Can pregabalin be started for anxiety while tapering off diazepam?

Starting Pregabalin During Diazepam Taper for Anxiety

Pregabalin can be started for anxiety while tapering diazepam, and evidence suggests this approach may actually facilitate benzodiazepine discontinuation by reducing both anxiety symptoms and withdrawal severity. 1

Evidence Supporting Concurrent Use

Direct Evidence for Switching Strategy

• A randomized controlled trial specifically evaluated switching from chronic benzodiazepines to pregabalin in patients with generalized anxiety disorder. 1 Patients stabilized on alprazolam 1-4 mg/day were randomized to either pregabalin 300-600 mg/day or placebo while undergoing a 25% per week benzodiazepine taper. 1

• Pregabalin demonstrated significantly greater anxiety reduction (HAM-A score change: -2.5 vs +1.3 for placebo, p<0.001) and lower withdrawal severity (PWC scores: 6.5 vs 10.3, p=0.012) during the taper period. 1

• While the primary outcome (remaining benzodiazepine-free) showed a non-significant trend favoring pregabalin (51.4% vs 37.0%), the anxiety and withdrawal measures strongly support pregabalin as a safe and effective method for discontinuing long-term benzodiazepine therapy. 1

Pregabalin's Anxiolytic Profile

• Pregabalin is approved for generalized anxiety disorder and has demonstrated efficacy at doses of 150-600 mg/day in multiple placebo-controlled trials. 2, 3

• Rapid onset of anxiolytic effect occurs within 1 week, similar to benzodiazepines but faster than SSRIs/SNRIs. 2, 4 This rapid action is particularly advantageous during benzodiazepine tapering when anxiety symptoms may emerge.

• Pregabalin effectively treats both psychic and somatic anxiety symptoms, with consistent effects across anxiety subtypes. 2

Practical Implementation Algorithm

Initiation Strategy

1. Start pregabalin at 50 mg three times daily or 75 mg twice daily while patient is still on stable diazepam dose. 5

2. Increase to 300 mg/day after 3-7 days, then by 150 mg/day every 3-7 days as tolerated, up to maximum 600 mg/day. 5

3. Begin diazepam taper only after pregabalin reaches therapeutic dose (typically 300-600 mg/day). 1

Benzodiazepine Taper Protocol

• Reduce diazepam by 25% of the daily dose every 1-2 weeks. 5 This gradual approach minimizes rebound anxiety and withdrawal symptoms.

• The Mayo Clinic guidelines specifically mention pregabalin as an adjunctive intervention to facilitate benzodiazepine tapering, though evidence quality is limited by study heterogeneity. 5

• Monitor for withdrawal symptoms using standardized scales during the taper period. 1

Critical Safety Considerations

Sedation Risk

• Both pregabalin and benzodiazepines cause dose-dependent dizziness and sedation. 5 During the overlap period, use lower pregabalin starting doses in elderly or frail patients.

• Tolerance to dizziness and somnolence typically develops within a few weeks of pregabalin initiation. 2

Respiratory Depression Warning

• Combining gabapentinoids with benzodiazepines can cause dangerous respiratory depression, particularly when opioids are also present. 5 Avoid concurrent opioid use during this transition period.

• The ESMO guidelines note caution with combining benzodiazepines and other sedating medications, with risk of oversedation. 5

Renal Dosing

• Both pregabalin and gabapentinoids require dose reduction in renal insufficiency, with adjustments based on creatinine clearance. 5 Check renal function before initiating pregabalin.

Advantages Over Alternative Approaches

• Unlike SSRIs/SNRIs, pregabalin does not require 4-6 weeks to achieve anxiolytic effect, making it superior for managing acute anxiety during benzodiazepine withdrawal. 2, 4

• Pregabalin has minimal withdrawal symptoms when discontinued gradually over 1 week, unlike benzodiazepines which require much longer tapers. 2, 6, 4

• Low abuse potential compared to benzodiazepines, though The Lancet Psychiatry notes gabapentinoids can cause reinforcing euphoria and have dependence risk when used long-term. 5

Common Pitfalls to Avoid

• Do not abruptly stop diazepam when starting pregabalin—maintain stable benzodiazepine dose until pregabalin reaches therapeutic levels. 5

• Avoid tapering both medications simultaneously—establish pregabalin first, then taper benzodiazepine. 5

• Do not use pregabalin long-term without reassessment—approximately 50% of patients prescribed gabapentinoids receive them continuously for ≥12 months, a practice of doubtful efficacy in many cases. 5

• Monitor for paradoxical anxiety or agitation, which can occur with any anxiolytic medication. 5