Emerging neuropsychiatric toxicities of opioids

Pain is a common complication of cancer. As a result of educational efforts, there has been an appropriate increase in the use of opioids. The increase has resulted in a greater detection of a spectrum of neuro-psychiatric adverse effects that include cognitive failure, hallucinations, delirium, severe sedation, generalized myoclonus, hyperalgesia, allodynia and seizures. Various putative mechanisms have been postulated including the neuro-sensitizing effects of opioid metabolites. Numerous metabolites including morphine-3-glucuronide, morphine-6-glucuronide, hydromorphone 3-glucuronide, and normeperidine have been implicated. Morphine-3-glucuronide appears to cause hyperexcitability via non-opioid receptor mechanisms which are not yet well defined. Renal impairment, high opioid doses, prolonged opioid administration, borderline cognition, dehydration, neuropathic pain and the presence of other psycho-active drugs have consistently been reported to be correlates of opioid associated CNS irritability. Various strategies have been proposed for the management of opioid neuropsychiatric toxicity including opioid switches, opioid dose reductions and hydration. Psychostimulants may reverse the adverse cognitive effects of opioids. There remains a need for increased opioid availability. The standard of care for pharmacotherapy in general should apply to patients requiring opioids, including the ability of clinicians to recognize and approxiately treat toxic reactions if they occur.