hydromorphone with gradual dose reduction, and subcutaneous clonidine 12.5-25 mcg TDS was initiated before transition to oral therapy. Within one week, neuroexcitatory symptoms resolved, pain scores improved from 9/10 to 4/10 on the Numerical Rating Scale, and total opioid requirements were substantially reduced while maintaining effective analgesia.
Conclusion:
This case highlights the potential role of clonidine as an adjuvant in the management of opioid-induced hyperalgesia in advanced cancer. Combined with opioid rotation and careful dose optimisation, clonidine was associated with improved analgesia, resolution of neuroexcitatory symptoms, and reduced opioid burden. Although further studies are required to define its efficacy and optimal dosing, clonidine may represent a valuable opioid-sparing option in selected patients with suspected OIH receiving oncological palliative care.