Drug overdoses, psychoses and (epileptic) seizures were registered separately throughout the trial. In total, 13 such events occurred during the 12 months experimental treatment phase of the study.

Drug overdoses
A drug overdose was defined as an intentional or unintentional intake of a drug dose in a much larger quantity than normal for the individual, or than normal in the context of treating a disease, which is likely to result in a severe toxic reaction or death. A severe toxic reaction was evident in case of a considerably diminished level of consciousness, ranging from clouded consciousness to coma, and in case of respiratory depression, which are life-threatening and/or require treatment with an antagonist.
Four drug overdoses were registered, all occurring in the co-prescribed heroin treatment group. The severity of one overdose event was considered as mild. Three overdoses were considered moderate in severity. One of the overdoses was considered to be an SAE (see Table 14). This overdose was registered in the SAE-category "life-threatening event". Due to an overdose of (non-prescribed) heroin and cocaine, the patient lost consciousness, and was admitted to a hospital. The same day, the patient left the hospital on his own initiative, without notifying the hospital staff. Later that day, the patient restarted the treatment with co-prescribed heroin. This SAE was judged to be not related to the heroin medication. Two other drug overdoses - involving two other patients - were considered to be definitely related to the co-prescribed heroin medication (right-hand column in Table 14). These were not registered as SAEs.

Psychoses
A psychosis was defined in terms of the diagnosis psychosis/hallucinosis, involving signs and symptoms which are observed during an acute schizophrenic episode, like hallucinations and delusions.
One psychosis was reported during the 12 months treatment period. The psychosis occurred in a patient who participated in the methadone alone treatment group, and - hence - was unrelated to the heroin medication. The psychosis was not registered as SAE.
Table 14. Relationship of drug overdoses, psychoses and seizures with heroin
medication during the experimental treatment phase of the trial

Seizures
An (epileptic) seizure was present (1) in case of a grand mal attack, or epileptic state which met the criteria usually applied in the treatment of epilepsy, and (2) in case of an epileptiform seizure, including all other types of seizures with contractions and diminished level of consciousness, which did not meet the criteria mentioned under (1).
Five patients reported a total of eight (epileptic) seizures. The four seizures in the methadone group involved three patients; one patient reported two seizures. The four seizures in the co-prescribed heroin group involved two patients, who each reported two seizures. Two of these seizures were registered as SAE. None were considered to be definitely related to the heroin medication.