Accession Number

Rationale: Because some anti-epileptic drugs (AEDs) are effective in bipolar affective disorders, the new AED topiramate (TPM) may be effective in psychiatric illnesses. TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs. Methods: Charts of 58 consecutive patients, 39 outpatients (15 males, 24 females) and 19 inpatients (6 males, 13 females) were reviewed. TPM 25 mg. b.i.d. was added to existing therapy and titrated in 50 mg increments every 3-7 days. Improvement was rated on a Likert global assessment scale of marked, moderate, mild, or no improvement or worse, based on quality of sleep, appetite, mood, and concentration. Results: Of the 58 patients with psychiatric disorders, 44 patients had rapid cycling bipolar disorders characterized by manic, hypomanic, or mixed episodes. Eighteen patients had previously failed to respond to lamotrigine and/or gabapentin in addition to conventional mood stabilizers. Fourteen were Bipolar I, six Bipolar II, and seven mixed, ten patients had cyclothymic disorder, seven had bipolar disorder not otherwise specified. Of the remaining 14 patients nine had schizoaffective disorder, three patients had dementia and two had psychosis. Mean duration of TPM treatment was 16.0 weeks; mean TPM dosage approximately 200 mg/day. Thirty-six of 58 (62%) patients exhibited marked or moderate improvement, usually within days or weeks. Twenty-three of 44 (52%) patients with bipolar affective disorders showed marked or moderate improvement. Minimal/no improvement was observed in 16; six were rated as worse. Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM (800 mg) and tranylcypromine sulfate (170 mg) combined with alcohol. Other adverse effects were minor and included: paresthesias, somnolence, fatigue, impaired concentration and memory; nausea, and diarrhoea. Limitations: This study was performed in a nonrandom open and retrospective fashion. Therefore, any findings are limited by the design of this study: Conclusion: TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation. [References: 20]

1

UI - 26775

AU - Calabrese J

AU - Shelton MD

AU - Keck PE

AU - McElroy SL

AU - Werkner JE

TI - Topiramate in Severe Treatment-Refractory Mania

AB - To review the pharmacology of a new anticonvulsant and

present preliminary data regarding the compound's efficacy in

reatment- refractory hospitalized mania.

Topiramate is a recently marketed, structurally novel compound with documented anticonvulsant efficacy and a good safety profile. It is a sulfamate-substituted derivative of the naturally occurring monosaccharide D-fructose with multiple mechanisms of action. The objective for this study was to evaluate the antimanic efficacy of topiramate in the acute management of treatment-refractory, hospitalized mania over a 28-day study period in patients with bipolar I disorder. After a washout period of approximately three days, a11 patients (mean age 42.4, 7 female/4 male) hospitalized for severe mania were given open-label topiramate in initial doses of 50 mg/day and titrated upward by 50-150 mg increments to a mean (range) last dose of 614 mg/day (50-1300 mg/d). Outcome measures included the Young Mania Rating Scale YMRS), the 17-item Hamilton Depression Rating Scale (HAM-D), and the Brief Psychiatric Rating Scale (BPRS). The mean range) baseline YMRS was 32 (26-40) and decreased to 23 (2-40). The baseline HAM-D was 27 (20-36) and increased to 28 (17-37). The baseline BPRS was 47 (29-68) and decreased to 39 (18-63). Three patients exhibited a >= 50% improvement in the YMRS and two exhibited 25% to 49% improvement. Side effects with incidence rates > 10% included paresthesia, anorexia/weight loss, constipation, and nausea. These preliminary data suggest topiramate may have efficacy in mania.

MH - TREATMENT REFRACTORY

MH - REVIEW

MH - DEPRESSION

T2 - American Psychiatric Association Annual Meeting

Y2 - 1999 May

RP - NOT IN FILE

SO - 999 May 1;:

2

UI - 26774

AU - Ketter T

AU - Frye M

AU - Kimbrell TA

AU - Post RM

TI - Pharmacology and pharmacokinetics of new anticonvulsants

AB - Five new anticonvulsants -- felbamate, gabapentin, lamotrigine, fosphenytoin, and topiramate -- have recently been marketed, and four more -- tiagabine, oxcarbazepine, vigabatrin, and zonisamide -- are in advanced stages of development. These agents have varying mechanisms, metabolism, drug interactions, and adverse effects. Two important complementary mechanisms are enhancing GABAergic inhibition and suppressing glutamatergic excitation.

Felbamate has antiglutamatergic, GABAergic, and sodium channel blocking properties, and is metabolized to inactive and glucuronide metabolites. Felbamate is restricted to refractory epilepsy due to aplastic anemia and fatal hepatitis.

Gabapentin is a substrate and inhibitor of the large neutral amino acid carrier system, blocks sodium

hannels, and is excreted unchanged in the urine. Gabapentin may cause sedation, dizziness, and ataxia.

Lamotrigine decreases glutamate release, blocks sodium channels and 5HT3 receptors, and is metabolized to inactive glucuronides. Lamotrigine may cause rash, headache, and sedation.

Topiramate has antiglutamatergic, GABAergic, sodium channel blocking, and carbonic anhydrase inhibiting properties, and is mainly excreted unchanged in the urine. Topiramate can cause sedation, fatigue, psychomotor slowing, and renal calculi.

Except for gabapentin, all of these agents have hepatically mediated drug interactions, and knowledge of their pharmacokinetics is required for optimal therapeutics, should they be combined with psychotropics in epilepsy or treatment-resistant affective illness, or with other (nonpsychotropic) drugs in patients with medical comorbidity.

MH - EPILEPSY

MH - DRUGS

T2 - American Psychiatric Association Annual Meeting

Y2 -

RP - NOT IN FILE

SO - 1998 May;:

3

UI - 26776

AU - Marcotte DB

TI - Use of the new antiepileptic drug topiramate as a mood stabilizer

AB - Rationale: Because some antiepileptic drugs (AEDs) are effective in bipolar affective disorders, the new AED topiramate (TPM) may be effective in psychiatric illnesses. TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs.

Methods: Charts of 23 consecutive outpatients (eight males, 15 females) were reviewed. TPM 25 mg bid was added to existing therapy and titrated in 50-mg increments every three to seven days. Improvement was rated with a global assessment of sleep, appetite, mood, and concentration.

Results: Of 21 patients with rapid-cycling bipolar disorders characterized by manic, hypomanic, or mixed episodes, 12 were bipolar I, six bipolar II, and three cyclothymic; one patient had general anxiety disorder and one had organic psychosis. Mean duration of TPM treatment was 8.4 weeks; mean TPM

dosage, 200 mg/day. 13 of 23 (57%) patients exhibited marked or moderate improvement, usually within days or weeks. Minimal/no improvement was observed in four; six were rated as worse. Most of those rated as worse experienced symptoms known to be TPM side effects, including agitation in one patient with generalized anxiety disorder and confusion and hallucinations when TPM was increased from 200 to 600 mg/day in one bipolar patient with previous and subsequent episodes of psychotic symptoms when not taking TPM. Other adverse events were somnolence, fatigue, and impaired concentration and memory. Conclusion: TPM may be useful in patients with mood disorders unresponsive to traditional therapy.

MH - Female

MH - Therapy

MH - Side Effect

MH - Agitation

MH - Symptom

MH - DRUGS

MH - AFFECTIVE DISORDERS

MH - SLEEP

T2 - Ammerican Psychiatric Association Annual Meeting

Y2 - 1998 May

RP - NOT IN FILE

UR - Gabapentin: An Effective Therapy for Patients with Bipolar Affective Disorder

SO - 1999;: