What is the typical dosage of gabapentin (Neurontin) for mood stabilization?

Gabapentin Dosing for Mood Stabilization

Gabapentin is not a first-line mood stabilizer and lacks robust evidence for this indication, but when used adjunctively for treatment-resistant bipolar mixed states, doses of 600-2000 mg/day (mean ~1130 mg/day) have shown potential benefit, particularly for depressive symptoms rather than manic symptoms. 1

Evidence Quality and Context

The evidence for gabapentin as a mood stabilizer is extremely limited compared to its well-established use in neuropathic pain. Only one small open-label study specifically examined gabapentin for mood stabilization in bipolar disorder 1. This stands in stark contrast to the extensive guideline-based dosing recommendations available for neuropathic pain conditions 2, 3.

Dosing Protocol for Mood Stabilization (Based on Limited Evidence)

Initial Dosing and Titration

• Start at 300 mg/day and titrate upward based on response and tolerability 1
• The effective dose range in the bipolar mixed states study was 600-2000 mg/day, with a mean final dose of 1130 mg/day 1
• Titration should be gradual, though the specific schedule was not detailed in the available mood stabilization literature 1

Expected Response Pattern

• Depressive symptoms showed significant improvement (Hamilton Depression Rating Scale decreased from 18.2 to 10.6, p<0.0001) 1
• Manic symptoms showed minimal and statistically insignificant reduction 1
• This suggests gabapentin's mood-stabilizing effect is primarily antidepressant rather than antimanic 1

Clinical Outcomes

• 10 of 21 patients (48%) were considered responders in the treatment-resistant bipolar mixed states study 1
• Response was maintained over 4-12 months in most responders, often allowing reduction of concomitant antidepressants and antipsychotics 1
• Only one patient discontinued due to adverse effects (irritability and ataxia) 1

Critical Caveats and Pitfalls

Evidence Limitations

• The mood stabilization evidence comes from a single open-label study of only 21 patients - this is extremely weak evidence compared to the moderate-quality evidence available for neuropathic pain 1, 4
• All patients in the study were treatment-resistant and receiving gabapentin as adjunctive therapy, not monotherapy 1
• No placebo-controlled trials exist for mood stabilization, unlike the extensive controlled trial data for pain conditions 4

Comparison to Established Mood Stabilizers

• Traditional mood stabilizers like divalproex sodium (125 mg twice daily initially, titrated to therapeutic levels of 40-90 mcg/mL) and carbamazepine (100 mg twice daily initially, titrated to 4-8 mcg/mL) have much stronger evidence bases 5
• These agents should be considered before gabapentin for mood stabilization 5

Dosing Considerations from Pain Literature (If Higher Doses Considered)

• For neuropathic pain, gabapentin demonstrates nonlinear pharmacokinetics with saturable absorption, requiring three-times-daily dosing for optimal effect 2, 3
• The therapeutic range for pain is 1800-3600 mg/day in three divided doses, substantially higher than the mood stabilization doses studied 2, 3
• Do not extrapolate pain dosing to mood disorders - the single mood study used much lower doses (mean 1130 mg/day) 1

Safety Profile

• Common adverse effects include dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%) at higher doses used for pain 4
• In the mood stabilization study, only one patient discontinued due to adverse effects 1
• No negative drug interactions were observed with concomitant psychotropic medications 1
• Renal dose adjustment is mandatory as gabapentin is renally eliminated 2, 3

Bottom Line for Clinical Practice

Given the extremely limited evidence (one small open-label study), gabapentin should only be considered for mood stabilization as adjunctive therapy in treatment-resistant cases after failure of established mood stabilizers like divalproex sodium or carbamazepine. 5, 1 Start at 300 mg/day and titrate to 600-2000 mg/day based on response, with realistic expectations that benefit will primarily target depressive rather than manic symptoms 1.