Pharmakologische Therapie manisch-depressiver Mischzustände

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 Cochrane-Controlled-Trials-Register-Suche identifiziert. Ergebnisse: Es fanden sich sehr wenige doppelblinde, placebokontrollierte 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.

Summary

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. 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.

Schlüsselwörter

Mischzustand - Diagnostik - Therapie - Valproinsäure - Olanzapin - Lithium - Antidepressiva

Keywords

Mixed state - diagnosis - treatment - valproate - olanzapine - lithium - antidepressan

• Literatur

• 1 Secunda SK, Swann A, Katz MM, Koslow SH, Croughan J, Chang S. Diagnosis and treatment of mixed mania. Am J Psychiatry 1987; 144: 96-98.
• 2 Cohen S, Khan A, Robison J. Significance of mixed features in acute mania. Compr Psychiatry 1988; 29: 421-426.
• 3 Krüger S, Cooke RG, Spegg C, Bräunig P. Relevance of the catatonic syndrome to the mixed manic episode. J Affect Disord 2003; 74: 279-285.
• 4 Goldberg JF, Garno JL, Leon AC, Kocsis JH, Portera L. Association of recurrent suicidal ideation with non-remission from acute mixed mania. Am J Psychiatry 1998; 155: 1753-1755.
• 5 Freeman MP, McElroy SL. Clinical picture and etiological models of mixed states. Psychiatr Clin North Am 1999; 22: 535-546.
• 6 Perugi G, Akiskal HS, Micheli C, Musetti L, Paiano A, Quilici C, Rossi L, Cassano GB. Clinical subtypes of bipolar mixed states: validating a broader European definition in 143 cases. J Affect Disord 1997; 43: 169-180.
• 7 Cole AJ, Scott J, Ferrier IN, Eccleston D. Patterns of treatment resistance in bipolar affective disorder. Acta Psychiatr Scand 1993; 88: 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 Stõrungen, ICD 10. Bern, Switzerland: Hans Huber; 1994
• 10 Freeman TW, Clothier JL, Pazzaglia P, Lesem MD, Swann AC. A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiatry 1992; 149: 108-111.
• 11 Clothier JL, Swann AC, Freeman TW. Dysphoric mania. J Clin Psychopharmacol 1992; 12 (01) 13S-16S.
• 12 Swann AC, Secunda SK, Katz MM, Koslow SH, Maas JW, Chuang S, Robins E. Lithium treatment of mania: Clinical characteristics, specificity of symptom change, and outcome. Psychiatry Research 1986; 18: 127-141.
• 13 Goldberg JF, Garno JL, Leon AC, Kocsis JH, 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: 320]. J Clin Psychiatry 1998; 59: 151-158.
• 14 Frye MA, Ketter TA, Leverich GS, Huggins T, Lantz C, Denicoff KD, Post RM. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry 2000; 61: 9-15.
• 15 Frye MA, Altshuler LL, Szuba MP, Finch NN, Mintz J. The relationship between antimanic agent for treatment of classic or dysphoric mania and length of hospital stay. J Clin Psychiatry 1996; 57: 17-21.
• 16 McElroy SL, Keck PEJ, Pope HGJ, Hudson JI. Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. J Clin Psychopharmacol 1992; 12: 42S-52S.
• 17 Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: 799-812.
• 18 Endicott J, Spitzer RL, Fleiss RL, 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 BH, Miller MR, Straumfjord AA. Valproate use in the older manic patient. J Clin Psychiatry 1990; 51: 479-481.
• 20 Calabrese JR, Markovitz PJ, Kimmel SE, Wagner SC. Spectrum of efficacy of valproate in 78 rapidcycling bipolar patients. J Clin Psychopharmacol 1992; 12 (Suppl. 01) 53S-56S.
• 21 Ballenger JC, Post RM. Carbamazepine in manicdepressive illness: a new treatment. Am J Psychiatry 1980; 137: 782-790.
• 22 Bowden CL. 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 RM, Rubinow DR, Uhde TW, Roy-Burne PP, Linnoila M, Rosoff A, Cowdry R. Dysphoric mania. Arch Gen Psychiatry 1989; 46: 353-358.
• 24 Ketter TA, Kalali AH, Weisler SSG. 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 MA. 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: 403-407.
• 28 Bowden CL, Calabrese JR, McElroy SL, Rhodes LJ, Keck Jr PE, 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: 953-958.
• 29 Calabrese JR, Bowden CL, Sachs GS, Ascher JA, Monaghan E, Rudd GD. A double-blind placebocontrolled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry 1999; 60: 79-88.
• 30 Calabrese JR, Bowden CL, McElroy SL, Cookson J, Andersen J, Keck Jr PE, Rhodes L, Bolden-Watson C, Zhou J. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry 1999; 156: 1019-1023.
• 31 Gidal BE, 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: 85-93.
• 32 Pande AC, Crockatt JG, Janney CA, Werth JL, Tsaroucha G. Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. Bipolar Disord 2000; 2: 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: 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: 217-222.
• 35 Larkin JG, McKee PJ, Forrest G, Beastall GH, Park BK, Lowrie LI, Lloyd P, Brody MJ. Lack of enzyme induction with oxcarbazepine (600mg daily) in healthy subjects. Br J Clin Pharmacol 1991; 31: 65-71.
• 36 Benedetti A, Lattanzi L, Pini S, Musetti L, Dell’Osso L, Cassano GB. Oxcarbazepine as Addon treatment in patients with bipolar manic, mixed or depressive episode. J Affect Disord 2004; 79: 273-277.
• 37 Ghaemi SN, Berv DA, Klugman J, Rosenquist KJ, Hsu DJ. Oxcarbazepine treatment of bipolar disorder. J Clin Psychiatry 2003; 64: 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: 431-435.
• 39 McElroy SL, Suppes T, Keck PE, Frye MA, Denicoff KD, Altshuler LL, Brown ES, Nolen WA, Kupka RW, Rochussen J, Leverich GS, Post RM. Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry 2000; 47: 1025-1033.
• 40 Chengappa KN, Rathore D, Levine J, Atzert R, Solai L, Parepally H, Levin H, Moffa N, Delaney J, Brar JS. Topiramate as add-on treatment for patients with bipolar mania. Bipolar Disord 1999; 1: 42-53.
• 41 Zarate Jr CA, Tohen M. Double-blind comparison of the continued use of antipsychotic treatment versus its discontinuation in remitted manic patients. Am J Psychiatry 2004; 161: 169-171.
• 42 Hirschfeld RM. The efficavy of atypical antispychotics in bipolar disorders. J Clin Psychiatry 2003; 64: 15-21.
• 43 Suppes T, McElroy SL, Gilbert G, Dessain EC, Cole JO. Clozapine in the treatment of dysphoric mania. Biol Psychiatr 1992; 32: 270-280.
• 44 Zarate Jr CA, Tohen M, Baldessarini RJ. Clozapine therapy in severe mood disorders. J Clin Psychiatry 1995; 56: 108-112.
• 45 Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KN, Daniel DG, Petty F, Centorrino F, Wang R, Grundy SL, Greaney MG, Jacobs TG, David SR, Toma V. Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. Am J Psychiatry 1999; 156: 702-709.
• 46 Tohen M, Jacobs TG, Grundy SL, McElroy SL, Banov MC, Janicak PG, Sanger T, Risser R, Zhang F, Toma V, Francis J, Tollefson GD, Breier A. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group. Arch Gen Psychiatry 2000; 57: 841-849.
• 47 Tohen M, Chengappa KN, Suppes T, Zarate Jr CA, Calabrese JR, Bowden CL, Sachs GS, Kupfer DJ, Baker RW, Risser RC, Keeter EL, Feldman PD, Tollefson GD, 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: 62-69.
• 48 Tohen M, Ketter TA, Zarate CA, Suppes T, Frye M, Altshuler L, Zajecka J, Schuh LM, Risser RC, Brown E, Baker RW. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Am J Psychiatry 2003; 160: 1263-1271.
• 49 Baker RW, Tohen M, Fawcett J, Risser RC, Schuh LM, Brown E, Stauffer VL, Shao L, Tollefson GD. Acute dysphoric mania: treatment response to olanzapine versus placebo. J Clin Psychopharmacol 2003; 23: 132-137.
• 50 Ketter TA, Winsberg ME, DeGolia SG, Dunai M, Tate DL, Strong CM. Rapid efficacy of olanzapine augmentation in nonpsychotic bipolar mixed states. J Clin Psychiatry 1998; 59: 83-85.
• 51 Zullino D, Baumann P. Olanzapine for mixed episodes of bipolar disorder. J Psychopharmacol 1999; 13: 198.
• 52 Sharma V, Pistor L. Treatment of bipolar mixed state with olanzapine. J Psychiatry Neurosci 1999; 24: 40-44.
• 53 Sachs GS, Grossman F, Ghaemi SN, Okamoto A, Bowden CL. 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 LN, Grossman F, Augustyns I, Vieta E, Ravindran AV. 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: 866-867.
• 56 Vieta E, Herraiz M, Parramon G, Goikolea JM, 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: 15-19.
• 57 DelBello MP, Schwiers ML, Rosenberg HL, Strakowski SM. A double-blind, randomized, placebocontrolled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry 2002; 41: 1216-1223.
• 58 Vieta E, Parramon G, Padrell E, Nieto E, Martinez-Aran A, Corbella B, Colom F, Reinares M, Goikolea JM, Torrent C. Quetiapine in the treatment of rapid cycling bipolar disorder. Bipolar Disord 2002; 4: 335-340.
• 59 Zarate Jr CA, Rothschild A, Fletcher KE, Madrid A, Zapatel J. Clinical predictors of acute response with quetiapine in psychotic mood disorders. J Clin Psychiatry 2000; 61: 185-189.
• 60 Keck Jr PE, Versiani M, Potkin S, West SA, 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: 741-748.
• 61 Keck Jr PE, 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: 1651-1658.
• 62 Post RM, Leverich GS, Nolen WA, Kupka RW, Altshuler LL, Frye MA, 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: 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 RM, Altshuler LL, Frye MA, Suppes T, Rush AJ, Keck Jr PE, McElroy SL, Denicoff KD, Leverich GS, Kupka R, NOlen WA. Rate of switch in bipolar patients prospectively treated with second- generation antidepressants as augmentation to mood stabilizers. Bipolar Disord 2001; 3: 259-265.
• 65 Peet M. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. Br J Psychiatry 1994; 164: 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: 249-255.
• 67 Ghaemi SN, Rosenquist KJ, Ko JY, Baldassano CF, Kontos NJ, Baldessarini RJ. Antidepressant treatment in bipolar versus unipolar depression. Am J Psychiatry 2004; 161: 163-165.
• 68 Bauer MS, Callahan AM, Jampala C, Petty F, Sajatovic M, Schaefer V, Wittlin B, Powell BJ. Clinical practice guidelines for bipolar disorder from the Department of Veterans Affairs. J Clin Psychiatry 1999; 60: 9-21.
• 69 Sachs GS, Printz DJ, Kahn DA, Carpenter D, Docherty JP. The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000. Postgrad Med 2000; Spec No 1-104.
• 70 Sachs GS. Decision tree for the treatment of bipolar disorder. J Clin Psychiatry 2003; 64 (Suppl. 08) 35-40.
• 71 Suppes T, Dennehy EB, Swann AC, Bowden CL, Calabrese JR, Hirschfeld RM, Keck Jr PE, Sachs GS, Crismon ML, Toprac MG, Shon SP. Report of the Texas Consensus Conference Panel on medication treatment of bipolar disorder 2000. J Clin Psychiatry 2002; 63: 288-299.
• 72 Goodwin GM. Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2003; 17: 149-173.
• 73 Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht RW, Vieta E, Möller HJ. 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: 5-13.
• 74 Grunze H, Walden J, Dittmann S, Berger M, Bergmann A, Braunig P, Dose M, Emrich HM, Gastpar M, Greil W, Krüger S, Möller HJ, Übelhack R. Psychopharmacotherapy of bipolar affective diseases. Nervenarzt 2002; 73: 4-17.
• 75 Licht RW, Vestergaard P, Kessing LV, Larsen JK, Thomsen PH. 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 (Suppl. 04) 1-50.
• 77 Hirschfeld RM, Baker JD, Wozniak P, Tracy K, Sommerville KW. 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: 841-846.
• 78 Oluboka OJ, Bird DC, Kutcher S, Kusumakar V. A pilot study of loading versus titration of valproate in the treatment of acute mania. Bipolar Disord 2002; 4: 341-345.
• 79 Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004; 65 (Suppl. 05) 7-12.
• 80 Easton MS, Janicak PG. Benzodiazepines (BZ) for the management of psychosis. Psychiatr Med 1991; 9: 25-36.
• 81 Menza MA, Harris D. Benzodiazepines and catatonia. An overview. Biol Psychiatry 1989; 26: 842-846.