Gabapentin is a drug that was approved by the FDA in 1993 as an adjunct treatment for epileptic seizures. It has since attained approval for the treatment of partial seizures in adults and children. In addition to its mechanism as an antiepileptic drug, Gabapentin functions as an analgesic, and was approved in 2004 for the treatment of neuropathic pain.
Despite its approved uses as an antiepileptic and analgesic, it is commonly prescribed off-label for a variety of conditions. In fact, some sources hypothesize that nearly 90% of Gabapentin prescriptions are off-label. In 2004, Pfizer (manufacturer of Gabapentin) settled for $430 million in a lawsuit regarding aggressive marketing of the drug for off-label purposes.
Regardless of the settlement outcome, Gabapentin (brand name “Neurontin”) is still commonly prescribed for a variety of off-label conditions including: fibromyalgia, chronic pain, bipolar disorder, alcohol withdrawal, and migraine headaches. Perhaps one of the more promising off-label uses for Gabapentin is for the treatment of anxiety disorders. There is mounting evidence that Gabapentin may be an effective intervention for various types of anxiety including: generalized anxiety disorder, social anxiety disorder, and panic disorder.
Gabapentin for Anxiety Disorders: The Research
There is considerable research documenting the efficacy and safety of Gabapentin for anxiety disorders. Research and interest in Gabapentin began in the 1990s for anxiety disorders due to its unique GABAergic mechanism of action. Nearly every published study has found Gabapentin to be superior in efficacy for the reduction of anxiety when compared to a placebo.
1999: Gabapentin has been researched since the 1990s for its effect as an anxiolytic agent. A randomized, placebo-controlled, double-blind study was conducted to determine the safety and efficacy of Gabapentin among individuals diagnosed with social anxiety disorder. A total of 69 participants were divided into two groups: one received Gabapentin (900 mg to 3600 mg daily) and the other received a placebo.
The study was conducted over a period of 14 weeks. Researchers noted that social anxiety levels plummeted among those taking the Gabapentin compared to the placebo. Social anxiety levels were interpreted by physician evaluations and patient rating scales. Side effects were more prevalent among those receiving the Gabapentin compared to the placebo – including dizziness, dry mouth, and nausea.
Authors of the study suggest that based on the limited data, Gabapentin has a favorable risk-benefit ratio for the treatment of social anxiety disorder. Even in the 1990s, there was notable evidence to suggest that Gabapentin may be a favorable intervention for anxiety – particularly social subtypes.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10440462
2002: In one study analyzing the efficacy of Gabapentin as an adjunct treatment for bipolar disorder, it was discovered that improvements were most notable on anxiety-somatization measures of the Hamilton Rating Scale for Depression (HAM-D). Results of the study suggest that those with bipolar disorder who attained the most benefit from Gabapentin had either comorbid panic disorders and/or a history of alcohol abuse.
This highlights the fact that Gabapentin may provide most relief to individuals with bipolar disorder that have comorbid anxiety. In addition to acting as an anxiolytic agent, Gabapentin may also improve mood via antidepressant mechanisms. The dosage of Gabapentin administered in this study ranged from 600 mg to 2400 mg.
It is difficult to draw generalized conclusions from the results of this study, but the outcome indicates that Gabapentin may be effective among individuals with panic disorder. Though the drug hasn’t been tested specifically for the treatment of panic disorder, additional research may be warranted.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12454558
2003: Many people experience significant anxiety during public speaking. For this reason, researchers decided to test the effect of Gabapentin on anxiety triggered by public speaking tasks. A total of 32 men between the ages of 17 and 30 participated in the study.
Researchers used a simulated public speaking (SPS) task to evaluate both level of anxiety and mood of the participants. The Visual Analogue Mood Scale (VAMS) and Profile of Mood State (POMS) were self-evaluated during the simulated public speaking (SPS) task. Secondary recordings of physiological arousal were documented in the form of heart rate and blood pressure.
Participants took either 400 mg Gabapentin or 800 mg Gabapentin. Researchers noted that those taking 800 mg experienced significant reductions on the VAMS scale. Individuals taking Gabapentin at both 400 mg and 800 mg experienced significant reductions in hostility ratings as measured by the POMS scale.
Results from this study provide additional evidence to support the anxiolytic effects of Gabapentin. Those prone to anxiety associated with public speaking tend to experience notable reductions when taking Gabapentin. The reduction in anxiety associated with public speaking may also have carryover effects for individuals with anxiety in social situations.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12870565
2005: Due to the fact that Gabapentin has both analgesic and anxiolytic properties, researchers hypothesized that administration of Gabapentin prior to a surgical procedure would reduce anxiety and provide post-surgery pain relief. To test their hypothesis, they recruited 40 patients scheduled for arthroscopic knee surgery. Of these 40 patients, they were randomly assigned to receive Gabapentin (1200 mg) or a placebo.
The administration of either Gabapentin or the placebo occurred approximately 2 hours before surgery. Results suggested that anxiety scores prior to operation (preoperative anxiety) were significantly lower among those administered Gabapentin compared to the placebo group. Furthermore, those receiving Gabapentin required less post-surgical morphine than the placebo group.
Authors concluded that administration of Gabapentin can mitigate preoperative anxiety and provide postoperative pain relief. This highlights the fact that Gabapentin may be an optimal drug for the reduction of both anxiety and pain associated with knee surgery.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15845693
2008: Another study conducted analyzed the effects of Gabapentin, morphine, and diazepam on a rodent model of HIV. Researchers conducted this study due to the fact that neuropathy is commonly associated with anti-retroviral therapy. In addition, anti-retroviral therapy is thought to potentially trigger anxiety-like behavior.
To get a better understanding of how various pharmaceutical agents affect neuropathic pain and comorbid anxiety-like behavior, they tested: 30 mg/kg Gabapentin and 2.5 mg/kg morphine compared to diazepam 1 mg/kg. The effect of Gabapentin and morphine wasn’t significantly different from diazepam. All interventions significantly reduced anxiety-like behavior in HIV model rodents.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706951/
2009: From 2005 to 2007, researchers at Eastern Virginia Medical School decided to test the efficacy of Gabapentin and Tiagabine for the treatment of social anxiety. Researchers decided it would be beneficial to document the safety and efficacy due to the fact that many patients with social anxiety don’t respond well to traditional treatment options (e.g. SSRIs). Gabapentin functions different than SSRIs in that it elicits GABAergic effects as opposed to serotonergic.
To test the efficacy of Gabapentin and Tiagabine for the treatment of social anxiety disorder, researchers recruited 8 adult participants (21 to 39 years old). All participants had been diagnosed with social anxiety disorder in accordance to DSM-IV criteria and had scores exceeding 30 on the Liebowitz Social Anxiety Scale (LSAS). The study was considered double-blind and randomized.
At the beginning of the study, participants were assigned to receive Gabapentin (1800 mg) or Tiabagine (2400 mg). All participants were titrated up to the aforementioned doses over a period of 2 weeks. At various 2-week intervals, anxiety levels were assessed among the patients with the Liebowitz Social Anxiety Scale (LSAS).
Results suggested that both Gabapentin and Tiagabine significantly reduced social anxiety according to the Liebowitz Social Anxiety Scale measures. Two of the subjects achieved complete remission and four reported substantial reductions in anxiety. Side effects associated with either treatment were considered minimal.
Although this was a very small-scale study, it provides additional evidence highlighting the efficacy of Gabapentin for social anxiety. Researchers also noted that both Gabapentin and Tiagabine may have favorable side effect profiles over traditional first-line options like SSRIs and benzodiazepines.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708011/
2012: To better understand the effects of Gabapentin on anxiety, amnesia, and sedation – researchers set up a randomized, placebo-controlled study. They hypothesized that administration of Gabapentin (1200 mg) prior to surgery (2 to 3 hours) would reduce preoperative anxiety. Their secondary hypothesis was that administration of Gabapentin would yield sedation, without memory impairment.
A total of 64 surgical patients were included in the study, 32 of whom were assigned to receive Gabapentin (1200 mg) and the other 32 of whom were given a placebo. Measures of anxiety, sedation, and amnesia were measured prior to medication, 2 hours after administration, and following their surgery. These were collected with the following respective scales: Spielberger State-Trait Anxiety Inventory (STAI), Visual Analogue Scale Anxiety (VAS), and Snodgrass and Vanderwart.
The results of the study suggested significant reductions in anxiety among those receiving Gabapentin compared to the placebo – specifically on the State-Trait Anxiety Inventory. No differences were reported between those receiving Gabapentin and those receiving a placebo in terms of sedation and memory. Authors concluded that Gabapentin at 1200 mg can significantly reduce anxiety without impairing memory and/or causing significant sedation.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22770920
2012: A publication from 2012 acknowledged that Gabapentin is commonly used as an off-label treatment for anxiety disorders. However, they noted that there wasn’t sufficient clinical evidence to support the off-label usage of Gabapentin for anxiety. To get a better idea of Gabapentin’s efficacy in terms of treating anxiety, researchers set up a randomized, double-blind, placebo-controlled trial.
This trial was conducted with 420 breast cancer patients that had completed chemotherapy. The group of 420 participants were randomly assigned to one of three groups that received: 300 mg Gabapentin, 900 mg Gabapentin, or a placebo. Prior to the study, their anxiety (“trait” and “state”) were measured via the Spielberger State-Trait Anxiety Inventory (SSTAI).
Measures of both “state” and “trait” anxiety were collected after 4 weeks of treatment, and after 8 weeks of treatment. Results of the study suggested that those receiving Gabapentin, regardless of whether the dosage was 300 mg or 900 mg, had significantly reduced “state” anxiety scores compared to the placebo group. This significant reduction in “state” anxiety was noted after 4 weeks and maintained throughout 8 weeks.
Researchers did note that those receiving the 300 mg (lower dose) had better treatment outcomes for most participants, except among individuals with high baseline levels of anxiety. Authors of this study concluded that Gabapentin may be considered an effective alternative therapeutic agent to traditional benzodiazepines for the treatment of anxiety among breast cancer survivors.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23053645
2013: A study published in 2013 compared the efficacy of Gabapentin and melatonin on measures of: anxiety, pain, sedation, and surgeon satisfaction following cataract surgery. A total of 130 individuals were included in the study and ranged from 35 to 85 years of age. All had planned on receiving cataract surgery, and researchers assigned the patients to receive either: Gabapentin (600 mg), Melatonin (6 mg), or a placebo.
These were administered approximately 90 minutes before the patient was relocated to the operating room. Upon administration, ratings of anxiety, pain, and sedation were recorded – as was the surgeon’s satisfaction with the surgery. Results indicated significantly reduced levels of anxiety among those receiving the Gabapentin (600 mg) or the Melatonin (6 mg) compared to the placebo.
Upon comparison of Gabapentin (600 mg) to the Melatonin (6 mg) – there was no significant difference in anxiety reduction. Gabapentin was also found superior to the other two options in reducing pain scores. Both Gabapentin and Melatonin were superior to the placebo in strength of sedation. There was no difference between the three groups in terms of surgical satisfaction as reported by the surgeon.
Researchers highlighted the fact that the anxiolytic effects of both Gabapentin and Melatonin were significant when compared to a placebo. This provides some evidence to suggest that Gabapentin may be an effective off-label anxiolytic option, especially among those scheduled for surgery.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24347765
2013: By 2010, Gabapentin had become a fairly popular off-label treatment for anxiety disorders. Despite some evidence suggesting its efficacy for anxiety, there was inconclusive evidence in regards to Gabapentin’s effect for the reduction of preoperative anxiety. The preoperative subtype of anxiety is associated with feeling uneasiness and dread prior to a surgical operation.
To get a better understanding of whether Gabapentin was effective for preoperative anxiety, researchers compared Gabapentin (1200 mg) to that of a placebo among individuals with moderate or high levels of preoperative anxiety. The study was carried out from 2009 to 2011 at a hospital with 50 female patients; 25 were assigned to the Gabapentin and the other 25 were assigned to receive the placebo.
Anxiety levels were recorded at baseline using various scales including: Spielberger State-Trait Anxiety Inventory (SSTAI), the Pain Catastrophizing Scale (PCS), Pain Anxiety Symptoms Scale (PASS), and the Richmond Agitation-Sedation Scale (RASS). Approximately 2 hours following administration of either Gabapentin (1200 mg) or the placebo, patients rated their anxiety, pain, and sedation. The new ratings were then recorded and compared to those attained at the baseline.
Results demonstrated that the 25 patients receiving Gabapentin (1200 mg) experienced significant reductions in preoperative anxiety, pain, and catastrophizing compared to the placebo. Individuals receiving Gabapentin reported higher levels of sedation than the placebo. Authors concluded that Gabapentin could be an effective pharmaceutical intervention for individuals with high levels of preoperative anxiety and/or catastrophizing.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23377862
Is there any evidence to suggest Gabapentin is ineffective for anxiety?
Due to the fact that Gabapentin hasn’t been extensively studied specifically for the treatment of anxiety, it is difficult to suggest that it is highly-effective. That said, most studies analyzing the anxiolytic properties of Gabapentin have noted that they are significant when compared to a placebo. The majority of research analyzing Gabapentin’s effect on anxiety is unfocused (in terms of anxiety-subtypes) and small-scale.
2010: Of all the published research available, there appears to be one study that found Gabapentin ineffective for reducing preoperative anxiety among individuals scheduled to undergo a surgical procedure. In this case, the surgical procedure was that of a total hip arthroplasty or replacement of the hip joint with an artificial prosthesis.
In the study, 22 patients received Gabapentin (600 mg) and the remaining 48 received a placebo. Both were administered approximately 2 hours before pre-surgical anesthesia. Anxiety was measured at baseline, prior to surgery, and post-surgery using a Visual Analogue Scale (VAS). Results indicated that anxiety scores weren’t significantly different between those receiving Gabapentin and those receiving the placebo.
Researchers concluded that 600 mg of Gabapentin is ineffective for reducing preoperative anxiety. This study is contradictory to the findings of other studies that have found Gabapentin effective for reducing preoperative anxiety. However, most other studies utilize other measurements for anxiety (in addition to the Visual Analogue Scale) and have utilized varying dosages of Gabapentin.
Significant contradictory evidence is apparent in a 2012 study of 130 adults undergoing surgery. In the newer study (with a larger sample size), Gabapentin was effective at the same dosage of 600 mg in reducing preoperative anxiety. Perhaps this study was too small-scale, limited in terms of anxiety measurement scales, and/or maybe the type of surgical procedure influenced the outcomes. In any regard, this study is an outlier in terms of its finding that Gabapentin failed to reduce anxiety.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20353411
How Gabapentin May Help Anxiety (Mechanism of Action)
The mechanism by which Gabapentin elicits an anxiolytic effect is not fully understood. It is considered structurally similar to the neurotransmitter GABA. The neurotransmitter GABA is known to produce a calming effect and relieve anxiety; this effect is apparent among those who use benzodiazepines and other drugs that target GABA. By comparison, Gabapentin does not actually bind to GABA receptors.
Instead, Gabapentin is thought to regulate glutamate decarboxylase and branched chain aminotransferase. Both glutamate decarboxylase and branched chain aminotransferase are enzymes aiding in the synthesis of GABA. Research suggests that Gabapentin is capable of increasing synthesis of GABA, which may explain its anxiolytic properties.
Among individuals with psychiatric conditions and comorbid anxiety, alcohol dependence, and/or insomnia, Gabapentin has been suggested to provide relief as a result of anxiolytic properties. These anxiolytic effects have been noted as similar in respect to diazepam (Valium), a popular benzodiazepine.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9686247
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9561320
Advantages of Using Gabapentin for Anxiety
There may be some advantages associated with using Gabapentin for anxiety over other medications. The most notable advantage is that Gabapentin has a different mechanism of action compared to standard first-line treatments of anxiety such as serotonergic antidepressants.
- Adjunct treatment: Gabapentin may be helpful for some individuals as an adjunct treatment. It is commonly used as an adjunct anticonvulsant and may be an effective adjunct to an antidepressant for the treatment of anxiety. Further investigation is warranted, but due to its unique mechanism of action, it may have synergistic effects when used with other meds.
- Alternative mechanism of action: Let’s face it, not everyone responds to traditional anxiolytic interventions for the treatment of anxiety. Traditional interventions include antidepressants and benzodiazepines. Those that don’t respond well to first-line treatments in terms of symptomatic reduction and tolerability may want to consider Gabapentin. Gabapentin is thought to function by increasing GABA synthesis by regulating enzymes.
- Anxiety reduction: Most studies suggest that Gabapentin is an effective treatment for anxiety. Although it hasn’t been formally approved by the FDA, nearly every study analyzing its anxiolytic effect has found some degree of benefit. In addition, it appears to be effective in treating a variety of different anxiety subtypes.
- Comorbid neuropathic pain: Those with anxiety and comorbid neuropathic pain (or vice-versa) may benefit significantly from Gabapentin. It is clinically approved and considered effective for various types of neuropathic pain, and preliminary evidence suggests that it reduces anxiety. Therefore individuals with anxiety and comorbid neuropathic pain may derive significant benefit from Gabapentin.
- Potential mood boost: There is some evidence to suggest that some people feel less depressed when they take Gabapentin. Although its mechanism of action isn’t well-understood, it may boost mood among those with depression or depressive features.
- Side effects: The side effect profile is considered minimal and may be favorable compared to other anxiolytic medications. Common side effects associated with Gabapentin include: dizziness, coordination problems, eye movements, and tremors. Due to the fact that no weight gain or significant sexual dysfunction is reported – Gabapentin may be preferred over SSRIs.
- Weight neutral: It appears as though Gabapentin is a “weight neutral” drug in that weight gain or loss is uncommon for the majority of users. While weight fluctuations may occur in some individuals, most users will maintain a baseline weight throughout treatment.
Disadvantages of Using Gabapentin for Anxiety
There are also some notable disadvantages associated with using Gabapentin for the treatment of anxiety. The most obvious disadvantage is that there aren’t enough large-scale, targeted studies to suggest Gabapentin is an effective anxiolytic.
- Children / adolescents: Most research of Gabapentin for anxiety has been conducted in adult populations. This means that the drug may not provide the same degree of efficacy among children and adolescents. There may also be a risk associated with the GABAergic mechanisms affecting developing brains of those under the age of 25.
- Limited evidence: There is certainly some evidence to suggest Gabapentin may provide relief from symptoms of anxiety. However, this evidence is limited to relatively small sample sizes. There have not been any long-term, thorough clinical trials analyzing the effect of Gabapentin for specific types of anxiety.
- Long-term effects: The long-term effects associated with Gabapentin are unknown. Despite claims that the drug may be safe when used over a long-term, users should be skeptical of potential permanent memory impairment and/or cognitive impairment as a result of GABAergic effects. Drugs like benzodiazepines are linked to dementia, and Gabapentin is thought to act similarly to Diazepam (Valium).
- Off-label: It is estimated that approximately 9/10 prescriptions for Gabapentin are “off-label” or for conditions that the drug isn’t approved to treat. Off-label prescriptions have a reduce chance of actually working for the treatment of anxiety. This also means that Gabapentin will be tougher to get a prescription for if you solely have anxiety.
- Questionable efficacy: Due to the lack of focused research specifically analyzing Gabapentin’s effect for the treatment of anxiety, its efficacy should be considered questionable. It cannot be universally recommended until more extensive research is conducted with larger sample sizes over a longer duration.
- Unapproved: The FDA has not approved Gabapentin for the treatment of anxiety. Currently the drug is approved for the treatment of epilepsy (as an adjunct) and neuropathic pain. Any usage other than the two approved conditions may not provide relief.
- Withdrawal: Most medical professionals consider Gabapentin withdrawal symptoms to be relatively minor or nonexistent. Little do they know that the discontinuation effects can be debilitating and protracted – lasting for a long-term. The withdrawal should not be taken lightly, some people claim that discontinuation of Gabapentin is as severe as nearly any other neurochemistry-altering drug.
Optimal Usage of Gabapentin for Anxiety: Who is most likely to benefit?
Certain individuals may get more benefit out of using Gabapentin for their anxiety than others. Not everyone with anxiety is going to find Gabapentin therapeutic; many individuals report experiencing no significant change in their level of anxiety as a result of treatment.
- Anxiety subtypes: Certain anxiety subtypes may react better to Gabapentin than others. Particularly cases of anxiety that are caused or influenced by neuropathic pain may respond better to Gabapentin. Additionally, anxious subtypes stemming from GABAergic dysfunction may stand to benefit more from this drug since it regulates GABA synthesis.
- Depression: While Gabapentin is not an antidepressant, there is subtle evidence suggesting that it may improve mood. It may be especially helpful at stabilizing mood as an adjunct when prescribed for bipolar disorder. Some studies suggest that the mood-boosting effect derived from Gabapentin for bipolar depression is a result of treating anxiety and altering GABAergic neurotransmission.
- Drug withdrawal: In select cases, this drug may be prescribed to help combat anxiety and other symptoms of drug or alcohol withdrawal. Many of the symptoms associated with alcohol withdrawal result from dysfunction in GABAergic neurotransmission. Some speculate that temporary usage of Gabapentin can ease difficult discontinuation from other drugs.
- Epilepsy: Those with epileptic seizures may get prescribed Gabapentin as an adjunct treatment. Should an individual with epilepsy also suffer from anxiety, they may find that this drug provides them with some additional relief – helping them stay calm.
- Hot flashes: Another fairly common off-label condition that may benefit from Gabapentin is that of hot flashes. Hot flashes are sometimes associated with excess stress and anxiety. Many anecdotal reports have suggested that Gabapentin is effective for the reduction of hot flashes.
- Migraines: The drug has had off-label success as a prescription to target migraine headaches. While it isn’t approved to reduce headaches, many anecdotal reports suggest that it is an effective option. Those with migraines and anxiety or anxiety so bad that migraines ensue, Gabapentin may provide some relief.
- Neuropathic pain: The drug is approved for the treatment of neuropathic pain, and if you have been diagnosed with this condition, it may be prescribed as a first-line treatment. As an added benefit, you may find that it’s also helping to reduce your anxiety. Think of the anxiety reduction as an added benefit of the drug.
- Poor response to first-line treatments: Individuals with refractory cases of anxiety that don’t respond to first-line treatments like antidepressants may end up trying Gabapentin. Due to the fact that it has a mechanism of action that differs from most treatments means that there’s a chance it may provide some relief in a way that another drug cannot.
- Surgery: Those getting surgery may benefit from Gabapentin as a pre-surgical treatment to help decrease preoperative anxiety and reduce post-surgical pain. There is mounting evidence to substantiate claims that Gabapentin is an effective drug to be used on a short-term basis for patients getting surgery.
Have you used Gabapentin for anxiety?
If you have personal experience using Gabapentin, did you notice a significant reduction in anxiety while taking it? Did you specifically take Gabapentin with the intention of treating anxiety or did you take it for an approved condition such as epileptic seizures and/or neuropathic pain? Feel free to share your experience in the comments section below.
To help others get an accurate understanding of your Gabapentin usage, be sure to document the dosage that you took, how long you’ve been taking it, and whether you experience a sustained anxiolytic effect. Understand that the efficacy may be subject to individual variation as well as specific subtype of anxiety (e.g. social, generalized, preoperative, etc.).