Alpha-2-delta Ligand (Voltage-gated Calcium Channel Modulator) — Anxiolytic Pregnancy: SPC §4.6: women of childbearing potential must use effective contraception during treatment. A Nordic observational study of more than 2700 first-trimester-exposed pregnancies showed a higher prevalence of major congenital malformations than in the unexposed population (5.9% vs 4.1%; adjusted prevalence ratio 1.14, 95% CI 0.96–1.35, and 1.29 (1.01–1.65) vs lamotrigine-exposed, 1.39 (1.07–1.82) vs duloxetine-exposed), with higher risks signalled for nervous system, eye, orofacial cleft, urinary and genital malformations on small, imprecise numbers. Animal studies show reproductive toxicity; pregabalin crosses the placenta in rats and may cross the human placenta. Should not be used during pregnancy unless clearly necessary (benefit to the mother clearly outweighing the potential risk to the foetus). Breast-feeding: pregabalin is excreted in human milk and the effect on newborns/infants is unknown — decide whether to stop breast-feeding or pregabalin, weighing the benefits of each.

Pregabalin (Psychiatric Use — GAD)

Brand names: Lyrica

This entry covers pregabalin used in psychiatry for generalised anxiety disorder, where it is an anxiolytic option licensed specifically for GAD in adults.

Adult dose

Dose: Generalised anxiety disorder: start 150 mg per day; based on response and tolerability increase to 300 mg/day after 1 week, then to 450 mg/day after a further week, and to a maximum of 600 mg/day after an additional week

Route: Oral (source product: Alzain 100 mg hard capsules; may be taken with or without food)

Frequency: Two or three divided doses per day

Max: 600 mg per day

SPC §4.2, Generalised Anxiety Disorder: 'The dose range is 150 to 600 mg per day given as two or three divided doses. The need for treatment should be reassessed regularly. Pregabalin treatment can be started with a dose of 150 mg per day. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after 1 week. Following an additional week the dose may be increased to 450 mg per day. The maximum dose of 600 mg per day may be achieved after an additional week.' Before starting, agree a strategy for ending treatment to minimise the risk of dependence, addiction and drug withdrawal syndrome; treatment should be given for the shortest possible duration. DISCONTINUATION: if pregabalin has to be stopped, taper gradually over a minimum of 1 week, regardless of indication. OTHER INDICATIONS on the same label (different escalation intervals): neuropathic pain — start 150 mg/day, increase to 300 mg/day after 3–7 days and, if needed, to a maximum of 600 mg/day after a further 7 days; epilepsy — start 150 mg/day, increase to 300 mg/day after 1 week, maximum 600 mg/day after an additional week. HEPATIC IMPAIRMENT: no dose adjustment required. ELDERLY: may require a dose reduction because of decreased renal function. PAEDIATRIC: safety and efficacy in children under 12 and adolescents 12–17 years have not been established and NO posology recommendation can be made — no structured paedDose is recorded; verify any under-18 use against a children's formulary.

Dose adjustments

Renal

SPC §4.2, Table 1 — pregabalin is eliminated primarily by renal excretion and clearance is directly proportional to creatinine clearance, so dose reduction must be individualised by CLcr. CLcr ≥60 mL/min: starting dose 150 mg/day, maximum 600 mg/day, BID or TID. CLcr ≥30 to <60 mL/min: starting dose 75 mg/day, maximum 300 mg/day, BID or TID. CLcr ≥15 to <30 mL/min: starting dose 25–50 mg/day, maximum 150 mg/day, once daily or BID. CLcr <15 mL/min: starting dose 25 mg/day, maximum 75 mg/day, once daily. Haemodialysis removes about 50% of drug in 4 hours — adjust the daily dose for renal function and give a supplementary single dose immediately after every 4-hour session: 25 mg (with the 25 mg/day regimen) up to 100 mg.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients

Side effects

Very common: dizziness, somnolence, headache
Common: ataxia, abnormal coordination, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoaesthesia, sedation, balance disorder, lethargy; blurred vision, diplopia
Common: euphoric mood, confusion, irritability, disorientation, insomnia, decreased libido; increased appetite; nasopharyngitis
Uncommon: syncope, stupor, myoclonus, loss of consciousness, dyskinesia, cognitive disorder, mental impairment; hallucination, panic attack, restlessness, agitation, depression, aggression, mood swings, depersonalisation; hypersensitivity, neutropenia, anorexia, hypoglycaemia
Rare/not known: angioedema and allergic reaction; severe cutaneous adverse reactions including Stevens–Johnson syndrome and toxic epidermal necrolysis (§4.4); disinhibition, suicidal behaviour and suicidal ideation; convulsions, Parkinsonism; drug dependence; renal failure and congestive heart failure reported post-marketing (§4.4)

Interactions

Pregabalin is excreted essentially unchanged in urine, undergoes negligible metabolism and does not bind plasma proteins, so pharmacokinetic interactions are unlikely; no pharmacokinetic interactions with carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital or topiramate (US label §7)
Oxycodone, lorazepam and ethanol — no pharmacokinetic interaction, but additive effects on cognitive and gross motor functioning were seen on co-administration (US label §7)
CNS depressants generally — respiratory depression may occur with pregabalin when used with concomitant CNS depressants or in underlying respiratory impairment; monitor and adjust dose (US label §5.4)
Thiazolidinedione antidiabetic agents — exercise caution on co-administration because of peripheral oedema (US label §5.7); diabetic patients who gain weight on pregabalin may need their hypoglycaemic medication adjusted (SPC §4.4)
Note: the fetched bundle did not include SPC §4.5, so this list is drawn from the US label and SPC §4.4 and should be checked against the full UK SPC

Clinical monograph

How it works

It binds the alpha-2-delta subunit of voltage-gated calcium channels, reducing presynaptic calcium influx and the release of excitatory neurotransmitters, which dampens neuronal excitability relevant to anxiety.

Prescribing in practice

It is a controlled drug with recognised dependence and misuse potential, so assess risk before prescribing, especially in people with a history of substance misuse.
There is an MHRA warning about serious, potentially fatal respiratory depression when combined with opioids or other CNS depressants, particularly in the elderly or those with respiratory compromise.
Discontinue gradually to avoid withdrawal symptoms, and reduce the dose in renal impairment as it is renally cleared.

Monitoring

Monitor anxiety response, mood and suicidal ideation, sedation, signs of misuse or dependence, and adjust for renal function as needed.

Counselling the patient

Do not stop suddenly; the dose should be tapered to avoid withdrawal effects.
It can cause drowsiness and dizziness, so take care with driving and avoid combining with alcohol or other sedatives.
Tell your prescriber about any history of dependence and report breathing problems if you also take opioids.

Evidence & guidelines

NICE recommends pregabalin as a treatment option for generalised anxiety disorder when an antidepressant is unsuitable or has not worked, with MHRA cautions on dependence and respiratory depression.

Reference: NICE NG106 (GAD); MHRA CD3 Reclassification 2019; MHRA Pregabalin + Opioid Warning; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways