Download PDF
Psychiatr Prax 2001; 28: 32-40
DOI: 10.1055/s-2001-15385
© Georg Thieme Verlag Stuttgart · New York

Die prophylaktische Langzeitbehandlung affektiver Störungen mit Lithium, Valproat und Carbamazepin

Ein Überblick zur Wirksamkeit und KosteneffektivitätProphylactic Long-Term Therapy of Affective Disorders with Lithium, Valproic Acid and Carbamazepine - Effectiveness and Cost-EffectivenessChristiane Roick1 , Bernd Ahrens2 , Thomas Becker1
  • 1Klinik für Psychiatrie, Universität Leipzig
  • 2Klinik für Psychiatrie und Psychotherapie, Medizinische Universität zu Lübeck
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die Public-Health-Relevanz phasischer affektiver Erkrankungen (Morbidität, Mortalität, Lebensqualität, Kosten) ist groß. Deshalb werden Therapiestudien mit Lithium, besonders zum Routineeinsatz der Substanz und zu Kostenaspekten im Überblick diskutiert. Aktuelle Übersichten bestätigen die prophylaktische Wirksamkeit von Lithium bei bipolaren affektiven Störungen. Allerdings ist die Lithiumresponserate im Routineeinsatz (effectiveness) niedriger als in kontrollierten Studien (efficacy). Non-Compliance ist ein wichtiger Grund dafür. In neueren Studien ist die Lithiumresponserate zudem wahrscheinlich aufgrund veränderter Diagnosegewohnheiten und eines breiteren Einsatzes niedriger. Therapieabbrüche unter Lithium begünstigen Rückfälle und erhöhen die Behandlungskosten. Deshalb kann Valproat hinsichtlich der Behandlungskosten Vorteile haben. Eine suizidpräventive Wirkung ist bislang nur für Lithium belegt. Für die optimale Nutzung des Lithiumpotenzials ist eine Complianceverbesserung wesentlich. In künftigen Studien müssen detailliertere Vergleiche zwischen Lithium, Valproat, Carbamazepin und neueren Behandlungsalternativen erfolgen.

Prophylactic Long-Term Therapy of Affective Disorders with Lithium, Valproic Acid and Carbamazepine - Effectiveness and Cost-Effectiveness

Affective disorders have a substantial public health impact due to morbidity, mortality, quality of life impairment and economic implications. There has been renewed debate of the efficacy and effectiveness of Lithium in long-term treatment of affective disorders. In the present paper current literature is discussed with a focus on the routine use of Lithium (effectiveness) and on cost aspects. Recent reviews have confirmed the prophylactic efficacy of Lithium in bipolar affective disorders. However, there is some evidence that effectiveness studies do not hold what efficacy research would promise. Non-compliance is likely to be a major reason for this. Lithium response rates have declined in recent studies. This may be related to diagnostic change (broader concept of affective disorders) and more widespread Lithium use. Non-compliance in patients taking Lithium is a primary factor in relapse with substantial cost effects (due to inpatient care). Current studies compare Lithium with Valproic acid/divalproex, and find cost advantages for the latter possibly due to better compliance. A special suicide-preventive effect has only been proven for Lithium. To ensure the full prophylactic potential of Lithium compliance needs to be improved. Future studies will compare Lithium with Valproic acid/divalproex, Carbamazepine and new treatment strategies more detailed.

Literatur

  • 1 Reifman A, Wyatt R J. Lithium: a brake in the rising cost of mental illness.  Arch Gen Psychiatry. 1980;  37 385-388
    PubMedGoogle Scholar
  • 2 Grof P. Has the effectiveness of lithium changed? Impact of the variety of lithium's effects.  Neuropsychopharmacology. 1998;  19 (3) 183-188
    CrossrefPubMedGoogle Scholar
  • 3 McCreadie R G. The epidemiology of lithium usage and its implications for health economics. In: Birch NJ Lithium: Inorganic Pharmacology and Psychiatric Use. Oxford; IRL Press 1988: 11-13
    Google Scholar
  • 4 Cording-Tömmel C, Wittchen H U, von Zerssen D. Evaluation des Verlaufs und Outcomes affektiver Psychosen. Implikationen für eine patientenorientierte Bedarfsplanung. In: Zweifel P (Hrsg) Bedarf und Angebotsplanung im Gesundheitswesen. Neue Ansätze der Bedarfsforschung und neue Formen der Angebotsplanung. Beiträge zur Gesundheitsökonomie, Bd. 17. Robert Bosch Stiftung. Gerlingen; Bleicher 1988: 179-222
    Google Scholar
  • 5 Olfson M, Pincus H A. Outpatient psychotherapy in the United States, II: patterns of utilization.  Am J Psychiatry. 1994;  151 1289-1294
    PubMedGoogle Scholar
  • 6 Johnson R E, McFarland B H. Lithium use and discontinuation in a health maintenance organization.  Am J Psychiatry. 1996;  153 993-1000
    PubMedGoogle Scholar
  • 7 Lehmann K, Ahrens B, Müller-Oerlinghausen B. Pharmakoökonomie der Lithiumprophylaxe. In: Müller-Oerlinghausen B, Greil W, Berghöfer A Die Lithiumtherapie, 2. Aufl. Berlin, Heidelberg, New York; Springer 1997: 457-466
    Google Scholar
  • 8 Baastrup P C, Poulsen J C, Schou M. et al . Prophylactic lithium: double-blind discontinuation in manic-depressive and recurrent-depressive disorders.  Lancet. 1970;  2 326-330
    PubMedGoogle Scholar
  • 9 Coppen A, Noguera R, Bailey J. et al . Prophylactic lithium in affective disorders: controlled trial.  Lancet. 1971;  2 275-279
    PubMedGoogle Scholar
  • 10 Hullin R P, McDonald R, Allsopp M NE. Prophylactic lithium in recurrent affective disorders.  Lancet. 1972;  1 1044-1046
    PubMedGoogle Scholar
  • 11 Stallone F, Shelley E, Mendlewicz J. et al . The use of lithium in affective disorders, III: a double-blind study of prophylaxis in bipolar illness.  Am J Psychiatry. 1973;  130 1006-1010
    PubMedGoogle Scholar
  • 12 Prien R F, Caffey E M, Klett C J. Prophylactic efficacy of lithium carbonate in manic-depressive illness.  Arch Gen Psychiatry. 1973;  28 337-341
    PubMedGoogle Scholar
  • 13 Suppes T, Baldessarini R J, Faedda G L. et al . Risk of recurrence following discontinuation of lithium treatment in bipolar disorder.  Arch Gen Psychiatry. 1991;  48 1082-1088
    PubMedGoogle Scholar
  • 14 Mander A J. Is there a lithium withdrawal syndrome?.  Br J Psychiatry. 1986;  149 498-501
    PubMedGoogle Scholar
  • 15 Moncrieff J. Lithium revisited. A re-examination of the placebo-controlled trials of lithium prophylaxis in manic-depressive disorder.  Br J Psychiatry. 1995;  167 569-573
    PubMedGoogle Scholar
  • 16 Markar H R, Mander A J. Efficacy of lithium prophylaxis in clinical practice.  Br J Psychiatry. 1989;  155 496-500
    PubMedGoogle Scholar
  • 17 Koufen H, Consbruch U. Langzeitkatamnese zur Frage von Nutzen und Nebenwirkungen der Lithiumprophylaxe der phasischen Psychosen.  Fortschr Neurol Psychiat. 1989;  57 374-382
    PubMedGoogle Scholar
  • 18 Harrow M, Goldberg J F, Grossman L S. et al . Outcome in manic disorders, a naturalistic follow-up study.  Arch Gen Psychiatry. 1990;  47 665-671
    PubMedGoogle Scholar
  • 19 Silverstone T, McPherson H, Hunt N. et al . How effective is lithium in the prevention of relapse in bipolar disorder? A prospective naturalistic follow-up study.  Aust NZ J Psychiatry. 1998;  32 61-66
    PubMedGoogle Scholar
  • 20 Jamison K R, Goodwin F K. Psychotherapeutic issues in bipolar illness, in Psychiatry Update. In: Grinspoon L The American Psychiatric Association Annual Review. Washington DC; American Psychiatric Association 1983 Vol. 2: 319-345
    Google Scholar
  • 21 Faedda G L, Tondo L, Baldessarini R J. et al . Outcome after rapid vs. gradual discontinuation of lithium treatment in bipolar disorder.  Arch Gen Psychiatry. 1993;  50 448-455
    CrossrefPubMedGoogle Scholar
  • 22 Bowden C L. Key treatment studies of lithium in manic-depressive illness: efficacy and side effects.  Journal of Clinical Psychiatry. 1998;  59 (6) 13-19
    PubMedGoogle Scholar
  • 23 Post R M, Leverich G S, Altschuler L. et al . Lithium discontinuation-induced refractoriness: Preliminary observations.  Am J Psychiat. 1992;  149 840-848
    PubMedGoogle Scholar
  • 24 Maj M, Pirozzi R, Magliano L. Nonresponse to reinstituted lithium prophylaxis in previously responsive bipolar patients: prevalence and predictors.  Am J Psychiatry. 1995;  152 1810-1811
    PubMedGoogle Scholar
  • 25 Tondo L, Baldessarini R J, Floris G. et al . Effectiveness of restarting lithium treatment after its discontinuation in bipolar I and bipolar II disorders.  Am J Psychiatry. 1997;  154 548-550
    PubMedGoogle Scholar
  • 26 Coryell W, Solomon D, Leon A C. et al . Lithium discontinuation and subsequent effectiveness.  Am J Psychiatry. 1998;  155 895-898
    PubMedGoogle Scholar
  • 27 Chen S T, Altshuler L L, Melnyk K A. et al . Efficacy of lithium vs. valproate in the treatment of mania in the elderly: a retrospective study.  J Clin Psychiatry. 1999;  60 (3) 181-186
    PubMedGoogle Scholar
  • 28 Gelenberg A J, Hopkins H S. Report on efficacy of treatments for bipolar disorder.  Psychopharmacol Bull. 1993;  29 (4) 447-456
    PubMedGoogle Scholar
  • 29 Bouman T K, Niemantsverdriet-van Kampen J G, Ormel J. et al . The effectiveness of lithium prophylaxis in bipolar and unipolar depressions and schizoaffective disorders.  J Affect Disord. 1986;  11 (3) 275-280
    CrossrefPubMedGoogle Scholar
  • 30 Himmelhoch J M, Garfinkel M E. Sources of lithium resistance in mixed mania.  Psychopharmacol Bull. 1986;  22 613-620
    PubMedGoogle Scholar
  • 31 Kukopulos A, Reginaldi D, Laddumada P. et al . Course of the manic-depressive cycle and changes caused by treatment.  Neuropsychopharmacology. 1980;  13 156-167
    PubMedGoogle Scholar
  • 32 Keller M B, Lavori P W, Coryell W. et al . Differential outcome in pure manic, mixed/cycling, and pure depressive episodes in patients with bipolar illness.  JAMA. 1986;  255 3138-3142
    CrossrefPubMedGoogle Scholar
  • 33 Maj M, Pirozzi R, Starace F. Previous pattern of course of the illness as a predictor of response to lithium prophylaxis in bipolar patients.  J Affect Disord. 1989;  17 237-241
    CrossrefPubMedGoogle Scholar
  • 34 Avery D, Winokur G. Mortality in depressed patients treated with electroconvulsive therapy and antidepressants.  Arch Gen Psychiatry. 1976;  33 1029-1037
    PubMedGoogle Scholar
  • 35 Schou M. The effect of prophylactic lithium treatment on mortality and suicidal behavior: a review for clinicans.  J Affect Disord. 1998;  50 253-259
    CrossrefPubMedGoogle Scholar
  • 36 Ahrens B, Müller-Oerlinghausen B, Grof P. Length of lithium treatment needed to eliminate the high mortality of affective disorders.  Br J Psychiatry. 1993;  163 (Suppl 21) 27-29
    PubMedGoogle Scholar
  • 37 Ahrens B, Grof P, Möller H J. et al . Extended survival of patients on long-term lithium treatment.  Can J Psychiatry. 40;  1995 241-246
    PubMedGoogle Scholar
  • 38 Ahrens B. Reduced mortality, the ultimate indicator of treatment efficacy.  Pharmacopsychiat. 1994;  27 (Suppl) 37-40
    PubMedGoogle Scholar
  • 39 Ahrens B, Müller-Oerlinghausen B, Schou M. et al . Excess cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis.  J Affect Disord. 1995;  33 67-75
    CrossrefPubMedGoogle Scholar
  • 40 Nilsson A. Mortality in recurrent mood disorders during periods on and off lithium. A complete population study in 362 patients.  Pharmacopsychiat. 1995;  28 8-13
    PubMedGoogle Scholar
  • 41 Armond A D. The social and economic effects of manic-depressive illness and of its treatment in lithium clinics.  Occup Med. 1998;  48 (8) 505-509
    PubMedGoogle Scholar
  • 42 McElroy S L, Keck P E, Pope H G. Sodium valproate: its use in primary psychiatric disorders.  J Clin Psychopharmacol. 1987;  7 16-24
    PubMedGoogle Scholar
  • 43 McElroy S L, Pope H G, Keck P E. et al . Treatment of psychiatric disorders with sodium valproate: a series of 73 cases.  Psychiatr Psychobiol. 1988;  3 81-85
    PubMedGoogle Scholar
  • 44 Placidi G F, Lenzi A, Lazzerini F. et al . The comparative efficacy and safety of carbamazepine versus lithium: a randomized, double-blind 3-year trial in 83 patients.  J Clin Psychiatry. 1986;  47 (10) 490-494
    PubMedGoogle Scholar
  • 45 Bowden C L, Brugger A M, Swann A C. et al . Efficacy of divalproex vs. lithium and placebo in the treatment of mania.  JAMA. 1994;  271 918-924
    CrossrefPubMedGoogle Scholar
  • 46 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
    PubMedGoogle Scholar
  • 47 Lambert P A, Venaud G. Etude comperative du valpromide versus lithium dans la prophylaxie des troubles thymiques.  Nervure. 1992;  5 57-65
    PubMedGoogle Scholar
  • 48 Keck P E, Nabulsi A A, Taylor J L. et al . A pharmacoeconomic model of divalproex vs. lithium in the acute and prophylactic treatment of bipolar I disorder.  J Clin Psychiatry. 1996;  57 213-222
    PubMedGoogle Scholar
  • 49 Hirschfeld R MA, Revicki D A, Keck P E. et al .Cost-effectiveness of divalproex sodium vs. lithium in long-term therapy for bipolar disorder. New research 686. Washington, DC; Presented at the 152nd annual meeting of the American Psychiatric Association 1999, May 20
    Google Scholar
  • 50 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 (5) 481-489
    CrossrefPubMedGoogle Scholar
  • 51 Schwartz T L, Boylan D, Kuhles D J. et al . Clinical effectiveness of divalproex Sodium in Lithium Carbonate Refractory Bipolar Spectrum Patients.  P&T. 2000;  25 (8) 410-417
    PubMedGoogle Scholar
  • 52 Conney J, Kaston B. Pharmacoeconomic and health outcome comparison of lithium and divalproex in a VA geriatric nursing home population: influence of drug-related morbidity on total cost of treatment.  Am J Manag Care. 1999;  5 197-204
    PubMedGoogle Scholar
  • 53 Müller-Oerlinghausen B, Wolf T, Ahrens B. et al . Mortality during initial and during later lithium treatment.  Acta Psychiatr Scand. 1994;  90 295-297
    PubMedGoogle Scholar
  • 54 Lerer B, Moore N, Meyendorff E. et al . Carbamazepine versus lithium in mania: a double-blind study.  J Clin Psychiatry. 1987;  48 89-93
    PubMedGoogle Scholar
  • 55 Small J G, Klapper M H, Milstein V. et al . Carbamazepine compared with lithium in the treatment of mania.  Arch Gen Psychiatry. 1991;  48 915-921
    PubMedGoogle Scholar
  • 56 Okuma T, Yamashita I, Takahashi R. et al . Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study.  Pharmacopsychiatry. 1990;  23 143-150
    PubMedGoogle Scholar
  • 57 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 (11) 470-478
    PubMedGoogle Scholar
  • 58 Watkins K, Callender D R, Thomas S F. et al . The effect of carbamazepine and lithium on remission from affective illness.  Br J Psychiatry. 1987;  150 180-182
    PubMedGoogle Scholar
  • 59 Greil W, Kleindienst N. The comparative prophylactic efficacy of lithium and carbamazepine in patients with bipolar I disorder.  Int Clin Psychopharmacol. 1999;  14 277-281
    CrossrefPubMedGoogle Scholar
  • 60 Greil W, Ludwig-Mayerhofer W, Erazo N. et al . Lithium vs. carbamazepine in the maintenance treatment of schizoaffective disorder: a randomised study.  Eur Arch Psychiatry Clin Neurosci. 1997;  247 42-50
    PubMedGoogle Scholar
  • 61 Simhandl C, Denk E, Thau K. The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders.  J Affect Disord. 1993;  28 221-231
    CrossrefPubMedGoogle Scholar
  • 62 Lusznat R, Murphy D P, Nunn C MH. Carbamazepine vs. lithium in the treatment and prophylaxis of mania.  Br J Psychiatry. 1988;  153 198-204
    PubMedGoogle Scholar
  • 63 Thies-Flechtner K, Müller-Oerlinghausen B, Seibert W. et al . Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Data from a randomized prospective study.  Pharmacopsychiatry. 1996;  29 103-107
    Google Scholar
  • 64 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 (10) 1456-1458
    PubMedGoogle Scholar
  • 65 Severus W E, Ahrens B. Omega-3-Fettsäuren in der Psychiatrie.  Der Nervenarzt. 2000;  1 58-62
    PubMedGoogle Scholar
  • 66 Müller-Oerlinghausen B, Berghöfer A, Bauer M. Rezidivprophylaxe bipolarer Störungen mit Lithium, Carbamazepin und Valproinsäure.  Psychopharmakotherapie. 2000;  7 (4) 146-154
    PubMedGoogle Scholar
  • 67 Robins L N, Regier D A. Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York; Free Press 1991
    Google Scholar
  • 68 Wyatt R J, Henter I. An economic evaluation of manic-depressive illness-1991.  Soc Psychiatry Psychiatr Epidemiol. 1995;  30 (5) 213-219
    PubMedGoogle Scholar
  • 69 Guscott R, Taylor L. Lithium prophylaxis in recurrent affective illness. Efficacy, effectiveness and efficiency.  Br J Psychiatry. 1994;  164 (6) 741-746
    PubMedGoogle Scholar
  • 70 Dardennes R, Lafuma A, Watkins S. Traitement préventif des troubles de l'humeur: comparaison cout-efficacité du lithium et de la carbamazépine.  L'Encéphale. 1999;  XXV 391-400
    PubMedGoogle Scholar
  • 71 Armond A D. Three Centuries without Lithium and Three and a Half Centuries on Lithium. In: Birch NJ, Padgham C, Huges MS Lithium in Medicine and Biology. Marius Press 1993
    Google Scholar
  • 72 Cusano P P, Mayo J, O'Connell R A. The medical economics of lithium treatment for manic-depressives.  Hosp Community Psychiatry. 1977;  28 169-173
    PubMedGoogle Scholar
  • 73 McCreadie R G. The Economics of Lithium Therapy. In: Johnson FN Depression and Mania: Modern Lithium Therapy. Oxford; IRL Press 1987: 257-259
    Google Scholar
  • 74 Keck P E, McElroy S L, Tugrul K C. et al . Valproate oral loading in the treatment of acute mania.  J Clin Psychiatry. 1993;  54 305-308
    PubMedGoogle Scholar
  • 75 Baker C B, Woods S W, Sernyak M J. Cost-effectiveness of divalproex versus lithium.  J Clin Psychiatry. 1997;  58 (8) 363
    PubMedGoogle Scholar
  • 76 Marken P A, McCray K E, Lacombe S. et al . Preliminary comparison of predictive and empiric lithium dosing: impact on patient outcome.  Ann Pharmacother. 1994;  28 1148-1152
    PubMedGoogle Scholar
  • 77 Keck P E, Bennett J A, Stanton S P. Dr. Keck and Colleagues Reply.  J Clin Psychiatry. 1997;  58 364
    PubMedGoogle Scholar
  • 78 Ushakov I UV, Kostiukova E G, Kalugina L I. et al . Sravnitelnaia otsenka klinicheskoi i ekonomicheskoi effektivnosti profilakticheskoi terapii affektivnykh i shizoaffektivnykh psikhozov.  Zh Nevropatol Psikhiatr Im S S Korsakova. 1990;  90 79-82
    PubMedGoogle Scholar
  • 79 Schou M. Has the time come to abandon prophylactic lithium treatment? A Review of Clinicians.  Pharmacopsychiat. 1998;  31 210-215
    PubMedGoogle Scholar
  • 80 Greil W, Ludwig-Mayerhofer W, Czernik A. et al .Lithium- oder Carbamazepinprophylaxe bei affektiven Psychosen?. In: Müller-Oerlinghausen B, Berghöfer A Ziele und Ergebnisse der medikamentösen Prophylaxe affektiver Psychosen. Stuttgart, New York; Thieme 1994: 113-120
    Google Scholar

Dr. med. Christiane Roick, MPH

Klinik und Poliklinik für Psychiatrie der Universität Leipzig

Johannisallee 20

04317 Leipzig

Email: roich@medizin.uni-leipzig.de

      >