Zusammenfassung
Die Behandlung der bipolaren Störung hat in den letzten Jahren einen Wandel erfahren: Bei leichten Verläufen von manischen und depressiven Episoden sind immer noch monotherapeutische Ansätze zielführend, wobei zunehmend häufiger neben den „klassischen” Medikamenten wie Lithium, Valproinsäure und Carbamazepin auch atypische Antipsychotika (AAP) eingesetzt werden. Für die Therapie der manischen Episode sind derzeit die meisten verfügbaren AAP zugelassen, und auch für die Rückfallprophylaxe und die Behandlung der depressiven Episode existieren bereits Zulassungen. Bei mittelschweren und schweren depressiven oder manischen Episoden werden zunehmend Kombinationen eingesetzt, da sie in der Regel schneller wirken und teilweise auch besser verträglich sind. In einer Vielzahl von Studien konnte die Überlegenheit der Kombinationsbehandlung im Gegensatz zu verschiedenen, etablierten Monotherapien gezeigt werden. Dieser Übersichtsartikel fasst die vorhandenen Studien und Ergebnisse mit Fokus auf die Kombinationsbehandlung zusammen, um aktuelle medikamentöse Therapieempfehlungen für eine effektive Behandlung der bipolaren Störung zu geben.
Abstract
In the course of time, the treatment regime of bipolar disorder has changed: in mild cases of manic and depressive episodes, monotherapeutic approaches are still commonly used. Besides the use of the common agents like lithium, valproatic acid and carbamazepine, other agents such as atypical antipsychotics (AAP) are used more frequently. For the therapy of manic episodes, most of the usual AAP are approved; some of them are or will be approved in the near future even for the continuation therapy and for depressive episodes. For moderate and severe courses of depressive or manic episodes, combination therapy strategies are used more often. Combination strategies seem to be more effective than monotherapeutic treatments, because of faster effects and better tolerance. In a lot of studies, these positive effects and advantages in contrast to monotherapeutic treatments could be proven. In this review article, studies and results with the focus on combination therapy will be summarised to recommend the ”state-of-the-art”-treatment for bipolar disorder.
Schlüsselwörter
bipolare Störung - Kombinationsbehandlung - Pharmakotherapie - Antipsychotika - Stimmungsstabilisierer
Key words
bipolar disorder - combination therapy - pharmacotherapy - antipsychotics - mood stabilizer
Literatur
-
1
Severus W E, Watzke S, Brieger P.
Bipolar affective disorders. Part II: Genetics, cognitions and therapy.
Fortschr Neurol Psychiatr.
2008;
76
294-304
-
2
Brieger P.
Bipolar affective disorders. Part I: diagnosis, epidemiology and course.
Fortschr Neurol Psychiatr.
2007;
75
673-682
-
3
Fountoulakis K N, Vieta E, Siamouli M. et al .
Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder.
Ann Gen Psychiatry.
2007;
6
27
-
4
Yatham L N, Kennedy S H, O’Donovan C. et al .
Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies.
Bipolar Disord.
2005;
7 (Suppl 3)
5-69
-
5
O’Dowd A.
NICE issues new guidance to improve the treatment of bipolar disorder.
BMJ.
2006;
333
220
-
6
American Psychiatric Association.
Practice guideline for the treatment of patients with bipolar disorder (revision).
Am J Psychiatry.
2002;
159
1-50
-
7
Muller-Oerlinghausen B, Ahrens B, Grof E. et al .
The effect of long-term lithium treatment on the mortality of patients with manic-depressive and schizoaffective illness.
Acta Psychiatr Scand.
1992;
86
218-222
-
8
Schou M.
Relapse prevention in manic depressive illness: important and unimportant factors.
Can J Psychiatry.
1991;
36
502-506
-
9
Roy-Byrne P P, Post R M, Hambrick D D. et al .
Suicide and course of illness in major affective disorder.
J Affect Disord.
1988;
15
1-8
-
10
Sussman N, Mullen J, Paulsson B. et al .
Rates of remission/euthymia with quetiapine in combination with lithium/divalproex for the treatment of acute mania.
J Affect Disord.
2007;
100 (Suppl 1)
S55-S63
-
11
Zarate C A, Quiroz J A.
Combination treatment in bipolar disorder: a review of controlled trials.
Bipolar Disord.
2003;
5
217-225
-
12
Miller D S, Yatham L N, Lam R W.
Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania.
J Clin Psychiatry.
2001;
62
975-980
-
13
Perlis R H.
Treatment of bipolar disorder: the evolving role of atypical antipsychotics.
Am J Manag Care.
2007;
13
S178-S188
-
14
Perlis R H, Welge J A, Vornik L A. et al .
Atypical antipsychotics in the treatment of mania: a meta-analysis of randomized, placebo-controlled trials.
J Clin Psychiatry.
2006;
67
509-516
-
15
Leverich G S, Altshuler L L, Frye M A. et al .
Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers.
Am J Psychiatry.
2006;
163
232-239
-
16
Young L T, Joffe R T, Robb J C. et al .
Double-blind comparison of addition of a second mood stabilizer versus an antidepressant to an initial mood stabilizer for treatment of patients with bipolar depression.
Am J Psychiatry.
2000;
157
124-126
-
17
Prien R F, Kupfer D J, Mansky P A. et al .
Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination.
Arch Gen Psychiatry.
1984;
41
1096-1104
-
18
Prien R F.
NIMH report. Five-center study clarifies use of lithium, imipramine for recurrent affective disorders.
Hosp Community Psychiatry.
1984;
35
1097-1098
-
19
Sachs G S, Nierenberg A A, Calabrese J R. et al .
Effectiveness of adjunctive antidepressant treatment for bipolar depression.
N Engl J Med.
2007;
356
1711-1722
-
20
Merkl Jr A, Regen F, Schindler F. et al .
Mixed episodes in bipolar disorder: a review.
Fortschr Neurol Psychiatr.
2007;
75
323-330
-
21
Grunze H, Kasper S, Goodwin G. et al .
World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of bipolar disorders. Part I: Treatment of bipolar depression.
World J Biol Psychiatry.
2002;
3
115-124
-
22
Post R M, Leverich G S, Altshuler L. et al .
Lithium-discontinuation-induced refractoriness: preliminary observations.
Am J Psychiatry.
1992;
149
1727-1729
-
23
Smith L A, Cornelius V, Warnock A. et al .
Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials.
Bipolar Disord.
2007;
9
394-412
-
24
Calabrese J R, Rapport D J.
Mood stabilizers and the evolution of maintenance study designs in bipolar I disorder.
J Clin Psychiatry.
1999;
60 (Suppl 5)
5-13
-
25
Bowden C L, Calabrese J R, McElroy S L. et al .
A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group.
Arch Gen Psychiatry.
2000;
57
481-489
-
26
Freeman T W, Clothier J L, Pazzaglia P. et al .
A double-blind comparison of valproate and lithium in the treatment of acute mania.
Am J Psychiatry.
1992;
149
108-111
-
27
Calabrese J R, Rapport D J, Kimmel S E. et al .
Rapid cycling bipolar disorder and its treatment with valproate.
Can J Psychiatry.
1993;
38
S57-S61
-
28
Davis L L, Bartolucci A, Petty F.
Divalproex in the treatment of bipolar depression: a placebo-controlled study.
J Affect Disord.
2005;
85
259-266
-
29
Gyulai L, Bowden C L, McElroy S L. et al .
Maintenance efficacy of divalproex in the prevention of bipolar depression.
Neuropsychopharmacology.
2003;
28
1374-1382
-
30
Owen R T.
Extended-release carbamazepine for acute bipolar mania: a review.
Drugs Today.
2006;
42
283-289
-
31
Hartong E G, Moleman P, Hoogduin C A. et al .
Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients.
J Clin Psychiatry.
2003;
64
144-151
-
32
Bowden C L, Calabrese J R, Sachs G. et al .
A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder.
Arch Gen Psychiatry.
2003;
60
392-400
-
33
Brown E B, McElroy S L, Keck P E. et al .
A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression.
J Clin Psychiatry.
2006;
67
1025-1033
-
34
Calabrese J R, Goldberg J F, Ketter T A. et al .
Recurrence in bipolar I disorder: a post hoc analysis excluding relapses in two double-blind maintenance studies.
Biol Psychiatry.
2006;
59
1061-1064
-
35
Calabrese J R, Bowden C L, Sachs G S. et al .
A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group.
J Clin Psychiatry.
1999;
60
79-88
-
36
Kushner S F, Khan Jr A, Lane R. et al .
Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials.
Bipolar Disord.
2006;
8
15-27
-
37
Vieta E, Manuel G J, Martinez-Aran A. et al .
A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive gabapentin for bipolar disorder.
J Clin Psychiatry.
2006;
67
473-477
-
38
Smith L A, Cornelius V, Warnock A. et al .
Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials.
Bipolar Disord.
2007;
9
551-560
-
39
Rendell J M, Gijsman H J, Bauer M S. et al .
Risperidone alone or in combination for acute mania.
Cochrane Database Syst Rev.
2006;
CD004043
-
40
Gopal S, Steffens D C, Kramer M L. et al .
Symptomatic remission in patients with bipolar mania: results from a double-blind, placebo-controlled trial of risperidone monotherapy.
J Clin Psychiatry.
2005;
66
1016-1020
-
41
Tohen M, Jacobs T G, Grundy S L. et al .
Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzapine HGGW Study Group.
Arch Gen Psychiatry.
2000;
57
841-849
-
42
Tohen M, Greil W, Calabrese J R. et al .
Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial.
Am J Psychiatry.
2005;
162
1281-1290
-
43
Bowden C L, Grunze H, Mullen J. et al .
A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder.
J Clin Psychiatry.
2005;
66
111-121
-
44
Cookson J, Keck P E, Ketter T A. et al .
Number needed to treat and time to response/remission for quetiapine monotherapy efficacy in acute bipolar depression: evidence from a large, randomized, placebo-controlled study.
Int Clin Psychopharmacol.
2007;
22
93-100
-
45
Weisler R H, Calabrese J R, Thase M E. et al .
Efficacy of Quetiapine Monotherapy for the Treatment of Depressive Episodes in Bipolar I Disorder: A Post Hoc Analysis of Combined Results From 2 Double-Blind, Randomized, Placebo-Controlled Studies.
J Clin Psychiatry.
2008;
69
769-782
-
46
Altamura A C, Salvadori Jr D, Madaro D. et al .
Efficacy and tolerability of quetiapine in the treatment of bipolar disorder: preliminary evidence from a 12-month open-label study.
J Affect Disord.
2003;
76
267-271
-
47
Keck P E, Marcus Jr R, Tourkodimitris S. et al .
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
-
48
Keck P E, Calabrese J R, McQuade R D. et al .
A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder.
J Clin Psychiatry.
2006;
67
626-637
-
49
Keck Jr P E, Calabrese J R, McIntyre R S. et al .
Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo.
J Clin Psychiatry.
2007;
68
1480-1491
-
50
Thase M E, Jonas Jr A, Khan A. et al .
Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies.
J Clin Psychopharmacol.
2008;
28
13-20
-
51
Keck P E, Versiani Jr M, Potkin S. et al .
Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial.
Am J Psychiatry.
2003;
160
741-748
-
52
Potkin S G, Keck P E, Segal Jr S. et al .
Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial.
J Clin Psychopharmacol.
2005;
25
301-310
-
53
Versiani M.
Ziprasidone in bipolar disorder.
Expert Opin Pharmacother.
2006;
7
1221-1228
-
54
Pande A C, Crockatt J G, Janney C A. et al .
Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group.
Bipolar Disord.
2000;
2
249-255
-
55
Muller-Oerlinghausen B, Retzow A, Henn F A. et al .
Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter study. European Valproate Mania Study Group.
J Clin Psychopharmacol.
2000;
20
195-203
-
56
Tohen M, Chengappa K N, Suppes T. et al .
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
-
57
Sachs G S, Grossman F, Ghaemi S N. et al .
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
-
58
Yatham L N, Grossman F, Augustyns I. et al .
Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial.
Br J Psychiatry.
2003;
182
141-147
-
59
Vieta E, Herraiz M, Parramon G. et al .
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
-
60
Vieta E, T’joen C, McQuade R D. et al .
Efficacy of Adjunctive Aripiprazole to Either Valproate or Lithium in Bipolar Mania Patients Partially Nonresponsive to Valproate/Lithium Monotherapy: A Placebo-Controlled Study.
Am J Psychiatry.
2008;
165
1316-1325
-
61
Sajatovic M, Brescan D W, Perez D E. et al .
Quetiapine alone and added to a mood stabilizer for serious mood disorders.
J Clin Psychiatry.
2001;
62
728-732
-
62
Delbello M P, Kowatch R A, Adler C M. et al .
A double-blind randomized pilot study comparing quetiapine and divalproex for adolescent mania.
J Am Acad Child Adolesc Psychiatry.
2006;
45
305-313
-
63
Sachs G, Chengappa K N, Suppes T. et al .
Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study.
Bipolar Disord.
2004;
6
213-223
-
64
Yatham L N, Paulsson B, Mullen J. et al .
Quetiapine versus placebo in combination with lithium or divalproex for the treatment of bipolar mania.
J Clin Psychopharmacol.
2004;
24
599-606
-
65
Yatham L N, Vieta E, Young A H. et al .
A double blind, randomized, placebo-controlled trial of quetiapine as an add-on therapy to lithium or divalproex for the treatment of bipolar mania.
Int Clin Psychopharmacol.
2007;
22
212-220
-
66
Vieta E, Panicali F, Goetz I. et al .
Olanzapine monotherapy and olanzapine combination therapy in the treatment of mania: 12-week results from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) observational study.
J Affect Disord.
2008;
106
63-72
-
67
Wehr T A, Goodwin F K.
Rapid cycling in manic-depressives induced by tricyclic antidepressants.
Arch Gen Psychiatry.
1979;
36
555-559
-
68
Quitkin F M, Kane J, Rifkin A. et al .
Prophylactic lithium carbonate with and without imipramine for bipolar 1 patients. A double-blind study.
Arch Gen Psychiatry.
1981;
38
902-907
-
69
Denicoff K D, Smith-Jackson E E, Disney E R. et al .
Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder.
J Clin Psychiatry.
1997;
58
470-478
-
70
Solomon D A, Ryan C E, Keitner G I. et al .
A pilot study of lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder.
J Clin Psychiatry.
1997;
58
95-99
-
71
Denicoff K D, Smith-Jackson E E, Bryan A L. et al .
Valproate prophylaxis in a prospective clinical trial of refractory bipolar disorder.
Am J Psychiatry.
1997;
154
1456-1458
-
72
Tohen M, Chengappa K N, Suppes T. et al .
Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone.
Br J Psychiatry.
2004;
184
337-345
-
73
Vieta E, Goikolea J M, Corbella B. et al .
Risperidone safety and efficacy in the treatment of bipolar and schizoaffective disorders: results from a 6-month, multicenter, open study.
J Clin Psychiatry.
2001;
62
818-825
-
74
Yatham L N, Binder C, Riccardelli R. et al .
Risperidone in acute and continuation treatment of mania.
Int Clin Psychopharmacol.
2003;
18
227-235
-
75
Vieta E, Suppes T, Eggens I. et al .
Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126).
J Affect Disord.
2008;
109
251-263
-
76
Altamura A C, Mundo E, Dell’Osso B. et al .
Quetiapine and classical mood stabilizers in the long-term treatment of Bipolar Disorder: A 4-year follow-up naturalistic study.
J Affect Disord.
2008;
110
135-141
-
77
Sachs G S, Lafer B, Stoll A L. et al .
A double-blind trial of bupropion versus desipramine for bipolar depression.
J Clin Psychiatry.
1994;
55
391-393
-
78
Nemeroff C B, Evans D L, Gyulai L. et al .
Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression.
Am J Psychiatry.
2001;
158
906-912
-
79
Young L T, Joffe R T, Robb J C. et al .
Double-blind comparison of addition of a second mood stabilizer versus an antidepressant to an initial mood stabilizer for treatment of patients with bipolar depression.
Am J Psychiatry.
2000;
157
124-126
-
80
Vieta E, Martinez-Aran A, Goikolea J M. et al .
A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers.
J Clin Psychiatry.
2002;
63
508-512
-
81
Tohen M, Vieta E, Calabrese J. et al .
Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.
Arch Gen Psychiatry.
2003;
60
1079-1088
Dr. med. Arnim Quante
Klinik und Hochschulambulanz für Psychiatrie und Psychotherapie, Charité – Campus Benjamin Franklin
Eschenallee 3
14050 Berlin
Email: arnim.quante@charite.de
