Gabapentinoids

Gabapentinoids are a class of prescription medicines that includes gabapentin and pregabalin. They are structurally similar to the neurotransmitter GABA but do not act on GABA receptors. Instead, they bind with high affinity to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system, which reduces the release of excitatory neurotransmitters and helps dampen neuronal excitability.

Clinical use is primarily for certain neuropathic pain conditions and as an adjunctive treatment for seizures. Gabapentin and pregabalin are approved for diabetic neuropathy and postherpetic neuralgia, among other neuropathic pain syndromes. Pregabalin has additional indications in various regions, including fibromyalgia and generalized anxiety disorder, reflecting regulatory differences by country. Off-label uses exist for other pain conditions, anxiety, and sleep disturbances, though evidence and guidelines vary.

Common adverse effects include dizziness, somnolence, peripheral edema, weight gain, and dry mouth. Sedation and cognitive slowing can occur, particularly at higher doses or in combination with other central nervous system depressants. There is a risk of misuse and dependence with prolonged use. Abrupt discontinuation may precipitate withdrawal symptoms such as insomnia, nausea, and sweating. Dose adjustments are often necessary in renal impairment, and exposure should be limited in pregnancy unless clearly indicated.

Pharmacokinetics and safety considerations include renal excretion, potential interactions with opioids or other sedatives, and the need for careful monitoring of mood and suicidality in line with clinical guidelines. Overall, gabapentinoids have a well-established role in treating certain neuropathic pain conditions, with variable efficacy for other indications.