Abstract
A noninvasive measure was used to assess the effects of alprazolam, imipramine and placebo on parasympathetic (vagal) cardiac control following 6-weeks of medication in patients with generalized anxiety disorder. Flexible dosage at therapeutic levels resulted in increased heart rate and blood pressure and in decreased cardiac vagal control in patients receiving imipramine but not alprazolam or placebo. About 50% of the variance in heart rate changes and changes in mean arterial blood pressure following treatment with imipramine could be accounted for by changes in cardiac vagal control. Decreased cardiac vagal control can now be added to the list of cardiovascular changes seen following several weeks of treatment with imipramine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
American Psychiatric Association Committee on Nomenclature and Statistics (1987) Diagnostic and statistical manual of mental disorders, revised 3rd edn. American Psychiatric Association, Washington, DC
Baldessarini RJ (1985) Drugs and the treatment of psychiatric disorders. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) Goodman and Gilman's. The pharmacological basis of therapeutics, 7th edn. Macmillan, New York, pp 387–445
Berne RM, Levy MN (1986) Cardiovascular physiology. CV Mosby, St. Louis
Billman GE, Dujardin J-P (1990) Dynamic changes in cardiac vagal tone as measured by time series analysis. Am J Physiol 258:H896-H902
Cheung MN, Porges SW (1977) Respiratory influences on cardiac responses during attention. Physiol Psychol 5:53–57
Eckberg DL (1983) Human sinus arrhythmia as an index of vagal cardiac outflow. J Appl Physiol: Respir Environ Exerc Physiol 54:961–966
Giardina EGV, Bigger T Jr, Glassman AH, Perel JM, Kantor SJ (1979) The electrocardiographic and antiarrhythmic effects of imipramine hydrochloride at therapeutic plasma concentrations. Circulation 60:1045–1052
Glassman AH, Bigger JT Jr (1981) Cardiovascular effects of therapeutic doses of tricyclic antidepressants. Arch Gen Psychiatry 38:815–820
Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55
Hayano J, Sakakibara Y, Yamada M, Kamiya T, Fujinami T, Yokoyama K, Wantanabe Y, Takata K (1990) Diurnal variations in vagal and sympathetic control. Am J Physiol 258:H642-H646
Hoehn-Saric R, McLeod DR, Zimmerli WD (1988) Differential effects of alprazolam and imipramine in generalized anxiety disorder: somatic versus psychic symptoms. J Clin Psychiatry 49:293–301
Jakobsen J, Hauksson P, Vestergaard P (1984) Heart rate variation in patients treated with antidepressants. An index of anticholinergic effects? Psychopharmacology 84:544–548
Johnsson G, Lundborg P, Welin-Fogelberg I (1979) Interaction studies between three antidepressant drugs (chlorimipramine, imipramine and zemelidine) and noradrenaline, tyramine and vagal stimulation on the heart rate and blood pressure in dogs. Acta Pharmacol Toxicol 45:192–197
Katona PG, Lipson D, Dauchot PJ (1977) Opposing central and peripheral effects of atropine on parasympathetic cardiac control. Am J Physiol 232:H146-H151
Lopes OU, Palmer JF (1976) Proposed respiratory “gating” mechanism for cardiac slowing. Nature 264:454–456
Malik R, Courtney KR, Jensen RA (1979) Imipramine affects autonomic control of sinoatrial rate in isolated right atrial preparations. J Pharmacol Exp Ther 211:284–289
McLeod DR, Hoehn-Saric R, Labib AS, Greenblatt DJ (1988) Six weeks of diazepam treatment in normal women: effects on psychomotor performance and psychophysiology. J Clin Psychopharmacol 8:83–99
McLeod DR, Hoehn-Saric R, Zimmerli WD, De Souza EB, Oliver LK (1990) Treatment effects of alprazolam and imipramine: physiological versus subjective changes in patients with generalized anxiety disorder. Biol Psychiatry 28:849–861
Mohrman DE, Heller LJ (1986) Cardiovascular physiology, 2nd edn. McGraw-Hill, New York
Parzen E (1961) Mathematical considerations in the estimation of spectra. Technometrics 3:167–190
Porges SW (1985) Method and apparatus for evaluating rhythmic oscillations in aperiodic physiological response systems. US Patent 451 0944, April 16, 1985
Porges SW (1986) Respiratory sinus arrhythmia: Physiological basis, quantitative methods, and clinical implications. In: Grossman P, Janssen KHL, Vaitl D (eds) Cardiorespiratory and cardiosomatic psychophysiology. Plenum Press, New York, pp 101–115
Porges SW (1991) Vagal mediation of respiratory sinus arrhythmia: implications for drug delivery. Ann NY Acad Sci 618:57–66
Porges SW, Bohrer RE (1990) The analysis of periodic processes in psychophysiological research. In: Cacioppo JT, Tassinary LG (eds) Principles of psychophysiology: physical, social, and inferential elements. Cambridge University Press, New York, pp 708–753
Risch SC, Groom GP, Janowsky DS (1982) The effects of psychotropic drugs on the cardiovascular system. J Clin Psychiatry 43:16–31
Roth WT, Telch MJ, Taylor CB, Agras WS (1988) Autonomic changes after treatment of agoraphobia with panic attacks. Psychiatry Res 24:95–107
Rudorfer MV, Potter WZ (1987) Pharmacokinetics of antidepressants. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 1353–1363
Spitzer RL, Williams JBW, Gibbon M (1987) Instruction manual for the structured clinical interview for DSM-III-R (SCID, 4/1/87 revision). Biometrics Research Department, New York State Psychiatric Institute, New York
Taylor CB, Hayward C, King R, Ehlers A, Margraf A, Maddock R, Clark D, Roth WT, Agras WS (1990) Cardiovascular and symptomatic reduction effects of alprazolam and imipramine in patients with panic disorder: results of a double-blind placebo controlled trial. J Clin Psychopharmacol 10:112–118
Author information
Authors and Affiliations
Additional information
This study was supported in part by NIMH grants MH35435 and MH42579, and by a grant from the Upjohn Company, Kalamazoo, Michigan. We thank Pamela A. Hipsley for assistance in data reduction and manuscript preparation.
Rights and permissions
About this article
Cite this article
McLeod, D.R., Hoehn-Saric, R., Porges, S.W. et al. Effects of alprazolam and imipramine on parasympathetic cardiac control in patients with generalized anxiety disorder. Psychopharmacology 107, 535–540 (1992). https://doi.org/10.1007/BF02245268
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245268