Lamotrigine bipolar disorder

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Lamotrigine is effective for the maintenance treatment of bipolar disorder. It is more effective for depression relapse prevention than for mania relapse. Its primary limitation as an acute treatment is the time required for titration to an effective dosage. In addition to maintenance monotherapy, it is sometimes used in combination with lithium or divalproex, although combination with divalproex increases the risk of rash, and lamotrigine dosage adjustment is required.37... 

Mechanism of Action The mechanism of action of lamotrigine appears to involve blockage of ion channels and effects on glutamate transmission, although the precise mechanism in bipolar disorder is not clear.33... 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Dosage regimen for bipolar disorder The target dose of lamotrigine is 200 mg/day (100 mg/day in combination with valproate and 400 mg/day in combination with carbamazepine or other enzyme-inducing drugs). Doses above 200 mg/day are not recommended. 

Escalation Regimen for Lamotrigine for Patients with Bipolar Disorder... 

Dosage adjustment for bipolar disorder If other drugs are subsequently introduced, the dose of lamotrigine may need to be adjusted. In particular, the introduction of... 

Discontinuation strategy in bipolar disorder As with other AEDs, lamotrigine should not be abruptly discontinued. 

Children Lamotrigine is indicated as adjunctive therapy for partial seizures in patients above 2 years of age and for the generalized seizures of Lennox-Gastaut syndrome. Safety and efficacy for other uses in patients younger than 16 years of age have not been established. Safety and efficacy in patients below the age of 18 years with bipolar disorder have not been established. 

Suicide The possibility of a suicide attempt is inherent in Bipolar Disorder, and close supervision of high-risk patients should accompany drug therapy. Write prescriptions for lamotrigine for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Overdoses have been reported for lamotrigine, some of which have been fatal. 

Fatemi, S.H., Rapport, D.J., Calabrese, J.R., and Thuras, P. (1997) Lamotrigine in rapid-cycling bipolar disorder. Clin Psychiatry 58 522-527. 

Calabrese JR, Suppes T, Bowden CL, et al A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. J Clin Psychiatry 61 841—850,... 

Manji HK, Chen G, Hsiao JK, et al Regulation of signal transduction pathways by mood-stabilizing agents implications for the delayed onset of therapeutic efficacy. J Clin Psychiatry 57 (suppl 13) 34 6, 1996 Marangell LB, Martinez JM, Ketter TA, et al Lamotrigine treatment of bipolar disorder data from the first 500 patients in STEP-BD. Bipolar Disord 6 139-143, 2004... 

On a slightly more positive note, combination treatments, such as combined mood stabilizers or mood stabilizer plus antidepressant, may decrease relapse rates early, aggressive intervention may shorten subsequent episodes and newer agents, such as VPA, CBZ, or lamotrigine may benefit previously resistant subgroups of bipolar disorders. It is also encouraging that patients in good remission on lithium often view themselves favorably compared with normal control subjects on life satisfaction and adjustment measures. 

Suppes T, Brown ES, McElroy SL, et al. Lamotrigine for the treatment of bipolar disorder a clinical case series. J Affect Disord 1999 53 95-98. 

Earl NL, Greene P, Ascher J, et al. Mood stabilization with lamotrigine in rapid-cycling bipolar disorder. Presented at the American Psychiatric Association Annual Meeting, Chicago, May 13-18, 2000. 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Lamotrigine a review of its use in bipolar disorder. Drugs. 2003 63 2029-2050. 

Valproate + lithium/+ lamotrigine III Bipolar disorder NIMH... 

Three antiepileptic drugs have now been FDA approved as mood stabilizers for the prevention of recurring episodes of mania divalproex sodium (Depakote), extended-release carbamazepine (Equetro), and lamotrigine (Lamictal). Many of these drugs are prescribed to children for the control of epilepsy and, increasingly, for bipolar disorder. A critical question is their effect on the developing mental and emotional function of children, but there is little research on the subject (Loring, 2005). 

The role of lamotrigine in the treatment of bipolar disorder has been reviewed, and combination therapy with lamotrigine plus other mood stabilizers, including lithium, has been particularly discussed (81). Lamotrigine has a favorable tolerability profile compared with lithium, but lithium has better antimanic effects than lamotrigine, which exerts its antidepressant effects sooner than lithium. 

Lamotrigine is approved for the treatment of bipolar depression. This anticonvulsant has been shown to have antidepressant properties that are apparently unique among other anticonvulsants currently used for the treatment of bipolar disorder. Although lamotrigine s antimanic properties may be modest, because of its contribution to the often difficult-to-treat bipolar depressive episodes, we are likely to see its use increase. 

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