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Fortschr Neurol Psychiatr 2000; 68(1): 17-24
DOI: 10.1055/s-2000-11639
ORIGINALARBEIT
Georg Thieme Verlag Stuttgart ·New York

Neue Antidepressiva im Vergleich zu klassischen Trizyklika

Wirkmechanismen und klinische BeurteilungAdvances in the Pharmacotherapy of Depression by New Antidepressants:A. Broocks, K. Junghanns, A. Thiel1 , C. H. Gleiter2 , B. Bandelow3
  • Klinik für Psychiatrie, Medizinische Universität zu Lübeck (Direktor: Prof. Dr. F. Hohagen)
  • 1Diakonie-Krankenhaus Rotenburg/Wümme (Chefarzt Priv.-Doz. Dr. A. Thiel)
  • 2Abt. für Klinische Pharmakologie der Universität Tübingen (Direktor Prof. Dr. C. H. Gleiter)
  • 3Klinik und Poliklinik für Psychiatrie der Universität Göttingen (Direktor: Prof. Dr. E. Rüther)
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Publication History

Publication Date:
31 December 2000 (online)

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Zusammenfassung:

In den letzten Jahren ist eine Reihe neuer Arzneimittel zur Behandlung depressiver Störungen zugelassen worden. Im Vergleich zu klassischen Antidepressiva verfügen diese Substanzen über günstigere Nebenwirkungsprofile und eine sehr geringe Toxizität. Die fehlenden sedierenden Wirkungen der selektiven Serotonin-Wiederaufnahmehemmer sind gerade in der Initialphase der Behandlung nicht immer vorteilhaft. Neuere Rezeptor-Antagonisten wie Mirtazapin und Nefazodon verfügen dagegen wieder über eine schlafanstoßende Wirkung. Auch bei selektiven Substanzen müssen Interaktionen mit anderen Pharmaka beachtet werden, deren Abbau erheblich verzögert sein kann. Klassische Antidepressiva haben nach wie vor einen wichtigen Platz in der Behandlung schwerer, stationär behandlungsbedürftiger depressiver Störungen und werden wegen der geringeren Behandlungskosten auch ambulant weiter verordnet. Auch neuere Antidepressiva führen über verschiedene synaptische Mechanismen zu einer erhöhten Verfügbarkeit monoaminerger Neurotransmitter. Aktuelle experimentelle Befunde weisen darauf hin, daß hierdurch andere neurobiologische Systeme beeinflußt werden, die möglicherweise direkt mit der depressiven Störung in Beziehung stehen. Im Mittelpunkt des Artikels stehen die Vor- und Nachteile der verschiedenen Substanzgruppen aus klinischer Sicht.

During the last decade several new agents have been introduced in the treatment of depressive disorders. In comparison to classical tricyclic antidepressants, these agents have less side effects and a very low toxicity. Selective inhibitors of serotonin reuptake do not produce sedation; however, in the initial phase of treatment this is not always an advantage. In contrast, receptor antagonists, such as mirtazapin and nefazodone have moderate sleep-inducing properties. Selective agents are also characterized by certain pharmacologic interactions which can lead to considerable inhibition of the metabolism of other drugs. Classical antidepressants still play an important role in the treatment of severe depressive episodes. Different synaptic effects of new antidepressants lead to an increased availability of monoaminergic neurotransmitters. The article summarizes the most important neurobiological consequences of these acute synaptic effects which might be more closely associated with neurobiological correlates of depression. The authors conclude about the advantages and disadvantages of the different classes of antidepressants from a clinical point of view.

Literatur

  • 1 Aldenhoff J B, Dumais H C, Fritzsche M, Sulger J, Vollmayr B. Altered Ca(2+)-homeostasis in single T-lymphocytes of depressed patients.  J Psychiatr Res. 1997;  31 315-322
    CrossrefPubMedGoogle Scholar
  • 2 Artigas F, Romero L, de M C, Blier P. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists.  Trends Neurosci. 19;  19 378-383
    PubMedGoogle Scholar
  • 3 Ball S E, Ahern D, Scatina J, Kao J. Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2.  Br J Clin Pharmacol. 1997;  43 619-626
    CrossrefPubMedGoogle Scholar
  • 4 Ballenger J C. Clinical evaluation of venlafaxine.  J Clin Psychopharmacol. 1996;  16 29-35S
    PubMedGoogle Scholar
  • 5 Barden N. Modulation of glucocorticoid receptor gene expression by antidepressant drugs.  Pharmacopsychiat. 1996;  29 12
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Barr L C, Goodman W K, McDougle C J, Delgado P L, Heninger G R, Charney D S, Price L H. Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors.  Arch Gen Psychiatry. 1994;  51 309-317
    PubMedGoogle Scholar
  • 7 Beasley C J, Dornseif B E, Bosomworth J C, Sayler M E, Rampey A J, Heiligenstein J H, Thompson V L, Murphy D J, Masica D N. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression [published erratum appears in Brit med J 1991 Oct 19; 303 (6808): 968] [see comments].  Brit med J. 1991;  303 685-692
    CrossrefPubMedGoogle Scholar
  • 8 Benkert O, Hippius H. Psychiatrische Pharmakologie: ein Grundriß für Ärzte und Studenten. Berlin; Springer-Verlag 1996
  • 9 Berzewski H, Van Moffaert M, Gagiano C A. Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive offsodes. Eur Neuropsychopharmacol 1997: S37-47
  • 10 Blier P, Bergeron R, de M C. Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response.  Neuropsychopharmacology. 1997;  16 333-338
    CrossrefPubMedGoogle Scholar
  • 11 Blier P, de M C. Clarifications on the effect of 5-HT1A agonists and selective 5-HT reuptake inhibitors on the 5-HT system [letter; comment].  Neuropsychopharmacology. 1996;  15 213
    CrossrefPubMedGoogle Scholar
  • 12 Bode L, Dietrich D E, Stoyloff R, Emrich H M, Ludwig H. Amantadine and human Borna disease virus in vitro and in vivo in an infected patient with bipolar depression [letter] [see comments].  Lancet. 1997;  349 178-179
    CrossrefPubMedGoogle Scholar
  • 13 Bode L, Ferszt R, Czech G. Borna disease virus infection and affective disorders in man.  Arch Virol. 1993;  Suppl 7 159-167
    PubMedGoogle Scholar
  • 14 Chen J, Rasenick M M. Chronic antidepressant treatment facilitates G protein activation of adenyl cyclase without altering G protein content.  J Pharmacol Exp Ther. 1995;  275 509-517
    PubMedGoogle Scholar
  • 15 Davies D S. Inhibitory Potential of Reboxetine on Major Drug Metabolizing Forms of P450 in Humans, Caligary. 
  • 16 Davis J M, Wang Z, Janicak P G. A quantitative analysis of clinical drug trials for the treatment of affective disorders.  Psychopharmacol Bull. 1993;  29 175-181
    PubMedGoogle Scholar
  • 17 Davis R, Whittington R, Bryson H M. Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression [see comments].  Drugs. 1997;  53 608-636
    PubMedGoogle Scholar
  • 18 Delgado P L, Price L H, Miller H L, Salomon R M, Aghajanian G K, Heninger G R, Charney D S. Serotonin and the neurobiology of depression. Effects of tryptophan depletion in drug-free depressed patients.  Arch Gen Psychiatry. 1994;  51 865-874
    PubMedGoogle Scholar
  • 19 Deuschle M, Bode L, Heuser I, Schmider J, Ludwig H. Borna disease virus proteins in cerebrospinal fluid of patients with recurrent depression and multiple sclerosis [letter].  Lancet. 1998;  352 1828-1829
    CrossrefPubMedGoogle Scholar
  • 20 Dietrich D E, Schedlowski M, Bode L, Ludwig H, Emrich H M. A viro-psychoimmunological disease-model of a subtype affective disorder [see comments].  Pharmacopsychiatry. 1998;  31 77-82
    PubMedGoogle Scholar
  • 21 DUAG . Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group.  J Affect Disord. 1990;  18 289-299
    CrossrefPubMedGoogle Scholar
  • 22 DUAG . Moclobemide: a reversible MAO-A-inhibitor showing weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group.  J Affect Disord. 1993;  28 105-116
    CrossrefPubMedGoogle Scholar
  • 23 Dubini A, Bosc M, Polin V. Noradrenaline-selective versus serotonin-selective antidepressant therapy: differential effects on social functioning. J Psychopharmacol 1997: S17-23
  • 24 Duman R S, Heninger G R, Nestler E J. A molecular and cellular theory of depression [see comments].  Arch Gen Psychiatry. 1997;  54 597-606
    CrossrefPubMedGoogle Scholar
  • 25 Gleiter C, Volz H P. [Moclobemide].  Dtsch Med Wochenschr. 1995;  120 1175-1176
    PubMedGoogle Scholar
  • 26 Gleiter H C, Volz H-P, Möller H-J. Serotonin-Wiederaufnahmehemmer. Pharmakologie und therapeutischer Einsatz. ISBN: 3804716385 ed. Stuttgart; Wissenschaftl VG 1999
  • 27 Goddard A W, Sholomskas D E, Walton K E, Augeri F M, Charney D S, Heninger G R, Goodman W K, Price L H. Effects of tryptophan depletion in panic disorder.  Biol Psychiatry. 1994;  36 775-777
    CrossrefPubMedGoogle Scholar
  • 28 Goodwin G M. How do antidepressants affect serotonin receptors? The role of serotonergic receptors in the therapeutic and side effect profile of the SSRIs.  J Clin Psychiatry. 1996;  (suppl 4) 9-13
    PubMedGoogle Scholar
  • 29 Gregor K J, Way K, Young C H, James S P. Concomitant use of selective serotonin reuptake inhibitors with other cytochrome P450 2D6 or 3A4 metabolized medications: how often does it really happen? [In Process Citation].  J Affect Disord. 1997;  46 59-67
    CrossrefPubMedGoogle Scholar
  • 30 Haddjeri N, Blier P, Montigny C. Noradrenergic modulation of central serotonergic neurotransmission: acute and long-term actions of mirtazapine [published erratum appears in Int Clin Psychopharmacol 1996 Jun;11(2):153].  Int Clin Psychopharmacol. 1995;  4 11-17
    PubMedGoogle Scholar
  • 31 Haddjeri N, Blier P, Montigny C. Effects of long-term treatment with the alpha 2-adrenoceptor antagonist mirtazapine on 5-HT neurotransmission.  Naunyn Schmiedebergs Arch Pharmacol. 1997;  355 20-29
    PubMedGoogle Scholar
  • 32 Heninger G R, Charney D S, Price L H. Noradrenergic and serotonergic receptor system function in panic disorder and depression.  Acta Psychiatr Scand Suppl. 1988;  341 138-150
    PubMedGoogle Scholar
  • 33 Heninger G R, Delgado P L, Charney D S. The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans.  Pharmacopsychiatry. 1996;  29 2-11
    PubMedGoogle Scholar
  • 34 Joffe R T, Bakish D. Combined SSRI-moclobemide treatment of psychiatric illness.  J Clin Psychiatry. 1994;  55 24-5
    PubMedGoogle Scholar
  • 35 Kasper S. Efficacy of antidepressants in the treatment of severe depression: the place of mirtazapine.  J Clin Psychopharmacol. 1997a;  17 19-28S
    CrossrefPubMedGoogle Scholar
  • 36 Kasper S. Hypericum perforatum in psychiatric practice (interview).  Nervenarzt. 1997b;  8
    PubMedGoogle Scholar
  • 37 Kasper S, Praschak R N, Tauscher J, Wolf R. A risk-benefit assessment of mirtazapine in the treatment of depression [published erratum appears in Drug Saf 1998 Feb;18(2):123].  Drug Saf. 1997a;  17 251-264
    PubMedGoogle Scholar
  • 38 Kasper S, Schindler S, Neumeister A. Risk of suicide in depression and its implication for psychopharmacological treatment.  Int Clin Psychopharmacol. 1996;  11 71-79
    PubMedGoogle Scholar
  • 39 Kasper S, Zivkov M, Roes K C, Pols A G. Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline.  Eur Neuropsychopharmacol. 1997b;  7 115-124
    CrossrefPubMedGoogle Scholar
  • 40 Keller M B, Baker L A. The clinical course of panic disorder and depression.  J Clin Psychiatry. 1992;  53 Suppl 5-8
    PubMedGoogle Scholar
  • 41 Kupfer D J, Frank E, Perel J M, Cornes C, Mallinger A G, Thase M E, McEachran A B, Grochocinski V J. Five-year outcome for maintenance therapies in recurrent depression.  Arch Gen Psychiatry. 1992;  49 769-773
    PubMedGoogle Scholar
  • 42 Lecrubier Y, Bourin M, Moon C A, Schifano F, Blanchard C, Danjou P, Hackett D. Efficacy of venlafaxine in depressive illness in general practice.  Acta Psychiatr Scand. 1997;  95 485-493
    CrossrefPubMedGoogle Scholar
  • 43 Lesch K P, Aulakh C S, Tolliver T J, Hill J L, Murphy D L. Regulation of G proteins by chronic antidepressant drug treatment in rat brain: tricyclics but not clorgyline increase Go alpha subunits.  Eur J Pharmacol. 1991;  207 361-364
    PubMedGoogle Scholar
  • 44 Lesch K P, Aulakh C S, Wolozin B L, Tolliver T J, Hill J L, Murphy D L. Regional brain expression of serotonin transporter mRNA and its regulation by reuptake inhibiting antidepressants.  Brain Res Mol Brain Res. 1993;  17 31-35
    CrossrefPubMedGoogle Scholar
  • 45 Li Q, Muma N A, Battaglia G, Kar Ld. A desensitization of hypothalamic 5-HT1A receptors by repeated injections of paroxetine: reduction in the levels of G(i) and G(o) proteins and neuroendocrine responses, but not in the density of 5-HT1A receptors.  J Pharmacol Exp Ther. 1997;  282 1581-1590
    PubMedGoogle Scholar
  • 46 Li Q, Muma N A, Kar Ld. Chronic fluoxetine induces a gradual desensitization of 5-HT1A receptors: reductions in hypothalamic and midbrain Gi and G(o) proteins and in neuroendocrine responses to a 5-HT1A agonist.  J Pharmacol Exp Ther. 1996;  279 1035-1042
    PubMedGoogle Scholar
  • 47 Lieb K, Hufert F T, Bechter K, Bauer J, Kornhuber J. Depression, Borna disease and amantadine [letter; comment].  Lancet. 1997;  349 958
    PubMedGoogle Scholar
  • 48 Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D. St John's wort for depression - an overview and meta-analysis of randomised clinical trials [see comments].  Bmj. 1996;  313 253-258
    PubMedGoogle Scholar
  • 49 Maes M, Meltzer H Y, Buckley P, Bosmans E. Plasma-soluble interleukin-2 and transferrin receptor in schizophrenia and major depression.  Eur Arch Psychiatry Clin Neurosci. 1995;  244 325-329
    PubMedGoogle Scholar
  • 50 Maj J, Moryl E. Effects of fluoxetine given chronically on the responsiveness of 5-HT receptor subpopulations to their agonists.  Eur Neuropsychopharmacol. 1993;  3 85-94
    CrossrefPubMedGoogle Scholar
  • 51 Masica D N, Kotsanos J G, Beasley C J, Potvin J H. Trend in suicide rates since fluoxetine introduction [letter].  Am J Public Health. 1992;  82 1295
    PubMedGoogle Scholar
  • 52 Massana J. Reboxetine versus fluoxetine: an overview of efficacy and tolerability.  J Clin Psychiatry. 1998;  14 8-10
    PubMedGoogle Scholar
  • 53 Montgomery S A, Kasper S. Depression: a long-term illness and its treatment. Int Clin Psychopharmacol 1998: S23-26
  • 54 Müller W E, Eckart A. Pharmakodynamische Grundlagen der Therapie mit spezifischen Serotonin-Wiederaufnahmehemmern.  Psychopharmakotherapie. 1997;  Suppl 7 2-8
    PubMedGoogle Scholar
  • 55 Muller W E, Kasper S. Clinically used antidepressant drugs [editorial].  Pharmacopsychiatry. 1997;  2 71
    PubMedGoogle Scholar
  • 56 Muller W E, Singer A, Wonnemann M, Hafner U, Rolli M, Schafer C. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract.  Pharmacopsychiatry. 1998;  1 16-21
    PubMedGoogle Scholar
  • 57 Murphy D L, Andrews A M, Wichems C H, Li Q, Tohda M, Greenberg B. Brain serotonin neurotransmission: an overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems and consequent implications for understanding the actions of serotonergic drugs [In Process Citation].  J Clin Psychiatry. 1998;  15 4-12
    PubMedGoogle Scholar
  • 58 Nemeroff C B, DeVane C L, Pollock B G. Newer antidepressants and the cytochrome P450 system [see comments].  Am J Psychiatry. 1996;  153 311-320
    PubMedGoogle Scholar
  • 59 Neumeister A, Praschak R N, Hesselmann B, Vitouch O, Rauh M, Barocka A, Kasper S. Effects of tryptophan depletion in fully remitted patients with seasonal affective disorder during summer [see comments].  Psychol Med. 1998;  28 257-264
    CrossrefPubMedGoogle Scholar
  • 60 Nibuya M, Morinobu S, Duman R S. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.  J Neurosci. 1995;  15 7539
    PubMedGoogle Scholar
  • 61 Nowak G, Legutko B, Skolnick P, Popik P. Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors.  Eur J Pharmacol. 1998;  342 367-370
    CrossrefPubMedGoogle Scholar
  • 62 Nowak G, Li Y, Paul I A. Adaptation of cortical but not hippocampal NMDA receptors after chronic citalopram treatment.  Eur J Pharmacol. 1996;  295 75-85
    CrossrefPubMedGoogle Scholar
  • 63 Nowak G, Ordway G A, Paul I A. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims.  Brain Res. 1995;  675 157-164
    CrossrefPubMedGoogle Scholar
  • 64 Owens M J, Morgan W N, Plott S J, Nemeroff C B. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites.  J Pharmacol Exp Ther. 1997;  283 1305-1322
    PubMedGoogle Scholar
  • 65 Pao M, Tipnis T. Serotonin syndrome after sertraline overdose in a 5-year-old girl [letter].  Arch Pediatr Adolesc Med. 1997;  151 1064-1067
    PubMedGoogle Scholar
  • 66 Paul I A, Layer R T, Skolnick P, Nowak G. Adaptation of the NMDA receptor in rat cortex following chronic electroconvulsive shock or imipramine.  Eur J Pharmacol. 1993;  247 305-311
    PubMedGoogle Scholar
  • 67 Paul I A, Trullas R, Skolnick R, Nowak G. Down-regulation of cortical beta-adrenoceptors by chronic treatment with functional NMDA antagonists.  Psychopharmacology (Berl). 1992;  106 285-287
    PubMedGoogle Scholar
  • 68 Preskorn S H. Clinically relevant pharmacology of selective serotonin reuptake inhibitors.  Clin Pharmacokinet. 1997;  23 Suppl 1 1-21
    PubMedGoogle Scholar
  • 69 Priest R G, Gimbrett R, Roberts M, Steinert J. Reversible and selective inhibitors of monoamine oxidase A in mental and other disorders.  Acta Psychiatr Scand. 1995;  Suppl 386 40-43
    PubMedGoogle Scholar
  • 70 Richelson E. Pharmacology of antidepressants - characteristics of the ideal drug.  Mayo Clin Proc. 1994;  69 1069-1081
    CrossrefPubMedGoogle Scholar
  • 71 Richelson E. Synaptic effects of antidepressants. J Clin Psychopharmacol 1996: 1-7S; discussion 7S - 9S
  • 72 Richelson E. Pharmacokinetic drug interactions of new antidepressants: a review of the effects on the metabolism of other drugs.  Mayo Clin Proc. 1997;  72 835-847
    CrossrefPubMedGoogle Scholar
  • 73 Siuciak J A, Lewis D R, Wiegand S J, Lindsay R M. Antidepressant-like effect of brain-derived neurotrophic factor (BDNF).  Pharmacol Biochem Behav. 1997;  56 131-137
    CrossrefPubMedGoogle Scholar
  • 74 Skolnick P, Layer R T, Popik P, Nowak G, Paul I A, Trullas R. Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression.  Pharmacopsychiatry. 1996;  29 23-26
    Article in Thieme ConnectPubMedGoogle Scholar
  • 75 Smith M A, Makino S, Kvetnansky R, Post R M. Effects of stress on neurotrophic factor expression in the rat brain.  Ann N Y Acad Sci. 1995;  771 234-239
    CrossrefPubMedGoogle Scholar
  • 76 Teufel M R, Gleitz J. Effects of long-term administration of hypericum extracts on the affinity and density of the central serotonergic 5-HT1A and 5-HT2A receptors.  Pharmacopsychiatry. 1997;  2 113-116
    PubMedGoogle Scholar
  • 77 Volz H P. Controlled clinical trials of hypericum extracts in depressed patients - an overview.  Pharmacopsychiatry. 1997;  2 72-76
    PubMedGoogle Scholar
  • 78 Volz H P, Gleiter C H. Monoamine oxidase inhibitors. A perspective on their use in the elderly [In Process Citation].  Drugs Aging. 1998;  13 341-355
    PubMedGoogle Scholar
  • 79 Volz H P, Gleiter C H, Moller H J. [Monoamine oxidase inhibitors in psychiatry. Status of current knowledge].  Nervenarzt. 1996;  67 339-347
    PubMedGoogle Scholar
  • 80 Young E A, Haskett R F, Murphy W V, Watson S J, Akil H. Loss of glucocorticoid fast feedback in depression [see comments].  Arch Gen Psychiatry. 1991;  48 693-699
    PubMedGoogle Scholar

Dr. Priv.-Doz. A. Broocks

Klinik für Psychiatrie

Medizinische Universität zu Lübeck

Ratzeburger Allee 160

D-23538 Lübeck

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