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Fortschr Neurol Psychiatr 2009; 77(6): 316-325
DOI: 10.1055/s-0028-1109338
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Kombination von Antidepressiva – eine sinnvolle Behandlungsstrategie bei therapieresistenten Depressionen?

Combining Antidepressants: a Useful Strategy for Therapy Resistant Depression?M. Schmauß1 , T. Messer1
  • 1Bezirkskrankenhaus Augsburg
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Publication History

Publication Date:
04 May 2009 (online)

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Zusammenfassung

Die folgende Arbeit fasst Nutzen und Risiken der bisher bekannten Kombinationsbehandlungen mit Antidepressiva bei therapieresistenten Depressionen zusammen. Die Literaturrecherche erfolgte mittels einer Medline-Datenbank-Recherche der Jahrgänge 1990 – 2006. Kombinationstherapien zweier Antidepressiva werden im klinischen Alltag sehr häufig durchgeführt. Sinnvolle Antidepressivakombinationen nutzen den Vorteil komplementärer Wirkmechanismen, um einen synergistischen Nutzen zu erzielen. Vorteile einer Kombinationstherapie bestehen in der Fortführung einer partiellen Response auf eine Monotherapie und dem gleichzeitig damit verbundenen Vermeiden der Gefahr einer Verschlechterung depressiver Symptome durch Absetzen des partiell wirksamen Antidepressivums. Nachteile dieser Strategie bestehen in dem Risiko von Arzneimittelwechselwirkungen, einer möglichen Potenzierung von unerwünschten Arzneimittelwirkungen und höheren Behandlungskosten. Obwohl Kombinationsstrategien in der klinischen Praxis oft angewandt werden, gibt es nur wenig kontrollierte Studien, um ihren Nutzen und ihre Wirksamkeit zu belegen (Evidenzlevel C, dies trifft auf alle Kombinationstherapien zu). Wichtig erscheint darauf hinzuweisen, dass die Zugabe eines SSRI zu einem Trizyklikum einen erhöhten Blutspiegel und eine verzögerte Metabolisierung des Trizyklikums herbeiführen kann, was eventuell ein erhöhtes Toxizitätsrisiko der trizyklischen Medikation nach sich führt. Die Kombination eines irreversiblen MAO-Hemmers mit Clomipramin, einem SSRI oder einem SSNRI sollte aufgrund eines möglichen Serotonin-Syndroms grundsätzlich vermieden werden.

Die detaillierte Kenntnis der dargestellten Kombinationsstrategien ermöglicht unter Umständen bessere Behandlungsergebnisse bei therapieresistenten Depressionen.

Abstract

Various pharmacological strategies have been developed to treat such refractory depression, of which combination therapies with antidepressants are one of the most important. This article reviews both benefits and risks of all known antidepressant combination strategies. The relevant literature was identified by means of a computerized MEDLINE research on the years 1990 – 2006 and scanning of review articles. The use of antidepressant combinations to overcome refractory depression is a common strategy in practice. Many antidepressants can be usefully combined especially if they engage separate mechanisms of action – like SSRIs with Reboxetine, Bupropion, Mirtazapine and Tricyclics – or on the other hand – Tricyclics with MAO-Inhibitiors. Combination strategies are effective treatment options, however they do have potential safety risks due to pharmacokinetic and pharmacodynamic interactions. Combinations including MAOIs can cause serotonin syndrome, and some SSRIs like Fluoxetine may elevate tricyclic plasma levels with the consequence of an increased risk of toxicity. The distinct knowledge of available antidepressant combination strategies may help to increase response – as well as remission rates in therapy resistant depression. However, further research is urgently needed to determine relative efficacy.

Schlüsselwörter

Antidepressiva - therapieresistente Depression - Kombinationen von Antidepressiva - Antidepressivanonresponse

Key words

antidepressants - therapy resistant depression - refractory depression - combination therapies with antidepressants

Literatur

  • 1 Amsterdam J D, Hornig-Rohan M. Treatment algorithms in treatment-resistant depression.  Psychiatr Clin North Am. 1996;  19 371-386
    Google Scholar
  • 2 Dunner D L, Rush A J, Russell J M. et al . Prospective long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression.  J Clin Psychiatry. 2006;  67 688-695
    Google Scholar
  • 3 Fawcett J. Progress in treatment-resistant and treatment-refractory depression: we still have a long way to go.  J Clin Psychiatry. 1994;  24 214-216
    Google Scholar
  • 4 Nelson J C. Managing treatment-resistant major depression.  J Clin Psychiatry. 2003;  64 5-12
    Google Scholar
  • 5 Nierenberg A A, Amsterdam J D. Treatment-resistant depression: definition and treatment approaches.  J Clin Psychiatry. 1990;  51 (Suppl 6) 39-47
    Google Scholar
  • 6 Souery D, Amsterdam J, Montigny de C. et al . Treatment resistant depression: methodological overview and operational criteria.  Eur Neuropsychopharmacol. 1999;  9 83-91
    Google Scholar
  • 7 Thase M E, Rush A J. When at first you don’t succeed: sequential strategies for antidepressant nonresponders.  J Clin Psychiatry. 1997;  58 (Suppl 13) 23-29
    Google Scholar
  • 8 Burrows G D, Norman T R. Treatment-resistant unipolar depression. Lader M, Naber D Difficult Clinical Problems in Psychiatry London; Martin Dunitz Ltd 1999: 57-75
    Google Scholar
  • 9 Guscott R, Grof P. The clinical meaning of refractory depression: a review for the clinician.  Am J Psychiatry. 1991;  148 695-704
    Google Scholar
  • 10 Rush A J. Aktueller Stand und Perspektiven der Forschung. Bauer M, Berghöfer A, Adli M Akute und therapieresistente Depressionen Heidelberg; Springer 2005: 3-19
    Google Scholar
  • 11 Schmauß M, Meller I. Die „therapieresistente” Depression – Ursachen und Behandlungsmöglichkeiten.  Psychiatr Prax. 1989;  16 101-108
    Google Scholar
  • 12 Helmchen H. Gestuftes Vorgehen bei Resistenz gegen Antidepressiva-Therapie. Möller HJ Therapieresistenz unter Antidepressiva-Behandlung Heidelberg; Springer 1990: 237-250
    Google Scholar
  • 13 Möller H J. Therapieresistenz auf Antidepressiva: Risikofaktoren und Behandlungsmöglichkeiten.  Nervenarzt. 1991;  62 658-669
    Google Scholar
  • 14 Möller H J. Non-response to antidepressants: risk factors and therapeutic possibilities.  In Clin Psychopharmacol. 1994;  9 (Suppl 2) 17-23
    Google Scholar
  • 15 Möller H J. Therapieresistenz auf Antidepressiva.  Nervenarzt. 2004a;  75 499-517
    Google Scholar
  • 16 Möller H J. Medikamentöse Therapiestrategien bei therapieresistenter unipolarer Depression.  Psychopharmakotherapie. 2004b;  11 34-41
    Google Scholar
  • 17 Sackheim H A. The definition and meaning of treatment-resistant depression.  J Clin Psychiatry. 2001;  62 (Suppl 16) 10-17
    Google Scholar
  • 18 Möller H J. Therapieresistenz unipolarer depressiver Erkrankungen: Häufigkeit, Prädiktoren, Risikofaktoren. Berghöfer A, Adli M Akute und therapieresistente Depressionen Heidelberg; Springer 2005: 21-37
    Google Scholar
  • 19 Fava M, Davidson K G. Definition and epidemiology of treatment-resistant depression.  Psychiatr Clin North Am. 1996;  19 179-200
    Google Scholar
  • 20 Fava M. Augmentation and combination strategies in treatment-resistant depression.  J Clin Psychiatry. 2001;  62 (Suppl 18) 4-11
    Google Scholar
  • 21 Fredman S J, Fava M, Kienke A S. et al . Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current ”next-step” practices.  J Clin Psychiatry. 2000;  61 403-408
    Google Scholar
  • 22 McIntyre R S, Muller A, Mancini D A. et al . What to do if an initial antidepresant fails?.  Can Fam Physician. 2003;  49 449-457
    Google Scholar
  • 23 Nelson J C. Augmentation strategies with serotonin-noradrenergic combinations.  J Clin Psychiatry. 1998a;  59 65-68
    Google Scholar
  • 24 Nelson J C. Treatment of antidepressant nonresponders: augmentation or switch?.  J Clin Psychiatry. 1998b;  59 (Suppl 15) 35-41
    Google Scholar
  • 25 Nelson J C. Augmentation strategies in depression 2000.  J Clin Psychiatry. 2000;  61 (Suppl 2) 13-19
    Google Scholar
  • 26 Nemeroff C B. Augmentation strategies in patients with refractory depression.  Depress Anxiety. 1996;  4 169-181
    Google Scholar
  • 27 Nierenberg A A, White K. What next? A review of pharmacologic strategies for treatment resistant depression, Psychopharmacol.  Bull. 1990;  26 429-460
    Google Scholar
  • 28 Nolen W A, Haffmans J. Treatment of resistant depression. Review on the efficacy of various biological treatments, specifically in major depression resistant to cyclic antidepressants.  Intern Clin Psychopharmacol. 1989;  4 217-228
    Google Scholar
  • 29 Pasternak M, Zimmerman M. Switching versus augmentation: a prospective, naturalistic comparison in depressed treatment resistant patients.  J Clin Psychiatry. 2001;  62 135-142
    Google Scholar
  • 30 Trivedi M H, Kleiber B A. Algorithm for the treatment of chronic depression.  J Clin Psychiatry. 2001a;  62 (Suppl 6) 22-29
    Google Scholar
  • 31 Trivedi M H, Kleiber B A. Using treatment algorithms for the effective management of treatment-resistant depression.  J Clin Psychiatry. 2001b;  62 (Suppl 18) 25-29
    Google Scholar
  • 32 Trivedi M H. Treatment-resistant depression: new therapies on the horizon.  Ann Clin Psychiatry. 2003;  15 59-70
    Google Scholar
  • 33 Fava M, Rush A J. Current status of augmentation and combination treatments for major depressive disorder: a literature review and a proposal for a novel approach to improve practice.  Psychother Psychosom. 2006;  3 139-153
    Google Scholar
  • 34 DeBattista C. Augmentation and combination strategies for depression.  J Psychopharmacol. 2006;  20 11-18
    Google Scholar
  • 35 Schmauß M. Kombinationstherapie nicht-selektiver Monoamin-Rückaufnahme-Inhibitoren mit MAO-Hemmern. Riederer P, Laux G, Pöldinger W Neuro-Psychopharmaka, Bd 3: Antidepressiva Phasenprophylaktika und Stimmungsstabilisierer Wien; Springer 2002: 551-557
    Google Scholar
  • 36 Dodd S, Horgan D, Malhi G S. et al . To combine or not to combine? A literature review of antidepressant combination therapy.  J Affect Disord. 2005;  89 1-11
    Google Scholar
  • 37 Tanum L H. Combination treatment with antidepressant in refractory depression.  Int Clin Psychopharmacoly. 1994;  9 37-40
    Google Scholar
  • 38 De la Gandara J, Aguera L, Rojo J E. et al . Use of antidepressant combinations: which, when and why? Results of a Spanish survey.  Acta Psychiatr Scand. 2005;  112 (Suppl. 428) 32-36
    Google Scholar
  • 39 Frye M A, Ketter T A, Leverich G S. et al . The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study.  J Clin Psychiatry. 2000;  61 9-15
    Google Scholar
  • 40 Schmauß M, Messer T. Augmentationsstrategien bei Therapieresistenz auf Antidepressiva.  Psychiat Prax. 2007;  34 165-174
    Google Scholar
  • 41 Murphy D L, Sunderland T, Cohen R M. Monoamine oxidase-inhibiting antidepressants – a clinical update.  Psychiatr Clin North Am. 1984;  7 549-562
    Google Scholar
  • 42 Schuckit M, Robins E, Feighner J. Tricyclic antidepressants and monoamine oxidase inhibitors.  Arch Gen Psychiatry. 1971;  24 509-514
    Google Scholar
  • 43 Cohen S N, Armstrong M F. Drug interactions: a handbook for clinical use. Baltimore; Williams & Wilkins 1974
    Google Scholar
  • 44 Sjöqvist F. Psychotropic drugs II: interaction between monoamine oxidase (MAO) inhibitors and other substances.  Proc R Soc Med. 1965;  58 967-978
    Google Scholar
  • 45 Ananth J, Luchins D A. A review of combined tricyclic and MAOI therapy.  Compr Psychiatry. 1977;  18 121-134
    Google Scholar
  • 46 Ponto L B, Perry P J, Liskow B I. et al . Drug therapy reviews: tricyclic antidepressant and monoamine oxidase inhibitor combination therapy.  Am J Hosp Pharm. 1977;  34 955-961
    Google Scholar
  • 47 White K, Simpson G. Combined MAOI-tricyclic antidepressant treatment. A reevaluation.  J Clin Psychopharmacol. 1981;  1 264-282
    Google Scholar
  • 48 White K, Simpson G. The combined use of MAOIs and tricyclics.  J Clin Psychiatry. 1984;  45 67-69
    Google Scholar
  • 49 Marks J. Interaction involving drugs used in psychiatry. Marks J, Pare CMB The scientific basis of drug therapy in psychiatry Oxford; Pergamon 1965: 191-201
    Google Scholar
  • 50 Davidson J. Adding a tricyclic antidepressant to a monoamine oxidase inhibitor.  J Clin Psychopharmacol. 1982;  3 216
    Google Scholar
  • 51 Lam R W, Wan D D, Cohen N L. et al . Combining antidepressants for treatment-resistant depression. A review.  J Clin Psychiatry. 2002;  63 685-693
    Google Scholar
  • 52 Berlanga C, Ortega-Soto H A. A 3-year follow-up of a group of treatment-resistant depressed patients with a MAOI/tricyclic combination.  J Affect Disord. 1995;  34 187-192
    Google Scholar
  • 53 Feighner J P, Herbstein J, Damlouji N. Combination MAOI, TCA, and direct stimulant therapy of treatment-resistant depression.  J Clin Psychiatry. 1985;  46 206-209
    Google Scholar
  • 54 Schmauß M, Kapfhammer H P, Meyr P. et al . Combined MAO-inhibitor and tri(tetra)cyclic antidepressant treatment in therapy resistant depression.  Prog Neuro Psychopharmacol Biol Psychiatry. 1988;  12 523-532
    Google Scholar
  • 55 Davidson J, Mc L eod MN, Law-Yone B. et al . A comparison of electroconvulsive therapy and combined phenelzine amitriptyline in refractory depression.  Arch Gen Psychiatry. 1978;  35 639-642
    Google Scholar
  • 56 Young J PR, Lader M H, Hughes W C. Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients.  Br Med J. 1979;  2 1315-1317
    Google Scholar
  • 57 Razzani J, White K, White J. et al . The safety and efficacy of combined amitriptyline and tranylcypromine antidepressant treatment.  Arch Gen Psychiatry. 1983;  40 657-661
    Google Scholar
  • 58 White K, Pistole T A, Boyd J. Combined monoamine oxidase inhibitor tricyclic antidepressant treatment. A pilot study.  Am J Psychiatry. 1980;  137 1422-1425
    Google Scholar
  • 59 O’Brien S, McKeon P, O’Regan M. The efficacy and tolerability of combined antidepressant treatment in different depressive subgroups.  Br J Psychiatry. 1993;  163 363-368
    Google Scholar
  • 60 Pande A C, Calarco M M, Grunhaus L J. Combined MAOI-TCA treatment in refractory depression. Amsterdam JD Advances in neuropsychiatry and psychopharmacology, vol 2: refractory depression New York; Raven Press 1991: 115-121
    Google Scholar
  • 61 Goldberg R S, Thornton W E. Combined tricyclic-MAOI therapy for refractory depression: a review, with guidelines for appropriate usage.  J Clin Pharmacol. 1978;  18 143-147
    Google Scholar
  • 62 Spiker D G, Pugh D D. Combining tricyclic and monoamine oxidase inhibitor antidepressants.  Arch Gen Psychiatry. 1976;  33 828-830
    Google Scholar
  • 63 Oefele v K, Grohmann R, Hippius H. et al . Unerwünschte Arzneimittelwirkungen bei der Kombinationsbehandlung mit trizyklischen Antidepressiva und Monoaminoxidase-Hemmern.  Nervenarzt. 1988;  59 118-123
    Google Scholar
  • 64 Beaumont G. Drug interactions with clomipramine (Anafranil).  J Int Med Res. 1973;  1 480-484
    Google Scholar
  • 65 Marley E, Wozniak K M. Clinical and experimental aspects of interactions between amine oxidase inhibitors and amine reuptake inhibitors.  Psychol Med. 1983;  13 735-749
    Google Scholar
  • 66 Amsterdam J D, Berwish N. Treatment of refractory depression with combination reserpine and tricyclic antidepressant therapy.  J Clin Psychopharmacology. 1992;  7 238-242
    Google Scholar
  • 67 Hüttemann K, Nowe T, Köhrmann M. et al . Maligne Hyperthermie und deren Differentialdiagnosen.  Fortschr Neurol Psychiat. 2009;  77 (im Druck)
    Google Scholar
  • 68 Sternbach H. Danger of MAOI therapy after fluoxetine withdrawal.  Lancet. 1988;  II 850-851
    Google Scholar
  • 69 Feighner J P, Boyer W F, Tyler D L. et al . Adverse consequences of fluoxetine-MAOI combination therapy, J.  Clin Psychiatry. 1990;  51 222-225
    Google Scholar
  • 70 Beasley C M, Masica D N, Heiligenstein J H. et al . Possible monoamine oxidase inhibitor serotonin uptake inhibitor interaction: Fluoxetine clinical data and preclinical findings.  J Clin Psychopharmacol. 1993;  13 312-320
    Google Scholar
  • 71 Hodgman M J, Martin T G, Krenzelok E P. Serotonin syndrome due to venlafaxine and maintenance tranylcypromine therapy.  Human and Exp Toxicology. 1997;  16 14-17
    Google Scholar
  • 72 Boyer E W, Shannon Jr M. The serotonin syndrome.  N Engl J Med. 2005;  352 1112-1120
    Google Scholar
  • 73 Steinberg R, Jost C, Weess H G. et al . Combination of tricyclic antidepressants with moclobemide or tranylcypromine – outcome data in therapy resistant MD.  Neuropsychopharmacology. 1994;  10 (Suppl) 62
    Google Scholar
  • 74 Koenig F, Wolfersdorf M. Combination therapy using moclobemide with tricyclic and tetracyclic antidepressants to treat therapy-resistant depression.  Pharmacopsychiatry. 1997;  30 93-96
    Google Scholar
  • 75 Koenig F, Wolfersdorf M, Loble M. et al . Trimipramine and maprotiline plasma levels during combined treatment with moclobemide in therapy-resistant depression.  Pharmacopsychiatry. 1997;  30 125-127
    Google Scholar
  • 76 Bakish D, Hooper C L, West D L. et al . Moclobemide and specific serotonin re-uptake inhibitor combination treatment of resistant anxiety and depressive disorders.  Hum Psychopharmacol. 1995;  10 105-109
    Google Scholar
  • 77 Joffe R T, Bakish D. Combined SSRI-moclobemide treatment of psychiatric illness.  J Clin Psychiatry. 1994;  55 24-25
    Google Scholar
  • 78 Ebert D, Albert R, May A. et al . Combined SSRI-RIMA treatment in refractory depression. Safety data and efficacy.  Psychopharmacology. 1995;  119 342-344
    Google Scholar
  • 79 Neuvonen P, Pohjola-Sintonen S, Tacke U. et al . Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses.  Lancet. 1993;  342 1419
    Google Scholar
  • 80 Hawley C J, Quick S J, Ratnam S. Safety and tolerability of combined treatment with moclobemide and SSRI: a systematic study of 50 patients.  Int Clin Psychopharmacol. 1996;  11 187-191
    Google Scholar
  • 81 Lejoyeux M, Adès J, Rouillon F. Serotonin syndrome. Incidence, symptoms and treatment.  CNS Drugs. 1994;  2 132-143
    Google Scholar
  • 82 Dams R, Benijts T H, Lambert W E. et al . A fatal case of serotonin syndrome after combined moclobemide-citalopram intoxication.  J Anal Toxicol. 2001;  25 147-151
    Google Scholar
  • 83 Volz H P, Gleiter C H, Möller H J. Monoaminoxidasehemmer in der Psychiatrie.  Nervenarzt. 1996;  67 339-347
    Google Scholar
  • 84 Bonnet U. Moclobemide: therapeutic use and clinical studies.  CNS Drug Rev. 2003;  9 97-140
    Google Scholar
  • 85 Weilburg J B, Rosenbaum J F, Biederman J. et al . Fluoxetine added to non-MAOI antidepressants converts nonresponders to responders: a preliminary report.  J Clin Psychiatry. 1989;  50 447-449
    Google Scholar
  • 86 Vaughan D A. Interaction of fluoxetin with tricyclic antidepressants (letter).  Am J Psychiatry. 1988;  145 1478
    Google Scholar
  • 87 Weilburg J B, Rosenbaum J F, Biedermann J. et al . Tricyclic augmentation of fluoxetine.  Ann Clin Psychiatry. 1991;  3 209-213
    Google Scholar
  • 88 Rosenthal J S, Kaswan M J, Hemlock C. et al .Fluoxetine enhancement of heterocyclic antidepressants. Amsterdam JD Advances in neuropsychiatry and psychopharmacology, vol 2: refractory depression New York; Raven Press 1991: 105-108
    Google Scholar
  • 89 Levitt A J, Joffe R T, Kamil R. et al . Do depressed subjects who have failed both fluoxetine and a tricyclic antidepressant respond to the combination?.  J Clin Psychiatry. 1999;  60 613-616
    Google Scholar
  • 90 Rothschild B S. Fluoxetine-nortriptyline therapy of treatment resistant major depression in a geriatric patient.  J Geriatric Psych Neurol. 1994;  7 137-138
    Google Scholar
  • 91 Seth R, Jennings A L, Bindman J. et al . Combination treatment with noradrenalin and serotonin reuptake inhibitors in resistant depression.  Br J Psychiatry. 1992;  161 562-565
    Google Scholar
  • 92 Zajecka J M, Jeffriess H, Fawcett J. The efficacy of fluoxetine combined with a heterocyclic antidepressant in treatment-resistant depression: a retrospective analysis.  J Clin Psychiatry. 1995;  56 338-343
    Google Scholar
  • 93 Baron B M, Ogden A, Seigel B W. et al . Rapid down regulation of β-adrenoreceptors by co-administration of desipramine and fluoxetine.  Eur J Pharmacol. 1988;  154 125-134
    Google Scholar
  • 94 Nelson J C, Mazure C M, Bowers M BJ. et al . A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression.  Arch Gen Psychiatry. 1991;  48 303-307
    Google Scholar
  • 95 Fava M, Rosenbaum J F, Mc Grath P J. et al . Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: A double blind controlled study.  Am J Psychiatry. 1994;  151 1372-1374
    Google Scholar
  • 96 Fava M, Alpert J, Nierenberg A A. et al . Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine.  J Clin Psychoharmacol. 2002;  22 379-387
    Google Scholar
  • 97 Perlis R H, Iosifescu D V, Alpert J. et al . Effect of medical comorbidity on response to fluoxetine augmentation or dose increase in outpatients with treatment-resistant depression.  Psychosomatics. 2004;  45 224-229
    Google Scholar
  • 98 Nelson J C, Mazure C M, Jatlow P I. et al . Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study.  Biol Psychiatry. 2004;  55 296-300
    Google Scholar
  • 99 Blecourt C V de, Gudde H. Surplus value of combining antidepressants in refractory depression. Second International Conference on Refractory Depression. Abstract Amsterdam; 24.–26. Juni 1992
    Google Scholar
  • 100 Lauritzen L, Clemmensen L, Klysner R. et al . Combined treatment with imipramine and mianserine. A controlled pilot study.  Pharmacopsychiatry. 1992;  25 182-186
    Google Scholar
  • 101 Klysner R, Geisler A. Rapid downregulation of cerebral β-adrenoreceptors by combined treatment with imipramine and mianserin. Amsterdam JD Advances in neuropsychiatry and psychopharmacology, vol 2: refractory depression New York; Raven Press 1991: 109-113
    Google Scholar
  • 102 Nierenberg A A, Cole J O, Glass L. Possible trazodone potentation of fluoxetine: a case series.  J Clin Psychiatry. 1992;  53 83-85
    Google Scholar
  • 103 Maes M, Vandoolaeghe E, Desnyder R. Efficacy of treatment with trazodone in combination with pindolol or fluoxetine in major depression.  J Affect Disord. 1996;  41 201-210
    Google Scholar
  • 104 Clark N A, Alexander B. Increased rate of trazodone prescribing with bupropion and selective serotonin-reuptake inhibitors versus tricyclic antidepressants.  Ann Pharmacother. 2000;  34 1007-1012
    Google Scholar
  • 105 Dam J, Ryde L, Svejso J. et al . Morning fluoxetine plus evening mianserin versus morning fluoxetine plus evening placebo in the acute treatment of major depression.  Pharmacopsychiatry. 1998;  31 48-54
    Google Scholar
  • 106 Ferreri M, Lavergne F, Berlin I. et al . Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone.  Acta Psychiatr Scand. 2001;  103 66-72
    Google Scholar
  • 107 Maes M, Libbrecht I, Hunsel van F. et al . Pindolol and mianserin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance.  J Clin Psychopharmacol. 1999;  19 177-182
    Google Scholar
  • 108 Licht R W, Qvitzau S. 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. 2002;  161 143-151
    Google Scholar
  • 109 Harkin A, Kelly J P, McNamara M. et al . Activity and onset of action of reboxetine and effect of combination with sertraline in an animal model of depression.  Eur J Pharmacol. 1999;  364 123-132
    Google Scholar
  • 110 Hawley C J, Sivakumaran T, Ochocki M. et al .Coadministration therapy with reboxetine and serotonin specific reuptake inhibitors in twenty-four patients with major depression (abstract). 23rd Congress of the Collegium Internationale Neuro-Psychopharmacologicum (CINP) Brussels; 2000
    Google Scholar
  • 111 Devarajan S, Dursun S M. Citalopram plus reboxetine in treatment-resistant depression.  Can J Psychiatry. 2000;  45 489-490
    Google Scholar
  • 112 Dursun S M, Devarajan S. Reboxetine plus citalopram for refractory depression not responding to venlafaxine: possible mechanisms.  Psychopharmacology. 2001;  153 497-498
    Google Scholar
  • 113 Lucca A, Serretti A, Smeraldi E. Effect of reboxetine augmentation in SSRI resistant patients.  Hum Psychopharmacol. 2000;  15 143-145
    Google Scholar
  • 114 Rubio G, San L, Lopez-Munoz F. et al . Reboxetine adjunct for partial or nonresponders to antidepressant treatment.  J Affect Disord. 2004;  81 67-72
    Google Scholar
  • 115 Carpenter L L, Jocic Z, Hall J M. et al . Mirtazapine augmentation in the treatment of refractory depression.  J Clin Psychiatry. 1999;  60 45-49
    Google Scholar
  • 116 Carpenter L L, Yasmin S, Price L H. A double-blind, placebo-controlled study of antidepresant augmentation with mirtazapine.  Biol Psychiatry. 2002;  51 183-188
    Google Scholar
  • 117 Debonnel G, Gobbi G, Turcotte J. et al .The alpha-2 antagonist mirtazapine combined with the SSRI paroxetine induces a greater antidepressant response: a double-blind controlled study. Presented at the 39th Annual Meeting of the American College of Neuropsychopharmacology, Dec 10 – 14,. San Juan, Puerto Rico; 2000
    Google Scholar
  • 118 Farah A. Relief of SSRI-induced sexual dysfunction with mirtazapine treatment (letter).  J Clin Psychiatry. 1999;  60 260-261
    Google Scholar
  • 119 McGrath P J, Stewart J W, Fava M. et al . Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a star*D report.  Am J Psychiatry. 2006;  163 1531-1541
    Google Scholar
  • 120 Boyer W F, Feighner J P. The combined use of fluoxetine and bupropion (abstract). 146th Annual Meeting of the American Psychiatric Association. San Francisco; 1993
    Google Scholar
  • 121 Brodkin J A, Lasser R A, Wines J DJ. et al . Combining serotonin reuptake inhibitors and bupropion in partial responders to antidepressant monotherapy.  J Clin Psychiatry. 1997;  58 137-145
    Google Scholar
  • 122 Lam R W, Hossie H, Solomons K. et al . Citalopram and bupropion SR: combining versus switching in patients with treatment-resistant depression.  J Clin Psychaitry. 2004;  65 337-340
    Google Scholar
  • 123 Marshall R D, Randall D, Johannet C M. et al . Bupropion and sertraline combination treatment in refractory depression.  J Psychopharmacol. 1995;  9 284-286
    Google Scholar
  • 124 Spier S A. Use of bupropion with SSRIs and venlafaxine.  Depress Anxiety. 1998;  7 73-75
    Google Scholar
  • 125 Papakostas G I, Worthington J J, Iosifescu D V. et al . The combination of duloxetine and bupropion for treatment-resistant major depressive disorder.  Depress Anxiety. 2006;  3 178-181
    Google Scholar
  • 126 Young S J. Panic associated with combining fluoxetine and bupropion (letter).  J Clin Psychiatry. 1996;  57 177-178
    Google Scholar
  • 127 Gerner R H, Kaufman K R, Rosen R. Seizures associated with bupropion and SSRI cotherapy (abstract).  Biol Psychiatry. 1998;  43 995
    Google Scholar
  • 128 DeBattista C, Solvason H B, Poirier J. et al . A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants.  J Clin Psychopharmacol. 2003;  23 27-30
    Google Scholar
  • 129 Clayton A H, McGarvey E L, Abouesh A I. et al . Substitution of an SSRI with bupropion sustained release following SSRI-induced sexual dysfunction.  J Clin Psychiatry. 2001;  62 185-190
    Google Scholar
  • 130 Kennedy S H, McCann S M, Masellis M. et al . Combining bupropion SR with venlafaxine, paroxetine or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects.  J Clin Psychiatry. 2000;  63 181-186
    Google Scholar
  • 131 Labbate L A, Grimes J B, Hines A. et al . Bupropion treatment of serotonin reuptake antidepressant-associated sexual dysfunction.  Ann Clin Psychiatry. 1997;  9 241-245
    Google Scholar
  • 132 Papakostas G I, Petersen T J, Green C. et al . A description of next-step switching versus augmentation practices for outpatients with treatment-resistant major depressive disorder enrolled in an academic speciality clinic.  Ann Clin Psychiatry. 2005;  3 161-165
    Google Scholar
  • 133 Trivedi M H, Fava M, Wisniewski S R. et al . Medication augmentation after the failure of SSRIs for depression.  N Engl J Med. 2006;  12 1243-1252
    Google Scholar
  • 134 Zisook S A, Rush A, Haight B R. Use of bupropion in combination with serotonin reuptake inhibitors.  Biol Psychiatry. 2006;  59 203-210
    Google Scholar
  • 135 Bondolfi G, Chautems C, Rochat B. et al . Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation.  Psychopharmacology. 1996;  128 421-425
    Google Scholar
  • 136 Hunchak J. SSRI combination: treatment for depression (letter).  Can J Psychiatry. 1994;  55 24-25
    Google Scholar
  • 137 Coryell W. Augmentation strategies for inadequate antidepressant response: a review of placebo-controlled studies.  Ann Clin Psychiatry. 2000;  12 141-146
    Google Scholar
  • 138 Bauer M, Linden M. Die Kombination verschiedener Antidepressiva in der Behandlung therapieresistenter Depressionen.  Nervenarzt. 1993;  64 343-347
    Google Scholar
  • 139 Bauer M, Whybrow P C, Angst J. et al . WFSBP-Guidelines for biological treatment of unipolar depressive disorders, Part 1: Acute and continuation treatment of major depressive disorder.  World J Biol Psychiatry. 2002;  3 5-43
    Google Scholar
  • 140 Härter M, Sitta P, Keller F. et al . Stationäre psychiatrisch-psychotherapeutische Depressionsbehandlung. Prozess- und Ergebnisqualität anhand eines Modellprojekts in Baden-Württemberg.  Nervenarzt. 2004;  75 1083-1091
    Google Scholar

Prof. Dr. Max Schmauß

Bezirkskrankenhaus Augsburg

Dr.-Mack-Str. 1

86156 Augsburg

Email: m.schmauss@bkh-augsburg.de

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