Phenobarbital

Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026

Phenobarbital is a long-acting barbiturate used for seizure disorders and, less commonly, sedative indications. It is habit-forming, can cause respiratory depression and profound sedation, and abrupt withdrawal after chronic use can precipitate seizures or death. Chronic enzyme induction can lower vitamin D and folate status and contribute to bone disease.

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Publication status

Exploratory record, not a reviewed medical publication.

See the editorial and medical-review policies for the publication gate.

This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.

In short

What the research says.

A quick, data-only summary. The full evidence, dosing, and sources are below.

Phenobarbital is a long-acting barbiturate used for seizure disorders and, less commonly, sedative indications. NutriStack rates the supporting evidence as strong. Common adult dosing is Adult anticonvulsant maintenance is commonly 60-200 mg/day individualized by response and serum levels; sedative dosing is lower and indication-specific., though a prescriber sets the actual dose. With long-term use it can deplete vitamin d, calcium, folate. This profile indexes 3 sources.

What it's good for

Long-term seizure prevention in selected generalized or focal seizure disorders²
Neonatal seizure management in specialist settings
Sedative-hypnotic use is now limited because safer alternatives usually exist

What to watch for

Sedation
Cognitive slowing
Ataxia
Hypersensitivity to barbiturates
Manifest or latent porphyria²

The bottom line

Evidence rating strong. Most-documented uses: long-term seizure prevention in selected generalized or focal seizure disorders, neonatal seizure management in specialist settings, sedative-hypnotic use is now limited because safer alternatives usually exist. 3 sources indexed (1968–2025), with 0 interaction records on file.

The science

How it works, mechanistically.

Core mechanism

Phenobarbital enhances GABA-A receptor-mediated inhibitory neurotransmission, mainly by prolonging chloride-channel opening, and at higher concentrations can reduce excitatory glutamate transmission. It is a strong inducer of hepatic drug-metabolizing enzymes, including CYP pathways and UGTs. Enzyme induction accelerates vitamin D catabolism and can reduce folate status, contributing to osteomalacia, low bone mineral density, and megaloblastic changes during prolonged therapy.^1,2

Class

Barbiturate anticonvulsant

Dosing

Dosing & protocol.

Common range

Adult anticonvulsant maintenance is commonly 60-200 mg/day individualized by response and serum levels; sedative dosing is lower and indication-specific.

Recommended form

Oral tablet or elixir for maintenance; injectable formulation in acute or inpatient settings

Can be taken with or without food. Avoid alcohol and other CNS depressants unless specifically supervised.

Depletions

What it depletes.

Nutrients this medication can lower over time, and what to replace.

Vitamin D

Significant

Phenobarbital induces hepatic enzymes that accelerate vitamin D catabolism, lowering 25-hydroxyvitamin D and reducing calcium absorption.

Replace Vitamin D3Monitor Serum 25-hydroxyvitamin DOnset Months to years of chronic therapy, with higher risk when intake or sunlight exposure is low

Calcium

Moderate

Reduced vitamin D activity decreases intestinal calcium absorption and can contribute to secondary hyperparathyroidism and bone loss.

Replace CalciumMonitor Serum calcium, parathyroid hormone, and bone density when indicatedOnset Months to years, usually secondary to vitamin D disruption

Folate

Moderate

Chronic enzyme-inducing anticonvulsant therapy can lower folate status through altered metabolism and absorption, increasing risk of megaloblastic changes.

Replace MethylfolateMonitor CBC, serum folate, red blood cell folate, and homocysteineOnset Months to years of long-term therapy

Full Phenobarbital depletion and interaction guide →

Safety

Full safety detail.

Side effects

Sedation
Cognitive slowing
Ataxia
Dizziness
Respiratory depression at high doses or with sedatives
Dependence and withdrawal seizures
Depression or behavioral changes
Rash or hypersensitivity
Megaloblastic anemia
Osteopenia or osteomalacia with chronic therapy
Suicidal thoughts or behavior warning for antiepileptic drugs

Contraindications

Hypersensitivity to barbiturates
Manifest or latent porphyria²
Marked hepatic impairment²
Respiratory disease with dyspnea or airway obstruction^1,2
Avoid abrupt discontinuation after chronic use

Sources

Sources, by evidence tier.

Numbered references. Citations throughout the page link here.

Reviews & position papers

1Antiepileptics and bone healthPack AM · Current Opinion in Neurology · 2004
Review links enzyme-inducing antiseizure drugs including phenobarbital with altered vitamin D metabolism and bone disease.

Reference material

2PHENOBARBITAL tablets, US Prescribing InformationURLU.S. National Library of Medicine · DailyMed · 2025
Labeling describes barbiturate warnings, contraindications, long half-life, and need for periodic laboratory evaluation with prolonged therapy.
3Folate deficiency and anticonvulsant therapyReynolds EH · Lancet · 1968
Classic clinical literature describes folate lowering during chronic anticonvulsant therapy.

FAQ

Common questions.

Quick answers about Phenobarbital, drawn from the data on this page.

What is Phenobarbital?

What is Phenobarbital used for?

Commonly cited benefits of Phenobarbital include: Long-term seizure prevention in selected generalized or focal seizure disorders; Neonatal seizure management in specialist settings; Sedative-hypnotic use is now limited because safer alternatives usually exist. NutriStack rates the overall evidence as strong.

What is a typical dose of Phenobarbital?

A typical adult dose of Phenobarbital is Adult anticonvulsant maintenance is commonly 60-200 mg/day individualized by response and serum levels; sedative dosing is lower and indication-specific.. The commonly recommended form is Oral tablet or elixir for maintenance; injectable formulation in acute or inpatient settings. These are general ranges, not personalized advice; confirm the right dose with a clinician.

What are the side effects of Phenobarbital?

Reported side effects include sedation, cognitive slowing, ataxia, dizziness, respiratory depression at high doses or with sedatives, dependence and withdrawal seizures. This is educational information; check with a healthcare professional before use.

How strong is the evidence for Phenobarbital?

NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.

Use this with your stack

Phenobarbital in NutriStack.

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