How to differentiate CFS from
Psychiatric Disorder
by Eleanor Stein, MD FRCP(C)
Psychiatrist in Private Practice
Calgary, Alberta, Canada
A recent publication in the Australian Medical Journal concluded that 6/10 patients presenting to general practitioners have a mental illness (somatization disorder) based on questionnaire self-report data of physical symptoms. These somatic symptoms are assumed to be without physical cause though this hypothesis is never tested or validated. It is a mistake to use screening instruments such as the Beck Depression Inventory, the General Health Questionnaire or the SPHERE to diagnose mental illness in persons with undiagnosed somatic complaints, including those with CFS, because of the unstated, unproven and incorrect assumption that the somatic complaints are of psychological origin.
This paper specifies the clinical differences between CFS and the two most common psychiatric disorders: anxiety and depression. A clinical psychiatric diagnosis rests upon the patient demonstrating the core psychiatric manifestations of depression (eg. anhedonia) or anxiety (eg. unrealistic fear) whereas a diagnosis of CFS requires the presence of 4 of 8 physical symptoms (eg. pain, sore throat) in addition to fatigue. A referenced handout summarizing the research literature differentiating between CFS and depression will be presented.
Depressive and anxious reactions to having a serious, chronic, unpredictable disorder lacking social legitimacy are common among CFS patients. A comorbid psychiatric diagnosis should only be considered if the psychiatric symptoms predated the onset of CFS, if the symptoms are generalized beyond health and quality of life issues affected by CFS or if the symptoms are so severe that they prevent a patient from participating in treatment. Management of the common psychological reactions to CFS and of comorbid psychiatric diagnoses will be discussed.
The objective of this paper is to assist general practitioners in making an accurate psychiatric differential diagnosis in patients with Chronic Fatigue Syndrome as defined by the CDC (either 1994 or 1988 criteria1,2). Three psychiatric categories will be considered: somatization disorder, the anxiety disorders and depression.
Somatization disorder
Somatization disorder is being discussed to be discarded. It is not a frequent comorbid condition in CFS but must be addressed because of recent publications suggesting that many if not most patients presenting in general practice with medically unexplained physical symptoms are in fact somatizing3. Somatization, originally called
“hysteria”, is a concept coined over a century ago in an attempt to explain physical symptoms reported by mostly young female patients for which no medical explanation could be found with the technology of the day. Rather than admitting the limitations of medical science, early psychiatrists developed the theory that the unattached libidinous energy of unresolved psychological conflicts was unconsciously transformed into physical symptoms in the absence of suitable behavioral outlets. The beauty of the inclusion of the unconscious in the hypothesis is that the patient could never argue against the diagnosis.With the advent of modern technology, virtually all psychiatric disorders are now known to be associated with measurable biochemical, neuropathological or metabolic abnormalities of the central nervous system. The concept of somatization has never been empirically substantiated. In fact the diagnosis of somatization in research studies depends upon patient reports of physical symptoms and the assumption by the researcher that there is no physical cause for the symptoms.
The dependence of diagnosis upon the subjective views of the researchers was elegantly shown by Johnson et al in subjects with CFS and MS4. Each subject completed a standardized psychiatric interview. The interviews were then rated twice: first with the assumption that the physical symptoms reported by the subjects were physical in origin ie due to the CFS or MS, and second with the assumption that the physical symptoms were psychological in origin. In the first case the prevalence of somatization disorder in CFS was zero and in the second case it was 90%.
In a recent paper, Merskey a world leader in the fields of pain and hysteria summarizes the problems
with the concept of somatization. He suggests that the term should be abandoned5. However the concept of somatization and its synonyms “functional somatic disorder” and “illness rather than disease” have recently been resurrected in relation to CFS3,6-8. If addressed, these sloppy references could lead to an unfortunate increase in skepticism and dismissal of the seriousness of CFS. Given the lack of evidence supporting the existence of somatization as a verifiable disorder and with the substantial evidence that the symptoms in CFS have biological correlates, consideration of a differential diagnosis of somatization in CFS is not warranted.Anxiety disorder
Anxiety disorder as defined in the DSM IV includes: panic disorder, agorophobia, generalized anxiety, social anxiety, PTSD, other trauma related reactions and anxiety due to medical conditions or substances9. The common feature of anxiety disorder is the presence of physical and/or mental features of anxiety that are inappropriate to the current situation and which significantly impact functioning or quality of life.There is no overlap in symptoms between anxiety disorders and the CDC definitions of CFS nor are there studies specifically examining the prevalence or presentation of anxiety in CFS. However many patients with CFS experience arrhythmias, postural hypotension, reactive hypoglycemia and irritable bowel and bladder which are often seen in patients with anxiety disorders and which are anxiety provoking.
Anxiety symptoms in CFS
Three types of anxiety are commonly seen in people with CFS:
1. anxiety due to uncertainty of diagnosis and prognosis
2. anxiety due to the impact of having CFS eg. loss of social connections, loss of family support and financial insecurity; and
3. comorbid anxiety disorder such as generalized anxiety disorder and social anxiety.The first two conditions account for 85-90% of anxiety reactions in CFS. They are understandable reactions to having a serious, uncertain, stigmatizing and chronic disorder. In full health people process anxiety and move on. However the chronicity of CFS, the variability and unpredictability of the symptoms and the social, financial and legal issues often connected with the disorder can mitigate against a person’sability to work through anxiety in a timely fashion.
Coping with anxiety reactions in CFS
Anxiety reactions may be overcome without treatment but will benefit from validation by the physician of the diagnosis of CFS and of the serious nature of CFS. The physician must spend the time to listen to the patient’s worries of possible differential diagnoses and must explain why certain diagnoses may or may not be relevant. Otherwise the patient will continue to worry in the belief that the physician has not “listened” to him/her. It is often appropriate to order investigations or referrals to help rule out feared diagnoses such as cancer, MS or heart disease if the patient’s symptoms are suggestive of these.The best remedy for anxiety is for the patient to experience improvement in physical health and quality of life. This requires appropriate management eg. ensuring adequate sleep, adequate diet, adequate rest and treatment of comorbid symptoms such as postural hypotension and secondary arrhythmias, reactive hypoglycemia, irritable bladder and bowel which can be very anxiety provoking. Many patients benefit from supportive counseling or therapy regarding losses of role in their career, peer group or family.
Most patients require the physician’s active support to obtain sustainable school/work conditions, temporary leave of absence from school or work or disability pension as circumstances dictate. Although this is time consuming for the physician, it gets easier with practice. Negotiation with family members regarding domestic duties and childcare may require the physician’s input as family members may be disbelieving of the patient’s disability since s/he may “look normal”.
Diagnosing anxiety disorder
Though most patients with CFS do not have an anxiety disorder, it should be considered if:
1. the anxiety symptoms predated the physical disorder;
2. the anxiety is generalized and not limited to health and health care related issues; or
3. the patient is unable to cope with or resolve anxiety over the long term.Management of anxiety disorder in CFS Comorbid anxiety should be treated similarly to anxiety in the absence of CFS except that the patient’s energy level, cognitive dysfunction and sensitivity to medication must be taken into account. For example patients may require explicit written instructions for cognitive homework assignments as working memory is negatively affected in CFS10. Cognitive behavior therapy to aid patients in identifying and confronting unrealistic fears or avoidance behavior is very useful. However cognitive behavior therapy with the aim of convincing patients of the unreality of their disorder is disrespectful, inappropriate and unlikely to benefit patients.
Psychotropic medication may be required if the anxiety symptoms interfere with sleep or quality of life. However about 50% of patients with CFS have Multiple Chemical Intolerance and therefore may react badly to even low doses of usually benign medications. Antidepressants decrease REM sleep and benzodiazepines decrease much needed deep sleep. It is best to avoid benzodiazepines if at all possible. Patients with CFS are more sensitive to the sleep and cognitive side effects and to the discontinuation effects of these drugs. Low doses of SSRIs are useful for control of anxiety symptoms. Many patients with CFS tolerate fluoxetine and paroxetine badly and do better with 25-50 mg sertraline or 10-20 mg citalopram.
Depression
In DSM IV the depression umbrella includes: major depression, dysthymia, depression due to medical disorder and to substances as well as adjustment disorder with depressed mood9. There is considerable research comparing major depression and CFS.Table 1 summarizes some of the findings. Although this table is not exhaustive, it is representative. No authors have concluded that depression and CFS are synonymous. The differences in centrally acting hormonal systems between the two conditions are replicable and undisputed.
Table 1. Experimental Differences between CFS and Depression Decreased urinary 24 hour cortisol11 Normal or increased urinary 24 hour cortisol Dexamethasone over-suppression Dexamethasone non-supression Decreased am salivary cortisol Salivary cortisol normal QEEG abnormalities different from depression12 QEEG abnormalities different from CFS Low prestimulus electrodermal level12 Normal prestimulus electrodermal level High prestimulus digital skin temperature12 Normal prestimulus skin temperature Cerebral blood flow decreased in brain stem13 Cerebral blood flow decreased in prefrontal cortex14 Differentiating CFS from depression
Although many authors report that CFS and depression are difficult to distinguish clinically, this is not the case if one knows the key traits that differentiate the two. Table 2 summarizes both clinical experience and research data about the clinical presentations of CFS and depression.
Clinical differences between CFS and Depression Fatigue is the primary symptom Mood change is the primary symptom Both physical and mental fatigue Physical fatigue rare Fatigue both physical and mental worsened by physical or mental exertion15 No change in fatigue or mood with exercise15 Decreased positive affect (energy, enthusiasm, happiness) Increased negative affect (apathy, hopelessness, suicidal ideation, self reproach) Attributional bias only for somatic complaints Generalized negative attributional bias Externalizing attributional style16 Internalizing attributional style16 Personality disorder no more common than control samples17 Increased prevalence of personality disorder17 Infectious onset in > 80% of cases Rarely follows infectious illness Physical (somatic) symptoms: requires at least 4
eg. swollen lymph nodes, sore throat, muscle
and/or joint pain and headache2Not usually associated with physical symptoms Cognitive dysfunction most problematic symptom present in absence of depression
(slow reaction time and slow effortful processing)18,10Similar to CFS but able to be differentiated on neuropsychological testing19 Orthostatic intolerance/autonomic dysfunction common20 No association with autonomic symptoms Sleep disorder common Sleep disorder common Diurnal variation with pm the worst time of day Diurnal variation with am the worst time of day Variability of severity and nature of symptoms Symptom variability not marked The sine qua non of clinical depression is a persistent low or irritable mood and anhedonia, the inability to enjoy oneself. If one is not sad and/or anhedonic the diagnosis of major depression cannot be made. One can ascertain the presence of anhedonia by asking which activities the patient enjoys when s/ he feels well or better or if this is never the case what s/he would enjoy if s/he woke up tomorrow completely well? If a patient can answer this question s/he is not likely to be depressed. Depressed patients report that they are unable to enjoy anything even on good days.
The sine qua non of CFS is persistent fatigue plus at least four physical symptoms as defined by the CDC 1994 criteria2. Those who think of CFS as “fatigue” and forget the importance of the other symptoms will be at risk of misdiagnosing patients with depression leading to inappropriate treatment recommendations. Although those (increasingly few) who view CFS as a type of depression use the “masked depression” argument ie CFS is actually a type of depression in which only physical symptoms are apparent, masked depression is not a DSM IV diagnosis and like somatization, there is no empirical evidence that it exists.
Mood and/or cognitive changes are reported by 80% of persons with CFS21. Four types of mood syndromes are common:
1. grief due to loss of health, social connections, family support, financial capability, career and uncertainty re all of these;
2. change in mood/cognition as part of the physical disorder of CFS (similar to mood change in MS or Parkinson’s disease);
3. comorbid depressive disorder and
4. mood change due to medication or food or withdrawal from either of these. These four types of depressive reactions can usually be differentiated by taking a careful history.However most patients will need to use written aids to remember their symptoms and notice connections between them. Completing daily ratings of core symptoms such as sleep, morning refreshment, pain and energy allows patients to reliably and efficiently report their symptoms at office visits and to identify connections between behavior and health.
Grief is the most common cause of mood change in CFS. The change in quality of life with CFS is profound; patients must adapt every aspect of existence and often resist acceptance of this unwanted change22,23. Grief cannot begin until a diagnosis is made and other diagnoses are ruled out. Diagnosis frees the patient to begin the process of grieving. Grief is not a disorder. It is a normal developmental process which enables people to deal with overwhelming loss. It is an understandable reaction to a serious, uncertain, stigmatizing and chronic disorder. Grief is therefore common during the initial post diagnostic period and may recur each time there are new changes in health or life situation.
If mood symptoms are a part of the patient’s physical disorder the patient will report that mood covaries with the core symptoms of CFS. For example virtually all patients functioning at energy levels below 60% using the adapted Karnofsky scale24 experience irritability (as opposed to sadness), slowed reaction times, difficulty with word finding and deficits in working memory. In comorbid depression, this covariation will not be seen, mood will be independent of energy and sleep. Reactions to food and medication are greatly under reported by patients because they use these substances daily and are therefore unable to notice variation. A Serum IgG antibody panel for common foods can speed up the treatment process considerably.
Coping with depressive reactions in CFS
Feelings of depression are normal and may be overcome without treatment but will benefit from validation by the physician of the diagnosis of CFS. As in management of anxiety, the best antidepressant is improved physical health. As with any depressive disorder patients must be asked about suicidal ideation. Although not reported in any peer reviewed publications, many consumer-sponsored surveys suggest that suicide is the most common cause of death in persons with CFS. For patients with a chronic, serious disorder lacking medical legitimacy, social or financial support, suicide can seem the least painful option.All patients should be given the opportunity to meet with a trained counsellor or therapist knowledgeable about CFS to discuss self esteem, career, peer group and family issues. As with anxiety, patients need their doctor’s active support to obtain sustainable school/work conditions, a leave of absence from school or work or disability pension depending upon their circumstances.
Diagnosing depression
Comorbid depression occurs in 10-15% of patients with CFS. It should be considered if the depressive symptoms predated the physical disorder, if pessimism and hopelessness is generalized beyond health and illness related issues or if depressive symptoms are not being resolved and are impairing quality of life.Managing depression in CFS
Depression in CFS should be treated similarly to depression in the absence of CFS, except that the patient’s energy level, cognitive dysfunction and drug sensitivity must be taken into account. It is tempting to use antidepressants to treat CFS but research evidence clearly shows that this approach is unsuccessful. No antidepressant has been shown to improve the core symptoms of CFS25,26. In fact, in these studies even depressive symptoms failed to respond to antidepressants in subjects with CFS.Low dose tricyclic antidepressants are helpful both for their sedative side effects and for their pain control effects. Approximately 40% of CFS patients are unable to tolerate tricyclic antidepressants but for the remainder the benefits are similar to those in other groups of chronic pain patients27. Antidepressant effects are not to be expected at the 10-50 mg amitriptylline equivalent usually tolerated by CFS patients. For the treatment of depression, low dose SSRIs can be tried. Antidepressant doses usually need to be lower than in other patients eg. citalopram 10-20 mg or venlafaxine 37.5-75 mg daily though some patients require and tolerate full doses. Many patients tolerate split doses of regular venlafaxine better than the sustained release preparations. Some patients will be unable to tolerate any antidepressant.
Cognitive behavior therapy can aid patients in identifying, questioning and overcoming illogical or catastrophic beliefs if these exist. However, cognitive behavior therapy designed to convince patients that they are not physically ill and should not rest when tired is disrespectful, inappropriate and not likely to benefit patients. A primary goal of psychotherapy is to assist patients with grieving and redefining life goals and meaning.
There is no evidence that CFS is caused by psychological stressors however psychological symptoms are a common part of the disorder and must be addressed. The concept of somatization ie the unconscious psychological causation of physical symptoms has never been proven. The concept is outdated, unscientific and should be dropped from the medical lexicon. Despite having a huge psychological, social and physical burden, most patients with CFS cope relatively well and have neither an axis I nor axis II psychiatric disorder.
Clinically, CFS can be differentiated from both anxiety and depression. The treatment of psychological symptoms in CFS is fourfold:
1. treat the physical illness,
2. actively advocate for the patient’s health, mental health and economic needs,
3. offer or refer for psychotherapy to support the patient’s grieving process and encourage the formation of sustainable values and expectations and
4. use low dose psychotropics for those in whom anxiety or depression symptoms are disabling and/ or are interfering significantly with quality of life.
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