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The drugs gabapentin and pregabalin are sometimes prescribed for people with bipolar disorder or insomnia. Research found little evidence that they are effective. The drugs have side effects and can be addictive; the team calls for further trials.

Gabapentin and pregabalin (collectively known as gabapentinoids) are licensed in the UK to treat pain and seizures. Pregabalin is also approved for generalised anxiety disorder (when people feel constantly anxious). Both drugs can have side effects, such as drowsiness, dry mouth, dizziness, headache, fatigue and visual disturbance. They can also be addictive.

At least half of gabapentinoid prescriptions in the UK are for conditions for which they are not approved. These conditions include insomnia (sleep problems) and bipolar disorder (people have extreme episodes of depression, followed by mania, when they feel high and hyperactive).

Researchers gathered existing research on gabapentinoid use in bipolar disorder, anxiety and insomnia. They found that the drugs had a moderate effect for some types of anxiety. But studies did not support the use of the drugs in bipolar disorder or insomnia. The team says these drugs should be used with extreme caution.

For further information about bipolar disorder, anxiety and insomnia, visit the NHS website.

What’s the issue?

Gabapentin and pregabalin (known as gabapentinoids) were introduced in the UK in 1993 and 2004, respectively. Gabapentin is approved for treating pain and seizures, and pregabalin, for treating pain, seizures and generalised anxiety disorder (people with this long-term condition feel anxious about many situations and issues).

Gabapentinoids have side effects (including drowsiness and dizziness), which are made worse if they are taken alongside pain-relieving opioid drugs, such as fentanyl and tramadol. The combination can increase the risk of physical accidents, road traffic incidents, and death. Despite this, about 1 in 5 people taking an opioid are also taking a gabapentinoid.

These drugs have been classified as controlled in the UK since 2019, meaning that strict regulations govern their use. However, at least half of all gabapentinoid prescriptions are for conditions for which they are not recommended by the UK’s National Institute for Health and Care Excellence (NICE). This includes some mental health conditions, such as bipolar disorder and insomnia.

This study explored existing evidence on the use of gabapentinoids to treat bipolar disorder, anxiety and insomnia.

What’s new?

This review included 70 studies of mixed quality. They explored gabapentinoid use in bipolar disorder, anxiety and insomnia. Most looked at anxiety.

Bipolar disorder
The researchers found 4 studies on gabapentin, but none on pregabalin. The studies included people with different symptoms and looked at different outcomes (hospital admissions, or changes in symptoms, for example). The researchers were therefore unable to pool the results and could not conclude that gabapentinoids are effective for bipolar disorder.

Anxiety
42 studies (most on pregabalin) looked at different types of anxiety disorder. Gabapentinoids were more effective than a dummy drug (placebo) in treating some severe anxiety disorders (including generalised anxiety, social anxiety, and post-traumatic stress disorder). Their effect was large in some studies; much less so in others.

Insomnia
8 studies looked at the effect of gabapentin on sleep outcomes such as sleep time and quality; only 1 study looked at pregabalin. The results were mixed, but generally suggested that gabapentinoids were not helpful for alcohol-related insomnia or for general sleep problems.

Side effects
Taking gabapentinoids was associated with drowsiness, dizziness, headaches, fatigue, sleep problems, weight gain, and dry mouth.

Why is this important?

Overall, the study found insufficient evidence to support the use of gabapentinoids in bipolar disorder or insomnia. There was moderate evidence that gabapentinoids can help people with some severe anxiety disorders. However, the researchers say that other drugs (which do not have the side effects of gabapentinoids) are already recommended for anxiety disorders.

These drugs are often prescribed for people who have more than one condition. This includes people who are in pain (this use is licensed) and who also have mental health conditions. Doctors may also be selecting gabapentinoids for the many people with bipolar disorder and anxiety.

The researchers stress that, given their side effects and the lack of evidence in some conditions, gabapentinoids should be used with caution.

What’s next?

GPs, psychiatrists and pain clinics need to know that there is little evidence to support gabapentinoid use for bipolar disorder or insomnia, the researchers say. There is moderate evidence for their use to treat severe anxiety disorders.

The researchers hope that new drugs, with fewer side effects, will be developed to target bipolar disorder and insomnia.

Members of the research team are now investigating exactly how many prescriptions for these drugs are given for these conditions in the UK.

You may be interested to read

This Alert is based on: Hong JSW, and others. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale. Molecular Psychiatry 2022;27:1339-1349.

Is increased gabapentinoid prescribing a problem?: Goodman CW, Brett AS. Gabapentin and pregabalin for pain – is increased prescribing a cause for concern? New England Journal of Medicine 2017;377:411–4.

Research describing the off-label prescribing of gabapentinoids in the UK: Montastruc F, and others. Trends in first gabapentin and pregabalin prescriptions in primary care in the United Kingdom, 1993–2017. Journal of the American Medical Association 2018;320:2149–2151.

NIHR-funded research looking at prescribing trends for gabapentinoids in primary care in the UK.

Recent NIHR evidence: Anti-inflammatory drugs do not lift depression in bipolar disorder

Funding: This work is supported by the NIHR Oxford Health Biomedical Research Centre.

Conflicts of Interest: Several authors have received funding from pharmaceutical companies, unrelated to this work. No relevant conflicts of interest were declared. A full declaration can be found on the original paper.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) at the time of publication. They do not necessarily reflect the views of the NHS, the NIHR or the Department of Health and Social Care.


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