Gabapentin for Mood Disorders: Not Recommended
Gabapentin should not be used as a treatment for mood disorders, as there is no high-quality evidence supporting its efficacy for bipolar disorder or major depressive disorder, and current clinical practice guidelines do not recommend it for these indications. 1, 2
Evidence Against Use in Mood Disorders
Bipolar Disorder
The American Academy of Child and Adolescent Psychiatry guidelines for bipolar disorder do not include gabapentin among recommended first-line or maintenance treatments, which consist of lithium, valproate, and atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone). 1
A systematic review of gabapentin in psychiatric disorders concluded that gabapentin has "less likely benefit adjunctively for bipolar disorder" with no quality evidence supporting its use. 2
A comprehensive review in The Annals of Pharmacotherapy explicitly stated that "gabapentin cannot be recommended for treatment of bipolar disorder" based on available data. 3
Major Depressive Disorder
The American College of Physicians guidelines for major depressive disorder recommend cognitive behavioral therapy or second-generation antidepressants as first-line treatments, with no mention of gabapentin as a treatment option. 4
The systematic review found no clear evidence for gabapentin therapy in depression. 2
Limited Supporting Evidence and Its Context
While some older, low-quality studies suggested potential benefit, these findings have critical limitations:
A retrospective chart review from 2001 showed 37% response rate when gabapentin was added to antidepressants in treatment-resistant depression, but this was uncontrolled, retrospective, and included patients with "soft bipolar features" rather than pure unipolar depression. 5
Small open-label studies (10-50 patients) from 1998-1999 suggested possible adjunctive benefit in mixed bipolar symptoms, but these were not controlled trials and showed only 30% moderate-to-marked effectiveness. 6, 7
These studies are now over 20 years old and have not been replicated in higher-quality controlled trials, which is why gabapentin failed to be incorporated into current evidence-based guidelines. 2, 3
Important Clinical Caveats
Approved Uses for Gabapentin
Gabapentin's only established psychiatric indication is for anxiety disorders (particularly social anxiety disorder), where some evidence exists, though it remains off-label. 2
It has clearer efficacy for alcohol craving and withdrawal symptoms and may have a role in adjunctive treatment of opioid dependence. 2
Risk of Dependence
Gabapentin carries risks of dependence and withdrawal symptoms, particularly when used long-term, which is a significant concern given the chronic nature of mood disorders. 4
In England, approximately 50% of patients prescribed gabapentinoids were treated continuously for at least 12 months, and sudden cessation can lead to physical and psychological withdrawal symptoms. 4
Potential for Misuse
- SSRIs and SNRIs should be used cautiously or potentially avoided in women with bipolar disorder/manic depression because of the risk of inducing mania, and while this specific warning applies to antidepressants, the principle of avoiding unproven agents in bipolar disorder applies equally to gabapentin. 4
Recommended Alternatives
For Bipolar Disorder
- First-line: Lithium, valproate, or atypical antipsychotics for acute mania/mixed episodes 1
- Maintenance: Lithium or valproate, with lithium showing superior long-term efficacy 1
- Bipolar depression: Olanzapine-fluoxetine combination or mood stabilizer with carefully added antidepressant 1
For Major Depressive Disorder
- First-line: Cognitive behavioral therapy or second-generation antidepressants (SSRIs/SNRIs such as sertraline, escitalopram, or venlafaxine) 4
- Second-line: Switching to another SGA or augmenting with bupropion or buspirone 4
Common Pitfall to Avoid
Do not use gabapentin as a "mood stabilizer" based on outdated anecdotal reports or small open-label studies from the 1990s. The lack of incorporation into current evidence-based guidelines after 25+ years indicates that initial promising signals did not translate into clinically meaningful benefit when subjected to rigorous evaluation. 1, 2, 3