Ameliorating Stressors May Alleviate MS

For 2 decades Maggie McPhersun's physicians had attributed her fatigue, episodes of choking, and periodic imbalance and numbness to chronic fatigue or depression. But the 51-year-old registered nurse and artist from Brunswick, Maine, knew that something was very wrong. When an MRI finally revealed multiple sclerosis (MS) lesions, the first thing McPhersun felt was relief. She finally had a sensible explanation for her symptoms. More than that, the MS diagnosis proved that she wasn't "crazy." As the gravity of the diagnosis sunk in, however, "it wasn't such a relief anymore," she remarked.¹

"It's easier to face a scary known than a scary unknown," says Darcy Cox, PsyD, a neuropsychologist working with patients who have MS. Because the course and prognosis of MS is so uncertain, an MS diagnosis creates more anxiety than a diagnosis that carries a potentially worse prognosis but has a more finite and predictable outcome, according to Cox.

Syed Rizvi, MD, director of Rhode Island Hospital's Multiple Sclerosis Center in Providence, finds that although his patients experience considerable apprehension during both the workup and diagnosis of MS, most accept the diagnosis, and their anxiety about having the disease diminishes within about 6 months.

Research confirms Rizvi's clinical impression. A recent study using standard rating scales for anxiety and depression and disease-related distress shows that distress related to having MS decreased over the 2 years following diagnosis.²

Nonetheless, as MS researcher David Mohr, PhD, points out, the consequences of MS present patients with continuing emotional threats. According to Mohr, a neuropsychologist and professor at Northwestern University's Feinberg School of Medicine, patients are often terrified about becoming dependent and worried that they will be a burden to their families. Those in ongoing relationships fear that their partner will abandon them, and those without a partner fear that they won't find one. The distress that patients experience as they confront the uncertainty of their prognosis and the physical, social, and psychological burdens of MS are, for the most part, normal responses to extraordinary difficulties.

Cox believes that patients with these concerns do not usually require formal psychotherapy or anxiety medication, but they do welcome and benefit from an opportunity to discuss their concerns. For example, patients can draw substantial benefit from a 15-minute conversation in which the clinician listens attentively and sympathetically, acknowledges the difficulties facing the patient, and lets the patient know that his or her worries are normal and to be expected.

Mohr recommends that someone in the neurologist's office or in the clinic should be available to talk with patients about their concerns, refer them for counseling when needed, and help them get suitable legal protection. Many chapters of the Multiple Sclerosis Society and a number of health care facilities offer support groups. Whether a patient will find such a group helpful depends on the leadership of the group and the participants, said Mohr. For some, it is important that fellow participants be at roughly the same stage of illness. An asymptomatic patient with newly diagnosed disease has a different set of concerns than a group of wheelchair-bound patients who are coping with late-stage disease. The asymptomatic patient is likely to find exposure to a disabled group more disconcerting than helpful.

NEEDLE PHOBIA AND DMMs

The availability of disease-modifying medications (DMMs) is a big plus for patients but not if they are squeamish about self-administration. All DMMs are administered by injection. This fact adds to the anxieties with which affected patients wrangle. This is not a trivial problem, according to Mohr. He pointed out that about 7% to 22% of the general population have needle and injection phobias and far more persons-regardless of fearing needles per se-have difficulty injecting themselves.

Problems with self-injection appear to be particularly prevalent in patients with MS. Mohr found that half of patients for whom interferon ß 1a (IFN-ß-1a; Avonex), which requires weekly intramuscular injections, was prescribed were unable to inject themselves.³ Ellen Lathi, MD, director of the MS Center at Caritas St Elizabeth's Medical Center in Boston, confirmed the magnitude of this problem. She told Applied Neurology that 90% of her patients have trouble with self-injection. She added that fear of self-administration of DMMs is a major barrier to therapeutic adherence.

Lathi and her staff help patients get around their fears of DMM self-administration by providing injection training. When patients cannot inject themselves, family members and friends are enlisted and trained to administer the injections. As a last resort, Lathi has patients visit the clinic to receive injections.

Despite its restrictions and safety concerns, Lathi and Rizvi both remarked that they welcome the newly approved agent, natalizumab (Tysabri), which is administered once a month by intravenous infusion. According to them, it provides an alternative for the many patients who cannot self-administer-or do not have someone available to administer-DMMs. Still these and other specialists agree that self-administration of MS medication is preferable to other therapeutic interventions, in part because of convenience and patient independence.

Cognitive-behavioral therapy

Recognizing the extent to which self-injection anxiety can deter patients' from receiving DMMs, Mohr, Cox, and their colleagues have developed a cognitive- behavioral treatment (CBT) program that empowers patients to self-administer DMMs. The treatment program uses a set of established techniques shown to alleviate a wide range of phobias. These include relaxation training, systematic desensitization (gradual exposure to the injection experience), and cognitive restructuring (identifying and helping the patient correct worrisome thoughts and misconceptions).⁴

The treatment works. In a pilot study, psychologists treated 8 patients for whom IFN-ß-1a was prescribed who were unable to give themselves intramuscular injections.³ After 6 weekly sessions, 7 (88%) of the 8 study participants were able to inject themselves. The eighth was able to do so during an additional seventh session. At 3-months' follow-up, 7 of the 8 patients continued to inject themselves.

In a second controlled study involving 30 patients, nurses at an MS center provided CBT.⁴ Controls received 6 weekly phone sessions that included instruction in self-injection, management of IFN-ß-1a adverse effects, and muscle relaxation, a protocol similar to the telephone education and support program offered by the manufacturer of IFN-ß-1a.

At the end of treatment, only 3 (25%) of the 12 patients who completed the control intervention were able to inject themselves, but 8 (73%) of the 11 who completed the CBT program were able to do so (P < .02).

Cox gives workshops on how to implement a CBT program. On the basis of the initial studies and the feedback she gets from the MS centers and clinics that offer the program, Mohr conjectures that close to 100% of the patients who have received CBT from clinical psychologists and about 70% who have received the treatment from nurses can successfully inject themselves. The counselor's manual and the accompanying patient workbook can be obtained from the Univer-sity of California, San Francisco, Behavioral Medicine Research Center's Web site at: www.ucsf.edu/bmrc/researchprograms/MSinjection.htm.

DOES STRESS CAUSE MS?

Charcot and other clinicians of his era noted that various types of adversity precede the onset of MS, and many of Charcot's patients believed their affliction was the consequence of "grief and vexation."⁵ Although neurologists today are less likely than their forebears to assign an etiologic role to stressful events, most patients with MS continue to believe that psychological stress can cause or exacerbate MS.⁶ They may be right. A number of articles-mostly from the 1950s when psychological stress was implicated in everything from rheumatoid arthritis to peptic ulcer- document cases of patients who experienced psychological trauma preceding the onset of MS and MS exacerbations. The emotional "precipitants" covered the gamut of human troubles from illegitimate pregnancy to failed love affairs to financial reversal.

The consensus among early investigators was that distress may contribute to MS exacerbations and may contribute to the initial event. Indeed, after describing several patients in whom MS seemed to be precipitated by emotional distress, one commentator stated that "there is evidence, however inconclusive, pointing to the fact that this appalling disease is a somatic reaction to intolerable mental conflict."⁷ Overall, investigators acknowledged, that in the absence of controlled studies, their conclusions were tentative.

Case-control and prospective studies began to appear in the 1980s, but their results are less than conclusive. A 1999 narrative review of these studies concluded that although a "relationship between antecedent stress and either MS onset or MS exacerbation is considered possible . . . the prospective data are insufficient to establish any such relationship with reasonable medical certainty."⁸ In 2004, Mohr and colleagues reported the results of a meta-analysis of 14 controlled studies examining the relationship between stressful life events and MS exacerbations. They found that stressful life events increased the risk of MS exacerbation but only to a modest degree (effect size, d = 0.53).⁶

In Mohr's view, an association exists between stress and MS, but stress in and of itself does not precipitate an MS exacerbation. Keeping the stress-MS link alive is the abundance of biologically plausible theories that could explain the connection. Stress-induced alterations in mast cell activity, cytokines, and the hypothalamic-pituitary-adrenal axis have all been proposed.

Among the methodological problems that bedevil assessment of a link between stress and MS exacerbation is the establishment of proper temporal parameters. Any attempt to pin down the relationship between stress and MS-and the mechanisms involved-requires a way to detect early physiological changes leading to lesion formation. Mohr and others have been using gadolinium-enhancing (Gd+) MRI, a marker of inflammation, to identify the time frame within which stress might influence lesion formation. Initial results show that new Gd+ MRI brain lesions show up 8 weeks after stressful events.

Mohr concedes that psychological stress may play only a minor role in MS exacerbations. Nevertheless, he believes efforts to reduce psychological stress in these patients are warranted. He is currently involved in an NIH-funded study to test the effect of a stress management program on the occurrence of new brain lesions. The results of this study may help identify a valuable adjunctive treatment for MS. Results also may shed light on the nature of the link, if any, between psychological stress and MS.

References:

REFERENCES

1.

Weir K. The art of adapting to MS.

The Scientist.

Available at:

www.the-scientist.com/2007/05/01/s6/1/

. Accessed June 7, 2007.

2.

Janssens AC, Buljevac D, van Doorn PA, et al. Prediction of anxiety and distress following diagnosis of multiple sclerosis: a two-year longitudinal study.

Mult Scler.

2006;12:794-801.

3.

Mohr DC, Cox D, Epstein L, et al. Teaching patients to self-inject: pilot study of a treatment for injection anxiety and phobia in multiple sclerosis patients prescribed injectable medications.

J Behav Ther Exp Psychiatry.

2002;33: 39-47.

4.

Mohr DC, Cox D, Merluzzi N. Self-injection anxiety training: a treatment for patients unable to self-inject injectable medications.

Mult Scler.

2005;11:1-4.

5.

Charcot JM.

Lectures on Diseases of the Nervous System.

London: New Sydenham Society; 1877.

6.

Mohr DC, Hart SL, Julian L, et al. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis.

BMJ.

2004;328:731.

7.

Inman WS. Can emotional conflict induce disseminated sclerosis?

Br J Med Psychol.

1948;21(part 2):135-154.

8.

Goodin DS, Ebers GC, Johnson KP, et al. The relationship of MS to physical trauma and psychological stress: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Neurology.

1999;52:1737-1745.