Fast Detoxification of Benzodiazepines With the Help of Antiepileptics

BEnzodiazepines are classified as γ-aminobutyric acid-A (GABA_A) receptor agonists. Greater affinity for GABA_A receptors for GABA increase the frequency of chloride channel opening and potentiate the inhibitory effect of GABA in the central nervous system.¹ In India, about 1.08% of people (about 11.8 million people) are currently using sedatives. Only a minority use sedatives in a harmful or addictive pattern. In the general population in India, about 0.11% (nearly 1.18 million people) use sedatives in a pattern of dependence.²

Individuals with opioid use disorders who use benzodiazepines are at increased risk for overdose. Interestingly, the use and abuse of benzodiazepines has contributed substantially to the current epidemic of opioid overdose, with benzodiazepines involved in almost 30% of opioid overdose deaths in 2015. ³

Abstinence or withdrawal from benzodiazepines results in withdrawal symptoms, which can be troublesome and potentially fatal. Withdrawal syndrome is usually characterized by sleep disturbances, irritability, increased tension and anxiety, panic attacks, hand tremors, sweating, difficulty concentrating, nausea, weight loss, palpitations, headaches, muscle aches and stiffness, and some perceptual disturbances.⁴ Gradual dose reduction is preferable to abrupt discontinuation of the benzodiazepine. In primary care patients who failed to discontinue benzodiazepines with minimal intervention, gradual dose reduction was more effective than routine care in achieving discontinuation (51% vs 15%).⁵ At 15-month follow-up, 36% of those receiving the tapered dose stopped based on the benzodiazepine prescription data, compared with 15% of those receiving regular maintenance.⁶ Other drugs, including carbamazepine, have been used to facilitate the management of benzodiazepine dependence. Klein and co⁷ reported the use of carbamazepine to facilitate withdrawal from alprazolam in 3 patients with panic disorder who could not tolerate gradual reduction.

Here, we present the case of a patient with opioid and benzodiazepine dependence, in whom benzodiazepine detoxification was accomplished by rapid reduction with long-acting benzodiazepines and the antiepileptic carbamazepine.

Case Report

A 36 year old, married, working man with a history of opioid dependence for 12 years took Spasmo-Proxyvon capsules (containing 10 mg dicyclomine, 325 mg paracetamol, and 50 mg tramadol). Patients demonstrated craving, tolerance, withdrawal, preoccupation, and an inability to control Spasmo-Proxyvon use, which increased to 30-40 capsules per day over time. He also has a tobacco addiction characterized by craving, tolerance, and loss of control. The patient came to our outpatient service in 2014 and was stabilized with buprenorphine tablets 14 mg/day. In the following years, the patient experienced multiple relapses and was re-admitted on demand, and, subsequently, the dose of buprenorphine was optimized to 20 mg/day, with which he remained abstinent from opioids.

Around 2018, the patient experienced adjustment problems due to fights with his partner and difficulty sleeping. He learned about alprazolam tablets from a nearby pharmacy. In the early days, she took alprazolam to help with her sleep disturbance, but over the next 2 to 3 weeks she developed a strong desire to take it and had to increase the number of tablets. He would experience headaches, anxiety symptoms, difficulty sleeping, and discomfort if he did not take his medication. This behavior continued, and she came to our center on withdrawal because of loss of control due to overuse of alprazolam tablets (70-80 0.5 mg tablets) after 7 months of drug use.

The patient had no history of premorbid anxiety or chronic sleep disturbance prior to the adjustment reaction. He will be taking benzodiazepines to improve sleep disturbances and anxiety due to ongoing psychosocial stress. He was diagnosed with benzodiazepine dependence syndrome and referred for inpatient detoxification. The patient was successfully detoxified with 70 mg diazepam tablets on the first day. She was started on carbamazepine 600 mg tablets as an antiepileptic cap at the start of the reduction process. The initial dose of diazepam tablets was reduced from 70 mg to 50 mg for the first 3 days. On the seventh day, the dose was reduced to 35 mg and discontinued for another 3 days (Figure 1). This reduction process was carried out for 10 days, because the patient stated that he could not stay in the hospital for a longer time. The dose of the opioid agonist (buprenorphine) did not change during tapering, whereas carbamazepine was discontinued on day 10. Withdrawal symptoms were monitored twice daily and assessed with the Clinical Institute Withdrawal Assessment–Benzodiazepine scale.⁸ She experienced moderate withdrawal symptoms during the first 3 days of her reduced dose schedule, and mild to no withdrawal symptoms continued thereafter in the form of difficulty sleeping, mild anxiety, and lightheadedness, which were managed symptomatically. The patient was discharged after the 12th day of admission, although on follow-up for another 7 months she complained of difficulty sleeping and required medication. She was prescribed diazepam 10 mg and mirtazapine 7.5 mg at follow-up and remains abstaining from non-prescription benzodiazepines. He regularly attends follow-up appointments and is able to work and spend time with family members. He continues to be well maintained on buprenorphine 20 mg tablets.

Discussion

There are no definitive guidelines for reducing the dose of benzodiazepines in patients with benzodiazepine dependence; however, they are often categorized into fast and slow tapers. In patients receiving benzodiazepines and opioids concomitantly and requiring dose reduction for both drugs, it is recommended to reduce the dose of opioids first to avoid anxiety. Abruptly discontinuing benzodiazepines after 1-6 months of use can cause life-threatening seizures and relapse to benzodiazepines, so the dose should be reduced gradually. The duration of weaning depends on the initial dose, duration of use, risk of recurrence, and how well the reduced dose is tolerated by the patient. Most studies in primary care have found that gradual withdrawal over at least 10 weeks achieves long-term abstinence.⁹ Several studies comment on the optimal rate and duration of reduction of benzodiazepines, which can range from several weeks to several months. Information in the literature is even more limited for the rapid reduction of benzodiazepines, although safe and successful rapid reduction of alprazolam using chlordiazepoxide has been established previously, in which short-acting benzodiazepines abused by individuals were replaced by long-acting benzodiazepines.¹⁰ For patients who have been taking benzodiazepines for more than 4 weeks or who have been taking high doses, gradual reduction may be better tolerated.

Rapid reduction is usually considered for patients who have been on benzodiazepines for less than 4 weeks. In this method, discontinuation of the benzodiazepine occurs with relatively larger dose reductions and more frequent dose reductions rather than slower dose reductions. Rapid reduction may involve reducing the initial dose by 25%–30% weekly until 50% of the dose is reached, followed by reducing the dose by 5%–10% weekly.⁵ There are reports in the literature of rapid reduction success. Fournier et al¹¹ reported a successful rapid reduction of benzodiazepines in adolescent boys (age 16 years) with severe benzodiazepine dependence (greater than 14 days) in an inpatient setting using an interdisciplinary approach.

In these cases, it was noted that the patient’s duration of use was longer than 4 weeks (ie, 5 to 6 months), although rapid reduction is still possible. The advantage of a fast taper is a shorter hospital stay, which leads to less resource requirements. Possible explanations for successful rapid detoxification include our patients’ motivation to expedite treatment and the use of antiepileptics for possible seizures. An added advantage of carbamazepine, besides its antiepileptic effect, is its mild anxiolytic properties,⁷ which helps relieve the withdrawal symptoms a person experiences during a quick benzodiazepine detox. Thus, rapid abbreviation of benzodiazepines with other benzodiazepines may be considered in some patients when necessary. However, further evidence is needed to expand the literature on the efficacy and safety of rapid detoxification of benzodiazepines.

Article Information

Published Online: August 17, 2023. https://doi.org/10.4088/PCC.22cr03457
© 2023 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2023;25(4):22cr03457
Sent: November 30, 2022; accepted March 8, 2023.
To quote: Munipati D, Mathur R, Sarkar S. Rapid detoxification in benzodiazepine-assisted adults with antiepileptic assistance. CNS Disord Primary Care Companion. 2023;25(4):22cr03457.
Author Affiliation: All Indian Institute of Medical Sciences, New Delhi, India (all authors).
Corresponding author: Rahul Mathur, MD, DNB, All India Institute of Medical Sciences, New Delhi, Delhi 110029, India (rahulmathur.jul20@aiims.edu).
Relevant Financial Relations: There isn’t any.
Funding/Support: There isn’t any.
Patient Consent: Consent was received from the patient to publish the case report, and the information, including the date, was de-identified to protect anonymity.