Winter 2005-6

January 1, 2005

Winter 2005 - 6  
David S. Bell, M.D. & Rosamund Vallings, MNZM, M.B., B.S.
Managing Editor
Greg Fillmore
Editorial Advisory Board
Leonard A. Jason, Ph.D. • Fred Friedberg, Ph.D. • David S. Bell, M.D.
Rosamund Vallings, MNZM, M.B., B.S. • Gudrun Lange, Ph.D

Letter from the President

A new name for our organization the IACFS:

Well its official, we are now the International Association for Chronic Fatigue Syndrome, and have dropped the AACFS moniker. Credit goes to board members Lee Meisel, Lenny Jason the rest of the IACFS board members who have voted for this change, and to the membership that have endorsed it. It's about time, as our organization is made up of members from around the world, and our board includes members from Sweden , Belgium , and Japan . And our mission is anything but parochial, as we take on the issues both in the United States and abroad. We are working to advance the science and its clinical applications as we work to become better advocates for the field and advocates for individuals that suffer from this disabling illness.

To that end, several members of the organization attended and presented an International Symposia held in Japan earlier this year and have strengthened ties to the Japanese organization of Fatigue Science researchers that have found a favorable climate for research in recent years. We have an international membership drive underway, so if you are reading this send the link to 10 of your colleagues, and encourage them to join the organization. Remember we now have patient members, who are critical to our mission, as they help keep us focused on the importance of this work, and can help with our mission of advocacy. So print this out and leave the newsletter in your patient's waiting room or bulletin board.

Of course are most effective tool in promoting both the science and quality clinical care in the field has been our biennial conference on research and clinical care. Our next conference will involve an international faculty, and will have State of the Science and State of the Art opening and closing lectures in each thematic session. Birgitta Evengard is the Chair of the Organizing Committee for the 8th International IACFS Conference on Chronic Fatigue Syndrome, Fibromyalgia and Other Related Illnesses (January 11-14 2007, Ft Lauderdale Fl), and assures the board that investigators from around the globe will be well represented in each session. 

This four day scientific medical conference will focus on integrative themes such as fatigue, pain, sleep, cognition & brain function. Each session will ask what is the science of the area (e.g. fatigue, pain etc), and close on the practical applications in the art of clinical medicine. There will be a panel discussion on the new pediatric case definition, and lectures on latest research , newest clinical protocols , a session on what genes can teach us and other innovative recent advances. Between formal sessions, interactive poster sessions, a banquet and cocktail party there will be opportunities to recognize top researchers and clinicians in our field and offer attendees formal and informal networking opportunities. New format changes for this conference will be the combining of clinical and research sections, bringing together researchers and clinicians in a joint educational effort.

Members of the board will continue to represent the organization at national and international meetings on science and health policy.Feel free to contact me or members of the board with your ideas as we expand to a more global scope.

Happy New Year,

Nancy Klimas MD
President, International Association for Chronic Fatigue Syndrome (IACFS)

Sleep Abnormalities in Chronic Fatigue Syndrome

David S. Bell MD, Board Member, AACFS

Sleep that does not result in waking refreshed as well as disrupted or fragmented sleep, hypersomnia, and insomnia constitute a significant part of CFS symptomatology. However, despite the symptoms of disturbed sleep being well documented in CFS, important unanswered questions exist. What role does abnormal sleep, if any, play in the symptomatology of CFS, and are sleep abnormalities part of the spectrum of CNS nervous system abnormalities or do they represent a separate, exclusionary conditions? In general the medical literature has struggled with these questions, and under the current diagnostic guidelines, primary sleep disorders such as narcolepsy and sleep apnea are exclusionary conditions for the research diagnosis of chronic fatigue syndrome (1). Depression, anxiety, pain, immunologic abnormalities, medication use, autonomic nervous system function, along with numerous other variables affect sleep quality, and just as these factors have complicated studies on immune function and emotions, these factors need to be addressed in the research on sleep disorders in CFS.

From a clinical standpoint, the medical provider is faced with the dilemma of what symptoms to treat in an attempt to improve both daily activity and function as well as the quality of life of the patient with CFS. Because of difficulties with both definitions and objective measures, there are few controlled treatment trials in the medical literature to guide us in our decisions. And, until the many basic questions are answered, there will continue to be a dearth of treatment studies. In this brief article I would like to review the role of sleep in CFS as described in selected articles from the literature, and offer some personal observations concerning the importance of treating sleep symptoms in the overall management of CFS.

Published Studies

In 1993, Richard Morriss from the Littlemore Hospital in Oxford and his co-workers published a case control study of twelve patients with CFS who did not have major depression by research criteria. Not surprisingly, CFS patients spent more time in bed (544 min) as compared to controls (465) but slept less efficiently. They woke more frequently and spent more time awake. Seven patients with CFS were diagnosed as having a sleep disorder; four patients had trouble getting to sleep, four had trouble maintaining sleep, and one had hypersomnia. None of the controls studied were diagnosed with a sleep disorder. Those patients with CFS with sleep disorder(s) had greater functional impairment, but no change in psychiatric scores. Moreover, they noted that shortened REM latency, characteristic of major depression, was not present in this group of CFS patients, again suggesting that CFS is distinct from major depression. The authors suggest that sleep disorders may be important in the etiology of chronic fatigue syndrome (2).

In a 1994 study by Anthony Komaroff and Dedra Buchwald the symptoms of CFS are reviewed in patients from their clinical practices. It was based on the authors' experience with two cohorts of approximately 510 patients with chronic debilitating fatigue (3). In a separate paper published the same year, Dr. Buchwald performed polysomnography on 59 patients who had sleep pathology suggested from a screening questionnaire. Overall, these patients had an overlap with major depression, but when separated into those meeting, or not meeting CFS criteria, there was little difference in the frequency of sleep disorders. Eighty-two percent of those meeting CFS criteria and 81% not meeting criteria had one or more sleep disorders. Of the whole group, the type of sleep disorder defined was as follows: sleep apnea 44%; idiopathic hypersomnia 12%; other disorder of excessive sleepiness 10%; restless legs 10%; excessive daytime sleepiness 10%; narcolepsy 5%; and other sleep disorders 5% (4).

In a paper reviewing immune function in CFS, the relationship between immune activation and abnormal sleep was discussed by Dr. J. M. Mulligan and co-workers at the Beth Israel Deaconess Medical Center in Boston . Immune stimulation is known to affect CNS mediated behaviors such as sleep, and they note that cytokine elevation is found in sleep deprivation. Given the complex relationship between CFS and cytokine abnormalities, a relationship may exist between immune state and degree of sleep abnormalities (5).

The pediatric literature also notes significant sleep disturbance as a prominent symptom (6, 7). In one paper comparing children with chronic fatigue syndrome who either met, or did not meet, criteria for primary juvenile fibromyalgia syndrome, one of the few differences between groups was that those children meeting criteria for both CFS and fibromyalgia had more severe sleep symptoms than those children meeting criteria for CFS alone (8). In a paper studying forty one adolescents, Akemi Tomoda and coworkers looked at the relationship between sleep and circadian rhythm disturbances. On the basis of a daily log of sleep time, all adolescent CFS patients in this study had one or more of the following sleep abnormalities: delayed sleep phase syndrome, non-24 hour sleep-wake syndrome, irregular sleep, or long sleeper (9). In a study from the Netherlands, Lidewij Knook and co-workers noted that, despite the symptom of unrefreshing sleep, melatonin levels were elevated in adolescents with CFS compared to controls (10).

Teruhyisa Miike from the department of child development at the Kumamoto Graduate School in Kumamoto Japan with co-workers have been evaluating CFS in children with school refusal. They note that 80% of these children have sleep abnormalities including day/night reversal, decreased NREM and delayed latency of REM sleep, suggesting deteriorated quality of night sleep. (11)

In a 2000 study attempting to answer the question of how significant primary sleep disorders are in CFS, Dr. Le Bon and coworkers emphasized that sleepiness and fatigue are not the same and attempted to address the issue with 53 patients from their fatigue clinic in Brussels . They showed a high incidence of primary sleep disorders, 46% in this patient group, and slee3piness was present in only one third of cases (12)

In a recent study which came as an outgrowth of the Centers for Disease Control population-based study of CFS, Elizabeth Unger and co-workers looked at subjective sleep in 339 patients with CFS. As a population based study, the patients with CFS were identified through telephone screening in Wichita , Kansas , rather than from self report. 81.4 % of patients had an abnormality in at least one sleep factor on the questionnaires utilized. From their data, the authors suggest that CFS patients are fatigued but not sleepy (13).

In a series of recent papers, Dedra Buchwald's group at the University of Washington has been examining monozygotic twins discordant for chronic fatigue syndrome (14-16), and these studies may change the views that have been built up over the past fifteen years. The sleep studies were conducted for monozygotic twin pairs, one twin healthy, and the other ill with CFS. The polysomnograms were conducted on the same night, and attention was paid to medications and other possible variables. The great strength of these studies is that the healthy twin is able to serve as a perfectly matched control for age, sex, genetic predisposition and many environmental influences.

In an evaluation of sleepiness using the Epworth Sleepiness and Stanford Sleepiness Scales along with a sleep diary, ill twins were quite different from their healthy siblings with subjectively poor sleep as would be expected. Objectively, polysomnograms were followed the next day with a four-nap multiple sleep latency test. The twenty twin pairs did not differ in either the presence of objective sleep disorders or the multiple sleep latency tests. Thus, CFS twins experience more subjective sleepiness without objective changes suggesting a sleep disorder. The authors offer the suggestion that there may exist an altered circadian rhythm with subjective sleepiness. Alternatively, CFS patients may experience a heightened perception of sleepiness or may be unable to distinguish fatigue and sleepiness. (15)

In another paper comparing the subjective and objective measures of sleep the authors note that CFS twins reported that they had slept less hours and were less well rested despite similar objective measures. The authors suggest that CFS twins suffer from an element of sleep-state misperception. (16)

In a study examining objective measures of sleep, also in the co-twin group, objective measures by polysomnography were examined for sleep latency, REM latency, sleep efficiency, awakenings, percentages of sleep stages 1 thru 4, percentage of REM sleep, periodic limb movements, leg arousal index, snoring, apnea-hypopnea index, upper airway resistance, and overall arousal. Only one CFS patient had a sleep disorder, sleep apnea. While there were two minor differences, the results of objective measures were remarkably similar for the healthy and CFS twin. These results do not provide strong evidence for a major role for abnormalities in sleep architecture in CFS. (14)

Primary or secondary?

The question remains: are the symptoms of CFS due to sleep abnormalities, or are the sleep abnormalities part of the global central nervous system symptomatology of CFS? As can be seen from the studies cited, clarity in this area is still lacking. However, as progress creeps along and we can now say a number of things about the relationship between sleep and CFS. First, it is clearly established that the subjective symptoms of unrefreshing and fragmented sleep are clearly an important part of CFS symptomatology. Yet objective measures of sleep pathology are of uncertain significance. With the current diagnostic guidelines, primary sleep disorders are exclusionary conditions for the diagnosis for chronic fatigue syndrome (1). Yet with some studies showing high frequencies of sleep disorders diagnosed over time, the question remains, are these sleep disorders primary or secondary? Does the presence of excessive daytime sleepiness or sleep apnea on testing that does not respond to CPAP treatment mean that a person cannot be diagnosed with CFS?

While it will take more experience for the academic community to come to a consensus on these issues, I would like to suggest that for the medical provider, the diagnosis of CFS remain clinical. That is, CFS can be diagnosed in patients with the pattern of exhaustion, pain and other symptoms as previously. If during the evaluation, a sleep disorder such as narcolepsy or sleep apnea is found and treatment for that sleep disorder removes the debilitating fatigue, the diagnosis of CFS is no longer valid. But if that treatment does little to improve the overall pattern of symptoms, the clinical diagnosis of CFS remains. In this latter case, the presence of a sleep disorder would be similar to the presence of treated hypothyroidism in that it does not serve to explain the clinical condition. As such, it should not be considered an exclusion in general clinical practice.

Clinical Experience

In general, it has been my experience that aggressive treatment of sleep disorders in patients with CFS has been disappointing. Yet, I also feel that it is one of the most important symptoms to aggressively pursue. The approach is one of common sense. If a patient with CFS identifies insomnia or unrefreshing sleep as one of the most disturbing symptoms present, I would treat this symptom aggressively.

Perhaps the first and most important aspect of treatment is sleep hygiene. Avoidance of stimulants, relaxing with wind-down time in the evening, and avoidance of television or computer use before bedtime should be emphasized. The CFS patient should not use the sleeping bed as a place for daytime resting, reading, watching TV or talking on the telephone. As with migraine, attempting to establish a consistent, but not rigid, schedule is also important.

Medications have a role, and most medical providers are very familiar with them in the patient with severe insomnia or fragmented sleep. These medications include tricyclics, trazedone, sedating muscle relaxants, and even benzodiazepines, all of which can help establish sleep to improve the symptom. Yet it has been my experience that while the patient may experience much improved sleep quality, the degree of their activity limitation rarely changes.

Clinically, the patient with CFS is very sensitive to medications which have a role in sleep symptomatology. With doxepin or other tricyclics, for example, the patient will frequently feel drugged in the morning and experience a hangover. I would not consider this a limiting side effect as reduction in the dosage often results in good sleep quality. Sometimes the liquid preparations are useful in that they permit very low doses.

It is important to differentiate those patients who have light, fractured sleep from those who have hypersomnia, as the former usually have more severe activity limitations and are more difficult to treat. Those patients with daytime somnolence and hypersomnia may respond to medications with stimulant properties, and the increased activity during the day may lead to a better quality of sleep at night. However, I no longer even try stimulant medications in those patients with insomnia. A good rule of thumb to separate these two groups of patients is their ability to tolerate coffee.

It is my feeling that patients with CFS have one or more central nervous system disturbance that causes the sleep symptomatology. Changing the diagnosis from CFS to sleep disturbance because the patient has a disturbance found on a questionnaire or even polysomnography will artificially lower the number of patients who carry the diagnosis of CFS but not result in improved quality of care. For example, in a recent paper on the clinical course of patients with CFS, at two and three years of follow-up, only 21% of the subjects were classified as having CFS (17). If this were entirely due to improvement of the degree of fatigue and other symptoms, this would be wonderful news. However, in this study, sleep apnea is listed as one of the more common causes of re-classification, yet we have no indication of whether the sleep apnea responded to appropriate treatment. For some clinicians reading this paper it appears that the original diagnosis of CFS was made in error, and that CFS is a benign condition - neither of which may be true. Most clinicians forget that the diagnostic criteria are for research purposes only.

Sleep symptoms should be pursued aggressively, and only if there is a good clinical response should the diagnosis be changed. Too often the patient with CFS hears the medical provider say, Aha, we have finally found the cause of your symptoms, only to be disappointed when treatment has little or no effect. This treatment failure then encourages alienation of the patient from the medical provider and increases both the frustration and confusion of the patient which, by itself, leads to greater distress.


1. Fukuda K, Straus S, Hickie I, Sharpe M, Dobbins J, Komaroff A, et al. The chronic fatigue syndrome. Ann Intern Med 1994;121:953-959.

2. Morriss R, Sharpe M, Cowen PJ, Hawton K, J. M. Abnormalities of sleep in patients with the chronic fatigue syndrome. BMJ 1993;306:1161-1164.

3. Komaroff A, Buchwald D. Symptoms and signs of chronic fatigue syndrome. J Rev Infect Dis 1994;13(Suppl 1).

4. Buchwald D, Pasacualy R, Bombardier C, Kith P. Sleep disorders in patients with chronic fatigue. Clin Inf Dis 1994;18((Suppl 1)):S68-S72.

5. Mullington J, Hinze-Selch D, Pollmacher T. Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions. Ann N Y Acad Sci 2001;933:201-210.

6. Bell D. Chronic fatigue syndrome in children and adolescents: a review. Focus & Opinion: Pediatrics 1995;1(5):412-420.

7. Jordan K, Landis D, Downey M, Osterman S, Thurm A, Jason L. Chronic fatigue syndrome in children and adolescents: a review. J Adol Health 1998;22:4-18.

8. Bell D, Bell K, Cheney P. Primary Juvenile fibromyalgia syndrome and chronic fatigue syndrome in adolescents. Clin Inf Dis 1994;18(Suppl 1):S21-S23.

9. Tomoda A, Jhodoi T, Miike T. Chronic fatigue syndorme and abnormal biological rhythms in school children. Journal of Chronic Fatigue Syndrome 2001;8(2):29-37.

10. Knook L, Kavelaars A, Sinnema G, Kuis W, Heijnen C. High nocturnal melatonin in adolescents with chronic fatigue syndrome. J Clin Endocrinol Metab 2000;85(10):3690-3692.

11. Miike T, Tomoda A, Jhodoi T, Iwatani N, Mabe H. Learning and memorization impairment in childhood chronic fatigue syndrome manifesting as school phobia in Japan. Brtain Dev 2003;xx.

12. Le Bon O, Fischler B, Hoffmann G, Murphy J, De Meirleir K, Cluydts R, et al. How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome? Sleep Res Online 2000;3(2):43-48.

13. Unger E, Nisenbaum R, Moldofsky H, Cesta A, Sammut C, Reyes M, et al. Sleep assessment in a population-based study of chronic fatigue syndrome. BMC Neurol 2004;4(1):6.

14. Ball N, Buchwald D, Schmidt D, Goldberg J, Ashton S, Armitage R. Monozygotic twins discordant for chronic fatigue syndrome: objective measures of sleep. J Psychosom Res 2004;56(2):207-212.

15. Watson N, Jacobsen C, Goldberg J, Kapur V, Buchwald D. Subjective and objective sleepiness in monozygotic twins discordant for chronic fatigue syndrome. Sleep 2004;27(5):973-977.

16. Watson N, Kapur V, Arguelles L, Goldberg J, Schmidt D, Armitage R, et al. Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome. Sleep 2003;26(3):324-328.

17. Nisenbaum R, Jones J, Unger E, Reyes M, Reeves W. A population-based study of the clinical course of chronic fatigue syndrome. Health and Quality of Life Outcomes 2003;1:49-58.

Diagnosing psychiatric disorder in patients with ME/CFS

Eleanor Stein MD FRCP(C);

Private practice psychiatry; Calgary , Alberta , Canada

A frequently voiced concern of physicians in clinical practice is how to accurately diagnose and treat psychiatric disorders in people with chronic fatigue syndrome (ME/CFS). The objective of this paper is to suggest some simple ways to differentiate between ME/CFS and primary depression and anxiety, as well as how to approach secondary psychiatric issues when they are present. These guidelines are based on close reading of the diagnostic criteria of ME/CFS, a review of the literature and clinical experience with both discrete and mixed populations.

I. Somatization Disorder

I will mention somatization disorder at the start only to dismiss it from further consideration. It is far too tempting for frustrated physicians to attribute symptoms for which no cause can be found with existing medical science to some "black box" psychological problem which cannot be disproven. Despite being written about for over one hundred years, somatization - the idea that unresolved, unconscious psychological conflict produces specific physical symptoms - has never been proven to exist. Several disorders which were previously thought to be psychosomatic in origin such as tuberculosis, asthma and peptic ulcer are now known to have biological causes and treatments.

It is clear that stress, life style, mood and attitude will affect physical health in indirect but measurable ways, and the mechanisms as to how this is brought about are being clarified. ME/CFS has been associated with numerous biochemical abnormalities such as abnormal functioning of the HPA axis (Scott and Dinan, 1998) brain blood flow (McHale et al, 2000) and metabolic changes (Wong et al, 1992; Lane et al, 1998) which are different from those found in psychiatric disorder. Johnson et al suggested that it is more likely that the concept of somatization is a function of the beliefs of the researcher rather than the psyche of the patients. They found that the rate of measured somatization in patients with CFS varied from 0% to 90% depending upon the whether the researcher assumed the physical complaints were psychological or physical in origin (Johnson et al, 1996).

II. Anxiety disorder

The common feature of the anxiety disorders is the presence of physical and/or mental features of anxiety which are inappropriate to the current situation and which significantly impact functioning and quality of life. There are three types of anxiety are commonly seen in patients with CFS:

1. anxiety about current state of health including cause of symptoms, the difficulty in lifestyle management because of the unpredictability of symptoms, and questions concerning long term prognosis.

2. anxiety as a result of the impact of having CFS such as the loss of social and family support, financial hardship, and loss of career. Anxiety about being denied disability payments is common.

3. comorbid anxiety disorder; GAD and social anxiety being the most common

Management of anxiety reactions to ME/CFS and its effects

Patients report that one of the most valuable aspects of a medical visit is validation of the ME/CFS diagnosis by the physician. An accurate and convincing diagnosis must consider the patient's and physician's worries about other causes of symptoms. This may require appropriate investigation and referral to rule out feared diagnoses such as cancer, MS or heart disease.

The best antidote to anxiety in my clinical experience is improvement in physical health. In almost 4 years of dedicated ME/CFS practice I have yet to see a patient who did not become less anxious and more active as health improved. Appropriate illness management by ensuring adequate sleep, adequate diet, adequate rest, and the treatment of comorbid symptoms such as postural hypotension, secondary arrhythmias, reactive hypoglycemia, irritable bladder and bowel can also contribute significantly to decreasing anxiety. Supportive counseling/therapy regarding career, peer group and family issues is indicated when those issues are a source of anxiety. Some patients will require active support to obtain access to sustainable school/work conditions or leave of absence from school or work, disability, and insurance.

Comorbid anxiety disorder

The diagnosis of co-morbid anxiety disorder should be considered when the emotional symptoms pre-date the physical symptoms, and when the anxiety is generalized and not limited to health and health care related issues. Moreover co-morbid anxiety would be considered when the patient is unable to cope with, or resolve anxiety over the long term of their illness. Most subjects with ME/CFS will have three or more of the following physical symptoms of Generalized Anxiety Disorder: 1) restlessness, 2) easy fatigability, 3) poor concentration, 4) irritability, 5) muscle tension and 6) sleep disturbance. And many of these patients are worried about their health and how it impacts their life. However few ME/CFS patients will be excessively worried about life every day and/or have difficulty controlling their worry. Therefore generalized daily worry, of a severity that interferes with daily life and difficulty controlling this worry points to the presence of an anxiety disorder, either instead of, or in addition to, ME/CFS.

The treatment of co-morbid anxiety disorders should be the same as in patients without ME/CFS. Cognitive Behavioral Therapy can help patients re-evaluate unrealistic fears. CBT to convince patient that s/he does not have a physical disorder is disrespectful and inappropriate. The patient s energy level, cognitive dysfunction and sensitivity to medication must be taken into account. For patients functioning at less than 40% energy as defined by the Karnofsky rating scale adapted by Dr. David Bell (Bell, DS, 1995, Appendix I) or unable to complete more than 2 hours per day of activity, mental energy may be insufficient to engage in therapy. Psychotropic medication such as low dose SSRIs can improve sleep and prevent excess energy drain in severely anxious patients. Clonazepam, a benzodiazepine with a mid range half life can decrease muscular tension and spasm. Alprazolam and lorazepam are the most effective agents for the psychic symptoms of anxiety if SSRIs are not effective or not tolerated. Many ME/CFS patients have concerns about addiction and use of benzodiazepines may required counseling about the low risk of addiction in people not already predisposed.

III. Depression

There is now an extensive literature comparing depression with ME/CFS and the two disorders have several measurable differences. Urinary 24 hour cortisol, QEEG, electrodermal, brain blood flow on SPECT are among some of these findings (Scott and Dinan, 1998; MacHale et al, 2000; Pazderka-Robinson et al, 2004). The argument that ME/CFS is a subset of depression rests on the similarity between some physical symptoms found in both disorders: 1) fatigue, 2) sleep disturbance, and 3) appetite disturbances. However ME/CFS requires the presence of other physical symptoms not seen in depression including: 1) post exertional fatigue, 2) sore throat, 3) swollen or tender lymph nodes, 4) irritable bowel, 5) temperature dysregulation and 6) vasomotor abnormalities. Depression cannot be diagnosed in the absence of depressed mood, anhedonia, negative attributional bias and guilt or self blame. A simple way to differentiate between fatigue and depression is to ask whether the patient enjoys the moments during which s/he feels better. People with ME/CFS who are not depressed maintain interests and are frustrated by their inability to pursue them. People who are depressed lose interest.

There are four types of depression commonly seen in CFS

1. Grief due to loss of health, social connections, family support, financial capability, and career.

2. Change in mood or cognition as part of the physical disorder of ME/CFS (similar to the mood change in multiple sclerosis or Parkinson's disease)

3. Comorbid depressive disorder

4. Mood change due to medication or food.

Management of depressive and grief reactions to CFS and its effects

As with anxiety, the best antidepressant for patients with ME/CFS is improved physical health and quality of life. Validation by the physician of the patients' difficult life situation due to illness and other circumstances is very important. My patients tell me that even if I cannot help them physically recover the validation and support are meaningful. It is important to ask about suicidal ideation. Suicide is thought to be the leading cause of death in CFS. Most severely ill patients, even those who are not depressed have considered suicide as a way to end the suffering and the burden their illness places on their family. Therapy aimed at restoring and maintaining hope can be helpful.

Recognition of, and grieving the huge losses caused by ME/CFS is critical to emotional function. The four phase model introduced by Patricia Fennell is an excellent guide for both patients and physicians (Fennell, 2001). It helps patients maintain hope by knowing that grief is a necessary process and that they can move from crisis through stabilization and finally to periods of integration of their pre and post illness selves. Specific exercises suggested by Fennell may facilitate this process.

Co-morbid depression should be considered when the depressive symptoms predated the physical disorder, pessimism is generalized beyond health and illness related issues or the patient is mired in a depressed state despite modest symptomatic improvement.

Co-morbid depression should be treated as in the absence of CFS. Remember that no antidepressant has been shown to improve the core symptoms of ME/CFS (White & Cleary, 1997) in the absence of depression (Vercoulen et al, 1996).Low dose tricyclics are often useful for sleep rehabilitation and pain management but rarely have antidepressant effect in the doses tolerated. Psychotropic medication may be tried if symptoms are interfering with sleep and rehabilitation. Like all other drugs, the antidepressant doses usually need to be lower that in other patients and due to sensitivity, some patients will be unable to tolerate any antidepressant. Cognitive Behavioral Therapy can help patients cope with unrealistic assumptions and expectations. Using CBT to convince patients that they do not have a physical disorder is disrespectful and inappropriate.

IV. Conclusions:

1. There is no evidence of psychological causation for CFS though psychological symptoms are a common part of the disorder

2. Despite the huge psychological, social and physical burden of having CFS, most patients cope relatively well.

3. CFS can be differentiated from anxiety and depression.

4. Treatment for CFS patients with psychological symptoms is fourfold: a) treat physical illness with symptomatic treatments. b) actively advocate for your patient's health, mental health and economic needs. c) offer or refer for psychotherapy to support the patient's grieving process and encourage the formation of sustainable values and expectations. d) use low dose psychotropics for those in whom anxiety or depression symptoms are disabling and/or are interfering with recovery.

V. References:

Bell , DS. The Doctor s Guide to Chronic Fatigue Syndrome. Addison-Wesley, Boston , MA . 1995.

Fennell , PA. The Chronic Illness Workbook, New Harbninger Publications, Inc, Oakland , CA . 2001.

Johnson , SK ; DeLuca, J; Natalson, BH. Assessing somatization disorder in the chronic fatigue syndrome. Psychosomatic Medicine. 1996: 58, 50-57.

Lane, RJ; Barrett, MC;Taylor, DJ; Kemp, GJ; Lodi , R. Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscular Disorders. 1998:8;204-209.

MacHale, SM, Lawrie, SM, Cavanaugh, JT; Glabus, MF; Murray CL; Goodwin GM, and Ebmeier KP. Cerebral perfusion in chronic fratigue syndrome and depression. British Journal of Psychiatry. 2000;176;550-556.

Pazderka-Robinson, H; Morrison, JT; Flor-Henry, P. Electroderman dissociation of chronic fatigue and depression: evidence for distinct physiological mechanisms. Int J Psychophysiol. 2004. 53. 171-182.

Scott, LV ; Dinan, TG. Urinary free cortisol excretion in chronic fatigue syndrome. Am J Affective Disorders. 1998; 47:49-54.

Vercoulen, JH; Swanink, CM; Zitman, FG; Vreden, SG; Hoofs, MP, Fennis JF; Galama, JM, van der Meer, JW; Bleijenberg, G. Randomized, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. Lancet. 1996; 347:858-861.

White, PD; Cleary KJ. An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome. International Clinical Psychopharmacology. 1997; 12: 47 -52.

Wong, R; Lopaschuk, G; Zhu, G; Walker, D; Catellier, D; Burton, D; Teo, K; Collins-Nakai, R; Montague, T. Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Chest. 1992;102:1716-1722.