Effects of sertraline on autonomic and cognitive functions in healthy volunteers

RationaleThough sertraline, a selective serotonin reuptake inhibitor (SSRI), causes autonomic and cognitive adverse events such as dry mouth and somnolence, there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature.ObjectiveTo compare the effects of sertraline on cognitive and autonomic functions with those of placebo in healthy humans.MethodA randomized, double blind, cross over study of 12 healthy male volunteers aged 24 (21– 32; median; range) years. Subjects orally received 50 mg sertraline and placebo once daily for periods of 14 days each with at least 14 days in between. Heart rate variability (HRV), skin conductance level (SCL) and skin conductance response (SCR) following sudden deep respiration were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. Measurements were performed repeatedly before the start of drug administration and on the last treatment day.ResultsSertraline caused a significant reduction of heart rate and SCL (P<0.05), whereas HRV and SCR were not changed. Cognitive functions such as flicker fusion frequency, memory, choice reaction time and psychomotor performance were not influenced by sertraline but slow and fast beta power density in the qEEG was increased.ConclusionCognitive and psychomotor performance are not altered in healthy humans receiving multiple dosing with sertraline. The observed decreases in heart rate and SCL may be due to a sympatho-inhibitory effect of sertraline.

[1]  F. Lombardi,et al.  Increased Release of Brain Serotonin Reduces Vulnerability to Ventricular Fibrillation in the Cat , 1987, Journal of cardiovascular pharmacology.

[2]  B. Saletu,et al.  Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine. , 1983, British journal of clinical pharmacology.

[3]  W. Biebl,et al.  Bradycardia and syncope induced by fluoxetine. , 1991 .

[4]  S. Schanberg,et al.  Central depression of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: influence of supracollicular areas of the brain. , 1977, The Journal of pharmacology and experimental therapeutics.

[5]  R. Pokorny,et al.  Quantitative Pharmaco-electroencephalographic Differentiation between the CNS Effects of Bromocriptine and Imipramine, Drugs with Qualitatively Different Antidepressant Properties , 1987, Pharmacopsychiatry.

[6]  B. Saletu,et al.  On central effects of serotonin re-uptake inhibitors: Quantitative EEG and psychometric studies with sertraline and zimelidine , 2005, Journal of Neural Transmission.

[7]  A. Foy,et al.  Citalopram-Induced Bradycardia and Presyncope , 2001, The Annals of pharmacotherapy.

[8]  E. Richelson,et al.  Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. , 1993, Life sciences.

[9]  O. Spigset Adverse Reactions of Selective Serotonin Reuptake Inhibitors , 1999, Drug safety.

[10]  W. Riedel,et al.  Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors , 2001, Journal of psychopharmacology.

[11]  B. Lüderitz,et al.  Serum Levels and Cardiovascular Effects of Tricyclic Antidepressants and Selective Serotonin Reuptake Inhibitors in Depressed Patients , 2001, Therapeutic drug monitoring.

[12]  M. Mueck‐Weymann,et al.  Short-term effects of intravenous benzodiazepines on autonomic neurocardiac regulation in humans: A comparison between midazolam, diazepam, and lorazepam , 2002, Critical care medicine.

[13]  E. Fallen,et al.  Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction. , 2001, American heart journal.

[14]  J. Bigger,et al.  Cardiovascular effects of fluoxetine in depressed patients with heart disease. , 1998, The American journal of psychiatry.

[15]  V. Yeragani,et al.  Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on long-term heart rate variability measures , 2002, Biological Psychiatry.

[16]  G. MacQueen,et al.  The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders. , 2006, CNS drug reviews.

[17]  B Lown,et al.  Neural activity and ventricular fibrillation. , 1976, The New England journal of medicine.

[18]  M. Siepmann,et al.  The effects of reboxetine on autonomic and cognitive functions in healthy volunteers , 2001, Psychopharmacology.

[19]  G. Zappala,et al.  Influence of different paths on spatial memory performance in the Block-Tapping Test. , 1983, Journal of clinical neuropsychology.

[20]  P. Stone,et al.  Use of skin conductance changes during mental stress testing as an index of autonomic arousal in cardiovascular research. , 1994, American heart journal.

[21]  B. Grubb,et al.  The Potential Role of Serotonin in the Pathogenesis of Neurocardiogenic Syncope and Related Autonomic Disturbances , 1998, Journal of Interventional Cardiac Electrophysiology.

[22]  M. Siepmann,et al.  The effects of St John's wort extract on heart rate variability, cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men. , 2002, British journal of clinical pharmacology.

[23]  Doogan Dp Toleration and safety of sertraline: experience worldwide. , 1991 .

[24]  S. Gibson,et al.  The measurement of mood states in older adults. , 1997, The journals of gerontology. Series B, Psychological sciences and social sciences.

[25]  N. Votolato,et al.  Serotonergic Antidepressants and Urinary Incontinence , 2000, International Urogynecology Journal.

[26]  R. Blakely,et al.  Pharmacological profile of antidepressants and related compounds at human monoamine transporters. , 1997, European journal of pharmacology.

[27]  P. Tanghøj,et al.  Cardiac safety of citalopram: prospective trials and retrospective analyses. , 1999, Journal of clinical psychopharmacology.

[28]  A. Mark,et al.  Serotonergic mechanisms mediate renal sympathoinhibition during severe hemorrhage in rats. , 1988, The American journal of physiology.

[29]  B. Saletu,et al.  Drug profiling by computed electroencephalography and brain maps, with special consideration of sertraline and its psychometric effects. , 1988, The Journal of clinical psychiatry.

[30]  P. Masand,et al.  Selective serotonin-reuptake inhibitors: an update. , 1999, Harvard review of psychiatry.

[31]  P. Low,et al.  In vivo studies on receptor pharmacology of the human eccrine sweat gland , 1992, Clinical Autonomic Research.

[32]  C. O'connor,et al.  An open-label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT Trial). Sertraline Anti-Depressant Heart Attack Trial. , 1999, American heart journal.

[33]  P. Blier,et al.  Effects of Serotonin (5-Hydroxytryptamine, 5-HT) Reuptake Inhibition Plus 5-HT2A Receptor Antagonism on the Firing Activity of Norepinephrine Neurons , 2002, Journal of Pharmacology and Experimental Therapeutics.

[34]  M. Dawson,et al.  The electrodermal system , 2007 .

[35]  R. Depue,et al.  Opposing roles for dopamine and serotonin in the modulation of human spatial working memory functions. , 1998, Cerebral cortex.

[36]  H Kobayashi,et al.  Heart rate variability; an index for monitoring and analyzing human autonomic activities. , 1999, Applied human science : journal of physiological anthropology.