Steering the pharmacological treatment along different metabolic pathways in response to outlying complicated benzodiazepine withdrawal – a case study

Purpose: In benzodiazepine (BZD)-addicted patients, as in alcohol-dependent ones, the complicated withdrawal syndrome may be efficiently treated with accumulated long-acting benzodiazepine. The following work presents an alternative that can be used when the procedure fails. Case description: A midazolam-dependent patient (1500 mg/d) was admitted to the hospital due to a withdrawal-induced status epilepticus. After treatment with barbiturates and megadoses of diazepam, the seizures subsided, but during the continuation of BZD (diazepam, clorazepate), consciousness disorders gradually developed culminating in a full loss of contact with the patient. The breakthrough occurred when lorazepam was used instead of previously administered substitute BZDs. Comment: Extreme midazolam abuse (with a possible contribution of barbiturates at emergency admission) induced hydroxylating liver enzymes. This meant a rapid conversion of nominally long-acting substitutes, as those are similarly metabolized. This extremely facilitated elimination hindered their accumulation to the needed satiation level. Lorazepam, short-acting but bypassing the accelerated metabolic pathway, at sufficient doses provided the satiation necessary to stabilize the patient.