Antidepressants strongly influence the relationship between depression and heart rate variability: findings from The Irish Longitudinal Study on Ageing (TILDA)

Background Heart rate variability (HRV) is known to be reduced in depression; however, is unclear whether this is a consequence of the disorder or due to antidepressant medication. Methods We analysed data on 4750 participants from the first wave of The Irish Longitudinal Study on Ageing (TILDA). Time [standard deviation of normal to normal intervals (SDNN ms2)] and frequency domain [low frequency (LF) and high frequency (HF)] measures of HRV were derived from 3-lead surface electrocardiogram records obtained during 10 min of supine rest. Depression was assessed using the Center for Epidemiologic Studies – Depression scale. Results Participants on antidepressants [with (n = 80) or without depression (n = 185)] differed significantly from controls (not depressed and not taking antidepressants n = 4107) on all measures of HRV. Depressed participants not taking antidepressants (n = 317) did not differ from controls on any measures of HRV. In linear regression analysis adjusted for relevant factors all antidepressants were associated with lower measures HRV. Participants on selective serotonin reuptake inhibitors (SSRIs) had higher measures of HRV relative to participants on tricyclic antidepressants or serotonin–norepinephrine reuptake inhibitors respectively. Conclusions Our results suggest that reductions in HRV observed among depressed older adults are driven by the effects of antidepressant medications. SSRIs have less impact on HRV than other antidepressants but they are still associated with lower measures of HRV. Study limitations include the use of a self-report measure of depression and floor effects of age on HRV could have limited our ability to detect an association between HRV and depression.

[1]  G. Huston The Hospital Anxiety and Depression Scale. , 1987, The Journal of rheumatology.

[2]  J. Jennings,et al.  Does aging differentially reduce heart rate variability related to respiration? , 1984, Experimental aging research.

[3]  Laguzzi Raul Serotonin2 Receptors in the Nucleus Tractus Solitarius: Characterization and Role in the Baroreceptor Reflex Arc , 2003, Cellular and Molecular Neurobiology.

[4]  Jeroen J. Bax,et al.  Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). , 2010, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[5]  A. Sherwood,et al.  Depression as a Risk Factor for Coronary Artery Disease: Evidence, Mechanisms, and Treatment , 2004, Psychosomatic medicine.

[6]  C. Jonker,et al.  Comorbidity and risk‐patterns of depression, generalised anxiety disorder and mixed anxiety‐depression in later life: results from the AMSTEL study , 2003, International journal of geriatric psychiatry.

[7]  B. Pollock,et al.  Comorbid anxiety disorders in depressed elderly patients. , 2000, The American journal of psychiatry.

[8]  A. Camm,et al.  Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). , 2010, European heart journal.

[9]  G. Jennings,et al.  Noradrenaline release and sympathetic nervous system activity. , 1985, Journal of hypertension.

[10]  D. Nunan,et al.  Association between RR interval and high-frequency heart rate variability acquired during short-term, resting recordings with free and paced breathing , 2008, Physiological measurement.

[11]  J. Pardey,et al.  The next-generation holter revolution: from analyse-edit-print to analyse-print , 2004, Computers in Cardiology, 2004.

[12]  Jonathan Rottenberg,et al.  Cardiac vagal control in depression: A critical analysis , 2007, Biological Psychology.

[13]  Organización Mundial de la Salud Guidelines for ATC classification and DDD assignment , 1996 .

[14]  C. Villalón,et al.  5-hydroxytryptamine and cardiovascular regulation. , 2008, Trends in pharmacological sciences.

[15]  A. Kemp,et al.  Is Heart Rate Variability Reduced in Depression Without Cardiovascular Disease? , 2011, Biological Psychiatry.

[16]  B. Laurent,et al.  Depressive symptoms and autonomic nervous system dysfunction in an elderly population-based study: the PROOF study. , 2012, Journal of affective disorders.

[17]  F. Zitman,et al.  Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA). , 2008, Archives of general psychiatry.

[18]  Philippe Van De Borne,et al.  Guidelines for the management of arterial hypertension , 2014 .

[19]  K. Felmingham,et al.  Depression, Comorbid Anxiety Disorders, and Heart Rate Variability in Physically Healthy, Unmedicated Patients: Implications for Cardiovascular Risk , 2012, PloS one.

[20]  Bruce H. Friedman,et al.  An autonomic flexibility–neurovisceral integration model of anxiety and cardiac vagal tone , 2007, Biological Psychology.

[21]  R. Goldsmith,et al.  Exercise and autonomic function in health and cardiovascular disease. , 2001, Cardiology clinics.

[22]  I. Lesser,et al.  Relationship of age, age at onset, and sex to depression in older adults. , 1998, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[23]  F. Fregni,et al.  Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study. , 2013, The international journal of neuropsychopharmacology.

[24]  Michael Böhm,et al.  2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). , 2007, Journal of hypertension.

[25]  Ferdinand J. Venditti,et al.  Reduced Heart Rate Variability and Mortalit Risk in an Elderly Cohort: The Framingham Heart Study , 1994, Circulation.

[26]  A. Folsom,et al.  Low Heart Rate Variability in a 2-Minute Rhythm Strip Predicts Risk of Coronary Heart Disease and Mortality From Several Causes: The ARIC Study , 2000, Circulation.

[27]  R. Carney,et al.  Depression and heart rate variability in patients with coronary heart disease , 2009, Cleveland Clinic Journal of Medicine.

[28]  W. Browner,et al.  Depression and heart rate variability in patients with stable coronary heart disease: findings from the Heart and Soul Study. , 2005, Archives of general psychiatry.

[29]  P. Kearney,et al.  COHORT PROFILE Cohort Profile: The Irish Longitudinal Study on Ageing , 2011 .

[30]  B. Penninx,et al.  Longitudinal Evidence for Unfavorable Effects of Antidepressants on Heart Rate Variability , 2010, Biological Psychiatry.

[31]  Nandini Dendukuri,et al.  Risk factors for depression among elderly community subjects: a systematic review and meta-analysis. , 2003, The American journal of psychiatry.

[32]  Hilary Cronin,et al.  Factors affecting continuous beat-to-beat orthostatic blood pressure response in community-dwelling older adults , 2012, Blood pressure monitoring.

[33]  R. Touyz Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II , 2005, Experimental physiology.

[34]  Marcus W. Agelink,et al.  Autonomic neurocardiac function in patients with major depression and effects of antidepressive treatment with nefazodone. , 2001, Journal of affective disorders.

[35]  K. Felmingham,et al.  Impact of Depression and Antidepressant Treatment on Heart Rate Variability: A Review and Meta-Analysis , 2010, Biological Psychiatry.

[36]  V. Yeragani,et al.  Effect of age on long-term heart rate variability. , 1997, Cardiovascular research.

[37]  Effect of fasting on participation in clinical research among older people , 2011 .

[38]  J. van Limbeek,et al.  Criterion validity of the Center for Epidemiologic Studies Depression scale (CES-D): results from a community-based sample of older subjects in The Netherlands. , 1997, Psychological medicine.

[39]  B. Ainsworth,et al.  International physical activity questionnaire: 12-country reliability and validity. , 2003, Medicine and science in sports and exercise.

[40]  M. Thase,et al.  Heart rate variability in depressed elderly. , 2008, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.