452017

2012
ANP461110.1177/0004867412452017Bauer et al.ANZJP Articles

Research

Australian & New Zealand Journal of Psychiatry

Brief depressive symptoms in patients 46(11) 1068­–1078

DOI: 10.1177/0004867412452017

with bipolar disorder: Analysis of long- © The Royal Australian and

New Zealand College of Psychiatrists 2012

term self-reported data Reprints and permission:

sagepub.co.uk/journalsPermissions.nav
anp.sagepub.com

Michael Bauer1, Tasha Glenn2, Michael Keil1, Rita Bauer3, Wendy

Marsh4, Paul Grof 5,6, Martin Alda7, Kemal Sagduyu8, Greg Murray9,
Danilo Quiroz10, Christopher Baethge11 and Peter C Whybrow12

Abstract
Objective: Most patients with bipolar disorder experience depressive symptoms outside of an episode of depression
as defined by DSM-IV criteria. This study explores the frequency of brief depressive episodes, lasting 1 to 4 days, using
daily self-reported mood ratings.
Method: Mood ratings were obtained from 448 patients (281 bipolar I, 167 bipolar II) using ChronoRecord software
(91,786 total days). Episodes of depression and days of depression outside of episodes were determined. The intensity
of depressive symptoms (mild versus moderate to severe) was compared.
Results: Using the DSM-IV length criteria, 61% of all depressive days occurred outside of a depressed episode. Decreas-
ing the minimum length criterion to 2 days, both the number of patients experiencing a depressed episode (128 to 317)
and the mean percent of days spent in a depressed episode by each patient (7.9% to 17.8.%) increased by about 2½
times, and 34.3% of depressed days remained outside of an episode. Depending on the episode length, the proportion
of days within an episode with severe symptoms varied from 1⁄3 to 1⁄4 for episodes lasting from 14 to 2 days, and 1⁄4 for
single-day episodes. There was no significant difference in the frequency of brief depressive episodes between bipolar I
and II disorders. For all episode lengths, patients taking antidepressants spent 4% more days within an episode and 6%
more days with depressive symptoms outside of an episode than those not taking antidepressants.
Conclusion: Brief depressive episodes lasting 1 to 4 days occur frequently in bipolar disorder and do not distinguish
between bipolar I and II disorders. Symptoms of moderate to severe intensity occur on 1⁄4 to 1⁄3 of the days in brief
depressive episodes. This study did not address brief depression in those without bipolar disorder. Patients taking anti-
depressants experienced more brief depressive episodes. Controlled trials are needed to assess the impact of antide-
pressants on subsyndromal depressive symptoms.

Keywords
Bipolar disorder, brief depressive episode, subsyndromal symptoms

1Department of Psychiatry and Psychotherapy, Universitätsklinikum
Carl Gustav Carus, Technische Universität Dresden, Dresden,
Germany
2ChronoRecord Association, Inc., Fullerton, USA
3Department of Psychiatry and Psychotherapy, University Medical
Center Regensburg, Regensburg, Germany
4Department of Psychiatry, University of Massachusetts School of
Medicine, Worcester, USA
5Department of Psychiatry, University of Toronto, Toronto, Canada
6Mood Disorders Center of Ottawa, Ottawa, Canada
7Department of Psychiatry, Dalhousie University, Halifax,
Canada
8Department of Psychiatry, University of Missouri Kansas City School of
Medicine, Kansas City, USA
9Facultyof Life and Social Sciences, Swinburne University of
Technology, Melbourne, Australia
10Mood Disorder Clinic EFESO, Santiago, Chile
11Department of Psychiatry and Psychotherapy, University of Cologne
Medical School, Cologne, Germany
12Department of Psychiatry and Biobehavioral Sciences, Semel Institute
for Neuroscience and Human Behavior University of California Los
Angeles (UCLA), Los Angeles, USA
Corresponding author:
Michael Bauer, Department of Psychiatry and Psychotherapy,
Universitätsklinikum Carl Gustav Carus, Technische Universität
Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Email: Michael.Bauer@uniklinikum-dresden.de

Australian & New Zealand Journal of Psychiatry, 46(11)

Bauer et al. 1069
Introduction
Depressive symptoms predominate in most patients with
bipolar disorder (Baldessarini et al., 2010; Judd et al., 2002,
2003a; Post et al., 2003). Frequently, these depressive
symptoms are brief in duration, do not meet the criteria for
a DSM-IV episode of depression, and are referred to as sub-
syndromal or subthreshold symptoms (Angst and
Merikangas, 1997; Bauer et al., 2007; Judd et al., 2002,
2003a; Paykel et al., 2006). Subsyndromal depressive
symptoms are associated with considerable functional and
psychosocial impairment (Altshuler et al., 2002; Bauer
et al., 2009; Goldberg and Harrow, 2011; Judd et al., 2005;
Marangell et al 2009), and an increased risk of relapse
(Perlis et al., 2006). We previously investigated the occur-
rence of brief depressive episodes lasting 2–4 days using
daily self-reported data from 203 patients who were diag-
nosed with bipolar disorder (Bauer et al., 2007). We found
that brief depressive episodes occurred frequently in both
bipolar I and bipolar II disorder, and that symptoms of
severe intensity occur during brief episodes in the same
proportion as in episodes that meet the DSM-IV criteria.
The purpose of this study is to repeat the prior analysis
using a larger sample, to include a length criterion of a sin-
gle day, and to further characterize the brief depressive epi-
sodes that occur in bipolar disorder.
Methods
All participants were outpatients, aged 18 years or older,
with a diagnosis of bipolar disorder by DSM-IV criteria that
was made by the prescribing psychiatrist during a clinical
interview. The participants agreed to record mood daily for 6
months using computer software in their native language
(ChronoRecord Association, Inc., Fullerton, CA, USA). All
participants volunteered, provided informed written consent,
and received pharmacological treatment as usual throughout
the study. The participants were recruited from university
mood clinics by the participating physicians, or by word of
mouth, and received no compensation other than being
allowed to use the software indefinitely. Data from our prior
investigation (Bauer et al., 2007) were included in this analy-
sis, although some patients provided additional data.
Daily mood ratings
All mood ratings were self-reported daily using Chrono
Record software. ChronoRecord was previously validated
with the Hamilton Depression Rating Scale (HAMD)
and Young Mania Rating Scale (YMRS), as described
elsewhere (Bauer et al., 2004, 2008). To record mood,
ChronoRecord contains a 100-unit visual analogue scale
between the extremes of mania and depression. During a half-
hour training session, personal anchor points were set by the
patient to describe the most depressed and most manic states
they ever experienced. The patient’s anchor point for mania,
and daily self-ratings of mania or hypomania reflect activa-
tion levels for either euphoric or dysphoric mood (Bauer
et al., 2004). The patients were instructed to enter a single
daily mood rating that best described their overall mood for
the prior 24 hours, and to calibrate the rating to their anchor
points. Based upon the validation studies (Bauer et al., 2004,
2008), a mood entry less than 40 was considered depression,
40–60 euthymia, and greater than 60 hypomania/mania. The
range of depression varied between mild symptoms (an entry
of 20–39) to moderate to severe symptoms (an entry of 0–19).
The range of mania varied from hypomania (an entry of 61–
80) to moderate to severe symptoms of mania (an entry of
81–100). Every day, the patients also recorded their sleep,
medications taken and any significant life events.
Data
Data were collected from 513 patients with bipolar disorder
who resided in the USA (361, 71%), Canada (58, 11%),
Germany (55, 11%), Poland (16, 3%), Chile (12, 2%) and
Australia (11, 2%). The demographic characteristics of the
513 patients were compared with other published studies of
patients with bipolar disorder in Table 1. Although the
patient sample in this study contains somewhat more
females and members of an ethnic minority, the demo-
graphic profile of the patients in this study was similar to
that of patients in other studies of bipolar disorder.
Statistical analysis
The demographic characteristics, mood ratings, and psycho-
tropic medications taken by the patients were obtained.
Patients were included in this analysis if they returned a
minimum of 150 days of data. To be considered using a
medication, a patient had to take any dose of the drug for at
least 50% of the days. The demographic characteristics and
medications of the patients with bipolar I and bipolar II dis-
order were compared using chi-squared tests for frequency
of categorical variables, or independent t-tests for mean val-
ues of continuous variables. Unequal variance was assumed
for all t-tests. Episodes of hypomania and depression based
on the DSM-IV length criteria were determined for each
patient using a published algorithm to calculate episodes
from daily self-reported mood data (Denicoff et al., 1997).
The episodes were then re-calculated using minimum length
criteria of 4, 3, 2, and 1 days. As the episode duration was
decreased, the mean percent of days in a depressed episode
was compared with that for 14 days using pairwise t-tests
for all patients. When comparing the mean percent of days
in a depressed episode between groups (bipolar I or bipolar
II, and patients taking or not taking antidepressants), inde-
pendent t-tests were used. A p-value of less than 0.05 was
considered statistically significant for all tests. SPSS 20.0
was used for all calculations.
Australian & New Zealand Journal of Psychiatry, 46(11)
1070 ANZJP Articles

Table 1.  Comparison of patient demographics with other studies of bipolar disorder.

ChronoRecord Step BD Stanley Registry Stanley Network BDI-BDC Judd Long-Term Study
(n = 513)a% (n = 1000)b% (n = 2839)c% (n = 261)d% (n = 217)e% (n = 206)f%

Age, mean 39 (11.4) 41 (12.6) Median 40.1 43 (1.3) 39 (12.6) 39 (13.5)

years (SD)

Sex
 Male 29 41 35 44 45 42
 Female 71 59 65 56 55 58

Ethnicity
 Caucasian 73 93 90 93  
 Other 27  7  7  

Marital status
 Married 47 36 33 43 36 45
 Separated/ 16 24 33 24 15 25
divorced
 Other 37 40 33 33 49 30

Education
 High school 15 18  7 34 42
or less
 Some college 85 82 60 93 66 58
or more

Employment status
 Full-time 47 35 39 24  
 Disabled 25 15 40  
 Other 28 50  

Age of onset, 22 (10.6) 17 (8.6) Mean 19.8 23 (10.4) 21 (7.9) 22 (9.9)

mean years (SD)

Diagnosis
  BP I 60 71 81 90 66
  BP II 35 24 16 10 34
  BP NOS/other  5  5  3  
a513in ChronoRecord database; 448 included in this analysis. bSystematic Treatment Enhancement Program for Bipolar Disorder (Kogan et al., 2004).
cStanleyCenter Bipolar Disorder Registry (Kupfer et al., 2002). dStanley Foundation Bipolar Network (Suppes et al., 2001). eBlack Dog Institute Bipolar
Disorders Clinic, Australia (Mitchell et al., 2009). fJudd Long-Term Study, results combined for 135 BPI and 71 BPII patients (Judd et al., 2003b).

Results
A total of 469 unique patients provided sufficient data to be
included in the study: 281 with a diagnosis of bipolar I disor-
der, 167 with bipolar II disorder, and 21 with bipolar NOS.
The small group with a diagnosis of bipolar NOS was
excluded, so a total of 448 patients were included in the anal-
ysis. The 448 patients returned a total of 91,786 days of data
(mean 204.9). There was no significant difference in the
mean days of data returned when comparing those with
bipolar I or II disorder (191.9 versus 226.7, p = 0.308), or
those taking or not taking antidepressants (189.9 versus
219.6, p = 0.333). The demographic characteristics of the
448 patients are shown in Table 2, comparing the patients
with bipolar I and bipolar II disorder. The patients with bipo-
lar I disorder had more hospitalizations (2.8 (SD 4.1) versus
1.7 (SD 4.2), p = 0.015), were less likely to be female (184,
66% versus 126, 75%, p = 0.027), were less likely to be tak-
ing antidepressants (118, 42% versus 104, 62%, p < 0.001) or
lamotrigine (91, 32% versus 76, 46%, p = 0.005) and more
likely to take lithium (87, 31% versus 32, 19%, p = 0.006)
than those with bipolar II disorder. No other significant dif-
ferences in demographic characteristics or medications were
found between those with bipolar I and bipolar II disorder.
Of the total 91,786 days of data from all patients, 18,845
(21%) were rated as depressed. Using the DSM-IV criteria,
128 (29%) patients experienced at least one depressed epi-
sode, with 39% of the 18,845 depressed days occurring

Australian & New Zealand Journal of Psychiatry, 46(11)

Bauer et al. 1071

Table 2.  Patient demographics (n = 448).

Bipolar I (n = 281) Bipolar II (n = 167) Total (n = 448) df p

Age, mean years (SD) 40.1 (11.1) 39.2 (11.6) 39.8 (11.3) 338.1a 0.466
Age of onset, mean years (SD) 22.3 (9.9) 21.1 (11.4) 21.9 (10.4) 274.3a 0.285
Years of illness, mean years (SD) 17.7 (11.9) 18.5 (13.0) 18.0 (12.3) 286.8a 0.531
Hospitalizations, mean n (SD) 2.8 (4.1) 1.7 (4.2) 2.4 (4.1) 306.8a 0.015
Sex
 Female, n (%) 184 (66) 126 (75) 310 (69) 1b 0.027
 Male, n (%) 97 (34) 41 (25) 138 (31)  
Education level
  High school, n (%) 40 (15) 20 (13) 60 (14) 2b 0.621
  Some college, n (%) 84 (32) 48 (30) 132 (32)  
  College graduate, n (%) 137 (53) 90 (57) 227 (54)  
Marital status
 Married, n (%) 119 (45) 81 (53) 200 (48) 2b 0.093
 Single, n (%) 100 (37) 55 (36) 155 (37)  
 Divorced, n (%) 49 (18) 17 (11) 66 (15)  
Number of daily medications, mean n (SD) 2.8 (1.7) 2.7 (1.6) 2.8 (1.6) 365.2a 0.423
Taking mood stabilizer, n (%) 231 (82) 125 (75) 356 (80) 1b 0.062
Taking lithium, n (%) 87 (31) 32 (19) 119 (27) 1b 0.006
Taking lamotrigine, n (%) 91 (32) 76 (46) 167 (37) 1b 0.005
Taking valproate, n (%) 49 (17) 25 (15) 74 (17) 1b 0.496
Taking antidepressants, n (%) 118 (42) 104 (62) 222 (50) 1b < 0.001
Taking antipsychotic, n (%) 128 (46) 65 (39) 193 (43) 1b 0.171
Taking benzodiazepine, n (%) 62 (22) 44 (26) 106 (24) 1b 0.302
Taking sleep medication, n (%) 20 (7) 10 (6) 30 (7) 1b 0.644
aStudent’s t-test, equal variances not assumed. bPearson chi-squared test.

within a depressed episode and 61% outside of an episode.
Table 3 presents the effects of decreasing the minimum
length criteria for an episode of depression. When the mini-
mum episode length was decreased from 14 to 2 days, there
was an increase of about 2½ times in both the number of
patients experiencing a depressed episode (128 to 317) and
the mean percent of days spent in a depressed episode by
each patient (7.9% to 17.8%). When the minimum episode
length was decreased to 2 days, 65.7% of depressed days
occurred in a depressed episode and 34.3% outside of an
episode. When the minimum episode length was decreased
from 14 days to 1 day, the number of patients experiencing
a depressed episode tripled (128 to 381), and the mean per-
cent of days spent in a depressed episode by each patient
was more than 2½ times greater (7.9% to 20.8%). With a
1-day length, some depressed days remained in hypomanic
episodes based on the algorithm. Using data from all
patients, the increase in the mean percent of days spent in
an episode as the minimum length decreased was signifi-
cant in all cases (p < 0.001 for all pairwise comparisons).
Of the total 18,854 depressed days, 4473 (24%) were
rated as having moderate to severe intensity. Using a 14-day
episode length, only 2505 (56%) of the 4473 days with
severe symptoms occurred within a depressed episode. As
shown in Table 4, patients routinely experienced symptoms
of moderate to severe intensity outside of DSM-IV episodes.
For patients with bipolar I disorder, the proportion of days
with severe symptoms within an episode ranged from 33.8%
with an episode length of 14 days to 25.7% with an episode
length of 2 days, and 23.0% for an episode length of 1 day.
For patients with bipolar II disorder, the proportion of days
with severe symptoms within an episode ranged from 34.5%
with an episode length of 14 days to 27.7% with an episode
length of 2 days, and 25.0% for an episode length of 1 day.
The pattern of change was also similar when comparing
patients taking or not taking antidepressants. Depending on

Australian & New Zealand Journal of Psychiatry, 46(11)

 Table 3.  Impact of changing the minimum episode length for depression on patients with bipolar disorder (n = 448).
1072

Depressed episode minimum length

  14 Days 4 Days 3 Days 2 Days 1 Day

14 to 1
  n % n % n % n % n % day% change

All patients (n = 448)

  Mean percent days in hypomanic episode  4.3% 4.1%  3.9%  3.6%  3.3% –23%
  Mean percent days in depressed episodea  7.9% 12.2% 15.0% 17.8% 20.8% 163%
  Number of hypomanic episodes 372 356 345 325 295 –21%
  Number of depressed episodes 376 762 1063 1695 3637 867%
  Number of patients with hypomanic episodes 117 118 117 114 106 –9%
  Number of patients with depressed episodes 128 212 255 317 381 198%

All hypomanic days (n = 7202)

  Percent hypomanic days in hypomanic episode 3162 43.9% 3086 42.8% 3019 41.9% 2908 40.4% 2765 38.4% –13%

Australian & New Zealand Journal of Psychiatry, 46(11)

  Percent hypomanic days not in hypomanic episode 4040 56.1% 4116 57.2% 4183 58.1% 4294 59.6% 4437 61.6% 10%

All depressed days (n = 18,854)

  Percent depressed days in depressed episode 7351 39.0% 9768 51.8% 10,961 58.1% 12,390 65.7% 14,242 75.5% 94%
  Percent depressed days not in depressed episode 11,503 61.0% 9086 48.2% 7893 41.9% 6464 34.3% 4612 24.5% –60%

All depressed days bipolar I (n = 11,113)

  Percent depressed days in depressed episode 4468 40.2% 5794 52.1% 6413 57.7% 7201 64.8% 8260 74.3% 85%
  Percent depressed days not in depressed episode 6645 59.8% 5319 47.9% 4700 42.3% 3912 35.2% 2853 25.7% –57%

All depressed days bipolar II (n = 7741)

  Percent depressed days in depressed episode 2883 37.2% 3974 51.0% 4548 58.8% 5189 67.0% 5982 77.3% 107%
  Percent depressed days not in depressed episode 4858 62.8% 3767 49.0% 3193 41.2% 2552 33.0% 1759 22.7% –64%

All depressed days taking antidepressants (n = 11,182)

  Percent depressed days in depressed episode 4472 40.0% 5884 52.6% 6534 58.4% 7305 65.3% 8338 74.6% 86%
  Percent depressed days not in depressed episode 6710 60.0% 5298 47.4% 4648 41.6% 3877 34.7% 2844 25.4% –58%

All depressed days not taking antidepressants (n = 7672)

  Percent depressed days in depressed episode 2879 37.5% 3884 50.6% 4427 57.7% 5085 66.3% 5904 77.0% 105%
  Percent depressed days not in depressed episode 4793 62.5% 3788 49.4% 3245 42.3% 2587 33.7% 1768 23.0% –63%
aComparison of mean percent days in depressed episode for the minimum number of depressed days for 14 vs 4, 14 vs 3, 14 vs 2, 14 vs 1, 4 vs 3, 4 vs 2, 4 vs 1, 3 vs 2, 3 vs 1, and 2 vs 1 days were all

significantly different by pairwise t-test with p < 0.001.

ANZJP Articles
 Table 4.  Impact of changing the minimum episode length on symptom severity (n = 448).

Depressed episode minimum length

Bauer et al.

  14 Days 4 Days 3 Days 2 Days 1 Day

  n % n % n % n % n %

All depressed days (n = 18,854)  

  Days in depressed episode
   Mild depressed days 4846 65.9% 6801 69.6% 7827 71.4% 9101 73.5% 10,843 76.1%
   Severe depressed days 2505 34.1% 2967 30.4% 3134 28.6% 3289 26.5% 3399 23.9%
   Total days in depressed episode 7351 100.0% 9768 100.0% 10,961 100.0% 12,390 100.0% 14,242 100.0%
  Days not in depressed episode
   Mild depressed days 9535 82.9% 7580 83.4% 6554 83.0% 5280 81.7% 3538 76.7%
   Severe depressed days 1968 17.1% 1506 16.6% 1339 17.0% 1184 18.3% 1074 23.3%
   Total days not in depressed episode 11,503 100.0% 9086 100.0% 7893 100.0% 6464 100.0% 4612 100.0%

All depressed days bipolar I (n = 11,113)

  Days in depressed episode
   Mild depressed days 2958 66.2% 4070 70.2% 4624 72.1% 5348 74.3% 6358 77.0%
   Severe depressed days 1510 33.8% 1724 29.8% 1789 27.9% 1853 25.7% 1902 23.0%
   Total days in depressed episode 4468 100.0% 5794 100.0% 6413 100.0% 7201 100.0% 8260 100.0%
  Days not in depressed episode
   Mild depressed days 5538 83.3% 4426 83.2% 3872 82.4% 3148 80.5% 2138 74.9%
   Severe depressed days 1107 16.7% 893 16.8% 828 17.6% 764 19.5% 715 25.1%
   Total days not in depressed episode 6645 100.0% 5319 100.0% 4700 100.0% 3912 100.0% 2853 100.0%

All depressed days bipolar II (n = 7741)

  Days in depressed episode
   Mild depressed days 1888 65.5% 2731 68.7% 3203 70.4% 3753 72.3% 4485 75.0%
   Severe depressed days 995 34.5% 1243 31.3% 1345 29.6% 1436 27.7% 1497 25.0%
   Total days in depressed episode 2883 100.0% 3974 100.0% 4548 100.0% 5189 100.0% 5982 100.0%
  Days not in depressed episode
   Mild depressed days 3997 82.3% 3154 83.7% 2682 84.0% 2132 83.5% 1400 79.6%
   Severe depressed days 861 17.7% 613 16.3% 511 16.0% 420 16.5% 359 20.4%
   Total days not in depressed episode 4858 100.0% 3767 100.0% 3193 100.0% 2552 100.0% 1759 100.0%

Australian & New Zealand Journal of Psychiatry, 46(11)

1073
 1074

Table 4. (Continued)

Depressed episode minimum length

  14 Days 4 Days 3 Days 2 Days 1 Day

  n % n % n % n % n %

All depressed days taking antidepressants (n = 11,182)

  Days in depressed episode
   Mild depressed days 2882 64.4% 4046 68.8% 4613 70.6% 5314 72.7% 6289 75.4%
   Severe depressed days 1590 35.6% 1838 31.2% 1921 29.4% 1991 27.3% 2049 24.6%
   Total days in depressed episode 4472 100.0% 5884 100.0% 6534 100.0% 7305 100.0% 8338 100.0%
  Days not in depressed episode

Australian & New Zealand Journal of Psychiatry, 46(11)

   Mild depressed days 5549 82.7% 4385 82.8% 3818 82.1% 3117 80.4% 2142 75.3%
   Severe depressed days 1161 17.3% 913 17.2% 830 17.9% 760 19.6% 702 24.7%
   Total days not in depressed episode 6710 100.0% 5298 100.0% 4648 100.0% 3877 100.0% 2844 100.0%

All depressed days not taking antidepressants (n = 7672)

  Days in depressed episode
   Mild depressed days 1964 68.2% 2755 70.9% 3214 72.6% 3787 74.5% 4554 77.1%
   Severe depressed days 915 31.8% 1129 29.1% 1213 27.4% 1298 25.5% 1350 22.9%
   Total days in depressed episode 2879 100.0% 3884 100.0% 4427 100.0% 5085 100.0% 5904 100.0%
  Days not in depressed episode
   Mild depressed days 3986 83.2% 3195 84.3% 2736 84.3% 2163 83.6% 1396 79.0%
   Severe depressed days 807 16.8% 593 15.7% 509 15.7% 424 16.4% 372 21.0%
   Total days not in depressed episode 4793 100.0% 3788 100.0% 3245 100.0% 2587 100.0% 1768 100.0%
ANZJP Articles
Bauer et al. 1075

the episode length, patients reported severe symptoms on
about ¼–⅓ of all days within episodes lasting 2–4 days, and
on ¼ of single-day episodes (Figure 1).
Regardless of episode length, there was no significant
difference in the distribution of patients with at least one
episode between those taking or not taking antidepressants.
However, patients taking antidepressants reported a larger
mean percent of depressed days, when considering all days
both within and outside of an episode, than those not taking
antidepressants (26.6% versus 18.8%, p = 0.001). The
mean percent of days spent in a depressed episode was sig-
nificantly larger for patients taking antidepressants by
about 4% for all episode lengths (Table 5A). The mean per-
cent of depressed days outside of an episode was also sig-
nificantly larger for patients taking antidepressants by
about 6% for all episode lengths (Table 6A). However, for
any episode length, there was no significant difference in
the mean percent of days with severe symptoms outside of
an episode between those taking and not taking antidepres-
sants (Table 6B).

Figure 1.  Distribution of depressed days by episode length and severity in patients with bipolar disorder.

Table 5A.  Percent of days in a depressed episode by episode length and taking antidepressants (n = 448).

Mean (SD) percent days in a depressed episode

Minimum depressed
episode length in daysa  Taking antidepressants (n = 222) Not taking antidepressants (n = 226) df tb p

14 Days 9.6% (18.5) 6.2% (14.7) 420.9 2.2 0.028

4 Days 14.4% (21.5) 10.1% (16.0) 408.7 2.4 0.015

3 Days 17.2% (22.7) 12.7% (17.8) 418.6 2.3 0.020

2 Days 20.0% (23.5) 15.6% (19.4) 428.2 2.2 0.030

1 Day 23.4% (23.8) 18.2% (20.4) 433.3 2.5 0.014

aFour-day hypomanic episode length for all depressed episode lengths. bUnequal variances assumed for t-test.

Table 5B.  Percent of days in a depressed episode by episode length and diagnosis (n = 448).

Mean (SD) percent days in a depressed episode

Minimum depressed episode length in daysa Bipolar I (n = 281) Bipolar II (n = 167) df tb p

14 Days   8.7% (17.8)   6.6% (14.7) 400.6 1.3 0.186

4 Days 12.9% (20.3) 11.1% (16.6) 402.9 1.0 0.308

3 Days 15.5% (21.7) 14.1% (18.2) 396.3 0.8 0.454

2 Days 18.3% (22.6) 17.0% (20.0) 382.9 0.6 0.538

1 Day 21.2% (23.1) 20.0% (20.8) 378.5 0.6 0.572

aFour-day hypomanic episode length for all depressed episode lengths. bUnequal variances assumed for t-test.

Australian & New Zealand Journal of Psychiatry, 46(11)

1076 ANZJP Articles

Table 6A.  Percent of depressed days not in a depressed episode-by-episode length and taking antidepressants (n = 448).

Mean (SD) percent depressed days not in a depressed episode

Minimum depressed
episode length in daysa Taking antidepressants (n = 222) Not taking antidepressants (n = 226) df tb p

14 Days 23.1% (25.0) 17.6% (21.6) 433.0 –2.5 0.014

4 Days 21.4% (25.4) 15.7% (21.2) 427.8 –2.6 0.011

3 Days 20.3% (26.3) 14.6% (21.1) 420.6 –2.5 0.013

2 Days 18.5% (26.8) 12.6% (21.1) 417.6 –2.6 0.010

1 Day 15.2% (27.7)   9.7% (21.5) 414.9 –2.3 0.020

aFour-day hypomanic episode length for all depressed episode lengths. bUnequal variances assumed for t-test.

Table 6B.  Percent of severe depressed days not in a depressed episode-by-episode length and taking antidepressants (n = 448).

Mean (SD) percent severe depressed days not in a depressed episode

Minimum depressed
episode length in daysa Taking antidepressants (n = 222) Not taking antidepressants (n = 226) df tb p

14 Days 6.0% (14.4) 4.6% (12.6) 434.5 –1.1 0.259

4 Days 5.7% (14.5) 4.1% (12.5) 432.3 –1.3 0.209

3 Days 5.6% (14.9) 3.9% (12.5) 428.7 –1.3 0.180

2 Days 5.5% (15.3) 3.7% (12.6) 425.6 –1.4 0.167

1 Day 5.2% (15.3) 3.4% (12.6) 425.7 –1.4 0.171

aFour-day hypomanic episode length for all depressed episode lengths. bUnequal variances assumed for t-test.

When considering all days both within and outside of
an episode, there was no significant difference between
the mean percent of depressed days between patients
with bipolar I and bipolar II disorders (22.0% versus
24.5%, p = 0.586). There was also no significant differ-
ence between the mean percent of days spent in a
depressed episode of any length between patients with
bipolar I and bipolar II disorders (Table 5B).
Discussion
Brief depressive episodes lasting between 1 and 4 days
occurred frequently in this study of patients with bipolar
disorder. In fact, 61% of all days of depression occurred
outside of a depressed episode when using the 14-day
DSM-IV length criterion. This high frequency of subsyn-
dromal depression in bipolar disorder is consistent with
prior research in which diverse methodologies were used to
measure symptoms (Angst and Merikangas 1997; Bauer
et al., 2010; Judd et al., 2002, 2003a). The occurrence of
brief depressive episodes could not be used to differentiate
between a diagnosis of bipolar I and bipolar II disorder, as
with prior findings (Bauer et al., 2007; Kupka et al., 2007;
Marangell et al., 2009).
Frequent brief depressive episodes are of concern for
many reasons. Depressive symptoms, rather than manic
symptoms, are the primary determinant of the quality of
life in bipolar disorder (Bowie et al., 2010; Michalak et al.,
2008; Vojta et al., 2001). Moreover, the functional burden
due to subsyndromal depressive symptoms is similar to that
from an episode of depression (Judd et al., 2005; Marangell
et al., 2009). Subsyndromal depressive symptoms are
equally impairing in both bipolar I and bipolar II disorder
(Judd et al., 2005), and are a predictor of both disability
(Bowie et al., 2010; Judd et al., 2005; Simon et al., 2007)
and reduced quality of life (Michalak et al., 2008).
Furthermore, the total time spent symptomatic may be a
better predictor of psychosocial functioning than the total
number of episodes, suggesting a cumulative effect from
all prior symptoms whether within or outside of an episode
(Bauer et al., 2001, Bauer et al., 2010; Gitlin et al., 1995;
Goldberg and Harrow, 2004). Subsyndromal depressive
symptoms are also associated with an increased risk of
relapse (Perlis et al., 2006). In a prior analysis of daily
patient mood ratings using the DSM-IV criteria, signifi-
cantly increased irregularity in mood occurred in the 60
days prior to an episode (Bauer et al., 2011).
In agreement with prior research, most of the depressive
symptoms in the current study were mild in intensity (Judd
et al., 2002, 2003a; Paykel et al., 2006). The proportion of
days within an episode with moderate to severe symptoms
was about ⅓ for episodes that met the DSM-IV criteria. The

Australian & New Zealand Journal of Psychiatry, 46(11)

Bauer et al. 1077
proportion remained about ⅓ within a 4-day episode,
decreasing to about ¼ for a single-day length. This pattern of
symptom intensity was similar regardless of diagnosis of
bipolar I or II, or if patients were taking or not taking antide-
pressants. Symptom intensity during brief depressive epi-
sodes is important since even modest increases in the severity
of depression are associated with a significant increase in
functional impairment and disability (Simon et al., 2007).
Patient perception of severity of depressive symptoms is also
associated with suicidal behaviour in patients with bipolar
disorder (Oquendo et al., 2004). Furthermore, the co-
occurrence of brief recurrent depression increases the
risk for suicidal behaviour in patients with unipolar depres-
sion (Altamura et al., 2011; Pezawas et al., 2005).
About 50% of the patients in this study were taking anti-
depressants, similar to prior reports of patients with bipolar
disorder in the USA and Europe (Baldessarini et al., 2007,
2008; Morselli et al., 2003). As in other observational stud-
ies, patients taking antidepressants experienced depressive
symptoms more frequently than those not taking antidepres-
sants (Bauer et al., 2007; Post et al., 2003). In this study,
patients taking antidepressants spent about 4% more days
within an episode of depression and 6% more days with
depressive symptoms outside of an episode, regardless of
episode length. The association between increased subsyn-
dromal depressive symptoms and taking antidepressants in
this observational study does not imply causality. Although
one possible hypothesis is that antidepressant use may con-
tribute to the increase in subsyndromal symptoms, a reverse
causality argument would suggest that increased vulnerabil-
ity to depression leads to an increased use of antidepres-
sants. Furthermore, many confounding factors beyond the
scope of this study may contribute to both depressive symp-
toms and antidepressant use, such as substance abuse or
anxiety disorders, general medical health, or economic sta-
tus. The treatment of bipolar depression with antidepres-
sants remains controversial (Fava, 2003; Gijsman et al.,
2004; Goldberg and Ghaemi, 2005; Licht et al., 2008).
However, given the widespread use of antidepressants,
including 11% of Americans over the age of 12 years in a
national sample of 14,000 (Pratt et al., 2011), there is a need
for controlled trials of the impact of antidepressants on sub-
syndromal depressive symptoms in affective disorders.
One strength of the present study is that the results are
consistent with our earlier findings, using a sample that is
about double in size (Bauer et al., 2007). Another strength
is that daily mood ratings were obtained prospectively from
a relatively large number of patients using validated soft-
ware. There are also several limitations. While an observa-
tional study reflects the heterogeneity of patients in clinical
practice, patients varied in severity, phase of the disorder,
symptoms experienced, and in medications taken. We can
only assume, but cannot confirm, that the patients taking
antidepressants were more depressed when they began tak-
ing antidepressants and have since improved. There were
fewer patients with bipolar II than bipolar I disorder in the
study, fewer males than females, and only outpatients were
included. Other limitations include the use of self-reported
mood ratings and the requirement for computer access.
Although self-reporting may affect the variable being mon-
itored, recent research did not find significant evidence
of measurement reactivity with daily ratings, including
depression (Hufford et al., 2002; Lenderking et al., 2008;
Simpson et al., 2005). A longer data collection period from
each patient would be preferable. This study did not address
the frequency of brief depressive symptoms in individuals
with bipolar disorder who were not taking medication.
Finally, there were no control groups, so this study cannot
compare the frequency or severity of brief depression with
conditions other than bipolar disorder. Future research on
brief depression in those without psychopathology and with
other psychiatric disorders is needed.
In conclusion, most patients with bipolar disorder expe-
rience brief depressive symptoms lasting between 1 and
4 days, regardless of a diagnosis of bipolar I or bipolar II
disorder. Symptoms of moderate to severe intensity occur
on ¼ to ⅓ of days in these brief depressive episodes.
Patients taking antidepressants experience brief depressive
symptoms more frequently. Controlled trials to explore the
impact of antidepressants on subsyndromal depressive
symptoms are indicated.
Funding
This project was funded entirely by local university funds.
Declaration of interest
The ChronoRecord Association is a 501(c)(3) nonprofit organi-
zation that aims to increase understanding of mood disorders
(www.chronorecord.org). None of the authors receive financial
compensation from the Association. Tasha Glenn and Peter C
Whybrow share a US patent for ChronoRecord software. Michael
Bauer, Paul Grof and Peter C Whybrow are on the Medical
Advisory Board.
References
Altamura AC, Buoli M, Dell’osso B, et al. (2011) The impact of brief
depressive episodes on the outcome of bipolar disorder and major
depressive disorder: A 1-year prospective study. Journal of Affective
Disorders 134: 133–137.
Altshuler LL, Gitlin MJ, Mintz J, et al. (2002) Subsyndromal depression
is associated with functional impairment in patients with bipolar dis-
order. Journal of Clinical Psychiatry 63: 807–811.
Angst J and Merikangas K (1997) The depressive spectrum: Diagnostic
classification and course. Journal of Affective Disorders 45: 31–39.
Baldessarini R, Henk H, Sklar A, et al. (2008) Psychotropic medications
for patients with bipolar disorder in the United States: Polytherapy
and adherence. Psychiatric Services 59: 1175–1183.
Baldessarini RJ, Leahy L, Arcona S, et al. (2007) Patterns of psychotropic
drug prescription for U.S. patients with diagnoses of bipolar disor-
ders. Psychiatric Services 58: 85–91.
Baldessarini RJ, Salvatore P, Khalsa HM, et al. (2010) Morbidity in
303 first-episode bipolar I disorder patients. Bipolar Disorders 12:
264–270.
Australian & New Zealand Journal of Psychiatry, 46(11)
1078 ANZJP Articles
Bauer M, Glenn T, Alda M, et al. (2011) Comparison of pre-episode and
pre-remission states using mood ratings from patients with bipolar
disorder. Pharmacopsychiatry 44(S1): S49–53.
Bauer M, Glenn T, Grof P, et al. (2007) Self-reported data from patients
with bipolar disorder: Frequency of brief depression. Journal of
Affective Disorders 101: 227–233.
Bauer M, Glenn T, Grof P, et al. (2009) Frequency of subsyndromal symp-
toms and employment status in patients with bipolar disorder. Social
Psychiatry and Psychiatric Epidemiology 44: 515–522.
Bauer M, Glenn T, Grof P, et al. (2010) Subsyndromal mood symp-
toms: A useful concept for maintenance studies of bipolar disorder?
Psychopathology 43: 1–7.
Bauer M, Grof P, Gyulai L, et al. (2004) Using technology to improve lon-
gitudinal studies: Self-reporting with ChronoRecord in bipolar disor-
der. Bipolar Disorders 6: 67–74.
Bauer M, Wilson T, Neuhaus K, et al. (2008) Self-reporting software for
bipolar disorder: Validation of ChronoRecord by patients with mania.
Psychiatry Research 159: 359–366.
Bauer MS, Kirk GF, Gavin C, et al. (2001) Determinants of functional
outcome and healthcare costs in bipolar disorder: A high-intensity
follow-up study. Journal of Affective Disorders 65: 231–241.
Bowie CR, Depp C, McGrath JA, et al. (2010) Prediction of real-world
functional disability in chronic mental disorders: A comparison of
schizophrenia and bipolar disorder. American Journal of Psychiatry
167: 1116–1124.
Denicoff KD, Smith-Jackson EE, Disney ER, et al. (1997) Preliminary
evidence of the reliability and validity of the prospective life-
chart methodology (LCM-p). Journal of Psychiatric Research 31:
593–603.
Fava GA (2003) Can long-term treatment with antidepressant drugs
worsen the course of depression? Journal of Clinical Psychiatry 64:
123–133.
Gijsman HJ, Geddes JR, Rendell JM, et al. (2004) Antidepressants for
bipolar depression: A systematic review of randomized, controlled tri-
als. American Journal of Psychiatry 161: 1537–1547.
Gitlin MJ, Swendsen J, Heller TL, et al. (1995) Relapse and impairment
in bipolar disorder. American Journal of Psychiatry 152: 1635–1640.
Goldberg JF and Ghaemi SN (2005) Benefits and limitations of antide-
pressants and traditional mood stabilizers for treatment of bipolar
depression. Bipolar Disorders 7(S5): 3–12.
Goldberg JF and Harrow M (2004) Consistency of remission and outcome
in bipolar and unipolar mood disorders: A 10-year prospective follow-
up. Journal of Affective Disorders 81: 123–131.
Goldberg JF and Harrow M (2011) A 15-year prospective follow-up of
bipolar affective disorders: Comparisons with unipolar nonpsychotic
depression. Bipolar Disorders 13: 155–163.
Hufford MR, Shields AL, Shiffman S, et al. (2002) Reactivity to ecologi-
cal momentary assessment: An example using undergraduate problem
drinkers. Psychology of Addictive Behaviors 16: 205–211.
Judd LL, Akiskal HS, Schettler PJ, et al. (2002) The long-term natural his-
tory of the weekly symptomatic status of bipolar I disorder. Archives
of General Psychiatry 59: 530–537.
Judd LL, Akiskal HS, Schettler PJ, et al. (2003a) A prospective investiga-
tion of the natural history of the long-term weekly symptomatic status
of bipolar II disorder. Archives of General Psychiatry 60: 261–269.
Judd LL, Akiskal HS, Schettler PJ, et al. (2003b) The comparative clini-
cal phenotype and long term longitudinal episode course of bipolar I
and II: A clinical spectrum or distinct disorders? Journal of Affective
Disorders 73: 19–32.
Judd LL, Akiskal HS, Schettler PJ, et al. (2005) Psychosocial disability in
the course of bipolar I and II disorders: A prospective, comparative,
longitudinal study. Archives of General Psychiatry 62: 1322–1330.
Kogan JN, Otto MW, Bauer MS, et al. (2004) Demographic and diagnostic
characteristics of the first 1000 patients enrolled in the Systematic
Australian & New Zealand Journal of Psychiatry, 46(11)
Treatment Enhancement Program for Bipolar Disorder (STEP-BD).
Bipolar Disorders 6: 460–469.
Kupfer DJ, Frank E, Grochocinski VJ, et al. (2002) Demographic and
clinical characteristics of individuals in a bipolar disorder case
registry. Journal of Clinical Psychiatry 63: 120–125.
Kupka RW, Altshuler LL, Nolen WA, et al. (2007) Three times more days
depressed than manic or hypomanic in both bipolar I and bipolar II
disorder. Bipolar Disorders 9: 531–535.
Lenderking WR, Hu M, Tennen H, et al. (2008) Daily process method-
ology for measuring earlier antidepressant response. Contemporary
Clinical Trials 29: 867–877.
Licht RW, Gijsman H, Nolen WA, et al. (2008) Are antidepressants safe
in the treatment of bipolar depression? A critical evaluation of their
potential risk to induce switch into mania or cycle acceleration. Acta
Psychiatrica Scandinavica 118: 337–346.
Marangell LB, Dennehy EB, Miyahara S, et al. (2009) The functional
impact of subsyndromal depressive symptoms in bipolar disorder:
Data from STEP-BD. Journal of Affective Disorders 114: 58–67.
Michalak EE, Murray G, Young AH, et al. (2008) Burden of bipolar
depression: Impact of disorder and medications on quality of life.
CNS Drugs 22: 389–406.
Mitchell PB, Johnston AK, Corry J, et al. (2009) Characteristics of bipo-
lar disorder in an Australian specialist outpatient clinic: Comparison
across large datasets. Australian and New Zealand Journal of
Psychiatry 43: 109–117.
Morselli PL, Elgie R; GAMIAN-Europe (2003) GAMIAN-Europe/
BEAM survey I—Global analysis of a patient questionnaire circu-
lated to 3450 members of 12 European advocacy groups operating in
the field of mood disorders. Bipolar Disorders 5: 265–278.
Oquendo MA, Galfalvy H, Russo S, et al. (2004) Prospective study of
clinical predictors of suicidal acts after a major depressive episode in
patients with major depressive disorder or bipolar disorder. American
Journal of Psychiatry 161: 1433–1441.
Paykel ES, Abbott R, Morriss R, et al. (2006) Sub-syndromal and syndro-
mal symptoms in the longitudinal course of bipolar disorder. British
Journal of Psychiatry 189: 118–123.
Perlis RH, Ostacher MJ, Patel JK, et al. (2006) Predictors of recurrence
in bipolar disorder: Primary outcomes from the Systematic Treatment
Enhancement Program for Bipolar Disorder (STEP-BD). American
Journal of Psychiatry 163: 217–224.
Pezawas L, Angst J and Kasper S (2005) Recurrent brief depression revis-
ited. International Review of Psychiatry 17: 63–70.
Post RM, Leverich GS, Nolen WA, et al. (2003) Stanley Foundation
Bipolar Network. A re-evaluation of the role of antidepressants in the
treatment of bipolar depression: Data from the Stanley Foundation
Bipolar Network. Bipolar Disorders 5: 396–406.
Pratt LA, Brody DJ and Gu Q (2011) Antidepressant use in persons aged
12 and over: United States, 2005–2008. NCHS Data Brief Number
76, October. Available at: www.cdc.gov/nchs/data/databriefs/db76.
htm (accessed 19 November 2011).
Simon GE, Bauer MS, Ludman EJ, et al. (2007) Mood symptoms,
functional impairment, and disability in people with bipolar disor-
der: Specific effects of mania and depression. Journal of Clinical
Psychiatry 68: 1237–1245.
Simpson TL, Kivlahan DR, Bush KR, et al. (2005) Telephone self-
monitoring among alcohol use disorder patients in early recovery: A
randomized study of feasibility and measurement reactivity. Drug and
Alcohol Dependence 79: 241–250.
Suppes T, Leverich GS, Keck PE, et al. (2001) The Stanley Foundation Bipolar
Treatment Outcome Network. II. Demographics and illness characteris-
tics of the first 261 patients. Journal of Affective Disorders 67: 45–59.
Vojta C, Kinosian B, Glick H, et al. (2001) Self-reported quality of life
across mood states in bipolar disorder. Comprehensive Psychiatry 42:
190–195.