Printed on: September 21st, 2026

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Gabapentinoids

This article discusses gabapentin and pregabalin. However, as you will read further down, a Swedish cohort study suggests that the risks may be different for each, so perhaps we shouldn’t lump them together as one!

This article was updated in November 2025.

There has been much published on this matter over recent years, and this was brought together in a great BMJ Therapeutics review (BMJ 2020;369:m1315). The key messages are fairly simple:

• Neuropathic pain: pregabalin and gabapentin can offer effective pain relief for some people with neuropathic pain, e.g. post-herpetic neuralgia and diabetic peripheral neuropathy, and should still be considered as first-line options. For these indications in people taking them for more than 8 weeks:
  • 4 out of 10 people taking pregabalin will get at least a 50% reduction in pain.
  • 3 out of 10 people taking gabapentin will get at least a 50% reduction in pain. 

(Note that the NNTs for amitriptyline (NNT 3.6) and SNRIs (NNT 6.4) are similar or better for neuropathic pain, and NICE guidance on neuropathic pain recommends we can choose ‘equally’ between amitriptyline, duloxetine, gabapentin and pregabalin as they have ‘similar’ efficacy. But remember, none of these drugs are without their problems! (BMJ 2020;369:m1315, NICE CG173 2013 (updated 2019))

• Fibromyalgia: there is an absence of evidence for gabapentin. For pregabalin, 1 out of 10 patients taking them will get a 30–50% reduction in pain over 12–26 weeks.
• Other uses: they have been demonstrated to be ineffective for low back pain, sciatica, spinal stenosis and migraine, and the article makes a strong recommendation that they should not be used off-label for these conditions.
• Side-effects are common (nearly 2/3 patients experience dizziness/drowsiness/oedema!), and we should discuss them and encourage patients to report them. If significant, we may need to taper and stop them.
• Co-prescribing with opiates increases the risk of harms and addiction.

You may find this table of numbers needed to treat and numbers needed to harm helpful when discussing with patients (the original BMJ article also has some nice 100-man diagrams for shared decision-making). 

Pregabalin and gabapentin are increasingly being used as drugs of abuse, both within the prison system and outside. An article in the DTB discussed this (DTB 2017;55(3):26).

It reminds us that:

• UK prescribing of pregabalin and gabapentin has increased by 350% and 150% respectively over the past 5 years.
• UK survey data indicates that the abuse of gabapentinoids, often alongside opiates, is common in the prison population.
• Pregabalin is felt to have greater abuse potential because in some users it produces a significant high or elevated mood.
• Use of both pregabalin and gabapentin has been implicated in abuse-related deaths.

Because of increasing concerns about the abuse of these drugs, in April 2019 pregabalin and gabapentin became schedule 3 (Class C) controlled drugs, which means (MHRA March 2019):

• The maximum quantity prescribed should not exceed 30 days.
• Scripts will be valid for 28 days from the date of issue.
• Prescribers must not issue repeatable prescriptions, e.g. repeat dispensing not requiring a signature. This is distinct from repeat prescriptions which can still be issued monthly with either a manual or e-signature.
• Controlled drug register entries are not required. 

Leaving aside the side-effects (see below) and risk of abuse, a Swedish cohort study looked at the risk of other adverse outcomes in those prescribed gabapentinoids. Importantly, it compared users with themselves at a time when they were not using them – removing some of the bias that may come from the type of person that might be prescribed this drug. Remember that cohort studies can only show associations, not causations (BMJ 2019;365:l2147).

• When analysing both drugs together, the study showed approximately a 1.2x increased risk of the following outcomes:
  • Suicidal behaviour and death from suicide.
  • Unintentional overdose.
  • Significant head/body injury.
  • Road traffic accidents and offences.
  • There was NO increased risk of arrests for violent crime.
• However, when analysing each drug separately, the study found:
  • Pregabalin was associated with an increased risk for all outcomes.
  • Gabapentin was not associated with an increased risk for any of them.
• Risks were greater in those aged 15–24y.

The accompanying editorial suggests that perhaps we should start seeing these drugs as two separate entities, although we should not see one as ‘good’ and one as ‘bad’ until we have more confirmatory data (BMJ 2019;365:l4021).

Gabapentinoid prescribing and self-harm risk 

A 2025 UK population-based study found that (BMJ 2025;389:e081627):

• Self-harm rates were higher in the 90 days before starting gabapentinoids, suggesting that prescriptions often coincide with periods of acute vulnerability.
• Risk was modestly raised in the early months of treatment, but returned to baseline with continued use.
• The greatest risk occurred in the 2w after stopping, when self-harm rates tripled – highlighting the need for close monitoring at both initiation and discontinuation. 

A BMJ editorial noted that these findings are reassuring in showing no direct effect of gabapentinoids on self-harm during stable use, but emphasised careful follow-up around treatment transitions (BMJ 2025;389:r634). It also pointed to possible higher risk in young adults and those with a history of self-harm but no psychiatric diagnosis, recommending particular vigilance in these groups.

Pregabalin in pregnancy

The MHRA has provided advice on the use of pregabalin in pregnancy (Drug Safety Update 2022;15(9):2). 

• Pregabalin in pregnancy should be avoided unless clearly necessary and the benefits to the woman outweigh the risks to the foetus.
• If a decision is made to use pregabalin, recommend the lowest possible dose.
• Women who are planning a pregnancy or are newly pregnant should be given information on the potential risks to facilitate shared decision-making.
• Women of childbearing age who are starting pregabalin should be counselled on the potential risks to an unborn baby and the need to use effective contraception during treatment.

This advice is based on a Nordic study showing a higher prevalence of major congenital malformations in babies exposed to pregabalin in the first trimester when compared with babies exposed to no antiepileptic drugs, or to lamotrigine or duloxetine. A useful way to explain this increased risk to patients is found in the associated MHRA patient information leaflet (link in useful resources, below). We have also included a link to the UK Teratology Information Service patient advice on their BUMPS (best use of medicines in pregnancy) website. 

"6 babies in 100 born to women who took pregabalin in the first 3 months of pregnancy had physical birth abnormalities, compared to 4 babies in every 100 born to women who were not treated with pregabalin or other epilepsy medicines in early pregnancy.”

Gabapentinoids and heart failure

A large US retrospective cohort study compared heart failure rates in those starting pregabalin with those starting gabapentin (JAMA Network Open 2025;8:e2524451). 250 000 patient records were involved (18 000 of whom were new users of pregabalin and the rest new users of gabapentin). All were aged ≥65y, two-thirds were female, the majority were White and all were Medicare recipients (not privately insured). The rate of heart failure was:

• 18.2 per 1000 person-years for pregabalin (95% CI 15–21).
• 12.5 per 1000 person-years for gabapentin (95% CI 12–13).

In terms of heart failure risk, this translates to an average hazard ratio of 1.5 for taking pregabalin vs. taking gabapentin.

Subgroup analysis found that in patients with pre-existing cardiovascular disease, those taking pregabalin had an average hazard ratio of 1.85 compared with those taking gabapentin (they were almost twice as likely to get heart failure).

This observational study has several limitations (older, White, predominantly female cohort in the US), but does strengthen the case for thinking carefully before prescribing pregabalin, especially in older patients with pre-existing cardiovascular disease.

While unable to prove causality, these kinds of cohort studies do help flag potential rarer adverse events which have not been discovered during earlier, smaller trials.

Gabapentinoids and COPD exacerbations

A Drug and Therapeutics Bulletin team update in 2025 reminded us of the potential for gabapentinoids to cause respiratory depression. The authors also described a large Canadian cohort study which demonstrated significantly increased risk of severe COPD exacerbations in those aged >55y when gabapentinoids were prescribed for any indication. The authors advise review of patients with COPD who are taking gabapentinoids, and caution before initiating these medications in patients with COPD (DTB 2025;63:84).

These are just the common ones and they occur in 1 in 3 people using the drugs! (from the BNF, 2019)

Given the issues with abuse and misuse, marginal benefits, and the increased risk of suicidal behaviour, unintentional overdose, trauma and road traffic offences, we need to be careful about initiating these drugs, ensuring they are only started for appropriate indications, and reviewing regularly to ensure they are still working and still needed. 

	Gabapentinoids Effective for some with post-herpetic neuralgia and diabetic peripheral neuropathy (but no more so than amitriptyline). Ineffective for low back pain, sciatica, spinal stenosis and migraine – we should not use them for this. Avoid co-prescription with opiates. Issues with abuse, self-harm, injury and offences, and significant side-effects. Are they really indicated and are you reviewing their use regularly? The MHRA advises avoiding pregabalin in pregnancy due to increased risk of congenital malformation.
	Have a look at your prescribing of gabapentinoids on Open Prescribing. Are you a low or high prescriber? Why might that be?  When did you last review all your patients on gabapentinoids?  You could audit all patients on gabapentinoids to look at the indication and when they were last reviewed. Consider discussing risk of COPD exacerbations with gabapentinoids with your team.
	Useful resources: Websites (all resources are hyperlinked for ease of use in Red Whale Knowledge) Live Well with Pain: ask yourself six questions (useful leaflet for if you want to start a conversation with patients about weaning or stopping gabapentinoids) gov.uk – pregabalin and risks in pregnancy (MHRA patient safety leaflet) UK Teratology Information Service – use of pregabalin in pregnancy