Clozapine and sudden death

Warner, Barbara B.; Alphs, Larry; Schaedelin, Juerg; Koestler, Thomas P.

doi:10.1016/s0140-6736(05)72452-1

Cited by 34 publications

(11 citation statements)

References 4 publications

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“…A pharmacovigilance data mining study using the World Health Organisation's database concluded that myocarditis and cardiomyopathy are significantly more often associated with clozapine than other antipsychotic medications (231 clozapine reports compared with 89 reported for all other antipsychotics) (Coulter et al, 2001). Estimates of the incidence of clozapine-related myocarditis have ranged from 1 in 500 patients (Killian et al, 1999) to 1 in 10 000 (Warner et al, 2000). A 2002 report from the drug's manufacturer found a total of 213 cases of myocarditis, internationally, including 50 deaths, and that 85% of all cases presented within the first 2 months of treatment (Novartis, 2002).…”

Section: Clozapinementioning

confidence: 99%

Cardiac side effects of psychiatric drugs

Mackin

2007

Hum. Psychopharmacol. Clin. Exp.

139

117

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Section: Clozapinementioning

confidence: 99%

Cardiac side effects of psychiatric drugs

Mackin

2007

Hum. Psychopharmacol. Clin. Exp.

139

117

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“…5 Estimation of the incidence of myocarditis in clozapine use ranges between one in 10 000 to one in 500. 6 Interpretation of case reports is complicated by the often non-specific symptoms and signs of myocarditis and cardiomyopathy. ECG changes reported are also non-specific and include sinus tachycardia, T-wave inversion, prolonged QTc, and ST flattening/depression.…”

Section: Discussionmentioning

confidence: 99%

Clozapine associated dilated cardiomyopathy

Tanner

Culling

2003

Postgraduate Medical Journal

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A 31 year old white man was referred for investigation of a persistent sinus tachycardia. His only significant past medical history was of chronic schizophrenia for which he had been taking clozapine for six years. An electrocardiogram demonstrated sinus tachycardia, voltage criteria for left ventricular hypertrophy, and a prolonged QTc. Echocardiographic findings were consistent with a dilated cardiomyopathy. Serious cardiac complications of clozapine use are rare but have been reported previously. It is important to note that sinus tachycardia may be the only obvious clinical sign, and that complications can manifest months or even years (as in this case) after starting the drug. Patients on clozapine should be informed of potential cardiac symptoms and doctors should maintain a high degree of clinical suspicion throughout the duration of treatment.A 31 year old white man was referred by his general practitioner to the cardiology outpatient department for investigation of a persistent sinus tachycardia. In general he felt well, with no recent history of fever, chest pain, cough, or symptoms suggestive of thyrotoxicosis. On direct questioning there was a history of gradually worsening exertional dyspnoea over several months. His only past medical history of note was chronic schizophrenia which was well controlled on clozapine 400 mg daily. This was prescribed six years previously when flupenthixol had failed to control psychotic symptoms. He was on no other regular medications and did not consume alcohol. He also denied any recreational drug use. His only significant coronary risk factor was a smoking habit of 10 cigarettes daily. There was no family history of either premature coronary disease or cardiomyopathy.On examination he was afebrile. There was a resting sinus tachycardia of 110 beats/min and blood pressure of 110/75 mm Hg. His jugular venous pressure was raised at 6 cm, but heart sounds were normal with no added sounds or murmurs. The rest of the physical examination was entirely normal.A resting electrocardiogram (ECG) confirmed sinus tachycardia and changes consistent with left ventricular hypertrophy. The corrected QT interval (QTc) was prolonged at 479 ms (380-460 ms). Chest radiography demonstrated an enlarged cardiothoracic ratio with clear lung fields.He proceeded to echocardiography which demonstrated a grossly dilated heart with a left ventricular diastolic dimension of 7.3 cm (3.5-5.6 cm). There was very poor global function with an estimated ejection fraction of 9% (>50%). There were no significant valvular abnormalities. Full blood count, urea and electrolytes, liver function tests, ferritin, C-reactive protein, erythrocyte sedimentation rate, thyroid function tests, and troponin I were all normal.In the absence of any other likely aetiology a presumptive diagnosis of clozapine-induced cardiomyopathy was made and he was admitted for further management. The Committee on Safety of Medicines (CSM) was informed via the yellow card reporting scheme. His clozapine was converted to olanzapine 10 ...

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“…Between 1 in 10 000 and 1 in 1000 patients on clozapine have been reported to develop myocarditis [43]. The drug's manufacturer international pharmacovigilance database reported 213 cases of myocarditis (including 50 deaths), 85% of which developed in the first 2 months of therapy, out of an estimated 3,000,000 patient-years of exposure to clozapine (1/14000 patient years) [44].…”

Section: Epidemiology Of Clozapine-related Myocarditismentioning

confidence: 99%

Update on the Adverse Effects of Clozapine: Focus on Myocarditis

Berardis¹,

Serroni²,

Campanella³

et al. 2012

CDS

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Clozapine, an atypical antipsychotic, is a dibenzodiazepine derivative and its therapeutic effects are probably mediated by dopaminergic and serotonergic activity. In accordance to several studies, it appears to be the most effective antipsychotic drug for treatment-resistant schizophrenia. Moreover, clozapine appears to be particularly beneficial in patients with schizophrenia who are suicidal and in those with comorbid substance use disorder. However, despite its efficacy, the general use of clozapine in clinical practice is somewhat limited because of the risk of several serious adverse effects such as agranulocytosis and thromboembolism. Clozapine may be associated with fatal myocarditis and cardiomyopathy in physically healthy young adults. Consequently, the FDA and the drug's manufacturer have strengthened warnings to include that a potentially fatal myocarditis may occur when taking clozapine. In the present paper the literature on clozapine-related myocardis will be reviewed and practical advice will be given concerning the diagnosis and management of such potentially fatal adverse effect.

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Clozapine and sudden death

Cited by 34 publications

References 4 publications

Cardiac side effects of psychiatric drugs

Cardiac side effects of psychiatric drugs

Clozapine associated dilated cardiomyopathy

Update on the Adverse Effects of Clozapine: Focus on Myocarditis

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