www.elsevier.com/locate/jad
Journal of Affective Disor
Brief report
Major depressive disorder in Latin America: The relationship
between depression severity, painful somatic symptoms, and
quality of life
Rodrigo A. Munoza, Margaret E. McBrideb,T, Alan J.M Brnabicb, Carlos J. Lopezc,
Luiz Alberto B. Hetemd, Ricardo Secine, Hector J. Duenasf
aUniversity of San Diego, CA, USAbEli Lilly Australia
cUniversidad de Antioquia, ColombiadUniversity of Sao Paulo, Sao Paulo, Brazil
eHospital Angeles del Pedregal, Mexico City, MexicofEli Lilly and Company, Mexico
Received 6 April 2004; received in revised form 21 December 2004; accepted 22 December 2004
Abstract
Background: We report on two multi-center, prospective, observational studies (H6U-BC-LRAG and H6U-BL-LRAH) to
determine the clinical profile of Latin American outpatients with major depressive disorder (MDD) and the relationship between
depression severity, painful somatic symptoms, and quality of life.
Method: Patients (n=989) with MDD were classified according to the presence (SS+) or absence (SS�) of painful somatic
symptoms using the Somatic Symptom Inventory (SSI). Visual Analogue Scale (VAS) quantified pain severity, HAMD17 and
CGI-S determined depression severity, while the Quality of Life in Depression Scale (QLDS) quantified subjective well-being.
Results: At baseline, patients had an average CGI score of 4.5 (F0.8) and HAMD17 score of 24.9 (F7.2). Of the patients
studied, 72.6% reported painful somatic symptoms (95% CI: 69.8, 75.4), with women 2.7 times more likely to be SS+ than men
( pb0.0001). Adjusted mean HAMD17 (26.79) and CGI-S (4.53) scores for SS+ patients were significantly ( pb0.0001) higher
than for SS� patients (HAMD17: 22.87; CGI-S: 4.28). SS+ patients had greater severity of pain across all VAS measures
( pb0.0001). The presence of somatic symptoms had a significantly deleterious effect on quality of life ( pb0.0001).
Conclusion: Greater severity of painful somatic symptoms was associated with increased depression severity and reduced quality
of life. We concluded that both emotional and physical manifestations of MDD must be addressed for successful treatment.
D 2005 Elsevier B.V. All rights reserved.
Keywords: Major depressive disorder; Painful somatic symptoms; Quality of life; Somatic symptom inventory; HAMD17
0165-0327/$ - s
doi:10.1016/j.jad
T Correspondi
E-mail addr
ders 86 (2005) 93–98
ee front matter D 2005 Elsevier B.V. All rights reserved.
.2004.12.012
ng author. Tel.: +61 2 8874 5753; fax: +61 2 8874 5733.
ess: [email protected] (M.E. McBride).
R.A. Munoz et al. / Journal of Affective Disorders 86 (2005) 93–9894
1. Introduction
Major depressive disorder (MDD) is a psychiatric
condition associated with stratified psychological,
behavioral, and physical symptoms. This condition
currently affects an estimated 340 million people
worldwide (Greden, 2003) and disrupts the lives of
10–25% of females and 5–12% of males at some
point in their life (American Psychiatric Association,
1994). Despite this high prevalence, researchers
speculate that depression is currently underestimated
as recognition may be compromised by the high
incidence of concomitant painful somatic symptoms,
which may mask the underlying emotional symp-
toms (Kirmayer et al., 1993). Current research
reveals that up to 76% of all patients with depression
report painful somatic symptoms (Kirmayer et al.,
1993; Corruble and Guelfi, 2000), while the reso-
lution of somatic symptoms is a strong predictor of
full remission in the treatment of major depression
(Paykel et al., 1995).
The high prevalence of painful physical symp-
toms in depressed patients has been established in
clinical trials in North American and Europe
(Bridges and Goldberg, 1985), but the Latin
American population has been largely overlooked.
We describe the current epidemiological profile of
Latin American patients with MDD while emphasiz-
ing the relationships between depression severity,
painful somatic symptoms, and quality of life.
2. Methods
2.1. Selection criteria
Outpatients over the age of 18 years who
presented with a current, new, or first episode of
MDD (DSM-IV or ICD-10) and were prepared to
take antidepressant medication were invited to
participate in this study. Prior to the onset of the
current episode, patients had to be free of any
symptoms of depression for at least 2 months and
the duration of the current episode could not exceed
two continuous years. Patients were excluded from
the study if they had been prescribed a monoamine
oxidase inhibitor (MAOI), undertaken at least one
course of electroconvulsive therapy (ECT), or had
treatment-resistant depression (a failure to respond to
two different classes of antidepressants at an accept-
able dose for at least 4 weeks each). Exclusion
criteria also included any previous or current
diagnosis of schizophrenia, schizophreniform disor-
der, schizoaffective disorder, bipolar disorder, or
dementia.
2.2. Study design
These prospective, observational studies involved
88 principal investigators from 80 study sites across
seven Latin American countries. The baseline
observations are reported at this time. The institu-
tional or ethical review board of each site approved
the study and consent to release information was
received from each patient or their legal representa-
tive prior to enrollment. Each investigator deter-
mined the optimal treatment strategy for each patient
based on their standard clinical practice.
Patients with a mean score z2 for the pain-
related items (2, 3, 9, 14, 19, 27, and 28) on the
Somatic Symptom Inventory (SSI) (Kroenke et al.,
1994) were classified as somatic symptom positive
(SS+) and were compared to somatic symptom
negative (SS�) patients in subsequent analyses.
The Visual Analogue Scale (VAS) quantified pain
severity (DeLoach et al., 1998), while depression
severity was determined using the 17-item Hamilton
Depression Rating Scale (HAMD17) and the Clinical
Global Impressions of Severity Scale (CGI-S) (Guy,
1976). The Quality of Life in Depression Scale
(QLDS) quantified subjective well-being (Hunt and
McKenna, 1992).
2.3. Statistical methods
For continuous outcomes (VAS, CGI-S, HAMD17,
and QLDS), comparisons were performed using
general linear models (GLM). Where appropriate,
adjustments were made for confounders or clinically
relevant predictors (gender, age, SSI mean score, and
country). Relationships between VAS, HAMD17,
CGI-S, demographic variables, and their effects on
QLDS were also determined using GLMs with all
response variables treated as continuous.
The Fisher exact test was used to compare
proportions for the categorical analysis of patients
R.A. Munoz et al. / Journal of Affective Disorders 86 (2005) 93–98 95
with or without somatic symptoms. Where the
response data were treated as dichotomous, logistic
regression was used for determining odds ratios.
Due to the number of hypotheses being tested and
the lower precision of naturalistic, observational
studies, stringent controls were imposed on the
statistical analyses. The level of significance was
established post hoc to be less than or equal to a
probability of 0.005.
Table 1
Socio-demographic characteristics and disease history for the total study
symptom negative (SS�) subgroups
Characteristic Total (N
Age (N=989) (mean, (S.D.)) 43.4 (13
Gender (N=969)b
Female % (n) 78.4 (76
Origin (N=982) % (n)c
African 1.8 (18
Asian 0.1 (1)
Caucasian 38.1 (37
Hispanic 50.7 (49
Mulatto 5.9 (58
Other 3.4 (33
Country (N=972) % (n)
Argentina 13.5 (13
Brazil 29.2 (28
Chile 6.3 (61
Colombia 7.2 (70
Mexico 30.5 (29
Peru 3.1 (30
Venezuela 10.3 (10
Previous episodes of MDD (N=988) % (n)
N4 13.6 (13
1–3 49.4 (48
None 37 (36
Previous episodes of MDD in last 24 months (N=963) % (n)
N4 1.2 (12
1–3 34.8 (33
None 64 (61
Duration of current episode (N=987) % (n)
N1–2 years 5.4 (53
6 months–1 year 14.6 (14
b6 months 80 (79
a Two patients were not classified as either somatic symptom positive (b Data were not recorded for all patients.c Due to rounding, some percentage calculations may not total 100%.
3. Results
A total of 989 patients were enrolled across seven
Latin American countries (Table 1). Patients were on
average 43.4 years of age (F13.99), with the majority
(78.4%) being female. Most patients (63%, n=622)
had experienced at least one previous episode of
MDD, 13.6% reported four or more previous episodes,
and 64% (n=616) had been free of MDD in the 2 years
population and the somatic symptom positive (SS+) and somatic
=989)a Somatic symptom positive
(SS+) (n=717, 72.6%)
Somatic symptom negative
(SS�) (n=270, 27.4%)
.99) 42.81 (13.18) 44.99 (15.85)
n=704 n=263
0) 83.4 (587) 65 (171)
n=710 n=270
) 1.4 (10) 3.0 (8)
0.1 (1) 0.0 (0)
4) 37.2 (264) 40.7 (110)
8) 53.0 (376) 44.8 (121)
) 4.8 (34) 8.5 (23)
) 3.5 (25) 3.0 (8)
n=702 n=268
1) 13.7 (96) 13.1 (35)
4) 25.8 (181) 38.1 (102)
) 8.0 (56) 1.9 (5)
) 8.3 (58) 4.5 (12)
6) 30.6 (215) 29.9 (80)
) 3.1 (22) 3 (8)
0) 10.5 (74) 9.7 (26)
n=717 n=269
4) 13.7 (98) 13.4 (36)
8) 49.7 (356) 48.7 (131)
6) 36.7 (263) 37.9 (102)
n=705 n=256
) 1.4 (10) 0.8 (2)
5) 34.8 (245) 34.8 (89)
6) 63.8 (450) 64.5 (165)
n=716 n=269
) 4.9 (35) 6.7 (18)
4) 13.8 (99) 16.7 (45)
0) 81.3 (582) 76.6 (206)
SS+) or somatic symptom negative (SS�).
R.A. Munoz et al. / Journal of Affective Disorders 86 (2005) 93–9896
preceding the current episode. The diversity of this
region is reflected in the ethnicity of enrolled patients.
Response to the pain-related items on the Symptom
Severity Inventory (SSI) was recorded for 987
patients and 72.6% (n=717; 95% CI: 69.75, 75.41)
were classified as SS+. Women were 2.7 times (95%
CI: 1.96, 3.72) more likely to be SS+ than men
( pb0.0001). No significant differences were found
between SS+ and SS� groups in terms of age, ethnic
origin, total number of MDD episodes, number of
episodes in the previous 2 years, or the duration of the
current MDD episode.
The most prevalent painful somatic symptoms
reported on the Somatic Symptom Inventory (SSI)
were muscle soreness (82.3%), neck pain (78.0%),
and headache (77.6%) (Fig. 1). The most prevalent
painful somatic symptoms were also the most trou-
bling, with a substantial proportion of patients
reporting being bothered either bquite a bitQ or bagreat dealQ over the previous week.
Patients with painful symptoms experienced a
significantly ( pb0.0001) greater severity of pain
Fig. 1. Patient response to the pain-related items
across all domains when compared with SS� patients
(Fig. 2). Notably, SS+ patients reported spending
almost 58% of their waking time in pain and this pain
severely interfered with daily activities.
The majority of this patient population was suffer-
ing from moderate to severe depression, but the
presence of painful symptoms was associated with
greater depression severity (Table 2). When adjust-
ments were made for gender, age, country, and mean
severity of pain, patients with painful somatic symp-
toms scored significantly ( pb0.0001) higher on both
HAMD17 and CGI-S measures. Indeed, SS+ patients
had significantly ( pb0.0001) higher mean scores on all
five HAMD17 subscales (core, maier, anxiety, retarda-
tion, and sleep) when compared with SS� patients.
The mean QLDS score for total group was 22.42
(F7.46), but the presence of painful somatic symp-
toms had a significantly negative impact on quality of
life (Table 2). Significantly ( pb0.0001) higher mean
QLDS scores were recorded for SS+ patients (repre-
senting a decrease in quality of life) when compared
with SS� patients. Regardless of the severity of pain
on the Somatic Symptom Inventory (SSI).
VAS Variables
VA
S o
vera
ll
Hea
dach
e se
verit
y
Bac
k pa
in s
ever
ity
Sho
ulde
r pa
in s
ever
ity
Pai
n in
terf
eren
ce
Tim
e aw
ake
in p
ain
Pai
n S
ever
ity
(+ 9
5% C
I)
0
10
20
30
40
50
60
70Patients with painful somatic symptoms (SS+)Patients without painful somatic symptoms (SS-)
* *
*
*
**
0001.* ≤p
Fig. 2. Mean pain severity as measured by the Visual Analogue Scale (VAS) for somatic symptom positive (SS+) and somatic symptom negative
(SS�) patients.
R.A. Munoz et al. / Journal of Affective Disorders 86 (2005) 93–98 97
as determined by VAS, an increase in HAMD17 total
score was associated with a significant ( pb0.0001)
decrease in quality of life.
4. Discussion
Although ethnicity has been found to influence the
somatic presentation of depression (Berganza et al.,
2001; Parker et al., 2001; Iwata and Buka, 2002), no
Table 2
Clinical status (CGI-S and HAMD17) and Quality of Life (QLDS) for the
somatic symptom negative (SS�) subgroups
Measure Total Somatic sympt
positive (SS+)
na Unadjusted mean (S.D.) Adjusted mean
CGI-S 985 4.5 (0.8) 4.53
HAMD17 979 24.9 (7.2) 26.79
QLDS 958 22.4 (7.5) 22.98
a Patient number refers only to unadjusted data.b Mean values were adjusted for gender, age, country, and pain severity
significant differences were detected between the
somatic and non-somatic groups in this study in terms
of ethnic origin. This finding is supported by Escobar
et al. (1983), who found the symptomatic manifes-
tations of depression to be similar for North and South
American patients.
When presenting to a clinician in a general practice
setting, many patients deemphasize psychosocial
symptoms while identifying pain as their primary or
sole complaint (Greden, 2003; Simon et al., 1999).
total study population and the somatic symptom positive (SS+) and
om Somatic symptom
negative (SS�)
Mean difference
(95% CI)
p value
b Adjusted meanb
4.28 0.25 (0.13–0.37) b0.0001
22.87 3.92 (2.99–4.85) b0.0001
19.68 3.29 (2.19–4.39) b0.0001
.
R.A. Munoz et al. / Journal of Affective Disorders 86 (2005) 93–9898
The present study was conducted using psychiatric
outpatient consultations and results confirm that
painful somatic symptoms are a frequent complaint
of depressed patients.
The likelihood of a psychiatric disorder has been
found to increase dramatically with the number of
physical complaints (Kroenke et al., 1994) and the
SS+ patients in this study experienced significantly
greater depression severity across all domains.
Clearly, the presence of painful somatic symptoms
was associated with an increased likelihood that the
patient experienced greater severity of depression.
The long-term goal of treatment for MDD is to
ensure that patients regain functionality and, as
such, the accurate and subjective assessment of
quality of life has become an increasingly important
issue in modern psychiatry. The presence of painful
somatic symptoms interfered with the patients’
normal daily activities and negatively affected
quality of life.
5. Concluding remarks
This study investigated the prevalence of painful
physical symptoms in Latin American patients with
depression and highlighted the complex relationships
between depression severity, painful physical symp-
toms, and quality of life. The high prevalence of
painful somatic symptoms in patients with depression
previously reported in general practice settings was
confirmed through psychiatric consultations in Latin
America. Continued psychiatric observation of
patients over the next 12 months will provide insight
into the breal worldQ presentation of MDD in clinical
practice and the clinical significance of painful
physical symptoms in patients with depression.
Acknowledgements
This study was supported by a research grant from
Eli Lilly and Company.
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