Is amitriptyline (tricyclic antidepressant) cream effective when combined with Voltaren (diclofenac) for pain management?

Efficacy of Amitriptyline Cream Combined with Voltaren for Pain Management

Topical amitriptyline cream combined with diclofenac (Voltaren) can be effective for certain types of neuropathic and localized pain, though controlled clinical trials show mixed results regarding this combination's efficacy. 1

Evidence for Combination Therapy

Mechanism of Action

• Amitriptyline: Works topically by blocking sodium channels required for neuronal impulses and inhibiting serotonin and norepinephrine reuptake 1
• Diclofenac (Voltaren): Acts as a topical NSAID to reduce local inflammation and pain

Clinical Evidence

• A case series of 36 patients with erythromelalgia showed that 75% experienced pain improvement with topical amitriptyline 1-2% compounded with ketamine 0.5% 1
• Topical amitriptyline has been used as a coanalgesic in combination with other agents for neuropathic pain components 1
• However, larger controlled trials have shown inconsistent results:
  • One randomized trial with 92 patients found no significant effect of topical amitriptyline alone or in combination with ketamine compared to placebo 1
  • Systematic reviews indicate limited evidence supporting topical amitriptyline's efficacy for neuropathic pain 2

Recommended Approach for Pain Management

Step 1: Determine Pain Type

• Neuropathic pain: Consider amitriptyline-diclofenac combination
• Inflammatory/musculoskeletal pain: Diclofenac alone may be sufficient
• Mixed pain syndromes: Combination therapy may be more beneficial

Step 2: Formulation and Application

• Recommended formulation: 1-2% amitriptyline with diclofenac gel (1-3%)
• Application frequency: Apply to affected areas up to 3 times daily 1
• Duration: Trial for at least 4 weeks before determining efficacy 1

Step 3: Monitoring and Adjustment

• Assess pain reduction after 2-4 weeks
• If inadequate response, consider increasing amitriptyline concentration (up to 2%) 1
• Monitor for local adverse reactions (skin irritation, burning sensation)

Important Considerations and Limitations

Patient Selection

• Best candidates include:
  • Patients with localized neuropathic pain
  • Those with contraindications to oral medications
  • Patients with erythromelalgia or other peripheral pain syndromes 1

Potential Advantages

• Minimal systemic absorption compared to oral medications
• Fewer systemic side effects than oral amitriptyline
• Targeted delivery to painful areas
• May be particularly useful for focal pain syndromes 1

Limitations and Caveats

• Evidence quality is limited; most positive results come from uncontrolled trials or case reports 2
• Compounded preparations require specialized pharmacy services
• Not FDA-approved as a combination therapy
• May be less effective for widespread pain conditions
• Patients with severe or refractory pain may require systemic therapy 1

Alternative Approaches

If the amitriptyline-diclofenac combination proves ineffective, consider:

• Lidocaine 5% patches for neuropathic pain 1
• Capsaicin cream (0.075%) for focal neuropathic pain 3
• Oral medications (gabapentin, pregabalin, duloxetine) for widespread pain 1
• Referral to pain management for refractory cases 1

The decision to use topical amitriptyline with diclofenac should be based on the specific pain syndrome, patient preferences regarding systemic side effects, and previous response to other pain management strategies.