Gabapentinoid Safety: Risks of Gabapentin and Pregabalin in Pain Management

Gabapentin and pregabalin, commonly prescribed for neuropathic pain, are associated with higher risks of adverse outcomes early in treatment, according to recent reporting. A MedPage Today article highlights findings indicating increased dangers during the initial phases of gabapentinoid therapy, prompting calls for greater clinician vigilance when prescribing these medications for pain management.

The medications, known as gabapentinoids, work by binding to the α2δ subunit of voltage-gated calcium channels in the nervous system, which reduces the release of excitatory neurotransmitters and can dampen neuronal hyperexcitability—a mechanism implicated in neuropathic pain. While they are licensed in the UK and European Union for neuropathic pain and as adjunct therapy for epilepsy (with pregabalin also approved for generalized anxiety disorder), their use has grown significantly over the past decade.

Despite being viewed as safer alternatives to opioid analgesics, accumulating real-world evidence has raised concerns about long-term adverse effects, including possible cognitive risks, tolerance, dependence, and misuse or diversion. Of particular concern is the dangerous interaction when gabapentinoids are combined with opioids or other sedatives, which significantly increases the risk of respiratory depression and other serious outcomes.

Prescribing data from approximately 2017–2018 indicated that around 3% of adults in England received at least one gabapentinoid prescription, while about 13% received an opioid prescription for chronic non-cancer pain. These figures reflect prescribed use only and do not account for illicit consumption, which has contributed to growing public health concerns.

Research cited in the MedPage Today report and supported by additional studies suggests that the early phase of treatment carries heightened risks, necessitating careful patient monitoring. Clinicians are advised to assess individual patient factors that may increase vulnerability to adverse effects, including concomitant use of central nervous system depressants, history of substance use disorders, and renal impairment, which can affect drug clearance.

Experts emphasize that medication-only strategies are frequently insufficient for persistent pain, which is often multifactorial. Many patients remain on gabapentinoids long-term despite limited benefit, accumulating adverse effects and increasing exposure to interacting medications. Alternative approaches, such as carefully selected interventional pain treatments guided by modern imaging, may help some patients reduce pain, improve function, and decrease reliance on long-term medication.

Ongoing research continues to evaluate the comparative effectiveness and safety of gabapentin versus pregabalin in treating neuropathic pain. While both medications are widely used, uncertainties remain regarding their relative efficacy and risk profiles, underscoring the need for individualized treatment decisions based on the latest evidence and patient-specific factors.