Clozapine, elevated heart rate and QTc prolongation

Kim, David D.; White, Ralph de Vere; Barr, Alasdair M.; Honer, William G.; Procyshyn, Ric M.

doi:10.1503/jpn.170135

Cited by 19 publications

(16 citation statements)

References 14 publications

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“…Clozapine dose reductions may be useful for QT prolongation, especially in the case of polypharmacy. 177 Clozapine-induced cardiomyopathy, myocarditis and pericarditis. Clozapine may be associated with the occurrence of severe cardiovascular side effects, including dilated cardiomyopathy, myocarditis and pericarditis, which may be fatal when not timely recognized and managed.…”

Section: Uncommon Adverse Effectsmentioning

confidence: 99%

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Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

Berardis¹,

Rapini²,

Olivieri³

et al. 2018

Therapeutic Advances in Drug Safety

156

125

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Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

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Section: Uncommon Adverse Effectsmentioning

confidence: 99%

“…Clozapine dose reductions may be useful for QT prolongation, especially in the case of polypharmacy. 177…”

Section: Clozapine Mechanism Of Action and Relationships With Adversementioning

confidence: 99%

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

Berardis¹,

Rapini²,

Olivieri³

et al. 2018

Therapeutic Advances in Drug Safety

156

125

View full text Add to dashboard Cite

show abstract

“…However, this finding would not be particularly illuminating because the reason for its inclusion in the model may have more to do with patterns in antipsychotic prescribing than the potential for clinical response. On the other hand, if clozapine were prescribed to all individuals, the greater likelihood of being discharged on clozapine if admitted on clozapine would likely reflect characteristics specific to the two subgroups: most who were admitted on clozapine likely tolerated the drug but were in need of optimization; but, some who were not prescribed clozapine at admission likely had to stop the treatment owing to adverse effects associated with its use [ 44 – 50 ].…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic prescribing patterns on admission to and at discharge from a tertiary care program for treatment-resistant psychosis

et al. 2018

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Retrospective data were collected from 330 individuals who were treated at a tertiary care program for treatment-resistant psychosis between 1994 and 2010. The main objectives were to compare the use of antipsychotic monotherapy to polypharmacy and to characterize within-individual changes in treatment and symptomatology between admission and discharge. At admission, individuals who were prescribed only one antipsychotic were comparable to those who were prescribed at least two antipsychotics with regard to demographics and symptom severity. The use of psychotropic medications other than antipsychotics was also similar between the two groups. However, the magnitude of antipsychotic utilization was greater in individuals who were receiving antipsychotic polypharmacy. In addition, a greater proportion received excessive doses at admission. Similar findings were observed when the two antipsychotic prescribing practices were compared at discharge. Three important patterns were identified when investigating within-individual changes. First, fewer individuals were prescribed more than one antipsychotic at discharge. This was accompanied by a general decrease in the magnitude of antipsychotic utilization. Second, the number of individuals who were prescribed clozapine had increased by discharge. Most who were already prescribed clozapine at admission had their doses increased. Third, improvements in symptomatology were observed across all of the subscales included in the Positive and Negative Symptom Scale (PANSS); 57.9% of individuals experienced a relative reduction in total PANSS scores exceeding 20%. Based on these findings, it is possible to alleviate symptom severity while reducing antipsychotic utilization when patients are treated at a tertiary care program for treatment-resistant psychosis.

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“…Administration of other APs, including clozapine, did not affect QTc Cohen et al 2001 83 30 Male Schizophrenia Clozapine: 500 mg/d QTc with clozapine 500 mg/d (monotherapy): 624 ms. QTc with olanzapine 10 mg/d + valproic acid 1800 mg/d: 504 ms Aripiprazole Karz et al 2015 70 80 Female Schizoaffective disorder, bipolar type Aripiprazole: 10 mg/d Fluoxetine: 20 mg/d Lisinopril: 5 mg/d Simvastatin: 10 mg/d Aspirin: 81 mg/d Aripiprazole was discontinued post-MI. QTc interval increased (475 to 568 ms), remained elevated for 2 weeks, and decreased to 444 ms after reinitiating aripiprazole, titrated to 15 mg/d Clozapine Kim et al 2018 85 45 Male Schizophrenia Clozapine: 400 mg/d QTcB: 508 ms QTcF: 484 ms QTc Framingham: 479 ms QTc Hodges: 475 ms Dewan et al 2004 84 45 Male Schizophrenia Clozapine: 150 mg/d Quetiapine: 800 mg/d QTc interval increased from 428 ms to 472 ms within 2 weeks of initiating clozapine; QTc returned to 428 ms ≤3 days of switching to quetiapine Tanner et al 2003 86 31 Male Schizophrenia Clozapine: 400 mg/d QTc 479 and tachycardia (HR 110 bpm) with clozapine; normal QTc interval and HR after switching to olanzapine 10 mg/d and antihypertensive drugs (beta blocker, loop diuretic, angiotensin-converting enzyme) Donepezil Vogel et al 2019 119 26 Female Major depressive disorder Quetiapine (100 mg in the morning, 200 mg midday, 300 mg before bed), divalproex sodium ER 500 mg BID, metoprolol ER 25 mg/d, montelukast 10 mg/d, polyethylene glycol-3350 17 g/d, calcium + vitamin D, pantoprazole 40 mg/d, cephalexin 50...…”

Section: Literature Searchmentioning

confidence: 99%

QTc Interval Prolongation with Therapies Used to Treat Patients with Parkinson’s Disease Psychosis: A Narrative Review

Torres‐Yaghi

Carwin

Carolan

et al. 2021

NDT

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In addition to the classic motor symptoms of Parkinson’s disease (PD), people with PD frequently experience nonmotor symptoms that can include autonomic dysfunction and neuropsychiatric symptoms such as PD psychosis (PDP). Common patient characteristics, including older age, use of multiple medications, and arrhythmias, are associated with increased risk of corrected QT interval (QTc) prolongation, and treatments for PDP (antipsychotics, dementia medications) may further increase this risk. This review evaluates how medications used to treat PDP affect QTc interval from literature indexed in the PubMed and Embase databases. Although not indicated for the treatment of psychosis, dementia therapies such as donepezil, rivastigmine, memantine, and galantamine are often used with or without antipsychotics and have minimal effects on QTc interval. Among the antipsychotics, data suggesting clinically meaningful QTc interval prolongation are limited. However, many antipsychotics have other safety concerns. Aripiprazole, olanzapine, and risperidone negatively affect motor function and are not recommended for PDP. Quetiapine is often sedating, can exacerbate underlying neurogenic orthostatic hypotension, and may prolong the QTc interval. Pimavanserin was approved by the US Food and Drug Administration (FDA) in 2016 and remains the only FDA-approved medication available to treat hallucinations and delusions associated with PDP. However, pimavanserin can increase QTc interval by approximately 5–8 ms. The potential for QTc prolongation should be considered in patients with symptomatic cardiac arrhythmias and those receiving QT-prolonging medications. In choosing a medication to treat PDP, expected efficacy must be balanced with potential safety concerns for individual patients.

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Clozapine, elevated heart rate and QTc prolongation

Cited by 19 publications

References 14 publications

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

Antipsychotic prescribing patterns on admission to and at discharge from a tertiary care program for treatment-resistant psychosis

QTc Interval Prolongation with Therapies Used to Treat Patients with Parkinson’s Disease Psychosis: A Narrative Review

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