Will hydroxyzine help manage withdrawal symptoms in a patient taking clonazepam and Ativan (lorazepam) who is at risk of withdrawal if Ativan (lorazepam) is stopped?

Hydroxyzine for Benzodiazepine Withdrawal Management

Hydroxyzine can be used as a supportive adjunctive medication during benzodiazepine withdrawal to help manage anxiety symptoms, but it should not replace a proper gradual taper protocol. 1, 2

Evidence for Hydroxyzine in Benzodiazepine Withdrawal

Direct Evidence from Withdrawal Studies

• A controlled study of 154 patients withdrawing from long-term lorazepam (mean 64 months) demonstrated that hydroxyzine 50 mg significantly improved anxiety levels (p < 0.007), reduced withdrawal symptoms, and decreased side effects compared to placebo during the withdrawal period. 1

• Hydroxyzine 25 mg also showed significant anxiety improvement (p < 0.012) during lorazepam withdrawal, though with less robust reduction in withdrawal symptoms than the 50 mg dose. 1

• A Russian study of 59 patients on long-term benzodiazepines found that abrupt benzodiazepine discontinuation with hydroxyzine substitution resulted in only 23.3% dropout rate compared to 65.6% dropout with placebo, with greater anxiety reduction in the hydroxyzine group. 2

Dosing Recommendations Based on Evidence

• For patients with marked anxiety during benzodiazepine withdrawal, hydroxyzine 25 mg can be prescribed as transient support. 1

• For patients presenting with significant withdrawal symptomatology, hydroxyzine 50 mg is more appropriate and demonstrated superior reduction in withdrawal symptoms. 1

• The most common side effect is daytime sleepiness, which occurs more frequently at the 50 mg dose. 1

Critical Framework: Hydroxyzine as Adjunct, Not Replacement

The Mandatory Gradual Taper Protocol

• When discontinuing benzodiazepines (clonazepam and lorazepam), you must implement a gradual taper reducing by 10-25% of the current dose every 1-2 weeks—hydroxyzine serves only as symptomatic support during this process, not as a substitute for proper tapering. 3

• Abrupt benzodiazepine discontinuation can cause seizures and death, making gradual tapering non-negotiable regardless of hydroxyzine use. 3

• The taper rate must be determined by the patient's tolerance, not a rigid schedule, with pauses acceptable when withdrawal symptoms emerge. 3

Which Benzodiazepine to Taper First

• When a patient is taking both clonazepam and lorazepam, taper the benzodiazepines first before addressing any other medications, as benzodiazepine withdrawal carries higher risks than opioid withdrawal. 3

• If both benzodiazepines need adjustment, consider consolidating to a single long-acting agent (like clonazepam) before tapering, though this requires careful dose equivalency calculation. 3

Practical Implementation Algorithm

Step 1: Assess and Prepare

• Check prescription drug monitoring program to identify all controlled substances. 3
• Assess for history of withdrawal seizures, psychiatric comorbidities, and concurrent substance use disorders. 3
• If history of withdrawal seizures exists, refer to specialist immediately—do not attempt office-based taper. 3

Step 2: Initiate Taper with Hydroxyzine Support

• Begin reducing benzodiazepine by 10-25% of current dose every 1-2 weeks. 3
• Simultaneously start hydroxyzine 25-50 mg based on anxiety severity and withdrawal symptom intensity. 1
• For marked anxiety: hydroxyzine 25 mg. 1
• For significant withdrawal symptoms: hydroxyzine 50 mg. 1

Step 3: Monitor and Adjust

• Follow up at least monthly, with more frequent contact during difficult phases. 3
• Monitor for withdrawal symptoms: anxiety, tremor, insomnia, sweating, tachycardia, seizures. 3
• If withdrawal symptoms emerge, slow the taper rate further—do not increase hydroxyzine as compensation for too-rapid tapering. 3

Step 4: Duration and Expectations

• The taper will require minimum 6-12 months, possibly longer—hydroxyzine is used transiently during this period, not as long-term maintenance. 3, 1
• After successful benzodiazepine discontinuation, hydroxyzine can be discontinued as anxiety typically improves (75% of patients in one study were drug-free with decreased anxiety at 3 months post-withdrawal). 1

Additional Supportive Measures

Cognitive Behavioral Therapy

• Integrating CBT during the taper significantly increases success rates and should be strongly recommended alongside hydroxyzine. 3

Other Pharmacological Adjuncts

• Gabapentin (100-300 mg titrated upward) can help mitigate withdrawal symptoms. 3
• Trazodone 25-200 mg for insomnia management without abuse potential. 3
• Carbamazepine or pregabalin may assist discontinuation. 3

Critical Pitfalls to Avoid

• Never use hydroxyzine as justification for rapid or abrupt benzodiazepine discontinuation—the taper must remain gradual regardless of adjunctive medications. 3, 1
• Do not substitute another benzodiazepine or Z-drug (zolpidem) thinking it's safer—these carry similar risks. 3
• Never abandon the patient if tapering is difficult; maintain therapeutic relationship and consider slower taper or temporary pause. 3
• Warn patients about daytime sleepiness with hydroxyzine, particularly at 50 mg dose. 1

Comparative Context: Hydroxyzine vs. Benzodiazepines

• Hydroxyzine preserves memory and attention while providing anxiolytic effects, unlike benzodiazepines which cause clear memory deficiencies. 4
• Hydroxyzine lacks dependency potential and organ toxicity, making it appropriate for transitional support. 5
• However, hydroxyzine's efficacy for generalized anxiety is less robust than benzodiazepines, which is why it serves as adjunctive support rather than primary treatment. 6