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Long-Term Prophylaxis in Bipolar Disorder

  • Therapy in Practice
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Abstract

Bipolar disorder is a major cause of disability, and the prevention of relapse is a key management goal. Pharmacological interventions, effectively delivered through enhanced clinical care, are central to long-term management.

This article summarises the available evidence for a range of pharmacological options, and provides guidance on common issues in clinical management in line with current practice guidelines. The use of medications for long-term prophylaxis should be considered in all patients meeting criteria for bipolar I disorder. Increasing high-quality evidence from randomised trials informs management decisions relating to both novel agents, such as lamotrigine and olanzapine, and longer-established therapies, such as lithium and valproate, in monotherapy. Medications taken long-term in bipolar disorder differ in the extent to which they protect against manic and depressive relapse. Consequently, the emerging challenge is to understand how combination treatments can enhance efficacy and effectiveness based on data from controlled trials rather than random polypharmacy.

Clinical care can be enhanced with effective education about the illness, and the use of strategies to improve treatment adherence and the recognition and management of Stressors or prodromal symptoms. Where available, a range of specific psychological interventions can be effective as an adjunct to medication.

When discontinuation of prophylaxis is necessary, gradual tapering of dose over weeks or months is recommended.

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References

  1. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349(9063): 1436–42

    Article  PubMed  CAS  Google Scholar 

  2. Malhi GS, Mitchell PB, Berk M, et al. Mood stabilizers: a labile label. Acta Psychiatr Scand Suppl 2005; (426): 5-6

  3. Goodwin GM, Young AH. The British Association for Psychopharmacology guidelines for treatment of bipolar disorder: a summary. J Psychopharmacol 2003; 17(4 Suppl.): 3–6

    PubMed  Google Scholar 

  4. Grunze H, Kasper S, Goodwin G, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders, part III: maintenance treatment. World J Biol Psychiatry 2004; 5(3): 120–35

    Article  PubMed  Google Scholar 

  5. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder. 2nd ed. Washington, DC: American Psychiatric Association, 2002

    Google Scholar 

  6. Yatham LN, Kennedy SH, 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; 7Suppl. 3: 5–69

    Article  PubMed  Google Scholar 

  7. Kessing LV, Hansen MG, Andersen PK, et al. The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders: a life-long perspective. Acta Psychiatr Scand 2004; 109(5): 339–44

    Article  PubMed  CAS  Google Scholar 

  8. Fagiolini A, Frank E, Scott JA, et al. Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Bipolar Disord 2005; 7(5): 424–30

    Article  PubMed  Google Scholar 

  9. Goodwin GM. Recurrence of mania after lithium withdrawal: implications for the use of lithium in the treatment of bipolar affective disorder. Br J Psychiatry 1994; 164(2): 149–52

    Article  PubMed  CAS  Google Scholar 

  10. Geddes JR, Burgess S, Hawton K, et al. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry 2004; 161(2): 217–22

    Article  PubMed  Google Scholar 

  11. Cipriani A, Wilder H, Hawton K, et al. Lithium in the prevention of suicidal behaviour and all-cause mortality in patients with mood disorders: a systematic review of randomised trials. Am J Psychiatry 2005; 162(10): 1805–19

    Article  PubMed  Google Scholar 

  12. Tondo L, Hennen J, Baldessarini RJ. Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand 2001; 104(3): 163–72

    Article  PubMed  CAS  Google Scholar 

  13. Bowden CL, Calabrese JR, McElroy SL, 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): 481–9

    Article  PubMed  CAS  Google Scholar 

  14. Macritchie KA, Geddes JR, Scott J, et al. Valproic acid, val-proate and divalproex in the maintenance treatment of bipolar disorder. Cochrane Database Syst Rev 2001; (3): CD003196

  15. Tohen M, Ketter TA, Zarate CA, et al. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Am J Psychiatry 2003; 160(7): 1263–71

    Article  PubMed  Google Scholar 

  16. Goodwin GM, Bowden CL, Calabrese JR, et al. A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry 2004; 65(3): 432–41

    Article  PubMed  CAS  Google Scholar 

  17. Tohen M, Greil W, Calabrese JR, 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(7): 1281–90

    Article  PubMed  Google Scholar 

  18. Tohen M, Calabrese JR, Sachs GS, et al. Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry 2006; 163(2): 247–56

    Article  PubMed  Google Scholar 

  19. Tohen M, Chengappa KN, Suppes T, et al. Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser vs mood stabiliser alone. Br J Psychiatry 2004; 184: 337–45

    Article  PubMed  Google Scholar 

  20. Davis JM, Janicak PG, Hogan DM. Mood stabilizers in the prevention of recurrent affective disorders: a meta-analysis. Acta Psychiatr Scand 1999; 100(6): 406–17

    Article  PubMed  CAS  Google Scholar 

  21. Greil W, Kleindienst N. The comparative prophylactic efficacy of lithium and carbamazepine in patients with bipolar I disorder. Int Clin Psychopharmacol 1999; 14(5): 277–81

    PubMed  CAS  Google Scholar 

  22. Hartong EG, Moleman P, Hoogduin CA, et al. Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients. J Clin Psychiatry 2003; 64(2): 144–51

    Article  PubMed  CAS  Google Scholar 

  23. Ghaemi SN, Lenox MS, Baldessarini RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry 2001; 62(7): 565–9

    Article  PubMed  CAS  Google Scholar 

  24. Altshuler L, Suppes T, Black D, et al. Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry 2003; 160(7): 1252–62

    Article  PubMed  Google Scholar 

  25. Soldani F, Ghaemi SN, Tondo L, et al. Relapse after antidepressant discontinuation. Am J Psychiatry 2004; 161(7): 1312–3 [author reply 1313]

    Article  PubMed  Google Scholar 

  26. McQuade RD, Sanchez R, Marcus R. Aripiprazole for relapse prevention in bipolar disorder: a 26-week placebo controlled study [abstract] Int J Neuropsychopharmacol 2004; 7(Suppl 1): 161

    Google Scholar 

  27. Denicoff KD, Smith-Jackson EE, Disney ER, et al. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry 1997; 58(11): 470–8

    Article  PubMed  CAS  Google Scholar 

  28. Geddes J, Goodwin G. Bipolar disorder: clinical uncertainty, evidence-based medicine and large-scale randomised trials. Br J Psychiatry 2001; 178Suppl. 41: S191–4

    Article  PubMed  Google Scholar 

  29. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  30. Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord 2000; 2 (3 Pt 2): 269–80

    Article  PubMed  CAS  Google Scholar 

  31. Scott J, Gutierrez MJ. The current status of psychological treatments in bipolar disorders: a systematic review of relapse prevention. Bipolar Disorders 2004; 6(6): 498–503

    Article  PubMed  Google Scholar 

  32. Suppes T, Baldessarini RJ, Faedda GL, et al. Discontinuation of maintenance treatment in bipolar disorder: risks and implications. Harv Rev Psychiatry 1993; 1(3): 131–44

    Article  PubMed  CAS  Google Scholar 

  33. Sproule BA, Hardy BG, Shulman KI. Differential pharmacokinetics of lithium in elderly patients. Drugs Aging 2000; 16(3): 165–77

    Article  PubMed  CAS  Google Scholar 

  34. Brockington IF. Motherhood and mental health. Oxford: Oxford University Press, 1996

    Google Scholar 

  35. Rosa FW. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med 1991; 324(10): 674–7

    Article  PubMed  CAS  Google Scholar 

  36. Kaneko S, Battino D, Andermann E, et al. Congenital malformations due to antiepileptic drugs. Epilepsy Res 1999; 33(2–3): 145–58

    Article  PubMed  CAS  Google Scholar 

  37. Hanson JW, Smith DW. The fetal hydantoin syndrome. J Pediatr 1975; 87(2): 285–90

    Article  PubMed  CAS  Google Scholar 

  38. Samren EB, van Duijn CM, Christiaens GC, et al. Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann Neurol 1999; 46(5): 739–46

    Article  PubMed  CAS  Google Scholar 

  39. Cohen LS, Friedman JM, Jefferson JW, et al. A reevaluation of risk of in utero exposure to lithium [published erratum appears in JAMA 1994 May 18; vn271 (19): 1485]. JAMA 1994; 271(2): 146–50

    Article  PubMed  CAS  Google Scholar 

  40. Brockington IF. Puerperal psychosis. In: Brockington IF, editor. Motherhood and mental health. Oxford: Oxford University Press, 1996: 200–84

    Google Scholar 

  41. Jones I, Craddock N. Bipolar disorder and childbirth: the importance of recognising risk. Br J Psychiatry 2005; 186: 453–4

    Article  PubMed  Google Scholar 

  42. Yonkers KA, Wisner KL, Stowe Z, et al. Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry 2004; 161(4): 608–20

    Article  PubMed  Google Scholar 

  43. Yoshida K, Smith B, Kumar R. Psychotropic drugs in mothers’ milk: a comprehensive review of assay methods, pharmacokinetics and of safety of breast-feeding. J Psychopharmacol 1999; 13(1): 64–80

    Article  PubMed  CAS  Google Scholar 

  44. Chaudron LH, Jefferson JW. Mood stabilizers during breastfeeding: a review. J Clin Psychiatry 2000; 61(2): 79–90

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Prof. G.M. Goodwin is in receipt of grant support from Sanofi-Aventis for the randomised trial BALANCE, has frequently spoken in industry-supported symposia and has advised most major pharmaceutical companies with an interest in this therapeutic area in the last 5 years. Dr M.J. Taylor has received an honorarium from AstraZeneca for workshop facilitation. Dr Taylor is funded by a Wellcome Trust Research Training Fellowship. No other external funding was used to assist in the preparation of this manuscript.

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  1. Department of Psychiatry, University of Oxford, Warneford Hospital, Warneford Lane, Oxford, OX3 7JX, UK

    Matthew J. Taylor & Guy M. Goodwin

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  1. Matthew J. Taylor
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Correspondence to Matthew J. Taylor.

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Taylor, M.J., Goodwin, G.M. Long-Term Prophylaxis in Bipolar Disorder. CNS Drugs 20, 303–310 (2006). https://doi.org/10.2165/00023210-200620040-00004

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