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Is dose escalation of antidepressants a rational strategy after a medium–dose treatment has failed?

A systematic review
  • M. Adli
  • Ch. Baethge
  • A. Heinz
  • N. Langlitz
  • M. Bauer
ORIGINAL PAPER

Abstract

Background

Maximizing the dose of antidepressants is widely recommended in cases of non–response to medium–dose treatment. However, scientific evidence supporting high–dose treatment is scarce. Systematic studies comparing dose escalation with alternative strategies for refractory depression (i. e. augmentation or change of compound) are lacking. The aim of this publication is to review available direct and indirect evidence concerning dose increase of antidepressants after a medium–dose trial has failed.

Method

We performed a systematic literature search of Medline (1966–2003) and reviewed studies and publication references for available evidence.

Data sources and study selection

Studies of the following types were included: 1) dose increase studies in treatment refractory patients, 2) comparative dose studies, 3) therapeutic drug monitoring studies.

Results

Available data suggest differential efficacy of various pharmacological classes at more than medium–dosage. Direct evidence shows no increase of efficacy with high–dose selective serotonin reuptake inhibitor (SSRI) treatment; however, indirect evidence suggests enhanced therapeutic efficacy with high–dose tricyclic antidepressants. Few clinical data show ultra–high–dose treatment with the irreversible monoamine–oxidase–(MAO–) inhibitor tranylcypromine to be effective for refractory depression. Data concerning other selective compounds are insufficient to allow any definitive conclusion on the benefit of high–dose treatment.

Conclusions

Based on available data highdose antidepressant treatment of patients refractory to medium–dose treatment is recommended for tricyclic compounds but not for SSRI. Some data suggest beneficial efficacy of ultra–high doses of the irreversible MAOI tranylcypromine. Research on other substance groups is limited and inconclusive. Prospective studies comparing dose escalation with alternative strategies for treatment of non–responding patients are needed.

Key words

antidepressants dose escalation treatment–refractory depression non–response review 

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References

  1. 1.
    Adli M, Berghöfer A, Linden M, Helmchen H, Müller-Oerlinghausen B, Mackert A, Stamm T, Bauer M (2003) Effectiveness and feasibility of a standardized stepwise drug treatment algorithm for inpatients with depressive disorders – results of a two-year observational study. J Clin Psychiatry 63:782–790Google Scholar
  2. 2.
    American Psychiatric Association (2000) Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 157(4 Suppl):1–44Google Scholar
  3. 3.
    Amin M, Lehmann H, Mirmiran J (1989) A double-blind, placebo controlled dosefinding study with sertraline. Psychopharmacol Bull 25:164–167PubMedGoogle Scholar
  4. 4.
    Amsterdam JD, Berwish NJ (1989) High dose tranylcypromine therapy for refractory depression. Pharmacopsychiat 22:21–25Google Scholar
  5. 5.
    Amsterdam JD (1991) Use of high dose tranylcypromine in resistant depression. In: Amsterdam JD (ed) Advances in Neuropsychiatry and Psychopharmacology. Vol 2: Refractory depression. Raven Press, New York, pp 123–129Google Scholar
  6. 6.
    Amsterdam JD, Hornig-Rohan M (1996) Treatment algorithms in treatment-resistant depression. Psychiatr Clin North Am 19:371–386PubMedCrossRefGoogle Scholar
  7. 7.
    Anderson IM, Nutt DJ, Deakin JFW (2000) Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. J Psychopharmacol 14:3–20PubMedCrossRefGoogle Scholar
  8. 8.
    Angst J (1970) Klinische Wirkung von Imipramin. In: Angst J, Theobald W, Bleuler M, Kuhn R (eds) Tofranil. Ciba-Geigy, Basel: Stämpfli, Bern, pp 3–82Google Scholar
  9. 9.
    Angst J, Amein R, Stabl M (1995) Moclobemide and tricyclic antidepressants in severe depression: meta-analysis and prospective studies. J Clin Psychopharmacol 15(Suppl 2):16–23CrossRefGoogle Scholar
  10. 10.
    Asberg M, Cronholm B, Sjöqvist F, Tuck D (1971) Relationship between plasma level and therapeutic effect of nortriptyline. BMJ 3:331–334PubMedCrossRefGoogle Scholar
  11. 11.
    Balant-Gorgia AE, Balant LP, Garrone G (1989) High blood concentrations of imipramine or clomipramine and therapeutic failure: a case resport study using drug monitoring data. Ther Drug Monit 11:415PubMedCrossRefGoogle Scholar
  12. 12.
    Bauer M, Forsthoff A, Baethge C, Adli M, Berghöfer A, Döpfmer S, Bschor T (2003) Lithium augmentation therapy in refractory depression update 2002. Eur Arch Psychiatry Clin Neurosci 253:132–139PubMedCrossRefGoogle Scholar
  13. 13.
    Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ (2002) World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and Continuation Treatment of Major Depressive Disorder. World J Biol Psychiatry 3:5–43PubMedGoogle Scholar
  14. 14.
    Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Gerlach M, Kuss HJ, Laux G, Muller-Oerlinghausen B, Rao ML, Riederer P, Zernig G (2004) The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 37:243–265PubMedGoogle Scholar
  15. 15.
    Beasley CM, Bosomworth JC, Wernicke JF (1990) Fluoxetine: relationships among dose, response, adverse events, and plasma concentrations in the treatment of depression. Psychopharmacol Bull 26:18–24PubMedGoogle Scholar
  16. 16.
    Benkert O, Szegedi A, Wetzel H (1996) Minimum effective dose for antidepressants – an obligatory requirement for antidepressant drug evaluation. Int Clin Psychopharmacol 11:177–185PubMedGoogle Scholar
  17. 17.
    Benkert O, Szegedi A, Wetzel H, Staab HJ, Meister W, Dose PM (1997) Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out-patients with inadequate treatment response. Acta Psychiatr Scand 95:288–296PubMedGoogle Scholar
  18. 18.
    Bjerkenstedt L, Flyckt L, Overo KF, Lingjaerde O (1985) Relationship between clinical effects, serum drug concentration, and serotonin uptake inhibition in depressed patients treated with citalopram: a double-blind comparison of three dose levels. Eur J Clin Pharmacol 28:553–557PubMedCrossRefGoogle Scholar
  19. 19.
    Bollini P, Pampallona S, Tibaldi G, Kupelnick B, Munizza C (1999) Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials. Br J Psychiatry 174:297–303PubMedGoogle Scholar
  20. 20.
    Braithwaite RA, Goulding R, Theano G, Bailey J, Coppen A (1972) Plasma concentration of amitriptyline and clinical response. Lancet 1:1297–1300PubMedGoogle Scholar
  21. 21.
    Coppen A, Ghose K, Montgomery S, et al. (1978) Amitriptyline plasma-concentration and clinical effect: a World Health Organization collaborative study. Lancet 1(7764):63–66PubMedGoogle Scholar
  22. 22.
    Corruble E, Guelfi JD (2000) Does increasing dose improve efficacy in patients with poor antidepressant response: a review. Acta Psychiatr Scand 101:343–348PubMedCrossRefGoogle Scholar
  23. 23.
    Danish University Antidepressant Group (DUAG) (1999) Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Clin Pharmacol Ther 66:152–165Google Scholar
  24. 24.
    Dornseif BE, Dunlop SR, Potvin JH, Wernicke JF (1989) Effect of dose escalation after low-dose fluoxetine therapy. Psychopharmacol Bull 25:71–79 PubMedGoogle Scholar
  25. 25.
    Dunbar GC, Stoker MJ (1991) Paroxetine in the treatment of melancholic and severely depressed hospitalized patients (abstract). Eur Neuropsychopharmacol 1:439CrossRefGoogle Scholar
  26. 26.
    Dunner DL, Dunbar GC (1992) Optimal dose regimen for paroxetine. J Clin Psychiatry 53(Suppl 2):21–26PubMedGoogle Scholar
  27. 27.
    Fabre LF, Abuzzahab FS, Amin M, Claghorn JL, Mendels J, Petrie WM, Dubé S, Small JG (1995) Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biol Psychiatry 38:592–602PubMedCrossRefGoogle Scholar
  28. 28.
    Fava M, Rosenbaum JF, Cohen L, Reiter S, McCarthy M, Steingard R, Clancy K (1992) High-dose fluoxetine in the treatment of depressed patients not responsive to a standard dose of fluoxetine. J Affect Disord 25:229–234PubMedCrossRefGoogle Scholar
  29. 29.
    Fava M, Rosenbaum JF, McGrath PJ, Stewart JW, Amsterdam JD, Quitkin FM (1994) Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: a double-blind, controlled study. Am J Psychiatry 151:1372–1374 PubMedGoogle Scholar
  30. 30.
    Fava M, Kendler KS (2000) Major Depressive Disorder. Neuron 28:335–341PubMedCrossRefGoogle Scholar
  31. 31.
    Fava M, Alpert J, Nierenberg A, Lagomasino I, Sonawalla S, Tedlow J, Worthington J, Baer L, Rosenbaum JF (2002) Double-blind study of high-dose fluoxetine versus lithium or despramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. J Clin Psychopharmacol 22:379–387PubMedGoogle Scholar
  32. 32.
    Fontaine R, Ontiveros A, Elie R, Kensler TT, Roberts DL, Kaplita S, Ecker JA, Faludi G (1994) A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry 55:234–241PubMedGoogle Scholar
  33. 33.
    Fredman SJ, Fava M, Kienke AS, White CN, Nierenberg AA, Rosenbaum JF (2000) Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "next-step" practices. J Clin Psychiatry 61:403–408PubMedGoogle Scholar
  34. 34.
    Friedel RO (1984) Relationship of desipramine plasma levels to therapeutic response: a critical reappraisal of the data. J Clin Psychiatry 45:46–49PubMedGoogle Scholar
  35. 35.
    Fritze J, Laux G, Sofic E, Koronakis P, Schoerlin MP, et al. (1989) Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines. Psychopharmacol 99:252–156Google Scholar
  36. 36.
    Gagiano CA, Müller FGM, Berk M, Joubert PM, Woods Brown RGC, Schall R (1995) Moclobemide twice daily in the treatment of major depressive episode: a double-blind, multicenter comparison with different three times daily dosage schedules. J Clin Psychopharmacol 15(Suppl 2):4–9Google Scholar
  37. 37.
    Garvey M, DeRubeis RJ, Hollon SD, Evans MD, Tuason VB (1991) Response of depression to very high plasma levels of imipramine plus desipramine. Biol Psychiatry 30:57–62PubMedCrossRefGoogle Scholar
  38. 38.
    Glassman AH, Perel JM, Shostak M, Kantor SJ, Fleiss JL (1977) Clinical implications of imipramine plasma levels for depressive illness. Arch Gen Psychiatry 34:197–204PubMedGoogle Scholar
  39. 39.
    Goethe JW, Szarek BL, Cook WL (1988) A comparison of adquately vs. inadequately treated depressed patients. J Nerv Ment Dis 176:465–470PubMedGoogle Scholar
  40. 40.
    Golden RN, DeVane CL, Laizure SC, Rudorfer MV, Sherer MA, Potter WZ (1988) Bupropion in depression II: the role of metabolites in clinical outcome. Arch Gen Psychiatry 45:145–149PubMedGoogle Scholar
  41. 41.
    Gram LF (1990) Inadequate dosing and pharmacokinetic variability as confounding factors in assessment of efficacy of antidepressants. Clin Neuropharmacol 13(Suppl 1):35–44Google Scholar
  42. 42.
    Gram LF (1993) Dose-effect relationships for tricyclic antidepressants: the basis for rational clinical testing of new antidepressants. In: Gram LF, Balant LP, Meltzer HY, Dahl SG (eds) Clinical Pharmacology in Psychiatry. Vol. 10. Strategies in Psychotropic Drug Development. Springer, Berlin Heidelberg New York, pp 163–173Google Scholar
  43. 43.
    Greden JF (2001) The burden of disease for treatment-resistant depression. J Clin Psychiatry 62(Suppl 16):26–31PubMedGoogle Scholar
  44. 44.
    Gringras M (1975) A comparison of a low and high dosage regimen of clomipramine (Anafranil). J Int Med Res 3(Suppl 1):47–54Google Scholar
  45. 45.
    Guy W, Manov G, Wilson WH (1986) Double-blind dose determination study of a new antidepressant – sertraline. Drug Dev Res 9:267–272CrossRefGoogle Scholar
  46. 46.
    Guze BH, Baxter LR, Rego J (1987) Refractory depression treated with high doses of a monoamine oxidase inhibitor. J Clin Psychiatry 48:31–32PubMedGoogle Scholar
  47. 47.
    Jenner PN (1992) Paroxetine: an overview of dosage, tolerability, and safety. Int Clin Psychopharmacol 6(Suppl 4):69–80PubMedGoogle Scholar
  48. 48.
    Kane JM, Cole K, Sarantakos S, Howard A, Borenstein M (1983) Safety and efficacy of bupropion in elderly patients: preliminary observations. J Clin Psychiatry 44:134–136PubMedGoogle Scholar
  49. 49.
    Kelly MW, Perry PJ, Holstad SG, Garvey MJ (1989) Serum fluoxetine and norfluoxetine concentrations and antidepressant response. Ther Drug Monit 11:165–170PubMedGoogle Scholar
  50. 50.
    Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmoller J (2004) Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 9:442–473 PubMedCrossRefGoogle Scholar
  51. 51.
    Kragh-Sorensen P, Asberg M, Eggert-Hansen C (1973) Plasma nortriptyline levels in endogenous depression. Lancet 1:113–115PubMedGoogle Scholar
  52. 52.
    Kragh-Sorensen P, Hansen CE, Baastrup PC, Hvidberg EF (1976) Self-inhibiting action of nortriptyline’s antidepressive effect at high plasma levels: a randomized double-blind study controlled by plasma concentrations in patients with endogenous depression. Psychopharmacologia 45:305–312PubMedGoogle Scholar
  53. 53.
    Kupfer DJ, Hanin I, Spiker DG, Grau T, Coble P (1977) Amitriptyline plasma levels and clinical response in primary depression. Clin Pharmacol Ther 22:904–911PubMedGoogle Scholar
  54. 54.
    Laux G (1990) Dosiserhöhung, Titration eines optimalen Wirkspiegels und Infusionstherapie als effiziente Möglichkeiten der Behandlung therapieresistenter Depressionen mit Antidepressiva. In: Möller HJ (ed) Therapieresistenz unter Antidepressivabehandlung. Springer, Berlin Heidelberg New York, pp 99–112Google Scholar
  55. 55.
    Lensch K, Fuchs G, Böning J, Milech U (1987) A clinical study of the selective MAO-A-inhibitor moclobemide (Ro11–1163): a comparison of 2 different dosages with particular reference to platelet MAO-activity and urinary MHPG-excretion. Int Clin Psychopharmacol 2:165–171PubMedGoogle Scholar
  56. 56.
    Leucht S, Steimer W, Kreuz S, Abraham D, Orsulak PJ, Kissling W (2001) Doxepin plasma concentrations: is there really a therapeutic range? J Clin Psychopharmacol 21:432–439PubMedCrossRefGoogle Scholar
  57. 57.
    Licht RW, Qvitzau S (2002) Treatment strategies in patients with major depression not responding to first-line sertraline treatment: a randomised study of extended duration of treatment, dose increase or mianserin augmentation. Psychopharmacology 161:143–151PubMedCrossRefGoogle Scholar
  58. 58.
    Liisberg P, Mose H, Amdisen A, et al. (1978) A clinical trial comparing sustained release amitriptyline (Saroten Retard) and conventional amitriptyline tablets (Saroten) in endogenously depressed patients with simultaneous determination of serum levels of amitriptyline and nortriptyline. Acta Psychiatr Scand 57:426–435PubMedGoogle Scholar
  59. 59.
    Lundmark J, Bengtsson F, Nordin C, Reis M, Wålinder J (2000) Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients. Acta Psychiatr Scand 101:354–359PubMedCrossRefGoogle Scholar
  60. 60.
    Magnus R, Preskorn S, Lane R (1996) Minimum effective doses of SSRIs (poster). XXth CINP, Melbourne, Australia, June 23–27, 1996Google Scholar
  61. 61.
    Mbaya P (2002) Safety and efficacy of high dose venlafaxine XL in treatment resistant major depression. Hum Psychopharmacol 17:335–339PubMedGoogle Scholar
  62. 62.
    Mendels J, Johnston R, Mattes J, Riesenberg R (1993) Efficacy and safety of b. i. d. doses of venlafaxine in a dose-response study. Psychopharmacol Bull 29:169–174PubMedGoogle Scholar
  63. 63.
    Mendels J, Reimherr F, Marcus RN Roberts DL, Francis RJ, Anton SF (1995) A double-blind, placebo-controlled trial of two dose ranges of nefazodone in the treatment of depressed outpatients. J Clin Psychiatry 56(Suppl 6):30–36 PubMedGoogle Scholar
  64. 64.
    Mendlewicz J, Linkowski P, Rees JA, et al. (1980) A double-blind comparison of dothiepin and amitriptyline in patients with primary affective disorder: serum levels and clinical response. Br J Psychiatry 136:154–160PubMedGoogle Scholar
  65. 65.
    Montgomery SA, McAuley R, Rani SJ, Montgomery DR, Braithwaite R, Dawling S (1979) Amitriptyline plasma concentration and clinical response (letter). BMJ 1:1711PubMedGoogle Scholar
  66. 66.
    Montgomery SA, Rasmussen JGC, Lyby K, Connor P, Tanghøj P (1992) Dose response relationship of citalopram 20 mg, citalopram 40 mg and placebo in the treatment of moderate and severe depression. Int Clin Psychopharmacol 6(Suppl 5):65–70PubMedGoogle Scholar
  67. 67.
    Montgomery SA, Pedersen V, Tanghoj P, Rasmussen JGC, Rioux P (1994) The optimal dosing regimen for citalopram – a metaanalysis of nine placebo-controlled studies. Int Clin Psychopharmacol 15(Suppl 1):35–40Google Scholar
  68. 68.
    Montgomery SA (1995) Selecting the optimum therapeutic dose of serotonin reuptake inhibitors: studies with citalopram. Int Clin Psychopharmacol 10(Suppl 1):23–27PubMedGoogle Scholar
  69. 69.
    Moyes ICA, Ray RL, Moyes RB (1980) Plasma levels and clinical improvement – a comparative study of clomipramine and amitriptyline in depression. Postgrad Med J 56(Suppl 1):127–129PubMedGoogle Scholar
  70. 70.
    Murphy GE, Simons AD, Wetzel RD (1985) Plasma nortriptyline and clinical response in depression. J Affect Disord 8:123–129 PubMedCrossRefGoogle Scholar
  71. 71.
    Nelson JC, Jatlow P, Quinlan DM, Bowers MB (1982) Desipramine plasma concentration and antidepressant response. Arch Gen Psychiatry 39:1419–1422PubMedGoogle Scholar
  72. 72.
    Nierenberg AA, Amsterdam JD (1990) Treatment-resistant depression: definition and treatment approaches. J Clin Psychiatry 51(Suppl 6):39–47PubMedGoogle Scholar
  73. 73.
    Nodine JH, Siegler PE, Bodi T, Mapp Y, Dykyj R (1965) A variable dose phase 3, human bioassay of nortriptyline. Am J Med Sci 250:443–447PubMedGoogle Scholar
  74. 74.
    Oliveira IR, Do Prado-Lima PAS, Samuel-Lajeunesse B (1989) Monitoring of tricyclic antidepressant plasma levels and clinical response: a review of the literature. I Psychiatry Psychobiol 4:43–60Google Scholar
  75. 75.
    O’Reardon JP, Amsterdam JD (2001) Overview of treatment-resistant depression and its management. In: Amsterdam JD, Hornig M, Nierenberg AA (eds) Treatment-resistant mood disorders. Cambridge, Cambridge University Press, pp 30–45Google Scholar
  76. 76.
    Pearlman C (1987) High dose tranylcypromine in refractory depression (letter). J Clin Psychiatry 48:423–424Google Scholar
  77. 77.
    Perry PJ, Zeilmann C, Arndt S (1994) Tricyclic antidepressant concentrations in plasma: an estimate of their sensitivity and specificity as a predictor of response. J Clin Psychopharmacol 14:230–240PubMedGoogle Scholar
  78. 78.
    Preskorn SH (1983) Antidepressant response and plasma concentrations of bupropion. J Clin Psychiatry 44:137–139PubMedGoogle Scholar
  79. 79.
    Preskorn SH, Dorey RC, Jerkovich GS (1988) Therapeutic drug monitoring of tricyclic antidepressants. Clin Chemistry 34:822–828Google Scholar
  80. 80.
    Preskorn SH, Fleck RJ, Schroeder DH (1990) Therapeutic drug monitoring of bupropion (letter to the editor). Am J Psychiatry 147:1690–1691PubMedGoogle Scholar
  81. 81.
    Preskorn SH (1991) Should bupropion dosage be adjusted based upon therapeutic drug monitoring? Psychopharmacol Bull 27:637–643PubMedGoogle Scholar
  82. 82.
    Preskorn SH, Janicak, PG, Davis JM, Ayd FJ (1995) Advances in the pharmacotherapy of depressive disorders. In: Janicak PG, Davis JM, Preskorn SH, Ayd FJ (eds) Principles and Practice of Psychopharmacotherapy, Vol. 1, No. 2, Baltimore, Williams and Wilkin, p 4Google Scholar
  83. 83.
    Preskorn SH (1997) Clinical pharmacology of selective serotonin reuptake inhibitors. Caddo, Oklahoma, Professional CommunicationsGoogle Scholar
  84. 84.
    Quitkin FM (1985) The importance of dosage in prescribing antidepressants. Br J Psychiatry 147:593–597PubMedCrossRefGoogle Scholar
  85. 85.
    Radat F, Berlin I, Spreux-Varoquaux O, Elatki S, Ferreri M, Puech AJ (1996) Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression: a randomized double blind study. Psychopharmacol 127:370–376Google Scholar
  86. 86.
    Ravaris CL, Nies A, Robinson DS, Ives JO, Lamborn KR, Korson L (1976) A multiple-dose, controlled study of phenelzine in depression- anxiety states. Arch Gen Psychiatry 33:347–350PubMedGoogle Scholar
  87. 87.
    Reimherr FW, Byerley WF, Ward MF, Lebegue BJ, Wender PH (1988) Sertraline, a selective inhibitor of serotonin uptake, for the treatment of outpatients with major depressive disorder. Psychopharmacol Bull 24:200–205PubMedGoogle Scholar
  88. 88.
    Reisby N, Gram LF, Bech P, Nagy A, Petersen GO, Ortmann J, Ibsen I, Dencker SJ, Jacobsen O, Krautwald O, Sondergaard I, Christiansen J (1977) Imipramine: clincal effects and pharmacokinetic variability. Psychopharmacol (Berl) 54:263–272Google Scholar
  89. 89.
    Risch S, Huey L, Janowsky D (1979) Plasma levels of tricyclic antidepressants and clinical efficacy: review of the literature – part II. J Clin Psychiatry 40:58–69PubMedGoogle Scholar
  90. 90.
    Robinson DS (1983) High-dose monoamine oxidase inhibitor therapy (letter). JAMA 250:2212Google Scholar
  91. 91.
    Robinson DS, Cooper TB, Ravaris CL, et al. (1979) Plasma tricyclic drug levels in amitriptyline-treated depressed patients. Psychopharmacol 63:223–231Google Scholar
  92. 92.
    Roose SP, Glassman AH, Walsh BT, Woodring S (1986) Tricyclic nonresponders: phenomenology and treatment. Am J Psychiatry 143:345–348PubMedGoogle Scholar
  93. 93.
    Rudolph RL, Fabre LF, Feighner JP, Rickels K, Entsuah R, Derivan AT (1998) A randomized, placebo-controlled dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry 59:116–122 PubMedGoogle Scholar
  94. 94.
    Rush AJ, Fava M, Wisniewski SR, Lavori PW, Trivedi MH, Sackeim HA, Thase ME, Nierenberg AA, Quitkin FM, Kashner TM, Kupfer DJ, Rosenbaum JF, Alpert J, Stewart JW, McGrath PJ, Biggs MM, Shores-Wilson K, Lebowitz BD, Ritz L, Niederehe G; STAR*D Investigators Group (2004) Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. Control Clin Trials 25:119–142PubMedGoogle Scholar
  95. 95.
    Schatzberg AF (1991) Dosing strategies for antidepressant agents. J Clin Psychiatry 52(Suppl 5):14–20PubMedGoogle Scholar
  96. 96.
    Schmauß M (1996) High-dose tranylcypromine in refractory depression (in German). Nervenarzt 67:390–393Google Scholar
  97. 97.
    Schweizer E, Rickels K, Amsterdam JD, Fox I, Puzzuoli G, Weise C (1990) What constitutes an adequate antidepressant trial for fluoxetine? J Clin Psychiatry 51:8–11PubMedGoogle Scholar
  98. 98.
    Schweizer E, Weise C, Clary C, Fox I, Rickels K (1991) Placebocontrolled trial of venlafaxine for the treatment of major depression. J Clin Psychopharmacol 11:233–236PubMedGoogle Scholar
  99. 99.
    Schweizer E, Rynn M, Mandos LA, Demartinis N, Garcia-Espana F, Rickels K (2001) The antidepressant effect of sertraline is not enhanced by dose titration: results from an outpatient clinical trial. Int Clin Psychopharmacol 16:137–143Google Scholar
  100. 100.
    Shrivastava R, Patrick R, Scherer N, Upton GV (1994) A doseresponse study of venlafaxine (abstract). Neuropsychopharmacol 10(Suppl):221Google Scholar
  101. 101.
    Simpson GM, Lee JH, Cuculic Z, Kellner R (1976) Two dosages of imipramine in hospitalized endogenous and neurotic depressives. Arch Gen Psychiatry 33:1093–1102PubMedGoogle Scholar
  102. 102.
    Simpson GM, White KL, Boyd JL, Cooper TB, Halaris A, Wison IC, Raman EJ, Rüther E (1982) Relationship between plasma antidepressant levels and clinical outcome for inpatients receiving imipramine. Am J Psychiatry 139:358–360PubMedGoogle Scholar
  103. 103.
    Tasker TC, Kaye CM, Zussman BD, Link CG (1989) Paroxetine plasma levels: lack of correlation with efficacy or adverse events. Acta Psychiatr Scand 350(Suppl):152–155Google Scholar
  104. 104.
    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 Psychiatry 142: 155–162Google Scholar
  105. 105.
    Thase ME, Rush AJ (1995) Treatment resistant depression. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: Fourth Generation of Progress. Raven Press, New York, pp 1081–1097Google Scholar
  106. 106.
    Thomson C, Lane R (1994) Sertraline 50 mg: optimal daily dose in depression (abstract). Neuropsychopharmacol 10(Suppl 3): 222Google Scholar
  107. 107.
    Trivedi MH, Rush AJ, Crismon ML, Kashner TM, Toprac MG, Carmody TJ, Key T, Biggs MM, Shores-Wilson K, Witte B, Suppes T, Miller AL, Altshuler KZ, Shon SP (2004) Clinical Results for Patients with Major Depressive Disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry 61:669–680PubMedGoogle Scholar
  108. 108.
    Tyrer P, Gardner M, Lambourn J, Whitford M (1980) Clinical and pharmacokinetic factors affecting response to phenelzine. Br J Psychiatry 136:359–366PubMedGoogle Scholar
  109. 109.
    Ulrich S, Läuter J (2002) Comprehensive survey of the relationship between serum concentration and therapeutic effect of amitriptyline in depression. Clin Pharmacokinet 41:853–876PubMedGoogle Scholar
  110. 110.
    Ulrich S, Northoff G, Wurthmann C, Partscht G, Pester U, Herscu H, Meyer FP (2001) Serum levels of amitriptyline and therapeutic effect in non-delusional moderately to severely depressed in-patients: a therapeutic window relationship. Pharmacopsychiatry 34:33–40PubMedCrossRefGoogle Scholar
  111. 111.
    Vandel S, Vandel B, Sandoz M, et al. (1978) Clinical response and plasma concentration of amitriptyline and its metabolite nortriptyline. Eur J Clin Pharmacol 14:185–190PubMedCrossRefGoogle Scholar
  112. 112.
    Walczak DD, Apter JT, Halikas JA, Borison RL, Carman JS, Post GL, Patrick R, Cohn JB, Cunningham LA, Rittberg B, Preskorn SH, Kang JS, Wilcox CS (1996) The oral dose-effect relationship for fluvoxamine: a fixed-dose comparison against placebo in depressed outpatients. Ann Clin Psychiatry 8:139–151PubMedCrossRefGoogle Scholar
  113. 113.
    Watt DC, Crammer JL, Elkes A (1972) Metabolism, anticholinergic effects, and therapeutic outcome of desmethylimipramine in depressive illness. Psychol Med 2:397–405PubMedCrossRefGoogle Scholar
  114. 114.
    Wernicke JF, Dunlop SR, Dornseif BE, Zerbe RL (1987) Fixeddose fluoxetine therapy for depression. Psychopharmacol Bull 23:164–168PubMedGoogle Scholar
  115. 115.
    Wernicke JF, Dunlop SR, Dornseif BE, Bosomworth JC, Humbert M (1988) Low-dose fluoxetine therapy for depression. Psychopharmacol Bull 24:183–188PubMedGoogle Scholar
  116. 116.
    Wilson IC, Vernon JT, Guin T, Sandifer MG (1962) A controlled study of treatments of depression. J Neuropsychiatry 4:331–332Google Scholar
  117. 117.
    Woggon B, Angst J, Gmuer M, Hess K, Hurwitz E, Martens H, Rothweiler R, Steiner A (1976) Clinical double-blind study with two different dosages of maprotiline (German). Arch Psychiat Nervenkr 222:13–25PubMedCrossRefGoogle Scholar
  118. 118.
    World Health Organization Collaborative Study (1986) Dose effects of antidepressant medication in different population. J Affect Disord (Suppl 2):1–40Google Scholar
  119. 119.
    Ziegler VE, Clayton PJ, Taylor JR, Co BT, Biggs JT (1976a) Nortriptyline plasma levels and therapeutic response. Clin Pharmacol Ther 20:458–463Google Scholar
  120. 120.
    Ziegler VE, Co BT, Taylor JR, Clayton PJ, Biggs JT (1976b) Amitriptyline plasma levels and therapeutic response. Clin Pharmacol Ther 19:795–801Google Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • M. Adli
    • 1
  • Ch. Baethge
    • 2
  • A. Heinz
    • 1
  • N. Langlitz
    • 1
  • M. Bauer
    • 1
  1. 1.Department of Psychiatry and PsychotherapyCharité—Universitätsmedizin Berlin, Campus Charité MitteBerlinGermany
  2. 2.Mailman Research CenterMcLean Hospital, Harvard Medical SchoolBelmont (MA)USA

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