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Rhabdomyolysis and brain ischemic stroke occurred in a heroin-dependent male under methadone maintenance therapy: Methadone is a synthetic opiate commonly used as an analgesic agent and as a replacement agent in heroin addiction which has shown evidence in reducing morbidity and mortality associated with opioid dependence and helps dependent patients to function better during recovery. Many clinical trials have reported favorable safety profile, with few adverse effects when used in appropriate dosage. It has been consistently noted that the risk of communicable disease like HIV, Hep C, is significantly reduced. Studies also have shown that patients who discontinue methadone therapy have increased mortality rates than those on methadone therapy (1, 2). Hsu et al. (3) have reported an interesting case of heroin-dependent male on methadone maintenance therapy published in this issue. The client presented in an altered state of consciousness after using IV heroin while on methadone maintenance therapy. Further assessment showed evidence of rhadbomyolysis and ischemic stroke. Methadone, when used inappropriately or in combination with heroin or other addictive substances, can do more harm with high rates of morbidity and often with fatal outcomes. Hsu has listed many health complications of heroin abuse . The most common toxic effects associated with methadone are respiratory depression, hypoxia, pulmonary oedema,aspiration and myocarditis. Rhabdomyolysis and ischemic stroke are potentially life threatening (4, 5). Hence it becomes further essential and important to estimate accurately the dosage of methadone at the initiation of the maintenance therapy to prevent overprescribing and associated complications. The usual maintenance dose of methadone depends on the opioid tolerance. In addition, simultaneous use of other CNS depressant such as opioids, alcohol, benzodiazepines, which acts synergistically as depressants, should be taken into consideration while prescribing methadone. The typical daily dose is around 20–100 mg daily (1, 6). In the current case the patient was on 150 mg of methadone. There is high possibility that the patient may have also been abusing methadone along with IV heroin which may have lead to current presentation. As it happens with most of the cases there is high probability that some other substance could have been combined which may have further complicated and worsened the presentation. The suggested causes of rhabdomyolysis could either be direct toxic effects of heroin, or due to vasoconstriction, shock, and depressed respiration, acidosis along with muscle compression and trauma which can lead to renal complications. It can be noted that in this case the patient was found lying on the floor during which time he may have suffered muscle compression due to prolonged posture or trauma with asphyxia . The role of other agents of abuse such as Ethanol, benzodiazepines, and some antidepressants which also have the potential for causing rhabdomyolysis cannot be ignored (7). The neurological deficits in this case were significant for a 33 year old which included poor cognitive functions, aphasia and weakness in extremities. Heroin and methadone are known to be associated with neurological complication. Apart from infections due to IV abuse and effects on CNS, heroin and methadone are also known for their effects on peripheral nervous system like plexopathy, poly and mononeuropathies. Ischemic stroke is one of the serious complications of heroin intoxication. Ischemic strokes are usually rare; this case report highlights the CNS involvement with changes in the bilateral globus pallidus as seen on MRI. Brain imaging confirmed both acute and chronic ischemic changes. The mechanism of stroke could be because of vasospasm, vasculities, hypersensitivity or embolism (8, 9). Hence, It s always a good practice to do a neurological examination on patients with heroin dependence on methadone therapy. However some patients with brain damage may not show significant neurological deficits on clinical examination, imaging could be one of the options if in doubt. It has been noted that, Heroin when abused with methadone can act synergistically leading to fatal complications (10). This warrants further research into the pattern of methadone abuse and complications when combined with heroin. Hence, it is worth exploring other safer alternatives in managing patients of opioid dependence with a focus on reducing the risk of morbidity and mortality. The other alternatives which have been tried are, LAAM, a long acting agent which requires less frequent dose than methadone. Buprenorphine is Invited comment