Is it normal for a patient with complex neuropathic pain or epilepsy to be on both Neurontin (gabapentin) and Lyrica (pregabalin) simultaneously?

Is It Normal for a Patient to Be on Both Neurontin and Lyrica?

No, it is not normal or recommended to prescribe both gabapentin (Neurontin) and pregabalin (Lyrica) simultaneously, as they have identical mechanisms of action and overlapping adverse effect profiles that create an unacceptable additive sedative burden without established efficacy benefits. 1

Why Combination Therapy Is Not Recommended

Identical Mechanisms and Redundant Effects

• Both medications are gabapentinoids that bind to the same α2δ-1 protein target and work through identical mechanisms 2
• There are no randomized controlled trials demonstrating that combining gabapentin and pregabalin is superior to optimizing the dose of either medication alone 1
• The combination creates redundant pharmacologic effects without proven additive analgesic benefit 1

Unacceptable Safety Profile

• Both medications cause identical adverse effects including dizziness (23-46%), somnolence (15-25%), peripheral edema, gait disturbance, and visual disturbances 1
• The additive pharmacodynamic effects create an unacceptable sedative burden, particularly dangerous in elderly patients who face increased risk of falls, confusion, and sedation 1
• Gabapentinoids increase postoperative sedation, dizziness, and visual disturbances, with synergistic effects when combined with opioids 1

Lack of Evidence-Based Support

• The combination of pregabalin and gabapentin should be avoided in routine practice, especially in elderly patients or those with fall risk 1
• No guideline societies recommend this combination approach 1
• Combination therapy with gabapentin or pregabalin plus other drug classes (such as opioids or tricyclic antidepressants) has demonstrated superiority over monotherapy, but no evidence supports combining two gabapentinoids together 1

Evidence-Based Alternatives When Monotherapy Fails

Optimize Single Agent First

• For pregabalin: ensure adequate trial of 4 weeks at 300 mg/day before declaring treatment failure 1
• For gabapentin: ensure adequate trial of 1800-3600 mg/day for 3-8 weeks plus 2 weeks at maximum dose 1
• The maximum dose of pregabalin is 600 mg/day, reserved only for patients with inadequate pain relief at 300 mg/day who tolerate the medication well 1

Proven Combination Strategies

• Combining pregabalin or gabapentin with nortriptyline has proven superiority over either medication alone in randomized controlled trials 1, 3, 4
• Combining pregabalin with extended-release opioids (morphine or oxycodone) provides better pain relief at lower doses of each medication compared to monotherapy 1, 3
• These combinations target different pain mechanisms and have established efficacy, unlike dual gabapentinoid therapy 1

Critical Clinical Pitfalls

When You Encounter This Combination

• This represents either prescribing error, lack of awareness that both are gabapentinoids, or inappropriate polypharmacy 1
• Immediately assess for excessive sedation, dizziness, fall risk, and cognitive impairment 1
• Consider tapering one agent gradually over minimum of 1 week to avoid withdrawal symptoms 1

Switching Between Agents (Not Combining)

• When switching from gabapentin to pregabalin, start pregabalin 75 mg twice daily while continuing morning dose of gabapentin for first few days, then gradually taper gabapentin over several days to weeks 1
• Pregabalin has more predictable absorption and linear pharmacokinetics compared to gabapentin's nonlinear absorption 1, 4
• Pregabalin may provide faster pain relief (within 1.5-3.5 days) compared to gabapentin which requires 2+ months for adequate trial 1

Special Populations at Highest Risk

• Elderly patients are particularly vulnerable to falls, confusion, and sedation from gabapentinoids 1
• Patients on concurrent opioids or benzodiazepines face compounded respiratory depression and sedation risks 1
• Those with renal impairment require mandatory dose reduction for both medications as they are eliminated unchanged by the kidneys 1