Background & Aims
Ziconotide has been recommended as a firstline intrathecal analgesia agent for refractory cancer pain.1 However, serious neuropsychic disorders (NPDs) have been reported with use of ziconotide as part of a combination intrathecal drug therapy.2 This study aimed to assess causality of NPDs in patients receiving intrathecal analgesic therapy for refractory cancer pain.
Methods
We retrospectively studied consecutive patients who received intrathecal analgesic therapy between 2010 and 2019, at the Integrated Oncology Centre of Angers, France. Both initial and maintenance intrathecal therapy included morphine, ropivacaine, and ziconotide. Ziconotide titration protocol consisted in a starting dose of 0.25-1.5 mcg/day, increased by 0.25-1.5 mcg/day every 1-2 weeks. NPDs included confusion, hallucinations, anguish, drowsiness and dizziness, and were regarded as “severe” when requiring emergency hospitalisation and/or antipsychotic treatment and/or sedation. NPDs occurrence and severity were retrieved from patients’ electronic medical files until 12 months after intrathecal drug delivery system implantation. The causality of ziconotide in NPDs occurrence was rated, according to Naranjo Scale, from 0 to ?9 (0 = doubtful and ?9 = definite).3
Results
Of 468 patients analysed, 280 (60%) experienced 1 or more NPDs episodes. Out of a total of 370 NPDs episodes, the causality of ziconotide was rated as “doubtful-to-possible” (Naranjo Scale 0 to 4) in 145 (39%), and “probable-to-definite” (Naranjo Scale ?5) in 225 (61%). In “probable-to-definite” ziconotide-induced NPDs, the daily dose of ziconotide was predictive of NPDs occurrence (AUC-ROC = 0.81 [95% CI 0.78–0.84], p <0.0001). A ziconotide daily dose of 1,47 mcg/day was the best threshold to predict NPDs, with a 77% [95% CI 71–82] sensitivity and a 75% [95% CI 72–78] specificity. Severe NPDs represented 35% (78 of 225) of “probable-to-definite” ziconotide-induced NPDs, as compared to 27% (39 of 145) of “doubtful-to-possible” ziconotide-induced NPDs (p < 0.0001).
Conclusions
Ziconotide appears to be frequently involved in the occurrence of NPDs in patients receiving intrathecal analgesic therapy for refractory cancer pain. The daily dose of ziconotide found to be predictive of NPDs onset is close to its minimum therapeutic dose, highlighting its narrow therapeutic index.
References
1.Deer TR, Pope JE, Hanes MC, and McDowel II G. Intrathecal therapy for chronic pain: a review of morphine and ziconotide as firstline options. Pain Medicine. 2019;20:784-798.
2.Karri J, Singh M, Modi DJ, et al. Combination intrathecal drug therapy strategies for pain management. Pain Physician. 2021;24:549-569.
3.Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239-245.
Presenting Author
Damien Leblanc
Poster Authors
Damien Leblanc
MD
Centre Hospitalier Universitaire, Angers, France
Lead Author
Topics
- Treatment/Management: Interventional Therapies – Intrathecal Drug Delivery