Ziconotide: A rapid detoxification protocol for the conversion from intrathecal morphine–The Raffaeli Detoxification Model

Abstract

Objectives: To assess the efficacy and the safety of our rapid detoxification protocol in preventing signs and symptoms of withdrawal and pain severity.Design: Prospective, open-label case series study.Settings: Public primary care at the Pain and Palliative Care Unit of the Infermi Hospital of Rimini, Italy.Patients: The authors studied 10 consecutive patients suffering from chronic noncancer pain who were refractory to intrathecal (IT) morphine, and hence indicated for ziconotide therapy.Interventions: IT pump was refilled with saline solution, and each patient received endovenous morphine, oral clonidine, ketoprofen, and lorazepam for the first 3 days, and slow-release tramadol, oral clonidine, and ketoprofen for 10 days. Ziconotide therapy was started at the end of the 2-week detoxification treatment.Main outcome measures: The observer-rated opioid withdrawal scale (OOWS) was used for the assessment of withdrawal signs, visual analogue scale was used for pain intensity assessment, and also adverse events were recorded.Results: Withdrawal symptoms were experienced by 3 patients (30 percent). Their average OOWS decreased significantly (p 0.05) from 4.3 ± 2.5 to 1.7 ± 0.6 at days 3 and 14 of protocol, respectively, with no increment of pain intensity. Withdrawal symptoms were resolved in 4 days on average without the need of adjuvant medications. One patient with high morphine dosage (20 mg/d), interestingly, did not show any withdrawal symptoms.Conclusions: The detoxification protocol was effective in preventing withdrawal signs without increasing pain severity, allowing to rapidly convert IT morphine to ziconotide monotherapy in patients who are refractory to morphine.

Italian Registry on Long-Term Intrathecal Ziconotide Treatment

“…This suggests that ziconotide can be an advantage compared to classic IT therapies (morphine, local anaestics, and baclofen), since the majority of therapies used with patients (73%) before ziconotide administration had not determined a satisfactory pain reduction, or those therapies were interrupted for their related side effects (10%). The mean initial ziconotide dose was 1.41 µg/d, in agreement with studies suggesting low doses (45) and similar to those reported by Wallace et al (38). We observed the most common ziconotide-related side effects as previously reported in the literature: altered mood, confusion, memory deficit, abnormal CPK levels, vertigo, nausea (28,38,39,45).…”

“…The mean initial ziconotide dose was 1.41 µg/d, in agreement with studies suggesting low doses (45) and similar to those reported by Wallace et al (38). We observed the most common ziconotide-related side effects as previously reported in the literature: altered mood, confusion, memory deficit, abnormal CPK levels, vertigo, nausea (28,38,39,45). They were mostly of mild or moderate intensity, however, no serious adverse events were observed and they did not always cause treatment interruption (18%).…”

“…Our data on ziconotide efficacy and safety were comparable with those reported in other studies; none were placebo-controlled clinical trials (38,39,45). Sixtyseven percent of patients reported a 30% mean reduction in pain intensity after 2 months of treatment; and 55% reported a 50% pain intensity reduction after 3 months of therapy.…”

“…The combination of ziconotide and other systemic or IT drugs is well reported (32,38,39). It has been observed, for example, that combined administration of ziconotide and baclofen might be an option to treat neuropathic pain associated with spasticity (40).…”

“…It has been observed, for example, that combined administration of ziconotide and baclofen might be an option to treat neuropathic pain associated with spasticity (40). Administration of ziconotide combined with IT morphine, moreover, might reduce pain intensity and allow lower systemic opioid consumption (38,39).…”