Atypical benzodiazepine misuse and withdrawal in patient with epilepsy: a case report

Background Benzodiazepines (BDZ) are a class of psychoactive drugs that have been widely used for the treatment of many medical conditions. In this paper, a case of an atypical pattern of diazepam dependence in a patient with epilepsy is presented. The article may be an interesting proposition for rational management in the treatment of benzodiazepine dependence in a patient with non-withdrawal and withdrawal seizures. Detoxification is used then to optimize neurological treatment. Case presentation A 52-year-old Caucasian male, diagnosed with epilepsy with partial complex, and rarely tonic-clonic seizures and benzodiazepine (diazepam) misuse, was admitted to a detoxification unit specialized to treat substance dependence. This patient presented an atypical schedule of substance misuse with a weekly dose of 40 to 45 mg of diazepam, taken once a week, every Saturday. The patient reported having a group of symptoms that usually preceded generalized seizures that were described as the “aura” manifesting as confusion, derealisation, anxiety, and difficulties in speaking. First Saturday after admission to the hospital, the first aura experience was reported, while diazepam level in serum was higher than usual, which was supporting also strong psychological background for withdrawal. On weekend days, 3 weeks after admission, when the patient was receiving 3 mg of diazepam daily, he developed a severe “aura.” The EEG showed no seizure activity. Two weeks later (again Friday to Saturday), the patient reported the occurrence of aura, the EEG recording showed paroxysmal discharges, generalized multiple spikes associated with slow waves, lasting about 30 s, accompanied by eyelid myoclonia and disturbed consciousness. A week later another aura developed that resolved spontaneously without a seizure. Twelve days later, diazepam was completely removed; the elimination of serum benzodiazepines took place. The patient did not report aura until the end of the stay and he was dismissed 5 weeks later. Conclusions The differential diagnosis of an aura can be challenging. Carefully proceed serum monitored elimination of benzodiazepines in epileptic patients may serve in safety benefits and helps to achieve detoxification goals. Hence, it is important to prevent, recognize, and treat benzodiazepine dependence in every patient and may improve epilepsy treatment outcome.

Pharmacological class interventions for benzodiazepine withdrawal discontinuation: a meta-analysis

Background Long-term benzodiazepine (BZD) use may lead to dependence, addiction, and neuropsychiatric disturbances. BZD discontinuation can cause severe withdrawal symptoms and resurgence of premorbid conditions. There are guidelines on how to stop BZD if it is necessary. Pharmacological management is an option among several other recommendations, but its benefit remains unclear. This study investigates whether certain pharmacological classes can manage or facilitate BZD withdrawal beyond BZD itself. . Methods Data collected from (1985 to 2018) in Google Scholar, Medline Ovid, Scopus, PsychInfo, ClinicalTrials.gov, Cochrane Review Database, Embase, Scopus, Pubmed, and Proquest databases: involved controlled clinical trials on drugs studied for BZD withdrawal discontinuation. Single drugs were clustered into their pharmacological class (domain). The Oxford Quality Scoring System assessed the quality of a trial. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was used for clinical practice recommendations. For publication bias, we visually inspected the Funnel plot. We adopted the Cochrane Risk of Bias Tool to assess biases inherent to individual trials. The standardized mean difference measured the magnitude of the benefit of a pharmacological class. Results We analyzed forty-nine controlled trials of 2815 assigned participants. Of fourteen classes, the BZD receptor antagonist class (d 0.671, CI 0.199 -1.143, p=0.005, I2=0),5-HT1A receptor partial agonist, and the glutamate class seemed to have the potentiality to manage BZD withdrawal discontinuation clinically. Around 61 % of the trials received an Oxford Quality score of three, 86% of the trials were granted a GRADE recommendation low. About 29 trials were at low risk of bias in general. Conclusions Even though we could not prove that the pharmacological classes of drugs we analyzed for the clinical management of BZD withdrawal discontinuation were efficacious, our investigation showed that some of these classes have the potentiality to manage BZD withdrawal discontinuation and clinically facilitate the process when it is necessary, relevant, and recommended based on established guidelines. Further investigations are warranted to support our findings. Keywords: benzodiazepine withdrawal, benzodiazepine discontinuation, benzodiazepine cessation, benzodiazepine dependence.