If a patient is not responding to the maximum dose of pregabalin (Pregabalin) and is starting a selective serotonin reuptake inhibitor (SSRI), should pregabalin be discontinued?

Managing Pregabalin and SSRI Combination Therapy

When starting an SSRI in a patient not responding to maximum dose pregabalin, you should continue the pregabalin and add the SSRI rather than discontinuing pregabalin. 1

Rationale for Continuing Pregabalin

• Clinical guidelines recommend that if patients have an inadequate response to pregabalin, clinicians should consider adding a serotonin-norepinephrine reuptake inhibitor (SNRI) or tricyclic antidepressant (TCA) rather than discontinuing pregabalin 1
• This approach applies similarly to SSRIs, which share mechanisms with SNRIs but with more selective serotonergic effects 1
• Even at maximum doses, pregabalin may still provide partial pain relief that would be lost if discontinued 2
• Different pain medications work through complementary mechanisms, potentially offering additive benefits when used in combination 1

Dosing and Titration Considerations

• When adding an SSRI to pregabalin therapy:
  • Start the SSRI at a low dose and increase slowly while monitoring for side effects 1
  • Pay particular attention to potential serotonergic effects during the first 24-48 hours after dosage changes 1
  • Consider using an SSRI with lower potential for drug interactions (e.g., citalopram/escitalopram) 1

Safety Considerations for Combined Therapy

• While combining pregabalin with an SSRI requires caution, this combination is not contraindicated and is commonly used in clinical practice 1
• Monitor for potential serotonin syndrome symptoms, including:
  • Mental status changes (confusion, agitation, anxiety)
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia)
  • Autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 1
• Abrupt discontinuation of pregabalin can cause withdrawal symptoms including insomnia, anxiety, and other psychiatric symptoms, even in patients taking regular therapeutic doses 3

Special Considerations

• If pain control remains inadequate despite combination therapy, other options to consider include:
  • Topical analgesics (particularly for localized neuropathic pain) 1
  • Alpha lipoic acid for certain neuropathic pain conditions 1
  • Capsaicin for peripheral neuropathic pain 1
• Pregabalin may provide additional benefits beyond pain control, including improvement in anxiety symptoms and sleep, which would be lost if discontinued 4, 5

Monitoring and Follow-up

• Assess response to combination therapy after 4-6 weeks of treatment at stable doses 1
• If the patient experiences intolerable side effects from the combination, consider:
  • Reducing the pregabalin dose rather than discontinuing it completely 1, 5
  • Switching to an alternative SSRI with fewer drug interactions 1
  • Monitoring for improvement in both pain scores and functional outcomes 2, 6

Remember that only a minority of patients will have substantial benefit with pregabalin alone, and many require combination therapy for optimal pain control 6. The goal should be to maximize pain relief while minimizing adverse effects through appropriate medication combinations rather than sequential monotherapy 1.