What is the recommended treatment approach for benzodiazepine (BZD) withdrawal?

From the Guidelines

The recommended treatment approach for benzodiazepine withdrawal is a gradual tapering schedule, with a reduction of the benzodiazepine dose by 25% every 1–2 weeks, as this approach has been used safely and with moderate success 1. This gradual approach is necessary because abrupt discontinuation can cause severe withdrawal symptoms including seizures, psychosis, and potentially life-threatening complications. The tapering strategy works by allowing GABA receptors to gradually readjust after being downregulated during chronic benzodiazepine use, minimizing withdrawal severity while the brain achieves a new homeostasis. Some key points to consider when implementing a benzodiazepine taper include:

• Using either the patient's current benzodiazepine or substituting with a long-acting benzodiazepine like diazepam
• Reducing the dose by 25% every 1-2 weeks, with slower reductions as the dose decreases
• Considering adjunctive medications like propranolol for tachycardia, anticonvulsants for seizure prevention, or hydroxyzine for anxiety
• Involving mental health professionals in the management of patients with anxiety or other mental health conditions
• Prioritizing patient goals, weighing risks of concurrent benzodiazepine and opioid exposure, and coordinating care 1. It's also important to note that cognitive-behavioral therapy (CBT) can increase tapering success rates and may be particularly helpful for patients struggling with a benzodiazepine taper 1. Additionally, the EMPOWER trial demonstrated success in benzodiazepine tapering by targeting education about benzodiazepine risks and benefits of tapering, with 62% of independent seniors expressing interest in benzodiazepine changes, and 27% of patients stopping benzodiazepines compared with 5% in the control group 1.

From the FDA Drug Label

To reduce the risk of withdrawal reactions, use a gradual taper to discontinue diazepam or reduce the dosage (a patient-specific plan should be used to taper the dose) Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use. Inform patients that discontinuation or dosage reduction of diazepam may require a slow taper

The recommended treatment approach for benzodiazepine (BZD) withdrawal is a gradual taper of the dosage to reduce the risk of withdrawal reactions. A patient-specific plan should be used to taper the dose. Patients who take higher dosages or have had longer durations of use are at an increased risk of withdrawal adverse reactions. A slow taper is required for discontinuation or dosage reduction of diazepam 2.

From the Research

Benzodiazepine Withdrawal Treatment Approaches

• The management of benzodiazepine (BZD) tolerance is divided into low- and high-dose withdrawal, with gradual tapering of the BZD over 4 weeks on an outpatient basis suggested for low-dose withdrawal 3.
• For high-dose withdrawal, patients are recommended to be tolerance tested with diazepam and, if tolerant, tapered off medication as inpatients at a rate of 10% per day 3.
• Triazolobenzodiazepines, such as alprazolam, may require special consideration, with a titration rate of 0.5 mg three times a day regardless of whether the patient is being tapered for low- or high-dose withdrawal 3.

Pharmacological Interventions for Benzodiazepine Discontinuation

• A review of pharmacological interventions for benzodiazepine discontinuation found potential benefits of valproate and tricyclic antidepressants in facilitating benzodiazepine tapering 4.
• Other interventions, such as pregabalin, captodiame, paroxetine, and flumazenil, may also have positive effects on benzodiazepine withdrawal symptoms, but the evidence is generally of low or very low quality 4.
• The review highlights the need for more randomized controlled trials with less risk of bias and better reporting of patient-centered and long-term clinical outcomes 4.

Alternative Treatment Approaches

• Chlordiazepoxide substitution and taper has been used as a treatment approach for alprazolam withdrawal, with a case series demonstrating its effectiveness in a small group of patients 5.
• Clonazepam is also used as a treatment for benzodiazepine withdrawal, with a study suggesting its potential benefits in reducing withdrawal symptoms 6.
• Other benzodiazepines, such as clobazam and clonazepam, may be used for seizure prophylaxis in patients with epilepsy refractory to multiple antiepileptic drugs 7.

Considerations for Benzodiazepine Withdrawal Treatment

• The treatment of benzodiazepine withdrawal requires careful consideration of the patient's individual needs and circumstances, including the dose and duration of benzodiazepine use 3, 6.
• The potential for addiction and misuse of benzodiazepines highlights the need for careful monitoring and management of patients undergoing benzodiazepine withdrawal treatment 7, 6.
• Future research is warranted to explore alternative methods of treating benzodiazepine withdrawal and to improve our understanding of the most effective treatment approaches 4, 6.