What are the potential consequences of abrupt cessation of benzodiazepines (Benzodiazepines), including increased COWS (Clinical Opiate Withdrawal Scale) score, vomiting, diarrhea, rebound sympathetic nervous system (SMS) activity, or clinical depression?

From the Guidelines

Abrupt cessation of benzodiazepines should be avoided due to the risk of severe withdrawal symptoms, and instead, a gradual tapering approach should be used to minimize the risk of increased COWS scores, vomiting, diarrhea, rebound sympathetic nervous system activity, and clinical depression. Benzodiazepine withdrawal should always be managed through gradual tapering rather than sudden discontinuation. A typical taper involves reducing the dose by 10-25% every 1-2 weeks, with slower reductions as the dose gets lower, as suggested by the EMPOWER trial 1. For example, if a patient is taking diazepam 40mg daily, an initial reduction might be to 30mg daily for two weeks, then 25mg daily for two weeks, and so on. Long-acting benzodiazepines like diazepam are often preferred for tapering due to their smoother withdrawal profile. The withdrawal syndrome occurs because benzodiazepines enhance GABA neurotransmission, and with chronic use, the brain adapts by downregulating GABA receptors. When the medication is suddenly removed, this results in a relative GABA deficiency and excess excitatory neurotransmission, leading to anxiety, autonomic hyperactivity, and in severe cases, seizures or psychosis. Patients should be monitored for withdrawal symptoms throughout the tapering process, and the schedule adjusted as needed based on their response. Some studies suggest that a reduction of the benzodiazepine dose by 25% every 1–2 weeks can be used safely and with moderate success 1. Additionally, cognitive-behavioral therapy (CBT) can increase tapering success rates and might be particularly helpful for patients struggling with a benzodiazepine taper 1. It is also important to consider the risks of concurrent use of benzodiazepines and opioids, as this can increase the risk of potentially fatal overdose 1. Overall, a gradual tapering approach, combined with careful monitoring and support, is the recommended approach for managing benzodiazepine withdrawal. Key considerations for tapering benzodiazepines include:

• Gradual reduction of the dose over a period of weeks or months
• Monitoring for withdrawal symptoms and adjusting the taper schedule as needed
• Use of long-acting benzodiazepines for tapering
• Consideration of CBT or other non-pharmacological interventions to support tapering
• Avoidance of concurrent use of benzodiazepines and opioids whenever possible.

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) Abrupt discontinuation or rapid dosage reduction of diazepam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months Inform patients that the continued use of diazepam may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of diazepam may precipitate acute withdrawal reactions, which can be life-threatening Instruct patients that discontinuation or dosage reduction of diazepam may require a slow taper

Abrupt cessation of benzodiazepines may result in withdrawal reactions, which can be life-threatening.

• Symptoms of withdrawal reactions may include:
  • Seizures
  • Rebound symptoms
  • Anxiety
  • Insomnia
  • Irritability
  • Depression
  • Nausea and vomiting
  • Diarrhea
• Protracted withdrawal syndrome may also occur, with symptoms lasting weeks to more than 12 months.
• To minimize the risk of withdrawal reactions, a gradual taper should be used to discontinue benzodiazepines or reduce the dosage.
• Patients should be informed of the risks of abrupt discontinuation or rapid dosage reduction and the importance of a slow taper. 2 2 3

From the Research

Abrupt Cessation of Benzodiazepines

• Abrupt discontinuation of benzodiazepine treatment may show a spectrum of symptoms similar to those observed from withdrawal of alcohol or barbiturates 4.
• The higher the dose and the longer the benzodiazepine is taken, the greater the risk of developing withdrawal symptoms 4.
• Withdrawal symptoms may occur in patients receiving recommended doses and/or short-term therapy 4.
• Rebound insomnia occurs with greater frequency and severity with the short-acting agents 4.

Symptoms of Benzodiazepine Withdrawal

• Symptoms of benzodiazepine withdrawal may include vomiting, diarrhea, rebound SMS activity, or clinical depression.
• Withdrawal seizures have occurred with short, medium, and long half-life benzodiazepine, if discontinued abruptly 5.
• The severity of seizures range from a single episode to coma and death 5.
• Benzodiazepine dose tapering can be done faster in a hospital setting in high-dose abusers, but must be done more slowly in the outpatient setting in therapeutic dosage users 5.

Management of Benzodiazepine Withdrawal

• Gradual tapering of benzodiazepines is the most common treatment strategy for benzodiazepine dependence 6.
• Pharmacological interventions such as valproate, tricyclic antidepressants, pregabalin, captodiame, paroxetine, and flumazenil may facilitate benzodiazepine tapering 7.
• However, the evidence for these interventions is of low or very low quality, and more randomized controlled trials are required to draw firm conclusions 7.

Persistent Withdrawal Syndromes

• Benzodiazepines may induce withdrawal syndromes and rebound upon discontinuation, even with slow tapering 8.
• The distress associated with benzodiazepines discontinuation appears to be short-lived 8.
• Certain benzodiazepines, such as alprazolam and lorazepam, are more likely to induce withdrawal 8.