Headache lamotrigine

Lamotrigine Modulate sodium channels Loading dose Not recommended due to increased risk of rash Maintenance dose 1 50-800 mg/day in 2-3 divided doses. Doses should be initiated and titrated according to the manufacturer s recommendations to reduce the risk of rash Half-life Not established Monotherapy 24 hours Concurrent enzyme inducers 12-15 hours Concurrent enzyme inhibitors 55-60 hours Apparent volume of distribution 1.1 L/kg Protein binding 55% Primary elimination route Hepatic Ataxia, drowsiness, headache, insomnia, sedation Rash... 

Lamotrigine Diplopia Dizziness Unsteadiness Headache Rash Not established... 

The most frequent side effects are diplopia, drowsiness, ataxia, and headache. Rashes are usually mild to moderate, but Stevens-Johnson reaction has also occurred. The incidence of the more serious rashes appears to be increased in patients who are also receiving valproic acid and who have rapid dosage titration. Valproic acid substantially inhibits the metabolism of lamotrigine. 

Lamotrigine is well tolerated and is not associated with hepatotox-icity, weight gain, or significant sedation. Common early side effects include headache, dizziness, gastrointestinal distress, and blurred or double vision. The most serious potential side effect is rash (described in the following subsection). 

The authors commented that the manic symptoms had probably been caused by glucocorticoids or glucocorticoid withdrawal. They concluded that patients with cluster headache and a history of affective disorder should not be treated with glucocorticoids, but with valproate or lithium, which are effective in both conditions. Lamotrigine, an anticonvulsive drug with mood-stabilizing effects, may prevent glucocorticoid-induced mania in patients for whom valproate or lithium are not possible (101). 

Side effects. The most common side effects are headache, nausea and vomiting, diplopia, dizziness, ataxia and tremor. There are also reports that lamotrigine can cause such psychiatric side effects as aggression, agitation, confusion, hallucinations and psychosis, some of these effects possibly being associated with a reduction in the glutamatergic system. Rashes are a frequent side effect, occurring in up to 5% of patients. Usually rashes are mild but occasionally can be severe and amount to a Stevens-Johnson syndrome. The severe rash occurs more commonly in children. 

A 36-year-old woman with rapid-cycling bipolar II disorder and premenstrual mood exacerbation was treated as an out-patient with lamotrigine 400 mg/day, clonazepam 0.5 mg tds, and quetiapine 100 mg/day. She gained 9 kg in 6 months and was advised to reduce the dose of quetiapine to 50 mg/day. After 1 day, she reported nausea, dizziness, headache, and anxiety severe enough to preclude normal daily activities. She was instructed to take quetiapine 75 mg/day, but her symptoms continued and only resolved when she took 100 mg/day. Slower reduction in the dose of quetiapine (by 12.5 mg/day every 5 days) with an antiemetic, ondansetron, also failed. On a third attempt, prochlorperazine successfully reduced her withdrawal symptoms, although moderate nausea persisted for 2 days after complete withdrawal. 

Lamotrigine has been nsed as maintenance monotherapy for rapid-cycling bipolar disorder in 324 patients (open label) and 182 patients (donble-bUnd) with rapidcycling bipolar disorder (5). In aU, 265 patients reported adverse events during the open phase. The most common adverse events (over 10%) were headache, infection, influenza, nausea, abnormal dreams, dizziness, and rash. During the donble-bUnd phase 122 patients reported adverse events, eqnaUy with lamotrigine and placebo. 

In 126 patients with carbamazepine-resistant or valproate-resistant epilepsy given lamotrigine, 50% during add-on therapy and 53% during lamotrigine monotherapy had at least 50% reduction in total seizures (15). There were adverse events in 49 patients, including respiratory tract infections n — 11), dizziness (n — 8), headache (n = 7), diplopia (n = 5), tremor (n = 5), somnolence (n — 4), insomnia (n = 4), nausea (n — 4), and weakness (n = 3). Treatment was discontinued in nine patients because of adverse events, in five cases because of rash. 

The most common adverse effects of lamotrigine include dizziness, weakness, headache, diplopia, ataxia, blurred vision, and somnolence (SEDA-18, 65) (SEDA-20, 63) (19). These effects resemble those seen with carbamaze-pine and can result from an adverse pharmacodynamic interaction. Tolerability is better when lamotrigine is given as monotherapy or with drugs other than carbama-zepine however, tremor develops in some patients taking valproate in combinations (SEDA-18, 66). During monotherapy, serum lamotrigine concentrations associated with intolerable adverse effects (mostly headache, dizziness, and ataxia) were 0.4-18.5 qg/ml and overlapped widely with those tolerated in other patients (20). 

Lamotrigine is reported to be generally well tolerated in maintenance studies, with the most common adverse events being headache, nausea, insomnia, and, to a lesser extent, tremor. Incidences of diarrhea and tremor are lower with lamotrigine than with litbium. 

Nervous system The effects of levetiracetam ( = 38), lamotrigine (n = 29), and phenobar-bital (n = 28) have been evaluated in patients with seizures and Alzheimer s disease in a prospective, randomized, three-arm parallel-group, case-control study with a 4-week dosage adjustment and a 12-month evaluation period [199. The adverse reactions were somnolence (5.7%), dizziness (2.8%), headache (2.8%), and weakness (5.7%). Neuropsychological examination showed improvement in attention, shortterm memory, and oral fluency in patients randomized to levetiracetam. 

Placebo-controUed studies In a 16-week, double-blind, placebo-controlled, flexible-dose study of lamotrigine in binge-eating disorder associated with obesity, 51 outpatients were randomized to either lamotrigine (n = 26) or placebo (n = 25) [146 ]. Four patients withdrew because of adverse events (lamotrigine, n = 3 placebo, n = 1), the most common of which were headache (35% versus 28%), insomnia (35% versus 20%), somnolence (27% versus 8%), rash (15% versus 12%), and dry mouth (15% versus 0%). 

Systematic reviews The major studies on the safety and tolerability of rufinamide were reviewed [157 ]. In placebo-controlled trials and pooled analyses, the most common adverse effects reported with rufinamide were somnolence and vomiting. Headache and pyrexia were also reported more frequently with rufinamide compared to placebo. In terms of drug-drug interactions, rufinamide may slightly increase the clearance of CBZ and lamotrigine and may slightly decrease the clearance of phenytoin and phenobarbital. VPA may significantly decrease the clearance of rufinamide. 

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