Continuous intraventricular clonidine infusion in controlled morphine withdrawal – case report

Abstract

A patient with atypical bilateral facial pain reported the loss of analgesic effect of intracerebroventricular morphine delivered continuously via an implanted pump, accompanied by intolerable adverse side effects associated with the administered high dose of morphine. Clonidine was substituted for morphine over a period of 3 weeks to achieve a drug holiday. The patient did not have significant withdrawal symptoms or major discomfort from pain, leading to a reduced quality of life during this period. Six months after the treatment, the patient continues to require a significantly lower daily dose of morphine. Morphine withdrawal with clonidine substitution produced a significant improvement in the analgesic efficacy of morphine and in the quality of life in the absence of undesirable side effects.

Neurobiological studies of chronic pain and analgesia: Rationale and refinements

“…The use of the ICV route of administration clinically is very limited; when accessed it is typically for delivery of opioid medication for palliative care (Raffa and Pergolizzi, 2012) in cases where systemically or spinally delivered opioids have become no longer effective. One case report (Lorenz et al, 2002) illustrated the effectiveness of substituting clonidine for morphine when ICV morphine became ineffective due to tolerance and/or disease progression. When morphine was reintroduced after a fourteen-day holiday, lower doses were effective when given in combination with ICV clonidine.…”

Adeno-associated virus-mediated gene transfer of arginine decarboxylase to the central nervous system prevents opioid analgesic tolerance

“…However, a panel of complex side effects accompanies long-term opioid pharmacotherapy, including, but not limited to, the development of opioid analgesic tolerance (1,2). The development of analgesic tolerance for patients on chronic opioid therapy can result in significant dose escalation (3) resulting in increased adverse side effects (4), a need for more invasive delivery approaches, or the inability to adequately control pain [ceiling effect (5)]. Multiple strategies are used with varying success for these patients, such as opioid rotation, drug holiday, or inclusion of adjuvant analgesics such as ketamine (5).…”

“…The development of analgesic tolerance for patients on chronic opioid therapy can result in significant dose escalation (3) resulting in increased adverse side effects (4), a need for more invasive delivery approaches, or the inability to adequately control pain [ceiling effect (5)]. Multiple strategies are used with varying success for these patients, such as opioid rotation, drug holiday, or inclusion of adjuvant analgesics such as ketamine (5). The application of ketamine as an analgesic adjuvant strategy (1,2) to reduce the induction of opioid analgesic tolerance is based on the well-established observation that antagonism of NMDA receptors reduces the development of opioid analgesic tolerance (6).…”