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DOI: 10.1055/s-2005-867019
Pharmakologische Therapie manisch-depressiver Mischzustände
Pharmacotherapy of Manic-Depressive Mixed StatesPublikationsverlauf
Publikationsdatum:
01. März 2006 (online)
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Zusammenfassung
Hintergrund: Manisch-depressive Mischzustände kommen in 40 % aller akuten bipolaren Episoden vor. Es handelt sich um komplexe, schwer zu behandelnde klinische Bilder. In diesem Beitrag soll ein Überblick über die Literatur zur Therapie der Mischzustände gegeben werden. Methode: Die Literatur wurde anhand von Medline-, Embase- und dem Cochrane-Controlled-Trials-Register-Suche identifiziert. Stichwörter waren „mixed mania”, „mixed state/(s)”, „mixed episode/(s)”, „treatment”, „therapy”, „study” und „trial”. Ergebnisse: Es fanden sich sehr wenige doppelblinde, plazebokontrollierte Studien, die sich speziell mit der Therapie manisch-depressiver Mischzustände beschäftigen. Stattdessen sind Patienten mit Mischzuständen oftmals eine Untergruppe der untersuchten Gesamtkohorte. Die verfügbaren Daten zeigen, dass akute Mischzustände nicht günstig auf Lithium ansprechen. Stattdessen sind Valproat und Olanzapin die Medikamente der ersten Wahl. Antidepressiva sollten vermieden werden, weil sie das intraepisodische Switching dieser Episoden verstärken können. Lamotrigin kann bei Mischzuständen mit überwiegend depressiven Symptomen eingesetzt werden. Schlussfolgerungen: Es sind mehr Studien nötig, die sich speziell mit der Therapie manisch-depressiver Mischzustände befassen. Behandlungsempfehlungen können nur vorläufig sein, weil die Datenlage eine definitive Therapieempfehlung zum jetzigen Zeitpunkt nicht zulässt.
Abstract
Objective: Mixed episodes comprise up to 40 % of acute bipolar admissions. They are difficult-to-treat, complex clinical pictures. This review provides an overview of the available literature on the pharmacotherapy of manic-depressive mixed states and suggests treatment options. Method: Literature was identified by searches in Medline, Embase and the Cochrane Controlled Trials Register. Studies were considered relevant if they contained the keywords mixed mania, mixed state (s), mixed episode (s), treatment, therapy, study or trial. Results: Overall, there were very few double-blind, placebo-controlled studies specifically designed to treat manic-depressive mixed states. Rather, patients with mixed states comprised a subgroup of the examined patient cohorts. Nevertheless, the data show that acute mixed states do not respond favourably to lithium. Instead, valproate and olanzapine are drugs of first choice. Carbamazepine may play a role in the prevention of mixed states. Antidepressants should be avoided, because they may worsen intraepisodic mood lability. Lamotrigine may be useful in treating mixed states with predominantly depressive symptoms. Conclusions: More treatment studies specifically designed to treat the complex clinical picture of mixed states are clearly needed. Current treatment recommendations for clinical practice based on the available literature can only target selected aspects of these episodes.
Literatur
- 1 Secunda S K, Swann A, Katz M M, Koslow S H, Croughan J, Chang S. Diagnosis and treatment of mixed mania. Am J Psychiatry. 1987; 144 (1) 96-98
- 2 Cohen S, Khan A, Robison J. Significance of mixed features in acute mania. Compr Psychiatry. 1988; 29 (4) 421-426
- 3 Krüger S, Cooke R G, Spegg C, Bräunig P. Relevance of the catatonic syndrome to the mixed manic episode. J Affect Disord. 2003; 74 (3) 279-285
- 4 Goldberg J F, Garno J L, Leon A C, Kocsis J H, Portera L. Association of recurrent suicidal ideation with non-remission from acute mixed mania. Am J Psychiatry. 1998; 155 (12) 1753-1755
- 5 Freeman M P, McElroy S L. Clinical picture and etiological models of mixed states. Psychiatr Clin North Am. 1999; 22 (3) 535-546
- 6 Perugi G, Akiskal H S, Micheli C, Musetti L, Paiano A, Quilici C, Rossi L, Cassano G B. Clinical subtypes of bipolar mixed states: validating a broader European definition in 143 cases. J Affect Disord. 1997; 43 (3) 169-180
- 7 Cole A J, Scott J, Ferrier I N, Eccleston D. Patterns of treatment resistance in bipolar affective disorder. Acta Psychiatr Scand. 1993; 88 (2) 121-123
- 8 American Psychiatric Association .Diagnostic and Statistical Manual of Mental Disorders. 4th edition ed. Washington, DC; American Psychiatric Press 1996
- 9 World Health Organization .Internationale Klassifikation psychischer Störungen, ICD 10. Bern, Switzerland; Hans Huber 1994
- 10 Freeman T W, Clothier J L, Pazzaglia P, Lesem M D, Swann A C. A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiatry. 1992; 149 (1) 108-111
- 11 Clothier J L, Swann A C, Freeman T W. Dysphoric mania. J Clin Psychopharmacol. 1992; 12 (1, Suppl) 13S-16S
- 12 Swann A C, Secunda S K, Katz M M, Koslow S H, Maas J W, Chuang S, Robins E. Lithium treatment of mania: Clinical characteristics, specificity of symptom change, and outcome. Psychiatry Research. 1986; 18 127-141
- 13 Goldberg J F, Garno J L, Leon A C, Kocsis J H, Portera L. Rapid titration of mood stabilizers predicts remission from mixed or pure mania in bipolar patients [published erratum appears in J Clin Psychiatry 1998; 59 (6): 320]. J Clin Psychiatry. 1998; 59 (4) 151-158
- 14 Frye M A, Ketter T A, Leverich G S, Huggins T, Lantz C, Denicoff K D, Post R M. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry. 2000; 61 (1) 9-15
- 15 Frye M A, Altshuler L L, Szuba M P, Finch N N, Mintz J. The relationship between antimanic agent for treatment of classic or dysphoric mania and length of hospital stay. J Clin Psychiatry. 1996; 57 (1) 17-21
- 16 McElroy S L, Keck P EJ, Pope H GJ, Hudson J I. Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. J Clin Psychopharmacol. 1992; 12 (1 Suppl) 42S-52S
- 17 Overall J E, Gorham D R. The Brief Psychiatric Rating Scale. Psychol Rep. 1962; 10 799-812
- 18 Endicott J, Spitzer R L, Fleiss R L, Cohen J. The global assessment of functioning scale: A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry. 1976; 33 766-771
- 19 McFarland B H, Miller M R, Straumfjord A A. Valproate use in the older manic patient. J Clin Psychiatry. 1990; 51 479-481
- 20 Calabrese J R, Markovitz P J, Kimmel S E, Wagner S C. Spectrum of efficacy of valproate in 78 rapid-cycling bipolar patients. J Clin Psychopharmacol. 1992; 12 (1 Suppl) 53S-56S
- 21 Ballenger J C, Post R M. Carbamazepine in manic-depressive illness: a new treatment. Am J Psychiatry. 1980; 137 782-790
-
22 Bowden C L.
Carbamazepine in bipolar disorder. In: Goodnick PJ (ed) Predictors of treatment response in mood disorders. Clinical Practice, No 34. Washington, DC, USA; American Psychiatric Press 1996: 119-132 - 23 Post R M, Rubinow D R, Uhde T W, Roy-Burne P P, Linnoila M, Rosoff A, Cowdry R. Dysphoric mania. Arch Gen Psychiatry. 1989; 46 353-358
- 24 Ketter T A, Kalali A H, Weisler S SG. A multicenter, open label evaluation of beaded, extended-release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry. 2004; 65 668-673
- 25 Hamilton M. A rating scale for depression. J Neuro Neurosurg Psychiatr. 1960; 23 56-62
- 26 Young R, Biggs J, Meyer D. A rating scale for mania. Br J Psychiatr. 1978; 133 429-435
- 27 Barbosa L, Berk M, Forster M A. Double-blind, placebo-controlled trial of augmentation with lamotrogine or placebo in patients concomitantly treated with fluoxetine for resistant depression. J Clin Psychiatry. 2003; 64 (4) 403-407
- 28 Bowden C L, Calabrese J R, McElroy S L, Rhodes L J, Keck Jr P E, Cookson J, Anderson J, Bolden-Watson C, Ascher J, Monaghan E, Zhou J. The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder. Biol Psychiatry. 1999; 45 (8) 953-958
- 29 Calabrese J R, Bowden C L, Sachs G S, Ascher J A, Monaghan E, Rudd G D. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry. 1999; 60 (2) 79-88
- 30 Calabrese J R, Bowden C L, McElroy S L, Cookson J, Andersen J, Keck Jr P E, Rhodes L, Bolden-Watson C, Zhou J. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry. 1999; 156 (7) 1019-1023
- 31 Gidal B E, Sheth R, Parnell J, Maloney K, Sale M. Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Epilepsy Res. 2003; 57 (2 - 3) 85-93
- 32 Pande A C, Crockatt J G, Janney C A, Werth J L, Tsaroucha G. Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. Bipolar Disord. 2000; 2 (3) 249-255
- 33 Perugi G, Toni C, Ruffolo G, Sartini S, Simonini E, Aksikal H. Clinical experience using adjunctive gabapentin in treatment resistant bipolar mixed states. Pharmacopsychiat. 1999; 32 (4) 136-141
- 34 Sokolski K, Green C, Maris D, DeMet E. Gabapentin as an adjunct to standard mood stabilizers in outpatients with mixed bipolar symptomatology. Ann Clin Psychiatry. 1999; 11 (4) 217-222
- 35 Larkin J G, McKee P J, Forrest G, Beastall G H, Park B K, Lowrie L I, Lloyd P, Brody M J. Lack of enzyme induction with oxcarbazepine (600 mg daily) in healthy subjects. Br J Clin Pharmacol. 1991; 31 (1) 65-71
- 36 Benedetti A, Lattanzi L, Pini S, Musetti L, Dell'Osso L, Cassano G B. Oxcarbazepine as add-on treatment in patients with bipolar manic, mixed or depressive episode. J Affect Disord. 2004; 79 (1 - 3) 273-277
- 37 Ghaemi S N, Berv D A, Klugman J, Rosenquist K J, Hsu D J. Oxcarbazepine treatment of bipolar disorder. J Clin Psychiatry. 2003; 64 (8) 943-945
- 38 Vieta E, Torrent C, Garcia-Ribas G, Gilabert A, Garcia-Pares G, Rodriguez A, Cadevall J, Garcia-Castrillon J, Lusilla P, Arrufat F. Use of topiramate in treatment-resistant bipolar spectrum disorders. J Clin Psychopharmacol. 2002; 22 (4) 431-435
- 39 McElroy S L, Suppes T, Keck P E, Frye M A, Denicoff K D, Altshuler L L, Brown E S, Nolen W A, Kupka R W, Rochussen J, Leverich G S, Post R M. Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry. 2000; 47 (12) 1025-1033
- 40 Chengappa K N, Rathore D, Levine J, Atzert R, Solai L, Parepally H, Levin H, Moffa N, Delaney J, Brar J S. Topiramate as add-on treatment for patients with bipolar mania. Bipolar Disord. 1999; 1 (1) 42-53
- 41 Zarate Jr C A, Tohen M. Double-blind comparison of the continued use of antipsychotic treatment versus its discontinuation in remitted manic patients. Am J Psychiatry. 2004; 161 (1) 169-171
- 42 Hirschfeld R M. The efficacy of atypical antispychotics in bipolar disorders. J Clin Psychiatry. 2003; 64 (8) 15-21
- 43 Suppes T, McElroy S L, Gilbert G, Dessain E C, Cole J O. Clozapine in the treatment of dysphoric mania. Biol Psychiatr. 1992; 32 (3) 270-280
- 44 Zarate Jr C A, Tohen M, Baldessarini R J. Clozapine therapy in severe mood disorders. J Clin Psychiatry. 1995; 56 108-112
- 45 Tohen M, Sanger T M, McElroy S L, Tollefson G D, Chengappa K N, Daniel D G, Petty F, Centorrino F, Wang R, Grundy S L, Greaney M G, Jacobs T G, David S R, Toma V. Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. Am J Psychiatry. 1999; 156 (5) 702-709
- 46 Tohen M, Jacobs T G, Grundy S L, McElroy S L, Banov M C, Janicak P G, Sanger T, Risser R, Zhang F, Toma V, Francis J, Tollefson G D, Breier A. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzapine HGGW Study Group. Arch Gen Psychiatry. 2000; 57 (9) 841-849
- 47 Tohen M, Chengappa K N, Suppes T, Zarate Jr C A, Calabrese J R, Bowden C L, Sachs G S, Kupfer D J, Baker R W, Risser R C, Keeter E L, Feldman P D, Tollefson G D, Breier A. Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatry. 2002; 59 (1) 62-69
- 48 Tohen M, Ketter T A, Zarate C A, Suppes T, Frye M, Altshuler L, Zajecka J, Schuh L M, Risser R C, Brown E, Baker R W. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Am J Psychiatry. 2003; 160 (7) 1263-1271
- 49 Baker R W, Tohen M, Fawcett J, Risser R C, Schuh L M, Brown E, Stauffer V L, Shao L, Tollefson G D. Acute dysphoric mania: treatment response to olanzapine versus placebo. J Clin Psychopharmacol. 2003; 23 (2) 132-137
- 50 Ketter T A, Winsberg M E, DeGolia S G, Dunai M, Tate D L, Strong C M. Rapid efficacy of olanzapine augmentation in nonpsychotic bipolar mixed states. J Clin Psychiatry. 1998; 59 (2) 83-85
- 51 Zullino D, Baumann P. Olanzapine for mixed episodes of bipolar disorder. J Psychopharmacol. 1999; 13 (2) 198
- 52 Sharma V, Pistor L. Treatment of bipolar mixed state with olanzapine. J Psychiatry Neurosci. 1999; 24 (1) 40-44
- 53 Sachs G S, Grossman F, Ghaemi S N, Okamoto A, Bowden C L. Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Am J Psychiatry. 2002; 159 1146-1154
- 54 Yatham L N, Grossman F, Augustyns I, Vieta E, Ravindran A V. Mood stabilisers plus risperidone or placebo in the treatment of acute mania. Br J Psychiatry. 2003; 182 141-147
- 55 Benabarre A, Vieta E, Colom F, Martinez A, Reinares M, Corbella B. Treatment of mixed mania with risperidone and mood stabilizers. Can J Psychiatry. 2001; 46 (9) 866-867
- 56 Vieta E, Herraiz M, Parramon G, Goikolea J M, Fernandez A, Benabarre A. Risperidone in the treatment of mania: efficacy and safety results from a large, multicentre, open study in Spain. J Affect Disord. 2002; 72 (1) 15-19
- 57 DelBello M P, Schwiers M L, Rosenberg H L, Strakowski S M. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry. 2002; 41 (10) 1216-1223
- 58 Vieta E, Parramon G, Padrell E, Nieto E, Martinez-Aran A, Corbella B, Colom F, Reinares M, Goikolea J M, Torrent C. Quetiapine in the treatment of rapid cycling bipolar disorder. Bipolar Disord. 2002; 4 (5) 335-340
- 59 Zarate Jr C A, Rothschild A, Fletcher K E, Madrid A, Zapatel J. Clinical predictors of acute response with quetiapine in psychotic mood disorders. J Clin Psychiatry. 2000; 61 (3) 185-189
- 60 Keck Jr P E, Versiani M, Potkin S, West S A, Giller E, Ice K. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry. 2003; 160 (4) 741-748
- 61 Keck Jr P E, Marcus R, Tourkodimitris S, Ali M, Liebeskind A, Saha A, Ingenito G. A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry. 2003; 160 (9) 1651-1658
- 62 Post R M, Leverich G S, Nolen W A, Kupka R W, Altshuler L L, Frye M A, Suppes T, McElroy S, Keck P, Grunze H, Walden J. A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network. Bipolar Disord. 2003; 5 (6) 396-406
- 63 Kusumakar V. Antidepressants and antipsychotics in the long-term treatment of bipolar disorder. J Clin Psychiatry. 2002; 63, Suppl 10 23-28
- 64 Post R M, Altshuler L L, Frye M A, Suppes T, Rush A J, Keck Jr P E, McElroy S L, Denicoff K D, Leverich G S, Kupka R, Nolen W A. Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers. Bipolar Disord. 2001; 3 (5) 259-265
- 65 Peet M. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. Br J Psychiatry. 1994; 164 (4) 549-550
- 66 Henry C, Sorbara F, Lacoste J, Gindre C, Leboyer M. Antidepressant-induced mania in bipolar patients: identification of risk factors. J Clin Psychiatry. 2001; 62 (4) 249-255
- 67 Ghaemi S N, Rosenquist K J, Ko J Y, Baldassano C F, Kontos N J, Baldessarini R J. Antidepressant treatment in bipolar versus unipolar depression. Am J Psychiatry. 2004; 161 (1) 163-165
- 68 Bauer M S, Callahan A M, Jampala C, Petty F, Sajatovic M, Schaefer V, Wittlin B, Powell B J. Clinical practice guidelines for bipolar disorder from the Department of Veterans Affairs. J Clin Psychiatry. 1999; 60 (1) 9-21
- 69 Sachs G S, Printz D J, Kahn D A, Carpenter D, Docherty J P. The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000. Postgrad Med. 2000; Spec No 1-104
- 70 Sachs G S. Decision tree for the treatment of bipolar disorder. J Clin Psychiatry. 2003; 64, Suppl 8 35-40
- 71 Suppes T, Dennehy E B, Swann A C, Bowden C L, Calabrese J R, Hirschfeld R M, Keck Jr P E, Sachs G S, Crismon M L, Toprac M G, Shon S P. Report of the Texas Consensus Conference Panel on medication treatment of bipolar disorder 2000. J Clin Psychiatry. 2002; 63 (4) 288-299
- 72 Goodwin G M. Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2003; 17 (2) 149-173
- 73 Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht R W, Vieta E, Möller H J. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders, Part II: Treatment of Mania. World J Biol Psychiatry. 2003; 4 (1) 5-13
- 74 Grunze H, Walden J, Dittmann S, Berger M, Bergmann A, Braunig P, Dose M, Emrich H M, Gastpar M, Greil W, Krüger S, Möller H J, Übelhack R. Psychopharmacotherapy of bipolar affective diseases. Nervenarzt. 2002; 73 (1) 4-17
- 75 Licht R W, Vestergaard P, Kessing L V, Larsen J K, Thomsen P H. Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark. Acta Psychiatr Scand Suppl. 2003; (419) 1-22
- 76 American Psychiatric Association . Practice guideline for the treatment of patients with bipolar disorder (Revision). Am J Psychiatry. 2002; 159 (4 Suppl) 1-50
- 77 Hirschfeld R M, Baker J D, Wozniak P, Tracy K, Sommerville K W. The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder. J Clin Psychiatry. 2003; 64 (7) 841-846
- 78 Oluboka O J, Bird D C, Kutcher S, Kusumakar V. A pilot study of loading versus titration of valproate in the treatment of acute mania. Bipolar Disord. 2002; 4 (5) 341-345
- 79 Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry. 2004; 65, Suppl 5 7-12
- 80 Easton M S, Janicak P G. Benzodiazepines (BZ) for the management of psychosis. Psychiatr Med. 1991; 9 (1) 25-36
- 81 Menza M A, Harris D. Benzodiazepines and catatonia. An overview. Biol Psychiatry. 1989; (26) 842-846
Priv.-Doz. Dr. med. Stephanie Krüger
Klinik und Poliklinik für Psychiatrie und Psychotherapie · Universitätsklinikum Carl-Gustav Carus
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