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A Comparison Study of Amitriptyline and Nortriptyline With Plasma Levels

A Comparison Study of Amitriptyline and Nortriptyline With Plasma Levels Abstract • Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptylinetreated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = —0.54, P <.025) and positive in the nortriptyline-treated patients (r = 0.49, P <.05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P<.001), Zung Score (P <.01), and percent recovered (P <.001), than those above or below the therapeutic range. References 1. Forrest AD, Affleck JW, Gibb IA, et al: Comparative trial of nortriptyline and amitriptyline . Scott Med J 9:341-344, 1964. 2. Leahy MR, Martin JCA: Double-blind comparison of nortriptyline and amitriptyline in depressive illness . Br J Psychiatry 113:1433-1434, 1967.Crossref 3. Rose JT, Leahy MR, Martin JCA, et al: A comparison of nortriptyline and amitriptyline in depression . Br J Psychiatry 111:1101-1103, 1965.Crossref 4. Mendels J: Comparative trial of nortriptyline and amitriptyline in 100 depressed patients . Am J Psychiatry 124:59-62, 1968. 5. Alexanderson LM, Evans DA, Sjöqvist F: Steady-state plasma levels of mortriptyline in twins . Br Med J 4:764-768, 1969.Crossref 6. Asberg M, Cröholm B, Sjöqvist F, et al: Relationship between plasma level and therapeutic effect of nortriptyline . Br Med J 3:331-334, 1971.Crossref 7. Kragh-Sørensen P, Asberg M, Eggert-Hansen C: Plasma-nortriptyline levels in endogenous depression . Lancet 1:113-115, 1973.Crossref 8. Braithwaite RA, Goulding R, Theano G, et al: Plasma concentration of amitriptyline and clinical response . Lancet 1:1297-1300, 1972.Crossref 9. Gram LF, Reisby N, Ibsen I, et al: Plasma levels and antidepressive effect of imipramine . Clin Pharmacol Ther 19:318-324, 1976. 10. Ziegler VE, Clayton PJ, Taylor JR, et al: Nortriptyline plasma levels and therapeutic response . Clin Pharmacol Ther 20:458-463, 1976. 11. Ziegler VE, Co BT, Taylor JR, et al: Amitriptyline plasma levels and therapeutic response . Clin Pharmacol Ther 19:795-801, 1976. 12. Whyte SF, Macdonald AJ, Naylor GJ, et al: Plasma concentrations of protriptyline and clinical effects in depressed women . Br J Psychiatry 128:384-390, 1976.Crossref 13. Montgomery S, Braithwaite R: The relationship between plasma concentration amitriptyline and therapeutic response. Read before the Joint British Scandinavian Associations of Psychopharmacology Meeting, London, July 1975. 14. Feighner JP, Robins E, Guze SB, et al: Diagnostic criteria for use in psychiatric research . Arch Gen Psychiatry 26:57-63, 1972.Crossref 15. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 23:56-62, 1960.Crossref 16. Zung WWK: A self rating depression scale . Arch Gen Psychiatry 12:63-70, 1965.Crossref 17. Åsberg M, Crönholm B, Sjöqvist F, et al: Correlation of subjective side effects with plasma concentrations of nortriptyline . Br Med J 4:18-21, 1970.Crossref 18. Biggs JT, Holland WH, Chang SS, et al: The electron beam ionization mass fragmentographic analysis of tricyclic antidepressants in human plasma . J Pharmacol Sci 65:261-268, 1976.Crossref 19. Siegel S: Non-parametric Statistics for the Behavioral Sciences . New York, McGraw-Hill Book Co Inc, 1956. 20. Detre TP, Jarecki HG: Modern Psychiatric Treatment . Philadelphia, JB Lippincott Co, 1971. 21. Sandifer MG, Wilson IC, Gambill JM: The influence of case selection and dosage in an antidepressant drug trial . Br J Psychiatry 111:142-148, 1965.Crossref 22. Biggs JT, Holland WH, Sherman WR: Steady-state protriptyline levels in an outpatient population . Am J Psychiatry 132:960-962, 1975. 23. Glassman AH, Hurwic MJ, Perel JM: Plasma binding of imipramine and clinical outcome . Am J Psychiatry 130:1367-1369, 1973. 24. Petit JM, Spiker DG, Ruwitch JF, et al: Tricyclic antidepressant plasma levels and adverse effects in 40 overdose cases . Clin Pharmacol Ther 21:47-51, 1977. 25. Beckmann H, Goodwin FK: Antidepressant response to tricyclics and urinary MHPG in unipolar patients . Arch Gen Psychiatry 32:17-21, 1975.Crossref 26. Schildkraut JJ: Norepinephrine metabolites as biochemical criteria for classifying depressive disorders and predicting responses to treatment: Preliminary findings . Am J Psychiatry 130:695-698, 1973. 27. Maas JW: Biogenic amines and depression . Arch Gen Psychiatry 32:1357-1361, 1975.Crossref 28. Kupfer DJ, Pichar P, Himmelhoch JM, et al: Are there two types of unipolar depression? Arch Gen Psychiatry 32:866-871, 1975.Crossref 29. Kupfer DJ, Foster FG, Reich L, et al: EEG sleep changes as predictors in depression . Am J Psychiatry 133:622-626, 1976. 30. Spiker DG, Weiss AN, Chang SS, et al: Tricyclic antidepressant overdose: Clinical presentation and plasma levels . Clin Pharmacol Ther 18:539-546, 1975. 31. Biggs JT, Chang SS, Sherman WR, et al: Measurement of tricyclic antidepressant levels in an outpatient clinic . J Nerv Ment Dis 162:46-51, 1976.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

A Comparison Study of Amitriptyline and Nortriptyline With Plasma Levels

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Publisher
American Medical Association
Copyright
Copyright © 1977 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1977.01770170117012
Publisher site
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Abstract

Abstract • Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptylinetreated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = —0.54, P <.025) and positive in the nortriptyline-treated patients (r = 0.49, P <.05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P<.001), Zung Score (P <.01), and percent recovered (P <.001), than those above or below the therapeutic range. References 1. Forrest AD, Affleck JW, Gibb IA, et al: Comparative trial of nortriptyline and amitriptyline . Scott Med J 9:341-344, 1964. 2. Leahy MR, Martin JCA: Double-blind comparison of nortriptyline and amitriptyline in depressive illness . Br J Psychiatry 113:1433-1434, 1967.Crossref 3. Rose JT, Leahy MR, Martin JCA, et al: A comparison of nortriptyline and amitriptyline in depression . Br J Psychiatry 111:1101-1103, 1965.Crossref 4. Mendels J: Comparative trial of nortriptyline and amitriptyline in 100 depressed patients . Am J Psychiatry 124:59-62, 1968. 5. Alexanderson LM, Evans DA, Sjöqvist F: Steady-state plasma levels of mortriptyline in twins . Br Med J 4:764-768, 1969.Crossref 6. Asberg M, Cröholm B, Sjöqvist F, et al: Relationship between plasma level and therapeutic effect of nortriptyline . Br Med J 3:331-334, 1971.Crossref 7. Kragh-Sørensen P, Asberg M, Eggert-Hansen C: Plasma-nortriptyline levels in endogenous depression . Lancet 1:113-115, 1973.Crossref 8. Braithwaite RA, Goulding R, Theano G, et al: Plasma concentration of amitriptyline and clinical response . Lancet 1:1297-1300, 1972.Crossref 9. Gram LF, Reisby N, Ibsen I, et al: Plasma levels and antidepressive effect of imipramine . Clin Pharmacol Ther 19:318-324, 1976. 10. Ziegler VE, Clayton PJ, Taylor JR, et al: Nortriptyline plasma levels and therapeutic response . Clin Pharmacol Ther 20:458-463, 1976. 11. Ziegler VE, Co BT, Taylor JR, et al: Amitriptyline plasma levels and therapeutic response . Clin Pharmacol Ther 19:795-801, 1976. 12. Whyte SF, Macdonald AJ, Naylor GJ, et al: Plasma concentrations of protriptyline and clinical effects in depressed women . Br J Psychiatry 128:384-390, 1976.Crossref 13. Montgomery S, Braithwaite R: The relationship between plasma concentration amitriptyline and therapeutic response. Read before the Joint British Scandinavian Associations of Psychopharmacology Meeting, London, July 1975. 14. Feighner JP, Robins E, Guze SB, et al: Diagnostic criteria for use in psychiatric research . Arch Gen Psychiatry 26:57-63, 1972.Crossref 15. Hamilton M: A rating scale for depression . J Neurol Neurosurg Psychiatry 23:56-62, 1960.Crossref 16. Zung WWK: A self rating depression scale . Arch Gen Psychiatry 12:63-70, 1965.Crossref 17. Åsberg M, Crönholm B, Sjöqvist F, et al: Correlation of subjective side effects with plasma concentrations of nortriptyline . Br Med J 4:18-21, 1970.Crossref 18. Biggs JT, Holland WH, Chang SS, et al: The electron beam ionization mass fragmentographic analysis of tricyclic antidepressants in human plasma . J Pharmacol Sci 65:261-268, 1976.Crossref 19. Siegel S: Non-parametric Statistics for the Behavioral Sciences . New York, McGraw-Hill Book Co Inc, 1956. 20. Detre TP, Jarecki HG: Modern Psychiatric Treatment . Philadelphia, JB Lippincott Co, 1971. 21. Sandifer MG, Wilson IC, Gambill JM: The influence of case selection and dosage in an antidepressant drug trial . Br J Psychiatry 111:142-148, 1965.Crossref 22. Biggs JT, Holland WH, Sherman WR: Steady-state protriptyline levels in an outpatient population . Am J Psychiatry 132:960-962, 1975. 23. Glassman AH, Hurwic MJ, Perel JM: Plasma binding of imipramine and clinical outcome . Am J Psychiatry 130:1367-1369, 1973. 24. Petit JM, Spiker DG, Ruwitch JF, et al: Tricyclic antidepressant plasma levels and adverse effects in 40 overdose cases . Clin Pharmacol Ther 21:47-51, 1977. 25. Beckmann H, Goodwin FK: Antidepressant response to tricyclics and urinary MHPG in unipolar patients . Arch Gen Psychiatry 32:17-21, 1975.Crossref 26. Schildkraut JJ: Norepinephrine metabolites as biochemical criteria for classifying depressive disorders and predicting responses to treatment: Preliminary findings . Am J Psychiatry 130:695-698, 1973. 27. Maas JW: Biogenic amines and depression . Arch Gen Psychiatry 32:1357-1361, 1975.Crossref 28. Kupfer DJ, Pichar P, Himmelhoch JM, et al: Are there two types of unipolar depression? Arch Gen Psychiatry 32:866-871, 1975.Crossref 29. Kupfer DJ, Foster FG, Reich L, et al: EEG sleep changes as predictors in depression . Am J Psychiatry 133:622-626, 1976. 30. Spiker DG, Weiss AN, Chang SS, et al: Tricyclic antidepressant overdose: Clinical presentation and plasma levels . Clin Pharmacol Ther 18:539-546, 1975. 31. Biggs JT, Chang SS, Sherman WR, et al: Measurement of tricyclic antidepressant levels in an outpatient clinic . J Nerv Ment Dis 162:46-51, 1976.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: May 1, 1977

References