title: Misdiagnosis, duration of untreated illness (DUI) and outcome in bipolar patients with psychotic symptoms: A naturalistic study.
abstract: BACKGROUND
  A number of data show the negative role of duration of untreated illness (DUI) on outcome in mood disorders, but no investigation has been carried out about the impact of this variable in bipolar disorder (BD) with psychotic symptoms. Clinical experience shows that many bipolar patients with psychotic symptoms receive other diagnoses and often are chronically treated with first generation antipsychotics, with the effect to reduce duration of untreated psychosis/untreated episode with psychotic symptoms (DUP), but not DUI. Purpose of the study was to define the rate of misdiagnosis and the impact of DUP/DUI on outcome of bipolar patients with psychotic symptoms.
  
  
  METHODS
  Clinical information (DUP, DUI, first received diagnosis) about bipolar outpatients with psychotic symptoms (N=240) were extrapolated through a retrospective review of the clinical charts, Lombardy database and, if necessary, through clinical interviews with patients and their relatives. Outcome measures included psychiatric and substance abuse comorbidity, occupational status, Global Assessment of Functioning (GAF), number of hospitalizations and of suicidal attempts, number of depressive/manic recurrences. Patients were divided in two groups according to the DUP (1 year) and DUI (8 years) median, and the groups were compared through analyses of variance (ANOVAs) for continuous variables or χ(2) tests for dichotomous ones. Multivariate analysis of variance (MANOVA) with duration of illness as covariate was then performed to eliminate the effect of this variable. Finally, binary logistic regressions were performed considering age at onset, DUI, DUP as independent variables and outcome variables as dependent ones (presence of hospitalizations/suicidal attempts, GAF scores<50, occupational status).
  
  
  RESULTS
  Most of patients (61.5%) received a first diagnosis different from BD with the most frequent DSM-diagnosis being delusional disorder (17.9%). Patients with longer DUP were not different in outcome measures with respect to patients with shorter DUP. Patients with a DUI >8 years presented higher number of hospitalizations (F=6.04, p=0.015), higher number of manic recurrences (F=5.25, p=0.023), higher number of depressive recurrences (F=7.13, p=0.008) and lower GAF scores (F=17.74, p<0.001). Statistical significance persisted for number of hospitalizations (p<0.001) and GAF scores (p=0.003) after MANOVA. Finally binary logistic regression showed that a longer DUI was predictive of GAF scores<50 (F=17.74, p<0.001).
  
  
  CONCLUSIONS
  More than half of bipolar patients with psychotic symptoms receive a different diagnosis at first contact with psychiatric services. DUI (but not DUP) is a predictor of outcome in bipolar patients with psychotic symptoms. This indicates that an early diagnosis and proper treatment with a mood stabilizer (or an atypical antipsychotic with mood stabilizing effects) may improve long-term outcome of these patients. In the light of the naturalistic design of the present paper, these results have to be considered as preliminary and have to be confirmed by prospective controlled studies.
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
authors.forename: A Carlo
authors.initials: AC
authors.lastname: Altamura
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. Electronic address: massimiliano.buoli@hotmail.it.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Buoli
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Caldiroli
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Lea
authors.initials: L
authors.lastname: Caron
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cumerlato Melter
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Dobrea
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cigliobianco
authors.affiliation: Department of Psychiatry, University of Milan, Fondazione IRCCS Ca׳Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zanelli Quarantini
mesh_terms: D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D015897:Comorbidity; D003951:Diagnostic Errors / Q000523:psychology / Q000706:statistics & numerical data*; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D012189:Retrospective Studies; D013406:Suicide, Attempted; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents
keywords: Duration of untreated illness (DUI); Misdiagnosis; Outcome; Psychotic bipolar disorder