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Keywords:

  • age;
  • bipolar;
  • chronicity;
  • course;
  • onset;
  • outcome

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Abstract To study course and outcome of Bipolar II disorder, 217 major depressive episode (MDE) patients were interviewed with Structured Clinical Interview for DSM-IV. Patients with more than three MDE and patients with fewer MDE were compared. Patients with more than three MDE were 77.8%. Comparisons, controlled for confounding effects of age and illness duration, found that patients with many MDE had significantly lower age at onset and more chronicity. Results support subtyping of Bipolar II in a small good-outcome group, and a large moderate–poor-outcome group.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Course and outcome have been studied more often for Bipolar I than for Bipolar II disorder.1,2 Two groups of Bipolar I patients with different outcomes have been found: a smaller (20%–40%) Bipolar I good-outcome group, with remission between episodes, and a larger moderate–poor-outcome group.3,4 It is not known if Bipolar II could be divided into two similar groups with different prognoses. Diagnostic stability, differences in family history, female to male ratio, course, and lithium response, suggest that Bipolar II is distinct from Bipolar I.5–8 Chronicity (a sign of worse outcome) was found in 51.2% of Bipolar II patients.9 The study aim was a retrospective assessment of the course and outcome of Bipolar II. The identification of Bipolar II groups with different outcomes as well as the variables related to a worse outcome, have important prognostic and treatment implications suggesting early intervention, long-term treatment, and close monitoring of the worse outcome group.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

The study was conducted by a senior psychiatrist of the Department of Psychiatry, National Health Service, of Forlì in Italy. The author had spent 16 years treating mood disorders, and had research experience.8,10–19 The study was conducted in the author's private practice, because private practice is more representative of mood patients in Italy, where it is the first (or second, after family doctors) line of treatment for mood disorders. Most severe mood patients are usually treated in national psychiatric services or in university centres. Mood patients from academic centres are thought to be not representative of typical mood patients.20

Two hundred and seventeen consecutive Bipolar II outpatients, presenting for major depressive episode (MDE) treatment with minimal or no concurrent psychopharmacology, were included in the study over 2 years. Informed consent was obtained after the procedure was fully explained. Substance abuse and severe personality disorders (diagnosed by clinical interview following DSM-IV criteria) were not included, because they may be confused with Bipolar II.21 Patients had no clinically significant general medical illness. Patients were interviewed during the first visit with the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version, Mood Disorder module (SCID-CV),22 the Montgomery Asberg Depression Rating Scale (MADRS),23 and the Global Assessment of Functioning (GAF) Scale.6 Family members or close friends supplemented clinical information during the interview. The DSM-IV criteria for the diagnosis of Bipolar II disorder are: (a) presence or history of one or more major depressive episodes; (b) presence or history of at least one hypomanic episode; (c) there has never been a manic episode or a mixed episode; (d) the mood symptoms in criteria a and b are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified; and (e) the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. As the modal duration of hypomania is 1–3 days, DSM-IV 4 days minimum duration of hypomania was not followed.21‘At least some days’ of hypomania were required. Most patients had experienced 2–3 days of hypomania, and all had had more than one hypomanic episode. Axis I comorbidity diagnoses were made by SCID-CV interview, when comorbidity was spontaneously reported. The sample was divided in a group with history of more than three MDE (+ 3 MDE), and a group with history of three or fewer MDE (–3 MDE), following Winokur's subdivision of Bipolar I.24,25 The study was a cross-sectional study, and data on number of MDE were based on the patient interview, and on information from family members and close friends. Variables studied were age, gender, first MDE age at onset, duration of illness from onset of the first MDE, number of previous MDE, chronicity (MDE/MDE without full interepisode recovery lasting more than 2 years), atypical and psychotic features, axis I comorbidity, and MDE severity at intake. A T-test for means, a two-sample test of proportions, linear and logistic regression, were used (STATA 5; Stata Corporation, College Station, TX, USA, 1997). The P values were two-tailed, and probability was P < 0.05.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Of the sample, 77.8% were +3 MDE, and 22.1% were –3 MDE. Chronicity was present in 40.2%. Comparisons between the two groups are presented in Table 1. The +3 MDE group had significantly lower age, lower age at onset, longer duration of illness, and more chronicity. Linear regression found significant correlations between age and age at onset (F = 134.0, d.f. = 1,216, P = 0.0000), duration of illness (F = 115.9, d.f. = 1,216, P = 0.0000), and chronicity (F = 8.7, d.f. = 1,214, P = 0.0034), and between duration of illness and age at onset (F = 16.6, d.f. = 1,216, P = 0.0001), and chronicity (F = 10.6, d.f. = 1,214, P = 0.0013). Logistic regression between number of MDE (+3 MDE and –3 MDE) and chronicity, controlled for age and duration of illness, found a significant association (odds ratio = 3.4, z = 2.3, P = 0.020). Logistic regres-sion between number of MDE and age at onset, controlled for age and duration of illness, found a significant association (odds ratio = 8.46e–13, z = − 673.7, P = 0.000).

Table 1.  Comparisons between patients with more than three MDE (+ 3 MDE) and patients with three or fewer MDE (− 3 MDE)
Variable+ 3 MDE− 3 MDE
Mean (SD)/%n = 169n = 48t/zd.f.P
  1. MDE, major depressive episode; MADRS, Montgomery Asberg Depression Rating Scale; GAF, Global Assessment of Functioning Scale.

Age (years)42.2 (13.4)34.4 (13.6)3.52150.0005
Age at onset (years)24.6 (10.9)29.8 (12.9)− 2.72150.0056
Duration of illness (years)17.5 (10.7)4.6 (6.2)7.92150.0000
MADRS28.1 (8.9)29.5 (7.9)− 0.92150.3258
GAF54.6 (8.5)52.9 (6.5)1.22150.2011
Female gender71.064.50.8 0.3878
Psychotic features9.48.30.2 0.8156
Chronicity48.212.54.4 0.0000
Atypical features60.954.10.8 0.3972
Axis I comorbidity61.566.6− 0.6 0.5192

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

A large +3 MDE group, and a small –3 MDE group were found. The +3 MDE proportion (77.8%) was in the range (63%–91%) found in Bipolar I with more than three episodes.2 Bipolar II chronicity (40.2%) was in line with a recent study.9 Comparisons between the two groups found significantly lower age at onset and more chronicity in the +3 MDE group. Differences were still significant when controlled for the confounding effects of age and illness duration differences. Different chronicity (48.2%vs 12.5%) suggests better outcome in the –3 MDE group. As different age at onset supports subtyping of mood disorders, different age at onset in the two groups suggests distinct subtypes: a good-outcome and a moderate–poor-outcome group.26 A good-outcome and moderate– poor-outcome group were observed also in Bipolar I.3,4 Prepharmacology era Bipolar I with more than three episodes had lower age at onset than Bipolar I with fewer episodes, as in the present Bipolar II study.2 In Bipolar I studies, associations were found among more than three episodes, higher age, and lower age at onset, and among more episodes, chronicity, and longer duration of illness, as in the present Bipolar II study.3,25,27 An association among lower age at onset, number of episodes, and poor outcome was found in a mixed sample of Bipolar I and Bipolar II.28 The worse outcome of the +3 MDE Bipolar II group may be related to increased chronicity caused by repeated episodes.29 The –3 MDE Bipolar II group had a better outcome but, as duration of illness was short, the number of episodes might increase with time leading to more chronicity. Logistic regression was used to control for this confounding factor. A significant association was still found between –3 MDE and less chronicity. The –3 MDE good-outcome group had later age at onset, supporting its separation from the +3 MDE poor-outcome group. However, only a long-term, prospective study could definitely show if later onset is associated with better outcome in Bipolar II, as suggested by Bipolar I studies.3,25,27,28 Variables which would be useful to support the subtyping (e.g. family history, treatment response, laboratory results, symptomatic profile) were not recorded. The clinical implications of the present study are important. Early treatment of Bipolar II, and prevention of recurrences, may improve long-term outcome by reducing the number of episodes and the related chronicity. As early-onset Bipolar II may have a worse outcome than late-onset Bipolar II, early intervention, close monitoring, and long-term treatment may be needed in this group.

The limitations of the study include: the moderate severity sample, the single interviewer and the non-blind, cross-sectional assessment. Substance abuse and severe personality disorders were excluded (eliminating a cause of Bipolar II misdiagnosis). Axis I comorbidity was not systematically assessed, leading to underreporting, but probably not affecting the selection bias. The clinical picture of DSM-IV hypomania is not clearly different from that of mania, and differential diagnosis depends on severity.6,21 Distinction between unipolar and Bipolar II depression is often based on a history of hypomania, which limits reliability.21 Unless skilfully interviewed about past hypomania, Bipolar II depression can be missed.21 A validated structured interview, a senior clinical and mood disorder research psychiatrist, presence of family members or close friends during the interview, standard assessment of all consecutive patients, and a systematic interview about past hypomania, may have reduced these limitations.2,5,6,21,26 The generality of the results might seem limited by the setting of the study (private practice). However, in Italy, private practice Bipolar patients are more representative of the Bipolar population because the Bipolar patients treated in the national health service or in university centres are usually the most severe. Mood disorder patients from academic centres are thought to be not representative of typical mood disorder patients.20

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES
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