Hazard ratio for coronary heart disease mortality for SMI patients versus controls (18-49 yrs) Hazard ratio for stroke

Transcription

1 By Michael Dixon

2 Contents Background to Bipolar Disorder and cardiac risk Mood stabilisers and cardiac risk factors Background to Depression and cardiac risk Antidepressants and cardiac risk factors Any questions?

3 Introduction Hazard ratio for coronary heart disease mortality for SMI patients versus controls (18-49 yrs) 3.22 (95% CI ) (Goodwin :4 ) Hazard ratio for stroke 2.53 (95% CI ) (Goodwin :4 ) For every 30 people who gain 4kg of weight, one will develop hypertension in the next 10 years Approx up to 70% of mental health patients smoke

4 Bipolar V Depression bipolar unipolar Osby U et al. 2001; 58

5 Background to Bipolar Disorder and Cardiac Risk (1) Patients with bipolar 1 may have double the cardiovascular risk of bipolar 2. After suicide and accidents, cardiovascular/all vascular diseases are leading cause of death in bipolar patients 17% have type 2 diabetes and 35% have hypertension (Goodwin :4 )

6 Background to Bipolar Disorder and Cardiac Risk (2) One study of outpatients with bipolar disorder (n=118, mean age 53 years) 84% had hyperlidaemia, 70% had hypertension and 25% had diabetes Clinically significant depressive symptoms raised odds of framingham score > 20%, 6 fold Depressive symptoms were also associated with increased BMI, glucose and BP Slomka JM et al. 2012; 138(3)

7 Fiedorowicz JG et al. 2009: 71.

8 Fiedorowicz JG et al. 2009: 71.

9 Mood stabilisers and cardiac risk (1) Lithium Lithium contra-indicated in cardiac disease Lithium usually benign cardiac side-effects in 20-30% of patients On average starting Lithium can increase QTc by 18.6msecs Weight gain is 2 nd highest reason for non-compliance with lithium (most often in 1 st two years) Significant weight gain (>7%) Odds ratio versus placebo of 1.89 (95% CI , p = 0.002). (McKnight R et al 2012; 379) Weight gain of lithium versus olanzapine odds ratio 0.32 (95% CI , p< , n=285) (McKnight R et al 2012; 379) Lithium versus aripiprazole over 52 weeks +0.74kg against +0.97kg (McIntyre RS et al. 2011; 13(6) )

10 Mood stabilisers and cardiac risk (2) Weight gain - clozapine/olanzapine > quetiapine/risperidone > lithium/valproate (Choong E et al (4) ) Others Carbamazepine can cause a rise in cholesterol, HDL and LDL Valproate and carbamazepine can cause weight gain Topiramate and lamotrigine don t cause weight gain

11 Bowden C et al. 2006: 163(7).

12 Monitoring of patients with Bipolar Disorder Everyone should have: - weight, diet, nutritional status - CVS status inc BP and pulse - Blood glucose and lipids - Liver - U&Es, TFTs and Ca 2+ for people on Li NICE sept 2014

13 Background to Depression and Cardiac Risk Patients with coronary heart disease have 3 times the risk of depression over general population Depressed patients are 2.7 times more likely to die from ischaemic heart disease (Surtees G et al. 2008: 165) Following acute coronary syndrome those who have severe depression have a doubling of their mortality over seven years over those without depression (hazard ratio % CI ) (Glassman A, Bigger Jnr TJ, Gaffney M. 2009;66(9) Diabetes doubles the odds of co-morbid depression

14 Depression and future cardiac disease Swedish twins study, twins Depression and antidepressant use associated with CVD development Risk highest in depressed patients who didn t use antidepressants (HR 1.48, CI ) When the CVD outcomes were split, the association was found with ischaemic stroke but not for coronary heart disease *Rahman I et al. 2013;28(7)

15 Surtees G et al. 2008: 165

16 ENRICHD study Antidepressant drug use was associated with a lower risk for death or nonfatal MI of an adjusted HR of 0.63 (95% CI, ) and decreased risk of dying, with an adjusted HR of 0.63 (95% CI, ).(Writing committee 2003;289) SADHEART sertraline v placebo over 2 years post MI - incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo (Glassman A et al. 2002;288) 7 year follow up of SADHEART - baseline depression severity (hazard ratio, 2.30; 95% confidence interval, ; P <.006) and failure of depression to improve with either sertraline or placebo (hazard ratio, 2.39; 95% confidence interval, ; P <.001) were strongly and independently associated with longterm mortality (Glassman A et al. 2009;66(9))

17 Stapleberg NJC et al. 2011; 45

18 Cardiac effects of antidepressants Drug Hear t rate BP QTc Arrhythmi a Conduction Tricyclics Increase Postural hypotension prolonged Common in O/D Slows conduction block Na/K channels Trazodone decrease or increase postural hypotension Can prolong Case reports unclear SSRIs (exc citalopram/e scitalopram) Citalopram/ escitalopram Venlafaxine Min/small decrease in HR Small decrease Marginal increase No effect Nil Nil nil Slight drop Depends on dose Doserelated increase Poss increase in O/D Mainly in O/D rare reports in O/D nil Rare reports Mirtazapine Minimal Minimal None None None

19 Antidepressants and risk of cardiovascular disease Scottish Health Survey, adults All cardiovascular events Hazard Ratios (95% CI) Non-medicated 1.00 (reference) TCAs 1.35 ( ) SSRIs 1.11 ( ) Other 0.88 ( ) Any antidepressant 1.19 ( ) *Hamer M et al. 2011; 32

20 Review of QTc prolongation No effect at therapeutic concentrations Mild effect (6-8ms) or only in cases of overdose or intoxication Moderate effect (10-15 ms) Severe effect (>17ms) Duloxetine Citalopram/escit alopram Clomipramine Amitriptyline Mirtazapine Trazodone Fluoxetine Doxepin Sertraline Venlafaxine Imipramine Wenzel-Seifert et al (2011). Nortriptyline

21 Citalopram/escitalopram and QTc Citalopram 20mg = 7.5 msecs 60mg = 16.7 msecs Dose restricted to max 40mg/day (20mg in elderly or hepatic impairment) Escitalopram 10mg = 4.3 msecs 30mg = 10.7 msecs Dose restricted to max 10mg/day in elderly or hepatic impairment Not to be used in patients with prolonged QTc or with other meds that prolong QTc MHRA. 2011; 5(5)

22 Mean (SD) corrected QT (QTc) interval recorded on electrocardiogram days after prescription of antidepressant or methadone, by drug dose Castro V et al. 2013; 346

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24 Antidepressants and weight gain (1) Weight gain or loss can be part of depression One study showed patients on antidepressant gained 1kg of weight over 12 year period Patten S et al. 2011; 134(1-3) Tricyclic antidepressants increased craving and decreased metabolic rate SSRIs tend to get weight loss initially over first month followed by weight gain in the long term Mirtazapine causes weight gain MAOIs can cause weight gain Least weight gain agomelatine, trazodone or reboxetine, venlafaxine or duloxetine

25 WHI study BMI (kg/m 2 ) Weight (kg) Baseline Year 3 Baseline Year 3 Not depressed Depressed No antidepressant Taking antidepressant Ma Y et al. 2013; 103.

26 Antidepressants and weight gain (2) Serretti A et al. 2010; 71(10).

27 Antidepressants and diabetes (1) 5 year absolute risk for developing diabetes - 1.1% for general population - 1.7% for standard doses of antidepressants ( doses/yr) - 2.3% for higher doses of antidepressants (>400 doses/yr) - OR for diabetes without severe depression 1.93 (95% CI ) and with severe depression OR 2.65 (95% CI ) - Average weight gain 2.5kg (control 1.4kg) (Kivimaki M et al. Antidepressant medication use, weight gain, and risk of type 2 diabetes: a population based study. Diabetes Care 2010; 33:2611-6)

28 Antidepressants and diabetes (2) Kivimaki M et al. 2010; 33.

29 Conclusion When considering the choice of medication for patients consider relevant cardiac risk factors and comorbidities Monitor the physical health side-effects of medication prescribed e.g. Lipids, glucose, weight gain, ECG

30 References (1) Bowden C et al. (2006) Impact of lamotrigine and lithium on weight in obese and non obese patients with bipolar 1 disorder. American Journal of Psychiatry; 163(7): Choong E et al. (2012) Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population. Journal of Psychiatric Research 46(4): Castro V et al. (2013) QT interval and antidepressant use: a cross sectional study of electronic health records BMJ 346:f288 doi: /bmj.f288 (Published 29 January 2013) Fiedorowicz JG et al. (2009) Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder. Psychosomatic Medicine,71, Glassman A et al. Sertraline Treatment of Major Depression in Patients With Acute MI or Unstable Angina. JAMA. 2002;288(6): Glassman A, Bigger Jnr JT, Gaffney M. (2009) Psychiatric Characteristics Associated With Long-term Mortality Among 361 Patients Having an Acute Coronary Syndrome and Major Depression: Seven-Year Follow-up of SADHART Participants. Archives of General Psychiatry; 2009; 66(9): Goodwin G et al. (2009) Evidence based guidelines for treating bipolar disorder: revised second edition recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology,23(4), Hamer M et al. (2011) Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey. European Heart Journal 32: Hawton K et al. (2010) Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose The British Journal of Psychiatry 196, Kivimaki M et al. (2010) Antidepressant medication use, weight gain, and risk of type 2 diabetes: a population based study. Diabetes Care; 33: Ma Y et al. (2013) Relations of Depressive Symptoms and Antidepressant Use to Body Mass Index and Selected Biomarkers for Diabetes and Cardiovascular Disease. American Journal of Public Health 103:e34 e43. doi: MHRA. (2011) Citalopram and escitalopram: QT interval prolongation new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings. Drug Safety Update 5(5); A1 Mcknight R et al. (2012) Lithium toxicity profile: a systematic review and meta-analysis. Lancet 379; , 25 February. McIntyre RS et al. (2011) A 52-week, double-blind evaluation of the metabolic effects of aripiprazole and lithium in bipolar 1 disorder. The primary care companion to CNS disorders 13(6). NICE. (2006) Bipolar Disorder, Clinical Guidelines 38, July.

31 References (2) Osby U et al. (2001) Excess mortality in bipolar and unipolar disorder in sweden. Archives of General Psychiatry 58: Patten S et al. (2011) Weight gain in relation to major depression and antidepressant medication use. Journal of Affective Disorders; 134(1-3): ) Rahman I et al. (2013) Clinical depression, antidepressant use and risk of future cardiovascular disease. European Journal of Epidemiology 28(7): Slomka JM et al. (2012) Mood disorder symptoms and elevated cardiovascular disease risk in aptients with bipolar disorder. Journal of Affective Disorders; 138(3): , May Serretti A et al. (2010) Antidepressants and body weight: A comprehensive review and meta-analysis. Journal of Clinical Psychiatry; 71(10): Stapleberg NJC et al. (2011) A topographical map of the causal network of mechanisms underlying the relationship between major depressive disorder and coronary heart disease. Australian and New Zealand Journal of Psychiatry; 45: Surtees G et al. (2008) Depression and Ischemic Heart Disease Mortality: Evidence From the EPIC-Norfolk United Kingdom Prospective Cohort Study American Journal of Psychiatry 165 (4) : Taylor D, Paton C, Kapur S. (2012) Prescribing Guidelines in Psychiatry 11 th ed, Chicester: Wiley Blackwell Wenzel-Seifert et al (2011). A review of QTc prolongation. In Bazire S (2014), Psychotropic Drug Directory (pg250), Lloyd-Reinhold Communications. Writing committee for the ENRICHD investigators. Effects of Treating Depression and Low Perceived Social Support on Clinical Events After Myocardial Infarction: The Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA. 2003;289(23):