Mood Stabilizers topiramate

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. 

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... 

Mood stabilizers phenytoin, valproate, topiramate Sedative/anxiolytics diazepam, barbiturates Beta-blockers propranolol... 

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. 

Virtually all anticonvulsants are or have been of interest for the treatment of bipolar disorder. However, the importance of controlled data cannot be understated. For example, gabapentin, an anticonvulsant that initially received much attention as a potential mood stabilizer, was compared with placebo and did not appear to stabilize mood (Frye et al. 2000 Pande et al. 2000). Similar negative results were seen with topiramate in placebo-controlled trials for the treatment of mania. Although these medications might be useful adjuncts in some patients, given the currently expanded pharmacopoeia of medications with positive controlled trial data in bipolar disorder, we do not recommend the primary use of agents that have only case reports as an evidence base or controlled studies with predominantly negative results. 

Marcotte D. Use of topiramate, a new anti-epileptic as a mood stabilizer. J Affect Disord 1998 50 245-251. 

Eads LA, Kramer T, Wooten G. Use of topiramate as a mood stabilizer. 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. 

Topiramate. Topiramate is another compound approved as an anticonvulsant and in clinical testing as a mood stabilizer. Its mechanism of action appears to be to enhance... 

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). 

A 28-year-old man with type I bipolar manic disorder was treated with clozapine 550 mg /day he gained 25 kg, and topiramate, a mood stabilizer increasingly used as a weight suppressor, was added (25 mg bd for 1 week increased to 200 mg bd for 5 weeks). His white blood cell count had been 9-10 xl09/l for 2 years while he was taking clozapine, and his complete blood counts were normal for 4 weeks after the addition of topiramate however, but at 5 weeks his white blood cell count was 3.7 xl09/l. 

A 41-year-old woman with a diagnosis of bipolar disorder developed severe suicidality when topiramate was added to her previous treatment (carbamazepine and levothyroxine) for mood stabilization (649). 

For bipolar patients, given the risk of relapse in the postpartum period, mood stabilizer treatment, especially with agents with better evidence of efficacy than topiramate, should generally be restarted immediately after delivery if patient is unmedicated during pregnancy... 

Chengappa KR, Gerstion S, Levine J. The evolving role of topiramate among other mood stabilizers in the management of bipolar disorder. Bipolar Disord. 2001 3 215-232. 

The use of antiepileptic drugs (gabapentin, lamotrigine, and topiramate) as mood stabilizers has been... 

The place in therapy of the newer anticonvulsants, such as gabapentin, levetiracetam, tiagabine, topiramate, and zon-isamide, is controversial. Many clinicians consider these agents to be less effective than established mood stabilizers based on initial studies and avoid them for monotherapy in bipolar disorder. 

Mood stabilizers can be used as augmentation therapy in cases of partial response to antidepressant therapy, especially those with prominent irritability or anger. Anticonvulsants (thought to exert their mechanism in part through antikindling effects) have been effective in treating PTSD. In a retrospective review topiramate reduced nightmares and flashbacks. Divalproex sodium was effective in an open trial. ... 

Topiramate also antagonizes the effects of glutamate at non-N-methyl-o-aspartate (non-NMDA) receptors, and it also inhibits certain isoenzymes of carbonic anhydrase, although this effect may not be a major feature of its antiepileptic/mood-stabilizing activity. 

All in all, compared with the well-established group of mood stabilizers (lithium, carbamazepine, and valproate), topiramate is currently considered the least potent/efficacious in ameliorating both manic and/or depressive symptoms (see Section 2.22). 

Gupta S, Masand PS, Frank B et al. Topiramate in bipolar and schizoaffective disorder mood stabilizing properties in treatment refractory patients. XXII Collegium Internationale Neuropsychopharmacologicum Conference, Brussels, Belgium, July 2000. 

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