Use of topiramate, a new anti-epileptic as a mood stabilizer

Marcotte, David

doi:10.1016/s0165-0327(98)00110-4

Cited by 178 publications

(91 citation statements)

References 14 publications

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“…Thus, in one open study, half of the 44 treatment-refractory bipolar disorder patients showed moderate or marked improvement in symptoms when topiramate was added to existing therapy (Marcotte, 1998). In a recent study, bipolar patients showed improvement in mood following topiramate, in particular when patients exhibited manic symptoms at initiation of treatment (McElroy et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Husum

Kammen

Termeer

et al. 2003

Neuropsychopharmacol

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Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY-and galanin-like immunoreactivities (LI) while NPY-and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.

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Section: Discussionmentioning

confidence: 99%

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Husum

Kammen

Termeer

et al. 2003

Neuropsychopharmacol

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“…When first evaluated in the treatment of bipolar disorder, topiramate showed promise, both for the initial positive reports in open trials 36 and for its documented weight-losing properties. 37,38 Unfortunately, in a series of controlled trials for acute mania, topiramate was no better than placebo.…”

Section: Anticonvulsantsmentioning

confidence: 99%

Treatment-resistant bipolar disorder

2006

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Despite the remarkable increase in medications validated as effective in bipolar disorder, treatment is still plagued by inadequate response in acute manic or depressive episodes or in long-term preventive maintenance treatment. Established first-line treatments include lithium, valproate and second-generation antipsychotics (SGAs) in acute mania, and lithium and valproate as maintenance treatments. Recently validated treatments include extended release carbamazapine for acute mania and lamotrigine, olanzapine and aripiprazole as maintenance treatments. For treatment-resistant mania and as maintenance treatments, a number of newer anticonvulsants, and one older one, phenytoin, have shown some promise as effective. However, not all anticonvulsants are effective and each agent needs to be evaluated individually. Combining multiple agents is the most commonly used clinical strategy for treatment resistant bipolar patients despite a relative lack of data supporting its use, except for acute mania (for which lithium or valproate plus an SGA is optimal treatment). Other approaches that may be effective for treatment-resistant patients include high-dose thyroid augmentation, clozapine, calcium channel blockers and electroconvulsive therapy (ECT). Adjunctive psychotherapies show convincing efficacy using a variety of different techniques, most of which include substantial attention to education and enhancing coping strategies. Only recently, bipolar depression has become a topic of serious inquiry with the dominant controversy focusing on the place of antidepressants in the treatment of bipolar depression. Other than mood stabilizers alone or the combination of mood stabilizers and antidepressants, most of the approaches for treatment-resistant bipolar depression are relatively similar to those used in unipolar depression, with the possible exception of a more prominent place for SGAs, prescribed either alone or in combination with antidepressants. Future work in the area needs to explore the treatments commonly used by clinicians with inadequate research support, such as combination therapy and the use of antidepressants as both acute and adjunctive maintenance treatments for bipolar disorder. With the first report of lithium's efficacy in 1949 by Cade, bipolar disorder has the longest record of treatment efficacy among the major Axis I disorders. Furthermore, after more than half a century of clinical research, multiple agents from many different pharmacological classes have shown at least some efficacy, while many other agents (albeit without a consistent database demonstrating their utility) are prescribed regularly by clinicians. Yet, despite this plethora of choices, treatment of bipolar disorder remains suboptimal from the points of view of clinicians and patients alike. Whether measured by recovery time from manic or depressive episodes or preventive efficacy of maintenance treatments, bipolar disorder is characterized by sluggish responses, inadequate responses, poor compliance and recurrences in controlled cli...

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“…In open stud ies and chart re views, topi ra mate has dem on strated broad spec trum thy mo lep tic ef fects in some bi po lar dis or der pa tients (75)(76)(77)(78)(79)(80)(81)(82). Con trolled tri als in acute ma nia are un derway.…”

Section: Treatmentmentioning

confidence: 99%

Antipsychotic Metabolic Effects: Weight Gain, Diabetes Mellitus, and Lipid Abnormalities

2001

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(Weight clas si fi ca tion by BMI is shown in Ta ble 1.) These preva lence sta tis tics re flect a rapid tra jec tory of change over the past 20 years (4). Obe sity increases the risk for a myr iad of medi cal dis or ders, some forms of can cer, and all-cause mor tal ity (1,5).Re ports of weight gain in duced by con ven tional an tipsy chotics (CAPs, for ex am ple, chlor pro maz ine) be gan to ap pear soon af ter their avail abil ity (6,7). Atypi cal an tipsy chot ics (AAs, for ex am ple, risperi done, ol an zap ine, queti apine, clozap ine) of fer en hanced ef fi cacy in the treat ment of psy chotic dis or ders and are rec om mended as a first-line phar ma cothera peu tic strat egy for schizo phre nia (8). Al though AAs offer an im proved neu ro logi cal side-effect pro file, sev eral AAs ap pear to pos sess greater weight gain li abil ity than CAPs.Antipsychotic-induced weight gain has been de scribed as highly dis tress ing to pa tients, ad versely af fect ing selfesteem, and, al though dif fi cult to quan tify, de creas ing treatment ad her ence (9).The es ti mated preva lence of obe sity among per sons with schizo phre nia con verges with and may ex ceed that of the gen eral popu la tion (10). Fur ther, chronic psy chi at ric pa tients ex hibit high rela tive rates of ad verse health be hav iours (such as smok ing) and sev eral medi cal dis or ders (11).This re view sum ma rizes AA-induced weight gain and the poten tial im pact of these agents on the glu cose ho meo static network and lipid mi lieu. Weight Gain: Comparative LiabilityAntipsychotic-induced weight gain is of ten re ported in an idio syn chra tic man ner. Most authors re port an ab so lute weight change; less re ported, but per haps more clini cally rele vant, are meas ure ments such as weight gain greater than or equal to 7% from base line or pe riph eral ver sus cen tral

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Use of topiramate, a new anti-epileptic as a mood stabilizer

Cited by 178 publications

References 14 publications

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Treatment-resistant bipolar disorder

Antipsychotic Metabolic Effects: Weight Gain, Diabetes Mellitus, and Lipid Abnormalities

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