Is melatonin a better option for sleep than cyclobenzaprine (Flexeril) in a patient with neuropathic pain taking chronic gabapentin and experiencing sleep disturbances?

Is Melatonin Better Than Cyclobenzaprine (Flexeril) for Sleep in This Setting?

No, neither melatonin nor cyclobenzaprine (Flexeril) should be used for sleep management in a patient with neuropathic pain on chronic gabapentin—instead, optimize the gabapentin dosing strategy and timing, or consider adding cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment.

Why Cyclobenzaprine Is Not Appropriate

• Cyclobenzaprine is a skeletal muscle relaxant approved only for acute musculoskeletal conditions and has shown benefit only for fibromyalgia among chronic pain conditions, not for neuropathic pain or primary insomnia 1
• Clinical practice guidelines explicitly state that muscle relaxants are not recommended for chronic insomnia management due to lack of efficacy and safety data, plus concerns about abuse and addiction potential 1
• The evidence base for cyclobenzaprine involves acute rather than chronic pain trials, making it inappropriate for long-term sleep management 1

Why Melatonin Is Not Appropriate

• Over-the-counter substances including melatonin are not recommended for treatment of chronic insomnia due to relative lack of efficacy and safety data 1
• The American Medical Association concluded that the efficacy of melatonin for insomnia is inconclusive 1
• A 2025 high-quality randomized controlled trial (n=31) found no difference between melatonin (mean dose 11.9 mg/day) and placebo for neuropathic pain intensity (4.1 vs 4.2 on 0-10 scale, P=0.8) or any secondary outcomes including sleep measures 2
• While one 2019 study suggested melatonin 3 mg might reduce gabapentin-induced daytime sleepiness 3, this addresses a different clinical question (managing a side effect) rather than treating primary sleep disturbance

The Correct Approach: Optimize Gabapentin Strategy

Leverage Gabapentin's Sedating Properties

• Gabapentin is recommended as first-line oral pharmacological treatment for chronic neuropathic pain and has the beneficial side effect of improving sleep 1, 4
• In the pivotal trial, gabapentin (up to 2400 mg/day) improved both pain visual analog scale measures and median sleep scores, with somnolence reported by 80% of patients 1
• A 2020 meta-analysis of 20 randomized controlled trials demonstrated significant improvement in sleep quality after 6 weeks of gabapentin treatment compared to placebo (standardized mean difference 0.39,95% CI 0.32-0.46, P<0.001) 5

Dosing Optimization Strategy

• Assess current gabapentin dose: Clinical practice often uses lower doses than the evidence-based range of 1800-3600 mg/day, potentially leading to suboptimal efficacy for both pain and sleep 4
• Timing adjustment: Administer a larger proportion of the daily gabapentin dose at bedtime to maximize sedating effects when desired 1
• Titration approach: If currently on suboptimal doses, gradually increase to therapeutic range (1800-3600 mg/day) while monitoring for adverse effects, particularly in older adults who should start at 100-200 mg/day 4

If Gabapentin Optimization Fails

First-Line Non-Pharmacological Approach

• Cognitive behavioral therapy for insomnia (CBT-I) should be used as first-line treatment, particularly in cancer populations and chronic pain patients 1
• CBT-I facilitates medication tapering and discontinuation when pharmacotherapy becomes necessary 1

Pharmacological Options (If Necessary)

The recommended sequence for chronic insomnia when non-pharmacological approaches fail 1:

1. Short-intermediate acting benzodiazepine receptor agonists (zolpidem, eszopiclone, zaleplon, temazepam) or ramelteon as first choice
2. Alternate BzRA or ramelteon if initial agent unsuccessful
3. Sedating antidepressants (trazodone, mirtazapine, doxepin) especially if comorbid depression/anxiety exists
4. Use lowest effective dose for shortest period possible, with regular follow-up every few weeks initially 1

Critical Pitfalls to Avoid

• Do not use antihistamines (including over-the-counter "sleep aids") due to daytime sedation and delirium risk, especially in older patients 1
• Do not use long-acting benzodiazepines (diazepam, clonazepam) due to accumulation, impaired clearance, and fall risk 1
• Do not use antipsychotics as first-line due to problematic metabolic side effects 1
• Avoid barbiturates entirely for sleep management 1

Monitoring Parameters

• Assess gabapentin adverse effects: somnolence, dizziness, peripheral edema (occurs in 7% of patients), and gait disturbance 4, 6
• In older adults or those with renal impairment, use lowest starting doses (100-200 mg/day) and adjust based on creatinine clearance 4
• If pharmacotherapy becomes necessary, accompany with patient education regarding treatment goals, safety concerns, potential side effects, and need for ongoing cognitive-behavioral treatments 1