Recurrent brief depression revisited.
ABSTRACT Recurrent Brief Depressive Disorder (RBD) is a well-defined and prevalent mood disorder with an increased risk of suicidal behavior and significant clinical impairment in the community and general practice. Occurring at least monthly with depressive episodes lasting only a few days defines recurrent Brief Depressive Disorder. The lifetime co-occurrence of both RBD and Major Depressive Disorder (MDD), called Combined Depression (CD), substantially increases the risk for attempted suicide, even more than that known for 'pure' MDD. The diagnostic criteria for RBD found in the ICD-10 and DSM-IV are helpful in research and clinical routine as well as several methodological issues, which make clinical diagnostic and drug response evaluation of RBD very different from MDD. Formal differences in the course of RBD and MDD require different designs for drug treatment studies. Denials of disorder, specific methodological requirements, and highly selected patient samples have probably been responsible for false negative results in double blind, placebo-controlled treatment studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, it is still not possible to deduce a treatment algorithm for RBD to date. Obviously future treatment studies without the limitations of previous studies are clearly required for RBD. Results of ongoing studies will soon provide the first data on the biological underpinnings of RBD.
- SourceAvailable from: Greg Murray[Show abstract] [Hide abstract]
ABSTRACT: Introduction: 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. Decreasing 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 ⅓ to ¼ for episodes lasting from 14 to 2 days, and ¼ 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 ¼ to ⅓ of the days in brief depressive episodes. This study did not address brief depression in those without bipolar disorder. Patients taking antidepressants experienced more brief depressive episodes. Controlled trials are needed to assess the impact of antidepressants on subsyndromal depressive symptoms.Australian and New Zealand Journal of Psychiatry 06/2012; · 3.29 Impact Factor
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ABSTRACT: The hypothesis defended here is that the process of mood-normalizing transitions fails in a significant proportion of patients suffering from major depressive disorder. Such a failure is largely unrelated to the psychological content. Evidence for the hypothesis is provided by the highly variable and unpredictable time-courses of the depressive episodes. The main supporting observations are: 1) mood transitions within minutes or days have been reported during deep brain stimulation, naps after sleep deprivation and bipolar mood disorders; 2) sleep deprivation, electroconvulsive treatment and experimental drugs (e.g. ketamine) may facilitate mood transitions in major depressive disorder within hours or a few days; 3) epidemiological and clinical studies show that the time-to-recovery from major depressive disorder can be described with decay models implying very short depressive episodes; 4) lack of relationship between the length of depression and recovery episodes in recurrent depression; 5) mood fluctuations predict later therapeutic success in major depressive disorder. We discuss some recent models aimed to describe random mood transitions. The observations together suggest that the mood transitions have a wide variety of apparently unrelated causes. We suggest that the mechanism of mood transition is compromised in major depressive disorder, which has to be recognized in diagnostic systems.Medical Hypotheses 01/2014; · 1.18 Impact Factor
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ABSTRACT: Depressive syndromes, including recurrent brief depression (RBD), have frequently been observed in association with chronic diseases characterized by immune activation, such as autoimmune thyroiditis or celiac disease. However, the association of RBD with chronic hepatitis C (CHC), a disease with an increased incidence of major depressive disorders, is unknown. Cases: 135 (83 males, 52 females) consecutive treatment-naïve patients with CHC. Exclusion criteria: previous treatment with IFN-alpha, co-infection with hepatitis C virus (HCV) and hepatitis B virus, infection with human immunodeficiency virus (HIV), drug or alcohol abuse, or malignancy. Controls: 540 (332 males, 208 females) subjects without evidence of hepatitis, randomly extracted from the database of a previous epidemiological study. The psychiatric diagnosis was based on the Composite International Diagnostic Interview Simplified (CIDI-S), containing a specific section on RBD. A significantly higher rate of RBD was observed among both male and female patients with CHC (n=21, 15.5%) as compared to controls (n=34, 6.3%) (OR=2.6, CI 95% from 1.37 to 4.93). The present study provides the first evidence of an association between CHC and RBD, independent of treatment with IFN-alpha and not influenced by substance or alcohol abuse. The results are similar to those found in other conditions with immune activation. RBD may be another expression of mood disorders in such conditions.Journal of affective disorders 05/2012; 141(2-3):361-6. · 3.76 Impact Factor
Recurrent brief depression revisited
LUKAS PEZAWAS1,2, JULES ANGST3, & SIEGFRIED KASPER1
1Department of General Psychiatry, Medical University of Vienna, Vienna, Austria,2Genes, Cognition and Psychosis
Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, USA, and
3Zurich University Psychiatric Hospital, Zurich, Switzerland
Recurrent Brief Depressive Disorder (RBD) is a well-defined and prevalent mood disorder with an increased risk of suicidal
behavior and significant clinical impairment in the community and general practice. Occurring at least monthly with
depressive episodes lasting only a few days defines recurrent Brief Depressive Disorder. The lifetime co-occurrence of both
RBD and Major Depressive Disorder (MDD), called Combined Depression (CD), substantially increases the risk for
attempted suicide, even more than that known for ‘pure’ MDD. The diagnostic criteria for RBD found in the ICD-10 and
DSM-IV are helpful in research and clinical routine as well as several methodological issues, which make clinical diagnostic
and drug response evaluation of RBD very different from MDD. Formal differences in the course of RBD and MDD require
different designs for drug treatment studies. Denials of disorder, specific methodological requirements, and highly selected
patient samples have probably been responsible for false negative results in double blind, placebo-controlled treatment
studies. Although several authors reported successful treatment of RBD with different compounds in about 60 patients, it is
still not possible to deduce a treatment algorithm for RBD to date. Obviously future treatment studies without the limitations
of previous studies are clearly required for RBD. Results of ongoing studies will soon provide the first data on the biological
underpinnings of RBD.
Recurrent brief depressive episodes persisting for a
few days and occurring spontaneously or triggered by
mild psychosocial stressors, is a common psychiatric
syndrome. These episodes are associated with sub-
stantial psychosocial impairment and an increased
risk of suicidal behavior (Pezawas et al., 2003b).
Depression (RBD) was first published in 1984
(Angst & Dobler-Mikola, 1985), recurrent short-
lived depressive episodes have been mentioned in
the 19th century
In 1852 Pohl reported episodes of ‘periodic mel-
ancholia’ lasting hours to days (Angst, 1994a) and
when Kraepelin published his pioneering work on
‘Manic-Depressive Illness’ in 1889, he even included
psychopathological symptoms such as hypomanic or
mild depressive moods of short duration in his
concept (Angst, 1994a). In 1915 Gregory published
a report on ‘Transient attacks of manic-depressive
insanity’ (Angst, 1994a). He mentioned in detail
the phenomenon of RBD: ‘Short attacks of a
manic-depressive psychosis, ranging in duration
from a few hours to several days, are very frequent’
and ‘...many sudden and unexpected suicides...are
due to fleeting attacks of a manic-depressive psy-
chosis. I am led to this belief from the examination of
hundreds of cases of attempted suicides’.
In 1929 Paskind underlined the clinical impor-
tance of brief depressions (Angst, 1994a). He was the
first psychiatrist, who recognized that the majority of
such patients are found more frequently in general
health care settings than in psychiatric institutions.
Read and Patrick confirmed the finding that recur-
rent brief depressions are significantly related to
suicidal behavior (Angst, 1994a).
In 1955 Busse reported: ‘The depressive periods
that we considered statistically had occurred at least
once a month, and their duration had varied from a
portion of an hour to a few days’ (Angst, 1994a). The
subjects reported that these episodes of depression
had not occurred in their younger years. Further
Correspondence: Dr Lukas Pezawas, Genes, Cognition and Psychosis Program, National Institute of Mental Health
(NIMH), National Institutes of Health (NIH), 10 Center Drive 4S235, Bethesda, MDD 20892-1379, USA. Tel: þ1 (301)
594 8393. Fax: þ1 (301) 594 8393. E-mail: firstname.lastname@example.org
ISSN 0954–0261 print/ISSN 1369–1627 online ? 2005 Institute of Psychiatry
International Review of Psychiatry, February 2005; 17(1): 63–70
he noted: ‘...these episodes can be termed ‘reactive’
In the late 1970s Spitzer et al. (Angst, 1994a)
developed some psychiatric Research Diagnostic
Criteria, including a category called ‘intermittent
depressive disorder’, characterizing patients being
bothered for at least two years by depressed mood
(like in Minor Depression) lasting from hours to
about week and being in a normal mood in between.
However, this definition was rarely used after its
introduction. More recently, in 1980 Clayton et al.,
called such depressions ‘very brief depressions’,
which has not been adopted by the scientific com-
munity either (Angst, 1994a). Similarly, in a study
London (1989), which explores treatment options
in repeated suicide attempters with comorbid bor-
derline personality disorder, Montgomery et al.,
reported patients suffering from severe recurrent
brief depressive episodes being associated with
suicidal behavior. He called them ‘intermittent
three-day depressions’ (Montgomery, Montgomery,
Baldwin & Green, 1989). In his later work, he
substituted this descriptive term by the diagnostic
category of RBD (Montgomery, Green, Bullock,
Baldwin & Montgomery, 1992).
In 1978, a longitudinal, epidemiological cohort
study of young adults assessing a continuum of
psychopathology from normal to disordered states
was launched in Zurich, Switzerland. The analysis of
the first follow-up interview showed the frequent
occurrence of depressive mood swings lasting less
than eight days (Angst & Dobler-Mikola, 1985).
Further research on this subject generated the first
operationalized definition of RBD, which has been
further revised (Angst, 1988). This definition of
RBD has been integrated in the ICD-10 system in
1992 (World Health Organization; WHO, 1992b).
Finally, a seasonal variant of RBD has been added
to its clinical picture (Kasper, Ruhrmann, Haase
& Moller, 1992; Kasper, Ruhrmann, Haase &
Moller, 1994). See Table I for a summary of the
history of RBD.
Table II summarizes prevalence rates for RBD in
different epidemiological samples. So far RBD has
been independently investigated in two longitudinal
and two cross-sectional community samples. The
Zurich study (Angst & Dobler-Mikola, 1985) has the
longest observation period of a community sample in
the context of RBD, starting its investigation at the
age of 19 until the last interview performed at the age
of 41 in 1999. Recent data are currently being
analyzed (Pezawas et al., 2003a). This study revealed
a lifetime prevalence rate of pure RBD without mood
disorder comorbidity of 12.5%, which is similar to
pure MDD without mood disorder comorbidity with
a prevalence rate of 14.7%. In contrast, gender
distribution of RBD is distinct from MDD showing
a balanced sex ratio in RBD (1:1.3) and female excess
in MDD (1:16.3). Duration patterns in RBD and
MDD also differ significantly with a median duration
of brief depressive episodes of three days in RBD an
about 10 weeks in MDD (Angst, 1994b). However,
the cumulative number of depressive days per year
has been shown to be less significantly different
in RBD (43 days) and MDD (75 days) within
the Zurich study. In accordance with the Zurich
study, a community sample in Mainz exhibited
similar prevalence rates (Maier et al., 1994a). A
slightly lower prevalence rate of 7.6% has been
reported in a large study (n¼1040) in Sardina
(Carta et al., 2003). Recently, epidemiological find-
ings of RBDhavebeen reinvestigatedina
Table I. History of recurrent brief depression (RBD).
Pohl 1852Described cases of multiple depressive episodes that lasted from hours to days; introduced
the term ‘periodic melancholia’
Described cases of multiple depressive episodes that lasted from hours to days; association
with ideas of suicide and impulse for self-destruction
Described cases of multiple depressive episodes that occurred independently from the
menstruation cycle; association with suicide attempts and unexpected suicides
Observed episodes of RBD in elderly patients
Increased suicidal behavior in brief depressions
Found that 14% of patients with manic depression also suffered from RBD
Attempted to operationalize an ‘intermittent depressive disorder’
Introduced the term ‘very brief depressions’
Introduced the first operationalized diagnostic category of brief depressions based on the
Zurich study, which he called RBD
Studied psychiatric patients with repeated suicide attempts and borderline comorbidity;
he introduced the term ‘intermittent 3-day depressions
Described a seasonal form of RBD
Inclusion of RBD as diagnostic category in ICD-10
L. Pezawas et al.
large community sample (n¼3021) of adolescents
and young adults within the Early Developmental
Stages of Psychopathology Study (EDSP) in Munich,
presenting prospective conservative estimations of
findings on prevalence, incidence, clinical correlates,
severity markers, comorbidity and course stability of
RBD and other mood disorders (Pezawas et al.,
2003b). Although this study applied conservative
measures to the phenomenon of RBD, previous
findings could be replicated in its core.
Support for community studies is also provided by
a comprehensive World Health Organization (WHO)
project on ‘Psychological Problems in General Health
Care’ (PPGHC) and further associated studies in
primary care settings (Sartorius et al., 1993). Notably
two centers, Mainz (Maier et al., 1994a; 1994b) and
Paris (Weiller, Boyer, Lepine & Lecrubier, 1994a)
confirmed patterns of clinical significance in a cross-
sectional study. Furthermore, prevalence rates of
RBD are available for 15 different primary care
France, Greece, India, Italy, Japan, the Netherlands,
Nigeria, China, Turkey, UK, and the USA (Weiller,
Lecrubier, Maier & Ustun, 1994b). A substantial
number (3.7%) of investigated primary care seekers
in a sample (including five centers) have been identi-
fied as suffering from RBD without mood disorder
comorbidity. Another sample that included 10
centers (n¼3527) using a slightly different definition
of RBD found a 5.7% prevalence of RBD.
So far epidemiological studies provided similar
findings on RBD demonstrating its significant
prevalence in the community and primary care,
and its clinical relevance.
in Brazil,Chile, Germany,
In 1994, RBD was integrated as a new diagnostic
category in ICD-10 (WHO, 1992a) and DSM-IV
(American Psychiatric Association; APA, 1994) due
to convincing epidemiological data (Table II).
While RBD represents a distinct clinical diagnosis
in ICD-10, DSM-IV classifies RBD into the
subcategory of depressive disorders ‘Not Otherwise
Specified (NOS)’. The DSM-IV manual offers
operational diagnostic criteria for scientific use
in the appendix but they do not qualify for
clinical use due to numerous exclusion criteria.
Psychopathological symptoms required for RBD
are absolutely the same as for MDD. Therefore
RBD cannot be thought a priori to be a milder form
of depression. As a matter of fact RBD can only be
distinguished from MDD by the duration criterion
(episode duration <14 days) and the frequency
criterion (approx. one episode/month). In addition,
the ICD-10 requires independence from the men-
strual cycle and an observation period of one year.
This also implies that RBD is not operationalized as
a course specifier of MDD as it is the case for
Seasonal Affective Disorder (SAD), for example.
Reports of the depression symptom profile of RBD
and MDD are provided by the Zurich and EDSP
study (Pezawas et al., 2003b) showing similar
patterns of depressive symptoms. Regarding symp-
toms reported in at least two thirds of subjects in the
Zurich study (Pezawas et al., 2003a), it is intriguing
Table II.Prevalence rates of RBD in the community.
Sample size Interview/method Prevalence 1-year Rates (%) lifetime
Zurich study 5.0–8.221.3
EDSP study, Munich– 2.6*
PPGHC study, Paris
PPGHC study, Mainz7.6–
PPGHC study, five centers3.7–
PPGHC study, 10 centers 5.7–
*Lower bound estimations.
Recurrent brief depression revisited
that most symptoms have been reported less
frequently in MDD in comparison to RBD. These
data confirm the relevance of the diagnostic concept
of RBD, demonstrating that RBD presents the full-
blown picture of depression. Similar findings have
also been reported in the EDSP study showing only
slightly less frequent reported depression symptoms
in RBD than MDD with the exception of sleeping
problems, which appear to be higher in RBD
(Pezawas et al., 2003b).
Within the Zurich study both RBD and MDD
patients reported a 50% family history of any kind of
depression (Pezawas et al., 2003a). This could be
taken as an argument for placing RBD within the
mood disorder spectrum. Suicide attempts were less
frequently reported in RBD (10.2%) without mood
disorder comorbidity, than in MDD (20.2%) in the
Zurich study—similar to the results of the EDSP
study (Pezawas et al., 2003b). However, general
practice studies have revealed even higher suicide
attempt rates: 16.1% in Mainz (Maier et al., 1994b),
23.3% in Paris (Weiller et al., 1994a), and 14% in
five WHO centers (Weiller et al., 1994b). The
relevance of suicidal behavior in RBD has also
been supported by clinical studies (Montgomery
et al., 1989; Pezawas et al., 2000) (Figure 1).
Furthermore, the concept of RBD and its clinical
significance has been underlined by studies on
occurrenceof both RBD
Combined Depression (CD) (Figure 1), which was
been introducedinto psychiatric
Montgomery (Montgomery et al., 1989), and further
(Angst & Hochstrasser, 1994; Maier et al., 1994b)
and clinical (Angst & Hochstrasser, 1994; Maier
et al., 1994b; Montgomery et al., 1989; Pezawas
et al., 2002b) studies demonstrated a dramatic
increase in suicide attempt rates and measures of
impairment in cases of CD in comparison to either
single RBD or MDD.
The differential diagnosis of both clinical phenom-
ena, RBD and MDD is based on their distinct
course pattern of depressive episodes (1–3 days
versus weeks or months).
From a clinical point of view it might be necessary
to differentiate other psychiatric disorders mainly
characterized by short-lived symptoms (Pezawas,
Stamenkovic & Kasper, 2001). The list comprises:
(1) Panic Disorder characterized by recurrent
unexpected panic attacks. However, the attacks
only last for minutes up to a few hours;
(2) Premenstrual Dysphoric Disorder (PMDD)
appearing exclusively in relation to the men-
strual cycle. Premenstrual Dysphoric Disorder
started in the last week of the luteal phase in
most menstrual cycles recorded over a year.
The symptoms begin to remit within a few days
of the onset of menses (the follicular phase) and
are always absent in the week following menses;
(3) Borderline Personality Disorder (BPD), which
in the case of affective instability, can be
associated with depressive mood fluctuations
that often persist for hours but also can last for
days. But the following characteristic symptoms
(according to the DSM-IV at least five symp-
toms) must be present in order to be able to
diagnose a BPD: frantic efforts to avoid real or
imagined abandonment, a pattern of unstable
and intense interpersonal relationships, identity
disturbance, impulsivity in areas that are poten-
tially self-damaging, recurrent suicidal behavior,
affective instability due to a marked reactivity of
mood, chronic feelings of emptiness, inappropri-
ate intense anger or difficulty controlling anger,
transient stress-related paranoid ideation or
severe dissociative symptoms. Low borderline
personality disorder comorbidity has been found
in our own clinical data (Pezawas et al., 2002b).
Another clinical study reported similar low
dimensional symptoms of personality disorders
in RBD and PMDD (Berlin, Raju, Schmidt,
Adams & Rubinow, 2001). Support also
comes from a recent study demonstrating that
endocrine responses to RBD and BPD differ
substantially (De La Fuente, Bobes, Vizuete &
(4) Rapid Cycling (RC) (>4 episodes/year), Ultra-
RC (episodes in a weekly rhythm) or
Ultra-Ultra-RC (ultradian episodes) Bipolar
Combined Depression, Recurrent Brief Depressive Disorder,
which is a distinct mood disorder in the ICD-10 system, can be
found in the appendix to DSM-IV as a diagnostic category
provided for further study. For clinical use subjects can be coded
as Depressive Disorder Not Otherwise Specified in DSM-IV.
1.Diagnosis of RecurrentBrief Depression and
L. Pezawas et al.
Disorders must show at least hypomanic (or
manic) episodes according to DSM-IV
(Kramlinger & Post, 1996). In the first case at
least one depressive episode must last for at least
14 days and in the last case the episodes may not
last longer than a day. Generally RC or Ultra-
RC are prognostic bad course specifiers for
Bipolar Disorder, which are developed by
15–20% (specifically RC) of bipolar patients
(Post & Weiss, 1998b) and differentiating them
from RBD rarely causes problems.
(5) Other affective disorders such as MDD,
Minor Depression (according to DSM-IV),
Bipolar Disorder, or Dysthymia can be easily
distinguished from RBD by the criterion of
duration of the depressive episode.
(6) Furthermore, it is necessary to distinguish RBD
from Drug induced Depression as found in
cocaine withdrawal, for example.
Recurrent brief depressive episodes have also been
described in the presence of somatic diseases, for
example, postictal dysphoria or the so-called inter-
ictal dysphoric disorder in epilepsy (Blumer, 2000).
Recurrent brief depressive episodes have been
reported to be associated with migraine plus aura
(Merikangas, Merikangas & Angst, 1993). One study
reported that about 70% of depressive episodes
occurring in patients suffering from idiopathic
Parkinson’s disease also meet the operationalized
criteriafor RBD (Wermuth
Furthermore, a case study of a patient suffering
from Prader-Willi Syndrome, who also met diag-
nostic criteria of RBD has been reported (Watanabe,
Ohmori & Abe, 1997), which is the only direct
evidence available so far that RBD could be caused
by genetic factors. Limited information is available
if the phenomenon of RBD in elderly populations
is distinct from RBD in younger cohorts (Heun,
Papassotiropoulos & Ptok, 2000). However, other
aging studies that indicate lower prevalence rates of
RBD (2.08%) in older cohorts are on their way
(Maercker et al., 2003).
Maier, 1998; Heun,
The longitudinal course of mood disorders is
characterized by a substantial diagnostic overlap
within these diagnostic groups (Pezawas et al.,
2003a). Therefore, longitudinal
studies like the Zurich study or EDSP study can
provide data on some critical issues concerning the
concept of RBD, evaluating the degree of evidence
that is given to rule out that RBD is not only a
prodromal or residual state of MDD or any other
Both studies indicate that RBD is not a prodromal
syndrome of MDD. The Zurich study indicated that
RBD cases became MDD cases more often than
vice versa. About 10% of all initially diagnosed MDD
cases developed RBD during follow-up and 20%
vice versa. This phenomenon was hypothetizised as
‘kindling-phenomenon’ by Angst (1994b) and is in
accordance with biological models dealing with the
longitudinal development of mood disorders (Post &
Concerning the hypothesis that RBD might be a
residual state of MDD, both studies found that only
a limited proportion of subjects developed RBD after
being diagnosed as MDD, which provides evidence
that RBD is not merely a residual state of MDD.
Hence the diagnostic stability over time is similar
for RBD and MDD.
Two thirds of all RBD patients seek professional help
in the course of their life (Angst, 1994b). One
quarter consult the general practitioner, one quarter
see a psychologist and the remaining half consult a
psychiatrist or neurologist. In the Zurich study,
almost all of these patients were stated as having
received psychotherapy treatment (Angst, 1994b).
However, RBD patients hardly ever receive pharma-
cological medication. The PPGHC study revealed
that the prescription rate of psychotropic substances
for patients with RBD in general practice was 19%.
This rate was the lowest and was three times lower
than the rate for patients with agoraphobia (Linden
et al., 1999). Furthermore, a substantial number of
patients with RBD that received previous treatment
frequently have a history of inadequate therapeutic
response to different pharmacological treatment
strategies normally offered by their general practi-
tioner (Kasper, Stamenkovic & Pezawas, 2000).
The fact that about 10% of all ‘pure’ RBD patients
and about 30% of all patients with a lifetime
depression) in the Zurich study attempted suicide
during the two decades of observation underlines
the need for sufficient treatment.
Almost two decades after the conceptualizing of
RBD, clinical trials concerning psychotherapy, as
well as biological treatment strategies (e.g., light
therapy), still have not been carried out, although
patients suffering from RBD frequently undergo
psychotherapy (Angst, 1994b). There is only one
case study about a patient suffering from a seasonal
type of RBD that describes the induction of ultradian
rapid cycling after light therapy (Meesters & Van
However, there are a few placebo-controlled
studies (Table III) and several case reports, a
and MDD (combined
Recurrent brief depression revisited
single-case analysis, and one open trial (Table IV)
assessing drug treatment of patients with RBD. All in
all those studies that chose a classical double-blind
placebo-controlled two-tailed design were not able to
demonstrate a successful treatment for RBD. Recent
findings indicate that studies should be conducted
using designs with an appropriate statistical sensitiv-
ity (e.g., single case analyses) and other statistical
evaluation procedures as well as longer observation
periods than used in MDD because of rapidly
undulating symptoms specific for RBD (Pezawas,
Stamenkovic, Aschauer, Moffat & Kasper, 2002a;
Post et al., 1998a). Maybe this is how false negative
study results came about and pessimism that was
brought up in these controlled studies concerning
possible successful therapy plans for RBD might be
inappropriate. Anyhow, this presumption is sup-
ported by successful results found in double-blind
placebo-controlled one-tailed single case analyses
with nimodipine, verapamil, and carbamazepine
(Pazzaglia, Post, Ketter, George & Marangell,
1993; Pazzaglia et al., 1998). However, controlled
studies were carried out with highly selected RBD
patient samples for example, patients with repeated
suicide attempts or comorbid borderline personality
disorder or somatic diseases (Kocmur, Dernovsek &
Tavcar, 1998; Montgomery et al., 1994; Verkes et al.,
1998; Wermuth et al., 1998), and this might have led
to a bias directed towards therapy resistance. Our
own positive experience concerning treatment with
mirtazapine (Stamenkovic, Pezawas, De Zwaan,
Aschauer, & Kasper, 1998), reboxetine (Pezawas
et al., 2002a), and fluoxetine, as well as other positive
results from case reports with lithium (Corominas,
Bonet & Nieto, 1998), carbamazepine (Gertz, 1992),
lamotrigine (Malt & Fladvad, 2001) and tranyl-
cypromine (Joffe, 1996) put the negative findings
from other studies due to the above mentioned
reasons in question (Pezawas et al., 2001).
In any case, to date, it is not possible to derive a
specific treatment strategy for RBD from the existing
data. Because the study results remain unclear and
contradictory, there is a great need for future
controlled clinical trials without the methodical
limitations of previous studies. Taking into consid-
eration that to date, successful treatment of RBD has
been reported for about 60 patients, a first choice
antidepressant treatment attempt with substances
lacking severe side effects seems to be justified.
Recurrent Brief Depressive Disorder originated from
epidemiological research, which distinguishes this
disorder from any other psychiatric disorder. So far
epidemiologic studies were able to elaborate clinical
features of RBD and estimate prevalence rates in
different populations. A substantial new piece of
information will be provided by new data of the
EDSP study, which included a parental psychiatric
interview as well as information on the early
developmental symptoms of their offspring. These
data (Pezawas et al., in preparation) demonstrate that
parents of RBD patients do not exhibit higher rates
of MDD than the normal population. This is a
surprising finding since MDD rates of parents of
MDD patients are dramatically elevated and support
the idea that MDD has a substantial genetic
component in its etiology. Our data suggests that
there might be a substantial difference between the
genetic risk factors of MDD and RBD. Furthermore,
these data demonstrates that RBD patients are
essentially more exposed to stress-related life events
than MDD patients.
The pessimism concerning the treatment of RBD
might be unjustified, due to false negative study
results. Recent progress has been made in the
case analyses) and two-tailed studies assessing treatment of
patients with RBD.
Double-blind, placebo-controlled, one-tailed (single
Kocmur et al., 1998a
Kasper et al., 2000
Montgomery et al., 1994b
Kasper et al., 2000
Montgomery et al.
(Kasper et al., 2000)
Pazzaglia et al., 1998c
Pazzaglia et al., 1998c
Pazzaglia et al., 1998c
Verkes et al., 1998b
Wermuth et al., 1998d
RBD, Recurrent Brief Depression; n, number of patients included
in the study;
nimodipine; þ response to treatment; ? no response to treatment.
aIntermittent Depressive Disorder;
csingle case analysis;
1Carbamazepine was prescribed as add-on treatment to
dParkinson patients with
providing drug treatment outcomes in RBD.
Open trials and single case analyses, and case reports
Amore et al., 1998a
Corominas et al., 1998a
Corominas et al., 1998a
Pezawas et al., 2002b
Stamenkovic et al., 2001c
Stamenkovic et al., 1998a
RBD, Recurrent Brief Depression; n, Number of patients included
in the study;
þ response to treatment; ? no response to treatment.
bsingle case analysis;
L. Pezawas et al.
prospective assessment of mood symptoms in such
rapid cycling depressive mood disorders like RBD.
It has been worked out that designs and statistical
methods used in clinical studies in the past have been
insufficient. However, several questions remain
concerning the optimal clinical study design, instru-
ments for assessing RBD symptoms, and appropriate
statistical methods. Future efforts in the field of RBD
should also include these methodological aspects.
The optimal treatment regime for RBD remains an
open question. Based on information from treatment
studies, a prescription with modern antidepressants
seems to be appropriate. As a second line treatment,
mood stabilizers can be considered. However, longer
response rates (weeks to a few months) than those
seen in MDD are characteristic for this disorder
since symptoms occur less frequently than in MDD.
Finally, there is very limited information available
on the biological features of RBD due to a lack
of ‘pure’ RBD patients in psychiatric institutions.
Supportive data might soon be available from
trytophan depletion studies in Vienna and electro-
physiological, structural and functional imaging
studies in Oslo (Malt, 2003).
Summarizing progress in RBD research, we
conclude that RBD is an epidemiological well-
characterized disorder that is common in primary
care and in the community, but less common in
psychiatric practice. Therefore, clinical studies are
lacking in the field of RBD research today and
further studies are clearly needed. The pessimism
concerning the drug treatment for this disorder
(originating from the first studies) seems to be
inappropriate today. Progress in methods, which
should be used for the assessment and evaluation
of this disorder, may contribute to the development
of better treatment strategies for this disorder.
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