Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-05T16:41:47.931Z Has data issue: false hasContentIssue false
  • English
  • Français

Abrupt Discontinuation of Tricyclic Antidepressant Drugs: Evidence for Noradrenergic Hyperactivity

Published online by Cambridge University Press:  29 January 2018

Dennis S. Charney ,
George R. Heninger ,
David E. Sternberg  and
D. Harold Landis
Dennis S. Charney*
Affiliation:
Department of Psychiatry and the Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA
George R. Heninger
Affiliation:
Department of Psychiatry and the Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA
David E. Sternberg
Affiliation:
Department of Psychiatry and the Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA
D. Harold Landis
Affiliation:
Department of Psychiatry and the Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA
*
∗ Correspondence.
Get access Rights & Permissions [Opens in a new window]

Summary

The effect of abrupt discontinuation of amitriptyline, desipramine, or imipramine) on norepinephrine turnover and specific symptoms in seven depressed patients was examined. Turnover, as determined by plasma and urinary 3 methoxy-4-hydroxy-phenylethylene glycol (MHPG), was increased to a peak during the second week following discontinuation. There were no changes in blood pressure or heart rate. Two of the seven patients experienced clear increases in anxiety. The implications for the role of noradrenergic function is discussed.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 141 , Issue 4 , October 1982 , pp. 377 - 386
Copyright
Copyright © Royal College of Psychiatrists, 1982 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aghajanian, G. K. (1978) Tolerance of locus coeruleus neurons to morphine and suppression of withdrawal response by clonidine. Nature, 276, 186–8.Google Scholar
Andersen, H. & Kristiansen, E. S. (1959) Tofraniltreatment of endogenous depressions. Acta Psychiatrica Neurologica Scandinavica, 34, 387–97.Google Scholar
Blomberg, P. A., Kopin, I. J., Gorden, E. K., Mackey, S. P. & Ebert, M. H. (1980) Conversion of MHPG to vanillyl-mandelic acid. Archives of General Psychiatry, 37, 1095–7.Google Scholar
Brown, G. M., Stancer, H. C., Moldofsky, H., Harman, J., Murphy, J. T. & Gupta, R. N. (1978) Withdrawal from long-term high-dose desipramine therapy. Archives of General Psychiatry, 35, 1261–4.Google Scholar
Bunney, W. E., Wehr, T. R., Gillin, J. C., Post, R. M., Goodwin, F. K. & Van Kammen, D. P. (1977) The switch process in manic-depressive psychosis. Annals of Internal Medicine, 87, 319–35.Google Scholar
Cedarbaum, J. M. & Aghajanian, G. K. (1977) Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. European Journal of Pharmacology, 44, 375–85.Google Scholar
Charney, D. S., Heninger, G. R., Sternberg, D. E. & Roth, R. H. (1981a) Plasma MHPG in depression: effects of acute and chronic desipramine treatment. Psychiatry Research, 5, 217–29.Google Scholar
Charney, D. S., Heninger, G. R., Sternberg, D. E., Redmond, D. E., Leckman, J. F., Maas, J. W. & Roth, R. H. (1981b) Presynaptic adrenergic receptor sensitivity in depression: the effect of chronic desipramine treatment. Archives of General Psychiatry, 38, 1334–40.CrossRefGoogle Scholar
Charney, D. S., Menkes, D. B. & Heninger, G. R. (1981c) Receptor sensitivity and the mechanism of action of antidepressant treatment: implications for the etiology and theory of depression. Archives of General Psychiatry, 38, 1160–80.Google Scholar
Charney, D. S., Sternberg, D. E., Kleber, H. D., Heninger, G. R. & Redmond, D. E. (1981d) The clinical use of clonidine in abrupt withdrawal from methadone. Archives of General Psychiatry, 38, 1273–8.Google Scholar
Crawley, J. N., Laverty, R. N. & Roth, R. H. (1979) Clonidine reversal of increased norepinephrine metabolite levels during morphine withdrawal. European Journal of Pharmacology, 57, 247–55.Google Scholar
Crews, F. T. & Smith, C. B. (1978) Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment. Science, 202, 422–3.Google Scholar
Crews, F. T. & Smith, C. B. (1980) Potentiation of responses to adrenergic nerve stimulation in isolated rat atria during chronic tricyclic antidepressant administration. Journal of Pharmacology and Experimental Therapeutics, 215, 143–9.Google Scholar
Dekirmenjian, G. & Maas, J. W. (1974) 3-methoxy-4-hydroxyphenethyleneglycol in plasma. Clinica Chimica Acta, 52, 203–10.Google Scholar
de Montigny, C. & Aghajanian, G. K. (1978) Tricyclic antidepressants: Long-term treatment increases responsivity of rat forebrain neurons to serotonin. Science, 202, 1303–6.Google Scholar
Elsworth, J. D., Redmond, D. E. & Roth, R. H. (1982) Plasma and cerebrospinal fluid 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG) as indices of brain norepinephrine metabolism in primates. Brain Research, (in press).Google Scholar
Garcia-Sevilla, J. A., Zis, A. P., Hollingsworth, P. A., Greden, J. F. & Smith, C. B. (1981a) Platelet alpha-2 adrenergic receptors in major depressive disorder: binding of tritiated clonidine before and after tricyclic antidepressant drug treatment. Archives of General Psychiatry, 36, 1327–33.Google Scholar
Garcia-Sevilla, J. A., Zis, A. P., Zelnik, R. & Smith, C. B. (1981b) Tricyclic drug treatment decreases alpha-2 adrenoceptors on human platelets membranes. European Journal of Pharmacology, 69, 121–3.Google Scholar
Gawin, F. H. & Markoff, R. A. (1981) Panic anxiety after abrupt discontinuation of amitriptyline. American Journal of Psychiatry, 138, 117–18.Google Scholar
Gloger, S., Grunhaus, L., Birmacher, B. & Troudart, T. (1981) Treatment of spontaneous panic attacks with chlorimipramine. American Journal of Psychiatry, 138, 1215–17.Google Scholar
Gold, M. S., Redmond, D. E. & Kleber, H. D. (1978) Clonidine blocks acute opiate withdrawal symptoms. Lancet, 2, 599–602.Google Scholar
Gower, A. J. & Marriott, A. S. (1980) The inhibition of clonidine induced sedation in the mouse by antidepressant drugs. British Journal of Pharmacology, 69, 287.Google Scholar
Gualtieri, C. T. & Staye, J. (1979) Withdrawal symptoms after abrupt cessation of amitriptyline in an eight-year-old boy. American Journal of Psychiatry, 136, 457–8.CrossRefGoogle Scholar
Heninger, G. R., French, N. H., Slavinsky, A. T., Davis, L. & Mueller, P. S. (1970) A short clinical rating scale for use by nursing personnel: II. Reliability, validity, and application. Archives of General Psychiatry, 23, 241–50.Google Scholar
Karoum, F., Mayer-Schwing, J., Potkin, S. G. & Wyatt, R. J. (1977) Presence of free sulfate, and glucuronide conjugated MHPG in human brain, cerebrospinal fluid, and plasma. Brain Research, 125, 333–9.Google Scholar
Klein, D. F., Zitrin, C. M. & Woerner, M. (1978) Antidepressants, anxiety, panic, and phobia. In Psychopharmacology: A Generation of Progress, (eds. Lipton, M. A., DiMascio, A. and Killam, D. F.). New York: Raven Press.Google Scholar
Kopin, I. J. (1978) Measuring turnover of neurotransmitters in human brains. In Psychopharmacology: A Generation of Progress, (eds. Lipton, M. A., DiMascio, A. and Killam, D. F.). New York: Raven Press.Google Scholar
Kramer, J. C., Klein, D. F. & Fink, M. (1961) Withdrawal symptoms following discontinuation of imipramine therapy. American Journal of Psychiatry, 118, 549–50.Google Scholar
Langer, S. Z., Briley, M. S. & Raisman, R. (1980) Regulation of neurotransmission through presynaptic receptors and other mechanisms: Possible clinical relevance and therapeutic potential. In Receptors for Neurotransmitters and Peptides, (eds. Pepau, G., Kuhan, M. J. and Enna, S. J.). New York: Raven Press.Google Scholar
Law, W., Petti, T. A. & Kazdin, A. E. (1981) Withdrawal symptoms after graduated cessation of imipramine in children. American Journal of Psychiatry, 138, 647–50.Google ScholarPubMed
Llorens, C., Martres, M. P., Baudry, M. & Schwartz, J. C. (1978) Hypersensitivity to noradrenaline in cortex after chronic morphine: Relevance to tolerance and dependence. Nature, 274, 603–5.Google Scholar
Maas, J. W., Hattox, S. E., Greene, N. M. & Landis, D. H. (1979) MHPG production by human brain in vivo. Science, 205, 1025–7.CrossRefGoogle ScholarPubMed
Maas, J. W., Landis, H. & Dekirmenjian, G. (1976) The occurrence of free vs conjugated MHPG in nonhuman and human primate brain. Psychopharmacology Communication, 2, 403–10.Google Scholar
Mann, A. M. & MacPherson, A. S. (1959) Clinical experience with imipramine (G22355) in the treatment of depression. Canadian Psychiatric Association Journal, 4, 38–47.Google Scholar
McMillen, B. A., Warnack, W., German, D. C. & Shore, P. A. (1980) Effects of chronic desipramine treatment on rat brain noradrenergic responses to alpha-adrenergic drugs. European Journal of Pharmacology, 61, 239–46.Google Scholar
Menkes, D. B., Aghajanian, G. K. & McCall, R. B. (1980) Chronic antidepressant treatment enhances alpha-adrenergic and serotonergic responses in the facial nucleus. Life Sciences, 27, 45–55.Google Scholar
Mirin, S. M., Schatzberg, A. F. & Creasey, D. E. (1981) Hypomania and mania after withdrawal of tricyclic antidepressants. American Journal of Psychiatry, 138, 87–9.Google Scholar
Nagy, A. (1977) Blood and brain concentrations of imipramine, chlorimipramine, and their monomethylated metabolites after oral and intramuscular administration in rats. Journal of Pharmaceutical Pharmacology, 29, 104–7.Google Scholar
Nathanson, J. A. & Redmond, D. E. Jr. (1981) Morphine withdrawal causes supersensitivity of adrenergic receptor response. Life Sciences, 28, 1353–60.Google Scholar
Nyback, H. V., Walters, J. R., Aghajanian, G. K. & Roth, R. H. (1975) Tricyclic antidepressants: effects on the firing rate of brain noradrenergic neurons. European Journal of Pharmacology, 32, 302–12.Google Scholar
Petti, T. A. & Law, W. (1981) Abrupt cessation of high-dose imipramine in children. Journal of the American Medical Association, 246, 768–9.Google Scholar
Potter, W. Z., Calil, H. M., Extein, I., Muscettola, G. & Goodwin, F. K. (1981) Crossover study of zimelidine and desipramine: Evidence for amine specificity. Psychopharmacology Bulletin, 17, 26.Google ScholarPubMed
Redmond, D. E. & Huang, Y. H. (1979) New evidence for a locus coeruleus-noradrenergic connection with anxiety. Life Sciences, 25, 2149–62.Google Scholar
Santos, A. B. & McCurdy, L. (1980) Delirium after abrupt withdrawal for doxepine: case report. American Journal of Psychiatry, 137, 239–40.Google Scholar
Sathananthan, G. L. & Gershon, S. (1973) Imipramine withdrawal; an akathisia-like syndrome. American Journal of Psychiatry, 130, 1286–7.CrossRefGoogle ScholarPubMed
Schildkraut, J. J., Winokur, A., Draskoczy, P. R. & Hensle, J. H. (1971) Changes in norepinephrine turnover during chronic administration of imipramine and protriptyline: A possible explanation for the delay of onset of clinical antidepressant effects. American Journal of Psychiatry, 127, 72–9.Google Scholar
Shatan, C. (1966) Withdrawal symptoms after abrupt termination of imipramine. Canadian Psychiatric Association Journal, 11 (Supplement), S150–8.Google Scholar
Sheehan, D. V., Ballenger, J. & Jacobsen, G. (1980) Treatment of endogenous anxiety with phobic, hysterical, and hypochondriacal symptoms. Archives of General Psychiatry, 37, 51–9.Google Scholar
Siever, L. F., Cohen, R. M. & Murphy, D. L. (1981) Antidepressants and alpha-2 adrenergic autoreceptor desensitization. American Journal of Psychiatry, 138, 681–2.Google Scholar
Smith, C. B., Garcia-Sevilla, J. A. & Hollingsworth, P. J. (1981) Alpha-2 adrenoceptors in rat brain are decreased after long-term tricyclic antidepressant drug treatment. Brain Research, 210, 413–18.Google Scholar
Spitzer, R. L., Endicott, J. & Robins, E. (1977) Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders, 3rd edition. New York: New York State Psychiatric Institute.Google Scholar
Sugrue, M. G. (1980a) Changes in rat brain monoamine turnover following chronic antidepressant administration. Life Sciences, 26, 423–33.Google Scholar
Sugrue, M. G. (1980b) Effects of acutely and chronically administered antidepressants on the clonidine-induced decrease in rat brain 3-methoxy-4-hydroxyphenethyleneglycol sulphate. Life Sciences, 28, 377–84.Google Scholar
Sulser, F., Vetulani, J. & Mobley, P. L. (1978) Mode of action of antidepressant drugs. Biochemical Pharmacology, 27, 257–61.Google Scholar
Svensson, T. H. & Usdin, T. (1978) Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: alpha receptor mediation. Science, 202, 1089–91.Google Scholar
Svensson, T. H. & Usdin, T. (1979) Alpha-adrenoceptor mediated inhibition of brain noradrenergic neurons after acute and chronic treatment with tricyclic antidepressants. In Catecholamines: Basic and Clinical Frontiers, (eds. Usdin, E., Kopin, I. J. and Barchas, J.). Oxford: Pergamon Press.Google Scholar
Sypraki, C. & Fibiger, H. C. (1980) Functional evidence for subsensitivity of noradrenergic receptors after chronic desipramine treatment. Life Sciences, 27, 1963–7.Google Scholar
Tallman, J. F., Paul, S. M., Skolnick, P. & Gallager, D. W. (1980) Receptors for the age of anxiety: Pharmacology of the benzodiazepines. Science, 207, 274–81.Google Scholar
Tang, S. W., Helmeste, D. M. & Stancer, H. C. (1978) The effect of acute and chronic desipramine and amitriptyline treatment on rat brain total 3-methoxy-4-hydroxyphenylglycol. Naunyn-Schmiedeberg's Archives of Pharmacology, 305, 207–11.Google Scholar
Tang, S. W., Helmeste, D. M. & Stancer, H. C. (1979) Interaction of antidepressants with clonidine on rat brain total 3-methoxy-4-hydroxyphenylglycol. Canadian Journal of Physiology and Pharmacology, 57, 435–7.Google Scholar
Wolfe, B. B., Harden, T. K., Sporn, J. R. & Molinoff, P. B. (1978) Presynaptic modulation of beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants. Journal of Pharmacology and Experimental Therapeutics, 207, 446–57.Google Scholar
Zitrin, C., Klein, D. F. & Woerner, M. G. (1978) Behavior therapy, supportive psychotherapy, imipramine, and phobias. Archives of General Psychiatry, 35, 307–16.Google Scholar
Zitrin, C., Klein, D. F. & Woerner, M. G. (1980) Treatment of agoraphobia with group exposure in vivo and imipramine. Archives of General Psychiatry, 37, 63–72.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.