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Chronological Milestones to Guide Drug Change: When Should Clinicians Switch Antidepressants?

Chronological Milestones to Guide Drug Change: When Should Clinicians Switch Antidepressants? Abstract Background: We attempt to identify the time when patients whose conditions are unimproved while receiving antidepressants are unlikely to respond and should have their treatment changed. Methods: A total of 593 patients were studied. The course of treatment for patients was examined to determine the weeks at which patients who received drug therapy had a better chance of being rated as responders at the study end (week 6) vs patients who received placebo. Results: At the end of week 3, 19 (32%) of the 59 patients who received drug therapy and 6 (10%) of the 57 patients who received placebo and who never minimally improved were rated as responders at week 6. For those who showed no improvement by week 4, the effects of drug therapy and the placebo were equal. Patients who received drug therapy and whose conditions were unimproved but who had been minimally improved at some point had a superior prognosis with drug therapy vs placebo until week 4. Of those unimproved at week 4 but minimally improved at some point previously, 20 (39%) of the 51 patients who received drug therapy vs 3 (8%) of the 36 patients who received pIacebo were rated as responders at week 6. Of the 75 patients who minimally improved while receiving drug therapy at the end of week 5, 33 (44%) had a chance of being rated a responder at the end of week 6 vs 9 (26%) of the 35 patients receiving placebo. Conclusions: Patients tolerant of an adequate dose, whose conditions have never been at least minimally improved by the end of week 4, should have their treatment regimen altered. These patients represented a minority of drug-treated patients in the sample studied (ie, 39/392 [10%]). Patients whose conditions minimally improve at some prior week but not after week 5 should have their treatment changed. Patients whose conditions minimally improve in week 5 should continue treatment until week 6. References 1. Klein DF, Gittelman-Klein R, Quitkin FM, Rifkin A. Diagnosis and Drug Treatment of Psychiatric Disorders . Baltimore, Md: Williams & Wilkins; 1980:276-283. 2. Joyce PR, Paykel ED. Predictors of drug response in depression . Arch Gen Psychiatry . 1989;46:88-89.Crossref 3. Bielski RJ, Friedel RO. Prediction of tricyclic antidepressant response . Arch Gen Psychiatry . 1976;33:1479-1489.Crossref 4. Katz MM, Koslow SH, Maas JW, Frazer A, Bowden CL, Casper R, Croughan J, Kocsis J, Redmond E Jr. The timing, specificity and clinical prediction of tricyclic drug effects in depression . Psychol Med . 1987;17:297-309.Crossref 5. Casper RC, Katz MM, Bowden CL, Davis JM, Koslow SH, Hanin I. The pattern of physical symptom changes in major depressive disorder following treatment with amitriptyline or imipramine . J Affect Disord . 1994;31:151-164.Crossref 6. Coryell W, Coppen A, Zeigler VE, Biggs JT. Early improvement as a predictor of response to amitriptyline and nortriptyline: a comparison of 2 patient samples . Psychol Med . 1982;12:135-139.Crossref 7. Stassen HH, Angst J, Delini-Stula A. Severity at baseline and onset of improvement in depression: meta-analysis of imipramine and moclobemide versus placebo . Eur Psychiatry . 1994;9:129-136. 8. Katz M, Maas J, Frazer A, Koslow SH. Onset of antidepressant activity, the structure of depression and multiple drug actions. Presented at the American College of Neuropsychopharmacology Meeting; December 4, 1994; San Juan, Puerto Rico. 9. McGrath PJ, Stewart JW, Nunes EV, Ocepek-Welikson K, Rabkin JG, Quitkin KM, Klein DF. A double-blind cross over trial of imipramine and phenelzine for outpatients with treatment refractory depression . Am J Psychiatry . 1993;150 ( (1) ):118-123. 10. Quitkin FM, Rabkin JG, Markowitz JM, Stewart JW, McGrath PJ, Harrison W. Use of pattern analysis to identify true drug response: a replication . Arch Gen Psychiatry . 1987;44:259-264.Crossref 11. Stewart J, Quitkin FM, Fyer A, Rifkin A, McGrath P, Liebowitz M, Rosnick L, Klein DF. Efficacy of desipramine in endogenmorphically depressed patients . J Affect Disord . 1980;2:165-176.Crossref 12. Stewart JW, Quitkin FM, McGrath PJ, Liebowitz MR, Klein DF. Efficacy of desipramine in mildly depressed patients: a double-blind placebo-controlled trial . Psychopharmacol Bull . 1981;17:159-161. 13. Quitkin FM, Liebowitz MR, Stewart JW, McGrath PJ, Harrison W, Rabkin JG, Markowitz J, Davies SO. /-Depreny I in atypical depressives . Arch Gen Psychiatry . 1984;41:777-781.Crossref 14. McGrath PJ, Quitkin FM, Harrison W, Stewart JW. Treatment of melancholia with tranylcypromine . Am J Psychiatry . 1984;141:288-289. 15. Liebowitz MR, Quitkin FM, Stewart JW, McGrath PJ, Harrison WM, Markowitz JS, Rabkin JG, Tricamo E, Goetz DM, Klein DF. Antidepressant specificity in atypical depression . Arch Gen Psychiatry . 1988;45:129-137.Crossref 16. Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Wager SG, Nunes E, Rabkin JG, Tricamo E, Markowitz J, Klein DF. Phenelzine and imipramine in mood reactive depressives: further delineation of the syndrome of atypical depression . Arch Gen Psychiatry . 1989;46:787-793.Crossref 17. McGrath PJ, Rabkin JG, Stewart JW, Harrison W, Quitkin FM, Markowitz J. Placebo-controlled study of mianserin in depressed outpatients . Neuropsychobiology . 1985;14:128-132.Crossref 18. Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Tricamo E, Wager SG, Ocepek Welikson K, Nunes E, Rabkin JG, Klein DF. Atypical depression, panic attacks and response to imipramine and phenelzine: a replication . Arch Gen Psychiatry . 1990;47:935-941.Crossref 19. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised . Washington, DC: American Psychiatric Association; 1987. 20. Stewart JS, McGrath PJ, Rabkin JG, Quitkin FM. Atypical depression: a valid clinical entity? Psychiatr Clin North Am . 1993;16:479-495. 21. Spitzer RL, Endicott J, Robins E. Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders . 3rd ed. New York, NY: New York State Psychiatric Institute, Biometrics Research; 1977:19. 22. Stark P, Hardison CD. A review of multicenter controlled studies of fluoxetine vs imipramine and placebo in outpatients with major depressive disorder . J Clin Psychiatry . 1985;46:53-58. 23. Beasley CM, Sayler ME, Potvin JH. Fluoxetine versus amitriptyline in the treatment of major depression: a multicenter trial . Int Clin Psychopharmacol . 1993;8:143-149.Crossref 24. Feighner JP, Cohn JB. Double blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder . J Clin Psychiatry . 1985;46( (3) , pt2):20-25. 25. Fabre LF, Crismon L. Efficacy of fluoxetine in outpatients with major depression . Curr Ther Res . 1985;37:115-123. 26. Rosenbaum JF, Fava M, Quitkin FM, McGrath PJ, Stewart JW. Time to remission of depression with acute fluoxetine treatment. Presented at the 34th Annual Meeting of the New Clinical Drug Evaluation Unit; June 3, 1994; Marco Island, Fla. 27. Heninger GR, Charnley DS, Steinberg DE. Lithium carbonate augmentation of antidepressant treatment . Arch Gen Psychiatry . 1993;40:1335-1342.Crossref 28. Prange AJ, Wilson IC, Rabon AM. Enhancement of imipramine antidepressant activity by thyroid . Am J Psychiatry . 1969;126:457-469. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1996 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1996.01830090031005
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Abstract

Abstract Background: We attempt to identify the time when patients whose conditions are unimproved while receiving antidepressants are unlikely to respond and should have their treatment changed. Methods: A total of 593 patients were studied. The course of treatment for patients was examined to determine the weeks at which patients who received drug therapy had a better chance of being rated as responders at the study end (week 6) vs patients who received placebo. Results: At the end of week 3, 19 (32%) of the 59 patients who received drug therapy and 6 (10%) of the 57 patients who received placebo and who never minimally improved were rated as responders at week 6. For those who showed no improvement by week 4, the effects of drug therapy and the placebo were equal. Patients who received drug therapy and whose conditions were unimproved but who had been minimally improved at some point had a superior prognosis with drug therapy vs placebo until week 4. Of those unimproved at week 4 but minimally improved at some point previously, 20 (39%) of the 51 patients who received drug therapy vs 3 (8%) of the 36 patients who received pIacebo were rated as responders at week 6. Of the 75 patients who minimally improved while receiving drug therapy at the end of week 5, 33 (44%) had a chance of being rated a responder at the end of week 6 vs 9 (26%) of the 35 patients receiving placebo. Conclusions: Patients tolerant of an adequate dose, whose conditions have never been at least minimally improved by the end of week 4, should have their treatment regimen altered. These patients represented a minority of drug-treated patients in the sample studied (ie, 39/392 [10%]). Patients whose conditions minimally improve at some prior week but not after week 5 should have their treatment changed. Patients whose conditions minimally improve in week 5 should continue treatment until week 6. References 1. Klein DF, Gittelman-Klein R, Quitkin FM, Rifkin A. Diagnosis and Drug Treatment of Psychiatric Disorders . Baltimore, Md: Williams & Wilkins; 1980:276-283. 2. Joyce PR, Paykel ED. Predictors of drug response in depression . Arch Gen Psychiatry . 1989;46:88-89.Crossref 3. Bielski RJ, Friedel RO. Prediction of tricyclic antidepressant response . Arch Gen Psychiatry . 1976;33:1479-1489.Crossref 4. Katz MM, Koslow SH, Maas JW, Frazer A, Bowden CL, Casper R, Croughan J, Kocsis J, Redmond E Jr. The timing, specificity and clinical prediction of tricyclic drug effects in depression . Psychol Med . 1987;17:297-309.Crossref 5. Casper RC, Katz MM, Bowden CL, Davis JM, Koslow SH, Hanin I. The pattern of physical symptom changes in major depressive disorder following treatment with amitriptyline or imipramine . J Affect Disord . 1994;31:151-164.Crossref 6. Coryell W, Coppen A, Zeigler VE, Biggs JT. Early improvement as a predictor of response to amitriptyline and nortriptyline: a comparison of 2 patient samples . Psychol Med . 1982;12:135-139.Crossref 7. Stassen HH, Angst J, Delini-Stula A. Severity at baseline and onset of improvement in depression: meta-analysis of imipramine and moclobemide versus placebo . Eur Psychiatry . 1994;9:129-136. 8. Katz M, Maas J, Frazer A, Koslow SH. Onset of antidepressant activity, the structure of depression and multiple drug actions. Presented at the American College of Neuropsychopharmacology Meeting; December 4, 1994; San Juan, Puerto Rico. 9. McGrath PJ, Stewart JW, Nunes EV, Ocepek-Welikson K, Rabkin JG, Quitkin KM, Klein DF. A double-blind cross over trial of imipramine and phenelzine for outpatients with treatment refractory depression . Am J Psychiatry . 1993;150 ( (1) ):118-123. 10. Quitkin FM, Rabkin JG, Markowitz JM, Stewart JW, McGrath PJ, Harrison W. Use of pattern analysis to identify true drug response: a replication . Arch Gen Psychiatry . 1987;44:259-264.Crossref 11. Stewart J, Quitkin FM, Fyer A, Rifkin A, McGrath P, Liebowitz M, Rosnick L, Klein DF. Efficacy of desipramine in endogenmorphically depressed patients . J Affect Disord . 1980;2:165-176.Crossref 12. Stewart JW, Quitkin FM, McGrath PJ, Liebowitz MR, Klein DF. Efficacy of desipramine in mildly depressed patients: a double-blind placebo-controlled trial . Psychopharmacol Bull . 1981;17:159-161. 13. Quitkin FM, Liebowitz MR, Stewart JW, McGrath PJ, Harrison W, Rabkin JG, Markowitz J, Davies SO. /-Depreny I in atypical depressives . Arch Gen Psychiatry . 1984;41:777-781.Crossref 14. McGrath PJ, Quitkin FM, Harrison W, Stewart JW. Treatment of melancholia with tranylcypromine . Am J Psychiatry . 1984;141:288-289. 15. Liebowitz MR, Quitkin FM, Stewart JW, McGrath PJ, Harrison WM, Markowitz JS, Rabkin JG, Tricamo E, Goetz DM, Klein DF. Antidepressant specificity in atypical depression . Arch Gen Psychiatry . 1988;45:129-137.Crossref 16. Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Wager SG, Nunes E, Rabkin JG, Tricamo E, Markowitz J, Klein DF. Phenelzine and imipramine in mood reactive depressives: further delineation of the syndrome of atypical depression . Arch Gen Psychiatry . 1989;46:787-793.Crossref 17. McGrath PJ, Rabkin JG, Stewart JW, Harrison W, Quitkin FM, Markowitz J. Placebo-controlled study of mianserin in depressed outpatients . Neuropsychobiology . 1985;14:128-132.Crossref 18. Quitkin FM, McGrath PJ, Stewart JW, Harrison W, Tricamo E, Wager SG, Ocepek Welikson K, Nunes E, Rabkin JG, Klein DF. Atypical depression, panic attacks and response to imipramine and phenelzine: a replication . Arch Gen Psychiatry . 1990;47:935-941.Crossref 19. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised . Washington, DC: American Psychiatric Association; 1987. 20. Stewart JS, McGrath PJ, Rabkin JG, Quitkin FM. Atypical depression: a valid clinical entity? Psychiatr Clin North Am . 1993;16:479-495. 21. Spitzer RL, Endicott J, Robins E. Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders . 3rd ed. New York, NY: New York State Psychiatric Institute, Biometrics Research; 1977:19. 22. Stark P, Hardison CD. A review of multicenter controlled studies of fluoxetine vs imipramine and placebo in outpatients with major depressive disorder . J Clin Psychiatry . 1985;46:53-58. 23. Beasley CM, Sayler ME, Potvin JH. Fluoxetine versus amitriptyline in the treatment of major depression: a multicenter trial . Int Clin Psychopharmacol . 1993;8:143-149.Crossref 24. Feighner JP, Cohn JB. Double blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder . J Clin Psychiatry . 1985;46( (3) , pt2):20-25. 25. Fabre LF, Crismon L. Efficacy of fluoxetine in outpatients with major depression . Curr Ther Res . 1985;37:115-123. 26. Rosenbaum JF, Fava M, Quitkin FM, McGrath PJ, Stewart JW. Time to remission of depression with acute fluoxetine treatment. Presented at the 34th Annual Meeting of the New Clinical Drug Evaluation Unit; June 3, 1994; Marco Island, Fla. 27. Heninger GR, Charnley DS, Steinberg DE. Lithium carbonate augmentation of antidepressant treatment . Arch Gen Psychiatry . 1993;40:1335-1342.Crossref 28. Prange AJ, Wilson IC, Rabon AM. Enhancement of imipramine antidepressant activity by thyroid . Am J Psychiatry . 1969;126:457-469.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Sep 1, 1996

References