Untreated patients with panic disorder have been shown to have altered α2-adrenoceptor sensitivity, as assessed by clonidine challenge testing. We investigated clonidine-induced biochemical, physiological, hor monal and psychological responses in six panic patients, before and after treatment with imipramine. Comparison of the clonidine-induced fall in plasma MHPG pre- and post-treatment showed it to be sig nificantly reduced after imipramine. Significantly smaller clonidine-induced falls in diastolic blood pressure and heart rate occurred after imipramine treatment. However, growth hormone and sedation responses were not altered. These data suggest that reduced sensitivity of some central α2-adrenoceptors occurs during treatment of panic disorder with imipramine. However, these changes do not fully explain the therapeutic actions of antidepressants in this condition.
Get full access to this article
View all access options for this article.
References
1.
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn. American Psychiatric Association, Washington, DC
2.
Bockaert J., Homberger V., Sladeczek F. (1990) Molecular pharmacology of adrenergic receptors and their cellular localization in brain cells in culture. In Heal D J, Marsden C A (eds), The pharmacology of noradrenaline in the central nervous system. Oxford University Press, Oxford, pp. 76-117
3.
Cameron O.G., Smith C.B., Hollingsworth P.J., Nesse R.M., Curtis G.C. (1984) Platelet alpha-2-adrenergic receptor binding and plasma catecholamines: before and during imipramine treatment in patients with panic anxiety. Arch Gen Psychiat41: 1144-1148
4.
Cassano G.B., Perugi G., McNair D.M. (1988) Panic disorder: review of the empirical and rational basis of pharmacological treatment. Pharmacopsychiatry21: 157-165
5.
Cedarbaum J.M., Aghajanian G.K. (1976) Noradrenergic rieurons of the locus coeruleus: inhibition by epinephrine and activation by the alpha-antagonist piperoxane . Brain Res12: 413-419
6.
Charney D.S., Heninger G.R. (1986) Abnormal regulation of noradrenergic function in panic disorders. Am J Psychiat43: 1042-1054
7.
Charney D.S., Redmond D.E. (1983) Neurobiological mechanisms in human anxiety. Neuropharmacology22: 1531-1536
8.
Charney D.S., Heninger G.R., Sternberg D.E., Roth R.H. (1981) Plasma MHPG in depression: effects of acute and chronic desipramine treatment. Psychiat Res5: 217-229
9.
Charney D.S., Heninger G., Sternberg D.E., Landis H. (1982) Abrupt discontinuation of antidepressant drugs: evidence for noradrenergic hyperactivityBr J Psychiat141: 377 -386
10.
Charney D.S., Heninger G.R., Sternberg D.E. (1982a). Assessment of alpha-2-adrenergic autoreceptor function in humans: effects of oral yohimbine. Life Sci30: 2033-2041
11.
Charney D.S., Heninger G.R., Sternberg D.E. (1982b) Failure of chronic antidepressant treatment to alter growth hormone response to clonidine. Psychiat Res7: 135-138
12.
Charney D.S., Heninger G.R., Sternberg D.E. (1983) Alpha-2-adrenergic receptor sensitivity and the mechanism of action of antidepressant therapy. Br J Psychiat142: 265-275
13.
Charney D.S., Heninger G.R., Breier A. (1984) Noradrenergic function and panic anxiety: effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiat41: 751-763
14.
Checkley S.A., Slade A.P., Shur E., Dawling S. (1981) A pilot study of the mechanism of action of desipramine . Br J Psychiat138 : 248-251
15.
Corn T.H., Thompson C., Checkley S.A. (1984) Effects of desipramine treatment upon central adrenoceptor function in normal subjects. Br J Psychiat145: 139-145
16.
Cowen P.J., Green A.R., Grahame-Smith D.G., Braddock L.E. (1985) Plasma melatonin during desmethylimipramine treatment: evidence for changes in noradrenergic transmission. Br J Clin Pharmacol19: 799-805
17.
Elliott J.M. (1984) Platelet receptor binding studies in affective disorders. J. Affect Dis6 : 219-239
18.
Glass I., Checkley S.A., Shur E., Dawling S. (1982) The effect of desipramine upon central adrenergic function in depressed patients. Br J Psychiat141: 372-376
19.
Glue P., Nutt D.J. (1988) Clonidine challenge testing of alpha-2-adrenoceptor function in man: the effects of mental illness and psychotropic medication . J Psychopharmacol2: 119-137
20.
Goodwin G.M., de Souza R.J., Green A.R. (1985) Presynaptic serotonin receptor-mediated response in mice attenutated by antidepressant drugs and electroconvulsive shock. Nature317: 531-533
21.
Green A.R., Nutt D.J. (1983) Antidepressants. In Grahame-Smith D G, Cowen P J (eds.), Psychopharmacology, part 1: preclinical psychopharmacology . Excerpta Medica, Amsterdam, pp. 1-37
22.
Green A.R., Nutt D.J. (1985) Antidepressants. In Grahame-Smith D G, Cowen P J (eds), Psychopharmacology 2, part 1: preclinical psychopharmacology . Elsevier, Amsterdam, pp. 1-34
23.
Heninger G.R., Charney D.S. (1987) Mechanism of action of antidepressant treatments: implications for the etiology and treatment of depressive disorders. In Meltzer H Y (ed), Psychopharmacology: the third generation of progress. Raven Press, New York , pp. 535-544
24.
Kahn R.S., Asnis G.M., Wetzler S., Van Praag H. (1988) Neuroendocrine evidence for serotonin receptor hypersensitivity in panic disorder. Psychopharmacology96: 360-364
25.
Ko G.N., Elsworth J.D., Roth R.H., Rifkin B.G., Leigh H., Redmond D.E. (1983) Panic-induced elevation of plasma MHPG levels in phobic-anxious patients: effects of clonidine and imipramine. Arch Gen Psychiat40: 365-375
26.
Lesch K-P., Muller U., Rupprecht R., Kruse K., Schulte H.M. (1989) Endocrine response to growth hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone in depression. Acta Psychiat Scand79: 597-602
27.
Lydiard R.B., Ballenger J.C. (1987) Antidepressants in panic disorder and agoraphobia . J Affect Disord13 : 153— 168
28.
Mavroidis M.L., Kanter D.R., Greenblum D.N., Garver D.L. (1984) Adrenergic-receptor desensitization and course of clinical improvement with desipramine treatment. Psychopharmacology83: 295-296
29.
Moller H.J., Kissling W., Botterman P. (1984) Serial application of clonidine tests during antidepressive treatment with chlorimipramine. Pharmacopsychiatry17: 184— 187
30.
Molyneux S.G., Franklin M. (1985) Routine determination of unconjugated 3-methoxy-4-hydroxyphenylglycol in plasma using high-performance liquid chromatography with electrochemical detectionJ Chromatog Biomed Appl341: 160-166
31.
Nutt D.J. (1986) Increased central alpha-2-adrenoceptor sensitivity in panic disorder. Psychopharmacology90: 268-269
32.
Nutt D.J. (1989) Altered alpha-2-adrenoceptor sensitivity in panic disorder. Arch Gen Psychiat46: 165—169
33.
Nutt D.J., Cowen P.J. (1987) Monoamine function in anxiety and depression: information from neuroendocrine challenge tests. Human Psychopharmacol2: 211-220
34.
Nutt DJ, George D.T. (1989) Serotonin and anxiety. In Burrows G D, Roth M, Noyes R (eds), Handbook of anxiety. Elsevier, Amsterdam, pp. 189-221
35.
Nutt D.J., Glue P. ( 1989) Clinical pharmacology of anxiolytics and antidepressants: a psychopharmacological perspective. Pharmacol Ther44: 309-344
36.
Nutt D.J., Glue P. ( 1991) Imipramine in panic disorder. Clinical response and pharmacological changes. J Psychopharmacol5: (in press)
37.
Nutt D.J., Glue P., Lawson C.W., Wilson S. (1990) Flumazenil provocation of panic attacks: evidence for benzodiazepine receptor sensitivity in panic disorder. Arch Gen Psychiat47: 917-925
38.
Nutt D.J., Glue P., Lawson C.W., Wilson S.J., Ball D.M. (1991) Do benzodiazepine receptors have a causal role in panic disorder? In British Association for Psychopharmacology monograph on panic disorder. Oxford University Press, Oxford (in press)
39.
Redmond D.E. (1986) The possible role of locus coeruleus noradrenergic activity in anxiety-panic. Clin Neuro-pharmacol9(suppl 4): 40-42
40.
Redmond D.E., Huang Y. (1979) Current concepts II: new evidence for a locus coeruleus-norepinephrine connection with anxiety. Life Sci25: 2149-2162
41.
Rifkin A., Klein D.F., Dillon D.J., Levitt M. (1981) Blockade by imipramine or desipramine of panic induced by sodium lactate. Am J Psychiat138: 676-677
42.
Schittecatte M., Charles G., Machowski R., Wilmotte J. (1989). Tricyclic washout and growth hormone response to clonidine.Br J Psychiat154: 858-863
43.
Siever L.J., Davis K.C. (1985) Towards a dysregulation hypothesis of depression . Am J Psychiat142: 1017—1031
44.
Smith C.B., Garcilla-Sevilla J.A., Hollingworth P.J. (1981) Alpha-2-adrenoceptors in rat brain are decreased after long-term tricyclic antidepressant drug treatment. Brain Res210: 413-418
45.
Smith C.B., Hollingworth P.J., Garcilla-Sevilla J.A., Zis A.P. (1983) Platelet alpha-2-adrenoceptors are decreased in number after antidepressant therapy. Progr Neuro-psychopharmacol Biol Psychiat7: 241-247
46.
Stanford C., Nutt D.J., Cowen P.J. (1983) Comparison of the effects of chronic desmethylimipramine administraton
47.
on alpha-2 and beta adrenoceptors in different regions of rat brain. Neuroscience8: 161-164
48.
Suranyi-Cadotte B.E. , Dam T.V., Quirion R. (1984) Antidepressant-anxiolytic interaction: decreased density of benzodiazepine receptors in rat brain following chronic administration of antidepressants. Eur J Pharmacol106: 673-675
49.
Svensson T.H. (1980) Effect of chronic treatment with tricyclic antidepressant drugs on identified brain noradrenergic and serotonergic neurons. Acta Psychiat Scand (suppl. 280): 121-131
50.
Svensson T.H. (1987) Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology. Psychopharmacology92: 1-7
51.
Svensson T.H., Usdin T. (1978) Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: alpha-receptor mediation. Science202: 1089-1091
52.
Uhde T.W., Vittone B.J., Siever L.J., Kaye W.H., Post R.M. (1986) Blunted growth hormone response to clonidine in panic disorder patients. Biol Psychiat21: 1077-1081
