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Pain as a symptom of depression: Prevalence and clinical correlates in patients attending psychiatric clinics
Journal of Affective Disorders 130 (2011) 106–112
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Journal of Affective Disorders j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j a d
Research report
Pain as a symptom of depression: Prevalence and clinical correlates in patients attending psychiatric clinics L. Agüera-Ortiz a, I. Failde b,⁎, J.A. Mico c, J. Cervilla d, J.J. López-Ibor e a Psychiatry Department, University Hospital 12 de Octubre, Complutense University, Madrid & Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain b Preventive Medicine and Public Health Area, University of Cádiz, Spain c Department of Neuroscience, Pharmacology and Psychiatry, School of Medicine, University of Cádiz & Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Cádiz, Spain d Psychiatry Department, University of Granada, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Granada, Spain e Department of Psychiatry, University Hospital San Carlos & Complutense University, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
a r t i c l e
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Article history: Received 25 August 2010 Accepted 10 October 2010 Available online 4 November 2010 Keywords: Pain Depression Psychiatric outpatients Anhedonia Loss of energy
a b s t r a c t Background: The need to assess the prevalence and characteristics of painful symptoms among depressed patients attended by psychiatrists in their regular clinical practice. Methods: A multi-centre, cross-sectional study was carried out in a large sample (n = 3566) of patients attending out-patient psychiatric facilities in Spain. All types of DSM-IV-TR depressive disorders were included. Data on the diagnosis, specific symptoms, intensity of depression and antidepressant and analgesic drug treatments were collected. The presence and characteristics of significant pain (visual analogue scale score N 40) at the time of the study were also recorded. Results: The prevalence of pain in depressed patients was 59.1% (CI 95%: 57.7%; 60.7%). Factors associated independently with the existence of significant pain were: being female, presence of loss of energy and the diagnosis of dysthymia or depression induced by physical disorders. In addition, age and the intensity of depression were two risk factors, where each year of age and each point in the Hamilton scale increased the risk of having pain by 2% and 8% respectively. The presence of anhedonia and the diagnosis of depression induced by illegal drugs were factors inversely related to pain. Limitations: The cross-sectional naturalistic characteristics of the study. Conclusion: Our data show a high prevalence of pain among depressive patients attending psychiatric clinics. Painful symptoms are modulated differently depending on the type of depression and the presence of specific symptoms, such as loss of energy or anhedonia. Psychiatrists should ask their depressive patients for the presence of pain on a regular basis. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Pain is an experience common to all human beings. Nevertheless, the variety of words to describe pain in different languages means that the experience is highly subjective, culture loaded and directly related with an affective correlate.
⁎ Corresponding author. Facultad de Ciencias de la Salud, Universidad de Cádiz, Avda. Ana de Viya 52, 11009 Cadiz, Spain. Tel.: + 34 956019025; fax: + 34 956019011. E-mail address: [email protected] (I. Failde). 0165-0327/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2010.10.022
The inclusive affective use of “pain” comprises meanings of “suffering”, “distress”, “uneasiness”, “displeasure”, and “unpleasure”. Pain and depressed mood are experiences that have more common characteristics than commonly thought. Pain is not just the sensation produced by injuries. The IASP (International Association for the Study of Pain) has reached after several attempts the pain definition as: “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (Merskey and Bogduk, 1994). Hence the unpleasantness of pain is often
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associated to anxiety or depressive feelings. The anxiety is evoked by the threat of damage and depression by the unpleasantness and the loss of healthy positive feelings. On the other hand, the association of tissue damage and pain is not always a direct one and many people report pain in the absence of tissue damage or any likely pathophysiological cause. Accordingly, the IASP avoids tying pain to a stimulus, and states that it is always a psychological state. Pain seems undoubtedly a common symptom of depressive disorders. Masked depression (Obiols and Ballús, 1979) and atypical depression were commonly used – and abused – concepts before DSM-III, and both included several painful manifestations. In spite of the fact that single episodes of masked depressions are present in ICD-10 (F32.8 Other depressive episodes), today, neither ICD-10 nor DSM-IV-TR mentions pain as a symptom of depressive disorder, but both include depression or mood disorders as exclusion criteria for persistent somatoform pain disorder or pain disorder. On the other hand, pain manifestations such as back, head or muscle aches are items present in several rating scales for depression (i.e., HDRS). Depression is currently viewed as a mental disorder comprising both emotional and somatic symptoms. The prevalence of somatic and physical symptoms in patients with major depressive disorder (MDD) in tertiary care is 30– 54% (Brecht et al., 2007; Giesecke et al., 2005; Lee et al., 2009). However, a number of studies have demonstrated that in almost half of all patients with physical symptoms, depression goes undiagnosed (Kessler et al., 2003) with the consequent increased risk of developing more severe depression and increased resistance to treatment (Bair et al., 2004). In addition, physical symptoms are associated with a greater likelihood of recurrence and new depressive episodes. Despite much epidemiological work done, the actual frequency of depression-related pain is not clear, with studies giving high ranges of prevalence. To cite only one of them, Blair and colleagues published a meta-analysis showing a prevalence of 65% of painful symptoms in patients with depression (Bair et al., 2003). Pain has also implications on therapy and resource utilization. It has been suggested that the presence of baseline pain is associated with fewer benefits from antidepressant therapy and worse quality of life outcomes (Bair et al., 2004). A population-based study found that people with depression and concomitant pain initiated 20% more visits to medical providers and their total medical costs were higher than people with depression but without pain (Bao et al., 2003). This is in keeping with the fact that the presence of pain is also associated with longer duration and increased severity of the depressive episode (Karp et al., 2005). The experience of pain and of negative feelings such as sorrow and depression shares common neurobiological substrates and mechanisms. For instance, in major depression a hyperactivity has been described in the perigenual anterior cingulate cortex, (Mayberg, 2007) a region which has been associated to pleasure and which receives important projections from the midbrain dopamine system. Activation of the brain's mesolimbic dopamine system apparently organizes reward oriented behaviour which prevents the appearance of some forms of mental pain. Dopamine neurons in the relevant midbrain area fire in response to painful aversive (Berridge
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and Winkielman, 2003) and avoidable stimuli, such as tail pinch, rather than only in response to ones we seek out and enjoy, so that the system seems to some to respond to both pleasure and pain and an insufficiency of dopamine neurotransmission at D2 receptors seems implicated in depression (Willner, 2002). Recently neuro-imaging studies have revealed a close relationship between brain areas implicated in the integration of the sensorial and emotional aspects of pain and areas modulated by depression (Ehnvall et al., 2009). In this sense, it seems evident that pain could be an important biological factor to be considered to improve the diagnosis and treatment of depression. The close relationship between the antidepressant mechanisms of action of antidepressants and their analgesic mechanisms of action (Mico et al., 2006) is evidence that mood and pain may share similar neurobiological mechanisms and neuro-anatomical substrates and consequently these two processes could co-exist in patients with depression. Considering all this epidemiological, clinical and neurobiological evidence, the need for a better understanding of the complex interplay between depression and painful physical symptoms is now recognized. Previous research examining the relationship between depression and painful physical symptoms has focused on patients selected on the basis of their painful physical condition who were subsequently examined for major depression. Furthermore, of the studies carried out in secondary care, most were in pain clinics, with a scarcity of studies performed in psychiatric settings (Garcia-Cebrian et al., 2006). The aim of our study and its originality was to estimate the prevalence of pain among depressive patients who are attended by psychiatrists in their regular clinical practice. A large and varied sample of patients has been examined to better understand the characteristics of depression in patients with and without pain, bearing in mind that pain might be considered in the future as a factor to be taken into account to improve depression diagnosis and general health outcomes. 2. Subjects and methods 2.1. Study design and sampling process A multi-centre, cross-sectional study was carried out in a sample of mental health care centres in Spain between April 2006 and December 2006. In order to obtain a representative sample, the number of psychiatric centres chosen in each Spanish region was proportional to the number of inhabitants in the region. In each centre, one psychiatrist was chosen at random, constituting a final sample of 400 researchers. The study was conducted in agreement with the Helsinki Declaration and with standard working procedures and protocols, and approved by a Clinical Research Ethics Committee, ensuring adherence to the norms of good clinical practice. 2.2. Patient population The study included men and women over 18 years old, visiting their psychiatrist for the first time and being diagnosed with depression according to the criteria of the
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DSM-IV-TR. Also, patients had to be mentally and physically able to participate in the study and give their written, informed consent. 2.3. Sample size Assuming a 65% prevalence of concomitant pain in depressed patients, to obtain a 95% confidence interval of width 6% (CI 95%: 62%; 68%) (Bair et al., 2003) and to be able to detect differences between subgroups defined by age, sex, and type of depression, a required sample of 2736 patients was calculated. A 10% rate of refusal to participate was assumed, resulting in 3010 patients being necessary for the study. 2.4. Recruitment To obtain the calculated number of patients, each of the 400 selected psychiatrists was to interview 8 consecutive patients coming for consultation who fulfilled the inclusion criteria for the study.
test, chi-squared test and correlation test were used to study associations between variables. The prevalence (with 95% CI) of pain was computed, and to study the factors associated with pain, crude and adjusted odds ratios (ORs) were calculated. For this purpose a logistic regression model was performed in which the outcome variable was the presence or absence of pain, and the variables included in the model were: sex, age, Hamilton scale score, type of depression (major depression, dysthymia, depression induced by illegal drugs, depression induced by physical disorders, depression induced by drugs and depression due to bipolar disorder) and specific symptoms of depression (anhedonia, loss of energy, sleep disorders, and depressive mood). A subset of the variables was selected that best predicted the presence or absence of pain using the Hosmer–Lemeshow test to identify the best model. An age– sex interaction term was also introduced into the model.
3. Results 3.1. Population characteristics
2.5. Measurements 3566 patients were finally included in the study. The average age of the population was 49.4 (SD: 13.02). 71.3% were female, and the women were generally older than the men (50.2 years (SD: 12.9) vs 47.6 years (SD 13.4); p b 0.001). 77.5% of the whole population had completed primary or secondary education and 64.9% lived with a partner. The type of mood disorder most frequently diagnosed was major depression, followed by dysthymia and depression induced by physical disorders (Fig. 1); and the most common symptoms observed were depressive mood, loss of energy, sleep disorders and anhedonia (Fig. 2). The mean number of episodes of depression suffered by the patients (including the current one) was 2.6 (SD: 2.2; median = 2); and the median duration of the current depressive episode was 7 months (P25 = 5; P75 = 13). Furthermore, 96.4% of the patients studied were undergoing some type of pharmacologic treatment at the time of 100 90 80
72,4
70 60
% 50 40 30 17,5
20 9,7
10
3,5
ym
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Fig. 1. Diagnostic of depression.
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2.6. Statistical analysis In the descriptive analysis, absolute frequency and central trend and dispersion measurements were calculated for qualitative and quantitative variables. The t-test, Wilcoxon
1,5
0,4
0 es
The interviews were performed at psychiatric out-patient centres. Depression was confirmed based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) and the intensity of depression was assessed by the 17-item Hamilton Depression scale validated in Spanish by Ramos-Brieva and Cordero-Villafafila (1988). Information about the duration of the current depressive episode and any history of depression up to the date of the study was also collected. Patients were asked about the presence of pain at the time of the study, lasting at least for the previous 6 weeks, and if present, pain characteristics were recorded. To assure a clearcut presence of painful symptoms, only patients with an intensity of pain over 40 on the visual analogue scale (VAS) in a range of 0–100, where 0 was no pain and 100 was the worst (Collins et al., 1997) were considered. Pain localization was recorded as well as its aetiology. Patients with pain were divided into two groups: subjects with a pain of known aetiology and subjects where the aetiology was unknown or only weakly explained. The interference of pain in the patients' everyday activities in the week before the study was also assessed using a visual analogue scale, where a score of 0 was no interference and 100 was total incapacity. Information related to socio-demographic variables (age, sex, educational level and social status), and clinical variables (intensity of pain, duration of pain, localization of pain, and treatment (i.e.: analgesics and/or psychotropics) was collected. Data collection forms were further monitored centrally to check and correct missing data or inconsistencies.
L. Agüera-Ortiz et al. / Journal of Affective Disorders 130 (2011) 106–112
100
109
Table 1 Characteristics of pain in 2107 depressed patients with pain.
90 Variables
80
Duration of pain (months)
70
Intensity of pain (VAS score)
% 60
Pain location a Head Neck Back Limbs Joints Specific known aetiology
50 40
ia Sl ee C tio ha p n ng D is e or of d er Bo s dy W Fe ei el gh in t gs o fG Lo ss ui Ps lt of yc En ho e m rg ot y or C Su ha ic ng id e al Id ea tio n
on
nt ra
SD: standard deviation; P25: 25th percentile; P75: 75th percentile; VAS: visual analogue scale. a More than 1 site was possible.
C on
ce
ed
N (%)
1038 48.3 (62.6) 24 (9; 61) 2107 68.2 (14.9) 2107 (100.0) 1376 (65.3) 1570 (74.5) 1697 (80.5) 1554 (73.8) 1551 (73.6) 1206 (57.2)
3.3. Factors associated with pain
D
im
in is he d
D ep re
ss
An h
ed
M
oo
d
30
N Mean (SD) Median (P25; P75) N Mean (SD) N (%)
Fig. 2. DSM-IV diagnostic criteria.
the study (N = 3440). 3.1% were on analgesics alone, 43.8% were on psychotropic drugs alone, and 49.5% were on both. Of the 1878 patients under treatment with analgesics (alone or in combination with psychotropic drugs), 94.4% were taking NSAIDs, in particular paracetamol (acetaminophen) (52.1%) or ibuprofen (37.5%), and 15.4% were taking opioid analgesics (in particular tramadol 7.5%). Of the 3328 patients taking psychotropic drugs (alone or in combination with analgesics), 96.1% were taking antidepressants and 71.4% were taking benzodiazepines (anxiolitics/ hypnotics). 3.2. Prevalence and characteristics of pain The prevalence of pain in patients with a depressive disorder was 59.1% (CI 95%: 57.7%; 60.7%). It was higher in the female population (63.8% vs 47.5%; p b 0.0001) and in patients older than 50 years of age (45.2% vs 54.8%; p b 0.001). Regarding the characteristics of the pain suffered (Table 1), the average duration of pain was 48.3 months (median 24 months; P25 = 9; P75 = 61), the mean intensity on the VAS was 68.2 (SD: 14.9), the most common location of pain was the back, and the average number of pain locations was 3.7 (SD: 1.3). Also, the aetiology of the pain was known and specified in 1206 patients (57.2%) (Table 1), with the most common cause being musculoskeletal or a connective tissue pathology (77.8%). Among patients with pain, a significant correlation was observed between the intensity of pain and the intensity of depression (p b 0001). Likewise, we observed higher scores on the Hamilton Depression scale in patients with a specific known aetiology of pain (vs patients with unknown aetiology; p b 0.01) and in patients with back pain (vs other pain locations; p b 0.03). On the other hand, the duration of the current depressive episode was longer in patients with pain (16.9 months; SD: 31.1 vs 11.0 months; SD: 14.1 p b 0.0001) and the patients' average score on the scale measuring inability to perform everyday activities due to pain was 55.9 (SD: 24.5).
The analysis of the factors associated with pain in patients suffering from depression can be seen in Table 2, which highlights the following factors as most strongly associated with pain: being female, being older, higher Hamilton scale score, being diagnosed with major depression, depression caused by physical disorder, depression caused by illegal drugs or dysthymia, and having certain DSM-IV-TR symptoms of depression, such as anhedonia, sleep disorders, loss of energy or depressive mood (Table 2). From the adjusted model, it can be observed that being female, the presence of loss of energy and the diagnosis of dysthymia or depression induced by physical disorders were risk factors associated independently with the presence of comorbid pain in these patients. Likewise, the age and the intensity of depression were two risk factors where each year of age and each point in the Hamilton scale increased the risk of having pain in 2% and 8% respectively. On the other hand, the presence of anhedonia and the diagnosis of depression induced by drugs were two factors inversely related to pain (Table 3). 4. Discussion Depression and chronic pain are highly comorbid conditions. These two entities have common and often overlapping symptoms. To date, most research has been done evaluating the presence of depression in patients afflicted with pain. The originality of our study is to investigate the presence of pain in a large sample of patients recently diagnosed of depression who were being attended by psychiatrists in their regular clinical practice in the out-patient setting. A high prevalence of pain in depressed patients was observed. Our findings showed that depression lasted longer in patients with pain, and the intensity of the depression was generally higher in patients with greater pain. Furthermore, our results showed that loss of energy was the depression symptom most closely related to the presence of pain, with a negative association existing with anhedonia. Thus, these data suggest that depression expresses itself or exerts an objective influence in pain itself, independently of a nociceptive stimulus.
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Table 2 Factors associated with the presence of pain. Variable
Label
N
OR
(95% CI)
p-value
Sex Age
Women ≥80 vs b 30 70–b80 vs b 30 60–b70 vs b 30 50–b60 vs b 30 40–b50 vs b 30 30–b40 vs b 30
3444 3322
1.95 3.82 1.75 1.77 2.19 1.45 0.93 1.02 0.56 0.71 3.76 3.01 0.29 1.64 2.41 0.73 1.11 1.41 1.01 1.07 1.78 1.13 0.97 1.07
(1.68; (1.90; (1.17; (1.28; (1.63; (1.08; (0.68; (1.02; (0.48; (0.49; (2.81; (0.86; (0.16; (1.37; (1.31; (0.59; (0.93; (1.14; (0.88; (0.93; (1.34; (0.97; (0.84; (1.05;
b 0.0001 b 0.0001
Age Major depression Bipolar disorder Depression induced by physical disorder Depression induced by drugs Depression induced by illegal drugs Dysthymia Depressed mood Anhedonia Diminished concentration Sleep disorders Change of body weight Feelings of worthlessness or guilt Loss of energy Psychomotor activity change Suicidal ideation Hamilton scale score
3322 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3392
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Our data are consistent with the study of Ohayon and Schatzberg (2003) that observed that in the general population 43.4% of patients with major depression has at least 1 chronic painful physical condition and the duration of the depression is nearly 6 months longer in patients with pain. In line with these results are those observed by Arnow et al. (2006) and Demyttenaere et al. (2006) as well as those obtained by Bair et al. (2003) when studying patients from psychiatric vs primary care settings. Regarding the psychological symptoms associated with pain, Ohayon (2004) observed that subjects who reported feeling sad or depressed were more likely to report chronic painful physical conditions than those who reported feeling hopeless, or than those who mentioned loss of interest or lack of pleasure. Likewise, the subjects who mentioned fatigue or loss of energy tended to report all types of chronic painful conditions. This is in agreement with our results where loss of energy was the symptom of depression most clearly associated with the presence of pain. Table 3 Logistic regression model of the variables associated with the presence of pain in patients with depression. Variable
Label
Adjusted OR
(Adjusted 95% CI)
p-value
Sex Depression induced by illegal drugs Depression induced by physical disorders Dysthymia Anhedonia Loss of energy Age (years) Hamilton Depression scale score
Female Yes
1.99 0.45
(1.68; 2.36) (0.21; 0.91)
0.000 0.028
Yes
4.41
(3.19; 6.08)
0.000
Yes Yes Yes
1.88 0.67 2.01 1.02 1.08
(1.52; 2.33) (0.51;0.86) (1.42; 2.83) (1.01; 1.03) (1.07;1.09)
0.000 0.002 0.000 0.000 0.000
Hosmer–Lemeshow = 6.477; p = 0.594.
2.27) 7.68) 2.63) 2.45) 2.96) 1.95) 1.27) 1.03) 0.66) 1.01) 5.01) 10.59) 0.52) 1.97) 4.41) 0.90) 1.32) 1.74) 1.16) 1.23) 2.37) 1.32) 1.12) 1.08)
b 0.0001 b 0.0001 0.0574 b 0.0001 0.0855 b 0.0001 b 0.0001 0.0046 0.0029 0.2550 0.0014 0.9047 0.3644 b 0.0001 0.1196 0.6626 b 0.0001
Von Korff and Simon (1996) compared the profile of the psychological symptoms among patients with pain and a population control group, and they observed that the feeling that everything is an effort, disturbed sleep, worry and low energy, were more common in patients with pain. Demyttenaere et al. (2006) observed that more severely depressed patients (higher number of positive DSM-IV criteria for major depression) have a higher prevalence of painful physical symptoms. In our study, a higher prevalence of pain was observed in patients with more severe depression as measured with the Hamilton Depression scale. However, the effect of the number of depressive symptoms was not studied. Furthermore, our results show that 43% of the depressed patients with pain had no known cause of pain or it was only weakly explained, which is in agreement with the data observed by Bair et al. (2003) who found that patients with depression have significantly more unexplained physical symptoms such as pain and fatigue and use more health resources than non-depressed patients. This supports again the hypothesis that pain can be a symptom of depression without the need of a nociceptive stimulus. Understanding the neurobiological basis of the relationship between pain and depression is important because the presence of comorbid pain contributes significantly to poorer outcomes and increased cost of treatment in major depressive disorder. However, despite their close relationship, the neurological basis of altered pain processing in patients with depression is poorly understood. In humans, neuro-imaging findings suggest that increased emotional reactivity in patients with depression may lead to an impaired ability to modulate pain experience (Strigo et al., 2008). This phenomenon could account for the augmented sensation of pain seen in depressed patients in our study. Regarding the CNS substrate for this association, the amygdala emerges as a possible candidate (Wiech and Tracey,
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2009). In fact, bilateral activation of the amygdala in humans has been found to correlate with perceived pain intensity (Bornhovd et al., 2002). In the same sense, activation of the amygdala has been consistently demonstrated in depression (Sheline, 2003). In our study, depressed patients with anhedonia reported less pain and fewer physical complaints. To our knowledge this is the first time that this association has been demonstrated, probably because in previous studies depressed patients with pain were not compared to depressed patients without pain. This opens the discussion about whether the role of the amygdala in the depression–pain relationship differs in depressed patients with and without pain. However, few neurobiological studies have addressed this issue. Our study demonstrated fewer pain complaints in patients who were depressed as a consequence of drug abuse. It is reasonable to think that because drugs of abuse such as opiates, stimulants (amphetamine or cocaine) or cannabinoids have analgesic properties, pain sensation might be significantly reduced in these patients. Some limitations in this study need to be pointed out. One is that other chronic medical or psychiatric conditions, such as hypertension (Pinto-Meza et al., 2006) or anxiety, have not been assessed and they are sometimes related to depression and often prevalent among people with chronic pain (Gureje, 2007; Scott et al., 2007). In a recent paper, Scott et al. (2007) noted the frequent association between pain, anxiety and depression and found a higher probability of chronic or multiple pains when depression and anxiety co-exist compared to when only one of them is present. Another limitation is that the survey conducted was a crosssectional study and consequently does not provide information about the direction of causality between pain and psychiatric disorders. We can therefore only speculate about the possible way in which the association between pain and depression is established. Some explanations have been offered; it has even been suggested that certain pain conditions, such as migraine (Breslau and Davis, 1993), share a common predisposition with some psychiatric disorders (Gureje et al., 2008). However, more follow-up studies are necessary to improve our understanding of pain–depression relationships. A strength of this study is that our results are based on a large dataset collected from a broad range of psychiatric centres with psychiatrists performing their usual clinical work. Also, the assessment of pain was performed by means of objective measures that enhanced accuracy and reduced the frequent subjectivity related to pain. 5. Conclusions This study shows a high prevalence of pain among depressive patients attending psychiatric clinics. Moreover, we observed that painful symptoms are modulated differently depending on the type and intensity of depression and the presence or not of specific symptoms, such as loss of energy or anhedonia, suggesting that depression exerts an objective influence in pain itself, independently of a nociceptive stimulus, and that pain can be a direct symptom of depression. Finally, we hypothesize that the neurobiological basis for the perception and/or interpretation of pain at the level of the mood–pain pathway is affected differently in
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accordance with the type and symptoms of depression. Given the high prevalence of pain found in our large sample, psychiatrists should be advised to ask their depressive patients for painful symptoms on a regular basis. Role of funding source This study was funded in part by Boehringer Ingelheim Spain with an unrestricted grant. No member of Boehringer Ingelheim staff had any role in the interpretation of data, in the writing of the report or in the decision to submit the paper for publication in the journal.
Conflict of interest The authors declare that they have no (financial and non-financial) competing interests related to this work. Dr. L Agüera-Ortiz had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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Lee, P., Zhang, M., Hong, J.P., Chua, H.C., Chen, K.P., Tang, S.W., Chan, B.T., Lee, M.S., Lee, B., Gallagher, G.L., Dossenbach, M., 2009. Frequency of painful physical symptoms with major depressive disorder in Asia: relationship with disease severity and quality of life. J. Clin. Psychiatry 70, 83–91. Mayberg, H.S., 2007. Defining the neural circuitry of depression: toward a new nosology with therapeutic implications. Biol. Psychiatry 61, 729–730. Merskey, H., Bogduk, N., 1994. Part III: pain terms. A current list definitions and notes on usage. In: Merskey, H., Bogduk, N. (Eds.), Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Task Force on Taxonomy. IASP Press, Seattle, pp. 209–214. Mico, J.A., Ardid, D., Berrocoso, E., Eschalier, A., 2006. Antidepressants and pain. Trends Pharmacol. Sci. 27, 348–354. Obiols, J., Ballús, C., 1979. Why do depressions become masked? In: Obiols, J., Ballús, C. (Eds.), Biological Psychiatry Today. Elsevier, North Holland, Amsterdam, pp. 509–514. Ohayon, M.M., 2004. Specific characteristics of the pain/depression association in the general population. J. Clin. Psychiatry 65 (Suppl 12), 5–9. Ohayon, M.M., Schatzberg, A.F., 2003. Using chronic pain to predict depressive morbidity in the general population. Arch. Gen. Psychiatry 60, 39–47. Pinto-Meza, A., Serrano-Blanco, A., Codony, M., Reneses, B., von Korff, M., Maria Haro, J., Alonso, J., 2006. Prevalencia y comorbilidad física y mental
del dolor dorsal y cervical crónicos en España: resultados del estudio ESEMeD. Med. Clín. 127, 325–330. Ramos-Brieva, J.A., Cordero-Villafafila, A., 1988. A new validation of the Hamilton Rating Scale for Depression. J. Psychiatr. Res. 22, 21–28. Scott, K.M., Bruffaerts, R., Tsang, A., Ormel, J., Alonso, J., Angermeyer, M.C., Benjet, C., Bromet, E., de Girolamo, G., de Graaf, R., Gasquet, I., Gureje, O., Haro, J.M., He, Y., Kessler, R.C., Levinson, D., Mneimneh, Z.N., Oakley Browne, M.A., Posada-Villa, J., Stein, D.J., Takeshima, T., Von Korff, M., 2007. Depression–anxiety relationships with chronic physical conditions: results from the World Mental Health Surveys. J. Affect. Disord. 103, 113–120. Sheline, Y.I., 2003. Neuroimaging studies of mood disorder effects on the brain. Biol. Psychiatry 54, 338–352. Strigo, I.A., Simmons, A.N., Matthews, S.C., Craig, A.D., Paulus, M.P., 2008. Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain. Arch. Gen. Psychiatry 65, 1275–1284. Von Korff, M., Simon, G., 1996. The relationship between pain and depression. Br. J. Psychiatry Suppl. (30), 101–108. Wiech, K., Tracey, I., 2009. The influence of negative emotions on pain: behavioral effects and neural mechanisms. Neuroimage 47, 987–994. Willner, P., 2002. Dopamine and depression. In: Di Chiara, Gaetano (Ed.), Handbook of Experimental Pharmacology, Vol. 154/II: Dopamine in the CNS II. Springer, Berlin, pp. 387–416.
Contents lists available at ScienceDirect
Journal of Affective Disorders j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j a d
Research report
Pain as a symptom of depression: Prevalence and clinical correlates in patients attending psychiatric clinics L. Agüera-Ortiz a, I. Failde b,⁎, J.A. Mico c, J. Cervilla d, J.J. López-Ibor e a Psychiatry Department, University Hospital 12 de Octubre, Complutense University, Madrid & Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain b Preventive Medicine and Public Health Area, University of Cádiz, Spain c Department of Neuroscience, Pharmacology and Psychiatry, School of Medicine, University of Cádiz & Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Cádiz, Spain d Psychiatry Department, University of Granada, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Granada, Spain e Department of Psychiatry, University Hospital San Carlos & Complutense University, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
a r t i c l e
i n f o
Article history: Received 25 August 2010 Accepted 10 October 2010 Available online 4 November 2010 Keywords: Pain Depression Psychiatric outpatients Anhedonia Loss of energy
a b s t r a c t Background: The need to assess the prevalence and characteristics of painful symptoms among depressed patients attended by psychiatrists in their regular clinical practice. Methods: A multi-centre, cross-sectional study was carried out in a large sample (n = 3566) of patients attending out-patient psychiatric facilities in Spain. All types of DSM-IV-TR depressive disorders were included. Data on the diagnosis, specific symptoms, intensity of depression and antidepressant and analgesic drug treatments were collected. The presence and characteristics of significant pain (visual analogue scale score N 40) at the time of the study were also recorded. Results: The prevalence of pain in depressed patients was 59.1% (CI 95%: 57.7%; 60.7%). Factors associated independently with the existence of significant pain were: being female, presence of loss of energy and the diagnosis of dysthymia or depression induced by physical disorders. In addition, age and the intensity of depression were two risk factors, where each year of age and each point in the Hamilton scale increased the risk of having pain by 2% and 8% respectively. The presence of anhedonia and the diagnosis of depression induced by illegal drugs were factors inversely related to pain. Limitations: The cross-sectional naturalistic characteristics of the study. Conclusion: Our data show a high prevalence of pain among depressive patients attending psychiatric clinics. Painful symptoms are modulated differently depending on the type of depression and the presence of specific symptoms, such as loss of energy or anhedonia. Psychiatrists should ask their depressive patients for the presence of pain on a regular basis. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Pain is an experience common to all human beings. Nevertheless, the variety of words to describe pain in different languages means that the experience is highly subjective, culture loaded and directly related with an affective correlate.
⁎ Corresponding author. Facultad de Ciencias de la Salud, Universidad de Cádiz, Avda. Ana de Viya 52, 11009 Cadiz, Spain. Tel.: + 34 956019025; fax: + 34 956019011. E-mail address: [email protected] (I. Failde). 0165-0327/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2010.10.022
The inclusive affective use of “pain” comprises meanings of “suffering”, “distress”, “uneasiness”, “displeasure”, and “unpleasure”. Pain and depressed mood are experiences that have more common characteristics than commonly thought. Pain is not just the sensation produced by injuries. The IASP (International Association for the Study of Pain) has reached after several attempts the pain definition as: “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (Merskey and Bogduk, 1994). Hence the unpleasantness of pain is often
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associated to anxiety or depressive feelings. The anxiety is evoked by the threat of damage and depression by the unpleasantness and the loss of healthy positive feelings. On the other hand, the association of tissue damage and pain is not always a direct one and many people report pain in the absence of tissue damage or any likely pathophysiological cause. Accordingly, the IASP avoids tying pain to a stimulus, and states that it is always a psychological state. Pain seems undoubtedly a common symptom of depressive disorders. Masked depression (Obiols and Ballús, 1979) and atypical depression were commonly used – and abused – concepts before DSM-III, and both included several painful manifestations. In spite of the fact that single episodes of masked depressions are present in ICD-10 (F32.8 Other depressive episodes), today, neither ICD-10 nor DSM-IV-TR mentions pain as a symptom of depressive disorder, but both include depression or mood disorders as exclusion criteria for persistent somatoform pain disorder or pain disorder. On the other hand, pain manifestations such as back, head or muscle aches are items present in several rating scales for depression (i.e., HDRS). Depression is currently viewed as a mental disorder comprising both emotional and somatic symptoms. The prevalence of somatic and physical symptoms in patients with major depressive disorder (MDD) in tertiary care is 30– 54% (Brecht et al., 2007; Giesecke et al., 2005; Lee et al., 2009). However, a number of studies have demonstrated that in almost half of all patients with physical symptoms, depression goes undiagnosed (Kessler et al., 2003) with the consequent increased risk of developing more severe depression and increased resistance to treatment (Bair et al., 2004). In addition, physical symptoms are associated with a greater likelihood of recurrence and new depressive episodes. Despite much epidemiological work done, the actual frequency of depression-related pain is not clear, with studies giving high ranges of prevalence. To cite only one of them, Blair and colleagues published a meta-analysis showing a prevalence of 65% of painful symptoms in patients with depression (Bair et al., 2003). Pain has also implications on therapy and resource utilization. It has been suggested that the presence of baseline pain is associated with fewer benefits from antidepressant therapy and worse quality of life outcomes (Bair et al., 2004). A population-based study found that people with depression and concomitant pain initiated 20% more visits to medical providers and their total medical costs were higher than people with depression but without pain (Bao et al., 2003). This is in keeping with the fact that the presence of pain is also associated with longer duration and increased severity of the depressive episode (Karp et al., 2005). The experience of pain and of negative feelings such as sorrow and depression shares common neurobiological substrates and mechanisms. For instance, in major depression a hyperactivity has been described in the perigenual anterior cingulate cortex, (Mayberg, 2007) a region which has been associated to pleasure and which receives important projections from the midbrain dopamine system. Activation of the brain's mesolimbic dopamine system apparently organizes reward oriented behaviour which prevents the appearance of some forms of mental pain. Dopamine neurons in the relevant midbrain area fire in response to painful aversive (Berridge
107
and Winkielman, 2003) and avoidable stimuli, such as tail pinch, rather than only in response to ones we seek out and enjoy, so that the system seems to some to respond to both pleasure and pain and an insufficiency of dopamine neurotransmission at D2 receptors seems implicated in depression (Willner, 2002). Recently neuro-imaging studies have revealed a close relationship between brain areas implicated in the integration of the sensorial and emotional aspects of pain and areas modulated by depression (Ehnvall et al., 2009). In this sense, it seems evident that pain could be an important biological factor to be considered to improve the diagnosis and treatment of depression. The close relationship between the antidepressant mechanisms of action of antidepressants and their analgesic mechanisms of action (Mico et al., 2006) is evidence that mood and pain may share similar neurobiological mechanisms and neuro-anatomical substrates and consequently these two processes could co-exist in patients with depression. Considering all this epidemiological, clinical and neurobiological evidence, the need for a better understanding of the complex interplay between depression and painful physical symptoms is now recognized. Previous research examining the relationship between depression and painful physical symptoms has focused on patients selected on the basis of their painful physical condition who were subsequently examined for major depression. Furthermore, of the studies carried out in secondary care, most were in pain clinics, with a scarcity of studies performed in psychiatric settings (Garcia-Cebrian et al., 2006). The aim of our study and its originality was to estimate the prevalence of pain among depressive patients who are attended by psychiatrists in their regular clinical practice. A large and varied sample of patients has been examined to better understand the characteristics of depression in patients with and without pain, bearing in mind that pain might be considered in the future as a factor to be taken into account to improve depression diagnosis and general health outcomes. 2. Subjects and methods 2.1. Study design and sampling process A multi-centre, cross-sectional study was carried out in a sample of mental health care centres in Spain between April 2006 and December 2006. In order to obtain a representative sample, the number of psychiatric centres chosen in each Spanish region was proportional to the number of inhabitants in the region. In each centre, one psychiatrist was chosen at random, constituting a final sample of 400 researchers. The study was conducted in agreement with the Helsinki Declaration and with standard working procedures and protocols, and approved by a Clinical Research Ethics Committee, ensuring adherence to the norms of good clinical practice. 2.2. Patient population The study included men and women over 18 years old, visiting their psychiatrist for the first time and being diagnosed with depression according to the criteria of the
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DSM-IV-TR. Also, patients had to be mentally and physically able to participate in the study and give their written, informed consent. 2.3. Sample size Assuming a 65% prevalence of concomitant pain in depressed patients, to obtain a 95% confidence interval of width 6% (CI 95%: 62%; 68%) (Bair et al., 2003) and to be able to detect differences between subgroups defined by age, sex, and type of depression, a required sample of 2736 patients was calculated. A 10% rate of refusal to participate was assumed, resulting in 3010 patients being necessary for the study. 2.4. Recruitment To obtain the calculated number of patients, each of the 400 selected psychiatrists was to interview 8 consecutive patients coming for consultation who fulfilled the inclusion criteria for the study.
test, chi-squared test and correlation test were used to study associations between variables. The prevalence (with 95% CI) of pain was computed, and to study the factors associated with pain, crude and adjusted odds ratios (ORs) were calculated. For this purpose a logistic regression model was performed in which the outcome variable was the presence or absence of pain, and the variables included in the model were: sex, age, Hamilton scale score, type of depression (major depression, dysthymia, depression induced by illegal drugs, depression induced by physical disorders, depression induced by drugs and depression due to bipolar disorder) and specific symptoms of depression (anhedonia, loss of energy, sleep disorders, and depressive mood). A subset of the variables was selected that best predicted the presence or absence of pain using the Hosmer–Lemeshow test to identify the best model. An age– sex interaction term was also introduced into the model.
3. Results 3.1. Population characteristics
2.5. Measurements 3566 patients were finally included in the study. The average age of the population was 49.4 (SD: 13.02). 71.3% were female, and the women were generally older than the men (50.2 years (SD: 12.9) vs 47.6 years (SD 13.4); p b 0.001). 77.5% of the whole population had completed primary or secondary education and 64.9% lived with a partner. The type of mood disorder most frequently diagnosed was major depression, followed by dysthymia and depression induced by physical disorders (Fig. 1); and the most common symptoms observed were depressive mood, loss of energy, sleep disorders and anhedonia (Fig. 2). The mean number of episodes of depression suffered by the patients (including the current one) was 2.6 (SD: 2.2; median = 2); and the median duration of the current depressive episode was 7 months (P25 = 5; P75 = 13). Furthermore, 96.4% of the patients studied were undergoing some type of pharmacologic treatment at the time of 100 90 80
72,4
70 60
% 50 40 30 17,5
20 9,7
10
3,5
ym
ia
gs Di
ga lD Ille D
Fig. 1. Diagnostic of depression.
sth
ru
ug Dr D
so r Di al sic
s
rs de
lar po Bi Ph y D
n sio De pr M
ajo r
2.6. Statistical analysis In the descriptive analysis, absolute frequency and central trend and dispersion measurements were calculated for qualitative and quantitative variables. The t-test, Wilcoxon
1,5
0,4
0 es
The interviews were performed at psychiatric out-patient centres. Depression was confirmed based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) and the intensity of depression was assessed by the 17-item Hamilton Depression scale validated in Spanish by Ramos-Brieva and Cordero-Villafafila (1988). Information about the duration of the current depressive episode and any history of depression up to the date of the study was also collected. Patients were asked about the presence of pain at the time of the study, lasting at least for the previous 6 weeks, and if present, pain characteristics were recorded. To assure a clearcut presence of painful symptoms, only patients with an intensity of pain over 40 on the visual analogue scale (VAS) in a range of 0–100, where 0 was no pain and 100 was the worst (Collins et al., 1997) were considered. Pain localization was recorded as well as its aetiology. Patients with pain were divided into two groups: subjects with a pain of known aetiology and subjects where the aetiology was unknown or only weakly explained. The interference of pain in the patients' everyday activities in the week before the study was also assessed using a visual analogue scale, where a score of 0 was no interference and 100 was total incapacity. Information related to socio-demographic variables (age, sex, educational level and social status), and clinical variables (intensity of pain, duration of pain, localization of pain, and treatment (i.e.: analgesics and/or psychotropics) was collected. Data collection forms were further monitored centrally to check and correct missing data or inconsistencies.
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100
109
Table 1 Characteristics of pain in 2107 depressed patients with pain.
90 Variables
80
Duration of pain (months)
70
Intensity of pain (VAS score)
% 60
Pain location a Head Neck Back Limbs Joints Specific known aetiology
50 40
ia Sl ee C tio ha p n ng D is e or of d er Bo s dy W Fe ei el gh in t gs o fG Lo ss ui Ps lt of yc En ho e m rg ot y or C Su ha ic ng id e al Id ea tio n
on
nt ra
SD: standard deviation; P25: 25th percentile; P75: 75th percentile; VAS: visual analogue scale. a More than 1 site was possible.
C on
ce
ed
N (%)
1038 48.3 (62.6) 24 (9; 61) 2107 68.2 (14.9) 2107 (100.0) 1376 (65.3) 1570 (74.5) 1697 (80.5) 1554 (73.8) 1551 (73.6) 1206 (57.2)
3.3. Factors associated with pain
D
im
in is he d
D ep re
ss
An h
ed
M
oo
d
30
N Mean (SD) Median (P25; P75) N Mean (SD) N (%)
Fig. 2. DSM-IV diagnostic criteria.
the study (N = 3440). 3.1% were on analgesics alone, 43.8% were on psychotropic drugs alone, and 49.5% were on both. Of the 1878 patients under treatment with analgesics (alone or in combination with psychotropic drugs), 94.4% were taking NSAIDs, in particular paracetamol (acetaminophen) (52.1%) or ibuprofen (37.5%), and 15.4% were taking opioid analgesics (in particular tramadol 7.5%). Of the 3328 patients taking psychotropic drugs (alone or in combination with analgesics), 96.1% were taking antidepressants and 71.4% were taking benzodiazepines (anxiolitics/ hypnotics). 3.2. Prevalence and characteristics of pain The prevalence of pain in patients with a depressive disorder was 59.1% (CI 95%: 57.7%; 60.7%). It was higher in the female population (63.8% vs 47.5%; p b 0.0001) and in patients older than 50 years of age (45.2% vs 54.8%; p b 0.001). Regarding the characteristics of the pain suffered (Table 1), the average duration of pain was 48.3 months (median 24 months; P25 = 9; P75 = 61), the mean intensity on the VAS was 68.2 (SD: 14.9), the most common location of pain was the back, and the average number of pain locations was 3.7 (SD: 1.3). Also, the aetiology of the pain was known and specified in 1206 patients (57.2%) (Table 1), with the most common cause being musculoskeletal or a connective tissue pathology (77.8%). Among patients with pain, a significant correlation was observed between the intensity of pain and the intensity of depression (p b 0001). Likewise, we observed higher scores on the Hamilton Depression scale in patients with a specific known aetiology of pain (vs patients with unknown aetiology; p b 0.01) and in patients with back pain (vs other pain locations; p b 0.03). On the other hand, the duration of the current depressive episode was longer in patients with pain (16.9 months; SD: 31.1 vs 11.0 months; SD: 14.1 p b 0.0001) and the patients' average score on the scale measuring inability to perform everyday activities due to pain was 55.9 (SD: 24.5).
The analysis of the factors associated with pain in patients suffering from depression can be seen in Table 2, which highlights the following factors as most strongly associated with pain: being female, being older, higher Hamilton scale score, being diagnosed with major depression, depression caused by physical disorder, depression caused by illegal drugs or dysthymia, and having certain DSM-IV-TR symptoms of depression, such as anhedonia, sleep disorders, loss of energy or depressive mood (Table 2). From the adjusted model, it can be observed that being female, the presence of loss of energy and the diagnosis of dysthymia or depression induced by physical disorders were risk factors associated independently with the presence of comorbid pain in these patients. Likewise, the age and the intensity of depression were two risk factors where each year of age and each point in the Hamilton scale increased the risk of having pain in 2% and 8% respectively. On the other hand, the presence of anhedonia and the diagnosis of depression induced by drugs were two factors inversely related to pain (Table 3). 4. Discussion Depression and chronic pain are highly comorbid conditions. These two entities have common and often overlapping symptoms. To date, most research has been done evaluating the presence of depression in patients afflicted with pain. The originality of our study is to investigate the presence of pain in a large sample of patients recently diagnosed of depression who were being attended by psychiatrists in their regular clinical practice in the out-patient setting. A high prevalence of pain in depressed patients was observed. Our findings showed that depression lasted longer in patients with pain, and the intensity of the depression was generally higher in patients with greater pain. Furthermore, our results showed that loss of energy was the depression symptom most closely related to the presence of pain, with a negative association existing with anhedonia. Thus, these data suggest that depression expresses itself or exerts an objective influence in pain itself, independently of a nociceptive stimulus.
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Table 2 Factors associated with the presence of pain. Variable
Label
N
OR
(95% CI)
p-value
Sex Age
Women ≥80 vs b 30 70–b80 vs b 30 60–b70 vs b 30 50–b60 vs b 30 40–b50 vs b 30 30–b40 vs b 30
3444 3322
1.95 3.82 1.75 1.77 2.19 1.45 0.93 1.02 0.56 0.71 3.76 3.01 0.29 1.64 2.41 0.73 1.11 1.41 1.01 1.07 1.78 1.13 0.97 1.07
(1.68; (1.90; (1.17; (1.28; (1.63; (1.08; (0.68; (1.02; (0.48; (0.49; (2.81; (0.86; (0.16; (1.37; (1.31; (0.59; (0.93; (1.14; (0.88; (0.93; (1.34; (0.97; (0.84; (1.05;
b 0.0001 b 0.0001
Age Major depression Bipolar disorder Depression induced by physical disorder Depression induced by drugs Depression induced by illegal drugs Dysthymia Depressed mood Anhedonia Diminished concentration Sleep disorders Change of body weight Feelings of worthlessness or guilt Loss of energy Psychomotor activity change Suicidal ideation Hamilton scale score
3322 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3566 3392
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Our data are consistent with the study of Ohayon and Schatzberg (2003) that observed that in the general population 43.4% of patients with major depression has at least 1 chronic painful physical condition and the duration of the depression is nearly 6 months longer in patients with pain. In line with these results are those observed by Arnow et al. (2006) and Demyttenaere et al. (2006) as well as those obtained by Bair et al. (2003) when studying patients from psychiatric vs primary care settings. Regarding the psychological symptoms associated with pain, Ohayon (2004) observed that subjects who reported feeling sad or depressed were more likely to report chronic painful physical conditions than those who reported feeling hopeless, or than those who mentioned loss of interest or lack of pleasure. Likewise, the subjects who mentioned fatigue or loss of energy tended to report all types of chronic painful conditions. This is in agreement with our results where loss of energy was the symptom of depression most clearly associated with the presence of pain. Table 3 Logistic regression model of the variables associated with the presence of pain in patients with depression. Variable
Label
Adjusted OR
(Adjusted 95% CI)
p-value
Sex Depression induced by illegal drugs Depression induced by physical disorders Dysthymia Anhedonia Loss of energy Age (years) Hamilton Depression scale score
Female Yes
1.99 0.45
(1.68; 2.36) (0.21; 0.91)
0.000 0.028
Yes
4.41
(3.19; 6.08)
0.000
Yes Yes Yes
1.88 0.67 2.01 1.02 1.08
(1.52; 2.33) (0.51;0.86) (1.42; 2.83) (1.01; 1.03) (1.07;1.09)
0.000 0.002 0.000 0.000 0.000
Hosmer–Lemeshow = 6.477; p = 0.594.
2.27) 7.68) 2.63) 2.45) 2.96) 1.95) 1.27) 1.03) 0.66) 1.01) 5.01) 10.59) 0.52) 1.97) 4.41) 0.90) 1.32) 1.74) 1.16) 1.23) 2.37) 1.32) 1.12) 1.08)
b 0.0001 b 0.0001 0.0574 b 0.0001 0.0855 b 0.0001 b 0.0001 0.0046 0.0029 0.2550 0.0014 0.9047 0.3644 b 0.0001 0.1196 0.6626 b 0.0001
Von Korff and Simon (1996) compared the profile of the psychological symptoms among patients with pain and a population control group, and they observed that the feeling that everything is an effort, disturbed sleep, worry and low energy, were more common in patients with pain. Demyttenaere et al. (2006) observed that more severely depressed patients (higher number of positive DSM-IV criteria for major depression) have a higher prevalence of painful physical symptoms. In our study, a higher prevalence of pain was observed in patients with more severe depression as measured with the Hamilton Depression scale. However, the effect of the number of depressive symptoms was not studied. Furthermore, our results show that 43% of the depressed patients with pain had no known cause of pain or it was only weakly explained, which is in agreement with the data observed by Bair et al. (2003) who found that patients with depression have significantly more unexplained physical symptoms such as pain and fatigue and use more health resources than non-depressed patients. This supports again the hypothesis that pain can be a symptom of depression without the need of a nociceptive stimulus. Understanding the neurobiological basis of the relationship between pain and depression is important because the presence of comorbid pain contributes significantly to poorer outcomes and increased cost of treatment in major depressive disorder. However, despite their close relationship, the neurological basis of altered pain processing in patients with depression is poorly understood. In humans, neuro-imaging findings suggest that increased emotional reactivity in patients with depression may lead to an impaired ability to modulate pain experience (Strigo et al., 2008). This phenomenon could account for the augmented sensation of pain seen in depressed patients in our study. Regarding the CNS substrate for this association, the amygdala emerges as a possible candidate (Wiech and Tracey,
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2009). In fact, bilateral activation of the amygdala in humans has been found to correlate with perceived pain intensity (Bornhovd et al., 2002). In the same sense, activation of the amygdala has been consistently demonstrated in depression (Sheline, 2003). In our study, depressed patients with anhedonia reported less pain and fewer physical complaints. To our knowledge this is the first time that this association has been demonstrated, probably because in previous studies depressed patients with pain were not compared to depressed patients without pain. This opens the discussion about whether the role of the amygdala in the depression–pain relationship differs in depressed patients with and without pain. However, few neurobiological studies have addressed this issue. Our study demonstrated fewer pain complaints in patients who were depressed as a consequence of drug abuse. It is reasonable to think that because drugs of abuse such as opiates, stimulants (amphetamine or cocaine) or cannabinoids have analgesic properties, pain sensation might be significantly reduced in these patients. Some limitations in this study need to be pointed out. One is that other chronic medical or psychiatric conditions, such as hypertension (Pinto-Meza et al., 2006) or anxiety, have not been assessed and they are sometimes related to depression and often prevalent among people with chronic pain (Gureje, 2007; Scott et al., 2007). In a recent paper, Scott et al. (2007) noted the frequent association between pain, anxiety and depression and found a higher probability of chronic or multiple pains when depression and anxiety co-exist compared to when only one of them is present. Another limitation is that the survey conducted was a crosssectional study and consequently does not provide information about the direction of causality between pain and psychiatric disorders. We can therefore only speculate about the possible way in which the association between pain and depression is established. Some explanations have been offered; it has even been suggested that certain pain conditions, such as migraine (Breslau and Davis, 1993), share a common predisposition with some psychiatric disorders (Gureje et al., 2008). However, more follow-up studies are necessary to improve our understanding of pain–depression relationships. A strength of this study is that our results are based on a large dataset collected from a broad range of psychiatric centres with psychiatrists performing their usual clinical work. Also, the assessment of pain was performed by means of objective measures that enhanced accuracy and reduced the frequent subjectivity related to pain. 5. Conclusions This study shows a high prevalence of pain among depressive patients attending psychiatric clinics. Moreover, we observed that painful symptoms are modulated differently depending on the type and intensity of depression and the presence or not of specific symptoms, such as loss of energy or anhedonia, suggesting that depression exerts an objective influence in pain itself, independently of a nociceptive stimulus, and that pain can be a direct symptom of depression. Finally, we hypothesize that the neurobiological basis for the perception and/or interpretation of pain at the level of the mood–pain pathway is affected differently in
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accordance with the type and symptoms of depression. Given the high prevalence of pain found in our large sample, psychiatrists should be advised to ask their depressive patients for painful symptoms on a regular basis. Role of funding source This study was funded in part by Boehringer Ingelheim Spain with an unrestricted grant. No member of Boehringer Ingelheim staff had any role in the interpretation of data, in the writing of the report or in the decision to submit the paper for publication in the journal.
Conflict of interest The authors declare that they have no (financial and non-financial) competing interests related to this work. Dr. L Agüera-Ortiz had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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