Pregabalin
Pregabalin is a potent gabapentinoid licensed for neuropathic pain, epilepsy and, in many countries, generalised anxiety disorder. It is more potent and more predictably absorbed than gabapentin. It has clear anxiolytic efficacy but also a recognised euphoria and dependence liability, and is now controlled in several jurisdictions.
01 Overview
Pregabalin shares gabapentin's mechanism but has higher affinity for the alpha-2-delta subunit and near-linear absorption, giving more consistent dosing. It is one of the few non-benzodiazepine anxiolytics with a formal GAD indication in Europe.
Euphoria, sedation and a sense of ease drive recreational use, particularly at supratherapeutic doses and in people with opioid or alcohol histories. Dependence and a withdrawal syndrome resembling benzodiazepine withdrawal are well documented, which prompted controlled-drug scheduling in the UK and elsewhere.
02 Mechanism
High-affinity ligand at the alpha-2-delta-1 subunit of voltage-gated calcium channels, decreasing depolarisation-evoked release of glutamate, noradrenaline and substance P.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Starting dose | 75–150 mg/day | Oral | Lower start reduces early dizziness. |
| GAD / neuropathic pain | 150–600 mg/day | Oral | Split into two or three doses; titrate from 150 mg/day. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| AnxiolysisReduces psychic and somatic anxiety in generalised anxiety disorder, with onset within a week. | Comparable to benzodiazepines in GAD | Clinical | |
| Neuropathic pain reliefEffective in diabetic neuropathy, postherpetic neuralgia and fibromyalgia. | NNT ~7 | Clinical | |
| Euphoria / relaxationAt higher doses produces euphoria and disinhibition that drive misuse. | Dose-dependent | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Dizziness and somnolenceDose-related drowsiness, dizziness and impaired concentration. | Mild | Very common | Clinical | |
| Weight gain and oedemaIncreased appetite, weight gain and peripheral oedema during chronic use. | Mild | Common | Clinical | |
| Dependence and withdrawalCraving, anxiety, insomnia, sweating and agitation on abrupt cessation. | Moderate | Common after chronic use | Clinical |