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Fortschr Neurol Psychiatr 2009; 77(7): 389-398
DOI: 10.1055/s-0028-1109455
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Anwendung von Moodstabilizern in der Psychopharmakotherapie der Borderline-Persönlichkeitsstörung

Moodstabilizer in the Psychopharmacotherapy of Borderline Personality DisorderD. M. Gescher1 , J. Malevani1
  • 1Klinik und Poliklinik für Psychiatrie und Psychotherapie, Heinrich-Heine-Universität (Prof. Dr. med. W. Gaebel), Düsseldorf
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Publication History

Publication Date:
19 May 2009 (online)

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Zusammenfassung

Die Borderline-Persönlichkeitsstörung (BPS) ist charakterisiert durch ein instabiles Muster tiefgreifender Schwierigkeiten in den Bereichen der Perzeption, der interpersonellen Beziehungsgestaltung, der Affektregulation und der Impulskontrolle. In der Behandlung dieser komplexen Störung spielt neben anderen die Psychopharmakotherapie eine zentrale stützende Rolle und erfolgt, ausgerichtet auf die psychopathologisch führende Kerndimension, mit atypischen Antipsychotika, Antidepressiva oder Stimmungsstabilisatoren (Moodstabilizern). Oft ergibt sich aufgrund der Mehrschichtigkeit der Symptome eine Polypsychopharmazie aus mehreren Substanzklassen. In dieser Arbeit soll eine Übersicht über die Ergebnisse der Gesamtstudienlage an Moodstabilizern in der Pharmakotherapie der BPS gegeben werden; speziell wurde der Einsatz von Lithium, Carbamazepin, Valproat, Topiramat und Lamotrigin untersucht. Mit Hinblick auf das überwiegend junge, weibliche Patientenkollektiv ist wegen der teratogenen Risiken eine kritische Abwägung erforderlich. In der Auswertung zeigten sich ein signifikanter Wirkeffekt auf Kernsymptome der BPS für alle untersuchten Substanzen, jedoch auch deutliche Einschränkungen in der Vergleichbarkeit und Aussagekraft aufgrund der Heterogenität von Untersuchungskollektiv, Studiendesign, Begleitmedikation und Messinventar. Trotz bisher fehlender Zulassung spiegeln die Ergebnisse den mittlerweile klinisch etablierten Einsatz der Moodstabilizer in dieser Indikation wider und unterstreichen die spezifische Relevanz von Moodstabilizern in der gezielten Behandlung von Kernsymptomen der BPS.

Abstract

Borderline Personality Disorder (BPD) constitutes a profound instability with dysfunction in three psychopathological dimensions as cognitive-perceptual symptoms, affective dysregulation and behavioral impulsivity. Psychopharmacotherapy has a crucial role in the treatment of this complex disorder and targets the respective core symptoms. It comprises basically atypical antipsychotics, antidepressant agents and moodstabilizers, often requiring a combination of these substances in case of complex, multidimensional symptoms. Regarding the predominantly young and female patients the teratogenic risk demands critical consideration. This study focuses on the use of moodstabilizers in the treatment of BPD and gives an overview of the currently available studies on this substance class, in particular on lithium, carbamazepine, divalproex sodium, topiramate and lamotrigine. Results show significant effects on core features of BPD, but nevertheless, there are considerable limits in comparability and validity among the studies because of heterogeneities in the patient groups, study design, additive medication and outcome measures. Disregarding the off-label use in this indication the data reflect however an established clinical practice of use for these substances and underline the pivotal impact of moodstabilizers in the treatment of core symptoms of BPD.

Schlüsselwörter

Borderline-Persönlichkeitsstörung - Moodstabilizer - Psychopharmakotherapie - Affektinstabilität - Schwangerschaft

Key words

Borderline Personality Disorder - moodstabilizer - psychopharmacotherapy - affective dysregulation - pregnancy

Literatur

  • 1 Herman J L, Perry J C, Kolk B A. Childhood trauma in borderline personality disorder.  Am J Psychiatry. 1989;  146 490-495
    Google Scholar
  • 2 American Psychiatric Association . Practice guidelines for the treatment of patients with borderline personality disorder.  Am J Psychiatry. 2001;  158 1-52
    Google Scholar
  • 3 Zanarini M C, Frankenburg F R, Hennen van der J. et al . Mental health service utilization by borderline personality disorder patients and Axis II comparison subjects followed prospectively for 6 years.  J Clin Psychiatry. 2004;  65 28-33
    Google Scholar
  • 4 Schulz S C, Camlin K L, Berry S A. et al . Olanzapine safety and efficacy in patients with borderline personality disorder and comorbid dysthymia.  Biol Psychiatry. 1999;  46 1429-1435
    Google Scholar
  • 5 Zanarini M C, Frankenburg F R. Olanzapine treatment of female borderline personality disorder patients: a double-blind, placebo-controlled pilot study.  J Clin Psychiatry. 2001;  62 849-854
    Google Scholar
  • 6 Rocca P, Marchiaro L, Cocuzza E. et al . Treatment of borderline personality disorder with risperidone.  J Clin Psychiatry. 2002;  63 241-244
    Google Scholar
  • 7 Rinne T, Brink van den W, Wouters L. et al . SSRI treatment of borderline personality disorder: a randomized, placebo-controlled clinical trial for female patients with borderline personality disorder.  Am J Psychiatry. 2002;  159 2048-2054
    Google Scholar
  • 8 Pascual J C, Oller S, Soler J. et al . Ziprasidone in the acute treatment of borderline personality disorder in psychiatric emergency services.  J Clin Psychiatry. 2004;  65 1281-1282
    Google Scholar
  • 9 Simpson E B, Yen S, Costello E. et al . Combined dialectical behavior therapy and fluoxetine in the treatment of borderline personality disorder.  J Clin Psychiatry. 2004;  65 379-385
    Google Scholar
  • 10 Soler J, Pascual J C, Campins J. et al . Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder.  Am J Psychiatry. 2005;  162 1221-1224. Erratum in: Am J Psychiatry 2005;165
    Google Scholar
  • 11 Villeneuve E, Lemelin S. Open-label study of atypical neuroleptic quetiapine for treatment of borderline personality disorder: impulsivity as main target.  J Clin Psychiatry. 2005;  66 1298-1303
    Google Scholar
  • 12 Nickel M K, Muehlbacher M, Nickel C. et al . Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study.  Am J Psychiatry. 2006;  163 833-838
    Google Scholar
  • 13 Weih M, Thürauf N, Bleich S. et al . Off-Label-Use in der Psychiatrie.  Fortschr Neurol Psychiat. 2008;  76 7-13
    Google Scholar
  • 14 Clivaz E, Chauvet I, Zullino D. et al . Topiramate and Panic Attacs in Patients with Borderline Personality Disorder.  Pharmacopsychiatry. 2008;  41 79
    Google Scholar
  • 15 Geisler A, Klysner R. The effect of lithium in vitro and in vivo on dopamine-sensitive adenylate cyclase activity in dopaminergic areas of the rat brain.  Acta Pharmacol Toxicol. 1985;  56 1-5
    Google Scholar
  • 16 Massot O, Rousselle J C, Fillion M P. et al . 5-HT1B receptors: a novel target for lithium. Possible involvement in mood disorders.  Neuropsychopharmacology. 1999;  21 530-541
    Google Scholar
  • 17 Jope R S. Anti-bipolar therapy: mechanism of action of lithium.  Mol Psychiatry. 1999;  4 117-128. Review
    Google Scholar
  • 18 Williams M B, Jope R S. Lithium potentiates phosphoinositide-linked 5-HT receptor stimulation in vivo.  Neuroreport. 1994;  5 1118-1120
    Google Scholar
  • 19 Williams R, Ryves W J, Dalton E C. et al . A molecular cell biology of lithium.  Biochem Soc Trans. 2004;  32 799-802
    Google Scholar
  • 20 Zanarini M C, Frankenburg F R, Gunderson J G. Pharmacotherapy of borderline outpatients.  Compr Psychiatry. 1988;  29 372-378
    Google Scholar
  • 21 Gardner D L, Cowdry R W. Pharmacotherapy of borderline personality disorder: a review.  Psychopharmacol Bull. 1989;  25 515-523, Review
    Google Scholar
  • 22 Stein D J, Simeon D, Frenkel M. et al . An open trial of valproate in borderline personality disorder.  J Clin Psychiatry. 1995;  56 506-510
    Google Scholar
  • 23 Rifkin A, Quitkin F, Carrillo C. et al . Lithium carbonate in emotionally unstable character disorder.  Arch Gen Psychiatry. 1972;  27 519-523
    Google Scholar
  • 24 Links P, Steiner M, Boiago I. et al . Lithium therapy for borderline patients: preliminary findings.  J Personal Disord. 1990;  4 173-181
    Google Scholar
  • 25 Sheard M H. Effect of Lithium on human aggression.  Nature. 1971;  230 113-114
    Google Scholar
  • 26 Sheard M H, Marini J L, Bridges C I. et al . The effect of lithium on impulsive aggressive behavior in man.  Am J Psychiatry. 1976;  133 1409-1413
    Google Scholar
  • 27 Gardner D L, Cowdry R W. Positive effects of carbamazepine on behavioral dyscontrol in borderline personality disorder.  Am J Psychiatry. 1986;  143 519-522
    Google Scholar
  • 28 Cowdry R W, Gardner D L. Pharmacotherapy of borderline personality disorder. Alprazolam, carbamazepine, trifluoperazine, and tranylcypromine.  Arch Gen Psychiatry. 1988;  45 111-119
    Google Scholar
  • 29 Fuente J M, Lotstra de la F. A trial of carbamazepine in borderline personality disorder.  Eur Neuropsychopharmacol. 1994;  4 479-486
    Google Scholar
  • 30 Bellino S, Paradiso E, Bogetto F. Oxcarbazepine in the treatment of borderline personality disorder: a pilot study.  J Clin Psychiatry. 2005;  66 1111-115
    Google Scholar
  • 31 Denicoff K D, Meglathery S B, Post R M. et al . Efficacy of carbamazepine compare with other agents: a clinical practice survey.  J Clin Psychiatry. 1994;  55 70-76
    Google Scholar
  • 32 Mattes J. Comparative effectiveness of carbamazepine and propranolol for rage outbursts.  J Neuropsychiatry Clin Neurosci. 1990;  2 159-164
    Google Scholar
  • 33 Hori A. Pharmacotherapy for personality disorders.  Psychiatry Clin Neurosci. 1998;  52 13-19
    Google Scholar
  • 34 Kravitz H M, Fawcett J. Carbamazepine in the treatment of affective disorders.  Med Sci Res. 1987;  15 1-8
    Google Scholar
  • 35 Blumer D, Heibronn M, Himmelhoch J. Indications for carbamazepine in mental illness: atypical psychiatric disorder or temporal lobe syndrome?.  Compr Psychiatry. 1998;  29 108-122
    Google Scholar
  • 36 Polc P. Enhancement of GABAergic inhibition: a mechanism of action of benzodiazepines, phenobarbital, valproate and L-cycloserine in the cat spinal cord.  Electroencephalogr Clin Neurophysiol Suppl. 1982;  36 188-198
    Google Scholar
  • 37 Wilcox J. Divalproex sodium in the treatment of aggressive behavior.  Ann Clin Psychiatry. 1994;  6 17-20
    Google Scholar
  • 38 Hollander E, Allen A, Lopez R P. et al . A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder.  J Clin Psychiatry. 2001;  62 199-203
    Google Scholar
  • 39 Hollander E, Tracy K A, Swann A C. et al . Divalproex in the Treatment of Impulsive Aggression: Efficacy in Cluster B Personality Disorders.  Neuropsychopharmacology. 2003;  28 1186-1197
    Google Scholar
  • 40 Hollander E, Swann A C, Coccaro E F. et al . Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality disorder.  Am J Psychiatry. 2005;  162 621-624
    Google Scholar
  • 41 Frankenburg F R, Zanarini M C. Divalproex sodium treatment of women with borderline personality disorder and bipolar II disorder: a double-blind placebo-controlled pilot study.  J Clin Psychiatry. 2002;  63 442-446
    Google Scholar
  • 42 Steiner H, Petersen M L, Saxena K. et al . Divalproex sodium for the treatment of conduct disorder: a randomized controlled clinical trial.  J Clin Psychiatry. 2003;  64 1183-1191
    Google Scholar
  • 43 Wilcox J A. Divalproex sodium as a treatment for borderline personality disorder.  Ann Clin Psychiatry. 1995;  7 33-37
    Google Scholar
  • 44 Stein G. Drug treatment of the personality disorders.  Br J Psychiatry. 1992;  161 167-184, Review
    Google Scholar
  • 45 Kavoussi R J, Coccaro E F. Divalproex sodium for impulsive aggressive behavior in patients with personality disorder.  J Clin Psychiatry. 1998;  59 676-680
    Google Scholar
  • 46 Townsend M H, Cambre K M, Barbee J G. Treatment of borderline personality disorder with mood instability with divalproex sodium: series of ten cases.  J Clin Psychol. 2001;  21 249-251
    Google Scholar
  • 47 Simeon D, Baker B, Chaplin W. et al . An open-label trial of divalproex extended-release in the treatment of borderline personality disorder.  CNS Spectr. 2007;  12 439-443
    Google Scholar
  • 48 Xie X, Hagan R M. Cellular and molecular actions of Lamotrigine: possible mechanisms of efficacy in bipolar disorder.  Neuropsychobiology. 1998;  38 119-130
    Google Scholar
  • 49 Schmitz B, Bergmann L. Lamotrigin bei Frauen (The use of lamotrigine in female patients).  Nervenarzt. 2007;  78 912-22
    Google Scholar
  • 50 Tritt K, Nickel C, Lahmann C. et al . Lamotrigine treatment of aggression in female borderline-patients: a randomized, double-blind, placebo-controlled study.  J Psychopharmacol. 2005;  19 287-291
    Google Scholar
  • 51 Leiberich P, Nickel M K, Tritt K. et al . Lamotrigine treatment of aggression in female borderline patients, Part II: an 18-month follow-up.  J Psychopharmacol. 2008;  22 805-808
    Google Scholar
  • 52 Pavlovic Z M. Lamotrigine for the treatment of impulsive aggression and affective symptoms in a patient with borderline personality disorder comorbid with body dysmorphic disorder.  J Neuropsychiatry Clin Neurosci. 2008;  20 121-122
    Google Scholar
  • 53 Rizvi S T. Lamotrigine and borderline personality disorder.  J Child Adolesc Psychopharmacol. 2002;  12 365-366
    Google Scholar
  • 54 Pinto O C, Akiskal H S. Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder.  J Affect Disord. 1998;  51 333-343
    Google Scholar
  • 55 Preston G A, Marchant B K, Reimherr F W. et al . Borderline personality disorder in patients with bipolar disorder and response to lamotrigine.  J Affect Disord. 2004;  79 297-303
    Google Scholar
  • 56 Weinstein W W, Jamison K L. Retrospective Case Review of Lamotrigine use for affective instability of borderline personality disorder.  CNS Spetr. 2007;  12 207-210
    Google Scholar
  • 57 White H S, Brown S D, Woodhead J H. et al . Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold.  Epilepsy Rs. 1997;  28 167-179
    Google Scholar
  • 58 Nickel M K, Nickel C, Mitterlehner F O. et al . Topiramate treatment of aggression in female borderline personality disorder patients: a double-blind, placebo-controlled study.  J Clin Psychiatry. 2004;  65 1515-1519
    Google Scholar
  • 59 Nickel M K. Topiramate reduced aggression in female patients with borderline personality disorder.  Eur Arch Psychiatry Clin Neurosci. 2007;  257 432-433
    Google Scholar
  • 60 Nickel M K, Nickel C, Kaplan P. et al . Treatment of aggression with topiramate in male borderline patient: a double-blind, placebo-controlled study.  Biol Psychiatry. 2005;  57 495-499
    Google Scholar
  • 61 Nickel M K. Topiramate treatment of aggression in male borderline patients.  Aust N Z J Psychiatry. 2007;  41 (5) 461-462
    Google Scholar
  • 62 Nickel M K, Loew T H. Treatment of aggression with topiramate in male borderline patients part II: 1-month follow-up.  European Psychiatry. 2008;  23 115-117
    Google Scholar
  • 63 Loew T H, Nickel M K, Muehlbacher M. et al . Topiramate treatment for women with borderline personality disorder.  J Clin Psychopharmacol. 2006;  26 61-66
    Google Scholar
  • 64 Loew T H, Nickel M K. Topiramate treatment of women with borderline personality disorder, Part II: an open 18-month follow-up.  J Clin Psychopharmacol. 2008;  28 355-357
    Google Scholar
  • 65 Cassano P, Lattanzi L, Pini S. et al . Topiramate for self-mutilation in a patient with borderline personality disorder.  Bipolar Disord. 2001;  3 161
    Google Scholar
  • 66 Segal H D, Salgado B R, Garcia A C. et al . Efficacy of topiramate in children and adolescents with problems in impulse control: preliminary results.  Actas Esp Psiquiatr. 2006;  24 280-282
    Google Scholar
  • 67 Arntz A, Hoorn van den M, Cornelis J. et al . Reliability and validity of the borderline personality disorder severity index.  J Personal Disord. 2003;  17 45-59
    Google Scholar
  • 68 Bohus M, Limberger M F, Frank U. et al . Entwicklung der Borderline-Symptom-Liste.  Psychother Psychosom Med Psychol. 2001;  51 201-211
    Google Scholar
  • 69 Linehan M M, Armstrong H E, Suarez A. et al . Cognitive-behavioral treatment of chronically parasuicidal borderline patients.  Arch Gen Psychiatry. 1991;  48 1060-1064
    Google Scholar
  • 70 Linehan M. Dialektisch-behaviorale Therapie bei Borderline-Persönlichkeitsstörung. München; CIP Medien 1996
    Google Scholar
  • 71 Lieb K, Zanarini M C, Schmahl C. et al . Borderline personality disorder.  Lancet. 2004;  364 453-461
    Google Scholar
  • 72 Giesen-Bloo J, Dyck van R, Spinhoven P. et al . Outpatient psychotherapy for borderline personality disorder: randomized trial of schema-focused therapy vs transference-focused psychotherapy.  Arch Gen Psychiatry. 2006;  63 649-658. Erratum in: Arch Gen Psychiatry 2006;63
    Google Scholar
  • 73 Linehan M M, Comtois K A, Murray A M. et al . Two-year randomized controlled trial and follow-up of dialectical behavior therapy vs therapy by experts for suicidal behaviors and borderline personality disorder.  Arch Gen Psychiatry. 2006;  63 757-766
    Google Scholar
  • 74 Zanarini M C, Frankenburg F R, Hennen J. et al . The longitudinal course of borderline psychopathology. 6-year prospective follow-up of the phenomenology of borderline personality disorder.  Am J Psychiatry. 2003;  160 274-283
    Google Scholar
  • 75 Zanarini M C, Frankenburg F R, Reich D B. et al . The subsyndromal phenomenology of borderline personality disorder: a 10-year follow-up study.  Am J Psychiatry. 2007;  164 929-935
    Google Scholar

Dr. med. Dorothee Maria Gescher

Klinik und Poliklinik für Psychiatrie und Psychotherapie Heinrich-Heine-Universität

Bergische Landstr. 2

40629 Düsseldorf

Email: dorothee.gescher@lvr.de

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