Summary
Amitriptyline (AT) and the noradrenaline reuptake inhibiting antidepressant oxaprotiline (OT = hydroxymaprotiline) were compared in 59 primary depressive inpatients in a 4-week double blind parallel group design. In the Hamilton Depression Rating Scale and 2 self-rating scales AT proved to be more efficient than OT, mainly with respect to disturbances of appetite and sleep. Agitated patients receiving OT needed more additional tranquilizing medication. The number of side-effects did not differ. Both drugs increased heart rate and skin resistance level (SRL) to about the same degree and did not influence the number of spontaneous fluctuations of SRL, habituation of SRL orienting responses (OR), frequencies of respiration and blinking. Salivation was temporarily more impaired by AT. All physiological variables differed between patients and 30 healthy controls during the whole 4-week trial. Clinical outcome showed a linear relation to OT plasma levels. For AT a therapeutic window was confirmed for concentrations of AT and its metabolite nortriptyline between 125 and 200 ng/ml. Patients whose SRL-OR habituated rapidly had a better outcome than slow habituators. Urinary excretion of 3-methoxy-4-hydroxyphenylglycol was lower in patients than in controls but could not predict outcome with either drug.
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Bente D, Fähndrich E (1980) Clinical and EEG effects of hydroxymaprotiline in depressive patients with special reference to responders and non-responders. Arzneim-Forsch/Drug Res 30 (II):1227
Breyer U, Villumsen K (1976) Plasma level measurement of tricyclic psychoactive drugs and their metabolites by UV reflectance photometry on thin layer chromatograms. Eur J Clin Pharmacol 9:457–465
Breyer-Pfaff U, Gaertner HJ, Giedke H (1982) Plasma levels, psychophysiological variables, and clinical response to amitriptyline. Psychiatry Res 6:223–234
Breyer-Pfaff U, Wiatr R, Nill K (1984) Measurement of maprotiline and oxaprotiline in plasma by high-performance liquid chromatography of fluorescent derivatives. J Chromatogr 309:107–114
Brunswick D, Amsterdam J, Mendels J, Stern S (1979) Prediction of steady-state imipramine and desmethylimipramine plasma concentrations from single-dose data. Clin Pharmacol Ther 25:605–610
Covi L, Rickets K, Lipman R, McNair D, Smith V, Downing R, Kahn R, Fisher S (1981) Effects of psychotropic agents on primary depression. Psychopharmacol Bull 17:100
Delini-Stula A, Bischoff S, Radeke E (1982a) Antiserotoninergic properties of maprotiline and a new antidepressant, oxaprotiline: two selective NA uptake inhibitors. Drug Dev Res 2:543–550
Delini-Stula A, Hauser K, Baumann P, Olpe HR, Waldmeier P, Storni A (1982b) Stereospecificity of behavioural and biochemical responses to oxaprotiline — a new antidepressant. In: Costa E, Racagni G (eds) Typical and atypical antidepressants. Adv Biochem Psychopharmacol 31:265–275
Feighner J, Brauzer B, Gelenberg A, Gomez E, Kiev A, Kurland M, Weiss B (1979) A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness. Psychopharmacology 61:217–225
Feighner J, Roffman M, Dixon R (1981) An early clinical trial of oxaprotiline in hospitalized patients with primary depression. Curr Ther Res 29:363–369
Frankenhaeuser M (1975) Experimental approaches to the study of catecholamines and emotion. In: Levi L (ed) Emotions. Raven Press, New York, pp 209–234
Frith C, Stevens M, Johnstone E, Crow T (1979) Skin conductance responsivity during acute episodes of schizophrenia as a predictor of symptomatic improvement. Psychol Med 9:101–106
Gaertner HJ, Wiatr G, Kuss HJ (1980) 4-Methoxy-3-hydroxyphenylglycol as an internal standard for the determination of 3methoxy-4-hydroxyphenylglycol in urine. Results obtained in depressed patients and healthy controls. J Clin Chem Clin Biochem 18:579–583
Gaertner HJ, Golfinopoulos G, Breyer-Pfaff U (1982a) Response to maprotiline treatment in depressive patients. Relationship to urinary MHPG excretion and plasma drug level. Pharmacopsychiatry 15:170–174
Gaertner HJ, Kreuter F, Scharek G, Wiatr G, Breyer-Pfaff U (1982b) Do urinary MHPG and plasma drug levels correlate with response to amitriptyline therapy? Psychopharmacology 76:236–239
Giedke H (1983) Zur Psychophysiologie von Depression und Manic. In: Saletu B, Berner P (Hgb) Zyklothymie. Excerpta Medica, Amsterdam, pp 29–39
Giedke H, Heimann H, Straube E (1982) Vergleichende Ergebnisse psychophysiologischer Untersuchungen bei Schizophrenien und Depressionen. In: Huber G (Hrsg) Endogene Psychosen: Diagnostik, Basissymptome und biologische Parameter. F. K. Schattauer, Stuttgart, New York, pp 295–312
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiat 23:56–62
Heimann H (1979) Psychophysiologie endogener Psychosen. Schweiz Arch Neurol Neurochir Psychiatr 125:231–252
Heimann H, Schmocker M, Straube E (1977) The psychophysiological basis of the pharmacotherapy of endogenous psychotics. In: Arieti S, Chrzanowski G (eds) New dimensions in psychiatry: a world view, vol 2, Wiley, New York, pp 363–374
Iacono W, Lykken D, Peloquin L, Lumry A, Valentine R, Tuason V (1983) Electrodermal activity in euthymic unipolar and bipolar affective disorders. Arch Gen Psychiatry 40:557–565
Iacono W, Lykken D, Haroian K, Peloquin L, Valentine R, Tuason V (1984) Electrodermal activity in euthymic patients with affective disorders: one-year retest stability and the effects of stimulus intensity and significance. J Abnorm Psychol 93:304–311
Johnstone E, Owens D, Frith D, Mcpershon K, Dowie C, Riley G, Gold A (1980) Neurotic illness and its response to anxiolytic and antidepressant treatment. Psychol Med 10:321–328
Kielholz P (1973) Diagnose und Therapie der Depressionen für den Praktiker. Lehmann, München
van der Kolk B, Shader R, Greenblatt D (1978) Autonomic effects of psychotropic drugs. In: Lipton M, DiMascio A, Killam K (eds) Psychopharmacology: A generation of progress. Raven Press, New York, pp 1009–1020
Maas J, Fawcett J, Dekirmenjian H (1972) Catecholamine metabolism, depressive illness and drug response. Arch Gen Psychiat 26:252–262
Madakasira S, Khazanie P, Sato T (1984) Single-dose single-point method in amitriptyline therapy. Psychopharmacology 84:574–576
Maitre L, Moser P, Baumann P, Waldmeier P (1980) Amine uptake inhibitors: criteria of selectivity. In: Svensson T, Carlsson A (eds) Biogenic amines and affective disorders. Acta Psychiatr Scand 61, (Suppl 280): 97–110
Montgomery S, McAuley R, Rani S, Montgomery D, Braithwaite R, Dawling S (1979) Amitriptyline plasma concentration and clinical response. Br Med J 1:230
Moyes ICA, Ray RL, Moyes RB (1980) Plasma levels and clinical improvement — a comparative study of clomipramine and amitriptyline in depression. Postgrad Med 156 (Suppl 1): 127–129
Müller A, Binz U, Wendt G (1983) A double blind comparison: oxaprotiline and maprotiline. VII World Congress of Psychiatry, Vienna, Austria, July 11–16 (poster 687)
Preskorn SH, Leonard K, Hignite C (1980) Liquid chromatography of amitriptyline and related tricyclic compounds. J Chromatogr 197:246–250
Redmond FC, Bowden CL, Lehmann LS, Stanton BC (1980) Single-dose prediction of amitriptyline and nortriptyline requirement in unipolar depression. Curr Ther Res 27:635–642
Rickets K (1981) Limbitrol (amitriptyline plus chlordiazepoxide) revisited. Psychopharmacology 75:31–33
Roffman M, Gould E (1982) Comparison of oxaprotiline to amitriptyline and placebo in depressed patients: relationship to MHPG. 13th CINP Congress, Jerusalem, Israel, June 20–25, Astracts vol II, p 624 (poster 47)
Roffman M, Gould E, Brewer S, Lau H, Sachais B, Dixon R, Kaczmarek L, LeSher A (1982) A double-blind comparative study of oxaprotiline with amitriptyline and placebo in moderate depression. Curr Ther Res 32:247–256
Roffman M, Gould E, Brewer S, Lau H, Sachais B, Dixon N, Kaczmarek L, LeSher A (1983) Comparative anticholinergic activity of oxaprotiline and amitriptyline. Drug Dev Res 3:561–566
SAS Institute (1982) SAS user's guide: statistics. Cary, North Carolina
Schatzberg J, Cole J (1978) Benzodiazepines in depressive disorders. Arch Gen Psychiatry 35:1359–1365
Schildkraut J (1974) Biochemical criteria for classifying depressive disorders and predicting responses to pharmacotherapy: Preliminary findings from studies of norepinephrine metabolism. Pharmacopsychiatry 7:98–107
Schmauss M, Laakmann G, Blaschke D, Büttermann M, Dieterle D, Kropp M (1980) Treatment of endogenous-depressed patients with hydroxymaprotiline — pilot study. Arzneim-Forsch/Drug Res 30 (II):1228–1229
Schmidlin O, Gundert-Remy U, Mäurer W, Weber E (1982) Differences of sympathomimetic and anticholinergic action of OH-maprotiline and its R(−)-enantiomer. Br J Clin Pharmacol 14:799–804
Schramm M, Selinger Z (1973) Operation of two epinephrine receptors and an acetylcholine receptor in the exocrine cell of the rat parotid gland. In: Usdin E, Snyder S (eds) Frontiers in catecholamine research. Pergamon Press, New York, pp 373–376
Sigg E (1968) In: Efron D (ed) Psychopharmacology, review of progress, 1957–1967. U. S. Government Printing Office, Washington, DC, pp 581–588
Spitzer R, Endicott J, Robins E (1978) Research Diagnostic Criteria. Arch Gen Psychiatry 35:773–782
Szabadi E, Gaszner P, Bradshaw C (1980) The peripheral anticholinergic activity of tricyclic antidepressants: comparison of amitryptiline and desipramine in human volunteers. Br J Psychiatr 137:433–439
Task Force on the Use of Laboratory Tests in Psychiatry (1985) Tricyclic antidepressants — blood level measurements and clinical outcome: an APA Task Force report. Am J Psychiatr 142:155–162
Vandel B, Vandel S, Allers G, Bechtel P, Volmat R (1979) Interaction between amitriptyline and phenothiazine in man: Effect on plasma concentration of amitriptyline and its metabolite nortriptyline and the correlation with clinical response. Psychopharmacology 65:187–190
Waldmeier P, Baumann P, Wilhelm M, Bernasconi R, Maitre L (1977) Selective inhibition of noradrenaline and serotonin uptake by C49802-B-Ba and CGP 6085 A. Eur J Pharmacol 46:387–391
Wolfersdorf M, Binz U, Metzger R, Studemund B, Wendt G, Hole G (1983) Double-blind study: oxaprotiline vs clomipramine. VII World Congress of Psychiatry, Vienna, Austria, July 11–16 (poster 653)
Zahn T, Carpenter W, McGlashan T (1981) Autonomic nervous system activity in acute schizophrenia. II. Relationships to short-term prognosis and clinical state. Arch Gen Psychiatry 38:260–266
von Zerssen D (1976) Klinische Selbstbeurteilungs-Skalen (KSb-S) aus dem Münchener Psychiatrischen Informationssystem (PSYCHIS München) Beltz Test Gesellschaft, Weinheim
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Giedke, H., Gaertner, H., Breyer-Pfaff, U. et al. Amitriptyline and oxaprotiline in the treatment of hospitalized depressive patients. Eur Arch Psychiatr Neurol Sci 235, 329–338 (1986). https://doi.org/10.1007/BF00381001
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DOI: https://doi.org/10.1007/BF00381001