Gabapentin and Pregabalin in Psychiatry: Evidence and Risks

Gabapentin and pregabalin, often grouped as gabapentinoids, are FDA-approved in the US for seizures and nerve pain (and, for pregabalin, fibromyalgia), not for any psychiatric condition, so their use for anxiety, alcohol use disorder or sleep is off-label. Pregabalin is approved for generalized anxiety disorder in the European Union, and a 2022 meta-analysis found moderate evidence that gabapentinoids help in anxiety states but minimal evidence in bipolar disorder and insomnia.

The risks are real and often underestimated. In 2019 the FDA warned that both drugs can cause serious breathing problems in people who also take opioids or other sedating drugs, who have lung disease such as COPD, or who are older. Pregabalin is a Schedule V controlled substance, and misuse of both has been reported. Whether either belongs in your treatment is a decision to make with a prescriber who knows your full medication list and history.

Gabapentin and pregabalin at a glance

How they work, briefly

Both drugs bind to the alpha-2-delta subunit of voltage-gated calcium channels in nerve cells. The European Medicines Agency describes pregabalin as thought to affect the way calcium enters nerve cells, which reduces the release of other neurotransmitters involved in pain, epilepsy and anxiety, though the exact mechanism is not fully understood. Gabapentin does not bind to benzodiazepine, opioid or cannabinoid receptors, according to its label. Even so, misuse has been reported after marketing, and in 2019 the FDA required manufacturers to study the drugs' abuse potential.

The evidence, use by use

Generalized anxiety disorder

Pregabalin has the strongest anxiety evidence of the two. The European Medicines Agency approved it for generalized anxiety disorder based on eight studies involving more than 3,000 patients, measured after four to eight weeks. A 2017 meta-analysis of eight randomized trials with 2,299 participants found pregabalin superior to placebo, with a modest effect size and dropout rates no higher than placebo. The same review reported that pregabalin was comparable to benzodiazepines in clinical response, with lower dropout rates than benzodiazepines. In the UK, NICE suggests considering pregabalin for GAD when a person cannot tolerate SSRIs or SNRIs, not as a first choice.

None of that makes pregabalin FDA-approved for anxiety in the United States; it remains off-label here. For most people with GAD, guidelines start with CBT or an SSRI or SNRI; see buspirone vs SSRIs for anxiety and anxiety treatment options compared.

Other anxiety states

Gabapentin's anxiety evidence is thinner. A 14-week placebo-controlled trial in 69 people with social phobia found a significant reduction in symptoms, and the authors called for further studies to confirm it. The 2022 meta-analysis found a consistent but not universal benefit across the anxiety spectrum, with both drugs notably more effective than placebo for anxiety before surgery.

Alcohol use disorder

Three medications, naltrexone, acamprosate and disulfiram, are approved in the United States for alcohol use disorder; gabapentin is not among them, so its use here is off-label. A 12-week randomized trial of 150 adults found that gabapentin, particularly at the higher dose studied, improved rates of abstinence and of no heavy drinking compared with placebo, along with sleep, mood and craving. A larger 2023 systematic review and meta-analysis of trials lasting at least 12 weeks, however, concluded that the evidence supports oral naltrexone and acamprosate, not gabapentin, as first-line medicines. The full comparison is in medications for alcohol use disorder compared.

Bipolar disorder and insomnia

The 2022 meta-analysis found only four double-blind trials of gabapentin and none of pregabalin in bipolar disorder, too varied to combine, and inconclusive results in insomnia. Its authors concluded that gabapentinoids should be used for these disorders only with strong justification. For proven bipolar options, see bipolar disorder medications compared. If sleep is the main complaint, options built for insomnia are compared in sleep medications compared.

Evidence summary

How the two differ from each other

The drugs are related but not identical, and the differences can matter when a prescriber chooses between them.

Breathing problems: the 2019 FDA warning

In December 2019 the FDA warned that gabapentin and pregabalin can cause serious breathing difficulties in people with respiratory risk factors, including use of opioid pain medicines and other drugs that depress the central nervous system, and conditions such as COPD that reduce lung function. The agency said the elderly are also at higher risk, required new respiratory depression warnings in the labels, and asked manufacturers to study abuse potential, particularly with opioids, because misuse of the combination was increasing.

The FDA tells patients and caregivers to seek medical attention immediately for confusion, unusual dizziness, extreme sleepiness, slowed, shallow or difficult breathing, unresponsiveness, or bluish skin on the lips, fingers or toes. The FDA also asks patients to tell their clinicians about every medicine they take, including over-the-counter products, and about alcohol. The American Geriatrics Society's Beers Criteria advise older adults to avoid combining opioids with gabapentin or pregabalin, except when transitioning from opioids or using them to reduce an opioid dose, and to avoid using three or more central nervous system-active drugs together because of fall and fracture risk.

Misuse, dependence and withdrawal

Pregabalin is a Schedule V controlled substance. In a study of recreational sedative users, a single dose of pregabalin produced ratings of "high" and "liking" similar to diazepam, and in controlled trials of more than 5,500 patients, 4% reported euphoria on pregabalin compared with 1% on placebo. Gabapentin is not federally controlled, but the label reports misuse and abuse after marketing, mostly in people with a history of polysubstance use, sometimes at higher than recommended doses for unapproved uses.

Both can cause withdrawal. The gabapentin label says withdrawal symptoms have occurred after short- and long-term use, usually within 48 hours of stopping. After abrupt or rapid discontinuation of pregabalin, some patients in trials reported insomnia, nausea, headache or diarrhea, and post-marketing reports include seizures, depression, suicidal thoughts and agitation; the label calls for tapering over at least one week. Abrupt stopping can also increase seizure risk. Do not stop either drug suddenly; ask your prescriber for a plan.

Like other antiseizure drugs, both carry a warning about suicidal thoughts and behavior, and prescribers are asked to monitor for them.

If you are thinking about suicide or are in crisis, call or text 988 (the 988 Suicide & Crisis Lifeline) or go to the nearest emergency room.

For anyone with a history of substance use, the decision deserves extra care. The addiction psychiatrist vs general psychiatrist guide covers when specialized help makes sense, and the practice's page on substance use disorders describes its general approach.

Everyday side effects

• Sleepiness and dizziness are labeled for both and can impair driving; the gabapentin label warns not to drive until you know how it affects you.
• Pregabalin can cause weight gain: in trials of up to 14 weeks, 9% of patients gained 7% or more of their body weight, compared with 2% on placebo.
• Pregabalin can cause swelling of the hands, legs and feet, and the label urges caution when combined with certain diabetes drugs.
• Serious allergic reactions are possible: angioedema with pregabalin and a multiorgan reaction called DRESS with gabapentin.
• Kidney function matters: the Beers Criteria call for reduced doses of both in older adults with reduced kidney function.

Weight change across psychiatric medicines is reviewed on the practice's page about psychiatric medications and weight.

If you already take one of them

• Keep an up-to-date list of every medicine, including opioids, sleep aids and over-the-counter products, and share it with each prescriber.
• Do not stop suddenly; withdrawal symptoms and, in people with epilepsy, seizures can follow abrupt discontinuation.
• Avoid alcohol unless your prescriber has said otherwise, because it adds to sedation and breathing risk; see psychiatric medications and alcohol.
• Ask whether your kidney function has been checked recently, since reduced kidney function calls for lower doses.
• Report new or worsening depression, unusual mood changes or thoughts of self-harm to your prescriber promptly.
• Store the medicine securely, particularly pregabalin, which is a controlled substance.

Common mistakes

• Assuming that because gabapentin is "not a controlled substance," it cannot be misused or cause withdrawal.
• Adding gabapentin to an opioid or benzodiazepine regimen without every prescriber knowing.
• Treating an EU approval for anxiety as proof the drug is a first-line choice in the US.
• Using a gabapentinoid for sleep without a full insomnia assessment, despite inconclusive evidence; see insomnia treatment options compared.
• Continuing it for years without a periodic review of whether it still helps.

When a prescriber might reasonably consider one

These are situations where the trade-off is sometimes judged worthwhile, not recommendations:

• GAD that has not responded to, or could not tolerate, SSRIs and SNRIs, which is where NICE places pregabalin.
• Anxiety alongside a condition for which the drug is FDA-approved, such as fibromyalgia or diabetic nerve pain with pregabalin, so one medicine addresses both.
• Alcohol use disorder when naltrexone and acamprosate are unsuitable, recognizing the mixed evidence.

And situations that usually weigh against them: taking opioids, benzodiazepines or other sedatives; COPD or other lung disease; older age with falls; a history of misusing prescription drugs; or kidney disease without dose adjustment.

What the evidence does not tell you

• Most anxiety trials are short, so long-term benefit and the balance against dependence are less clear.
• Gabapentin's psychiatric evidence relies on few and small trials.
• An EU approval does not mean the FDA reviewed and accepted the same evidence for US use.
• No study predicts who will develop misuse or withdrawal problems.

Questions to ask your prescriber

• Is this an FDA-approved use for me, or off-label, and why this medicine over the standard options?
• What are we treating, and how will we know within a few weeks whether it is helping?
• How does it interact with my other medicines, especially opioids, sleep aids or anxiety medicines?
• Do my kidney function or age change the dose?
• What withdrawal symptoms should I expect if we stop, and how slowly will we taper?
• Given my history, what is my risk of misuse, and how will we watch for it?

If you are already taking one of these and are unsure why, a structured review can help; see getting a second opinion on your psychiatric medication.

How this practice approaches off-label prescribing

Ongoing care at the practice includes psychiatric evaluation and medication management, psychotherapy including CBT and DBT, lab testing, and nutrition and lifestyle psychiatry. The team includes psychiatrists and psychiatric nurse practitioners alongside psychotherapists, so medication questions can be weighed with non-drug options. You can read about medication management at the practice, and individual care starts with the Patient Interest Form. More decision guides are in Choosing Psychiatric Care.

Frequently asked questions

Is gabapentin FDA-approved for anxiety?

No. In the US, gabapentin is approved for postherpetic neuralgia and as add-on treatment for partial-onset seizures. Its use for anxiety is off-label.

Is pregabalin approved for anxiety anywhere?

Yes. The European Medicines Agency has approved pregabalin for generalized anxiety disorder in adults. It is not FDA-approved for anxiety in the United States.

Is gabapentin a controlled substance?

Not under federal law; its label says it is not a controlled substance. Pregabalin is federally Schedule V. Misuse of both has been reported.

Can I take gabapentin with an opioid or a benzodiazepine?

Only if your prescribers know and agree. The FDA warned in 2019 that combining gabapentinoids with opioids or other sedating drugs can cause serious breathing problems.

Will I have withdrawal if I stop gabapentin?

You might. The label reports withdrawal symptoms, usually within 48 hours of stopping, after both short- and long-term use. A gradual taper planned with your prescriber lowers the risk.

Does pregabalin cause weight gain?

It can. In trials of up to 14 weeks, about 9% of people on pregabalin gained at least 7% of their body weight, compared with 2% on placebo.

Is gabapentin a good treatment for alcohol use disorder?

It is an off-label option with mixed evidence. One trial was positive, but a 2023 systematic review supported naltrexone and acamprosate, not gabapentin, as first-line medicines.

Sources

1. NEURONTIN (gabapentin) prescribing information. DailyMed / U.S. FDA label (Viatris), 2026. dailymed.nlm.nih.gov
2. LYRICA (pregabalin) prescribing information. DailyMed / U.S. FDA label (Viatris), 2025. dailymed.nlm.nih.gov
3. Neurontin, Gralise, Horizant (gabapentin) and Lyrica, Lyrica CR (pregabalin): Drug Safety Communication - Serious Breathing Problems. U.S. Food and Drug Administration, 2019. fda.gov
4. Lyrica: EPAR - Medicine overview. European Medicines Agency, 2023. ema.europa.eu
5. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Molecular Psychiatry (PubMed 34819636), 2022. pubmed.ncbi.nlm.nih.gov
6. Pregabalin for generalized anxiety disorder: an updated systematic review and meta-analysis. International Clinical Psychopharmacology (PubMed 27643884), 2017. pubmed.ncbi.nlm.nih.gov
7. Generalised anxiety disorder and panic disorder in adults: management (CG113), Recommendations. National Institute for Health and Care Excellence (NICE), 2011, updated 2022. nice.org.uk
8. Treatment of social phobia with gabapentin: a placebo-controlled study. Journal of Clinical Psychopharmacology (PubMed 10440462), 1999. pubmed.ncbi.nlm.nih.gov
9. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Internal Medicine (PubMed 24190578), 2014. pubmed.ncbi.nlm.nih.gov
10. Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis. JAMA (PMC10630900), 2023. pmc.ncbi.nlm.nih.gov
11. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society (PMC12478568), 2023. pmc.ncbi.nlm.nih.gov
12. Treatment for Alcohol Problems: Finding and Getting Help. National Institute on Alcohol Abuse and Alcoholism (NIH), 2025. niaaa.nih.gov

Educational information, not medical, tax or legal advice. Decisions about diagnosis, medication and treatment belong with a clinician who knows your history.