Chronic Psychological and Medical Conditions That Often Coexist with Chronic Fatigue Syndrome
Robert: I spend a lot of time looking for health information on the internet because I am desperate to feel better! My doctor doesn’t know what’s wrong with me, and despite all the blood tests and X-rays and CT scans, he still can’t figure out what’s causing my problems. He probably thinks I’m a raging hypochondriac. But I know what it’s like to feel healthy, and it’s nothing like this! My wife thinks I’m really uptight and that I spend too much time trying to find something, anything that will explain what’s wrong with me! I even thought maybe I had cancer at one point, but no, that wasn’t it. Of course I’m glad I don’t have cancer, but the NOT knowing why I feel so poorly is so depressing. I read that if there is no other explanation for exhaustion and forgetfulness, I might have chronic fatigue syndrome. I will ask Dr. Brown about it today.
Dr. Brown: When I see Robert’s name on the daily schedule, my heart sinks, and I can’t help it. I wonder what disease he thinks he has now. I’ve ordered plenty of bloodwork, and it all comes back perfectly normal, as did the CT scans. A few months ago, Robert was convinced he had pancreatic cancer, but he had no symptoms and his tests were negative, which I told him. A few weeks later, he was back, and this time he was sure his exhaustion meant he had leukemia. He didn’t have that either. His latest idea (probably from Dr. Google) was that maybe he has chronic fatigue syndrome, a disease I’m not sure is even real. I do know that he always seems frustrated and unhappy. I will send Robert to a therapist to treat him for his anxiety.
Dr. Brown had been investigating potential causes of Robert’s fatigue for a couple of years. This medical workup (outlined in Chapter 3) was negative. Robert did not have thyroid disease, cancer, anemia, or any rheumatological disease. No overlooked medical illness seemed to explain any of the intermittent symptoms that so frequently brought Robert into the office. Finding no concrete medical answers to explain the fatigue, Dr. Brown seized on Robert’s anxious state and referred him for mental health care. Robert left the office feeling defeated and misunderstood.
Robert’s case illustrates that often, it is the informed patient who pushes his doctor to consider the possibility of CFS. In fact, most of what Robert learned about CFS came from online searches. CFS is a diagnosis of exclusion, yet even after his full medical work yielded no findings, Dr. Brown did not stop to consider that CFS might be the accurate diagnosis. Rather, the doctor felt stuck and shifted his focus to Robert’s anxiety and depression. In so doing, Dr. Brown minimized the debilitating impact of fatigue and signaled to his patient that although he could not offer anything to alleviate the fatigue, emotional support and a gentle antidepressant could help Robert live with the chronic illness. In fact, for most CFS patients, their secondary psychiatric symptoms comprise what others view as their true illness. Like Robert, the majority of CFS patients are diagnosed with an anxiety or depressive disorder—and are treated with anxiety or antidepressant medications. This is generally a positive move; these medications do relieve anxiety and depression.
A more effective treatment directly treats the fatigue. Once the fatigue is addressed, the secondary symptoms of anxiety and depression greatly diminish. Robert is my favorite type of referral because it is so gratifying to offer a new approach to someone who has been written off as a hypochondriac and has lost hope that doctors could help. I receive equal pleasure explaining to my medical colleagues this novel approach to CFS.
This chapter explores health problems that are often present in people with CFS. The first part of this chapter offers an overview of the complex relationship between depression, anxiety, and CFS. These problems often co-occur with CFS and need to be identified and distinguished from CFS. Although CFS is intertwined with these psychiatric symptoms, it needs to be emphasized that the American Psychiatric Association does not list CFS as a psychiatric condition, and there is no psychiatric condition that fully explains CFS.
In the second part of the chapter, I explore common medical problems that frequently appear along with CFS, such as fibromyalgia, migraine headaches, tinnitus, painful bladder syndrome, and myofascial temporomandibular disorder (mTMD). Each of these conditions has unique symptoms, affects different parts of the body, and is addressed by different medical specialties—yet they are strikingly similar in that all these patients complain of persistent and intermittent symptoms and have unremarkable lab values. These conditions are poorly understood, and the failure to treat them results in human suffering and high rates of disability. Using case studies, these conditions are contextualized within the CFS framework, along with the argument that long-acting stimulant medications have a common place in treatment.
Let’s start with one of the most prevalent psychiatric problems in the world: Depression.
Depression
Serious depression is a growing problem throughout the world. According to the National Institute of Mental Health (NIMH), in 2017, 17 million Americans adults experienced a major depressive episode.1 Depression is characterized by feelings of sadness and hopelessness in episodes that last two weeks or longer. The person may also experience fatigue, weight fluctuations, and changes in sleep and appetite patterns. Many depressed patients develop recurrent thoughts of death and suicidal impulses. According to the NIMH, 8.7 percent of American women were clinically depressed in 2017, compared to 5.3 percent of adult males. Women are more likely to reach out for professional help for themselves and on behalf of their family.2
Studies have shown depressive disorders are much more common among people diagnosed with CFS than among people with other health problems. For example, a large study compared depressive rates among nearly 23,000 Canadians with cancer, heart disease, and other serious disorders. The disease that won the dubious honor of experiencing the highest prevalence of mood disorders was CFS: 37 percent of CFS patients had mood disorders, followed by nearly 27 percent of patients with fibromyalgia. In contrast, only 10 percent of the patients with cancer were depressed, as were 9 percent of patients with diabetes.3 (See Table 4.1 for more information). This is an unexpected finding; in my opinion, very few doctors would predict that CFS patients are more likely to be depressed than patients diagnosed with cancer.
Other research confirms and extends this finding. In another Canadian study, 36 percent of 1,045 subjects with CFS were found to have a mood disorder, and nearly one-quarter of these individuals reported that they had considered suicide in the past year. Depressed patients with CFS had many physical concerns. On average, they visited their family doctors 11 times per year, compared to 7.0 visits for the CFS patients who were not depressed. In addition, one in every 11 depressed patients with CFS had seen their family doctor 30 or more times in the previous year.4 This high utilization rate reveals that while CFS patients are able to gain access to the Canadian health care system, physicians may not be providing them with the right type of relief. No doubt the situation is similar in the United States.
Table 4.1 Prevalence of Mood Disorders in Individuals with Chronic Conditions, Ontario, 2005
Characteristic |
Total Number |
% with mood disorder |
Men |
10,105 |
6.5% |
Women |
12,528 |
10.5% |
Age group, years |
||
12 to 29 |
3,721 |
8.1% |
30 to 49 |
7,512 |
10.9% |
50 to 69 |
7,699 |
8.7% |
70+ |
3,701 |
4.9% |
Married/common-law |
14,803 |
7.6% |
Single/Sep/Div/Widowed |
7,811 |
10.8% |
Education level: |
||
Less than second. school |
4,975 |
8.6% |
Second. school grad. |
3,670 |
9.1% |
Some post-secondary |
1,621 |
10.8% |
Post-secondary graduate |
11,571 |
8.4% |
Immigrant |
6,421 |
7.2% |
Canadian-born |
15,500 |
9.4% |
Income within Ontario: |
||
Low |
6,127 |
11.2% |
Middle |
7 727 |
8.6% |
High |
5,490 |
6.6% |
Food allergies |
2,108 |
11.7% |
Other allergies |
7,636 |
10.9% |
Asthma |
3,325 |
11.4% |
Fibromyalgia |
637 |
26.5% |
Arthritis/rheumatism |
7,140 |
10.9% |
Other back problems |
8,089 |
11.7% |
High blood pressure |
6,365 |
8.1% |
Migraine headaches |
4,721 |
14.1% |
Bronchitis |
1,009 |
16.9% |
Diabetes |
2,014 |
9.3% |
Epilepsy |
215 |
13.5% |
Heart disease |
1,997 |
9.8% |
Cancer |
621 |
10.1% |
Stomach/intestinal ulcers |
1,296 |
17.0% |
Effects of smoke |
476 |
15.5% |
Bowel disorder |
1,672 |
17.3% |
Cataracts |
1,861 |
8.2% |
Glaucoma |
610 |
6.9% |
Thyroid conditions |
2,183 |
10.9% |
Chronic fatigue syndrome |
543 |
37.2% |
Source: T. Gadalla, “Association of Comorbid Mood Disorders and Chronic Illness with Disability and Quality of Life in Ontario, Canada,” Chronic Diseases in Canada 28, n. 4 (2008): Table 2, page 151, https://www.canada.ca/content/dam/phac-aspc/migration/phac-aspc/publicat/hpcdp-pspmc/28-4/pdf/cdic28-4-4eng.pdf (accessed March 6, 2019). © All rights reserved. Association of comorbid mood disorders and chronic illness with disability and quality of life in Ontario, Canada. Public Health Agency of Canada. Adapted and reproduced with permission from the Minister of Health, 2019.
Explaining Depression in CFS
Depression can result from biologic causes, which means that some people are genetically predisposed to developing depression. This means that even in the absence of stressful circumstances, a percentage of the population is at risk of developing depression. It’s not uncommon for me to evaluate a person with a good job, healthy family, and supportive friends who also happens to have an incapacitating depression. In these predisposed individuals, depression can come unexpectedly, with no clear triggering event. For others predisposed to depression, everyday life stress can provoke a new episode of depression. For example, depression can take root when an individual loses a relationship or encounters a hostile workplace. In a person predisposed to depression, a worsening of CFS or fibromyalgia symptoms can trigger mood symptoms. The unique suffering of CFS patients is reflected by the fact that CFS patients report higher levels of depressive disorders than cancer patients. One reason for this high rate of depression may be that CFS-associated pain and fatigue feels omnipresent and inescapable. (Note that I have many suggestions for relief in this book!) Furthermore, cancer patients have a nonstigmatized diagnosis and a structured treatment plan. Most CFS patients have neither one.
A positive trend in modern medicine is an increased sensitivity to a patient’s mental health concerns. In previous generations, doctors did not fully appreciate that treating existing anxiety and depression greatly improves their patient’s quality of life. The introduction of safe and effective antidepressant medications, coupled with the rise of patient advocacy movements and changes to federal and state laws in the last 20 years, have helped to ensure that medical providers screen for and treat patients with depression. Some major insurance companies measure the rate at which a medical office screens for depression and uses the data as a quality control measure. If the medical office does not administer the Patient Health Questionnaire (PHQ-9) routinely (a simple test for depression), then the doctor’s “report card” suffers, which jeopardizes their per-patient reimbursement. Because of these types of initiatives, more people than ever are receiving mental health treatment.
Signs and Symptoms of Depression and CFS Overlap
Table 4.2 compares the symptoms of depression and CFS symptoms. Note that some of the signs and symptoms of depression sound very similar to the signs and symptoms of CFS. For example, feeling tired and unmotivated is common among both groups. Most ratings scales like the PHQ-9 are not sensitive enough to distinguish between CFS and depression. This high degree of symptom overlap is why so many physicians confuse CFS with depression. As a point of distinction, CFS patients experience more fatigue and pain than depressed patients do. While depressed patients report that they feel worthless, CFS patients endorse feeling frustrated with their low energy level.
Often, physicians do not distinguish between CFS and depression, and depression becomes the default diagnosis. For this reason, most patients with CFS are prescribed antidepressant medications. Serotonin reuptake inhibitor antidepressants (SRIs) elevate mood, diminish anxiety, and extinguish suicidal thoughts. However, SRIs do not dramatically improve energy or combat brain fog, and it is these cognitive complaints that truly debilitate people with CFS.
Table 4.2 Comparing Symptoms of Depression and CFS
Symptom |
Depression |
CFS |
Extreme fatigue |
Sometimes |
Always; fatigue does not improve with sleep |
Lack of motivation to do anything |
Sometimes |
Common |
Feeling like nobody cares about you |
Often |
Less common |
Brain fog |
Sometimes |
Always or often |
Sleeping disturbance |
May have insomnia or excessive sleep |
Inefficient sleep; time in bed much greater than time sleeping; sleep is not refreshing |
Loss of interest in activities that the person used to like |
Common. Interest returns as depression lifts |
Less common; interested in life activities but has trouble finding energy to actively participate |
Depressed mood |
Always; sadness is defining feature, and life does not feel worth living Questions the meaning of their existence |
Frustrated with their condition rather than feeling hopeless and worthless |
Suicidal thoughts |
Common |
Not typical |
Medications and Other Treatments for Depression
Many antidepressant medications effectively treat depression. Patients with CFS who also have depression benefit from these medications. Most increase the concentrations of the neurotransmitter serotonin in the prefrontal cortex and limbic regions of the brain.
First-Line Antidepressants, SRIs, SNRIs, and Trintellix
As mentioned earlier, SRIs are considered the first-line treatment for depression and are widely prescribed. Prozac (fluoxetine) is the most widely known SRI, and there are half dozen others, including Zoloft (sertraline), Paxil (paroxetine), and Lexapro (escitalopram).
A related class of antidepressants are the serotonin norepinephrine uptake inhibitors (SNRI). Some SNRIs are effective for anxiety and diabetic nerve pain, increasing brain concentrations of both serotonin and norepinephrine. The most commonly known medication of this class is duloxetine (Cymbalta). Other SNRIs include venlafaxine (Effexor XR), desvenlafaxine (Pristiq), and levomilnacipran (Fetzima).
Trintellix (vortioxetine) is another type of drug that has a more complicated action mechanism. As with the older medications, Trintellix blocks the reuptake of serotonin, but it also modulates various serotonin receptors. Beyond its effectiveness as an antidepressant for adults, Trintellix has been shown to speed certain cognitive tasks. This property has made Trintellix an appealing antidepressant to use in patients with cognitive deficits such as brain fog.
Antidepressant medications usually take effect within two weeks, and their full effects may not be realized for six weeks. They may cause significant side effects and should not be prescribed casually. Antidepressants are associated with sexual dysfunction and weight gain, and some patients feel emotionally blunted when on antidepressants. It is not uncommon for a patient to report, “Before, I used to cry too easily; now, on medications, I can barely cry at funerals.”
Second-Line Medications for Depression
When depressed patients do not respond to first-line antidepressants, antipsychotic medications (Abilify, Rexulti) and mood stabilizing agents (Lamictal) are often added to the SRI or SNRI. In the most severe cases of patients with treatment-resistant depression, Electroconvulsive therapy (ECT) can be administered. The FDA recently approved the antidepressant esketamine (Spravato), a dissociative anesthetic that quickly reverses depression symptoms. Many psychiatrists believe esketamine will prove to be a significant advancement in the treatment of depression and related conditions.
For CFS patients with depression, antidepressant medications are partially helpful. Conversely, a large subgroup of patients with CFS are misdiagnosed with depression and are improperly placed on these medications. Predictably, they do not improve, and unless there is a course correction, they find themselves on increasingly complicated antidepressant medication regimens.
Distinguishing CFS from depression and specifically treating the fatigue and cognitive symptoms of CFS decreases the likelihood of overtreatment with unnecessary medications.
Adjunctive Use of Modafinil (Provigil)
Modafinil (Provigil), a wakefulness-promoting drug, can be added to antidepressant medication in depressed patients with severe tiredness and impaired concentration. Modafinil is a schedule IV drug, and is less regulated than other stimulants (schedule II) because of its low addiction risk. In a study of 60 depressed patients with remitted depression, 30 were treated with modafinil and 30 with a placebo. When comparing the cognition and memory of the subjects in the two groups, the researchers found that the subjects treated with modafinil had significant improvements in the their memory.5
In a larger meta-analysis compiling six studies involving 568 patients with major depression and 342 with bipolar depression, modafinil was shown to improve symptoms of fatigue.6
In another study, Robert C. Bransfield analyzed 237 patients, with diagnoses ranging from depression to Lyme disease and ADHD. All participants had cognitive complaints, including fatigue, apathy, and concentration impairments. Only a few patients had a sleep disorder. Most of the patients were receiving antidepressants (60 percent) or anticonvulsants (15 percent). Bransfield found that adding modafinil to their baseline treatment improved fatigue, excessive sleepiness, executive dysfunction, and apathy/poor motivation.7
Please note that modafinil is not approved by the FDA for depression or for CFS; however, doctors legally may prescribe this drug if they feel it is appropriate. Although technically, it is not a stimulant, modafinil shares certain properties with stimulants. The medication is generally well tolerated but is less effective in CFS than the traditional stimulants I will describe in Chapter 6.
Psychotherapy
For individuals suffering from both CFS and depression, psychotherapy is a meaningful addition to antidepressant medications. A patient’s connection to a thoughtful therapist can be powerful. Therapists can explore with clients their feelings about depression, helping them to identify and neutralize negative thought patterns. The therapist can educate her patient that CFS and depression are separate conditions, though often interrelated. She may also educate patients that extended periods of fatigue can give rise to depressive symptoms and that these conditions are rooted biologically. There is no reason for patients to blame themselves for their illness. Therapy involves listening and educating and is most effective in correlation with medication treatment.
Anxiety and Trauma Disorders
Anxiety exacts a heavy toll, and CFS patients are at risk for developing the entire gamut of anxiety disorders, including generalized anxiety disorder (GAD), panic disorder, and post-traumatic stress disorder (PTSD).
Generalized Anxiety Disorders
Generalized anxiety disorder is characterized by excessive worry over a long period. This deeply uncomfortable sensation is accompanied by restlessness, fatigue, impaired concentration, and muscle tension. Individuals with GAD often complain of sleep disturbances and decreased interest in social interactions.
Typically, the GAD patient is consumed with baseless worries about work or the health and well-being of a family member. The patient with GAD has trouble embracing happiness, convinced that good news inevitably will be counterbalanced by something terrible. Everyone encounters transient anxiety on some occasion, but the person with GAD is flooded with persistent worry that lasts at least six months. The anguish is so deep that the person does not gain comfort by a doctor’s or friend’s reassurance. Women suffer more from GAD than men, with 3.4 percent of all women affected compared to 1.9 percent of men.8
Certain behavioral patterns occur in GAD:
•Worried thoughts in a loop (thinking the same worries, over and over)
•Feeling that something must be done—but not knowing what to do or how to get started
•Worry that they will cause problems for other people in their life
•Fears about personal safety and the well-being of friends and family
Becca, a human resources manager with GAD, described the endless loop of her intimate thoughts.
I know I have to solve the staffing problem at work, but I don’t know what more to do. I’ve tried everything that I can think of, but nothing has worked so far. If I do not solve the problem, I could lose my job! Then we won’t have any money to pay the bills, and I’ll probably lose my house and our health insurance. I can’t tell my boss that I’m stumped because when I do turn to him, he doesn’t make me feel better. He would probably fire me. I must solve this problem, but I don’t know how! What the heck am I going to do? I must do something, but what?
Becca displays a thought process of “catastrophizing,” believing that the worst possible outcome will happen. While she knows intellectually that her boss has no intention of firing her and that the company’s current staffing problems are manageable, she finds little comfort in these facts. While Becca welcomes reassurance from others, the relief does not last long, and the worry quickly resurfaces. GAD is addressable with medications and therapy.
Panic Attacks
Panic attacks come out of nowhere. Within minutes of its onset, the patient develops heart palpitations, sweating, shortness of breath, trembling and shaking, chills, and hot flashes. Along with these physical symptoms, an impending sense of doom engulfs the patient. The fear of dying is overwhelming, and a high percentage of people experiencing their first panic attack end up in the hospital emergency room, certain they are having a heart attack or stroke.
Panic attacks usually dissipate as quickly as they appear, but sometimes the patient starts to fear that the attack will recur. The experience is so unpleasant that sufferers modify their lives to decrease the likelihood of having another panic attack. Patients develop avoidances; for instance, if they had a panic attack on the freeway, then they avoid the freeway or avoid driving altogether. If the panic attack occurred at the supermarket, they may avoid the store or refuse to shop alone.
Post-traumatic stress disorder can develop when an individual is exposed to overwhelming events such as combat or a natural disaster. Post-traumatic stress disorder can also emanate from abusive experiences in childhood or a physical or sexual assault. Some of the symptoms closely resemble those of GAD and panic disorder, but PTSD patients uniquely experience an altered sensation of reality, referred to as dissociation, as well as an inescapable feeling that they are constantly reliving the trauma.
The Link between CFS and Anxiety
It is important to unravel why CFS patients are more likely than others to have anxiety. People with CFS seem to overreact to their environment and feel unduly threatened. Panic symptoms then follow.
While they are no more likely to experience a hurricane or a robbery than the average person, they may have a harder time calming themselves in the aftermath of a threatening event, and this increases their likelihood of developing PTSD. In other parts of the book, I assert that many adults with CFS also have lifelong ADHD, a condition that starts in childhood. Children and adults with ADHD are more likely than others to have experienced traumatic experiences. For example, in a study of 216 adults with ADHD compared to 123 adults who did not have ADHD, 10 percent of the adults with ADHD had PTSD, compared to about 2 percent of the controls.9
Another factor contributing to anxiety is that CFS patients may be accused of malingering, or faking their illness. Others may believe they are lazy or deluding themselves into thinking they are sick in order to gain sympathy. Some people with CFS have been suspected of gaming the system to receive disability payments or even to create an excuse for their tepid performance at work or home. The burden of feeling exhausted and in pain is hard enough, but feeling invalidated and manipulative compounds the discomfort.
It may also be that people with chronic fatigue too successfully hide their symptoms and how they feel about them. There is also experimental evidence that CFS patients may process emotions differently than others, specifically by suppressing their underlying feelings. In a study of 80 adults with CFS and 80 healthy controls, researchers exposed all subjects to an upsetting movie clip. Half of each group were told to suppress their feelings, while the other half was encouraged to express their feelings as they wished. Electrodes placed on the skin measured the subjects’ physiological responses to the movie clip. Third-party observers were told to report levels of distress among the subjects. Based on their skin measurements, the CFS subjects had significantly more distress than the healthy controls; however, the observers perceived low levels of distress in the CFS subjects. To clarify, the CFS subjects were actually quite upset based on their physiological responses, but they did not seem upset to others. The researchers questioned whether this disparity accounts for CFS patients being less able to utilize social supports during periods of stress.10
Although the study concludes that CFS patients process emotions differently from normal controls, it still does not answer the pivotal question: does CFS cause anxiety, or does early-life trauma trigger fatigue?
Somatic Symptoms Disorder, Anxiety, and Chronic Fatigue Syndrome
Patients with CFS are especially susceptible to somatic anxiety, or excessive worrying about one’s health. In a British study of 45 patients with CFS, including 31 women and 14 men, the researchers administered the Short Health Anxiety Inventory and the Hospital Anxiety and Depression Scale. They found that 42 percent of the subjects had significantly elevated levels of health anxiety. This far exceeded the rate of health anxiety found in patients with other health issues.1
It is interesting to speculate as to why this happens. The authors of the study conclude that patients with CFS feel “delegitimized” by their symptoms, and this leads to uncontrollable anxiety. This, along with their misperceptions of symptoms, the tendency to catastrophize, and the proclivity to feel overwhelmed offers sober explanation. Patients with CFS resent their fatigue and grow endlessly frustrated by not having good treatments or explanations.
There is some good news to counter these sober observations. When I have used stimulant medication to treat CFS, the anxiety symptoms decreased. This is contrary to what most people would predict, but in a double-blind study of lisdexamphetamine (LDX) versus placebo in the CFS patients, their anxiety scales declined significantly with active treatment. Clinically, I have found that treated patients become less preoccupied with anxiety and health concerns. The medication appears to allow them to “filter out” distractions, which allows them to process baseless worries into more productive thoughts. With long-acting stimulant medications, the patient’s compulsion to visit the doctor for every health concern diminishes. Chapter 5 explores this study in depth.
Note
1.Jo Daniels, Brigden, Amberly, and Kacorova, Adela, “Anxiety and Depression in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): Examining the Incidence of Health Anxiety in CFS/ME,” Psychology and Psychotherapy: Theory, Research and Practice (2017), https://onlinelibrary.wiley.com/doi/abs/10.1111/papt.12118 (accessed February 1, 2019).
Other Medical Problems That May Coexist with CFS
Patients with CFS frequently present with nebulous medical conditions that interfere with their quality of life. Many of these conditions are poorly understood, and while some treatments are available, the response to treatment is highly variable. I will discuss five of these interrelated conditions: fibromyalgia, chronic headaches, painful bladder (also known as interstitial cystitis), ear ringing (tinnitus) and mTMD. Each condition affects a different region of the body and the attention of a different medical specialist. For instance, neurologists quarterback headaches, urologists handle bladder concerns, and ENTs and dentists examine patients with tinnitus and jaw pain. Because these conditions are dispersed among medical specialists, and as fatigue complaints are overlooked, it is challenging to draw common conclusions about these disparate medical problems, but I will try to do so.
Several features are common to all these complaints. First, they are all associated with chronic fatigue. Second, the examining doctor often cannot find an anatomical reason for the complaints. Finally, the symptoms arise, dissipate, and arise again over time. Most importantly, I have found that in the presence of chronic fatigue, treatment with long-acting stimulant medications forces many of the physical symptoms into retreat. Let’s discuss each with greater detail and an anecdote of a successful treatment outcome in each case.
Fibromyalgia
The muscular aches and pains of fibromyalgia are commonly seen in outpatient clinics. Fibromyalgia often occurs in people with CFS, and many clinicians lump the two medical conditions together as one entity. Although they can occur together, fibromyalgia and CFS are officially distinct ailments. Fibromyalgia is characterized by occasional fatigue and so-called tender points, along with migrating pain through the body. Conversely, some pain might be reported with CFS, but the fatigue is the defining feature. According to the CDC, fibromyalgia affects an estimated four million people in the United States.11
Common symptoms of fibromyalgia include the following:
•Stiffness and pain throughout the body
•Sleep problems
•Fatigue and tiredness
•Struggles with memory and concentration
•Frequent headaches, such as migraines12
Other symptoms may include the following:
•Muscle fatigue and cramps
•Irritable bowel syndrome
•Temperature sensitivity
•Depression or anxiety13
Fibromyalgia is most common among middle-aged individuals, although the disorder can occur in people of any age. Women are about twice as likely as men to have fibromyalgia.14 Other factors linked to fibromyalgia include obesity and past injuries.
Treatment for Fibromyalgia
In the past decade, three medications have been developed for fibromyalgia, while CFS remains an orphan illness, with no single medication yet approved. Duloxetine (Cymbalta) is an SNRI approved by the FDA for the treatment of fibromyalgia, as is a related drug, milnacipran (Savella) that is less popular. Pregabalin (Lyrica), which is not an antidepressant, can also be used to treat diabetic nerve pain. Patients with fibromyalgia may also receive both prescribed and over-the-counter anti-inflammatory medications and pain control agents. Opioids should be avoided for this chronic condition.
Physical therapy is a mainstay of fibromyalgia treatment. Exercise is also recommended, although some research suggests that for those who have both fibromyalgia and CFS, exercise may worsen symptoms. Cognitive-behavioral therapy may play a productive role, and stress-management techniques such as yoga, meditation, and acupuncture may help certain patients, at least in the short term.
Headaches
Headache pain is associated with tension in the neck, shoulders, and crown of the skull. Frequent headaches may be linked to stressful circumstances and elicited by certain foods.15 Migraines are a specific type of headache characterized by an aura (seeing flashing lights or smelling something that is not there) prior to the onset of the actual headache. Chronic migraines are headaches occurring at least 15 days each month, and they affect about 1 percent of the population, according to the American Migraine Foundation.16
Risk factors for chronic migraines include the presence of other pain disorders, the presence of a back or neck injury, and obesity. Migraine rates are higher in those with a diagnosis of anxiety and/or depression.17 Often, migraine sufferers endure both classic migraine and tension headaches.
Success rates of treatment vary widely. Medications may include over-the-counter drugs, such as acetaminophen or ibuprofen. Prescribed medications are primarily in the triptan category, such as sumatriptan (Imitrex) and rizatriptan (Maxalt), among others. Botox injections are also increasingly common treatments. In addition, biofeedback and relaxation therapy may both be helpful techniques for migraine sufferers.
Because my colleagues know I have an interest in the underpinnings of chronic medical conditions, I have often been asked to evaluate patients who seek help for headache and migraine. One of my patients was Cary, a 47-year-old engineer. Cary had chronic fatigue and migraines and had been on triptans and Botox injections. Of concern was that he had used opiate medications for years, and his new doctor did not want to continue his prescription.
After a formal evaluation, I diagnosed Cary with ADHD, predominantly inattentive type, and with CFS, and his prescription was Adderall XR twice daily, a standard treatment for ADHD. I fully expected his inattentive symptoms to improve, and they did. An added benefit was the reduction in his profound fatigue. An unexpected byproduct of the Adderall XR treatment was a decrease in the frequency and intensity of his headaches. Cary now uses triptans (migraine medications) rarely, and he also discontinued the expensive Botox injections. Both Cary and his internist are delighted that he no longer needs opioid analgesic medications.
Other researchers have explored the connection of migraine to CFS. In one study, 82 percent of subjects with CFS experienced migraines, compared to 13 percent of healthy controls.18 If the hypothesis that CFS responds to long-acting stimulants proves valid, then it might also represent a plausible treatment for chronic migraine. It is also worth noting that caffeine, a stimulant, has long been added to headache medications, including the iconic brand Excedrin. Complicated patients such as Cary, who have migraines, CFS, and ADHD, may benefit from further research.
Painful Bladder Syndrome (Interstitial Cystitis)
Painful bladder syndrome is a chronic condition experienced by up to eight million people in the United States, primarily females. Whereas the average woman urinates four to seven times per day, women with painful bladder syndrome may have the urge 40 times a day. Other symptoms may include pain during sexual intercourse and pain in the lower back or abdomen that escalates during the menstrual period.19
Initially, the presentation of severe bladder pain may point to a bladder infection, but the urinalysis and culture are both negative. This problem can be further analyzed with a cystoscopy, or an internal examination of the bladder by a urologist. Other tests may include a biopsy of the bladder to check for bladder cancer. With the patient under sedation, the urologist may fill the bladder with fluid to stretch it and to determine how much fluid the bladder can hold. During this procedure, the urologist may or may not find lesions on the bladder wall.
Urologists have difficulty understanding why some women have excruciating bladder pain in the absence of lesions, and others have lesions but no pain. This does not mean the pain is not real in some people, but the intermittent nature of the complaints is mysterious. It is noted that IC often runs with other chronic health problems such as CFS and fibromyalgia.
Traditional treatment for painful bladder syndrome often does not work dependably because the underlying cause is unclear. Proposed treatments may include over-the-counter painkillers or prescription medications such as pentosan (Elmiron). Antihistamines and/or antidepressants may help, as might Botox injections. Surgery to clear the lesions has not been widely adopted. Women are advised to stop smoking and to avoid citrus fruits, alcohol, tomatoes, and chocolate—all foods that can irritate the bladder.20
Interstitial cystitis (IC) patients come to my clinic because they are frustrated with their unrelenting pain. My patient Ellie had all the symptoms of IC, painful bladder syndrome. Despite close adherence to her treatment plan, including taking scheduled pain medications and limiting her diet, she still had persistent bladder pain. Our evaluation determined that in addition to anxiety, Ellie also had ADHD, predominantly inattentive type, and CFS. I added Vyvanse to her long-standing antidepressant medication.
My primary goal was that the medication help Ellie focus and concentrate, and she did appreciate relief quickly. She also noticed a lessening of her bladder pain. Over time, Ellie reported that she used her IC medications less often. Her urge to void decreased, and intercourse became less painful.
When I questioned Ellie, she emphasized that the pain was not gone, but she felt less preoccupied by the sensation of bladder discomfort. The discomfort was more evident in the morning before she took her Vyvanse and in the evening after the medication wore off. On the days that Ellie did not take Vyvanse, her pain resurfaced. I concluded that not only did Vyvanse enhance her attention but it also distracted her from the unpleasant physical sensation emanating from her bladder. This helps explain the intermittent nature of physical complaints; whether the pain comes from a lesion or another source, the brain has the ability to filter out irritating signals. Medications such as Vyvanse can temporarily district the brain from registering the discomfort.
Ringing in the Ears (Tinnitus)
Not a day goes by in an ENT’s office when a patient does not complain of tinnitus. The description of the sound varies—a ringing or crackling in the ears; sometimes constant and other times intermittent. The sound may be a clicking or hissing type of noise, and it may be either low-pitched or high-pitched. There are some known causes of tinnitus, such as a noise-induced hearing loss and ear or sinus infections. Many can empathize with tinnitus sufferers; indeed about 10 percent of American adults have experienced at least five minutes of tinnitus in the past year.21 For those who experience tinnitus chronically, the problem can lead to impaired quality of life and debility.
Causes of Tinnitus Are Unclear
Scientists disagree on why people develop chronic tinnitus; it may stem from damage to the inner ear’s signaling action in part of the brain. People with chronic tinnitus may gain some relief through wearable or tabletop sound generators, which help drown out the internal noises that the person constantly hears. For those who have experienced hearing loss along with their tinnitus, hearing aids may help. More sophisticated and elaborate treatments include acoustic neural stimulation with headphones and a handheld device that sends a broadband acoustic signal embedded in music. This treatment may desensitize the person to the tinnitus, and it has been effective in volunteer testers.22
As the referral activity between otolaryngologists and psychiatrists is minimal, I assume I see only a smattering of tinnitus patients. My impression, however, is that currently available treatment is often ineffective. The strategy of mechanically distracting the patient with other sounds does not consistently work. Because effective treatments are elusive, tinnitus patients are a great source of frustration for their doctors. In kind, tinnitus patients express their dissatisfaction for the care they receive.
The Case of Barry
Barry suffers from tinnitus. His ear ringing began after he sat under the speakers at a loud concert in an enclosed room. “Several times that night, the high-pitched feedback from the speaker jarred me,” he said. In the succeeding weeks, Barry was so impaired that he could not go to work. He was a dedicated triathlete, and to make matters worse, a recent tear to his Achilles tendon dropped his exercise to nothing. Barry became irritable, and his relationship with his family and work colleagues deteriorated. Over the next few months, he saw two ENT physicians, and over the next year, he tried many different treatments. He attended his son’s wedding wearing noise-cancelling headphones—but received more odd stares than relief.
Barry was disturbed to learn that a prestigious clinic refused to see him, stating that they had nothing more to offer for his tinnitus. He came to me to seek help regarding his fatigue, poor motivation, and family conflict. Barry’s wife bitterly complained of his compulsive need to exercise for up to six hours per day, an unexpected behavior in a man suffering from fatigue. During Barry’s evaluation, I learned that two of his children had long been treated for ADHD. When asked, he reported that he had always been fidgety. “That’s why I always exercise. If I don’t move, I feel like crawling out of my skin.” Barry’s diagnosis was clear: ADHD, hyperactive-impulsive type.
I started Barry on Mydayis, a stimulant medication, and he engaged in talk therapy. Within a few weeks, many of his complaints lifted, and his ear ringing reemerged only in emotionally stressful circumstances. Mydayis arrived in Barry’s life in time to salvage his job, and he was able to avoid filing for disability insurance. Barry realized that since starting treatment, he felt calmer, and upon recovery from surgery, he no longer craved endless exercise. A 45-minute workout three or four times weekly was sufficient.
Myofascial Temporomandibular Disorder (mTMD)
Myofascial temporomandibular disorder (mTMD) is a common type of temporomandibular disorder. The temporomandibular joint includes the bones, muscles, and tissues forming the area between the upper and lower jaw. Clinical signs of mTMD include muscle tenderness upon pressure to the joint or surrounding area, causing restrictions on movements of the mouth. The patient may notice clicking noises when opening and closing the jaw.23 This medical problem is associated with pain upon awakening, muscle tenderness, and severe migraine or tension headaches. Often the pain comes on suddenly, rather than increasing slowly over a period. Nearly half of all patients with oral and facial pain have mTMD.24
Before making the diagnosis, the doctor should rule out other conditions that can cause facial pain. These include dental cavities, a cracked tooth, sinusitis, and irritation of the trigeminal nerve in the cheekbone area (trigeminal neuralgia).25
Dentists are usually the ones who treat mTMD. Dental appliances can be fitted and are often used in tandem with naproxen (Naprosyn) or another nonsteroidal anti-inflammatory drug (NSAID). Injections of local anesthetic is a more invasive approach. Other drugs that may be employed are anticonvulsant medications such as gabapentin (Neurontin) and pregabalin (Lyrica) and a tricyclic antidepressant—most often amitriptyline (Elavil). Benzodiazepines medications such as diazepam (Valium) and clonazepam (Klonopin) may help combat muscle tension in the short term, but they have fallen out of favor due to the potential for addiction and the risk of severe complications when used with muscle relaxants such as cyclobenzaprine (Flexeril) and opiate medications.26
Because traditional treatments for mTMD are problematic, many doctors refer patients to PT. If PT fails, alternative treatments such as acupuncture or biofeedback therapy remain. Biofeedback therapy teaches the patient to relax when pulse or blood pressure increase during pain. Some patients obtain short-term relief from these approaches, but they rarely work over a longer period.
Wrapping It Up
Although mTMD, chronic migraine, IC, and tinnitus all affect different parts of the body, they share common features: waxing and waning pain complaints, often with no corresponding physical finding for the pain. Most of them, certainly mTMD, present commonly among people with fibromyalgia and/or CFS.27
Other medical maladies too numerous to detail also fall under this general description. They include irritable bowel syndrome (IBS), some aspects of premenstrual syndrome (late luteal dysphoric disorder), lower back pain, and a controversial condition called postural orthostatic tachycardia syndrome (POTS). There are clear causes for some cases of these conditions, but for many patients, there is no answer. The treatments that do exist help select patient but not others. Sometimes patients gain hope when a specialist appears, offering a new approach, and lose hope after she leaves, mission not accomplished. Even well-meaning and enthusiastic doctors must move on—leaving their patients feeling abandoned.
In my experience among the heterogenous conditions discussed in this chapter, CFS is often a common denominator. Modulating central dopamine channels with long-acting stimulant medication alleviates fatigue and allows the brain to filter out painful stimuli. Further research in the use of this class of medications holds promise for many of the patients discussed in this chapter.
This chapter covered other issues that people with chronic fatigue commonly experience, ranging from depression and anxiety to health problems such as fibromyalgia, tinnitus, and other issues.
In the next chapter, I dig deeper into my own research and describe the findings of the RCS, which compared a long-acting stimulant to placebo in a CFS population. I follow this with a discussion of the types of medications that may be helpful in making a meaningful difference in the lives of people with chronic fatigue.
Notes
1.National Institute of Mental Health, “Major Depression,” November 2017, https://www.nimh.nih.gov/health/statistics/major-depression.shtml (accessed February 1, 2019).
2.Ibid.
3.T. Gadalla, “Association of Comorbid Mood Disorders and Chronic Illness with Disability and Quality of Life in Ontario, Canada,” Chronic Diseases in Canada 28, n. 4 (2008): 148–154.
4.Esme Fuller-Thomson and Nimigon, Jodie, “Factors Associated with Depression among Individuals with Chronic Fatigue Syndrome: Findings from a Nationally Representative Study,” Family Practice Advance Access (October 2008), https://academic.oup.com/fampra/article/25/6/414/480969 (accessed February 8, 2019).
5.Muzaffer Kaser, et al., “Modafinil Improves Episodic Memory and Working Memory Cognition in Patients with Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study,” Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2, n. 2 (2017): 115–122.
6.Alexander J. Goss, et al., “Modafinil Augmentation Therapy in Unipolar and Bipolar Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials,” Journal of Clinical Psychiatry 74, n. 11 (November 2013): 1101–1107.
7.Robert C. Bransfield, “Potential Uses of Modafinil in Psychiatric Disorders,” Journal of Applied Research 4, n. 1 (2004): 198–207.
8.National Institute of Mental Health, “Generalized Anxiety Disorder,” November 2017, https://www.nimh.nih.gov/health/statistics/generalized-anxiety-disorder.shtml (accessed February 1, 2019).
9.Kevin M. Antshel, et al., “Posttraumatic Stress Disorder in Adult Attention-Deficit/Hyperactivity Disorder: Clinical Features and Familial Transmission,” Journal of Clinical Psychiatry 74, n. 3 (2013): e197–e204.
10.Katharine A. Rimes, et al., “Emotional Suppression in Chronic Fatigue Syndrome: Experimental Study,” Health Psychology 35, n. 9 (2016): 979–986.
11.Centers for Disease Control and Prevention, “Fibromyalgia,” October 11, 2017, https://www.cdc.gov/arthritis/basics/fibromyalgia.htm (accessed February 1, 2019).
12.Ibid.
13.Office on Women’s Health, “Fibromyalgia,” August 22, 2017, https://www.womenshealth.gov/files/documents/fact-sheet-fibromyalgia.pdf (accessed February 7, 2019).
14.Ibid.
15.Joseph Kandel and Sudderth, David, The Headache Cure: How to Uncover What’s Really Causing Your Pain and Find Lasting Relief. New York: McGraw-Hill, 2006.
16.American Migraine Foundation, “Chronic Migraine,” May 2008, https://americanmigrainefoundation.org/resource-library/chronic-migraine/ (accessed February 1, 2019).
17.Ibid.
18.National Headache Foundation, “Illness, Chronic Fatigue Syndrome and Migraine,” March 15, 2013, https://headaches.org/2013/09/15/illness-chronic-fatigue-syndrome-and-migraine/ (accessed February 7, 2019).
19.Office on Women’s Health, “Bladder Pain,” December 27, 2018, https://www.womenshealth.gov/a-z-topics/bladder-pain (accessed February 7, 2019).
20.Ibid.
21.National Institute on Deafness and Other Communications Disorders, “Tinnitus,” March 6, 2017, https://www.nidcd.nih.gov/health/tinnitus (accessed February 7, 2019).
22.Ibid.
23.Robert L. Gauer and Semidey, Michael J., “Diagnosis and Treatment of Temporomandibular Disorders,” American Family Physician 91, n. 6 (May 15, 2015): 378–386.
24.César Fernandez-de-las Penas and Svensson, Peter, “Myofascial Temporomandibular Disorder, Current Rheumatology Reviews 12, n. 1 (2016): 40–54.
25.Robert L. Gauer and Semidey, Michael J., “Diagnosis and Treatment of Temporomandibular Disorders,” American Family Physician 91, n. 6 (May 15, 2015): 378–386.
26.Ibid.
27.No author, “Options and Perceptions: Rethinking Treatment for Facial Pain,” Pain Week, February 5, 2019, https://www.painweek.org/media/news/options-and-perceptions-rethinking-treatment-facial-pain (accessed February 7, 2019).