Duration of untreated illness and suicide in bipolar disorder: a naturalistic study

  • A. Carlo Altamura
  • Bernardo Dell’Osso
  • Heather A. Berlin
  • Massimiliano Buoli
  • Roberta Bassetti
  • Emanuela Mundo
Original Paper


The aim of this naturalistic study was to evaluate the potential influence of the duration of untreated illness (DUI)—defined as the time elapsed between the occurrence of the first mood episode and the first adequate pharmacological treatment with mood stabilizers—on the clinical course of bipolar disorder (BD). Three hundred and twenty outpatients (n = 320) with a DSM-IV diagnosis of BD—either Type I or Type II—were interviewed; their clinical features were collected and they were naturalistically followed-up for 5 years. At the end of the follow-up observation, the sample was subdivided into two groups: one group with a DUI ≤2 years (n = 65) and another group with a DUI >2 years (n = 255). The main demographic and clinical variables were analyzed and compared between the two subgroups of patients using chi-square tests for dichotomous variables or Mann–Whitney U tests for continuous variables. Patients with a longer DUI showed a higher frequency of suicide attempts (Z = −2.11, P = 0.035), a higher number of suicide attempters (χ2 = 4.13, df = 1, P = 0.04), and a longer duration of illness (Z = −6.79, P < 0.0001) when compared to patients with a shorter DUI. Moreover, patients with a longer DUI had a depressive first episode more frequently than patients with a shorter DUI (χ2 = 11.28, df = 2, P = 0.004). A further analysis performed dividing the total sample into two subgroups on the basis of a DUI of 6 years (corresponding to the median value of the DUI in the study sample) confirmed prior findings. Results indicate a potential association between a longer DUI and a worse outcome in BD, particularly in terms of suicidality, and confirm the clinical relevance of early diagnosis and pharmacological intervention with mood stabilizers in BD.


Bipolar disorder Duration of untreated illness Suicidality Clinical course 


  1. 1.
    Altamura AC, Bassetti R, Sassella F, Salvadori D, Mundo E (2001) Duration of untreated psychosis as a predictor of outcome in first-episode schizophrenia: a retrospective study. Schizophr Res 52:29–36CrossRefPubMedGoogle Scholar
  2. 2.
    Altamura AC, Bassetti R, Bignotti S, Pioli R, Mundo E (2003) Clinical variables related to suicide attempts in schizophrenic patients: a retrospective study. Schizophr Res 60:47–55CrossRefPubMedGoogle Scholar
  3. 3.
    Altamura AC, Dell’Osso B, Mundo E, Dell’Osso L (2007) Duration of untreated illness in major depressive disorder: a naturalistic study. Int J Clin Pract 61:1697–1700CrossRefPubMedGoogle Scholar
  4. 4.
    Altamura AC, Dell’osso B, Vismara S, Mundo E (2008) May duration of untreated illness influence the long-term course of major depressive disorder? Eur Psychiatry 23:92–96CrossRefPubMedGoogle Scholar
  5. 5.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. Text revision, Washington, DCGoogle Scholar
  6. 6.
    American Psychiatric Association (2006) Practice guidelines for the treatment of psychiatric disorders (compendium). Arlington, VAGoogle Scholar
  7. 7.
    Angst J, Gerber-Werder R, Zuberbühler HU, Gamma A (2004) Is bipolar I disorder heterogeneous? Eur Arch Psychiatry Clin Neurosci 254:82–91CrossRefPubMedGoogle Scholar
  8. 8.
    Akiskal HS, Benazzi F (2005) Psychopathologic correlates of suicidal ideation in major depressive outpatients: is it all due to unrecognized (bipolar) depressive mixed states? Psychopathology 38:273–280CrossRefPubMedGoogle Scholar
  9. 9.
    Baethge C, Gruschka P, Smolka MN, Berghöfer A, Bschor T, Müller-Oerlinghausen B, Bauer M (2003) Effectiveness and outcome predictors of long-term lithium prophylaxis in unipolar major depressive disorder. J Psychiatry Neurosci 28:355–361PubMedGoogle Scholar
  10. 10.
    Baethge C, Tondo L, Bratti IM, Bschor T, Bauer M, Viguera AC, Baldessarini RJ (2003) Prophylaxis latency and outcome in bipolar disorders. Can J Psychiatry 48:449–457PubMedGoogle Scholar
  11. 11.
    de Diego-Adeliño J, Portella MJ, Puigdemont D, Pérez-Egea R, Alvarez E, Pérez V (2009) A short duration of untreated illness (DUI) improves response outcomes in first-depressive episodes. J Affect Disord (in press)Google Scholar
  12. 12.
    Duffy A (2000) Toward effective early intervention and prevention strategies for major affective disorders: a review of antecedents and risk factors. Can J Psychiatry 45:340–348PubMedGoogle Scholar
  13. 13.
    First MB, Spitzer RL, Gibbon M et al (1997) Structured clinical interview for DSM-IV Axis I (SCID-I), clinician version. American Psychiatric Press, Washington, DCGoogle Scholar
  14. 14.
    Goldberg JF, Ernst CL (2002) Features associated with the delayed initiation of mood stabilizers at illness onset in bipolar disorder. J Clin Psychiatry 63:985–991PubMedGoogle Scholar
  15. 15.
    Gonzalez-Pinto A, Mosquera F, Alonso M, López P, Ramírez F, Vieta E, Baldessarini RJ (2006) Suicidal risk in bipolar I disorder patients and adherence to long-term lithium treatment. Bipolar Disord 8:618–624CrossRefPubMedGoogle Scholar
  16. 16.
    Gormley N, O’Leary D, Costello F (1999) First admissions for depression: is the ‘no-treatment interval’ a critical predictor of time to remission? J Affect Disord 54:49–54CrossRefPubMedGoogle Scholar
  17. 17.
    Grunze H, Kasper S, Goodwin G, Bowden C, Möller HJ (2004) WFSBP Task Force on Treatment Guidelines for Bipolar Disorders. 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 5:20–35CrossRefGoogle Scholar
  18. 18.
    Harrigan SM, McGorry PD, Krstev H (2003) Does treatment delay in first-episode psychosis really matter? Psychol Med 33:97–110CrossRefPubMedGoogle Scholar
  19. 19.
    Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T (2005) Association between duration of untreated psychosis and outcome in cohorts of first-episode patients; a systematic review. Arch Gen Psychiatry 62:975–983CrossRefPubMedGoogle Scholar
  20. 20.
    Martinez JM, Marangell LB, Simon NM, Miyahara S, Wisniewski SR, Harrington J, Pollack MH, Sachs GS, Thase ME (2005) Baseline predictors of serious adverse events at one year among patients with bipolar disorder in STEP-BD. Psychiatr Serv 56:1541–1548CrossRefPubMedGoogle Scholar
  21. 21.
    Pompili M, Ehrlich S, De Pisa E, Mann JJ, Innamorati M, Cittadini A, Montagna B, Iliceto P, Romano A, Amore M, Tatarelli R, Girardi P (2007) White matter hyperintensities and their associations with suicidality in patients with major affective disorders. Eur Arch Psychiatry Clin Neurosci 257:494–499CrossRefPubMedGoogle Scholar
  22. 22.
    Rizzo CJ, Esposito-Smythers C, Swenson L, Birmaher B, Ryan N, Strober M, Chiappetta L, Valeri S, Hunt J, Axelson D, Leonard H, Keller M (2007) Factors associated with mental health service utilization among bipolar youth. Bipolar Disord 9:839–850PubMedGoogle Scholar
  23. 23.
    Rosa AR, Andreazza AC, Kunz M, Gomes F, Santin A, Sanchez-Moreno J, Reinares M, Colom F, Vieta E, Kapczinski F (2008) Predominant polarity in bipolar disorder: diagnostic implications. J Affect Disord 107:45–51CrossRefPubMedGoogle Scholar
  24. 24.
    Scott J, Eccleston D, Boys R (1992) Can we predict the persistence of depression? Br J Psychiatry 161:633–637CrossRefPubMedGoogle Scholar
  25. 25.
    Simon GE, Hunkeler E, Fireman B, Lee JY, Savarino J (2007) Risk of suicide attempt and suicide death in patients treated for bipolar disorder. Bipolar Disord 9:526–530CrossRefPubMedGoogle Scholar
  26. 26.
    Suominen K, Mantere O, Valtonen H, Arvilommi P, Leppämäki S, Paunio T, Isometsä E (2007) Early age at onset of bipolar disorder is associated with more severe clinical features but delayed treatment seeking. Bipolar Disord 9:698–705CrossRefPubMedGoogle Scholar
  27. 27.
    Tondo L, Isacsson G, Baldessarini RJ (2003) Suicidal behavior in bipolar disorder: risk and prevention. CNS Drugs 17:491–511CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • A. Carlo Altamura
    • 1
  • Bernardo Dell’Osso
    • 1
  • Heather A. Berlin
    • 2
  • Massimiliano Buoli
    • 1
  • Roberta Bassetti
    • 3
  • Emanuela Mundo
    • 1
  1. 1.Department of PsychiatryUniversity of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina ElenaMilanItaly
  2. 2.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA
  3. 3.Department of Clinical Sciences L. SaccoMilanItaly

Personalised recommendations