Depression, Pain, and Self-Efficacy in Fibromyalgia Syndrome

Perhaps, the most contentious issue in the study of the fibromyalgia syndrome (FMS) has been the role of major depression in its presentation, its natural history and its pathogenesis. Having lost confidence in hope, patients with depression, in any setting, may experience a feeling of sadness or apathy along with other symptoms that are severe enough to interrupt daily activities and persist for at least two consecutive weeks. Like FMS, depression is defined by a pattern of symptoms that adversely impact usual functions and fail to resolve in what is considered to be a reasonable period of time.

Many patients with FMS argue vehemently that they are not depressed. Not uncommonly a FMS patient will make one or more of the following composite of statements:

I am not depressed!! Don’t say I am depressed! It is just this pain that saps my energy. My inability to achieve restorative sleep night after night is probably the cause of the horrible tiredness that my doctors call fatigue. All of it together makes me feel sluggish, frustrated, discouraged and sometimes tearful. I want my energy and enthusiasm back. I want to be productive. There is so much I still want to do and be.

Hudson and colleagues (1) were among the first to explore the relationship between depression and FMS. They conducted National Institute of Mental Health Diagnostic Interview Schedule evaluations of three clinical groups: sequential tertiary care FMS patients, pain control rheumatoid arthritis (RA) patients and affective control depressed patients. They also evaluated first degree relatives of all three clinical groups. They found that 26% of FMS patients were depressed at the time of the interview (equivalent to saying “at any point in time”). In addition, 45% of the FMS patients had a history of depression at some time in the past.

The curious thing about those findings was that current and past depression were presented in a table by these authors as being mutually exclusive (1). That is, currently depressed patients were not listed as having a past history of depression and none of those with a past history of depression were listed as being currently depressed. The implication of that finding is not clear. For example, one could ask if it is safe to encourage depressed FMS patients by saying: “Once you get this depression phase behind you, it is done, it is not likely to come back.” Perhaps all of the authors’ previously depressed FMS patients had been placed on an antidepressant medicine and were still taking it. If that were to be the explanation, then the depression in the previously depressed FMS patients must have resolved with medication therapy. That kind of response would have been substantially better than occurs with patients who have depression alone. For non-FMS depressed patients, selective serotonin reuptake inhibitors have induced remission from depression in less than 30% (2,3). Using data from the authors’ own Table 1 (1), it is possible to calculate group values for the current Hamilton Depression Scale (HDS) scores for those FMS patients with a history of past depression (23.0 ± 7.0) and show that they were numerically similar to the HDS scores of the currently depressed FMS patients (18.8 ± 7.6), suggesting that past depression had not completely resolved. On the other hand, only the HDS scores of the currently depressed patients differed statistically (p < 0.01) from the HDS scores of those FMS patients (9.8 ± 5.8) with no past or current findings to support a diagnosis of depression, supporting the authors’ apparent contention that the past depression had resolved.

Table 1. Prevalence of depression in fibromyalgia syndrome patients and their first degree relatives (1).

Item	FMS (n = 31)	RA (n = 14)	Major depression (n = 24)
Depression – current	26%	–	–
Depression – past	45%	–	–
Depression – lifetime	71%	14%	100%
Depression among first degree relatives	9% (n = 223)	3% (n = 94)	14% (n = 108)

When Hudson and colleagues (1) combined the two depression prevalence numbers (26% of FMS currently depressed and 45% of FMS with depression in the past), they had generated an overall prevalence of 71% of tertiary care FMS patients who were depressed at some point in time during their lives. The comparable number for RA from that study was 14% depressed at some point in time. Additional differences were derived when the same authors (1) assessed the prevalence of depression in first degree relatives. Nine percent of first degree relatives of FMS patients were found to exhibit depression compared with 14% of the relatives of non-FMS depressed patients, whereas depression was diagnosed in only 3% of first degree relatives of RA patients. Since so many numbers in a paragraph of text can lead to confusion, the quoted values are provided in Table 1.

Ahles and colleagues (4) conducted an assessor-blinded study of FMS and RA patients and found a prevalence of 34% with current depression among FMS patients recruited from a secondary/tertiary care center (quite similar to the 26% value reported by Hudson et al. (1)). It is interesting to note that the Ahles et al. study found that the prevalence of depression in FMS was not significantly greater than was the prevalence of depression among patients with RA (4).

A more recent estimate of depression prevalence in FMS is 22% (5). Of course, 22–34% is higher than the 5–8% prevalence of depression in the general population (5–7) and higher than the 10–20% prevalence of depression in patients having almost any underlying major illness (8).

One reason that some clinicians may be quick to implicate depression as a contributor to pain is the belief that depression itself increases the perception of pain (lowers the pain threshold) (9). That explanation is unsatisfying, however, because many (60–70%) of FMS patients are not currently depressed and about 30% of otherwise typical FMS patients have never experienced depression.

Bradley and colleagues (10) studied FMS “non-patients,” meaning that they met 1990 ACR Classification Criteria for FMS, but had not sought medical care for their FMS symptoms. These non-patients with FMS were less likely to exhibit psychiatric comorbidity (including depression) than were FMS patients who had actively pursued medical care for their FMS symptoms. It was perceived that psychiatric comorbidity in a person with FMS may have made the FMS symptoms more intolerable and prompted the affected individuals to seek medical attention for their FMS. It is also possible that FMS non-patients, lacking psychiatric comorbidity, may represent a stable subgroup of FMS which is persistently different from FMS with psychiatric comorbidity (11,12).

Perhaps, some of the confusion regarding the overlap between FMS and depression is not only related to real overlap between the clinical disorders but also facilitated by overlaps in key wording in the questionnaire instruments developed to diagnose these disorders or to characterize their relative severities. These same concerns have been raised regarding the evaluation of FMS patients using the Minnesota Multiphasic Personality Inventory, where endorsement of certain physical symptoms was considered psychopathological (13). Compare some of the following informational components designed to assess either depression or FMS:

Hamilton Depression Scale (14)

• Insomnia (early in the night, middle of the night, late in the night).

• Somatic symptoms (gastrointestinal).

• Hypochondriasis.

• Stopped working because of present illness.

M.I.N.I. International Neuropsychiatric Interview, Depression Section (15)

• Did you have trouble sleeping nearly every night (difficulty falling asleep, waking up in the middle of the night, early morning wakening or sleeping excessively)?

• Did you feel tired or without energy almost every day?

Fibromyalgia Impact Questionnaire (Revised) (16)

• Please rate your quality of sleep.

• Please rate your level of energy.

• Please rate your level of depression.

• Fibromyalgia prevented me from accomplishing my goals for the week.

OMERACT-approved Domains of FMS (17)

There are six core domains to be assessed in every clinical trial involving treatment of FMS patients. Major depression is not one of those six domains. However, the OMERACT panel recommended that depression be assessed in some trials.

There are several other curious wrinkles in the fabric of the relationship between depression and FMS. For example, substance P is substantially (two- to threefold) elevated in the spinal fluid of people with FMS (18) but much less so in major depression (19). That is relevant to the discussion because substance P is known to cause or facilitate depression, as evidenced by the potent antidepressant effects of molecules which bind to and prevent substance P from binding to its neurokinin-1 receptor (20).

Although the historical consensus has been that depression facilitates or amplifies the perception of pain (21,22), new evidence favors situations in which depression is associated with a reduced perception of experimental pain (23). For example, in a complex meta-analysis of depression and pain perception, Dickens and colleagues (24) concluded that depression was associated with higher pain thresholds (rather than lower pain thresholds that would facilitate pain) and attributed that finding to inattention. In a follow-up of mood and pain after a course of cognitive behavioral therapy involving patients with chronic pain, there were shifts in pain and mood but more pain one day preceded negative mood the next day rather than the expected sequence of worsening depression leading to increased perception of pain (25). Similarly, patients with FMS treated with transcranial magnetic stimulation first experienced a reduction in the severity of their pain which preceded improvement in depression (26).

In many clinical studies, exemplified by one purely clinical trial (27) and another based on imaging outcomes (28), it has been observed that there is no statistical relationship between the more organic manifestations of FMS (e.g. pain, sleep dysfunction) and depression. The favored conclusion to this debate is that depression and FMS are occasionally comorbid with each other in FMS because of overlapping mechanisms of pathogenesis. They seem to represent conditions existing in parallel but it is unclear how they influence each other in people with FMS.

Hudson and colleagues (29) pointed this out when they addressed the comorbid, epidemiological, overlapping relationship between FMS and depression. In their view this relationship need not be considered etiological for either condition. They state as follows:

Note that this hypothesis does not imply that any one of these disorders causes another (i.e., FMS does not cause major depression or vice versa). Indeed, since the disorders often do not coexist simultaneously in a given patient, it is unlikely that any one disorder is primary, or the cause of the other. The data are most consistent with the possibility of a shared, possibly heritable, abnormality that is necessary, but not sufficient, for these disorders to occur. Thus, FMS might share a genetic abnormality with disorders such as migraine and major depression, but different genetic or environmental factors, such as susceptibility or exposure to certain viral antigens, may be necessary for the development of FMS.

This statement would seem prophetic when considering a recent finding that FMS is highly associated with a locus on chromosome #17 (30).

The lead article for this issue of the Journal of Musculoskeletal Pain (JMP) comes from investigators in San Diego, California, USA and Indianapolis, Indiana, USA (31). They bring to light an entirely new way of viewing the relationship between depression and pain in FMS. According to their analysis, the key to this conundrum is self-efficacy. The methodology is challenging, as every new innovation of science makes us study, learn and ponder. The authors have provided an informative introduction, so the reader is encouraged to digest that, even if it takes more than one careful reading. The Results and the Discussion sections open up what would appear to be new vistas on a well-trodden landscape. As mentioned above, we are already accustomed to hearing about FMS subgroups (11,12).

The second original contribution comes from the same psychology research group in San Diego, California, USA (32). Twenty-six men with FMS were compared with 130 men with osteoarthritis with regard to psychological well-being, including depression, self-efficacy over their condition, health status and actual health care costs for the year prior to their recruitment into the study. This study has several direct ties to the lead article in this issue. The research findings are remarkable in about four ways. The reader will be well rewarded by reading the results and the subsequent discussion of this study. With reference to the above discussion of depression in FMS, pay special attention to the correlation of depression with cost of care and the effect size of depression across study groups.

A study reported from Ankara, Turkey (33) evaluated attentional impairment, a component of cognitive dysfunction, in FMS with a goal of determining predictive factors for that very important symptom. They studied 98 premenopausal women distributed in three groups which were age- and educationally matched. The three groups were: FMS as the group of interest, RAas a chronic pain control and healthy normal controls (HNC) as disease free controls. They found a convincing answer and their work will likely be the reference for this important discovery. Don’t miss the opportunity to read about it before it becomes common knowledge.

A report from Granada, Spain (34) summarizes a subset of data derived from a larger ongoing clinical study. This interim report involved both women and men with FMS. Symptom domains for these FMS patients were compared with demographically matching HNC women and men. This kind of comparison study is important because FMS is so much less common in men than in women. As a consequence, many studies exclude males from FMS clinical evaluations because it is difficult to recruit statistically meaningful numbers of males with FMS. Even though the approach involved a focus on male FMS, the numbers are still small and the authors do call for greater efforts to study male FMS.

The relationship between primary dysmenorrhea and FMS is explored in a report from Disparta, Turkey (35). Both FMS and primary dysmenorrhea are chronic pain conditions. The findings of this study identify primary dysmenorrhea as another medical condition which can be comorbid with FMS and vice versa. The underlying pathogenesis of FMS (36) would predict that the pain of dysmenorrhea would be amplified by the comorbidity of FMS.

Finally, authors from Duzce, Turkey conducted an epidemiological study on the prevalence of FMS in patients with nasal septum deviation (37). The authors offer an important contribution by determining the prevalence of FMS in patients with nasal septal deviation, which is a recognized cause of sleep dysfunction. In addition, the authors have summarized in their discussion the overlapping prevalence of many painful and non-painful conditions that are now recognized to be comorbid with FMS.

From Valencia, Spain is offered a Research Idea involving vibratory therapy for patients with FMS (38). The authors point out that a few investigators have studied the utility of vibratory therapy for a number of medical conditions, including cerebral palsy, multiple sclerosis, Parkinson’s disease and FMS. The authors propose a treatment protocol for studying this therapy for FMS. Typically, the treatment subject would stand on a plate which is vibrating in one axis (either x, y or z) direction and the direction of the vibration may actually matter. Since the available studies to date have only involved a small number of subjects and some of the references are still at the abstract-only stage, it seems premature to include this intervention among those well-documented to be clinically beneficial for patients with FMS.

There is an interesting case report with a helpful literature review coming from Avcılar-İstanbul, Turkey (39). The case involves a cauda equina syndrome that developed in an elderly male with ankylosing spondylitis who developed spondylolisthesis at the L4-5 level following a low-energy fracture. Cauda equina syndrome is an important neurological complication characterized by low back and leg pain, impotence, urinary incontinence, sensory deficits and motor dysfunction.

Please note the book report (40) and the special interest columns which provide reviews of papers published in other medical journals since the previous issue of the JMP. The topical categories of these reviews are FMS, myofascial pain syndrome and other soft tissue pain syndromes.

As always, readers of the JMP are invited to submit original manuscripts for blinded peer review, case reports of general interest, research ideas to promote further investigation and letters to keep us all informed. The JMP editorial office frequently receive relevant books to be evaluated by and for the benefit of our readers. Book reviewers are allowed to keep the featured book after their evaluation report is completed. Readers who would be interested in being a book reviewer for the JMP, please communicate that to the editor ([email protected]). Potential authors of contributions to the JMP should note that submissions and all communications between the authors and the JMP staff are to be accomplished online. Visit http://mc.manuscriptcentral.com/wjmp for more details.

The clear mandate of the International MYOPAIN Society (IMS), for which the JMP is the official journal, is to perpetuate the international meeting (MYOPAIN) that has been held every 3 years, but is moving soon to an every 2 years schedule. The next International MYOPAIN Meeting will be MYOPAIN 2013 which will be held in the beautiful Pacific seacoast town of Seattle, Washington, USA. Dr. Philip Mease, IMS Vice President and Program Chairman for the Seattle meeting is working closely with the IMS Board to make plans for the Seattle meeting. Two years after that meeting, the International MYOPAIN 2015 Meeting will be held on an elegant Pacific coast town of Sydney, Australia, as the IMS hopes to better serve our growing numbers of members from Asia and the Pacific Rim. The IMS website http://www.myopain.com will offer details as they become available.

Be aware that Regional IMS Chapters are beginning to form. The first to be officially organized was in Thailand. Please contact Pradit Prateepavanich, MD, PhD, (Department of Rehabilitation Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Emails: [email protected], [email protected]) if you wish to learn how.

In previous editorials, it was announced that Larry Bodkin was serving as the executive manager of the IMS but unfortunately, Mr. Bodkin proved untrustworthy. The new IMS administrator is Donna Cameron, CAE, President; Melby, Cameron & Anderson; 23607 Highway 99, Suite 2C, Edmonds, WA 98026; [email protected]; http://www.mcamgmt.com; phone [phone], fax [phone]. The IMS Website still is http://www.myopain.org. Members are urged to pay their dues for 2013 because dues payment makes them eligible to receive the JMP. Dues payment and new member applications can be tendered via the www.myopain.org website. The current IMS Board Chairman is Bob Gerwin, MD, [phone], [email protected]. If you have questions about anything pertaining to IMS, Ms. Cameron will soon have all of the answers. Communications regarding IMS operations should be directed to Donna Cameron and her staff. With Ms. Cameron’s experienced leadership, we can expect growth and progress on many fronts.