Mood stabilizers lamotrigine

Optimize the dose of mood stabilizing medication(s) before adding on lithium, lamotrigine, or antidepressant (e.g., bupropion or an SSRI) if psychotic features are present, add on an antipsychotic ECT used for severe or treatment-resistant depressive episodes or for psychosis or catatonia... 

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. 

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). 

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). 

First, initiate anchor optimize mood-stabilizing medica- First, two or three drug combinations lithiumP lion lithiumP or lamotrigine ... 

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. 

The mainstay of therapy, a mood stabilizer, should be continued at the same dose that was used to achieve remission during acute phase therapy. Ongoing use of the mood stabilizer requires periodic monitoring of medication levels to ensure compliance. In addition to other laboratory evaluations such as complete blood counts, liver, kidney, and thyroid studies are needed to ensure that the mood stabilizer is being well tolerated. Lamotrigine is the only mood stabilizer that does not require periodic laboratory monitoring. 

Recently, other medications have been evaluated as mood stabilizers. This includes gabapentin (Neurontin), lamotrigine (Lamictal), and topiramate (Topamax). Only lamotrigine has been shown in controlled trials to be effective in the treatment... 

Treatment of choice - mood stabilizer with or without an antidepressant (e.g. lithium, valproate, carbamazepine, lamotrigine). Antidepressants include an SSRI, venlafaxine, mirtazepine as possibilities but few controlled trials to substantiate choice. 

Controlled trials of combinations of mood stabilizers with single mood stabilizer, or of the newer anticonvulsants (e.g., lamotrigine and topiramate) are in process. Open trials have included add-on medications and heterogeneous samples. 

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. 

It is very important to choose medications with the least possibility of making an ill pediatric patient suffer additional morbidity from side effects to medication directed at mood or behavior. For these reasons, mood stabilizers such as lamotrigine (which carries with it the risk of a severely toxic rash) should be seen only as third- or fourth-line agents. 

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... 

Lamotrigine, another anticonvulsant, has been shown to be a potentially good mood stabilizer with both antidepressant and antimanic efficacy (Fatemi et ul., 1997 Calabrese et al., 1999). 

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. 

Anticonvulsants, such as lamotrigine, valproate, or CBZ, with or without other mood stabilizers... 

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. 

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. 

Lamotrigine. Lamotrigine is approved as an anticonvulsant but not as a mood stabilizer. It is postulated to inhibit sodium channels and to inhibit the release of glu-... 

For maintenance treatment, failure of first-line mood stabilizers or second-line atypical antipsychotics to control symptoms adequately may lead to monotherapy trials with other anticonvulsants such as carbamazepine, lamotrigine, gabapentin, and topiramate (third-line monotherapy). 

To review the mechanism of action of lithium and five anticonvulsants used as mood stabilizers (valproic acid, carbamazepine, lamotrigine, gabapentin and topiramate). 

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). 

Mood stabilizers, such as lithium, lamotrigine, and carba-mazepine, may be effective in treating glucocorticoid-induced mood symptoms. In an open trial, 12 patients with glucocorticoid-induced manic or mixed symptoms were treated with olanzapine 2.5 mg/day initially, increasing to a maximum of 20 mg/day 11 of the 12 patients had significant improvement (505). 

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. 

In a double-blind, placebo-controlled study, 175 manic or recently manic patients were stabilized over 8-16 weeks with lamotrigine 100-400 mg/day (n = 59), lithium in a dose sufficient to produce a serum concentration of 0.8-1.1 mmol/1 (n = 46), or placebo and were then randomized to continued treatment (94). Both lamotrigine and lithium were superior to placebo in prolonging the time to the next episode of any mood disturbance. Lamotrigine, but not lithium, was superior to placebo in prolonging the time to a depressive episode. Lithium, but not lamotrigine, was superior to placebo in prolonging the time to a manic, hypomanic, or mixed episode. 

While there are no absolute contraindications to lithium, patients with advanced kidney disease or unstable fluid/ electrolyte balance may be more safely treated with an alternative mood stabilizer, such as carbamazepine, valproate, lamotrigine, or olanzapine. 

Dembowski C, Rechlin T. Successful antimanic treatment and mood stabilization with lamotrigine, clozapine, and valproate in a bipolar patient after lithium-induced cerebellar deterioration. A case report. Pharmacopsychiatry 2003 36(2) 83-6. 

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