CDC-FACT.TXT ------------ Below is the text of the booklet "The Facts About Chronic Fatigue Syndrome" published in August 1994 by the U.S. Centers for Disease Control and Prevention. An earlier draft of this text was scanned into an electronic file by Chuck Moss, and that was revised by Maryka Ford and Roger Burns to yield the current file. ------------------------------------------------------------------------ The Facts About Chronic Fatigue Syndrome Answers to Commonly Asked Questions About Chronic Fatigue Syndrome National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, Georgia, August, 1994 Use of trade names or commercial sources is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services. Background Chronic fatigue syndrome, or CFS, is a debilitating disorder characterized by profound tiredness or fatigue. Patients with CFS may become exhausted with only light physical exertion. They often must function at a level of activity substantially lower than their capacity prior to the onset of illness. In addition to these key defining characteristics, patients generally report various nonspecific symptoms, including weakness, muscle aches and pains, excessive sleep, malaise, fever, sore throat, tender lymph nodes, impaired memory and/or mental concentration, insomnia, and depression. CFS can persist for years. The cause of CFS has not been identified and no specific diagnostic tests are available. Moreover, incapacitating fatigue can be associated with a wide range of well-defined illnesses, such as cancer, depression, autoimmune diseases, hormonal disorders, and subacute infections. Since many of these disorders are treatable, other causes of fatigue must be ruled out before a diagnosis of CFS can be made. Although it can be diagnosed only through this process of elimination, CFS is a genuine clinical condition whose cause and treatment are the focus of intense research. Reports about CFS have been presented at scientific meetings and published in peer-reviewed research journals. However, the body of information is still small, and many findings are preliminary. Finally, unsubstantiated anecdotal information about CFS has confused some patients and physicians regarding what is speculation and what is scientific fact. The purpose of this brochure is to provide answers to the most commonly asked questions about CFS and to clarify areas that are often misunderstood. CLINICAL ASPECTS AND DEMOGRPAHICS Why is this illness called chronic fatigue syndrome? A number of names have been proposed over the years to describe clinical features similar to the syndrome we now call CFS. These names include chronic Epstein-Barr virus disease, chronic fatigue immune dysfunction syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. The term "chronic fatigue syndrome" was agreed upon in 1988 by a group of experts studying the illness. The group unanimously selected chronic fatigue syndrome because they believed the use of a more specific name would be misleading, given the current knowledge about the disease, and would apply only to some symptoms and patients. For example, no characteristic profile of immune dysfunction has been identified that defines chronic fatigue syndrome, and most patients do not have encephalomyelitis (inflammation of the brain and spinal cord). If my symptoms do not fit the published case definition of CFS does that mean I do not have CFS? The case definition published in 1988 (Holmes et al, Ann Intern Med 108:387-9) was produced by medical and public health experts at a meeting sponsored by the Centers for Disease Control (CDC)(Appendix A). The case definition was deliberately designed to define a narrow group of patients for research purposes. Scientists working on CFS need to study patients who have the same, carefully defined illness characteristics. Only by studying relatively homogenous groups of patients are researchers likely to identify a causative agent, physiologic abnormality, or laboratory marker for CFS. This research definition was not designed to be used in the clinical diagnosis of CFS. How many people in the United States have CFS? On the basis of results from the first 3 years of its ongoing physician referral-based surveillance study, CDC estimates the minimum prevalence rate of CFS in the United States at 4 to 10 cases per 100,000 adults 18 years of age or older (adjusted for age, sex, and race). Although some media reports have indicated that more than 5 million persons in the United States have CFS, these estimates are not supported by scientific studies. Who gets CFS? In the United States, the majority of diagnosed cases of CFS occur in women, most of whom are white. In the CDC's surveillance study, approximately 80% of the cases identified were in women. Most patients are 25 to 45 years old. However, CFS has been diagnosed in a wide range of age groups, including adolescents, and in persons of different races. How frequently CFS occurs among various demographic groups is uncertain but being investigated. Diagnosis of CFS among some groups may reflect differences in culture and factors such as access to medical care. Carefully designed surveillance studies of CFS must be performed before a clear picture of its distribution in the population emerges. What types of cognitive dysfunction are associated with CFS? CFS patients commonly report one or more symptoms of cognitive dysfunction, including confusion, difficulty concentrating, impaired thinking, and forgetfulness. Patients often regard these symptoms among the most debilitating features of CFS. Are there any long-term health problems associated with having CFS? No scientific evidence exists for any long-term risks associated with CFS. There are anecdotal reports of increased rates of cancer, multiple sclerosis, and other illnesses among CFS patients, but none of these claims have been scientifically established. Unlike immune deficiency diseases, such as AIDS, CFS is not associated with opportunistic infections. Unsubstantiated claims have been made that CFS patients are more prone to suicide, but there are no data to indicate that the suicide rate among CFS patients is higher than that for the general population. What is the prognosis for CFS -- will I get better? Very little is known about the clinical course of CFS. It is among the most important areas of CFS research by both CDC and National Institutes of Health (NIH). The course of this illness differs widely among patients. Some patients recover completely with time, while others seem to grow progessively worse. Often, the illness follows a cyclical course, alternating bewteen periods of illness and relatively good health. Some patients improve to a certain extent but never fully recover. Is CFS contagious? There are no published data indicating that CFS is communicable through either casual or intimate contact. Studies of groups of CFS patients and their contacts have shown no evidence of person-to-person transmission of the illness. Several cluster outbreaks of unexplained fatigue reported to CDC in recent years are being investigated. Furthermore, reports that pets are involved in the transmission of CFS, or that they can contract the disorder, are unsubstantiated. Is it safe for me to become pregnant if I have CFS? Some physicians have informally noted that the symptoms associated with CFS appear to recede during pregnancy. No controlled studies of CFS and pregnancy have been done. How is CFS treated? Without knowing the cause of CFS, it is difficult to identify effective treatments. Medications prescribed for CFS usually are intended to provide symptomatic relief and not a cure. However, a number of unproven and potentially dangerous treatments and diagnostic tests have been given to CFS patients at exorbitant cost. Some of the more common remedies and prescription medicines provided to CFS patients are listed in Appendix B. Are there certain medications I should avoid? In most circumstances, patients should trust the advice of their physician. However, certain treatments, such as cyclophosphamide, azathioprene, methotrexate, and hydrogen peroxide injection, are potentially life-threatening, wholly unproven to relieve the symptoms of CFS, and should be avoided. If in doubt, call your local medical society, university medical school, or another physician. Is a particular dietary or vitamin supplement regimen recommended for people with CFS? There are no studies to suggest that dietary or vitamin supplements relieve the symptoms of or cure CFS. A list of dietary supplements and vitamins commonly used by CFS patients is included in Appendix B. Does exercise relieve symptoms or make them worse? Exercise, as well as other physically and mentally challenging activities, can exacerbate fatigue and other symptoms associated with CFS. Patients report that the effects of exercise may not be felt until 1 or 2 days after the activity. Studies are under way to determine the cause and to characterize the nature of this phenomenom. It is clear, however, that lack of exercise leads to deconditioning. Therefore, a regular regimen of moderate exercise, determined by individual tolerance, is generally recommended. Can I continue to work if I have CFS (or, can my child with CFS continue to attend school)? CFS patients may experience a variety of potentially debilitating conditions, including fatigue, arthralgia/myalgia, and difficulty concentrating, that can affect their performance on the job or in school. There is no evidence, however, that CFS can be spread from person to person. Therefore, if you feel well enough to continue working, there is no reason not to. Is it safe for me to donate blood if I have been diagnosed with CFS? Since the cause of CFS is unknown, and since it may represent a general set of symptoms caused by a variety of factors, there is currently no formal policy or recommendation concerning donation of biological products, such as blood, by CFS patients. There are no cases of persons who acquired CFS after blood transfusion. In general, however, persons who are not in good health, including those with CFS, are discouraged from donating blood and blood products. If you suspect you have CFS or a similar condition, inform officals at the blood collection center that you have CFS. The blood bank may have specific regulations concerning CFS or comparable illnesses. POSSIBLE CAUSES OF CFS What causes CFS? The cause of CFS has not been identified, but there are several theories. Numerous well-characterized viruses are known to cause severe fatigue during acute infection. While some viruses, such as Epstein-Barr virus (EBV), occasionally establish a chronic active infection that results in persistent fatigue, no single virus has been firmly associated with CFS. One hypothesis is that a virus, stress, or other transient traumatic condition may chronically activate the immune system. According to this hypothesis, the immune system, which ordinarily gears down after an infection has been eliminated, remains activated after the initiating infection has passed. The result is that unusually high concentrations of immune activating factors, some of which are known to cause fatigue at high doses, persist in the bloodstream. Other theories involve proposed disturbances in the hormonal (endocrine) system, and some fatigue may be induced by psychological conditions. Another possibility is that a single causative agent, as yet unidentified, causes CFS. Is CFS caused by an uncharacterized human retrovirus? One report in the scientific literature described possible retrovirus DNA sequences in lymphocytes from CFS patients that were not present in healthy persons. Despite intensive efforts, several laboratories could not confirm the results of this study. Anecdotal reports that CFS is caused by a human spuma virus are unsubstantiated. In addition, CFS does not have any relationship to a recently reported rare disease, human immunodeficiency virus (HIV)-negative AIDS. There is also no evidence to suggest that CFS is caused by HIV 1, the virus that causes AIDS. Reduced CD4 counts are rarely observed in CFS patients. There is no evidence of life-threatening or clinically noteworthy compromise of the immune system in CFS patients. Retrovirus involvement in CFS is unlikely, although it continues to be investigated. Does human herpesvirus type 6 (HHV-6) cause CFS? HHV-6 is an extremely common herpesvirus infection that causes roseola in children and infects at least 95% of persons older than 1 year. Like all herpesviruses, HHV-6 normally remains latent within infected persons but can be reactivated periodically. Some studies have reported inconclusive evidence of HHV-6 reactivation in CFS patients; others have found no correlation between HHV-6 infection and CFS. However, since it is virtually ubiquitous in the general population, HHV-6 infection cannot be used to diagnose CFS. Do enteroviruses cause CFS? Like herpesviruses, some enteroviruses are known to cause severe fatigue and muscle weakness. Enteroviruses have been studied by several groups for their involvement in CFS. As with other potential viral causes, no strong associations can be made between recent infection by enteroviruses and CFS. DIAGNOSIS OF CFS Can CFS be diagnosed by laboratory tests? No diagnostic test exists for CFS. Currently, laboratory tests are useful solely to rule out other causes of fatigue. The same is true of serologic tests for certain viruses. Numerous scientific reports have documented immunologic differences between groups of CFS patients and healthy controls, but differences are not observed consistently, and test results between individual patients and controls overlap considerably. In other words, the test values for a randomly chosen CFS patient and those for a randomly chosen healthy person may both fall into the normal range for any of these tests. How is CFS diagnosed? CFS is currently diagnosed by a history of illness suggestive of CFS, and through the systematic exclusion of other possible causes. A patient must first have profound fatigue for a minimum of 6 months. To complete the diagnosis, a physician must rule out the many clinically defined (and often treatable) causes of chronic fatigue by using a panel of routine diagnostic tests. Consult Appendix A for specific examples of illnesses that may cause severe fatigue. Are there CFS specialists who are more qualified than physicians in general practice to diagnose this illness? As with any illness, some physicians are more familiar with CFS than others but any licensed physician should be able to diagnose CFS. Persons who suspect they might have CFS should seek a doctor with whom they have a comfortable rapport, and who has knowledge of or is open to learning about CFS. Call the nearest university-based medical center if you have difficulty locating a physician who is familiar with the syndrome. Can CFS be diagnosed by using extremely sensitive molecular tests to demonstrate the presence of retrovirus-like DNA sequences? No. One published report has been erroneously interpreted to indicate that CFS can be diagnosed by using the polymerase chain reaction method to detect human T-cell lymphotrophic virus type II (HTLV-II)-like DNA sequences in the Iymphocytes of patients. However, more recent studies do not support this view. As such, this expensive research test is not useful in the diagnosis of CFS (see Possible Causes of CFS). Should diagnostic imaging techniques, such as MRI, PET scan, and SPECT scan, be used in the diagnosis of CFS? Several reports in the peer-reviewed clinical literature have described CFS patients with recognizable abnormalities seen in MRI or SPECT scans of the brain. However, these preliminary reports have not been confirmed by definitive follow-up studies and did not identify abnormalities in all CFS patients. Since the importance of these early reports is not known, these costly procedures are not appropriate for the clinical diagnosis of CFS. CFS patients have been shown to have increased antibody levels (i.e., elevated titers) to various infectious agents, including EBV, cytomegalovirus, HHV-6, rubella, enteroviruses, and Borrelia. Does this observation indicate that CFS can be triggered by the reactivation of latent infections? Some viruses, most notably the herpesviruses, can establish a state of prolonged dormancy, known as a latent infection, within their host. Such viruses normally reactivate periodically and consequently restimulate the immune system. Published studies have reported elevated titers to a number of these agents among CFS patients compared with controls. However, test values between individual patients and controls broadly overlap, indicating that such tests cannot be used to diagnose CFS. Early studies concluded that there was an association between high levels of serum antibody to EBV (which is known to cause fatigue) and CFS. However, more recent studies have shown that elevated EBV titers are not correlated with CFS. Rubella, enteroviruses, and Borrelia cannot produce a latent infection, but they can persist for prolonged periods in an infected person. Finally, because persons within a given population exhibit a broad range of titers to viruses that establish latent infections, "elevated titer" is difficult to define. ABNORMALITIES OF THE IMMUNE SYSTEM Do CFS patients have lower-than-normal numbers of natural killer cells or natural killer cells with impaired function? Some investigators have reported lower numbers of natural killer cells or lower levels of natural killer cell activity in CFS patients than in controls. Others have been unable to observe any natural killer cell abnormalities among CFS patients. No study of natural killer cells in CFS patients has ever defined an abnormality that consistently identifies the patients. As with other experimental assays, measured levels of natural killer activity varied greatly among patients and controls, and individual test results overlapped considerably; thus no clearly abnormal values separated all (or most) cases from all (or most) controls. Are T-cell activation markers present on a higher number of immune cells in CFS patients? One study showed that the CD8 T-cell subpopulation contained an increased number of cells expressing the activation markers CD38 and HLA-DR in a subset of CFS patients who were very ill. This finding was true for a large proportion of CFS patients (90%), but only a small fraction of healthy controls (10%). However, similar shifts in the expression of activation markers have been observed for various acute viral infections and would be expected of any active infection. The usefulness of activation markers in diagnosing CFS remains to be established. Could elevated levels of serum cytokines indicate CFS? One of the more intriguing theories about the cause of CFS is that one of a number of possible "triggering events" results in a chronic activation of the immune system in these patients. If this theory is correct, one or more serum cytokine levels of CFS patients may be more elevated than those of healthy controls. Such results have been reported anecdotally for interleukin-1, for example, but no characteristic pattern of serum cytokines has been established. If I have allergies, am I more prone to get CFS? Several studies have demonstrated that some, but by no means all, CFS patients have a history of allergies. Allergy could be one predisposing factor for CFS, but it cannot be the only one, since not all CFS patients have allergies. Appendix A The case definition of CFS for research purposes, from Holmes et al, Ann Intern Med (1988) 108:387-9. A case of chronic fatigue syndrome must fulfill both major criteria listed below, and the following minor criteria: 6 or more of the 11 symptom criteria and two or more of the three physical criteria; or eight or more of the 11 symptom criteria. Major Criteria 1. New onset of persistent or relapsing, debilitating fatigue or easy fatiguability in a person who has no previous history of similar symptoms, that does not resolve with bedrest, and that is sufficiently severe to reduce or impair average daily activity below 50% of the patient's activity before onset, for a period of at least 6 months. 2. Other clinical conditions that may produce similar symptoms must be excluded by thorough evaluation, based on history, physical examination, and appropriate laboratory findings. These conditions include malignancy, autoimmune disease, localized infection (such as occult abscess), chronic or subacute infection (such as endocarditis, Lyme disease, or tuberculosis), fungal disease (such as histoplasmosis, blastomycosis, or coccidiomycosis), and parasitic disease (such as toxoplasmosis, amebiasis, giardiasis, or helminthic infestation); disease related to (HIV) infection; chronic psychiatric disease, either newly diagnosed or by history (such as endogenous depression, hysterical personality disorder, anxiety neurosis, schizophrenia, or chronic use of major tranquilizers, lithium, or antidepressive medications); chronic inflammatory disease (such as sarcoidosis, Wegener granulomatosis, or chronic hepatitis); neuromuscular disease (such as multiple sclerosis or myesthenia gravis); endocrine disease (such as hypothyroidism, Addison disease Cushing syndrome, or diabetes mellitus); drug dependency or abuse (such as alcohol, controlled prescription drugs, or illicit drugs), side effects of a chronic medication or other toxic agent (such as a chemical solvent, pesticide, or heavy metal); or other known or defined chronic pulmonary, cardiac, gastrointestinal, hepatic, renal, hematologic disease. Minor Criteria Symptom Criteria For inclusion in the definition of a case, a symptom must have begun at or after onset of fatigue, and must have persisted for at least 6 months (individual symptoms may or may not have occurred simultaneously): 1. Mild fever (37.5 C to 38.6 C) or chills 2. Sore throat 3. Painful lymph nodes 4. Unexplained generalized muscle weakness 5. Muscle discomfort or myalgia 6. Prolonged (24 hours or greater) generalized fatigue after levels a exercise that would have been easily tolerated prior to the onset of chronic fatigue 7. Generalized headaches (of a type, severity, or pattern that is different from that of headaches the patient may have had before onset of the chronic fatigue) 8. Migratory arthralgia without joint swelling or redness 9. Neuropsychologic complaints (one or more of the following: sensitivity to light, temporary visual blind or dark spots, forgetfulness, excessive irritability, confusion, difficulty thinking, inability to concentrate, depression) 10. Sleep disturbance (hypersomnia or insomnia) 11. Description of the main symptom complex as initially developing over a few hours to a few days (this is not a true symptom, but may be considered as equivalent to the above symptoms in meeting the requirements of the case definition). Physical Criteria 1. Low grade fever (oral temperature between 37.6 C and 38.6 C, or rectal temperature between 37.8 C and 38.8 C) 2. Nonexudative pharyngitis 3. Palpable or tender anterior or posterior cervical or axillary lymph nodes (note: lymph nodes greater than 2 cm in diameter suggest other causes. Further evaluation is warranted) Appendix B Medications, herbal preparations, and miscellaneous treatments which have been used against CFS Key: X = no proven utility for CFS; S = useful for relief of symptoms; U = use unjustified for CFS; F = no known clinical value; C = conflicting findings in clinical tests; P = clinical findings in progress, no published findings to date Vitamins, coenzymes, and minerals _______________________________________________________________ Treatment Name Value in Side effects associated treating with the use of this treatment CFS* --------------------------------------------------------------- Coenzyme Q-10 F harmful effects unknown Vitamin B-12 X harmful effects unknown Vitamin C X long term use at high dose may cause development of kidney stones Vitamin A X high doses of this vitamin can cause a wide variety of clinical symptoms including permanent liver damage Selenium X compounds of this element may cause gastrointestinal disturbances and some are carcinogenic Germanium X harmful effects unknown Zinc X harmful effects unknown Iron X high doses of iron salts may be toxic Adenosine F harmful effects unknown monophosphate L-tryptophan F contaminated lots have been implicated in triggering eosinophilia- myalgia syndrome Magnesium sulfate X harmful effects unknown --------------------------------------------------------------- *X = no proven utility for CFS; F = no known clinical value Herbal Preparations _______________________________________________________________ Treatment Name Value in Side effects associated treating with the use of this treatment CFS* --------------------------------------------------------------- Astralagus X harmful effects unknown Echinacea X harmful effects unknown Garlic X harmful effects unknown Ginseng X moderate use considered safe but allergic reactions have been reported. High doses may cause a variety of adverse symptoms Gingko biloba F harmful effects unknown Comfrey X contains tannin and lasiocarpine both of which are considered carcinogenic. Alkaloids in comfrey may result in liver damage Primrose oil C harmful effects unknown Shitake mushroom F harmful effects unknown extract Borage seed oil F harmful effects unknown Quercetin X harmful effects unknown Bromolain X "therapeutic doses" may cause nausea vomiting diarrhea skin rash and menorrhagia --------------------------------------------------------------- *X = no proven utility for CFS; F = no known clinical value; C = conflicting findings in clinical trials Analgesics _______________________________________________________________ Treatment Name Value in Examples Side effects associated treating with the use of this CFS* treatment --------------------------------------------------------------- Nonsteroidal anti- S naproxen abdominal pain/dyspepsia/ inflammatory ibuprofen nausea/vomiting drug (NSAID) piroxicam /drowsiness/headache/ depression/fatigue/ naproxen may impair some immune functions Other S cyclobenza- gastrointestinal prine bleeding/drowsiness/ dry mouth/dizziness ________________________________________________________________ *S = useful for relief of symptoms Acute anxiety _______________________________________________________________ Treatment Name Value in Examples Side effects associated treating with the use of this CFS* treatment --------------------------------------------------------------- Benzodiazepines S alprazolam sedation/anterograde lorazepam amnesia/withdrawal symptoms Other S buspirone dizziness/headache/ drowsiness/nausea _______________________________________________________________ *S = useful for relief of symptoms Hypnotics _______________________________________________________________ Treatment Name Value in Examples Side effects associated treating with the use of this CFS* treatment --------------------------------------------------------------- Benzodiazepines S clonazepam hallucinations/ataxia/ triazolam depression temazepam Other S zolpidem dizziness/headache Other S trazodone drowsiness/headache/ gastrointestinal bleeding ________________________________________________________________ *S = useful for relief of symptoms Antidepressants _______________________________________________________________ Treatment Name Value in Examples Side effects associated treating with the use of this CFS* treatment --------------------------------------------------------------- Tricyclic S doxepin dry mouth/drowsiness/ amitriptyline weight gain/ desipramine tachycardia/weakness/ nortriptyline fatigue Serotonin S fluoxetine headache/tremor/ reuptake sertraline agitation/nervousness inhibitors paroxetine Other S bupropion anxiety/agitation/ insomnia/tremor/ anorexia/seizures ______________________________________________________________ *S = useful for relief of symptoms Additional drug therapies _______________________________________________________________ Treatment Name Value in Examples Side effects associated treating with the use of this CFS* treatment --------------------------------------------------------------- Calcium channel X nimodipine dizziness/ blockers nicardipine hypotension/ cardene headache/nausea H-2 blockers X ranitidine headache/dizziness/ cimetidine nausea/rashes/ myalgia/impotence/ has been reported to alter immune function Immune U cyclophos- destruction of immune suppressants phamide cells/hair loss/liver azathioprine damage/kidney damage/ methotrexate toxicity to developing embryos/ interstitial pneumonitis Other X naltrexone insomnia/liver damage Other X pentoxifylline gastrointestinal upset/dizziness _________________________________________________________________ *X = no proven utility for CFS; U = use unjustified for CFS Allergy medications _______________________________________________________________ Treatment Name Value in Examples Side effects associated treating with the use of this CFS* treatment --------------------------------------------------------------- Non-sedating S terfenadine drowsiness/interaction antihistamines astemizole with erythromycin loratidine Antihistamines S diphenhydra- drowsiness mine Other S hydroxyzine sedation ________________________________________________________________ *S = Useful for relief of symptoms Miscellaneous therapies _______________________________________________________________ Treatment Name Value in Side effects associated treating with the use of this treatment CFS* --------------------------------------------------------------- Gamma globulin C harmful effects unknown Ampligen P harmful effects unknown Kutapressin X allergic reactions Hydrogen F this treatment is considered peroxide injection highly unorthodox and could initiate a stroke High colonic F known to promote enemas intestinal disease ________________________________________________________________ *x = no proven utility for CFS; F = no known clinical value; C = conflicting findings in clinical trials Generic and trade names of drugs used to manage patients with CFS Generic name Trade name Alprazolam Xanax Amitryptline Elavil, Endep, Etrafon, Limbitrol, Triavil Bupropion Wellbutrin Buspirone BuSpar Cimetidine Tagament Clonazpam Klonopin Cyclobenzaprine Flexeril Desipramine Norpramin Doxepin Adapin, Sinequan Fluoxetine Prozac Lorazepam Ativan Nortriptyline Aventyl, Pamelor Paroxetine Paxil Pentoxifylline Trental Ranitidine Zantac Sertraline Zoloft Temazepam Restoril Trazodone Desyrel Triazolam Halcion Zoldipem Ambien ============================================================== _________________ Treatment Name Value in Examples Side effects associated treating with the use of this CFS* treatment --------------------------------------------------------------- Tricyclic S doxepin dry mouth/drowsiness/ amitriptyline weight gain/ desipramine tachycardia/weakness/ nortriptyline fatigue Serotonin S fluoxetine headache/tremor/ reuptake sertraline agitation/nervousness inhibitors paroxetine Other