Journal Mobile Options
Table of Contents
Vol. 43, No. 1, 2010
Issue release date: December 2009

Subsyndromal Mood Symptoms: A Useful Concept for Maintenance Studies of Bipolar Disorder?

Bauer M. · Glenn T. · Grof P. · Schmid R. · Pfennig A. · Whybrow P.C.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Objective: To explore the measurement of subsyndromal mood symptoms in relation to studies of maintenance therapy for bipolar disorder. Methods: Literature review of the Medline database using the following selection criteria: (1) ‘bipolar disorder’ plus ‘inter-episode or interepisode or subsyndromal or subclinical or residual or subthreshold’ and (2) ‘bipolar disorder’ plus ‘maintenance or prophylaxis or longitudinal’. Studies of children or adolescents and non-English-language reports were excluded. Results: Of the studies published between 1987 and October 2007, 77 articles about subsyndromal mood symptoms and 257 studies of maintenance therapy agents were found. Only 11 of the 257 studies of maintenance therapy agents discussed subsyndromal mood symptoms. Of the 77 articles, two thirds were published after 2000. Inconsistent definitions of subsyndromal mood symptoms and different evaluation tools and methodologies were used in the studies. Conclusions: There is a need to standardize definitions and validate measuring approaches for subsyndromal mood symptoms. However, when measured in both naturalistic studies and clinical trials, subsyndromal mood symptoms were frequently reported by patients receiving maintenance therapy and were associated with poor functioning. As with other chronic illnesses, knowledge of the patient’s perspective of daily morbidity is important for improving the clinical outcome. Studies of maintenance therapy for bipolar disorder, regardless of the approach, should measure subsyndromal mood symptoms as an additional outcome.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Angst J, Merikangas K, Scheidegger P, Wicki W: Recurrent brief depression: a new subtype of affective disorder. J Affect Disord 1990;19:87–98.
  2. Akiskal HS: The prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. J Clin Psychopharmacol 1996;16(2 suppl 1):4S–14S.

    External Resources

  3. Angst J, Merikangas K: The depressive spectrum: diagnostic classification and course. J Affect Disord 1997;45:31–39.
  4. Angst J: The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998;50:143–151.
  5. Akiskal HS, Pinto O: The evolving bipolar spectrum. Prototypes I, II, III, and IV. Psychiatr Clin North Am 1999;22:517–534.
  6. Angst J, Gamma A, Benazzi F, Ajdacic V, Eich D, Rossler W: Diagnostic issues in bipolar disorder. Eur Neuropsychopharmacol 2003;13(suppl 2):S43–S50.
  7. Benazzi F, Akiskal H: The duration of hypomania in bipolar-II disorder in private practice: methodology and validation. J Affect Disord 2006;96:189–196.
  8. Bauer M, Grof P, Rasgon NL, Marsh W, Munoz RA, Sagduyu K, et al: Self-reported data from patients with bipolar disorder: impact on minimum episode length for hypomania. J Affect Disord 2006;96:101–105.
  9. Bauer M, Glenn T, Grof P, Pfennig A, Rasgon NL, Marsh W, et al: Self-reported data from patients with bipolar disorder: frequency of brief depression. J Affect Disord 2007;101:227–233.
  10. Denicoff KD, Smith-Jackson EE, Disney ER, Suddath RL, Leverich GS, Post RM: Preliminary evidence of the reliability and validity of the prospective life-chart methodology (LCM-p). J Psychiatr Res 1997;31:593–603.
  11. Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, et al: The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002;59:530–537.
  12. Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, et al: A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 2003;60:261–269.
  13. Post RM, Denicoff KD, Leverich GS, Altshuler LL, Frye MA, Suppes TM, et al: Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH life chart method. J Clin Psychiatry 2003;64:680–690.
  14. Kupka RW, Luckenbaugh DA, Post RM, Suppes T, Altshuler LL, Keck PE Jr, et al: Comparison of rapid-cycling and non-rapid-cycling bipolar disorder based on prospective mood ratings in 539 outpatients. Am J Psychiatry 2005;162:1273–1280.
  15. Paykel ES, Abbott R, Morriss R, Hayhurst H, Scott J: Sub-syndromal and syndromal symptoms in the longitudinal course of bipolar disorder. Br J Psychiatry 2006;189:118–123.
  16. Kupka RW, Altshuler LL, Nolen WA, Suppes T, Luckenbaugh DA, Leverich GS: Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord 2007;9:531–535.
  17. Frye MA, Yatham LN, Calabrese JR, Bowden CL, Ketter TA, Suppes T, et al: Incidence and time course of subsyndromal symptoms in patients with bipolar I disorder: an evaluation of 2 placebo-controlled maintenance trials. J Clin Psychiatry 2006;67:1721–1728.
  18. Vieta E, Sánchez-Moreno J, Lahuerta J, Zaragoza S; EDHIPO Group (Hypomania Detection Study Group): Subsyndromal depressive symptoms in patients with bipolar and unipolar disorder during clinical remission. J Affect Disord 2008;107:169–174.
  19. Dion GL, Tohen M, Anthony WA, Waternaux CS: Symptoms and functioning of patients with bipolar disorder six months after hospitalization. Hosp Community Psychiatry 1988;39:652–657.
  20. Bauwens F, Tracy A, Pardoen D, Vander Elst M, Mendlewicz J: Social adjustment of remitted bipolar and unipolar out-patients. A comparison with age- and sex-matched controls. Br J Psychiatry 1991;159:239–244.
  21. Gitlin MJ, Swendsen J, Heller TL, Hammen C: Relapse and impairment in bipolar disorder. Am J Psychiatry 1995;152:1635–1640.
  22. Serretti A, Cavallini MC, Macciardi F, Namia C, Franchini L, Souery D, et al: Social adjustment and self-esteem in remitted patients with mood disorders. Eur Psychiatry 1999;14:137–144.
  23. Bauer MS, Kirk GF, Gavin C, Williford WO: Determinants of functional outcome and healthcare costs in bipolar disorder: a high-intensity follow-up study. J Affect Disord 2001;65:231–241.
  24. MacQueen GM, Marriott M, Begin H, Robb J, Joffe RT, Young LT: Subsyndromal symptoms assessed in longitudinal, prospective follow-up of a cohort of patients with bipolar disorder. Bipolar Disord 2003;5:349–355.
  25. Yatham LN, Lecrubier Y, Fieve RR, Davis KH, Harris SD, Krishnan AA: Quality of life in patients with bipolar I depression: data from 920 patients. Bipolar Disord 2004;6:379–385.
  26. Judd LL, Akiskal HS, Schettler PJ, Endicott J, Leon AC, Solomon DA, et al: Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study. Arch Gen Psychiatry 2005;62:1322–1330.
  27. Altshuler LL, Post RM, Black DO, Keck PE Jr, Nolen WA, Frye MA, et al: Subsyndromal depressive symptoms are associated with functional impairment in patients with bipolar disorder: results of a large, multisite study. J Clin Psychiatry 2006;67:1551–1560.
  28. Huxley N, Baldessarini RJ: Disability and its treatment in bipolar disorder patients. Bipolar Disord 2007;9:183–196.
  29. Goodnick PJ, Fieve RR, Schlegel A, Kaufman K: Inter-episode major and subclinical symptoms in affective disorder. Acta Psychiatr Scand 1987;75:597–600.
  30. Keller MB, Lavori PW, Kane JM, Gelenberg AJ, Rosenbaum JF, Walzer EA, et al: Subsyndromal symptoms in bipolar disorder. A comparison of standard and low serum levels of lithium. Arch Gen Psychiatry 1992;49:371–376.
  31. Kleindienst N, Greil W: Inter-episodic morbidity and drop-out under carbamazepine and lithium in the maintenance treatment of bipolar disorder. Psychol Med 2002;32:493–501.
  32. Tohen M, Bowden CL, Calabrese JR, Lin D, Forrester TD, Sachs GS, et al: Influence of sub-syndromal symptoms after remission from manic or mixed episodes. Br J Psychiatry 2006;189:515–519.
  33. Martinez-Aran A, Vieta E, Torrent C, Sanchez-Moreno J, Goikolea JM, Salamero M, et al: Functional outcome in bipolar disorder: the role of clinical and cognitive factors. Bipolar Disord 2007;9:103–113.
  34. Fava GA: Subclinical symptoms in mood disorders: pathophysiological and therapeutic implications. Psychol Med 1999;29:47–61.
  35. Benazzi F: Is 4 days the minimum duration of hypomania in bipolar II disorder? Eur Arch Psychiatry Clin Neurosci 2001;251:32–34.
  36. Altshuler LL, Gitlin MJ, Mintz J, Leight KL, Frye MA: Subsyndromal depression is associated with functional impairment in patients with bipolar disorder. J Clin Psychiatry 2002;63:807–811.
  37. Morriss R: Clinical importance of inter-episode symptoms in patients with bipolar affective disorder. J Affect Disord 2002;72 (suppl 1):S3–S13.
  38. Joffe RT, MacQueen GM, Marriott M, Trevor Young L: A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders. Bipolar Disord 2004;6:62–66.
  39. Marangell LB: The importance of subsyndromal symptoms in bipolar disorder. J Clin Psychiatry 2004;65(suppl 10):24–27.

    External Resources

  40. Denicoff KD, Leverich GS, Nolen WA, Rush AJ, McElroy SL, Keck PE, et al: Validation of the prospective NIMH-Life-Chart Method (NIMH-LCM-p) for longitudinal assessment of bipolar illness. Psychol Med 2000;30:1391–1397.
  41. Molnar G, Fava GA, Zielezny M, Spinks MT, Loretan A: Measurement of subclinical changes during lithium prophylaxis: a longitudinal study. Psychopathology 1987;20:155–161.
  42. Benazzi F: Prevalence and clinical correlates of residual depressive symptoms in bipolar II disorder. Psychother Psychosom 2001;70:232–238.
  43. Calabrese JR, Hirschfeld RM, Frye MA, Reed ML: Impact of depressive symptoms compared with manic symptoms in bipolar disorder: results of a U.S. community-based sample. J Clin Psychiatry 2004;65:1499–1504.
  44. Keitner GI, Solomon DA, Ryan CE, Miller IW, Mallinger A, Kupfer DJ, et al: Prodromal and residual symptoms in bipolar I disorder. Compr Psychiatry 1996;37:362–367.
  45. van Gorp WG, Altshuler L, Theberge DC, Wilkins J, Dixon W: Cognitive impairment in euthymic bipolar patients with and without prior alcohol dependence. A preliminary study. Arch Gen Psychiatry 1998;55:41–46.
  46. Thompson JM, Gallagher P, Hughes JH, Watson S, Gray JM, Ferrier IN, et al: Neurocognitive impairment in euthymic patients with bipolar affective disorder. Br J Psychiatry 2005;186:32–40.
  47. Robinson LJ, Ferrier IN: Evolution of cognitive impairment in bipolar disorder: a systematic review of cross-sectional evidence. Bipolar Disord 2006;8:103–116.
  48. Jaeger J, Berns S, Loftus S, Gonzalez C, Czobor P: Neurocognitive test performance predicts functional recovery from acute exacerbation leading to hospitalization in bipolar disorder. Bipolar Disord 2007;9:93–102.
  49. Goswami U, Sharma A, Khastigir U, Ferrier IN, Young AH, Gallagher P, et al: Neuropsychological dysfunction, soft neurological signs and social disability in euthymic patients with bipolar disorder. Br J Psychiatry 2006;188:366–373.
  50. Harvey AG, Schmidt DA, Scarna A, Semler CN, Goodwin GM: Sleep-related functioning in euthymic patients with bipolar disorder, patients with insomnia, and subjects without sleep problems. Am J Psychiatry 2005;162:50–57.
  51. Holmes MA, Erickson K, Luckenbaugh DA, Drevets WC, Bain EE, Cannon DA, et al: A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression. Poster session, 2nd Biennial Conference of the International Society for Bipolar Disorders, Edinburgh, August 2006.
  52. McElroy SL, Kotwal R, Keck PE, Akiskal HS: Comorbidity of bipolar and eating disorders: distinct or related disorders with shared dysregulations? J Affect Disord 2005;86:107–127.
  53. Bowden CL, Calabrese JR, Sachs G, Yatham LN, Asghar SA, Hompland M, 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.
  54. Tohen M, Greil W, Calabrese JR, Sachs GS, Yatham LN, Oerlinghausen BM, 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.
  55. Temple R: Are surrogate markers adequate to assess cardiovascular disease drugs? JAMA 1999;282:790–795.
  56. Evans WE, McLeod HL: Pharmacogenomics – drug disposition, drug targets, and side effects. N Engl J Med 2003;348:538–549.
  57. Boissel JP, Collet JP, Moleur P, Haugh M: Surrogate endpoints: a basis for a rational approach. Eur J Clin Pharmacol 1992;43:235–244.
  58. Fleming TR, DeMets DL: Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996;125:605–613.
  59. Wells KB: Treatment research at the crossroads: the scientific interface of clinical trials and effectiveness research. Am J Psychiatry 1999;156:5–10.
  60. Streiner DL: The 2 ‘Es’ of research: efficacy and effectiveness trials. Can J Psychiatry 2002;47:552–556.
  61. Solomon DA, Ristow WR, Keller MB, Kane JM, Gelenberg AJ, Rosenbaum JF, et al: Serum lithium levels and psychosocial function in patients with bipolar I disorder. Am J Psychiatry 1996;153:1301–1307.
  62. 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.
  63. Fava GA, Bartolucci G, Rafanelli C, Mangelli L: Cognitive-behavioral management of patients with bipolar disorder who relapsed while on lithium prophylaxis. J Clin Psychiatry 2001;62:556–559.
  64. Scott J, Garland A, Moorhead S: A pilot study of cognitive therapy in bipolar disorders. Psychol Med 2001;31:459–467.
  65. Lam DH, Watkins ER, Hayward P, Bright J, Wright K, Kerr N, et al: A randomized controlled study of cognitive therapy for relapse prevention for bipolar affective disorder: outcome of the first year. Arch Gen Psychiatry 2003;60:145–152.
  66. Miklowitz DJ, George EL, Richards JA, Simoneau TL, Suddath RA: A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder. Arch Gen Psychiatry 2003;60:904–912.
  67. Kukopulos A, Reginaldi D, Laddomada P, Floris G, Serra G, Tondo L: Course of the manic-depressive cycle and changes caused by treatment. Pharmakopsychiatr Neuropsychopharmakol 1980;13:156–167.
  68. Wehr TA, Goodwin FK, Wirz-Justice A, Breitmaier J, Craig C: 48-hour sleep-wake cycles in manic-depressive illness: naturalistic observations and sleep deprivation experiments. Arch Gen Psychiatry 1982;39:559–565.
  69. Acquadro C, Berzon R, Dubois D, Leidy NK, Marquis P, Revicki D, et al: Incorporating the patient’s perspective into drug development and communication: an ad hoc task force report of the Patient-Reported Outcomes (PRO) Harmonization Group meeting at the Food and Drug Administration, February 16, 2001. Value Health 2003;6:522–531.
  70. U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health: Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes 2006;4:79.
  71. Willke RJ, Burke LB, Erickson P: Measuring treatment impact: a review of patient-reported outcomes and other efficacy endpoints in approved product labels. Control Clin Trials 2004;25:535–552.
  72. Wells G, Boers M, Tugwell P: Low disease activity state in rheumatoid arthritis: concepts and derivation of minimal disease activity. Clin Exp Rheumatol 2006;24(6 suppl 43):S52–S59.
  73. Schärer LO, Hartweg V, Hoern M, Graesslin Y, Strobl N, Frey S, et al: Life charts on a palmtop computer: first results of a feasibility study with an electronic diary for bipolar patients. Bipolar Disord 2002;4(suppl 1):107–108.
  74. Bauer MS, Crits-Christoph P, Ball WA, Dewees E, McAllister T, Alahi P, et al: Independent assessment of manic and depressive symptoms by self-rating. Scale characteristics and implications for the study of mania. Arch Gen Psychiatry 1991;48:807–812.
  75. Bauer M, Grof P, Gyulai L, Rasgon N, Glenn T, Whybrow PC: Using technology to improve longitudinal studies: self-reporting with ChronoRecord in bipolar disorder. Bipolar Disord 2004;6:67–74.
  76. Bauer M, Wilson T, Neuhaus K, Sasse J, Pfennig A, Lewitzka U, et al: Self-reporting software for bipolar disorder: validation of ChronoRecord by patients with mania. Psychiatry Res 2008;159:359–366.
  77. Michalak EE, Yatham LN, Lam RW: Quality of life in bipolar disorder: a review of the literature. Health Qual Life Outcomes 2005;3:72.
  78. Kaufman KR: Comparative bioethics in bipolar and epilepsy research. Seizure 2002;11:51–56.
  79. Baldessarini RJ: A plea for integrity of the bipolar disorder concept. Bipolar Disord 2000;2:3–7.
  80. Rush AJ, Giles DE, Schlesser MA, Fulton CL, Weissenburger J, Burns C: The Inventory for Depressive Symptomatology (IDS): preliminary findings. Psychiatry Res 1986;18:65–87.
  81. Endicott J, Spitzer RL: A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978;35:837–844.
  82. Keller MB, Lavori PW, Friedman B, Nielsen E, Endicott J, McDonald-Scott P, et al: The Longitudinal Interval Follow-up Evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies. Arch Gen Psychiatry 1987;44:540–548.
  83. Angst J, Dobler-Mikola A, Binder J: The Zurich study – a prospective epidemiological study of depressive, neurotic and psychosomatic syndromes. I. Problem, methodology. Eur Arch Psychiatry Neurol Sci 1984;234:13–20.
  84. Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, Keck PE Jr, et al: Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry 2000;157:1873–1875.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50