Gabapentin for Anxiety: Uses, Dosage, and Side Effects

If you have anxiety, you’re not alone. Anxiety is the most common mental health disorder in the U.S., affecting about 40 million adults every year.

While there are many different types of anxiety disorders, symptoms often include feeling excessively worried or physiologically stressed.

If you’re looking for a way to cope with your anxiety, you may be considering taking gabapentin. It’s known as an anticonvulsant or antiepileptic drug.

Though it is commonly used to treat seizures, it can also help relieve pain and anxiety.

This article will give you all the information you need to know about gabapentin for anxiety, its effects, dosage, and side effects.

What is Gabapentin? 

Gabapentin (Neurontin, Gralise, Horizant) is a medicine used to treat partial seizures, nerve pain from shingles, and restless leg syndrome.

It is a prescription drug that comes as an oral capsule, an immediate-release oral tablet, an extended-release oral tablet, and an oral solution.

How Does Gabapentin Work?

Gabapentin may be used for the treatment of certain seizure disorders or nerve pain.

Research has shown that gabapentin binds strongly to a specific site (called the alpha2-delta site) on voltage-gated calcium channels.

This action is thought to be the mechanism for the way it relieves nerve pain and lowers the risk of seizures. Gabapentin belongs to the group of medicines known as anticonvulsants.

Gabapentin Uses

Gabapentin is used to:

• Prevent and control partial seizures. Gabapentin can be used in adults and children aged 3 and older who have partial seizures.
• Relieve nerve pain following shingles in adults. Shingles is a painful rash that develops many years after you’ve had chickenpox. The virus that causes chickenpox stays dormant in a portion of your spinal nerve root called the dorsal root ganglion. For whatever reason, this otherwise dormant virus gets reactivated — usually by stress — causing a shingles rash. Nerve pain following a case of shingles is called postherpetic neuralgia (PHN).
• Treat moderate-to-severe primary restless legs syndrome.

The branded gabapentin products Neurontin and Gralise are approved for partial seizures and PHN. The branded gabapentin enacarbil product Horizant is approved for restless legs syndrome and PHN.

Gabapentin Dosage

Typically the effective dose of gabapentin for anxiety ranges anywhere from 300 mg daily to 3,600 mg daily, with higher doses generally divided into three smaller doses a day.

Your healthcare provider will help you choose the best dose for you. 

Potential Side Effects

Some common side effects of gabapentin can include:

• Feeling sleepy, tired or dizzy
• Nausea
• Vomiting
• Diarrhea
• Mood changes
• Swollen arms and legs
• Blurred vision
• Dry mouth
• Difficulty getting an erection
• Weight gain
• Memory problems
• Headaches
• Getting more infections than usual

There are also a few serious side effects which include:

• Thoughts of harming or killing yourself
• A high temperature
• Swollen glands that do not go away
• Unusual bruises or bleeding
• Severe tiredness or weakness
• Unexpected muscle pain or weakness, with or without a rash
• Long-lasting stomach pain
• Feeling nauseous, with or without vomiting
• Hallucinations

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to gabapentin.

How Long Does it Take Gabapentin to Work for Anxiety?

Gabapentin may be an effective treatment for anxiety based on several reports.

It may take a few weeks or longer to see benefits from gabapentin for anxiety.

Research shows that gabapentin is typically effective after 4 weeks of treatment, and the benefits continue after 8 weeks of treatment.

Gabapentin Alternatives 

There are a few alternative treatments to gabapentin, including the below:

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants.

They can ease symptoms of moderate to severe anxiety, are relatively safe and typically cause fewer side effects than other types of antidepressants do.

SSRIs approved by Food and Drug Administration (FDA) include:

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac)
• Paroxetine (Paxil, Pexeva)
• Sertraline (Zoloft)

Serotonin-Norepinephrine Reuptake Inhibitors

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that are effective in treating depression.

SNRIs are also sometimes used to treat other conditions, such as anxiety disorders and long-term (chronic) pain, especially nerve pain. They may be helpful if you have chronic pain in addition to depression.

SNRIs approved by Food and Drug Administration (FDA) to treat anxiety include:

• Duloxetine (Cymbalta)
• Venlafaxine (Effexor XR)

Other Anxiety Treatment Options 

Other anxiety treatment options include the following: 

Therapy

If you have anxiety, you may benefit from psychotherapy (a type of counseling).

Cognitive-behavioral therapy (CBT) is a type of psychotherapy that can be effective for treating anxiety.

During CBT, you work with a therapist to decrease triggers of anxiety, work with unhelpful behaviors and thoughts that have a negative impact on your life, and learn healthy coping strategies.

CBT can take place in individual therapy sessions or in group therapy.

Some people find that alternative treatments, such as acupuncture, massage therapy, or aromatherapy, help ease their anxiety.

Lifestyle Changes

Making lifestyle changes can also help ease anxiety.

Some lifestyle changes that may help include:

• Exercising regularly
• Eating a healthy diet
• Getting enough sleep
• Limiting alcohol intake
• Avoiding caffeine
• Practicing relaxation techniques, such as yoga, meditation, or deep breathing
• Joining support groups

Self-Care

Self-care is important because it can help improve your mood, mental health, and overall well-being.

It doesn’t have to be expensive or time-consuming.

There are plenty of simple things you can do every day to take care of yourself. Here are some self-care ideas to get you started:

• Get enough sleep: Most adults need 7-8 hours of sleep per night. Consider going to bed and waking up at the same time each day to help regulate your body’s natural sleep rhythm.
• Eat healthy: Eating nutritious foods helps your body to function at its best. Make sure to include plenty of fruits, vegetables, and whole grains in your diet.
• Stay active: Exercise releases endorphins, which have mood-boosting effects. A moderate amount of exercise is the key; too much or too little can actually increase anxiety levels.
• Take breaks: When you’re feeling overwhelmed, take a few minutes to yourself to relax and rejuvenate. Take a hot bath, read your favorite book, or take a walk outdoors.
• Connect with loved ones: Spending time with people you care about can help reduce stress and promote positive emotions. Whether you stay in touch via text, social media, or in person, quality time with loved ones is crucial for a healthy mind and body.

When to See a Medical Professional

You should see your healthcare professional if anxiety is affecting your daily life or causing you distress.

They can diagnose your condition based on your symptoms, which may include feeling restless or on edge, being irritable, feeling unable to concentrate, feeling tense or jumpy, and having trouble sleeping.

If your healthcare professional determines that you have an anxiety disorder, they will likely recommend treatment.

How K Health Can Help

At this time, K Health does not prescribe gabapentin.

Did you know you can get affordable mental health care  with the K Health app?

Download K to check your symptoms, explore conditions and treatments, and if needed text with a healthcare provider in minutes. K Health’s AI-powered app is HIPAA compliant and based on 20 years of clinical data.

Frequently Asked Questions

How long before gabapentin works for anxiety?

It typically takes a few weeks for gabapentin to start working for anxiety. However, some people may experience relief from their symptoms sooner.

Is gabapentin used for anxiety or depression?

Gabapentin is a medication that is approved to treat seizures and nerve pain. While it is not specifically approved to treat anxiety, it is commonly prescribed off-label for this use. Gabapentin is generally considered effective for reducing anxiety levels.

How does gabapentin make you feel?

The most common side effects of gabapentin for anxiety include dizziness, drowsiness, and fatigue. Other side effects include dry mouth, nausea, and vomiting.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

K Health has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions,
and medical associations. We avoid using tertiary references.

• Anxiety & Depression Association of America. (ND.)
  https://adaa.org/understanding-anxiety/facts-statistics

• Mechanisms of the gabapentinoids and α 2 δ‐1 calcium channel subunit in neuropathic pain. (2016.)
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804325/

• Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years – evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial. (2019)
  https://pubmed.ncbi.nlm.nih.gov/30646965/

• Efficacy of gabapentin for prevention of postherpetic neuralgia: study protocol for a randomized controlled clinical trial. (2017.)
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237496/

• A Randomized, Controlled, Double-Blinded Clinical Trial of Gabapentin 300mg versus 900mg versus Placebo for Anxiety Symptoms in Breast Cancer Survivors. (2012.)
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411951/

• Treatment of social phobia with gabapentin: a placebo-controlled study. (1999.)
  https://pubmed.ncbi.nlm.nih.gov/10440462/

• Treatment of Generalized Anxiety Disorder with Gabapentin. (2017.)
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745655/

• Gabapentin and Tiagabine for Social Anxiety: A Randomized, Double-Blind, Crossover Study of 8 Adults. (2009.)
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708011/

• Selective Serotonin Reuptake Inhibitors (SSRIs) Information. (2014.)
  https://www.fda.gov/drugs/information-drug-class/selective-serotonin-reuptake-inhibitors-ssris-information

• Depression Medicines. (2019.)
  https://www.fda.gov/consumers/free-publications-women/depression-medicines

• FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. (2020.)
  https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class

• Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence. (2015.)
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610618/

Gabapentin for Depression, Mania, and Anxiety

iStockPhoto. com/William DondyK

Gabapentin is an anticonvulsant prescription drug that goes by several brand names including, Neurontin, Gralise, Gabarone, and Fanatrex. It was approved by the FDA in December 1993 for the following main uses.

1. Controlling certain types of seizures in people who have epilepsy

2. Relieving nerve pain (think: burning, stabbing, or aches) from shingles

3. Calming restless legs syndrome

But since it’s been available, gabapentin has also been used off-label in psychiatry to treat patients with treatment-resistant mood and anxiety disorders as well as alcohol-withdrawal and post-traumatic stress. It works by decreasing abnormal excitement in the brain for seizures and changing the way the body senses pain for nerve pain. Researchers don’t know exactly how it works for psychiatric conditions. (*Note: Some states have recently classified gabapentin as a controlled substance due to the potential for it to be abused and contribute to death from overdose. )

What to Know Before Starting Gabapentin

Treatment with Gabapentin: Important Things to Know Before Taking Gabapentin

Before you start gabapentin therapy, you should have a thorough medical exam to rule out any medical issues. This includes any blood or urine tests. Medical evaluations are important as gabapentin can induce hormonal imbalances. Like any other drug, you should not take gabapentin if you’re allergic to it.

There are side effects—more on that in a minute. But a few of the most important things your doctor will want to find out before prescribing gabapentin is if you have or have had any of the following:

• Diabetes

• Drug or alcohol addiction

• Kidney problems (or if you’re on dialysis)

• Liver or heart disease

• Lung disease (see the warning above on respiratory issues)

• Mood disorders, depression or bipolar; or if you’ve ever thought about suicide or attempted suicide

• Seizures (unless, of course, you’re taking it for seizures)

You should also know that not enough studies have been done to understand the exact risks of gabapentin if you’re pregnant or breastfeeding.

Gabapentin for Anxiety and Depression

How Gabapentin Is Used to Treat Anxiety Mood Disorders Like Depression

Gabapentin isn’t usually used to treat anxiety alone. More often, it’s given to ease anxiety symptoms for someone who also has depression or bipolar disorder. (Anxiety is commonly comorbid with depression and bipolar.) The reason is that it may not be effective for just anxiety. A close look comparing seven different clinical trials on how successful gabapentin is for anxiety shows that gabapentin may be better than a placebo to treat generalized anxiety disorder (GAD), but not much better. Results may be slightly more promising for social anxiety disorder.

The clinical trials for treating depression with gabapentin are also pretty lackluster. To date, there are no scientific studies showing it’s effective—either on its own or as part of some other therapy. Still, there is some anecdotal evidence that it’s helpful, especially with patients who don’t seem to improve with more standard antidepressants.

How Gabapentin for Mixed Bipolar States

More specifically, can it prevent future episodes of mania and depression? Right now, there is no good evidence that gabapentin can be used for treating people with bipolar disorder. High-quality, randomized controlled studies found that gabapentin was not effective.¹˒²

Gabapentin and AUD

Gabapentin and Alcohol Use Disorder

Gabapentin may be helpful in treating alcohol use disorder and withdrawal. Between 2004 and 2010, The Veterans Affairs Department conducted a double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women over 18, struggling with alcohol dependence.³ The results of the study showed that gabapentin (particularly the 1800 mg dosage) was effective in safely treating alcohol dependence and relapse-related symptoms including insomnia, dysphoria, and cravings.

Gabapentin Side Effects

Side Effects of Gabapentin

As with any medication, there may be some side effects. Some of these are more likely to happen when you first start taking the medication.

Common side effects:

• Dizziness

• Double Vision

• Fatigue

• Nystagmus (involuntary eye movement)

• Sleepiness

• Tremors

• Unsteadiness

Less common side effects:

• Abnormal stool (black and tarry)

• Chest pain

• Chills

• Cough

• Depression, irritability, or other mood or mental changes

• Fever

• Fatigue

• Memory loss

• Pain (or swelling) in the arms or legs

• Painful or difficult urination

• Shortness of breath

• Sore throat/swollen glands

Common side effects for those with mental illness:

• Agitation

• Decreased libido

• Depersonalization

• Increased libido

• Mania

• Paranoia

Dose and Administration

Gabapentin Dosage and Administration

Typically, your doctor will prescribe 300 mg once a day, usually in the evening, to start. The dose will then be increased every three to five days. Some people will take 600 mg/day, others will increase to 3,600 mg/day—the maximum dose approved by the FDA.

If used as a mood stabilizer or anti-depressant, the dose is usually between 900 and 2,000 mg a day. But, it may also be increased for better results. Some people see improvement in their symptoms about a week after starting treatment. Others need about a month before they see significant improvement.

Gabapentin has a half-life of about six hours, so it must be taken three to four times a day.

How to Discontinue Gabapentin

How To Discontinue Gabapentin

Like other psychotropic drugs, you should ease off gabapentin gradually. There are some known withdrawal symptoms. This mostly comes from people who take high doses of the drug and suddenly stop. You should only abruptly discontinue this drug because of a serious side effect, and even then, it should be done with your doctor’s supervision and direction.

Overdose and Toxicity

Gabapentin Overdose and Toxicity

It’s possible to fatally overdose on gabapentin. Reports of gabapentin being abused alone, and with opioids, prompted the FDA to release a warning statement (in December 2019) about the fatal risk of respiratory depression. Signs of overdose include:

• Ataxia (decreased muscle coordination)

• Diarrhea

• Drooping eyelid

• Drowsiness and lethargy

• Double vision

• Excitation

• Hypoactivity

• Labored breathing

• Marked sedation

• Slurred speech

If you suspect an overdose, you need immediate medical treatment. The only way to remove the drug is through kidney dialysis in the emergency room.

10 Most Common Questions About Gabapentin

1. Is there a generic version of gabapentin available? Since its manufacturer no longer has patent protection on the drug, there are generic versions on the market. They include Neurontin, Gralise, Gabarone, and Fanatrex.

2. How much does gabapentin cost? According to GoodRx.com, generic Gabapentin can cost between $7-$27 for ninety 100mg or 300mg capsules and between $14-$53 for ninety 400mg capsules.

3. What is the difference between gabapentin and other mood-stabilizing medications?This is kind of a trick question. Technically, even though we hear the term “mood stabilizer” quite often, especially in the context of bipolar disorder, the FDA doesn’t officially recognize the term. Not only that but even researchers and psychiatrists can’t come with a definition everyone agrees on. That said, lithium (which is probably the drug anyone with bipolar disorder is most familiar with) has significant differences from gabapentin. Lithium is in a class called bipolar disorder agents. Gabapentin is in a class called anticonvulsants. Their chemical structures are not the same and they work differently in the body. In addition to being used for bipolar, both have also been used for epilepsy.

4. How is gabapentin different from valproate and carbamazepine? There are claims that gabapentin was successful in helping with rapid cycling and mixed bipolar states in people who have not received relief from valproate or carbamazepine. It appeared that gabapentin helped more with anxiety and agitation than the other two drugs. Likewise, it has been shown to be beneficial with certain types of tardive dyskinesia.

5. Are there potential interaction issues for people taking carbamazepine, valproate or lithium? No interactions between gabapentin and valproate, carbamazepine or lithium have been reported.

6. Does gabapentin interact with any other prescriptions or over-the-counter medications, such as MAO inhibitors? There are only a few interaction issues that are known. Antacids have been known to decrease the absorption of the drug. Gabapentin could also increase the level of concentration of some oral contraceptives by up to 13 percent. As far as MAO’s, this particular combination doesn’t present any special issues, but you should always let your doctor and pharmacist know all the medications you are taking.

7. Are there any interaction issues between gabapentin and alcohol? Alcohol has been known to increase the discomfort of Gabapentin’s side effects.

8. Is it safe for a woman who is pregnant, about to become pregnant, or nursing to take gabapentin? The FDA placed gabapentin in pregnancy category C. According to studies done on animals, there has been evidence of fetal loss. However, there have been no studies done on humans. Despite all this, experts believe that the benefits gained from taking gabapentin may outweigh its risks.

9. Can children and adolescents safely take gabapentin? What about the elderly? Gabapentin may be used to treat seizures in children as young as 3 years old. The dosages will be different from what you’d give an adult, and the doctor may specify a particular brand name, such as Neurontin. Similar to children, the elderly may start on a lower dose.

10. Why do doctors prescribe gabapentin when there are other mood-stabilizing medications that have been around for many years? True, there are medications that have been shown to be more effective in double-blind studies that are placebo-controlled. But there are two reasons why physicians prescribe Gabapentin over more established drugs. One: not everyone improves with the older, more established medications. Two: some people can’t deal with the side effects of the other drugs.

DISCLAIMER: The information contained in this article should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. This article mentions drugs that were FDA-approved and available at the time of publication and may not include all possible drug interactions or all FDA warnings or alerts. The author of this page explicitly does not endorse this drug or any specific treatment method. If you have health questions or concerns about interactions, please check with your physician or go to the FDA site for a comprehensive list of warnings.

Warning: The Food and Drug Administration issued a serious warning about gabapentin in 2019. According to the FDA, breathing difficulties may occur in patients who have underlying respiratory problems (or in the elderly) when gabapentin (Neurontin, Gralise, Horizant) or pregabalin (Lyrica, Lyrica CR) is taken with other medicines that depress the central nervous system. There is evidence of risk with gabapentinoids alone in otherwise healthy people too; though this evidence is not as strong and is still being monitored.

Additionally, note that there are not a lot of comprehensive studies that look at Gabapentin as a way to treat anxiety, mood disorders, or tardive dyskinesia (uncontrollable movements). As with any medication, always talk to your health care professional if you have any questions or concerns.

Notes: This article was originally published August 21, 2021 and most recently updated June 8, 2022.

1. Pande AC, Crockatt JG, Janney CA, Werth JL, Tsaroucha G. Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. Bipolar Disord. 2000 Sep;2(3 Pt 2):249-55. doi: 10.1034/j.1399-5618.2000.20305.x. PMID: 11249802. Accessed October 22, 2020.
2. Frye MA, Ketter TA, Kimbrell TA, Dunn RT, Speer AM, Osuch EA, Luckenbaugh DA, Cora-Ocatelli G, Leverich GS, Post RM. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol. 2000 Dec;20(6):607-14. doi: 10.1097/00004714-200012000-00004. PMID: 11106131. Accessed October 22, 2020.
3. Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174(1):70-77. doi:10.1001/jamainternmed.2013.11950 Accessed October 22, 2020.

Our Review Process

What is it, effects and possible consequences

Content

• 1 Gabapentin: what is this drug, how does it work and what are the possible consequences?
  • 1.1 Gabapentin: what is it?
  • 1.2 How gabapentin affects the human body
  • 1.3 Gabapentin and pain
  • 1.4 Gabapentin and anxiety
  • 1.5 Gabapentin and depression
  • 1.6 Gabapentin and bipolar disorder o
  • 1.7 Gabapentin: what it is, effects and possible effects
    • 1.7.1 Gabapentin and sleep disorders
  • 1.8 Gabapentin and seizures
  • 1.9 Gabapentin and panic attacks
  • 1.10 Methods of administration and dosage of gabapentin
    9 0005 1.10.1 Methods of application
    • 1.10.2 Dosage
  • 1.11 Compatibility of gabapentin with other drugs
  • 1.12 Contraindications for taking gabapentin
  • 1.13 Side effects when taking gabapentin
  • 1.14 Signs of an overdose of gabapentin
    • 1. 14.1 Fatigue and drowsiness
    • 1.14.2 Problems with coordination of movements
    • 1.14.3 Problems with vision
    • 1.14.4 Increased irritability and aggression
    • 1.14.5 Stomach and intestinal problems
  • 1.15 How properly stop gabapentin
  • 1.16 Alternative therapies to replace gabapentin
    • 1.16.1 1. Physiotherapy
    • 1.16.2 2. Herbs and supplements
    • 1.16.3 3. Acupuncture
    • 1.16.4 4. Natural medicines
    • 1.16.5 5. Psychotherapy
  • 1.17 Medical consultation
  • 1.18 Related videos:
  • 1.19 Q&A: 90 004
  • • 1.19.0.1 What is gabapentin?
    • 1.19.0.2 How does gabapentin work?
    • 1.19.0.3 How often should I take gabapentin?
    • 1.19.0.4 What side effects can gabapentin cause?
    • 1.19.0.5 Can I drink alcohol while taking gabapentin?
    • 1.19.0.6 Can gabapentin be addictive?
    • 1.19.0.7 Can pregnant women take gabapentin?
    • 1. 19.0.8 Can gabapentin be used to treat pain?

Find out what gabapentin is, how it affects the body, what side effects it can have and what are the consequences of its use. Read the article and stay informed!

Gabapentin is a drug used to treat epilepsy, pain syndromes, and certain mental disorders. The mechanism of action of gabapentin is based on its effect on the central nervous system. In particular, this drug reduces the excitability of nerve cells, and also increases the synthesis of gamma-aminobutyric acid (GABA).

Although gabapentin is a relatively safe drug, it has a number of side effects. Some of them are related to the central nervous system: drowsiness, dizziness, impaired coordination of movements, etc. Other side effects may be associated with metabolism, such as increased appetite, thickening of the waist or weight loss.

Gabapentin can cause flare-ups if used incorrectly or at the wrong dose. This drug can also worsen the symptoms of many other conditions, such as depression and bipolar disorder. Gabapentin may be contraindicated in certain categories of patients, such as pregnant women and people with severe liver or kidney failure. Therefore, before you start using gabapentin, be sure to consult with a specialist.

Do not forget that self-medication can be hazardous to health. It is important to follow the instructions for use of gabapentin and not to exceed the dosage indicated by the specialist.

Gabapentin: what is this drug?

Gabapentin is a medicine used in medicine to treat a variety of conditions. The drug was created in the late 1970s and today is one of the most popular drugs in the world. Gabapentin belongs to a group of medicines called antiepileptics, but is also used for other purposes.

Gabapentin is generally safe and effective, but like any drug, it has potential side effects. Some of these side effects can be serious, so it’s important to see your doctor if you experience any problems while taking the medicine.

How gabapentin affects the human body

Gabapentin is an anticonvulsant that has an antiepileptic effect on the human body. This drug is aimed at improving the transport of the neurotransmitter gamma-aminobutyric acid (GABA), which has a calming effect on the human body.

Gabapentin is also used to treat other conditions such as neuropathic pain. Acting on the peripheral nerves and the central nervous system, gabapentin reduces the excitability of neurons and reduces pain in the nerve endings.

In addition, gabapentin may have a sedative effect that improves sleep quality in patients with anxiety disorders and insomnia. But do not abuse this drug, as its improper use can lead to serious health consequences.

• Side effects of gabapentin:

– Dizziness
– Drowsiness
– Tremor
– Irritability
– Dry mouth
– Vision problems 9013 5 – Muscle weakness
– Edema of the extremities
– Excessive sweating

It must be remembered that that gabapentin can interact with other medicines, so before you start taking it, you should consult your doctor and warn him about all the medicines you take, including those that can be bought without a prescription.

Gabapentin and pain

Gabapentin is a drug used in medicine in the treatment of diseases of the nervous system. It is used as a drug to regulate pain sensitivity, resulting in a reduction in pain sensation.

Gabapentin is able to protect nerve cells from damage and reduce the possibility of developing pain syndromes. It can be used in the treatment of diseases such as: epilepsy, anxiety disorders, bipolar disorder, pain in the nervous system.

Treatment with gabapentin usually involves dose control by a physician. This medicine should only be used with a doctor’s prescription as it may cause unwanted side effects.

Gabapentin and anxiety

Gabapentin is an anticonvulsant medication that is prescribed to treat tension, pain, anxiety and other symptoms. However, gabapentin has been found to cause anxiety in some patients.

If you are taking gabapentin and notice an increase in anxiety and nervousness, you should tell your doctor. He may make a dosage adjustment or prescribe a different drug that does not cause these side effects.

Gabapentin and depression

Gabapentin, originally intended for the treatment of epilepsy, may also be used to treat chronic pain and anxiety disorders. It may also be effective against depression, although it is not approved for this purpose by the FDA (Food and Drug Administration).

Some studies suggest that gabapentin may help reduce symptoms of depression, especially in patients whose depression is associated with anxiety or pain.

However, a physician should be consulted before prescribing gabapentin for the treatment of depression. Patients should not use gabapentin alone or for purposes for which it is not approved by the FDA without consulting a physician.

1. Gabapentin may help manage depression in patients who have depression associated with anxiety or pain.
2. But the use of gabapentin for the treatment of depression must be prescribed by a doctor.
3. Patients should not self-administer gabapentin for purposes for which it is not approved by the FDA.

Gabapentin and bipolar disorder

Bipolar disorder, also known as manic-depressive disorder, is a mental illness characterized by mood instability that can range from euphoria to deep depression.

Gabapentin is a drug commonly used to treat epilepsy, neuropathic pain, and some psychiatric disorders, including generalized anxiety disorder and bipolar disorder. Like many medicines, gabapentin can have side effects such as dizziness, drowsiness and incoordination. However, for most patients it is safe and well tolerated.

Some studies suggest that gabapentin may be effective in treating bipolar disorder and reducing anxiety in patients. However, it must be borne in mind that each person is unique and the reaction to the drug may vary. Therefore, before starting gabapentin to treat bipolar disorder, you should discuss it with your doctor and consider all possible side effects and health risks.

It is also worth noting that gabapentin is not the first choice drug for bipolar disorder and should only be recommended when other drugs have failed.

• Conclusion: Gabapentin may be effective in treating bipolar disorder and reducing anxiety in patients. However, its use should be carried out only under the close supervision of a physician, since each patient may have an individual reaction to the drug.

Gabapentin: what it is, effects and possible effects

Gabapentin and sleep disorders

Gabapentin is a medicine used to treat neurological diseases and pain syndromes. Although gabapentin is not a hypnotic, it may affect the quality and duration of sleep in patients.

Some patients taking gabapentin report sleep problems such as insomnia and daytime sleepiness. These symptoms may be caused by the effect of the drug on the nervous system, which can either improve or worsen the quality of sleep.

However, the effect of sleep disturbances depends on the dosage and individual characteristics of the patient. Some patients report that gabapentin improves their sleep, reduces insomnia, and lowers anxiety levels, allowing them to sleep better.

If you have trouble sleeping while taking gabapentin, you are advised to discuss this with your doctor. He may recommend dosage changes or prescribe a different drug to improve sleep quality.

Gabapentin and seizures

Gabapentin is a drug used to treat various neurological conditions such as epilepsy, neuropathic pain and sores caused by herpes or postherpetic neuralgia.

However, if gabapentin is used incorrectly, a serious side effect of seizures can occur. This side effect may occur in people taking gabapentin for a chronic condition such as kidney failure.

Seek immediate medical attention at the first sign of seizures. Seizures are a serious side effect and can negatively affect the health of the patient. Seizures can be avoided by controlling the dosage and following your doctor’s instructions for taking gabapentin.

Thus, gabapentin is an effective drug for the treatment of neurological diseases, but it is necessary to follow the doctor’s instructions regarding dosage in order to exclude possible seizures – a serious side effect.

Gabapentin and panic attacks

Gabapentin is an anticonvulsant that is often used in the treatment of neuropathic pain. But besides this, it can be used to treat other conditions, including anxiety disorders such as panic attacks.

Although gabapentin is not a first-line treatment for panic attacks, some studies have shown it to be effective in reducing their frequency and severity. However, as with any drug, gabapentin can cause side effects such as drowsiness, dizziness, and depression.

It is important to know that taking gabapentin without a doctor’s recommendation can lead to dangerous consequences, including worsening symptoms of panic disorder. Also, you cannot expect immediate results from gabapentin – it must be taken for some time to achieve maximum effectiveness.

If you suffer from panic attacks, you should consult a qualified specialist who will help you choose the most appropriate treatment and prescribe the correct dosage of gabapentin.

As a result of an integrated approach to the treatment of panic attacks, gabapentin can become one of the components of an effective therapy.

Methods of administration and dosages of gabapentin

Methods of administration

Gabapentin is usually taken orally, in the form of capsules or tablets, with or without food, depending on the doctor’s recommendations. The drug must be taken whole and fed with a sufficient amount of water. In some cases, an injectable formula of the drug may be prescribed.

It is important that you follow your doctor’s instructions on how to use your medicine.

Dosage

The dosage of gabapentin depends on many factors such as age, weight, medical condition and diagnosis. The general starting dose for adults is 300 mg per day, which should be increased gradually to 1800 mg per day. For children, the dosage is calculated by weight.

Always follow your doctor’s instructions and do not exceed the recommended dose. Avoid changing the dosage without consulting your doctor.

If a dose is missed, take it as soon as possible. If the next dose is close, you should skip the missed dose and continue taking the drug as scheduled.

Compatibility of gabapentin with other drugs

Before starting treatment with gabapentin, you should discuss with your doctor all medications, including those previously prescribed, as well as nutritional supplements and herbal preparations. Gabapentin can interact with some medications, so self-medication, changing the dosage, or stopping other medications without consulting your doctor may result in unwanted health effects.

Gabapentin may increase the sedative effect of other medicines such as diazepam, lorazepam and alcohol. Co-administration of gabapentin and morphine may result in increased sedation and reduced respiratory function.

Gabapentin may affect the blood concentrations of lamotridine, topiramate and phenytoin, so dosage adjustment may be necessary if these drugs are taken concomitantly. In addition, gabapentin can enhance the effect of insulin and hypoglycemic drugs, so it is necessary to control blood sugar levels when they are used simultaneously.

• Taking gabapentin may increase the concentration of calcium in the blood, therefore, while taking gabapentin and digoxin, it may be necessary to control the level of calcium in the blood and adjust the dosage of digoxin.
• Please note that the drugs listed are not a complete list of drugs that may interact with gabapentin. Before you start taking gabapentin, it is important to consult with your doctor and discuss all possible risks and side effects.

Contraindications for taking gabapentin

Gabapentin is a powerful drug that can only be prescribed for certain indications. However, like any other medicine, it has its contraindications.

• Allergic reaction. People who are allergic to any of the components of gabapentin should not take this drug.
• Kidney problems. Gabapentin is eliminated from the body through the kidneys, so people with problems in their system should take this drug very carefully.
• Overdose. Long-term use of high doses of gabapentin can lead to overdose, leading to serious consequences.
• Pregnancy and breastfeeding. Such cases have not yet been studied scientifically, so the use of gabapentin during this period may be hazardous to the health of the mother and child.

In any case, before taking gabapentin, you should always consult with your doctor to make sure that you have no contraindications to its use.

Side effects of gabapentin

Gabapentin may cause a variety of side effects including drowsiness, dizziness, headache, fatigue, changes in appetite, agitation, depression, anxiety, muscle cramps, cold tremors, incoordination.

Some patients may experience more serious health problems such as seizures or an increased risk of depression and suicide. There may also be swelling of the face and throat, speech disturbances, breathing problems, and other signs of an allergic reaction.

If you notice any side effects, you should report them to your doctor immediately, as some of them can be life-threatening, especially if they occur in combination.

• drowsiness,
• dizziness,
• changes in appetite,
• agitation,
• muscle cramps,
• cold trembling,
• hand trembling b,
• delirium,
• ataxia,
• impaired coordination of movements.

Gabapentin may also contribute to the development of Parkinson’s disease or various forms of dementia. In addition, taking this drug may increase the risk of suicidal thoughts. Therefore, long-term use of gabapentin should be monitored regularly by a specialist.

Signs of gabapentin overdose

Fatigue and drowsiness

Signs of gabapentin overdose may include fatigue, which may increase and become more pronounced over time.
An excessive feeling of drowsiness is also possible, which can be dangerous, especially if the person is driving or doing other activities that require a high concentration of attention.

Problems with motor coordination

One of the most obvious signs of a gabapentin overdose is problems with motor coordination. The person may have difficulty performing activities that require precision and good coordination, such as walking or exercising.

Vision problems

An overdose of gabapentin may cause vision problems such as double vision, blurry or blurred vision. This can lead to difficulties in daily life and even dangerous situations, such as when driving.

Increased irritability and aggression

Another sign of gabapentin overdose may be increased irritability and aggression. The person may become unbalanced and prone to fits of rage, which may lead to conflicts or damage to one’s own skin.

Stomach and intestinal problems

An overdose of gabapentin may also cause stomach and intestinal problems such as nausea, vomiting, diarrhea or constipation. The person may also experience abdominal pain or other symptoms associated with digestive dysfunction.

How to properly stop taking gabapentin

Stop taking gabapentin gradually and only after consulting your doctor. Stopping abruptly can cause serious side effects such as headaches, insomnia, anxiety, and even seizures.

To stop taking gabapentin, the “pull” method is usually used, which is based on lowering the dosage of the drug gradually over a week or two. Start lowering the dose as soon as you get your doctor’s advice.

It should be noted that long-term use of gabapentin leads to addiction. Withdrawal symptoms may occur upon discontinuation and should be taken seriously. If you experience any problems while lowering your dose, contact your doctor immediately.

It is also important to take steps to reduce stress and maintain a healthy lifestyle when stopping gabapentin. Your doctor may suggest that you take up exercise, meditation, yoga, or other methods to help manage the stress and discomfort associated with drug withdrawal.

Alternative therapies to replace gabapentin

1. Physiotherapy

Physiotherapy may be an effective alternative to gabapentin for pain and inflammation reduction. These include electrotherapy, laser therapy, ultrasound therapy and massage. They help improve blood circulation, reduce pain and relax muscles.

2. Herbs and supplements

Some herbs and supplements can help with pain and infection. For example, turmeric and ginseng can help relieve pain and inflammation, while magnesium can help relieve muscle tension. Be sure to discuss with your doctor which herbs and supplements are safe for you, especially if you are already taking any medications.

3. Acupuncture

Acupuncture may be an effective alternative to gabapentin in the treatment of pain. It consists in inserting needles into certain points on the body to relieve pain. It can help reduce nerve firing, reduce inflammation, and improve circulation.

4. Natural medicines

Some natural medicines, such as salvia and lemon balm, may have sedative properties that can help relieve pain and relax muscles. As with herbs and supplements, be sure to discuss this with your doctor.

5. Psychotherapy

Psychotherapy can help not only with pain, but also with anxiety and depression, which can exacerbate symptoms. Psychotherapy can help improve mood and improve emotional well-being.

Consult a physician

It is important to consult a physician or healthcare professional before taking gabapentin. The doctor will be able to assess your health status and provide individual recommendations for dosage and duration of treatment.

You should also be aware of possible interactions between gabapentin and other drugs you may be taking. In case of side effects, you should immediately contact your doctor.

Be especially careful if you are pregnant or breastfeeding as gabapentin may affect your baby’s health. Only your doctor can determine if gabapentin is right for you and how to use it safely.

Related videos:

Q&A:

What is gabapentin?

Gabapentin is a drug used to treat neurological conditions such as epilepsy, pain caused by nerve damage, and depression associated with bipolar disorder. It works at the level of gamma-aminobutyric acid (GABA), which is an important neurotransmitter in the central nervous system.

How does gabapentin work?

Gabapentin works by increasing the level of GABA in the brain, which leads to a decrease in arousal in the nervous system and a decrease in symptoms. It also reduces the release of pain mediators such as glutamate, which reduces pain associated with nerve damage.

How often should I take gabapentin?

The dosage and regimen of gabapentin administration depends on the disease for which it is prescribed and the individual characteristics of the patient. The doctor usually prescribes an initial dose, which can be increased as needed.

What side effects can gabapentin cause?

This may cause side effects such as drowsiness, dizziness, incoordination, changes in appetite, as well as dry mouth and constipation. More serious side effects may also occur, such as seizures, heart rhythm disturbances, or kidney problems. Before you start taking gabapentin, you should discuss any potential side effects and health risks with your doctor.

Can I drink alcohol while taking gabapentin?

No, alcohol is not recommended while taking gabapentin as it may increase the risk of side effects, especially incoordination and drowsiness.

Can gabapentin be addictive?

No, gabapentin is not addictive like drugs do. However, with prolonged use and withdrawal of the drug, a withdrawal syndrome may occur, which can lead to pain and other side effects. Therefore, when gabapentin is stopped, the doctor’s instructions should be followed and the dosage should be gradually reduced.

Can pregnant women take gabapentin?

The use of gabapentin in pregnant women may be unreliable due to the lack of data regarding its safety during pregnancy. Therefore, all potential risks and benefits should be discussed with your doctor before you start taking gabapentin.

Can gabapentin be used to treat pain?

Yes, gabapentin is sometimes prescribed to treat pain caused by nerve damage, such as Parkinson’s disease, chronic pain syndrome, and fibromyalgia. It works by changing the amount of pain mediators, which can reduce pain.

Gabapentin and pregabalin for bipolar disorder, anxiety and insomnia

Gabapentin is licensed in the US for the treatment of focal seizures and postherpetic neuralgia and in the UK for the treatment of focal seizures and neuropathic pain. Pregabalin has a similar indication and is also indicated for fibromyalgia in the US and generalized anxiety disorder (GAD) in the UK.

Put into practice at 1993, these drugs have become one of the most frequently prescribed drugs, with a significant proportion of prescriptions being off-label prescriptions. A 2002 American study [1] showed that 95% of gabapentin prescriptions are for off-label indications, in at least 10% of psychiatric cases. In the UK, at least half of all prescriptions for gabapentinoids are off-label, and one in five is co-prescribed with opioids. A 2021 study using the American electronic health record network Trinetx [2] showed that gabapentin was prescribed at least once in 13.6% of patients with bipolar disorder (BDD), 11.5% of patients with anxiety disorders, and 12.7 % of patients with insomnia; for pregabalin, these figures were 2.9%, 2.6%, 3.0% respectively.

Despite the widespread use of off-label gabapentin in bipolar disorder, the question of its effectiveness remains unclear. A 2011 meta-analysis of pharmacological treatments for acute mania found no superiority of gabapentin over placebo [3]. Systematic reviews of gabapentin treatment of psychiatric and/or substance use disorders have not shown conclusive evidence for its efficacy in bipolar disorder, but have identified possible efficacy in the treatment of anxiety disorders.

In addition to its licensed use for GAD in the UK, pregabalin is used to treat other anxiety disorders and acute anxiety conditions such as preoperative anxiety. The effectiveness of pregabalin for GAD has been established, but its effectiveness is unclear for other anxiety disorders such as social anxiety disorder. Gabapentinoids may also be useful in the treatment of insomnia, but again, firm evidence is lacking.

Overall, studies show that there is only limited evidence of the effectiveness of gabapentinoids in the disorders they are used to treat. Moreover, these drugs have potential risks, including a number of serious side effects, as well as abuse and dependence, which led to their reclassification as controlled drugs in the UK in 2019. In the US, pregabalin (but not gabapentin) has since is a federally controlled drug due to the risk of dependence and abuse.

A priori, due to their mode of action, gabapentinoids are attractive candidate molecules for use in psychiatry. They act primarily by inhibiting the activity of voltage-gated calcium channels (VGCCs) by binding to the α2δ accessory subunit, which regulates channel traffic and function. Although the genes encoding the α2δ subunits have not yet been associated with psychiatric phenotypes, other VGCC genes, in particular CACNA1C, which encodes a protein of the same name, show strong transdiagnostic associations with various disorders, including bipolar disorder. Administration of calcium channel blockers, which block the α-1 subunit of L-type VGCC, is associated with a reduction in hospital admissions in patients with severe mental illness. Cellular calcium dysregulation has been observed in patients with bipolar disorder and some other psychiatric disorders.

Given the potential risks of gabapentinoids and their widespread off-label use, it is important to carefully assess the evidence base for their use. This systematic review and meta-analysis focuses on the efficacy and tolerability of gabapentin and pregabalin in the treatment of bipolar disorder, anxiety and insomnia.

Published studies were searched in the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, MEDLINE In-Process and PsycINFO in the time range from their inception to August 4, 2020. Unpublished studies were searched in international research registries ( ClinicalTrials.gov; ICTRP) and regulatory websites.

Of the 4268 studies initially identified, 70 studies were included in the review: 55 double-blind RCTs and 15 open-label studies. The risk of bias was unclear for most studies; in a significant proportion of studies, there was an increased risk of error due to dropout.

Four double-blind RCTs were found investigating the efficacy of gabapentin in bipolar disorder. 101 patients were randomized to receive gabapentin, 81 to placebo, 30 to lamotrigine, and 19- carbamazepine. The mean age of all randomized patients was 37.5 years, 64.1% were women.

Three studies evaluated gabapentin in the treatment of acute bipolar disorder in heterogeneous groups of patients with manic/hypomanic, depressive and/or mixed symptoms. In each study, the efficacy of gabapentin was assessed using different outcome measures.

Gabapentin was significantly more effective than lamotrigine and carbamazepine in reducing depressive symptoms on the MMPI-2 depression subscale (50%, 33.5% and 13.6% reductions, respectively), but no difference in improvement on the MMPI mania subscale -2 was not observed. Based on the Global Clinical Impression Scale (CGI-BP), treatment response rates of 50% for lamotrigine, 33% for gabapentin, and 18% for placebo were observed in the clinical global bipolar version in the first phase of the study, but without clear statistical significance.

In a study investigating the addition of gabapentin to the main treatment, a significantly greater improvement in the total score on the YMRS Mania Rating Scale in the placebo group was reported, with no significant difference between groups on the Hamilton Rating Scale for Depression (HAM-D).

One long-term (1-year treatment) study of 25 bipolar patients in clinical remission (13 on gabapentin, 12 on placebo) showed a significant benefit of gabapentin versus placebo in terms of CGI.

Forty-two double-blind RCTs investigating anxiety disorders/conditions (GAD; social anxiety disorder; preoperative anxiety; PTSD; OCD; panic disorder) were selected. 3539 patients were randomized to receive pregabalin, 525 to gabapentin, 2280 to placebo and 937 to active comparators. The mean age of all randomized patients was 43 years, 60.4% were women. Data were analyzed on 5190 patients from eligible anxiety studies.

Gabapentinoids are more effective than placebo for a range of disorders on the anxiety spectrum.

Pregabalin is more effective than placebo in the treatment of GAD (SMD -0.37; 95% CI -0.45 to -0.29). The relative risk of withdrawal from the study for all reasons was comparable for pregabalin and placebo. Compared with placebo, pregabalin significantly reduced the relative risk of discontinuation due to failure (RR 0.44; 95% CI 0.28–0.70), but showed a trend towards an increased relative risk of discontinuation due to adverse events (RR 1, 30, 95% CI 0.99 – 1.71).

Pregabalin is more effective than placebo in treating exacerbations of social anxiety (SMD -0.25; 95% CI -0.45 to -0.04). There was no significant difference in the relative risk of dropping out of the study for all reasons or because of adverse events. Compared with placebo, pregabalin showed a trend towards a lower relative risk of dropout due to failure (RR 0.39; 95% CI 0.15 – 1.03).

A 14-week study of gabapentin in social anxiety disorder showed improvement over placebo on several rating scales. A 26-week study investigating pregabalin for relapse prevention found that a fixed dose of 450 mg/day reduced the overall relapse rate compared with placebo (27.5% vs. 43.8%, based on CGI criteria).

Compared to placebo, both pregabalin (SMD -0.55; 95% CI -0.92 to -0.18) and gabapentin (SMD -0.92; 95% CI -1.32 – -0.52) are more effective in reducing preoperative anxiety. Due to the heterogeneity of the studies, a subgroup analysis was performed based on empirically determined threshold doses of dose-response efficacy.

High doses (>600 mg) of gabapentin are effective in reducing preoperative anxiety (SMD -1.30; 95% CI -1.72 to -0.87), while low doses (600 mg) are ineffective. Due to the high degree of heterogeneity among studies in the high dose group, the validity of the estimate of the effect of high doses remains uncertain. Visual inspection of the gabapentin vs. placebo graph suggests possible effects from small trials, with larger effect sizes seen in high-dose gabapentin trials with smaller sample sizes. There was no significant difference between the low (≤150 mg) and high (300 mg) pregabalin dose subgroups. Interestingly, low dose pregabalin was more effective than placebo (SMD -0.29; 95% CI -0.54 – -0.05), while the high dose does not.

It is not possible to conduct a meta-analysis of the tolerability of pregabalin and gabapentin in studies of preoperative anxiety. The short evaluation time (lasting hours rather than weeks) means that dropouts have occurred in very few studies. In such cases, dropout was due to the practicalities of the preoperative procedures rather than the decision of the participants.

Three double-blind RCTs were included in the review, two of which evaluated the addition of pregabalin to the treatment of PTSD and OCD, and one evaluated the effect of gabapentin in the treatment of panic disorder. Pregabalin supplementation is more effective than placebo in chronic post-combat PTSD and in OCD refractory to SSRIs. However, eight weeks of flex-dose gabapentin is no more effective than placebo in patients with panic disorder.

Eight double-blind RCTs evaluated the efficacy of gabapentin in sleep disorders. In two studies, 111 patients were randomized to gabapentin and 60 to placebo (mean age 44.8 years; 44.9% women). In participants with alcohol dependence and related sleep disorders, gabapentin did not show improvement in sleep scores compared to placebo. The relative risk of withdrawal from the study for all reasons was comparable for gabapentin and placebo.

Only one double-blind RCT evaluated the efficacy of pregabalin (n=121) versus venlafaxine (n=125) and placebo (n=128) in the treatment of sleep disorders (mean age of all randomized patients 40.8 years, 60.7% women). Pregabalin significantly reduced sleep problems scores compared to placebo at weeks 4 and 8.

Compared to previous studies, this systematic review covers more disorders and databases, considers only double-blind RCTs to summarize evidence of efficacy, and includes unpublished data.

Review shows minimal evidence to support the use of gabapentinoids for bipolar disorder and insomnia.

Moderate effect size observed across the spectrum of anxiety disorders; a significant effect is observed in certain anxiety states; The effect of gabapentin on preoperative anxiety is dose dependent.

With regard to BAD, the small number of double-blinded RCTs investigating gabapentin and the lack of studies on pregabalin do not support evidence of efficacy of gabapentinoids. Quantitative synthesis was not performed due to the heterogeneity of the study population, study design, and outcome scoring systems. The evidence collected is inconclusive and does not justify the use of gabapentinoids in the treatment of bipolar disorder.

An analysis of anxiety-related studies showed a statistically significant effect size in favor of gabapentinoids across the spectrum of anxiety disorders/conditions. This transdiagnostic effect is explained by the fact that anxiety, anxiety proneness, and pathological anxiety are all mediated by the same neural network and common phenotype seen in anxiety disorders.

There is a dose-dependent effect of gabapentin on preoperative anxiety, with >600 mg required to treat acute anxiety. The analysis was performed post-hoc when examining significant study heterogeneity, and its findings should be used to develop hypotheses for future studies. The choice of dose cut-offs was based on empirical reports of dose-dependent effects in GAD, which is a limitation of this subgroup analysis.

In GAD, remission/moderate anxiety was observed at total daily doses of gabapentin ≥900 mg/day, recurrent severe anxiety at <600 mg/day. A similar approach was used for pregabalin, based on reports of differences in efficacy between 150 mg/day and 200–600 mg/day for GAD.

A meta-analysis of studies on alcohol-related insomnia found that gabapentin was no better than placebo. Gabapentinoids may improve sleep in patients with a range of clinical conditions, such as insomnia associated with GAD and neuropathic pain, but the extent to which direct or indirect effects influence sleep parameters in these conditions is unclear. While the studies of pregabalin for GAD included in this review reported improvements in HAM-A sleep, they were not included in the meta-analysis due to doubts about the validity of the HAM-A subscales for insomnia.

On the one hand, there is a limited nature of evidence for the effectiveness of gabapentinoids, on the other hand, there is strong evidence for their side effects and potential harm. Gabapentinoids commonly cause central nervous system depressant side effects, such as drowsiness and dizziness, which increase the risk of accidental physical injury and traffic accidents. There is also growing concern about the addictive potential and harms of gabapentinoids when used with opioids.

An important weakness of the evidence is its methodological quality and the risk of bias in the studies. The prominent side effects of gabapentinoids make it difficult to blind study participants, possibly leading to an overestimation of effect sizes. Therefore, the results of studies indicating the effectiveness of gabapentinoids should be treated with caution, especially when such results justify their off-label use. Against this background, the widespread use of off-label gabapentinoids seems unreasonable and requires more careful study.

Neurobiological and pharmacological considerations supporting the choice of drug target should never take precedence over empirical clinical evidence of efficacy and safety. However, they may be useful for further research.

The role of VGCC in psychiatric disorders is supported by genomic data. The strongest evidence is for schizophrenia and bipolar disorder, with associations with VGCC seen in a range of psychiatric disorders (albeit not yet found in anxiety disorders). Genetic associations with VGCC are mainly associated with α-1 and β subunits; but we do not have reliable information about the genes of the α2δ subunits.

In addition, the desired nature and direction of manipulation required to achieve therapeutic benefit remains to be determined. While the current understanding of VGCC is based on channel blocking, alternative and more subtle approaches are likely to be useful as well.

For example, the VGCC genes encode several isoforms with different properties, including sensitivity to existing channel blockers, and with varying tissue expression. The impact of rare mutations also points to the need to modulate rather than simply block VGCC function in psychiatric disorders. In the case of CACNA1C, gain-of-function mutations cause Timothy Syndrome, which is characterized by autism, but autism is also known to occur with loss-of-function mutations. All of this highlights the need for therapeutic agents capable of fine-tuning function, perhaps by targeting specific isoforms or through homeostatic action, which should ultimately maximize clinical benefit and minimize side effects.

Targeting the α2δ subunits characteristic of gabapentinoids may lead to subtle modulation of VGCC function. α2δ subunits increase the density of VGCC on the plasma membrane, direct the traffic of these channels to subcellular sites, and enhance function by changing their biophysical properties. Gabapentin reduces the number of α2δ and α-1 subunits on the cell surface and attenuates VGCC activity, indicating its inhibitory role. However, the exact effect of gabapentin on calcium channels depends on the stoichiometry of the VGCC accessory subunits, which, like other VGCC subunits, vary in number in different tissues, due to which gabapentinoids may have different effects on VGCC in different cell types.

It is possible that the effect of gabapentinoids on anxiety is mediated by α2δ-dependent but VGCC-independent mechanisms. Notably, α2δ-1 interacts with NMDA receptors (NMDARs), promoting dendritic spine maturation and NMDAR traffic.

Thus, it is interesting not only to elucidate the clinical effect of gabapentinoids, but also to establish their molecular mechanisms of action in order to understand the pathophysiology and identify new therapeutic strategies. A strategy for personalized medicine should take into account genomic and other factors influencing VGCC function and psychiatric disorders.

Gabapentinoids are generally effective across the spectrum of anxiety disorders, and it is likely that this is due to pharmacological effects on transdiagnostic anxiety phenotypes mediated by α2δ-dependent mechanisms. Anxiety is the most common comorbid pathology in patients with bipolar disorder [4], which partly reflects a common genetic predisposition [5]. Comorbid anxiety is associated with greater symptom severity and worse clinical outcomes. To date, there are no clinical studies on the effectiveness of gabapentinoids in the treatment of anxiety in bipolar disorder. The development of treatments for “bipolar anxiety” using gabapentinoids or modified α2δ ligands may become a promising area of ​​research in the future.

Systematic review and meta-analysis show that widespread psychiatric prescription of off-label gabapentinoids is not supported by reliable evidence, except for certain anxiety conditions. Thus, despite the attractive genetic and pharmacological rationale for their use, caution should be exercised until evidence of efficacy and safety is found. Presumably, it is possible to develop modified α2δ ligands that target specific subtypes or isoforms with a more favorable therapeutic profile.

Translated by: Filippov D.S.

Source: Hong, J.S.W., Atkinson, L.Z., Al-Juffali, N. et al. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Mol Psychiatry (2021).

References:

[1] Hamer AM, Haxby DG, McFarland BH, Ketchum K. Gabapentin use in a managed Medicaid population. J Manag Care Spec Pharm. 2002;8:266–71.

[2] Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236,379 COVID-19 survivors: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021;8:416–27.

[3] Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis.