lamotrigine LAMICTAL
Class: AED/Mood StabilizerFDA Indications: Bipolar Disorder, Epilepsy
Off-Label Use: Neuropathic Pain, Trigeminal Neuralgia, Cluster Headaches, Migraines, OCD, PTSD, Schizoaffective Disorder, Borderline Personality Disorder, Hallucinogen Persisting Perception Disorder, Depersonalization Disorder, Behavioral Disturbances With Dementia, Delirium (with lorazepam)
Prescribing
Forms: 25, 100, 150, 200 mg tablet; 25, 50, 100, 200, 250, 300mg Tablet Extended Release 24 Hour; 25, 50, 100, 200mg ODTDose Range: 100-400 mg/day
Starting: Initial: Weeks 1 and 2: 25 mg qd; Weeks 3 and 4: 50 mg qd; Week 5: 100 mg qd; Week 6 and maintenance: 200 mg qd
Stopping: ↓ dose by ~50% per week, over at least 2 weeks unless safety concerns require a more rapid withdrawal.
Monitoring: Serum levels of concurrent anticonvulsants, LFTs, renal function
Precautions
Serious Side Effects: Stevens-Johnson syndrome (0.08-0.3%), aseptic meningitis, myoclonus after 2-3 years of treatment; lamotrigine is the third most common drug associated with DRESS; there have been 8 cases of Lamotrigine-Associated Hemophagocytic Lymphohistiocytosis since its FDA approval in 1994.Side Effects: headache, sedation/somnolence, dizziness, diarrhea, nausea, vomiting, benign rash (10-11%)
Pharmacodynamics
1° MOA: Inhibits release of glutamate and inhibits voltage-sensitive Na+ channels, which stabilizes neuronal membranes; weak inhibitory effect on the 5HT3 receptorPharmacokinetics
t½: 25 (15-35)° TMAX: 1-3°Substrate of: N-glucuronidation via UGT1A4; UGT1A1, UGT2B7
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - valproic acid inhibits lamotrigine glucuronidation, doubling its t½, so need to half lamotrigine dose
- - carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, and atazanavir/ritonavir all induce lamotrigine glucuronidation
- - birth control pills, because of their enzyme induction, can ↓ lamotrigine levels
Misc
- - one of the best tolerated mood stabilzers with little weight gain or sedation
- - if a patient discontinues for ≥5 half-lives, initial dosing titration must be restarted
- - more effective in preventing depressive episodes than preventing mania, "a better floor than a ceiling," i.e. does not have good efficacy for acute bipolar mania
Special Populations
Category C—Fetal and/or placental concentrations similar to those in maternal plasma, generally considered by OBGYNs to be the mood stabilizer of choice during pregnancy
RID 9.2%; Limited Human Data—Potential Toxicity
Clearance is reduced by about a third in the elderly
There are no dosage adjustments required though t½ is longer in patients with renal failure
Moderate to severe impairment without ascites: ↓ initial, escalation, and maintenance doses by ~25%
Moderate to severe impairment with ascites: Decrease initial, escalation, and maintenance doses by ~50%
References
Lamictal Package InsertApplied Clinical Pharmacokinetics And Pharmacodynamics Of Psychopharmacological Agents
Concise Guide To Drug Interaction Principles For Medical Practice
Foye's Principles Of Medicinal Chemistry
Successful Psychopharmacology: Evidence-Based Treatment Solutions For Achieving Remission
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