Mania lamotrigine

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... 

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. 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

Turning to the pharmacotherapy for mania, for decades lithium was the only effective drug treatment. More recently, a number of antiepileptic drugs including carba maze pine, lamotrigine and valproate have been shown to also act as mood stabilisers and are becoming established for the treatment and prophylaxis of both unipolar mania and bipolar manic depressive disorders. 

Agents that increase GABA activity or decrease glutamate activity are used for the treatment of mania and for mood stabilization (eg, benzodiazepines, lamotrigine, lithiurn, or valproic acid). 

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. 

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

Lamotngine (Lamictal). Lamotrigine, another anticonvulsant used to treat BPAD, is currently FDA approved for the prevention of both depressive and manic episodes during BPAD maintenance therapy. This represents a shift in the paradigms for BPAD therapy, as medications used to treat acute episodes have also typically been used for antimanic prophylaxis. Lamotrigine is not effective in the acute treatment of mania but has become for many the drug of choice for bipolar depression as well as for prevention of subsequent mood episodes of either polarity. 

In addition to these drugs, many of the newer antiepileptic drugs such as lamotrigine have found a place in the therapeutic management of mania. These are extensively covered in Chapter 12. 

There are three reports (Hsu and Starzinsi, 1986 Woolston, 1999 Craven and Murphy, 2000) on a total of six bipolar adolescents treated with CBZ—three with acute mania, two of whom responded (Hsu and Starzinski, 1986). As in studies of adults, antipsychotic and/or antianxiety medications were frequently used adjunctively in subjects of these reports. Gabapentin, topiramate, and lamotrigine have been minimally studied for the treatment of acute mania in youth. Davanzo and McCracken review these limited data in Chapter 25 in this volume. 

These data suggest that there is more available information for use of lithium than for other mood stabilizers, and that adolescents hospitalized with adolescent-onset, acute mania have rates of response between 50% and 80%. Supplementation with sedating medication appears to be common but not systematically evaluated. Children hospitalized with mania also respond to lithium, but their comorbid disorders often need separate attention. Open trials with DVP in hospitalized adolescents are also supported. There is much less information on CBZ and there are no data on newer anticonvulsants such as lamotrigine, topiramate, or gabapentin. These data are largely consistent with data from studies of hospitalized adults with classic mania. 

Ichim, L., Berk, M., Brook, S. Lamotrigine compared with lithium in mania a doubleblind randomized controlled trial. Am. J. Ctin. Psychiatry 12, 5—10, 2000. 

ECT should be considered for more severe forms of depression (e.g., those associated with melancholic and psychotic features, particularly when the patient exhibits an increased risk for self-injurious behavior) or when there is a past, well-documented history of nonresponse or intolerance to pharmacological intervention. Limited data indicate that bipolar depressed patients may be at risk for a switch to mania when given a standard TCA. A mood stabilizer alone (i.e., lithium, valproate, carbamazepine, lamotrigine), or in combination with an antidepressant, may be the strategy of choice in these patients. Some elderly patients and those with acquired immunodeficiency syndrome may also benefit from low doses of a psychostimulant only (e.g., methylphenidate) (see also Chapter 14, The HIV-Infected Patient ). Fig. 7-1 summarizes the strategy for a patient whose depressive episode is insufficiently responsive to standard therapies. 

Lamotrigine has been approved as an adjunctive treatment for partial and generalized seizures. Its mechanism of action is thought to involve inhibition of glutamate release (227, 228). Open-label, case series reports and ongoing double-blind, controlled trials have explored this agent s usefulness in both bipolar mania and depression (229, 230). 

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. 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

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). 

Mazure CM. Lamotrigine as prophylaxis against steroid-induced mania. J Clin Psychiatry 1999 60(10) 708-9. 

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). 

Lithium is an alkaline earth element that is used medicinally in the form of salts such as lithium chloride and lithium carbonate. Its main use is in the prevention or attenuation of recurrent episodes of mania and depression in individuals with bipolar mood disorder (manic depression). Lithium also has clearly established antima-nic activity, although its relatively slow onset of action often necessitates the use of ancillary drugs, such as antipsychotic drugs and/or benzodiazepines, at the start of therapy. If lithium alone is ineffective for recurrent bipolar mood disorder, combining it or replacing it with car-bamazepine or valproate may be of value reports with lamotrigine and olanzapine are also encouraging. 

In a subanalysis of two 18-month maintenance studies of the use of lithium, lamotrigine, or placebo in delaying relapse in subjects with type I bipolar illness, 98 subjects 55 years of age or older were identified (82). Lithium delayed the time to mania compared with placebo, but lamotrigine also delayed the time to either mania or depression compared with placebo. 

The adverse effects of lithium in elderly patients include cognitive status worsening, tremor, and hypothyroidism. The authors suggested that divalproex is also useful in elderly patients with mania and that concentrations of divalproex in the elderly are similar to those useful for the treatment of mania in younger patients. They noted that carbamazepine should be considered a second-line treatment for mania in the elderly. A partial response would warrant the addition of an atypical antipsychotic drug. For bipolar depression, they recommended lithium in combination with an antidepressant, such as an SSRI. They also noted that lamotrigine may be useful for bipolar depression. Electroconvulsive therapy (ECT) may also be useful, but there have been no comparisons of ECT and pharmacotherapy in elderly patients with bipolar depression. 

Use alone or in combina tion with other drugs (e.g, lithiunry catbatnaz-epin antipsychoti(3) for the acute treatment of mania and for rtrainte-nance trealmenl Use caution when combining with lamotrigine because ot potential drug interaction. 

Addition of a mood stabilizing anticonvulsant such as valproate, carbamazepine, or lamotrigine may be helpful in both schizophrenia and bipolar mania... 

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