Anticonvulsants | Right Decisions

Summary of recommendations: anticonvulsants

Conditional recommendation

Gabapentin or pregabalin could be considered for individuals with the specific conditions of post herpetic neuralgia or painful diabetic neuropathy^44,46

Good practice point

Evidence indicates maximal dose of pregabalin 600mg daily/gabapentin 3600mg daily to achieve 30-50% pain intensity reduction), but if tolerated, minimum effective dose should be used^44,90

Conditional recommendation

Gabapentin or pregabalin could be considered for individuals with fibromyalgia, although this is unlicensed⁴⁶

Strong recommendation

Prescribers and individuals should be aware there is a significant risk of adverse effects with gabapentinoids, including drowsiness, dizziness, nausea, weight changes (abnormal appetite), cognition, speech problems and ataxia^83,88

Strong recommendation

Gabapentinoids should not be used in lower back pain, sciatica (lumbar radiculopathy) and spinal stenosis^45,88

Conditional recommendation

Carbamazepine could be considered for trigeminal neuralgia, but individuals should be advised of adverse drug effects and interactions⁸⁹

Good practice point

Review effectiveness of any gabapentinoid/carbamazepine after four to six weeks of therapy and discontinue if ineffective

Indications and effectiveness

Anticonvulsants could be considered to manage neuropathic pain (see the table below)
Much of the trial data for the effectiveness of gabapentinoids is limited to 12-16 weeks duration⁴⁴
Gabapentinoids should not be used in low back pain, sciatica (lumbar radiculopathy) and spinal stenosis⁸⁸
Gabapentin or pregabalin could be considered for individuals with the specific conditions of post herpetic neuralgia or painful diabetic neuropathy⁴⁴^,⁴⁶
Gabapentin or pregabalin could be considered for individuals with fibromyalgia, although this is unlicensed⁴⁶
Good practice point: Evidence indicates maximal dose of pregabalin 600mg daily/gabapentin 3600mg daily to achieve 30-50% pain intensity reduction)44^,90 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 interactions⁸³^,89
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 chronic pain therapy for other anticonvulsants and they 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
It is good practice that, prior to commencement, agreement is established between the individual and clinician that prescribing is a trial and that if treatment is ineffective (or no improvement in function), it will not be continued

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

Numbers needed to treat and harm for gabapentinoids with 50% pain intensity reduction (based on trial evidence)

Medication	Indication	NNT	NNH
Gabapentin44 doses up to 3600mg daily⁹⁰	Post herpetic neuralgia	8⁴⁴	8.6⁴⁴
Gabapentin doses up to 3600mg daily⁹⁰	Painful diabetic neuropathy	5.9⁴⁴	8.6⁴⁴
Gabapentin maximum2400mg daily⁹⁰	Fibromyalgia	5.4	8.6
Pregabalin 600mg daily⁴⁴	Post herpetic neuralgia	3.9	11
Pregabalin 600mg daily⁴⁴	Painful diabetic neuropathy	7.8	11
Pregabalin 600mg daily⁴⁴	Central neuropathic pain	9.8	13.9
Pregabalin 600mg daily⁴⁴	Fibromyalgia	11	11
Carbamazepine⁴⁴^,91	Trigeminal neuralgia (50% pain reduction)	1.7	2.1

Risks and harms

Prescribers and individuals should be aware there is a significant risk of adverse effects with gabapentinoids, including drowsiness, dizziness, nausea, weight changes (abnormal appetite), cognition, speech problems and ataxia^83,88
Adverse events lead to cessation of therapy in 18-28% of people⁴⁴^,⁸³^,⁸⁸
Reduced renal function - requires dose reduction of gabapentinoids 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
- Clinical calculators are available to support calculation for example MedicinesComplete — Calculators

Maximum recommended dose for gabapentin based on renal function

CrCl ml/min^*	Maximum recommended dose (BNF)	Additional info
50-79	600-1800mg daily in 3 divided doses	-
30-49	300-900mg daily in 3 divided doses	-
15-29	150-600mg daily in 3 divided doses	150mg dose to be given as 300mg in 3 divided doses on alternate days
<15	150-300mg daily in 3 divided doses	150mg dose to be given as 300mg in 3 divided doses on alternate days

^*Doses based on Creatinine Clearance (CrCl) and not eGFR

Maximum recommended dose for pregabalin based on renal function

CrCl ml/min^*	Maximum recommended dose (BNF)
30-60	Initially 75mg daily and maximum 300mg daily in 2-3 divided doses
15-30	Initially 25-50mg daily and maximum 150mg daily in 1-2 divided doses
<15	Initially 25mg once daily and maximum 75mg once daily

^*Doses based on Creatinine Clearance (CrCl) and not eGFR

Respiratory depression
- Risk of severe respiratory depression noted with both gabapentin and pregabalin⁷⁸^,⁷⁹
- 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 medications, is associated with a slight increased risk of major congenital malformations⁹² if used in the first trimester
- 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 risks

High risk individual due to high dose opioid, polypharmacy and multiple co-morbidities

A 55-year-old woman with complex regional pain syndrome, multiple co-morbidities and with polypharmacy was identified for review by the Scottish Therapeutics Utility (STU) high dose opiate search and the mental health ‘triple whammy’ search. She has asthma, sleep apnoea, type 2 diabetes, ischaemic heart disease, depression and obesity (BMI 50kg/m²). She is at high risk of opiate toxicity as she is prescribed 300mg of morphine daily and is also prescribed a benzodiazepine, a z-drug, gabapentin and pregabalin, two antidepressants and an antipsychotic.

She has poor engagement with services and frequently does not attend appointments or reviews. Following multiple attempts, she agreed to come in for a pharmacist medication review. Her pain was assessed using the brief pain inventory and her pain scores and functional impact scores were high. She was unsure if her pain medication was effective and recognised that many symptoms that she was experiencing were due to side-effects of medication.

Discussion was had regarding maximum recommended dose of morphine, the cumulative effects of central nervous system medications and the risk of toxicity due to polypharmacy and sleep apnoea. She was signposted to self-help resources and acknowledged the importance of self-management in chronic pain.

Following this consultation she agreed to slowly withdraw her pregabalin. With the support of the pharmacist this has now stopped. She has agreed a tapering plan for her morphine and has currently reduced her total daily morphine dose by 60mg, to 240mg daily, and plans to continue to reduce this. She has built a good rapport with the practice pharmacist and is now engaging with the practice nurse to address other co-morbidities, including control of her asthma and diabetes.