carbamazepine

General Information

Carbamazepine is an anticonvulsant used off-label as a mood stabiliser for acute mania and maintenance when lithium or valproate are ineffective or poorly tolerated.

Autoinduction and extensive drug interactions require careful titration and monitoring.

The contrast view can help compare dosing, metabolic burden, and monitoring requirements; carbamazepine-focused evidence and the carbamazepine print page can support shared decision-making and counseling.

The bipolar disorder hub supports mania-management workflows and guidance on mood stabiliser combinations.

Considered second-line in bipolar disorder due to complex kinetics, hematologic risk, and drug interactions; valuable in mixed and rapid-cycling presentations.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Blocks voltage-gated sodium channels and reduces glutamate release, stabilizing neuronal firing.

Induces hepatic enzymes, influencing many psychotropic drug levels.

• Voltage-gated sodium channel blocker with downstream modulation of excitatory neurotransmission.

Metabolism and Pharmacokinetics

• Oral bioavailability 70–80%; peak 4–8 h (IR) or 6–24 h (XR).
• Metabolized via CYP3A4 to active 10,11-epoxide; autoinduction lowers half-life to 12–17 h after chronic dosing.
• Eliminated renally as metabolites.
• Autoinduction develops over the first several weeks; serum levels may fall after an initially stable dose, so a planned level recheck after 3–4 weeks helps avoid underdosing.

Dosing and Administration

• Typical start is 200 mg BID; increase by 200 mg/day every 3–5 days to 800–1,200 mg/day (max 1,600 mg).
• Target serum concentration 4–12 µg/mL; levels are often checked 3–5 days after dose changes and again after 3–4 weeks to account for autoinduction.
• When sedation, dizziness, or diplopia limit titration, slower dose increases (smaller steps with longer intervals) are often better tolerated than rapid escalation.

Monitoring & Labs

• Baseline: CBC (including WBC/ANC), LFTs, sodium; HLA-B*1502 testing in at-risk ancestry.
• Ongoing: periodic CBC, LFTs, and sodium; monitoring for rash and hyponatremia/SIADH.
• Serum levels: trough monitoring can be helpful in select cases; autoinduction and strong CYP induction create many drug interactions.
• Recheck serum level after 3–4 weeks on a stable dose to account for autoinduction, and again after adding or stopping strong CYP3A4 inhibitors/inducers.
• Medication reconciliation at each visit (oral contraceptives, warfarin or other anticoagulants, antipsychotics) because enzyme induction can lower exposure and change clinical response.
• Contraception interactions and rash/fever warning signs are typically reviewed.

Sources: FDA label; guideline recommendations; pharmacogenetics advisories. Because carbamazepine is a strong inducer with autoinduction, documentation of the monitoring plan (CBC/LFT/sodium cadence, level timing, and contraception counseling) helps reduce avoidable adverse events, especially in complex polypharmacy in most clinical settings.

Adverse Effects

Interactions

• Strong inducer of CYP3A4, CYP1A2, CYP2C, and UGT—reduces levels of antipsychotics, antidepressants, oral contraceptives.
• Reduced hormonal contraceptive efficacy is common; backup or non-hormonal contraception planning is typically discussed when pregnancy is possible.
• Enzyme induction can also lower exposure to some anticoagulants and other narrow-therapeutic-index drugs; clinical response monitoring and dose adjustments are often needed rather than assuming medication failure.
• CYP3A4 inhibitors (erythromycin, ketoconazole) raise carbamazepine levels—risk toxicity.
• Valproate inhibits epoxide hydrolase, increasing active metabolite; toxicity monitoring is important.

Other Useful Information

• Baseline labs typically include CBC, CMP, pregnancy test, and HLA screening (as indicated).
• Contraception planning matters because carbamazepine reduces efficacy of hormonal contraceptives.
• Rash and infection symptoms requiring urgent evaluation are typically reviewed with patients.
• Printable counselling guidance from the carbamazepine print page can reinforce contraception planning and monitoring expectations.
• Abrupt discontinuation is generally avoided; tapering plans help prevent seizure rebound (in epilepsy) and mood destabilization (in bipolar disorder).
• Grapefruit or other strong CYP3A4 inhibitors can raise carbamazepine levels and are generally avoided; sudden level increases can lead to dizziness, diplopia, and ataxia.

References

1. TEGRETOL (carbamazepine) prescribing information — DailyMed (2025)
2. CANMAT/ISBD 2021 guidelines for the management of bipolar disorder — Bipolar Disorders (2021)
3. Bipolar disorder: assessment and management (CG185) — National Institute for Health and Care Excellence (2014)
4. Clinical pharmacokinetics of carbamazepine — Clinical Pharmacokinetics (1978)
5. Extended Release Carbamazepine Capsules IN THE Treatment OF Acute Mania — American Journal of Psychiatry (2004)
6. FDA Carbamazepine Pharmacogenetics 2024