Effect of Topiramate on Plasma Concentrations of Clozapine, Olanzapine, Risperidone, and Quetiapine in Patients With Psychotic Disorders

Migliardi, Gaetana; D'Arrigo, Concetta; Santoro, Vincenza; Bruno, Antonio; Cortese, Lara; Campolo, Domenica; Cacciola, Massimo; Spina, Edoardo

doi:10.1097/01.wnf.0000240955.49315.65

Cited by 26 publications

(12 citation statements)

References 28 publications

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“…A randomized, double‐blind, placebo‐controlled trial in patients with treatment‐resistant schizophrenia has shown that the addition of topiramate, 300 mg/day, to an ongoing treatment with newer antipsychotics did not significantly alter plasma concentrations of clozapine and olanzapine in 12 and 5 patients, respectively [144]. A recent study in 38 patients with psychotic disorders has documented that topiramate, at the dosages up to 200 mg/day, does not affect steady‐state plasma levels of the new antipsychotics clozapine, olanzapine, risperidone and quetiapine [145].…”

Section: Metabolic Drug Interactions Of Newer Antipsychoticsmentioning

confidence: 99%

Metabolic Drug Interactions with Newer Antipsychotics: A Comparative Review

Spina

Leon

2006

Basic Clin Pharma Tox

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232

174

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Newer antipsychotics introduced in clinical practice in recent years include clozapine, risperidone, olanzapine, quetiapine, sertindole, ziprasidone, aripiprazole and amisulpride. These agents are subject to drug-drug interactions with other psychotropic agents or with medications used in the treatment of concomitant physical illnesses. Most pharmacokinetic interactions with newer antipsychotics occur at the metabolic level and usually involve changes in the activity of the major drug-metabolizing enzymes involved in their biotransformation, i.e. the cytochrome P450 (CYP) monooxygenases and /or uridine diphosphate-glucuronosyltransferases (UGT). Clozapine is metabolized primarily by CYP1A2, with additional contribution by other CYP isoforms. Risperidone is metabolized primarily by CYP2D6 and, to a lesser extent, CYP3A4. Olanzapine undergoes both direct conjugation and CYP1A2-mediated oxidation. Quetiapine is metabolized by CYP3A4, while sertindole and aripiprazole are metabolized by CYP2D6 and CYP3A4. Ziprasidone pathways include aldehyde oxidase-mediated reduction and CYP3A4-mediated oxidation. Amisulpride is primarily excreted in the urine and undergoes relatively little metabolism. While novel antipsychotics are unlikely to interfere with the elimination of other drugs, co-administration of inhibitors or inducers of the major enzymes responsible for their metabolism may modify their plasma concentrations, leading to potentially significant effects. Most documented metabolic interactions involve antidepressant and anti-epileptic drugs. Of a particular clinical significance is the interaction between fluvoxamine, a potent CYP1A2 inhibitor, and clozapine. Differences in the interaction potential among the novel antipsychotics currently available may be predicted based on their metabolic pathways. The clinical relevance of these interactions should be interpreted in relation to the relative width of their therapeutic index. Avoidance of unnecessary polypharmacy, knowledge of the interaction profiles of individual agents, and careful individualization of dosage based on close evaluation of clinical response and, possibly, plasma drug concentrations are essential to prevent and minimize potentially adverse drug interactions in patients receiving newer antipsychotics.

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Section: Metabolic Drug Interactions Of Newer Antipsychoticsmentioning

confidence: 99%

Metabolic Drug Interactions with Newer Antipsychotics: A Comparative Review

Spina

Leon

2006

Basic Clin Pharma Tox

Self Cite

232

174

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“…Antidepressants, such as paroxetine (Saito et al 2005), sertraline (Spina et al 2004), and fluoxetine (Bondolfi et al 2002), can increase the concentration of risperidone and its metabolite paliperidone, but this is not the case for valproic acid (Ravindran et al 2004; Yoshimura et al 2007), topirimate (Migliardi et al 2007), lamotrigine (Spina et al 2006), mirtazapine (Loonen et al 1999), and venlafaxine (Amchin et al 1999). Carbamazapine can decrease the concentration of the metabolite paliperidone in patients receiving risperidone (Spina et al 2000).…”

Section: Development Of Paliperidonementioning

confidence: 99%

Paliperidone: the evidence of its therapeutic value in schizophrenia

Kantrowitz

Citrome²

2007

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Introduction:Paliperidone, the 9-hydroxy metabolite of risperidone, is a second-generation antipsychotic that was recently approved for the treatment of schizophrenia. It is marketed as an improvement over risperidone, but is likely to be considerably more costly when risperidone is no longer protected by patent.Aims:To review the evidence for the clinical impact of paliperidone in the treatment of patients with schizophrenia, particularly in contrast to risperidone.Evidence review:Paliperidone is primarily metabolized and excreted renally, and thus may be of particular utility for patients with hepatic impairment. There is clear evidence that paliperidone is more efficacious than placebo in reducing the positive and negative symptoms of schizophrenia. In patients with schizophrenia, paliperidone has been shown to stabilize acute psychotic symptoms. There is some evidence that it can prevent relapse in stabilized patients. Studies on the cost effectiveness of paliperidone are needed. Most importantly, there are no trials comparing paliperidone directly with other second-generation antipsychotics.Place in therapy:Until direct efficacy and cost effectiveness comparisons are made with risperidone, it is difficult to justify paliperidone use over risperidone. It will become even harder to justify when risperidone becomes available as a less expensive generic medication.

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“…Plasma concentrations of quetiapine were found to be either unchanged or increased in psychiatric patients during coadministration with valproic acid [10][11][12]. There is limited or no information concerning the effect of lamotrigine and other antiepileptic agents that are also occasionally used to treat psychiatric disorders, such as topiramate and oxcarbazepine, on the pharmacokinetics of quetiapine [11,13].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Quetiapine: Effect of Coadministration with Antiepileptic Drugs in Patients with Psychiatric Disorders

Santoro¹,

D'Arrigo²,

Migliardi³

et al. 2008

TOCCHEMJ

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Antiepileptic agents, particularly those with mood-stabilizing properties, are increasingly used in the management of psychiatric disorders and may be prescribed in combination with antipsychotics. Aim of the present study was to evaluate the pharmacokinetic interaction between various antiepileptics and quetiapine, a second-generation antipsychotic, in psychiatric patients, by using data from a therapeutic drug monitoring service. Steady-state plasma concentrations of quetiapine were compared in patients treated with quetiapine alone (controls, n=35) and in patients comedicated with valproic acid (n=19), lamotrigine (n=16), carbamazepine (n=6), topiramate (n=6) and oxcarbazepine (n=5). The six groups were matched for sex, age and daily dose of quetiapine. Dose-normalized plasma concentrations of quetiapine were significantly lower in the carbamazepine group than in the control group (p<0.001), while there were no differences in plasma quetiapine concentrations between the valproic acid, lamotrigine, topiramate or oxcarbazepine groups and the control group. In 5 patients assessed on and off carbamazepine comedication, dose-normalized plasma concentrations of quetiapine were significantly lower during combination therapy than on quetiapine alone (p<0.01). By contrast, no appreciable changes in plasma levels of quetiapine were found in the 8 and 6 patients assessed on and off valproic acid or lamotrigine comedication, respectively. These findings confirm that carbamazepine decreases markedly steady-state plasma concentrations of quetiapine, presumably by inducing its CYP3A4-mediated biotransformation. Conversely, concomitant administration of therapeutic doses of valproic acid, lamotrigine, topiramate or oxcarbazepine does not appear to affect significantly plasma levels of quetiapine.

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Effect of Topiramate on Plasma Concentrations of Clozapine, Olanzapine, Risperidone, and Quetiapine in Patients With Psychotic Disorders

Abstract: These findings indicate that topiramate, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of the new antipsychotics-clozapine, olanzapine, risperidone, and quetiapine.

Cited by 26 publications

References 28 publications

Metabolic Drug Interactions with Newer Antipsychotics: A Comparative Review

Metabolic Drug Interactions with Newer Antipsychotics: A Comparative Review

Paliperidone: the evidence of its therapeutic value in schizophrenia

Therapeutic Drug Monitoring of Quetiapine: Effect of Coadministration with Antiepileptic Drugs in Patients with Psychiatric Disorders

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