What is Gabapentin?
Gabapentin is an anticonvulsant prescription medication first approved by the FDA in 1993 [1.2.3, 1.2.8]. It is sold under brand names like Neurontin, Gralise, and others [1.2.3]. Its primary, FDA-approved uses are for treating postherpetic neuralgia (nerve pain from shingles) and as an adjunctive therapy for partial seizures in adults and children [1.2.5]. Despite these specific indications, a significant portion of gabapentin prescriptions are for off-label uses, meaning for conditions not officially approved by the FDA [1.3.4, 1.2.4]. Studies show that over 99% of its outpatient prescriptions between 2011 and 2016 were for such unapproved applications [1.2.4]. These off-label uses include anxiety disorders, fibromyalgia, alcohol withdrawal, and bipolar disorder [1.2.5].
Understanding Mood Stabilizers
Technically, "mood stabilizer" is not an official FDA classification, and even among researchers, there isn't a universally agreed-upon definition [1.2.3]. Generally, these medications are used to treat bipolar disorder and other mood disorders by preventing both manic and depressive episodes. The most well-known mood stabilizer is lithium [1.2.3]. Other medications used to manage mood swings in bipolar disorder include anticonvulsants like valproic acid and lamotrigine, and antipsychotics [1.2.1]. A key characteristic of a true mood stabilizer is its ability to treat acute mood episodes without worsening other aspects of the illness and to prevent future episodes.
Is Gabapentin an Effective Mood Stabilizer for Bipolar Disorder?
The consensus from robust clinical research is that gabapentin is not an effective mood stabilizer for bipolar disorder [1.2.1, 1.3.1]. Multiple randomized controlled trials have shown that gabapentin is no more effective than a placebo in treating either mania or depression associated with bipolar disorder, whether used as a monotherapy or as an add-on treatment [1.2.1, 1.2.2]. In some studies, it was even found to be inferior to a placebo [1.2.1].
This widespread off-label use for bipolar disorder was fueled in the 1990s by a misleading and illegal marketing campaign by its original manufacturer, which promoted the drug for unapproved uses without sufficient scientific backing [1.2.1, 1.3.4]. This led to a $430 million settlement in 2004 [1.2.8]. Major health organizations, including the American Psychological Association, have since stated that gabapentin is "largely discredited as a mood stabilizer for bipolar disorder" [1.2.1].
What About for Anxiety?
The evidence for gabapentin's use in anxiety disorders is more mixed but shows some potential benefits [1.3.1]. Research suggests gabapentin may be effective for certain specific anxiety conditions:
- Social Phobia: A 14-week study found gabapentin to be superior to a placebo in treating symptoms of social phobia [1.2.2, 1.3.1].
- Preoperative Anxiety: Several studies have shown that a single dose of gabapentin (often 1,200 mg) can effectively reduce anxiety before surgery [1.2.2, 1.3.1].
- Panic Disorder: Evidence here is weaker, with one controlled trial finding no significant difference between gabapentin and a placebo, although a subset of patients with more severe symptoms did see some benefit [1.2.2].
There is currently no clear evidence supporting gabapentin's use for Generalized Anxiety Disorder (GAD) or Obsessive-Compulsive Disorder (OCD) [1.2.2, 1.3.1].
Mechanism of Action: How Does Gabapentin Affect Mood?
Gabapentin's exact mechanism of action is not fully understood [1.4.2]. Although it is structurally similar to the neurotransmitter GABA (gamma-aminobutyric acid), it does not bind to GABA receptors [1.4.3]. Instead, its primary action is believed to be binding to the α2δ-1 subunit of voltage-gated calcium channels in the brain [1.4.3, 1.4.7]. This action appears to inhibit the release of excitatory neurotransmitters like glutamate, which can decrease abnormal excitement in the brain [1.2.3, 1.4.8]. This mechanism is thought to contribute to its anticonvulsant and pain-relieving effects [1.4.5]. Its potential effects on mood may be related to this modulation of neurotransmitter release, but the specific pathways remain unclear [1.4.5]. Some research also suggests it may influence the dopamine system, which is involved in mood and reward [1.4.1].
Comparison: Gabapentin vs. Traditional Mood Stabilizers
When compared directly to established mood stabilizers, gabapentin falls short, particularly for bipolar disorder.
| Feature | Gabapentin | Traditional Mood Stabilizers (e.g., Lithium, Valproate) |
|---|---|---|
| Primary Class | Anticonvulsant [1.2.3] | Bipolar Disorder Agents (Lithium), Anticonvulsants (Valproate) [1.2.3] |
| Mechanism | Binds to α2δ-1 subunit of voltage-gated calcium channels, modulating neurotransmitter release [1.4.3]. | Complex and varied; Lithium affects intracellular signaling pathways; Valproate increases GABA levels [1.2.3]. |
| Efficacy for Bipolar | Ineffective; not superior to placebo in multiple controlled trials [1.2.1, 1.2.2]. | Proven efficacy for treating acute mania and preventing mood episode recurrence [1.2.1]. |
| Efficacy for Anxiety | Some evidence for social phobia and preoperative anxiety [1.2.2]. | Often used to treat anxiety comorbid with bipolar disorder, but not a primary anxiolytic. |
| Common Side Effects | Drowsiness, dizziness, fatigue, unsteadiness, weight gain [1.6.1, 1.6.2]. | Nausea, tremor, weight gain (Lithium); stomach upset, weight gain, liver issues (Valproate). |
| Monitoring | Dose adjustment needed for kidney problems [1.6.5]. | Requires regular blood tests to monitor drug levels and check for thyroid and kidney function (Lithium) or liver function (Valproate). |
Risks and Side Effects
Gabapentin is associated with a range of side effects. Common ones include drowsiness, dizziness, fatigue, headache, and unsteadiness [1.6.1]. More serious risks, though less common, can occur.
Key Considerations:
- Mental Health Changes: A small number of users may experience unusual changes in mood or behavior, including new or worsening depression and suicidal thoughts [1.6.1, 1.6.3].
- Respiratory Depression: The FDA has issued a warning that serious breathing problems can occur when gabapentin is taken with other central nervous system depressants like opioids, especially in older adults or those with lung conditions like COPD [1.6.3].
- Withdrawal Symptoms: Suddenly stopping gabapentin can lead to withdrawal symptoms such as anxiety, insomnia, nausea, pain, and sweating [1.6.1]. It is crucial to taper off the medication under a doctor's supervision.
- Potential for Misuse: There is growing concern about the misuse and abuse of gabapentin, particularly in combination with opioids, as it can enhance euphoric effects [1.4.8, 1.7.6].
Conclusion
While gabapentin is a widely prescribed medication, the evidence does not support its use as a primary mood stabilizer for conditions like bipolar disorder [1.2.1, 1.3.2]. High-quality clinical trials have consistently failed to show its efficacy over a placebo for treating manic or depressive episodes [1.2.2]. Its history is marked by illegal off-label promotion that created a lasting misconception about its role in mood stabilization [1.3.4]. Gabapentin does show some limited, anxiolytic properties for specific situations like social phobia and pre-operative anxiety [1.3.1]. However, it is not a first-line treatment for mood disorders. Patients should be aware of its potential side effects, including the risk of mood changes and serious breathing problems when combined with other depressants [1.6.3].
For more information from an authoritative source, you can visit the National Institutes of Health's MedlinePlus page on Gabapentin. [1.6.1]
