Antimanic Efficacy of Topiramate in 11 Patients in an Open Trial With an On-Off-On Design

Grunze, Heinz; Normann, Claus; Langosch, Jens M.; Schaefer, Martin; Amann, Benedikt L.; Sterr, Andrea; Schloesser, Sandra; Kleindienst, Nikolaus; Walden, J.

doi:10.4088/jcp.v62n0610

Cited by 61 publications

(37 citation statements)

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“…Diminished GR sensitivity has been associated with MDD (for a review see Pariante and Miller, 2001). That TPM might increase the sensitivity of GR is consistent with observed effects of this compound in mood disorders (Chengappa et al, 1999;Grunze et al, 2001;Carpenter et al, 2002). On the other hand, in some subjects, primarily those with PTSD whose pretreatment lysozyme IC 50 values were relatively low, TPM had the effect of reducing the sensitivity of the receptor, similar to what was observed in rats who demonstrated decreased mRNA expression following treatment with TPM.…”

Section: Discussionsupporting

confidence: 56%

Effect of Topiramate on Glucocorticoid Receptor Mediated Action

Yehuda

Yang

Golier

et al. 2003

Neuropsychopharmacol

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This study examined the effects of topiramate (TPM) on glucocorticoid receptors (GRs) in mononuclear leukocytes of nine men and four women with chronic and recurring post-traumatic stress disorder (PTSD) and a group of comparison subjects (nine men, four women). A measure of 60 ml of blood was withdrawn by venipuncture at 0800 and mononuclear leukocytes were isolated. The cells were incubated with a series of concentrations of dexamethasone (DEX) without or with 50 mmol/l of TPM to evaluate the effects of DEX to inhibit lysozyme activity and the effect of TPM on it. ANCOVA compared the IC 50 for lysozyme inhibition under conditions of DEX only and TPM+DEX. TPM affected lysozyme IC 50 in the direction of increasing the sensitivity of the receptor in the sample as a whole. This effect was more pronounced in the mononuclear leukocytes from participants in the PTSD group, particularly in cells from subjects whose pretreatment lysozyme IC 50 was relatively higher (eg, reflecting decreased glucococorticoid receptor responsiveness), compared to the rest of the sample. In conclusion, further investigation of the actions of TPM on GR and other neuroendocrine systems may prove useful in understanding some of the other established clinical effects of this agent.

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Section: Discussionsupporting

confidence: 56%

Effect of Topiramate on Glucocorticoid Receptor Mediated Action

Yehuda

Yang

Golier

et al. 2003

Neuropsychopharmacol

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“…The reduction in arachidonic acid turnover in rats chronically administered lithium or carbamazepine was associated with decreases in the activity, protein, and mRNA of the arachidonic acid-selective cPLA 2 (31,32) as well as its transcription factor, activator protein-2 (56-58), whereas valproate likely targeted an arachidonic acid-selective fatty acyl-CoA synthetase (59). Topiramate, a drug that initial nonrandomized trials suggested was effective in bipolar disorder (60,61) and that was later found to have no therapeutic effect (62,63), upon chronic administration to rats did not alter arachidonic acid turnover in brain phospholipids (54,64). Because increased NMDA receptor-mediated signaling has been implicated in bipolar disorder (10,65,66) and because chronic NMDA has the opposite effect on brain arachidonic acid kinetics compared with each of the three effective antimanic drugs in rats, chronic NMDA-treated rats may represent a model of upregulated brain arachidonic acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Chronic N-methyl-d-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat

Lee

Rao

Chang

et al. 2008

Journal of Lipid Research

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Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive Nmethyl-D-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain arachidonic acid turnover, rats were daily administered NMDA (25 mg/kg, ip) or vehicle for 21 days. In unanesthetized rats, on day 21, [1-14 C]arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was euthanized at 5 min and its microwaved brain was subjected to chemical and radiotracer analysis. Using equations from our in vivo fatty acid model, we found that compared with controls, chronic NMDA increased the net rate of incorporation of plasma unesterified arachidonic acid into brain phospholipids (25-34%) as well as the turnover of arachidonic acid within brain phospholipids (35-58%). These changes were absent at 3 h after a single NMDA injection. The changes, opposite to those after chronic administration of antimanic drugs to rats, suggest that excessive NMDA signaling via arachidonic acid may be a model of upregulated arachidonic acid turnover in brain phospholipids.-Lee, H-J., J. S. Rao, L. Chang, S. I. Rapoport, and R. P. Bazinet. Chronic N-methyl-Daspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat. J. Lipid Res. 2008. 49: 162-168.

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“…Although its mechanisms of action have not been fully elucidated, TPM is known to enhance the activity of g-aminobutyric acid (GABA) through interaction with GABA A receptors, as well as to block voltage-dependent sodium channels and kainate/ [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors (Schneiderman, 1998). Emerging evidence indicates that TPM might offer promising applications for the therapy of other neurological conditions, such as neuropathic pain and essential tremor (Chong and Libretto, 2003;Connor, 2002), as well as several psychiatric disorders, such as bipolar disorder (Calabrese et al, 2001;Grunze et al, 2001), schizoaffective disorder (Deutsch et al, 2003), posttraumatic disorder (Berlant and Van Kammen, 2002), Tourette's syndrome (Abuzzahab and Brown, 2001) and some clusters of schizophrenia (Drapalski et al, 2001). The therapeutic potential of TPM for these disorders, however, is disputed on account of contrasting findings (Arnone, 2005;Millson et al, 2002) and in view of its numerous cognitive and affective side effects, such as depression, hallucinosis and cognitive deterioration (Matthews and Miller, 2001).…”

Section: Introductionmentioning

confidence: 99%

Effects of Topiramate on the Prepulse Inhibition of the Acoustic Startle in Rats

Frau

Orrù

Fà

et al. 2006

Neuropsychopharmacol

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The anticonvulsant topiramate (TPM) has been recently proposed as a novel adjuvant therapy for bipolar disorder and schizophrenia, yet its efficacy remains controversial. As both disorders are characterized by gating deficits, we tested the effects of TPM on the behavioral paradigm of prepulse inhibition (PPI) of the acoustic startle response, a validated animal model of sensorimotor gating. TPM (10, 18, 32, 58, 100 mg/kg, intraperitoneal, i.p.) enhanced PPI in rats in a dose-dependent fashion, prevented the PPI reduction mediated by the dopaminergic agonist apomorphine (0.25 mg/kg, subcutaneous, s.c.) and potentiated the effects of the antipsychotic drugs haloperidol (0.05, 0.1 mg/kg, i.p.) and clozapine (2.5, 5 mg/kg, i.p.). Conversely, TPM elicited no significant effect on the PPI disruption mediated by the NMDA receptor antagonist dizocilpine (0.05, 0.1 mg/kg, s.c.) and surprisingly antagonized the attenuation of dizocilpine-induced PPI disruption mediated by clozapine (5 mg/kg, i.p.). Our results suggest that TPM may exert diverse actions on the neural substrates of sensorimotor gating. While the pharmacological mechanisms of such effects are still elusive, our findings might contribute to shed light on some controversies on the therapeutic action of TPM, and point to this drug as a putative novel adjuvant therapy for some clusters of gating disturbances.

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Antimanic Efficacy of Topiramate in 11 Patients in an Open Trial With an On-Off-On Design

Cited by 61 publications

References 0 publications

Effect of Topiramate on Glucocorticoid Receptor Mediated Action

Effect of Topiramate on Glucocorticoid Receptor Mediated Action

Chronic N-methyl-d-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat

Effects of Topiramate on the Prepulse Inhibition of the Acoustic Startle in Rats

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