Massive Creatine Kinase Elevations with Quetiapine: Report of Two Cases
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Abstract:
Massive elevations of serum creatine kinase (CK) can occur in a significant number of patients treated with neuroleptics in the absence of neuroleptic malignant syndrome (NMS). We report two cases of CK-elevations associated with quetiapine treatment, which disappeared after drug discontinuation. To our knowledge, case number one is the first case of quetiapine-induced CK elevation in a neuroleptic-naïve patient. We thus suggest CK assessment when myalgia occurs with neuroleptic treatment.Keywords:
Discontinuation
Creatine kinase
Quetiapine Fumarate
myalgia
Neuroleptic Malignant Syndrome
Quetiapine is an atypical antipsychotic with a good safety profile permitting its administration beyond the maximum dose of 800 mg/day. We report the case of a patient with a resistant schizophrenia treated with high doses of quetiapine (up to 2000 mg/day) combined with drug monitoring and with favourable therapeutic response and tolerance.
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We describe a case of concomitant use of carbamazepine and quetiapine, with a highly relevant interaction that requires attention. The combination of these drugs can be prescribed in psychiatry, for example in bipolar disorder, but also in other disciplines. Pharmacotherapy is one of the cornerstones in the treatment of bipolar disorders, and a combination of drugs is frequently used. Carbamazepine, an anti-epileptic drug that is effective as a mood stabilizer, and quetiapine, a second-generation antipsychotic, are both recommended in the Dutch guideline. Besides monotherapy is a combination of both drugs possible. It is striking that carbamazepine and quetiapine have a strong pharmacokinetic interaction via the metabolizing liver enzyme, CYP3A4. This interaction results in a factor 10 reduction of quetiapine blood levels. This may result in a possible loss of clinical efficacy of quetiapine.
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Quetiapine is an atypical antipsychotic, licensed in the UK for the treatment of schizophrenia. This review of published literature identifies the evidence that quetiapine is both effective and well-tolerated and highlights the particular indications in which quetiapine will be of most value to clinicians and patients.
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Neuroleptic malignant syndrome (NMS) is an uncommon but potentially life‐threatening adverse effect associated with conventional antipsychotic agents. The syndrome is characterized by muscular rigidity, hyperpyrexia, altered consciousness, and autonomic dysfunction. Few cases of quetiapine‐induced NMS have been reported. A 54‐year‐old man was unsuccessfully challenged with quetiapine after conventional antipsychotic‐induced NMS.
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Abstract: The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR) and as an extended release (XR) formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse), the treatment of bipolar disorder (manic and depressive episodes), and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D 2 receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT) 2A receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS). The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily) dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability) also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation. Overall, evidence from clinical trials suggests that quetiapine XR is an effective and generally well-tolerated treatment option in patients with schizophrenia and bipolar disorder. Keywords: quetiapine, extended release, schizophrenia, bipolar disorders
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INTRODUCTION Neuroleptic malignant syndrome is a rare adverse effect of antipsychotic agents. The most common signs and symptoms are hyperthermia, muscle rigidity, changes in mental status, and autonomic instability.1 The prevalence of neuroleptic malignant syndrome in association with the use of typical antipsychotics is estimated at 0.5% to 1%.1 Atypical antipsychotics such as quetiapine have greater affinity for serotonin 5-HT2A receptors than for dopamine D2 receptors. Therefore, it is believed that atypical antipsychotics are less likely to cause this condition. This article describes a patient treated with quetiapine who presented with biochemical and clinical evidence of neuroleptic malignant syndrome.
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Atypical antipsychotic drugs are well tolerated and thus often preferred in women of fertile age; yet the information on their placental transfer and use during the prenatal period is limited. The aim of this study was to study the placental transfer of quetiapine, a widely used atypical antipsychotic, with special reference to the role of the placental transporter protein, P-glycoprotein (P-gp). This was performed in 18 dually perfused placentas, using the well established P-gp inhibitors PSC833 (valspodar) and GG918 to inhibit the function of P-gp. We also aimed to clarify the significance of two potentially functional ABCB1 single nuclear polymorphisms (SNPs), 2677G> T/A and 3435C> T, on the transplacental transfer (TPT) of quetiapine. The placental transfer of quetiapine in the control group as measured by TPTAUC % (absolute fraction of the dose crossing placenta) was 3.7%, which is 29% less than the transfer of the freely diffusible antipyrine, which was 5.2%. The P-gp inhibitors had no significant effect on the transfer of quetiapine as measured by TPTAUC % ( P = 0.77). No correlation was found between the transplacental transfer of quetiapine (TPTAUC %) and placental P-gp expression ( P = 0.61). The 3435T allele in exon 26 was associated with significantly higher placental transfer of quetiapine ( P = 0.04). We conclude that quetiapine passes the human placenta but that the blood—placental barrier partially limits the transplacental transfer of quetiapine. Administration of P-gp inhibiting drugs with quetiapine is not likely to increase fetal exposure to quetiapine, although the ABCB1 C3435T polymorphism may contribute to inter-individual variation in fetal exposure to quetiapine.
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