Can I take pregabalin and gabapentin (GABA analogs) together?

Concurrent Use of Pregabalin and Gabapentin

Taking pregabalin and gabapentin together is not recommended due to their similar mechanisms of action, overlapping side effect profiles, and potential for increased adverse effects without additional therapeutic benefit. 1

Mechanism of Action and Redundancy

• Both pregabalin and gabapentin are α2δ ligands that work through similar mechanisms, binding to calcium channels in the brain and spinal cord to inhibit release of excitatory neurotransmitters involved in pain 2
• Using both medications simultaneously provides pharmacological redundancy rather than complementary effects, as they target the same receptor sites 3

Adverse Effects and Safety Concerns

• Concurrent use increases risk of overlapping side effects including dizziness, drowsiness, fatigue, ataxia, and cognitive impairment 1
• Both medications can cause significant adverse effects individually, including:
  • Moderate to large increased risk of withdrawal due to adverse events 2
  • Large increases in blurred vision, dizziness, weight gain, and cognitive effects 2
  • Peripheral edema and sedation, particularly with pregabalin 2, 4
• Case reports document patients experiencing intensified adverse effects when both medications were prescribed together, which resolved when one was discontinued 1

Pharmacokinetic Considerations

• While pregabalin and gabapentin don't have significant pharmacokinetic interactions with each other 5, their combined use amplifies their overlapping side effect profiles 1
• Both medications are eliminated unchanged in urine, requiring dose adjustments in patients with renal impairment 5, 3

Clinical Guidance for Pain Management

• For neuropathic pain, either pregabalin OR gabapentin should be used as a single agent, not in combination 2
• When additional pain control is needed, combining a gabapentinoid (either pregabalin OR gabapentin) with medications from different classes is more appropriate:
  • Tricyclic antidepressants like nortriptyline provide complementary pain relief through different mechanisms 6
  • The combination of nortriptyline and a single gabapentinoid has been shown to be superior to either medication alone 6

Special Populations and Considerations

• Elderly patients are at particularly high risk for adverse effects from gabapentinoids, including sedation, dizziness, and falls 2
• The American Geriatrics Society recommends avoiding medications that cause sedation in older adults due to increased risk of cognitive impairment and falls 2
• Both medications have been associated with potential for misuse and diversion, particularly in patients with history of substance use disorders 7

Alternative Approach

• If current gabapentinoid therapy is insufficient:
  • Optimize the dose of a single gabapentinoid (either pregabalin OR gabapentin) to the maximum tolerated dose before considering alternatives 2
  • Consider adding a medication from a different class, such as a tricyclic antidepressant, which works through a different mechanism 2, 6
  • For localized pain, topical agents like lidocaine patches or topical NSAIDs may provide additional relief 6

In conclusion, while there have been some research and clinical situations where the combination has been used 8, the most recent evidence and case reports indicate significant risks without clear additional benefits 1. The safer approach is to optimize therapy with a single gabapentinoid and add medications from different classes when additional pain control is needed.