What is the role of gabapentin (Neurontin) in treating treatment-resistant depression?

Gabapentin for Treatment-Resistant Depression

Gabapentin is not recommended as a primary treatment for treatment-resistant depression due to insufficient evidence supporting its efficacy for this specific indication.

Evidence on Gabapentin for Depression

• Gabapentin (Neurontin) is primarily approved and recommended for neuropathic pain conditions, including diabetic neuropathy and postherpetic neuralgia, not for depression 1
• Clinical practice guidelines do not include gabapentin among recommended treatments for treatment-resistant depression 1
• Controlled studies in adults have not found gabapentin to be helpful for bipolar disorder, which suggests limited mood-stabilizing properties 1

Current First-Line Approaches for Treatment-Resistant Depression

Treatment-resistant depression (TRD) is typically defined as depression that has failed to respond to at least two adequate trials of antidepressants with different mechanisms of action 1. The recommended approaches include:

• Switching to a different antidepressant class (SSRI to SNRI or vice versa) 1
• Augmentation strategies with evidence-based options such as:
  • Second-generation antipsychotics 1
  • Lithium 1
  • Thyroid hormone 1

Limited Research on Gabapentin for Depression

The research on gabapentin for depression is limited and consists primarily of small, open-label studies:

• A retrospective chart review of 27 patients with treatment-resistant depression showed that 37% responded to adjunctive gabapentin, with most responders having prominent anxiety or soft bipolar features 2
• Studies examining gabapentin have focused primarily on bipolar disorder rather than unipolar depression 3, 4, 5
• When gabapentin showed benefit in bipolar patients, it appeared to work better for:
  • Those with comorbid anxiety disorders 4
  • Those with alcohol abuse 4
  • Depressive symptoms within mixed bipolar states 5, 6

Potential Niche Uses

Gabapentin might be considered in specific clinical scenarios:

• For patients with treatment-resistant depression who also have comorbid:
  • Neuropathic pain conditions 1
  • Anxiety symptoms 4
  • Alcohol use disorder 4

Safety Considerations

If considering gabapentin despite limited evidence:

• Start with low doses (100-300 mg at bedtime) and titrate slowly, especially in older adults 1
• Monitor for common side effects including:
  • Dizziness, drowsiness, and unsteadiness 1
  • Fatigue and sedation 2
  • Gastrointestinal symptoms 2
• Dosage should be reduced in patients with renal impairment 1

Conclusion

• Current evidence does not support gabapentin as a standard treatment for treatment-resistant depression 1
• For treatment-resistant depression, evidence-based approaches should be prioritized, including switching antidepressants, augmentation with approved agents, or referral for non-pharmacological treatments like ECT 1
• If gabapentin is considered, it should be as an adjunctive treatment in patients with specific comorbidities like neuropathic pain, anxiety, or alcohol use disorder where it may provide additional benefit 1, 4