Anticonvulsants

Prior to commencement, it is good practice that agreement is established between the individual and prescriber that prescribing of gabapentinoids is a trial and that if treatment is ineffective (or no improvement in function), they will not be continued.

Benefits:

• Gabapentin and pregabalin have a specific place in therapy
• Carbamazepine should be considered for those with trigeminal neuralgia

Risks of medication-related harm:

• Older adults, frailty, multimorbidity, polypharmacy, and renal impairment
• Gabapentin and pregabalin have been associated with a rare risk of severe respiratory depression^181,182 even without concomitant opioid medicines

Evidence for effectiveness and risks

• Much of the trial data for the effectiveness of gabapentinoids is limited to 12-16 weeks duration156
• Gabapentinoids should not be used in low back pain, sciatica and spinal stenosis¹⁹¹
• Gabapentin or pregabalin could be considered for individuals with the specific conditions of post herpetic neuralgia or painful diabetic neuropathy^156,192
• Gabapentin or pregabalin could be considered for individuals with fibromyalgia, although this is unlicensed¹⁹²
• Good practice point: Evidence indicates maximal dose of pregabalin 600mg daily/gabapentin 3600 mg daily to achieve 30-50% pain intensity reduction),^156,193 but if tolerated, minimum effective dose should be used
• Carbamazepine could be considered for trigeminal neuralgia, but individuals should be advised of adverse drug effects and interactions^188,194
• Review effectiveness of gabapentinoids or carbamazepine after four to six weeks of therapy and discontinue if ineffective
• Good practice point: there is limited place in therapy for other anticonvulsants and should not be started in non-specialist settings
• To minimise the risk of side effects with gabapentin and pregabalin, it is good practice to start at lower doses and titrate to lowest effective dose

Numbers needed to treat and harm for gabapentinoids with 50% pain intensity reduction

Please note that the table below may need to be scrolled horizontally or vertically in order to view all information, depending on your device.

• Prescribers and individuals should be aware there is a significant risk of adverse effects with gabapentinoids, including drowsiness or somnolence, dizziness, nausea, weight changes (abnormal appetite), cognition and speech problems/ataxia^188,191
• Individuals should be advised about the high incidence of adverse events leading to cessation of therapy in 18%-28% of patients^{156,157,188,191}
• Reduced renal function - requires dose reduction to reduce risk of toxicity and side effects
• eGFR is frequently used to quantify the degree of renal impairment and is readily available on laboratory results and clinical systems. However, the licences for gabapentin and pregabalin are based on creatinine clearance (CrCl) which usually relies on manual calculation. These are shown in the two tables below.
• Clinical calculators are available to support calculation

Please note that the tables below may need to be scrolled horizontally or vertically in order to view all information, depending on your device. On a mobile device you can also turn your phone to landscape to view tables.

Gabapentin

Pregabalin

*doses based on Creatinine Clearance (CrCl) and not eGFR

• Respiratory depression
  Risk of severe respiratory depression noted with both gabapentin and pregabalin.^181,182
  Individuals at higher risk who may require adjustments in dose or dosing regimen include:

• • compromised respiratory function, respiratory or neurological disease
  • renal impairment
  • those using concomitant central nervous system (CNS) depressants e.g. opioids, benzodiazepines
  • people older than 65 years

• Risk of foetal abnormalities
  • MHRA noted findings from a study that showed that pregabalin, like some other antiseizure drugs, is associated with a slight increased risk of major congenital malformations if used in the first trimester¹⁹⁷
  • Advice for health professionals can be found in the MHRA Pregabalin Drug Safety Update
  • More research is required to define the pregnancy safety profile of gabapentin. Pregnant women and women of childbearing potential should be made aware of the lack of data for most pregnancy outcomes. Gabapentin should only be used during pregnancy where benefits of treatment are considered to outweigh any potential risks¹⁹⁸

Gabapentinoids

• Slowly reducing the dose will minimise symptoms of withdrawal when reducing gabapentinoids
• Suggested reduction regime for analgesic use would be:
  • Gabapentin: reduce at maximum daily rate of 300mg every week
  • Pregabalin: reduce at maximum daily rate of 50-100mg every week
• Faster reduction may be considered (e.g. every two to three days) depending on patient response.