Switching from Alprazolam to a Longer‑Acting Benzodiazepine and Tapering
For a patient taking alprazolam 0.5 mg three times daily (total 1.5 mg/day), the safest approach is to convert to an equivalent dose of diazepam using a gradual cross‑taper, then reduce the diazepam by 10–25% of the current dose every 1–2 weeks, with the entire process likely requiring 6–12 months minimum. 1
Why Switch to Diazepam?
- Diazepam is preferred for benzodiazepine tapering because its longer half‑life (20–120 hours, including active metabolites) provides more protection against seizures and withdrawal symptoms compared with short‑acting agents like alprazolam. 1, 2
- Alprazolam has a short half‑life of 12–15 hours and causes more severe interdose rebound anxiety, making direct taper more difficult and increasing the risk of withdrawal symptoms such as panic attacks, malaise, weakness, insomnia, tachycardia, and lightheadedness. 3, 4
- Abrupt discontinuation of alprazolam can cause seizures and death—never stop suddenly. 1
Step 1: Convert Alprazolam to Diazepam Equivalent Dose
- Use a conversion ratio of alprazolam 0.5 mg = diazepam 5 mg. 1
- For this patient taking alprazolam 1.5 mg/day total, the equivalent diazepam dose is 15 mg/day. 1
- Perform a gradual cross‑taper over 1–2 weeks: 1
- Week 1: Reduce alprazolam to 1 mg/day (0.5 mg morning, 0.25 mg noon, 0.25 mg evening) while introducing diazepam 5 mg/day (split into 2.5 mg twice daily). 1
- Week 2: Reduce alprazolam to 0.5 mg/day (0.25 mg morning, 0.25 mg evening) while increasing diazepam to 10 mg/day (5 mg twice daily). 1
- Week 3: Discontinue alprazolam entirely and increase diazepam to 15 mg/day (7.5 mg twice daily or 10 mg morning + 5 mg evening). 1
Step 2: Begin Diazepam Taper
- Reduce diazepam by 10–25% of the current dose every 1–2 weeks for patients on benzodiazepines less than 1 year. 1
- For patients on benzodiazepines longer than 1 year, slow the taper to 10% of the current dose per month to minimize withdrawal symptoms. 1
- The taper rate must be determined by the patient's tolerance, not a rigid schedule—pauses in the taper are acceptable and often necessary when withdrawal symptoms emerge. 1
Sample Taper Schedule (Starting from Diazepam 15 mg/day):
| Week | Diazepam Dose | Reduction |
|---|---|---|
| 1–2 | 15 mg/day | Baseline (after cross‑taper) |
| 3–4 | 11–12 mg/day | 20–25% reduction |
| 5–6 | 9 mg/day | 20–25% of current dose |
| 7–8 | 7 mg/day | 20–25% of current dose |
| 9–10 | 5 mg/day | 20–25% of current dose |
| 11–12 | 4 mg/day | 20% of current dose |
| 13–14 | 3 mg/day | 25% of current dose |
| 15–16 | 2 mg/day | 33% of current dose |
| 17–18 | 1 mg/day | 50% of current dose |
| 19–20 | 0.5 mg/day | 50% of current dose |
| 21+ | Discontinue | Final step |
- Once the smallest available dose (diazepam 2 mg) is reached, extend the interval between doses (e.g., every other day, then every third day) before complete discontinuation. 1
Step 3: Monitor for Withdrawal Symptoms
- Follow up at least monthly during the taper, with more frequent contact during difficult phases. 1
- Monitor for withdrawal symptoms including anxiety, tremor, insomnia, sweating, tachycardia, headache, weakness, muscle aches, nausea, confusion, and seizures. 1
- Clinically significant withdrawal symptoms signal the need to further slow the taper rate or pause entirely for 2–4 weeks. 1
- Screen for depression, anxiety, and substance use disorders that may emerge during tapering. 1
Step 4: Integrate Cognitive‑Behavioral Therapy (CBT)
- Cognitive‑behavioral therapy during the taper significantly increases success rates and should be incorporated whenever possible. 1, 5
- Reduction in the fear of anxiety symptoms (anxiety sensitivity) is the best predictor of patients' ability to achieve and maintain drug abstinence. 5
- Additional supportive measures include mindfulness and relaxation techniques, sleep hygiene education, and exercise and fitness training. 1
Step 5: Consider Adjunctive Medications for Withdrawal Symptoms
- Gabapentin can help mitigate withdrawal symptoms: 1
- Start with 100–300 mg at bedtime or three times daily.
- Increase by 100–300 mg every 1–7 days as tolerated.
- Adjust dosage in patients with renal insufficiency.
- Carbamazepine may assist benzodiazepine discontinuation, though it may affect alprazolam metabolism. 1
- Pregabalin has shown potential benefit in facilitating benzodiazepine tapering. 1
- SSRIs (particularly paroxetine or sertraline) may help manage underlying anxiety during tapering. 1
- Trazodone 25–200 mg can be used for short‑term insomnia management without abuse potential. 1
Critical Safety Warnings
- Abrupt discontinuation of benzodiazepines is never appropriate and can lead to seizures, delirium, and death—equivalent to suddenly stopping antihypertensives or antihyperglycemics. 1
- Benzodiazepine withdrawal carries greater risks than opioid withdrawal and should always be conducted gradually. 1
- Advise patients of increased overdose risk if they return to previous doses after tolerance is lost. 1
- Never use straight‑line percentage reductions from the starting dose, as this subjects patients to disproportionately large final decrements. 1
Common Pitfalls to Avoid
- Do not taper too quickly: Even a 10% reduction every 3 days resulted in only 24% of patients completing withdrawal successfully. 1, 3
- Do not abandon the patient: Maintain the therapeutic relationship even if tapering is unsuccessful, and consider maintenance therapy as a legitimate outcome. 1
- Do not add new psychotropic medications during the taper unless absolutely necessary. 1
- Do not prescribe additional CNS depressants during the tapering period. 1
Expected Timeline and Realistic Goals
- The taper will likely take 6–12 months minimum, and possibly longer for patients on benzodiazepines for more than 1 year. 1
- Patient agreement and interest in tapering is a key component of success—use shared decision‑making and explain the risks of continued use versus benefits of discontinuation. 1
- Tapers may be considered successful as long as the patient is making progress; the goal is durability of the taper, not speed. 1
- Both complete discontinuation and attainment of a reduced, functionally acceptable dose are considered acceptable outcomes. 1
When to Refer to a Specialist
- Patients with a history of withdrawal seizures should be referred to a specialist immediately. 1
- Patients with unstable psychiatric comorbidities, co‑occurring substance use disorders, or previous unsuccessful office‑based tapering attempts should be referred to a specialist. 1
- Pregnant patients should not taper benzodiazepines during pregnancy without specialist consultation, as withdrawal can cause spontaneous abortion and premature labor. 1