Hearts and Minds An ECG Update. Tuesday 18 th November The Met Hotel, Leeds

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1 Hearts and Minds An ECG Update Tuesday 18 th November The Met Hotel, Leeds

2 Ashleigh Bradley Specialist Clinical Pharmacist for Mental Health and Lithium Clinic Airedale NHS Foundation Trust

3 Introduction Clinical Consequences of Side-effects Weight Gain Postural Hypotension and Syncope Hyperlipidemia Diabetes Hypertension QTc Prolongation and Sudden Death Myocarditis

4 Patients with severe mental illnesses (SMI) lose 25 or more years of life expectancy. Suicide within this population is a wellrecognised cause of death. Most common cause of natural death is cardiovascular disease, (CVD).

5 CVD implicated in 34% of male deaths and 31% of female deaths within the schizophrenic population higher than in the general population. Due to risk factors such as smoking, poor diet, substance abuse and a lack of physical activity.

6 Patient distress and decreased quality of life Reduce patient compliance with medications Knowing the prevalence and severity of adverse effects between specific anti-psychotics will minimise their occurrence.

7 Obesity is a significant independent risk factor for Cardio Vascular Disease, (CVD). Obesity within mental illness is accentuated further by weight gain caused by antipsychotic medications.

8 Incidence of obesity within medicated individuals with SMI is between 40% and 60% - nearly double that of the general population!!! Mechanism responsible Theoretically linked to increase in appetite via 5-HT2c antagonism, increased sedation and decreased activity via H1 antagonism.

9 Antipsychotics Long term change (kg) Clozapine 5.7 Olanzapine 4.2 Quetiapine 2.5 Risperidone 1.7 Haloperidol 0.5 Trifluoperazine 0.3 Bazire S. Psychotropic Drug Directory 2012.

10 The most common autonomic side-effect of anti-psychotics. Occurs more commonly when two antipsychotics are prescribed in combination. Has been shown that patients reporting a side-effect of dizziness may not always have clinically detectable postural hypotension.

11 Clozapine is the drug most often associated with postural hypotension. Benign sustained tachycardia occurs in up to 25% of patients treated with Clozapine. Heart rate increases on average between 10 and 15 beats per minute.

12 Rarely postural hypotension may result in syncope. Incidence of syncope is around 0.2% in Olanzapine and Risperidone, and up to 6% in patients exposed to Clozapine.

13 Elderly patients Patients already taking anti-hypertensive s Impaired renal or hepatic function Individuals with known variation in phenotypes resulting from genetic polymorphisms within the Cytochrome P450 enzyme system.

14 Hyperlipidaemia reported with most antipsychotics Most profound effect on triglycerides Dramatic increases reported with SGA s.

15 Data is continuing to provide evidence that there is a correlation between weight gain caused by SGA and an increase in triglycerides. Olanzapine may increase triglycerides by up to 40% and is three times more likely than FGA s to give raised lipids.

16 Decreasing incidence: Clozapine> Olanzapine> Risperidone> Quetiapine>Typicals> Aripiprazole. Reducing the risk can be done through patient education, monitoring cholesterol, switching antipsychotics or adding in cholesterol lowering medications.

17 Rate of diabetes among schizophrenic patients is approximately double that of the general population. Major risk factor for CVD. Clozapine and Olanzapine are the antipsychotics most strongly linked with diabetes.

18 Following 12 months of treatment exposure, patients had a significant risk for developing diabetes while on Clozapine or Olanzapine treatment compared to no treatment. Clozapine - (OR 7.44;95% CI = ) Olanzapine (OR 3.10; 95% CI = ) Gianfrancesco et al Antipsychotic induced type 2 diabetes: evidence from a large health plan database. Journal of Clinical Psychopharmacology 23:

19 Kessing LV et al. Treatment with antipsychotics and the risk of diabetes in clinical practice. British Journal of Psychiatry 2010; 197:

20 Drug Clozapine Olanzapine Quetiapine Risperidone Phenthiazines Haloperidol Aripiprazole Asenapine Amisulpride Risk of diabetes/impaired glucose tolerance High Moderate Low Minimal Taylor D et al. Maudsley Prescribing in Psychiatry. 11 th ed.

21 1. Slow steady rise in pressure over time Possibly linked to weight gain 2. Unpredictable rapid increase in blood pressure on initiating a new drug. Theoretical mechanism of action linked to antagonistic effects on α2 adrenergic receptors.

22 Antipsychotics can block cardiac potassium channels lead to prolongation of QTc. QTc interval is an imprecise indicator of torsade de pointes. QTc >500ms, or an absolute increase of 60ms compared to baseline is considered to be a significant risk factor.

23 Systemic disease Electrolyte imbalance Cardiac disease Female gender Taking concurrent medications that also prolong the QTc.

24 Rate of sudden cardiac death (versus non-users)* - Typicals - incidence ratio 1.99 (95%CI ) - Atypicals incidence ratio 2.26 (95%CI ) - Atypical versus typical 1.14 (95%CI ) Haloperidol 1.61, thioridazine 3.19, clozapine 3.67, olanzapine 2.04, quetiapine 1.88, risperidone Dose-dependent effect *Ray W et al. Atypical antipsychotic drugs and risk of sudden cardiac death. NEJM 2009; 360(3)

25 Taylor D et al. Maudsley Prescribing in Psychiatry. 11 th ed.

26 Baseline ECG and electrolytes taken prior to initiation of any antipsychotic. Repeated 6 monthly or after any increase in dose. Concerns should be raised if there is an increase in QTc of 30ms from baseline and intervention should be considered if the increase is >60ms, especially if it exceeds 500ms.

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28 Rare but serious side-effect that can occur with Clozapine. Incidence ranges from 0.015% %. Clozapine induced Myocarditis will rapidly progress and has a mortality rate of approximately 50%. Patients on Clozapine also five times more likely to develop dilated cardiomyopathy. Breden et al Metabolic and Cardiac side-effects of second generation antipsychotics: What every clinician should know. Journal of Pharmacy Practice. 22:478.

29 When considering the choice of medication for psychotic patients clinicians should: consider all relevant cardiac risk factors and co-morbidities. Ensure that all monitoring for antipsychotics are carried out on a regular basis. e.g. Lipids, glucose, electrolytes, weight gain and ECG. Extra monitoring is required when patients are on high doses!!

30 Barnett et al Minimising metabolic and cardiovascular risk in schizophrenia: diabetes, obesity and dyslipidaemia. Breden et al Metabolic and Cardiac side-effects of second generation antipsychotics: What every clinician should know. Journal of Pharmacy Practice. 22:478 Haddad and Sharma Adverse effects of atypical antipsychotics: Differential risk and clinical implications. CNS Drugs Mackin Cardiac side-effects of psychiatric drugs. Human Psychopharmacology Clinical and Experimental Ray W et al. Atypical antipsychotic drugs and risk of sudden cardiac death. NEJM 2009; 360(3) Taylor D et al. Maudsley Prescribing in Psychiatry. 11 th ed. Gianfrancesco et al Antipsychotic induced type 2 diabetes: evidence from a large health plan database. Journal of Clinical Psychopharmacology 23:

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32 Hearts and Minds An ECG Update Tuesday 18 th November The Met Hotel, Leeds