Ansiedad, depresion y su relacion con el dolor y la gravedad de la fibromialgia.
Chronic pain is often associated with comorbidities such as anxiety and depression, resulting in a low health-related quality of life (Bennett, Jones, Turk, Russell, & Matallana, 2007; Silverman, Harnett, Zlateva, & Mardekian, 2010; Wilson, Robinson, & Turk, 2009; Wolfe et al., 1990) and poor daily functioning (Ramirez y Valdivia, 2003). Fibromyalgia has been found to be strongly associated with depressive and anxiety symptoms, a personal or family history of depression, and accompanying antidepressant treatment (Arnold, 2008). Many individuals with fibromyalgia also have comorbid psychiatric disorders, which can present diagnostic dilemmas and require additional treatment considerations to optimize patient outcomes (Silverman et al., 2010). Furthermore, Gormsen, Rosenberg, Bach, & Jensen (2010), observed that patients with fibromyalgia have more psychological symptoms such as depression and anxiety than patients with neuropatic pain. Moreover, associations between pain intensity and mood phenomena were only found in fibromyalgia patients. On the other hand, Jensen et al. (2010), observed that negative mood in fibromyalgia patients can lead to a poor perception of one's physical health (and vice-versa) but do not influence the performance in clinical and experimental pain assessments.
Despite relevant evidence of physical illness promoting fibromyalgia syndrome, some authors claim that it is a psychological disorder, or due to "psychological amplification". More evidence for such views is lacking. The physical distress of fibromyalgia syndrome can increase both anxiety and depression. Current imaging studies support the view that central effects connected with fibromyalgia syndrome relate to the processing of noxious stimulation more than affective disorder (Merskey, 2008).
Although there are several studies investigating the relationship between depressive disorders and symptoms of fibromyalgia, data regarding the impact of anxiety and depression on perceived pain and tenderness in fibromyalgia patients are still scarce and inconclusive. The aim of the present study was to analyze the relationship of anxiety and depression with fibromyalgia perceived pain (as measured by questionnaires) and tenderness (measured by tender points count and algometer score) and fibromyalgia severity (global affectation) in women. Moreover, the relationship between anxiety and depression and fibromyalgia pain and severity has never been explored in Spanish population.
The study sample comprised 127 women aged 51.3 [+ or -] 7.3 years diagnosed as having fibromyalgia by a rheumatologist following the American College of Rheumatology criteria (Wolfe et al., 1990). Women were recruited from different fibromyalgia associations via e-mail, letter or telephone. 48% patients had been diagnosed five or less years ago and 52% had been diagnosed of fibromyalgia more than 5 years ago. 70% were postmenopausal, the majority of the participants were married (73%). 8% of the sample had unfinished studies, 42% finished primary school, 21% secondary school and 29% had a University degree. The participants had varied levels of occupations: 60% were employed at home (housewife), 25% working, 7% retired, 7% unemployed and 2% were students.
* Stadiometer Seca 22 (Hamburg, Germany) and InBody 720 Biospace (Seoul, Korea). Height (cm) was measured using a stadiometer (Seca 22, Hamburg, Germany) and weight (kg) with a scale (InBody 720, Biospace, Seoul, Korea). Body mass index (BMI) was calculated as weight (in kilograms) divided by height squared (in meters) and categorized using the international criteria: underweight (<18.5 kg/[m.sup.2]), normal weight (18.5-24.99 kg/[m.sup.2]), overweight (25.0-29.99 kg/[m.sup.2]) and obese ([greater than or equal to] 300 kg/[m.sup.2]).
* The Hospital Anxiety and Depression Scale (HADS; Zigmond & Snaith, 1983), the Spanish version by Quintana et al. (2003). The HADS was developed to identify caseness (possible and probable) of anxiety disorders and depression among patients in non-psychiatric hospital clinics. It was divided into an Anxiety subscale (HADS-Anxiety) and a Depression subscale (HADS-Depression) both containing seven intermingled items. HADS has been found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression in both somatic, psychiatric and primary care patients and in the general population (Bjelland, Dahl, Haug, & Neckelmann, 2002). The HADS contains 14 statements, ranging from 0 to 3 in which a higher score indicates a higher degree of distress. The scores build 2 subscales: anxiety (0-21) and depression (0-21) (Zigmond & Snaith, 1983). Interpretation of the HADS is based primarily on the use of cut-off scores, although there is no generally accepted cut-off to define anxiety or depression (Bjelland et al., 2002). Some authors recommend that scores of between 8 and 10 identify mild cases, 1115 moderate cases, and 16 or above, severe cases (Snaith & Zigmond, 1994). In most studies, an optimal balance between sensitivity and specificity was achieved with a score of 8 or higher on both HADS-Anxiety and HADS-Depression (Abiodun, 1994; Bjelland et al., 2002; Zigmond & Snaith, 1983). In the present study we have used both types of cut-off scores as appropriated. The Spanish version of the HADS test-retest reliability presented correlation coefficients above 0.85. The internal consistency was high, with Cronbach's alphas coefficients of 0.86 for anxiety and 0.86 for depression (Quintana et al., 2003).
* The Short-Form-36 Health Survey (SF36; Jenkinson, Coulter, & Wright (1993), the Spanish version by Alonso, Prieto, & Anto (1995). The SF-36 was used to assess health-related quality of life. The SF36 is composed of 36 items, grouped into eight scales, which include both physical and mental health, assessing eight dimensions: physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, mental health and general health. Each subscale score is standardized and ranges from 0 to 100, where 0 indicates the worst possible health status and 100 the best possible. The scores represent the percentage of the total possible score achieved (Ware & Sherbourne, 1992). The test-retest reliability and internal consistency of the Spanish version of this questionnaire has been studied (Alonso et al., 1995). Correlation coefficients between the test and retest were between 0.58 for SF36-emotional role subscale to 0.99 for SF36-physical role. Internal consistency showed Cronbach's alpha coefficients between 0.78 for SF36-vitality subscale to 0.96 for SF36-physical role subscale.
* The Fibromyalgia Impact Questionnaire (FIQ; Burckhardt, Clark, & Bennett, 1991). We used the Spanish version (Rivera & Gonzalez, 2004) of FIQ to assess fibromyalgia severity. The FIQ assesses the components of health status that are believed to be most affected by fibromyalgia. It is composed of ten subscales: physical impairment, overall well being, work missed and a seven items of a visual analogy scale (VAS) marked in 1-cm increments on which the patient rates the job difficulty, pain, fatigue, morning tiredness, stiffness, anxiety and depression. The FIQ total score ranges from 0 to 100 and a higher value indicates a greater impact of the disorder (Bennett, 2005). Correlation coefficients between the test and retest were between 0.58 for VAS-anxiety to 0.83 for work missed days. Internal consistency showed Cronbach's alpha coefficients of 0.82 for the total items of the FIQ; alpha=0.79 for the 8 items, without the 2 items concerning work, and alpha=0.86 for the 9 sub-items of the physical impairment (Rivera & Gonzalez, 2004). Patients were categorized as having moderate or severe fibromyalgia according to the FIQ cut-off proposed by Bennet, Bushmakin, Cappelleri, Zlateva, & Sadosky (2009): FIQ <59 vs. [greater than or equal to] 59 for moderate and severe fibromyalgia, respectively.
* Algometer EFFEGI, FPK 20 (Alfonsine, Italy). We assessed 18 tender points according to the American College of Rheumatology criteria for classification of fibromyalgia (Wolfe et al., 1990). A standard pressure algometer (EFFEGI, FPK 20, Alfonsine, Italy) was used to measure tender point count. The pain threshold at each tender point was determined by applying increasing pressure with the algometer perpendicular to the tissue, at a rate of ~1 kg/s. Patients were asked to say 'stop' at the moment pressure became painful. The mean of two successive measurements at each tender point was used for the analysis. Tender point scored as positive when the patient noted pain at pressure of 4 kg/[cm.sup.2] or less. The total of such positive tender points was recorded as the individual's tender point count. An algometer score was calculated as the sum of the pain-pressure values obtained for each tender point. This examination was conducted by a trained physiotherapist.
All patients were informed about the study and signed a written informed consent to participate. Inclusion criteria for the data analysis were not to have other rheumatic diseases and/or severe disorders such as cancer, severe coronary disease, or schizophrenia, and to have valid data in the Hospital Anxiety and Depression Scale (HADS) (Quintana et al., 2003). The study was reviewed and approved by the Ethics Committee of the "Hospital Virgen de las Nieves" of Granada.
Data collection was conducted for all the patients in the fibromyalgia association in two different occasions separated by one day. The first day weight, height and tender points were assessed and the questionnaires were administered in the second appointment. All measurements were performed by the same trained researchers group in order to reduce inter-examiners error.
One-way analysis of covariance (ANCOVA) with adjustment by age and BMI was used to compare pain across HADS-anxiety and HADS-depression status categories. Pairwise comparisons were performed with Bonferroni's adjustment. Standardized effect size statistics and its exact confidence interval were estimated by Cohen's d. Taking into account the cut-off established by Cohen, the effect size (Cohen'd) can be small (~0.2), medium (~0.5) or large (~0.8). Binary logistic regression after adjustment for age and BMI was used to further study the relationship of high HADS-anxiety and high HADS-depression with fibromyalgia severity (FIQ [greater than or equal to] 59 or FIQ [greater than or equal to] 70) and Type II fibromyalgia. We adjusted by BMI as covariable because a high BMI has been associated with worse quality of life, pain and symptomatology in fibromyalgia patients (Aparicio, Ortega, Carbonell-Baeza, Camiletti et al., 2011; Aparicio, Ortega, Carbonell-Baeza, Femia et al., 2011; Yunus, Arslan & Aldag, 2002). All analyses were conducted using SPSS version 16.0 for Windows (SPSS, Chicago, IL). The level of significance was set at p<.05.
Physical and psychological characteristics of the study sample are shown in table 1. We analyzed the differences in perceived pain, as measured by FIQ and SF36 questionnaires and tenderness (algometer score and tender points count) across the three categories of HADS-anxiety and HADS-depression status proposed by Snaith & Zigmond (1994). We additionally included the cut-off of HADS-anxiety and HADS-depression [less than or equal to] 8 proposed by several authors (Abiodun, 1994; Bjelland et al., 2002; Zigmond & Snaith, 1983) (table 2). Perceived pain, as measured by SF36-pain, differed across anxiety and depression categories (p<.01 and p<.05, respectively). SF36-pain scores were significantly worse in the severe anxiety group compared to the low and mild-anxiety groups (12.1 [+ or -] 3.4 vs. 27.0 [+ or -] 2.9 and 27.9 [+ or -] 3.1; respectively, both p<.05). Likewise, SF36-pain scores were lower in the severe-depression group compared with the low and mild-depression groups (7.5 [+ or -] 5.4 vs. 26.4 [+ or -] 2.2 and 24.4 [+ or -] 2.2, respectively, p<.01 and p<.05). There were also differences on perceived pain, as measured by FIQ, between the severe and low-anxiety groups (8.1 [+ or -] 0.4 vs. 6.6 [+ or -] 0.3; respectively, p<.05). There were no significant differences on FIQ-pain, algometer score and tender points count across HADS-depression and HADS-anxiety categories.
Logistic binary regression analysis adjusted by age and BMI was used to analyze the relationship between higher levels of anxiety and depression (HADS [greater than or equal to] 8) and severe fibromyalgia (FIQ [greater than or equal to] 59). HADS-anxiety scores [greater than or equal to] 8 were associated with an increased odds ratio (OR) of severe fibromyalgia (OR= 4.98; 95% confidence interval CI: 2.03-12.21). Likewise, HADS-depression scores [greater than or equal to] 8 were associated with severe fibromyalgia (OR= 4.95; 95% CI: 2.02-12.10).
The present study shows that high levels of anxiety and depression are associated with higher perceived pain (as measured by questionnaires) but not with higher tenderness (measured by tender points count and algometer score) in women with fibromyalgia. Furthermore, HADS-anxiety and HADS-depression scores [greater than or equal to] 8 were associated with increased risk of having severe fibromyalgia.
Fibromyalgia patients have more psychological distress, including depression and anxiety, than healthy controls (Gormsen et al., 2010). In our study, mean values of depression and anxiety were not pathological (HADS-anxiety and HADSdepression scores higher to 16), such as has also been reported in other similar studies (Gormsen et al., 2010; Jensen et al., 2010). However, to note is that in some studies, like the one performed by Aguglia, Salvi, Maina, Rossetto, & Aguglia (2010), the 83% of the fibromyalgia patients had clinically significant depressive symptoms.
We have observed a relationship between anxiety and perceived pain, as measured by VAS and SF36-pain scores whereas in the study by Jensen et al. (2010) anxiety symptoms did not correlate with clinical pain or experimental pain ratings. Fibromyalgia patients tend to report more stressful life events than controls (Stisi, Venditti, & Sarracco, 2008). Stisi et al. (2008) observed that this phenomena was due to the tendency of fibromyalgia patients to rate more severely mild stressful events. Therefore, they concluded that the particularly high number of events in their patients might be due to increased perception of stress.
The relationship between depressive symptoms and pain in fibromyalgia patients has been further explored in similar studies that have focused on the influence of depressive symptoms on pain processing (Aguglia et al., 2010; Giesecke et al., 2005; Jackson, O'Malley, & Kroenke, 2006; Jensen et al., 2010). We have observed an association between depression and higher levels of perceived pain, as measured by SF36-pain, but not with VAS scores (FIQ-pain). In the study by Aguglia et al. (2010), patients with depressive symptoms displayed significantly higher VAS scores, lower quality of life scores, and a higher Paykel Scale scores, than those without depressive symptoms. The patients with depressive symptoms from the study by Jackson et al. (2006), also displayed significantly higher VAS scores. In contrast, in the study by Jensen et al. (2010), depressive symptoms, anxiety and catastrophizing did not correlate with any measure of pain sensitivity and the authors did not support pronounced affective pain modulation in fibromyalgia. Instead, the significant correlation between depression, anxiety and the subjective rating on one's health (general health score from SF36 and FIQ questionnaires) that they obtained suggests that negative mood affects the perception of one's health status. Negative mood in fibromyalgia patients could thus lead to a poor perception of one's physical health but not to poor performance in clinical and experimental pain assessments as tenderness. Gieseke et al. (2005) also observed that depressive symptoms had no influence on the intensity of clinical pain or the sensory discriminative processing of induced pressure pain. However, with increasing depressive symptoms, activity in two brain regions pertaining to emotional processing, i.e. insula and amygdala, increased during sustained pain provocation (Giesecke et al. 2005). A similar study performed in rheumatoid arthritis patients (Schweinhardt et al. 2008) showed no relationship between depressive symptoms and cerebral pain processing in rheumatoid arthritis patients during experimental pain (heat). However, there was a positive correlation between ratings of depressive symptoms and activation of the medial prefrontal cortex during provoked joint pain.
Alterations in central processing of sensory input may also contribute to the cardinal symptoms of fibromyalgia, persistent widespread pain and enhanced pain sensitivity (Bradley, 2008). Exposure to psychosocial and environmental stressors, as well as altered autonomic nervous system and neuroendocrine responses, can induce to alterations in pain perception or pain inhibition. Understanding the pathophysiology of fibromyalgia and co-occurring disorders may help clinicians to provide the most appropriate treatment for each patient (Bradley, 2008).
There have been speculations about a generally exaggerated emotional response among fibromyalgia patients, suggesting that fibromyalgia was a virtual disease, caused by psychological vulnerability (Ehrlich, 2003). However, the effects of antidepressants on pain seem to be independent of mood, since the antidepressant and analgesic effects are independent of each other in clinical trials (Arnold et al., 2005; Russell et al., 2008). On the other hand, the role of psychological factors in the pathogenesis of fibromyalgia is controversial. Depressive symptoms are often present, but it has been difficult to determine if depressive disorders are a primary cause of fibromyalgia, or a reaction to the debilitating symptoms of this disease (Jackson et al., 2006).
Another explanation for the higher perception of pain in fibromyalgia patients with depressive symptoms is the tendency of depressed patients to adopt coping strategies defined as "catastrophizing" (Aguglia et al., 2010; Roth, Geisser, Theisen-Goodvich, & Dixon, 2005). Catastrophizing increases the perception of pain through the modification of attention and the anticipation of the pain itself, emphasizing emotional responses. Depression and catastrophizing are critically important variables in understanding the experience of pain in patients with rheumatologic disorders (Edwards, Calahan, Mensing, Smith, & Haythornthwaite, 2011). Pain, depression, and catastrophizing might all be uniquely important therapeutic targets in the multimodal management of fibromyalgia (Edwards et al. 2011). Another factor that influences pain perception and pain coping strategies are personality traits. It has been observed that some personality traits, such as harm avoidance (characterized by pessimism, fear, shyness and fatigability), influence the adoption of maladaptive strategies to cope with pain and pain perception (Cuevas, Lopez, Garcia & Diaz, 2008; Cuevas & Torrecillas, 2008). Therefore, high harm avoidance scores are associated with higher scores on depression (Mazza et al., 2009) and may negatively influence both adaptive coping pain strategies and a greater perception of pain.
Psychological interventions, and particularly cognitive behavioral therapy, can reduce catastrophizing, harm avoidance, anxiety and depression (Glombiewski et al., 2010). Intervention studies will confirm or contrast the potential long-term benefits of reducing such aspects in fibromyalgia patients, focusing particularly on studies of tailored early intervention (Evers, Kraaimaat, van Riel, & de Jong, 2002) that may help to move patients from a 'high-risk' to a relatively lower-risk profile in order to improve long-term pain outcomes.
Some limitations of the present study need to be mentioned. First, the study was developed just in women and thus, research on depression and anxiety presence and its relationship with pain in male fibromyalgia patients are needed. Second, individually tailored medication such as analgesics, antidepressants and anxiolytics, usually employed by patients to manage fibromyalgia symptoms, might have had some influence on pain, anxiety and depression levels. On the other hand, one of the strengths of the present study is that we have analyzed pain across low, mild, moderate and severe depression and anxiety subgroups, which allows us to compare between different anxiety and depression intensities.
Overall, high levels of anxiety and depression were associated with higher perceived pain but not with higher tenderness. Furthermore, patients with higher levels of anxiety and depression presented increased risk of severe fibromyalgia. Since these anxiety and depressive symptoms are associated with increased pain perception, anxiety and depression should be diagnosed and properly treated in order to improve fibromyalgia symptoms.
Future studies will confirm or contrast the present findings. Taking into account the present results, it would be of interest to analyze if psychological interventions focus on anxiety and depression could reduce fibromyalgia pain and severity.
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Received: Mai 6, 2012
Accepted: October 10, 2012
Virginia A. Aparicio (1), Francisco B. Ortega (1), Ana Carbonell-Baeza (2), Ana Maria Cuevas (1), Manuel Delgado-Fernandez (1), Jonatan R. (1)
(1) University of Granada (Spain); (2) University of Cadiz (Spain)
Correspondence: Virginia Aparicio, School of Sport Sciences, University of Granada, Carretera de Alfacar, s/n, 18011 Granada (Spain). E-mail: email@example.com
Table 1 Physical and psychological characteristics of the study sample (n= 127) Variable Range M (SD) Age (years) 31-70 51.9 (7.2) Height (cm) 139-178 157.3 (5.0) Weight (kg) 43-118 70.3 (13.6) Body mass index (kg/[m.sup.2]) 18-46 28.4(5.6) Weight status (%) UW/NW/OW/OB -- 1/32/35/32 FIQ total score 14-92 66.8 (14.0) Tender Points Count 4-18 16.6 (2.8) Algometer Score 24-87 48.4 (13.5) HADS-anxiety 0-20 10.6 (4.8) HADS-depression 1-20 8.6 (4.4) SF36 Mental Health 4-96 47.1 (20.8) Bodily pain 0-68 22.7 (16.9) Social functioning 0-100 42.9 (24.5) Physical functioning 0-90 36.6 (19.0) Vitality 0-80 21.5 (16.1) Emotional Role 0-100 34.9 (43.3) Physical role 0-100 5.5 (19.5) General Health 0-85 30.5 (15.9) Note: UW= underweight; NW= normal weight; OW= overweight; OB= obese; FIQ= Fibromyalgia Impact Questionnaire; SF36= General Health Short-Form Survey; HADS= Hospital Anxiety and Depression Scale. Table 2 Relationship between HADS-anxiety, HADS-depression and pain (measured by four indicators) HADS-Anxiety Low <8 (n= 30) Mild 8-10 (n= 26) SF36 * 27.0 (2.9) (a) 27.9 (3.1) (b) VAS from FIQ 6.5 (0.3) (a) 7.2 (0.4) Alqometer score 45.1 (2.7) 51.7 (3.2) Tender points count 16.9 (0.5) 16.1 (0.6) HADS-depression SF36 * Low <8 (n= 55) Mild 8-10 (n= 30) VAS from FIQ 26.4 (2.2) (a) 24.4 (3.0) (b) Alqometer score 6.9 (0.3) 6.9 (0.3) Tender points count 50.2 (2.1) 46.4 (2.8) 15.9 (0.4) 17.3 (0.5) HADS-Anxiety F Moderate Severe [greater 11-15 (n= 46) than or equal to] 16 (n= 23) SF36 * 21.6(2.4) 12.1 (3.4) (ab) 5.433 VAS from FIQ 6.9 (0.3) 8.1 (0.4) (a) 3.389 Alqometer score 49.4(2.4) 48.1 (3.5) 0.964 Tender points count 16.4(0.4) 16.9 (0.6) 0.571 HADS-depression F SF36 * Moderate Severe [greater 11-15 (n=31) than or equal to] 16 (n= 9) VAS from FIQ 19.5(2.9) 7.5 (5.4) (ab) 4.110 Alqometer score 7.2 (0.3) 8.4 (0.7) 1.559 Tender points count 47.4(3.1) 45.4 (5.6) 0.833 17.2 (0.5) 16.7 (0.9) 1.871 [rho] Effect size (severe vs. low anxiety) ([dagger]) SF36 * 0.002 0.927 (0.349; 1.51) VAS from FIQ 0.021 0.905 (0.329; 1.48) Alqometer score 0.427 0.191 (-0.359; 0.742) Tender points count 0.614 0 (-0.549; 0.549) [rho] Effect size (severe vs. low depression) SF36 * by Cohen's d VAS from FIQ 0.008 1.129 (0.593; 1.66) Alqometer score 0.209 -0.679(-1.191; -0.167) Tender points count 0.650 0.305 (-0.196; 0.806) 0.117 -0.272 (-0.773; 0.228) Notes: Values are means (standard deviation). HADS= Hospital Anxiety and Depression Scale; SF36= General Health Short-Form Survey; FIQ= Fibromyalgia Impact Questionnaire; VAS= visual analogical scale. (a,b) Common superscripts in a same raw indicate a significant difference (p < .05); Pairwise comparisons were performed with Bonferroni's adjustment. * Lower scores indicate higher pain. ([dagger]) Effects size statistics between low and severe groups are expressed as Cohen's d (95% exact confidence interval).