Skip to main content

Advertisement

SpringerLink
Log in

Effects of sertraline on autonomic and cognitive functions in healthy volunteers

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Though 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.

Objective

To compare the effects of sertraline on cognitive and autonomic functions with those of placebo in healthy humans.

Method

A 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.

Results

Sertraline 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.

Conclusion

Cognitive 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agelink MW, Mayewsky T, Andrich J, Mück-Weymann M (2002) Short term effects of intravenous bezodiazepines on autonomic neurocardiac regulation: a comparison between midazolam, diazepam and lorazepam. Crit Care Med 30:997–1006

    CAS  PubMed  Google Scholar 

  • Bolden-Watson C, Richelson E (1993) Blockade by newly developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 52:1023–1029

    CAS  PubMed  Google Scholar 

  • Dawson ME, Schell AM, Filion DL (2000) The electrodermal system. In: Cacioppo JT, Tassinary LG, Berntson GC (eds) Handbook of psychophysiology. Cambridge University Press, Cambridge, pp 200–223

  • Doogan DP (1991) Toleration and safety of sertraline: experience worldwide. Int Clin Psychopharmacol 6:47–56

    PubMed  Google Scholar 

  • Edwards JG, Anderson I (1999) Systematic review and guide to selection of selective serotonin reuptake inhibitors. Drugs 57:507–533

    CAS  PubMed  Google Scholar 

  • Feder R (1991) Bradycardia and syncope induced by fluoxetine. J Clin Psychiatry 52:138–139

    Google Scholar 

  • Fuller RW (1995) Neural functions of serotonin. Sci Am Sci Med 4:48–57

    Google Scholar 

  • Gibson SJ (1997) The measurement of mood states in older adults. J Gerontol Psychol Sci 52B:P167–P174

    Google Scholar 

  • Grubb BP, Karas BJ (1998) The potential role of serotonin in the pathogenesis of neurocardiogenic syncope and related autonomic disturbances. J Interv Electrophysiol 2:352–332

    Google Scholar 

  • Isbister GK, Prior FH, Foy A (2001) Citalopram-induced bradycardia and presyncope. Ann Pharmacother 35:1552–1555

    Article  CAS  PubMed  Google Scholar 

  • Jacobs SC, Friedman R, Parker JD, Tofler GH, Jimenez AH, Muller JE, Benson H, Stone PH (1994) Use of skin conductance changes during mental stress testing as an index of autonomic arousal in cardiovascular research. Am Heart J 128:1170–1177

    CAS  PubMed  Google Scholar 

  • Kerr JS, Hindmarch I (1996) Citalopram and other antidepressants: comparative effects on cognitive function and psychomotor performance. J Serotonin Res 3:123–129

    CAS  Google Scholar 

  • Kobayashi H, Ishibashi K, Noguchi H (1999) Heart rate variability; an index for monitoring and analyzing human autonomic activities. Appl Hum Sci 18:53–59

    CAS  Google Scholar 

  • Lehnert H, Lombardi F, Raeder EA, Lorenzo AV, Verrier RL, Lown B, Wurtman RJ (1987) Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat. J Cardiovasc Pharmacol 10:389–397

    CAS  PubMed  Google Scholar 

  • Low PA, Opfer-Gehrking TL, Kihara M (1992) In vivo studies on receptor pharmacology of the human eccrine sweat gland. Clin Autonom Res 2:29–34

    CAS  Google Scholar 

  • Lown B, Verrier RL (1976) Neural activity and ventricular fibrillation. N Engl J Med 294:1165–1170

    CAS  PubMed  Google Scholar 

  • Luciana M, Collins PF, Depue RA (1998) Opposing roles for dopamine and serotonin in the modulation of human spatial working memory function. Cereb Cortex 8:218–226

    CAS  PubMed  Google Scholar 

  • MacQueen G, Born L, Steiner M (2001) The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders. CNS Drug Rev 7:1–24

    CAS  PubMed  Google Scholar 

  • Masand PS, Gupta S (1999) Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry 7:69–84

    CAS  PubMed  Google Scholar 

  • Mattila MJ, Saarialho-Kere U, Mattila M (1988) Acute effects of sertraline, amitriptyline, and placebo on the psychomotor performance of healthy subjects over 50 years of age. J Clin Psychiatry 49:52–58

    PubMed  Google Scholar 

  • McFarlane A, Kamath MV, Fallen EL, Malcolm V, Cherian F, Norman G (2001) Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction. Am Heart J 142:617–623

    Article  CAS  PubMed  Google Scholar 

  • Morgan DA, Thoren P, Wilczynski E, Victor RG, Mark AL (1988) Serotonergic mechanisms mediate renal sympathoinhibition during severe hemorrhage in rats. Am J Physiol 255:H496–502

    CAS  PubMed  Google Scholar 

  • Mück-Weymann M (2000) Methoden und Technik [Methods and techniques]. In: Mück-Weymann M (ed) Autonome Funktionskreise in Psychosomatik und Psychiatrie. Nicht-invasives Biomonitoring in der Psychopharmakotherapie. [Autonomic functions in psychosomatic medicine and psychiatry. Non-invasive monitoring of psychopharmacological therapy]. Hans Jacobs, Lage, pp 28–38

  • Mück-Weymann M, Acker J, Agelink M (2001) Autonomic responses of blood vessels and sweat glands in patients with schizophrenia treated with olanzapine or clozapine. Psychopharmacology 157:368–372

    Article  PubMed  Google Scholar 

  • Rasmussen SL, Overo KF, Tanghoj P (1999) Cardiac safety of citalopram: prospective trials and retrospective analyses. J Clin Psychopharmacol 19:407–415

    Google Scholar 

  • Rodriguez de la Torre B, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H, Luderitz B, Rao ML (2001) Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients. Ther Drug Monit 23:435–440

    Article  PubMed  Google Scholar 

  • Roose SP, Glassman AH, Attia E, Woodring S, Giardina EG, Bigger JT Jr (1998) Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 155:660–665

    CAS  PubMed  Google Scholar 

  • Saletu B, Grunberger J (1988) Drug profiling by computed electroencephalography and brain maps, with special consideration of sertraline and its psychometric effects. J Clin Psychiatry 49:59–71

    PubMed  Google Scholar 

  • Saletu B, Grünberger J, Rajna P (1983) Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine. Br J Clin Pharmacol 15:369S–384S

    Google Scholar 

  • Saletu B, Grunberger J, Linzmayer L (1986) On central effects of serotonin re-uptake inhibitors: quantitative EEG and psychometric studies with sertraline and zimeldine. J Neural Transm 67:241–266

    CAS  PubMed  Google Scholar 

  • Schmitt JAJ, Kruizinga MJ, Riedel WJ (2001) Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors. J Psychopharmacol 15:73–179

    Google Scholar 

  • Shapiro PA, Lesperance F, Frasure-Smith N et al. (1999) An open label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT trial). Am Heart J 137:1100–1106

    CAS  PubMed  Google Scholar 

  • Siepmann M, Mück-Weymann M, Joraschky P, Kirch W (2001) The effects of reboxetine on autonomic and cognitive functions in healthy volunteers. Psychopharmacology 157:202–207

    CAS  PubMed  Google Scholar 

  • Siepmann M, Krause S, Joraschky P, Mück-Weymann M, Kirch W (2002) The effects of St John`s wort extract on heart variability, cognitive functions and quantitative EEG—a comparison with amitriptyline and placebo in healthy men. Br J Clin Pharmacol 54:277–282

    Article  CAS  PubMed  Google Scholar 

  • Smirni P, Villardita C, Tappala G (1983) Influence of different paths on spatial memory performance in the block-tapping test. Clin Neuropsychol 5:355–359

    CAS  Google Scholar 

  • Spigset O (1999) Adverse reactions of selective serotonin reuptake inhibitors: reports from a spontaneous reporting system. Drug Safety 20:277–287

    CAS  PubMed  Google Scholar 

  • Szabo ST, Blier P (2002) Effects of serotonin (5-hydroxytryptamine, 5HT) reuptake inhibition plus 5-HT (2A) receptor antagonism on the firing activity of norepinephrine neurons. J Pharmacol Exp Ther 302:983–991

    Article  CAS  PubMed  Google Scholar 

  • Tadepalli AS, Mills E, Schanberg SM (1977) Central depression of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: influence of supracollicular areas of the brain. J Pharmacol Exp Ther 202:310–319

    CAS  PubMed  Google Scholar 

  • Tatsumi M, Groshan K, Blakely RD, Richelson E (1997) Pharmacological profile of antidepressants and related compounds at human monoamine transporters Eur J Pharmacol 340:249–258

    Google Scholar 

  • Votolato NA, Stern S, Caputo RM (2000) Serotonergic antidepressants and urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 11:386–388

    Article  CAS  PubMed  Google Scholar 

  • Yamadera H, Ferber G, Matejcek M, Pokorny R (1987) Quantitative pharmaco-electroencephalographic differentiation between the CNS effects of bromocriptine and imipramine, drugs with qualitatively different antidepressant properties. Pharmacopsychiatry 20:54–59

    Google Scholar 

  • Yeragani VK, Pesce V, Jayaraman A, Roose S (2002) Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on long-term heart rate variability measures. Biol Psychiatry 52:418–429

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was part of a thesis. The authors are sincerely thankful to Mrs. E. Hempel for her assistance in conducting the study.

Author information

Authors and Affiliations

  1. Institute of Clinical Pharmacology, Medical Faculty, Technical University, Fiedlerstrasse 27, 01307, Dresden, Germany

    Martin Siepmann, Jens Grossmann & Wilhelm Kirch

  2. Clinic for Psychosomatic Medicine and Psychotherapy, Medical School, Technical University, Fetscherstrasse 74, 01307, Dresden, Germany

    Michael Mück-Weymann

  3. Institute of Molecular and Cellular Physiology, Friedrich-Alexander-University, Waldstrasse 6, 91054, Erlangen, Germany

    Michael Mück-Weymann

Authors
  1. Martin Siepmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jens Grossmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Mück-Weymann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wilhelm Kirch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Siepmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siepmann, M., Grossmann, J., Mück-Weymann, M. et al. Effects of sertraline on autonomic and cognitive functions in healthy volunteers. Psychopharmacology 168, 293–298 (2003). https://doi.org/10.1007/s00213-003-1448-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-003-1448-4

Keywords

Search

Navigation