Gabapentinoids (antiepileptics)
ATC code: N03AX12 (Gabapentin)
Brand names
Neurontin, Gralise, Horizant
Structural analogue of GABA that does not bind GABA receptors. Binds the α2δ subunit of voltage-gated calcium channels in the CNS, reducing presynaptic calcium influx and release of excitatory neurotransmitters (glutamate, noradrenaline, substance P). Bioavailability is dose-dependent (saturation of intestinal transporter) — above 1800 mg/day, further increases produce diminishing plasma rises.
First line
First-line for neuropathic pain per NeuPSIG 2015 and IASP 2022. Used in diabetic polyneuropathy, post-herpetic neuralgia, and trigeminal neuralgia. Start 300 mg at bedtime, titrate to 900–3600 mg/day in three divided doses. Effect develops over 2–4 weeks. NNT for PHN — 7; for diabetic neuropathy — 6.
First line
First-line for post-herpetic neuralgia. Dose 1800–3600 mg/day. Alternatives: pregabalin, amitriptyline, duloxetine, topical lidocaine and capsaicin. PHN prevention: Shingrix vaccination in adults over 50.
First line
Per 2020, first-line in RLS is gabapentin enacarbil (Horizant) with a 'strong' recommendation. Plain gabapentin (off-label) is second-line. Start 300 mg 2 hours before bed; titrate to 1200–1800 mg.
Primarily gabapentin enacarbil (Horizant), not registered in Russia. Plain gabapentin is used off-label.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Gabapentin is an antiepileptic drug prescribed for partial epilepsy, neuropathic pain, and restless legs syndrome. It is often prescribed as a sleep aid outside an epilepsy, neuropathic pain, or RLS indication, purely because of its sedative side effect. International insomnia guidelines ( 2021, ESRS 2017, NG219) do not support this use: for primary insomnia the first line is cognitive-behavioral therapy for insomnia (CBT-I), and medication is matched to the diagnosis. Clinical trials of gabapentin for primary insomnia are few and heterogeneous. The drug has specific risks: dizziness, next-day sedation, peripheral edema, respiratory depression when combined with opioids ( warning, 2019), and potential for dependence and misuse. If gabapentin was prescribed for sleep outside an RLS or neuropathic pain indication, consider seeking a second opinion.
Not recommended
Gabapentin for non-clinical anxiety or stress is not mentioned in or mental health guidelines. Off-label use is widespread but unjustified — efficacy is doubtful and dependence/abuse risks are real. Since 2018, gabapentin and pregabalin are Schedule 3 controlled substances in the UK.
4 pairs found. Sorted from critical to minor.
Mechanism
Gabapentin reduces morphine clearance and potentiates CNS depression. issued a 2019 warning about increased respiratory depression risk with the combination.
Symptoms
Drowsiness, slowed breathing (rate below 12/min), cyanosis of lips. Severe cases include respiratory arrest. Older patients: fall risk.
Management
The combination is possible in neuropathic or palliative pain. Keep doses minimal, start low. Provide naloxone to the patient and family. Monitor respiratory rate and saturation.
Mechanism
Additive CNS depression. Gabapentin does not lower the seizure threshold, but opioid-gabapentinoid combinations are associated with respiratory depression risk, especially in older patients.
Symptoms
Drowsiness, slowed breathing (rate below 12/min), cyanosis of lips. Severe cases include respiratory arrest. Older patients: fall risk.
Management
The combination is possible in neuropathic pain. Keep doses minimal, start low. Warn the patient about drowsiness and ataxia. Older patients: enhanced fall monitoring.
Mechanism
Additive CNS depression via different mechanisms: alprazolam (GABAergic) and gabapentin (α2δ calcium channel inhibition). Sedation, ataxia, and fall risk amplify.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk. Ataxia and fall risk are especially pronounced in older patients.
Management
On starting the combination, begin both at minimal doses. Avoid the combination in older patients — fall and fracture risk. In neuropathic pain and anxiety, alternative: low-dose amitriptyline (10–25 mg at bedtime) with buspirone. If unavoidable, watch for sedation signs and check heart rate and BP at one week.
Mechanism
Additive CNS depression via different mechanisms. Sedation, dizziness, and fall risk amplify, especially in older patients.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk.
Management
For neuropathic pain (diabetic neuropathy, post-herpetic neuralgia), start both at minimum doses: amitriptyline 10 mg at bedtime, gabapentin 100 mg three times daily. Up-titrate every 1–2 weeks as tolerated. Avoid in older patients — fall risk. Alternatives: duloxetine with topicals (capsaicin, lidocaine patch).
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FDA categories were retired in 2015. Pregnancy safety data are limited. Use in pregnant patients with severe neuropathic pain or epilepsy is individualized with a neurologist.
Transfers into breast milk. Per LactMed, use is acceptable with monitoring for infant sedation and poor weight gain.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Gabapentin is evaluated for the following indications with varying evidence strength: Post-herpetic neuralgia (evidence tier A), Neuropathic pain (evidence tier A), Restless legs syndrome (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Gabapentin (≥ 1 in 100): Somnolence, sedation (especially first weeks), Dizziness, Ataxia, gait disturbance, Peripheral edema, Weight gain, Dry mouth. See the Safety section for uncommon and serious reactions.
FDA category C. FDA categories were retired in 2015. Pregnancy safety data are limited. Use in pregnant patients with severe neuropathic pain or epilepsy is individualized with a neurologist.
Transfers into breast milk. Per LactMed, use is acceptable with monitoring for infant sedation and poor weight gain.
Gabapentin is contraindicated in: Hypersensitivity; Age under 3 (in epilepsy). Full list in the Safety section.