Which is the recommended treatment for myoclonus induced by high doses of morphine?

Fråga: Which is the recommended treatment for myoclonus induced by high doses of morphine?

Sammanfattning: Morphine induced myoclonus is a frequently seen phenomena especially with high doses. The dose can be reduced or another opioid can be used alternatively (such as hydromorphone). Clonazepam, lorazepam or diazepam can be added in the next step. If necessary midazolam can be given as continuous infusion.

Svar: Successful pain control in 70-90 per cent of the cancer patients can be achieved by appropriate dosing of morphine (1). On the other hand opioid-related myoclonus has been reported in a wide range from 2.7 to 87 per cent of the cancer patients (2). It is associated with especially high doses of morphine and use of concomitant neuroleptic drugs (1). Myoclonus has been experienced after oral, intravenous and spinal administration and with hydromorphine, mephendine, fentanyl and its derivatives as well as morphine (1).

There are a few hypothesis for the mechanism of myoclonus. Accumulation of morphine metabolites, morphine 3 glucuronide and morphine 6 glucuronide may be linked to myoclonus (3, 4). Antiglycinergic effect of morphine and its metabolites in dorsal nucleus of spinal cord resulting in disinhibition of excitatory tonus can cause myoclonus (1, 2).

For the treatment of myoclonus induced by morphine, reducing the amount of opiate given or switching to another opioid may be the first alternative. Some opioids, such as fentanyl, sufentanyl and methadone should not be the first alternatives because of the active metabolites and of non-opioid receptor effects (2). On the other hand pain control should be the main aim. Hydromorphone or levorphanol have been suggested as substitution in a recent article evaluating the control of myoclonus after high dosage morphine (3). Traditional antiepileptic drugs are not effective in this case (3). If the control of myoclonus is not successful, clonazepam, lorazepam and diazepam can be added (3). If it is not still overcome, another opioid can be given alternatively. Midazolam is recommended as last choice because of its cost and short half life on the other hand it is convenient for continuous infusion (3). 1 Holdsworth MT, Adams VR, Chavez CM, Vaughan LJ, Duncan MH: Continuous midazolam infusion for the management of morphine-induced myoclonus. Ann Pharmacother 1995; 29: 25-29 2 Mercadante S: Pathophysiology and treatment of opioid-related myoclonus in cancer patients. Pain 1998; 74: 5-9 3 Ferris DJ: Controlling myoclonus after high-dosage morphine infusions. Am J Health-Syst Pharm 1999; 56: 1009-1010 4 Tiseo PJ, Thaler HT, Lapin J, Inturrisi CE, Portenoy RK, Foley KM: Morphine-6-glucuronide concentrations and opioid-related side effects: a survey in cancer patients. Pain 1995; 61: 47-54