Is it safe to use gabapentin and hydroxyzine (Hydroxyzine) together for anxiety?

Gabapentin and Hydroxyzine Combination for Anxiety

Yes, gabapentin and hydroxyzine can be used together for anxiety, but this combination requires careful monitoring for additive central nervous system (CNS) depression effects, particularly sedation, dizziness, and respiratory depression. 1

Primary Safety Concerns

The main risk when combining these medications is additive CNS depression. Both agents independently cause sedation and dizziness, and their combined use amplifies these effects. 1 The American Geriatrics Society specifically warns about using gabapentinoids together with other CNS-active drugs, recommending minimization of total CNS-active medications when possible. 1

Evidence for Individual Agents in Anxiety

Hydroxyzine

• Hydroxyzine demonstrates superiority over placebo for generalized anxiety disorder (GAD), with efficacy evident from the first week of treatment. 2, 3
• The medication shows particular benefit for cognitive components of anxiety and maintains efficacy throughout 4 weeks of treatment without withdrawal symptoms upon discontinuation. 3
• Standard dosing is 50 mg for GAD, with acceptability and tolerability comparable to benzodiazepines and buspirone. 2

Gabapentin

• Evidence for gabapentin in anxiety is limited to case reports showing dose-response patterns in GAD symptoms. 4
• Critical concern: Gabapentinoids carry risks of tolerance, dependence, addiction, and withdrawal symptoms similar to benzodiazepines. 5
• Deaths involving pregabalin (a related gabapentinoid) now exceed those from diazepam, particularly when combined with opioids or other drugs. 5
• Long-term efficacy data for anxiety is lacking, with only short-term trials showing marginal differences from placebo. 5

Practical Prescribing Algorithm

Initiation Strategy

• Start gabapentin at 100-300 mg at bedtime or three times daily, increasing by 100-300 mg every 1-7 days as tolerated. 1
• Monitor specifically for excessive sedation or dizziness at each dose increase. 1
• Maximum dose typically 3600 mg/day in three divided doses, though adequate trials may require 2 months or more of titration. 1

Monitoring Requirements

• Assess for excessive sedation, dizziness, ataxia, and cognitive impairment at each dose adjustment. 1
• Monitor for respiratory depression, especially if opioids or benzodiazepines are co-prescribed. 1
• Document clinical rationale for combining these medications and the monitoring plan in the medical record. 1
• Educate patients about avoiding alcohol and exercising caution with activities requiring alertness until combined effects are known. 1

Special Population Considerations

Geriatric Patients

• Exercise particular caution in older adults, as both medications independently increase fall risk and cognitive impairment. 1
• Start with the lowest possible doses and titrate more slowly than in younger adults. 1
• The American Geriatrics Society Beers Criteria specifically warns about gabapentinoid use with other CNS-active drugs in this population. 1

Renal Impairment

• Gabapentin requires dose adjustment in proportion to creatinine clearance in patients with impaired kidney function. 1
• Failure to adjust dosing increases risk of accumulation and toxicity. 1

Important Caveats

Long-term Use Concerns

• Approximately 50% of patients prescribed gabapentinoids receive them continuously for at least 12 months, a practice not recommended by clinical guidelines or of doubtful efficacy. 6
• Sudden cessation after long-term use can lead to physical and psychological withdrawal symptoms; patients should be offered careful tapering and support if discontinuation is planned. 6

Polypharmacy Risk

• When three or more CNS-active drugs are used together, the risk of adverse effects increases substantially. 1
• Minimize the total number of CNS-active medications whenever clinically feasible. 1

Alternative Considerations

• For anxiety disorders in children and adolescents (6-18 years), SSRIs are first-line pharmacotherapy with stronger evidence than gabapentinoids. 6
• Hydroxyzine may be preferable to benzodiazepines when combined with serotonergic antidepressants, as benzodiazepines can antagonize antidepressant effects. 7