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: mcbride_peggy_e@lilly.com (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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