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Cases that Test Your Skills

Something in the air

Mrs. A, age 64, has persistent depressive and physical symptoms that worsen in winter. In December, she reports that her symptoms have suddenly disappeared. Why?

Vol. 3, No. 12 / December 2004


Mrs. A, age 64, lives alone in an old farmhouse. For approximately 8 months, she had complained of depressed mood, decreased interest, difficulty sleeping, low energy, decreased concentration, and feelings of hopelessness. She met DSM-IV-TR criteria for major depressive disorder with underlying anxiety.

Mrs. A also reported having sinus headaches throughout the fall and winter. Blood chemistry, CBC with differential, thyroid profile including T4& TSH, urine drug screen, urine analysis, and ECG results were normal.

In April, Mrs. A was enrolled in an outpatient study of depression relapse prevention treatment. After taking the active study drug for 2 months, she reported continued low mood, low energy, difficulty concentrating, poor sleep and worsening headaches. Because her depression did not improve sufficiently, she was dropped from the study.

In July, Mrs. A saw a psychiatrist and was started on sertraline, 50 mg/d. By November, the dosage had been increased to 150 mg/d. At this time, she reported unsteadiness, dizziness, frequent falls, and intolerable headaches in addition to her depressive symptoms. She was referred to a neurologist to rule out a neurologic disorder.

Table 1

Symptoms that suggest major depression and/or chronic CO poisoning


Major depression

Chronic low-level CO poisoning

Depressed mood



Diminished interest



Weight loss



Decreased appetite



Difficulty sleeping



Diminished concentration



Suicidal thoughts



Fatigue, weakness









Shortness of breath






Abdominal pain












Diminished cognitive function



Sexual dysfunction



+ = suggests disorder

- = does not suggest disorder

CO = Carbon monoxide

Source: Diagnostic and Statistical Manual of Mental Disorders (4th ed, rev).

Copyright 2000. American Psychiatric Association; and Tierney LM, McPhee SJ, Papadakis MA (eds). Current Medical Diagnosis and Treatment. New York: McGraw Hill, 2003.

The authors’ observations

Chronic fatigue syndrome is characterized by severe unexplained fatigue that persists for >6 months. The new-onset fatigue is not abated with rest. Other symptoms include impaired memory or concentration, sore throat, tender lymph nodes, muscle pain, headaches, pain in several joints, and disturbed sleep.1

Mrs. A, however, never complained of sore throat or joint or muscle pain, and her laboratory findings were normal.

Seasonal affective disorder (SAD) is characterized by a temporal relationship between onset of depressive symptoms and a particular time of year (eg, symptoms emerge each winter) for at least 2 years. Full remission also occurs at a characteristic time (eg, each summer).2

Mrs. A’s headaches, frequent falls, dizziness, and difficulties with balance do not suggest SAD. Also, these symptoms have not persisted long enough for an SAD diagnosis.

Thyroid disorder. Hypothyroidism symptoms—particularly low mood, decreased energy, fatigue, psychomotor retardation, and lack of motivation—can mimic depression. Mrs. A’s T4 and TSH readings were normal, however.

Metabolic dysfunction. Symptoms secondary to decreased serum concentrations of sodium, potassium, magnesium, or calcium can mimic depression, but blood tests showed Mrs. A has normal electrolyte levels.

Brain tumor. Patients with a brain tumor can present with mood symptoms, psychosis, headaches, mania, cognitive impairments, seizure problems, and other symptoms depending on the tumor’s size and location.


By late November Mrs. A’s fatigue, once present only mornings, plagued her throughout the day. We considered changing antidepressants because of her complaints and sertraline’s lack of efficacy.

The following month, however, Mrs. A told us that her fatigue and headaches were gone. Mood, sleep, and concentration were also improved. Her Hamilton Rating Scale for Depression score had improved from 21 when she entered the study—indicating moderate severity—to 6, indicating remission. Her neurologic referral was cancelled.

Mrs. A then mentioned that her home’s water heater had been malfunctioning for several months. She said she could not afford to get it repaired during the summer but finally hired plumbers to fix it in late November.

After working all day in Mrs. A’s basement, two workers suffered acute headaches and nausea. The symptoms prompted the workers to search the basement for a carbon monoxide leak; they found a small leak in the water heater, which they replaced.

The next morning, Mrs. A said, her headache disappeared. Her other symptoms were gone within 4 days.

The authors’ observations

The sudden disappearance of Mrs. A’s symptoms after her water heater was replaced and emergence of severe physical symptoms in the two plumbers suggest carbon monoxide (CO) poisoning, a common and potentially lethal medical problem.

Low-level CO poisoning usually results from repeated exposure to incomplete combustion in a defective heating appliance, such as a water heater (Box 1). 3,4 Symptoms usually surface in the winter, when heating appliance use peaks and windows are left closed, allowing indoor CO to accumulate in high concentrations.7

Box 1

Indoor heating systems: Leading cause of death by CO poisoning

Carbon monoxide (CO) poisoning is preventable yet causes more than 2,000 deaths each year in the United States. 3,5 CO poisoning may result from intentional or accidental exposure to motor vehicle exhaust, malfunctioning home heating systems, and improperly vented combustion appliances.

Indoor heating systems account for about 75% of CO poisoning-related deaths. 5 Fatal CO exposure has also been attributed to charcoal grills/burning charcoal, gas water heaters, camp stoves, lanterns, kitchen gas ranges/ovens, and other fuel-burning products.5

Although most states do not require residential use of CO detectors, clinicians should encourage patients to install at least one CO detector near their beds.5,6

Whereas severe, acute CO poisoning typically is detected immediately after exposure, symptoms of chronic low-level CO exposure are easily mistaken for a primary depressive (Table 1) or other neuropsychiatric disorder—or overlooked altogether. Some cases persist for months before CO exposure is diagnosed. Clinicians often give unnecessary—sometimes costly—medical treatment while ignoring the underlying poisoning.

Mechanism of action. CO binds with hemoglobin (with an affinity >200 times that of oxygen) to form carboxyhemoglobin (COHb), which causes cellular anoxia by blocking transport of oxygen to the tissues, including the brain.4,6,8

CO poisoning symptoms vary depending on COHb concentration (Table 2). COHb >5% in a symptomatic nonsmoker may indicate chronic low-level CO poisoning and require further evaluation. 9 Levels >10% are common in heavy smokers (2 to 4 packs/day). It should be noted that Mrs. A does not smoke.

Presentation. Patients with chronic low-level CO poisoning often present with vague, nonspecific symptoms, such as weakness and fatigue, abdominal pain, nausea, vomiting, diarrhea, decreased concentration, diminished cognitive abilities, persistent headaches, and trouble sleeping. 4,8,10,11 Patients age >65 especially may present with multiple cognitive and somatic complaints that suggest Parkinson’s disease, chronic fatigue syndrome, dementia, or—in Mrs. A’s case—depression. 5,10,12

Table 2

Signs, symptoms of CO poisoning that emerge at different carboxyhemoglobin levels

Carboxyhemoglobin level (% HgB)

Signs, symptoms

5-10 %

Exacerbates angina in some patients with heart disease

10-20 %

Mild headache, breathlessness on exertion

20-30 %

Throbbing headache, irritability, mental status changes, fatigue

30-40 %

Severe headache, weakness, nausea, dizziness, visual problems, confusion


Increased confusion, hallucinations, severe ataxia, rapid breathing

50-60 %

Syncope or coma with convulsions, tachycardia with weak pulse

60-70 %

Deep coma, incontinence


Profound coma, depressed respiration, absent reflexes

>80 %

Rapid death from respiratory arrest

Source: Adapted from Gilman AG, Rall TW, Nies AS, Taylor P (eds). Goodman and Gilman’s the pharmacological basis of therapeutics (8th ed). New York: Pergamon Press, 1990.

Health effects of CO exposure range from subtle cardiovascular and neurobehavioral sequelae at low concentrations to loss of consciousness and death after acute exposure to higher concentrations.3,5

Hypoxia of the brain and other organs resulting from low-level CO poisoning can cause a range of physiologic effects, including mental status changes. 10,11 Low-level CO exposure is particularly dangerous to pregnant women and to patients with a pre-existing ischemic illness.

Pregnancy. Chronic low-level CO exposure during pregnancy can harm the fetus, leading to low birth weight, short neonatal length, prematurity, perinatal death, and increased risk of developmental dysfunction. 13

Ischemic illnesses. Because COHb cannot transport oxygen, the tissues that demand the most oxygen—such as the brain, heart, and skeletal muscles—are most affected. Because cardiac muscles extract approximately 75% of available oxygen from blood, patients with cardiac and pulmonary ischemic illnesses face a high risk for tissue injury with CO poisoning. At COHb levels >10%, patients with pre-existing cardiac disease experience increased severity and duration of angina; concentrations >15% place them at risk of myocardial infarction. 6

Length of recovery from chronic CO exposure varies widely depending on severity of exposure and the patient’s general health. 3,5 CO has a 4- to 6-hour half-life and is excreted via the lungs fairly rapidly, so recovery can be swift once CO exposure is stopped. Emergency room referral depends upon severity of symptoms and CO exposure duration and nature (accidental or intentional).

The authors’ observations

CO poisoning can lead to long-term mental status changes. In a 3-year follow-up of patients repeatedly exposed to low CO levels:

  • 43% developed neurologic sequelae including memory impairment
  • 33% experienced personality changes including irritability, verbal aggression, violence and impulsivity, moodiness, distractibility, and sexual promiscuity
  • 11% suffered gross neuropsychological effects, including psychosis, disorientation, and blindness. 4

Primary care physicians and psychiatrists should monitor patients who have recovered from CO poisoning for symptoms of these disorders.


Mrs. A’s case illustrates the seriousness and diagnostic complexity of chronic low-level CO exposure in older patients, especially during the fall and winter with increased home heating appliance use. 7 CO exposure was not considered as a cause of Mrs. A’s symptoms until heating contractors found the water heater leak.

Watch for patients whose neuropsychiatric symptoms do not respond to treatment. Ask them about possible environmental, seasonal, or diurnal variations in symptoms. Also ask if the patient’s home heating system or water heater is ≥10 years old or has been malfunctioning (Box 2).

Checking COHb blood levels is the simplest way to confirm CO poisoning. 6,14

Box 2

Seven questions to ask patients when you suspect chronic CO poisoning

  1. Is your home heating system or water heater 10 or more years old or malfunctioning?
  2. Do you use a gas range or stove for supplemental heat?
  3. Do symptoms improve or worsen in certain environments or at a certain time of day?
  4. Have fireplace flues and/or chimney vents been checked within the past year?
  5. Has another household member—including a pet—also been ill?
  6. Is a family member who remains at home persistently ill, whereas others who leave periodically improve?
  7. Do symptoms improve or worsen during certain months or seasons?


Mrs. A’s depressive symptoms, headaches, dizziness, and balance problems have not returned. Her underlying anxiety symptoms worsened, however, when the psychiatrist tried to taper sertraline. She was diagnosed with generalized anxiety disorder and continued on sertraline, 100 mg/d.

The psychiatrist sees her every 4 to 6 weeks, and she routinely sees her primary care physician. No long-term effects of CO poisoning have been found.

Related resources

  • U.S. Centers for Disease Control and Prevention. Enter “carbon monoxide poisoning” in search field.
  • Kao LW, Nanagas KA. Carbon monoxide poisoning. Emerg Med Clin North America 2004;22:985-1018.

Drug brand names

  • Sertraline • Zoloft


Drs. Khan and D’Empaire report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Preskorn has been a speaker for, consultant to, or principal investigator for several antidepressant manufacturers, including Pfizer Inc.


1. Sadock BJ, Sadock VA. Kaplan and Sadock’s synopsis of psychiatry: behavioral sciences/clinical psychiatry (9th ed). Philadelphia, PA: Lippincott Williams & Wilkins, 2003:662.

2. Diagnostic and statistical manual of mental disorders (4th ed. rev). Washington, DC: American Psychiatric Association, 2000.

3. Mott JA, Wolfe MI, Alverson CJ, et al. National vehicle emissions policies and practices and declining US carbon monoxide-related mortality. JAMA 2002;288:988-95.

4. Thorpe M. Chronic carbon monoxide poisoning. Can J Psychiatry 1994;39:59-61.

5. Knobeloch L, Jackson R. Recognition of chronic carbon monoxide poisoning. WMJ 1999;98(6):26-9.

6. Turner M, Hamilton-Farrell MR, Clark RJ. Carbon monoxide poisoning: an update. J Accid Emerg Med 1999;16:92-6.

7. Unintentional carbon monoxide poisoning following winter storm—Washington January 1993. MMWR. 1993;42:109-11.

8. Wright J. Chronic and occult carbon monoxide poisoning: we don’t know what we’re missing. Emer Med J 2002;19:386-90.

9. Wald N, Idle M, Smith PG. Carboxyhaemoglobin levels in smokers of filter and plain cigarettes. Lancet 1977;1:110-12.

10. Raub JA, Benignus VA. Carbon monoxide and the nervous system. Neurosci Biobehav Rev 2002;26:925-40.

11. Ryan CM. Memory disturbances following chronic, low-level carbon monoxide exposure. Arch Clin Neuropsychol 1990;5:59-67.

12. Webb CJ, 2nd, Vaitkevicius PV. Dementia with a seasonal onset secondary to carbon monoxide poisoning. J Am Geriatr Soc 1997;45:1281-2.

13. Farrow JR, Davis GJ, Roy TM, et al. Fetal death due to nonlethal maternal carbon monoxide poisoning. J Forens Sci 1990;35:1448-52.

14. Vreman HJ, Mahoney JJ, Stevenson DK. Carbon monoxide and carboxyhemoglobin. Adv Pediatr 1995;42:303-34.

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