Caffeine-related disorders

---

---

Photo by: Subbotina Anna

Definition

Caffeine is a white, bitter crystalline alkaloid derived from coffee or tea. It belongs to a class of compounds called xanthines, its chemical formula being 1,3,7-trimethylxanthine. Caffeine is classified together with cocaine and amphetamines as an analeptic, or central nervous system stimulant. Coffee is the most abundant source of caffeine, although caffeine is also found in tea, cocoa, and cola beverages as well as in over-the-counter and prescription medications for pain relief.

In the clinician's handbook for diagnosing mental disorders (the Diagnostic and Statistical Manual of Mental Disorders , known as the DSM-IV-TR ), caffeine-related disorders are classified under the rubric of substance-related disorders. DSM-IV-TR specifies four caffeine-related disorders: caffeine intoxication, caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeinerelated disorder not otherwise specified. A fifth, caffeine withdrawal, is listed under the heading of "Criteria Sets and Axes Provided for Further Study."

Caffeine-related disorders are often unrecognized for a number of reasons:

• Caffeine has a "low profile" as a drug of abuse. Consumption of drinks containing caffeine is unregulated by law and is nearly universal in the United States; one well-known textbook of pharmacology refers to caffeine as "the most widely used psychoactive drug in the world." In many countries, coffee is a social lubricant as well as a stimulant; the "coffee break" is a common office ritual, and many people find it difficult to imagine eating a meal in a fine restaurant without having coffee at some point during the meal. It is estimated that 10–12 billion pounds of coffee are consumed worldwide each year.
• People often underestimate the amount of caffeine they consume on a daily basis because they think of caffeine only in connection with coffee as a beverage. Tea, cocoa, and some types of soft drink, including root beer and orange soda as well as cola beverages, also contain significant amounts of caffeine. In one British case study, a teenager who was hospitalized with muscle weakness, nausea, vomiting, diarrhea, and weight loss was found to suffer from caffeine intoxication caused by drinking 8 liters (about 2 gallons) of cola on a daily basis for the previous two years. She had been consuming over a gram of caffeine per day. Chocolate bars and coffee-flavored yogurt or ice cream are additional sources of measurable amounts of caffeine.
• Caffeine has some legitimate medical uses in athletic training and in the relief of tension-type headaches. It is available in over-the-counter (OTC) preparations containing aspirin or acetaminophen for pain relief as well as in such OTC stimulants as NoDoz and Vivarin.
• Caffeine is less likely to produce the same degree of physical or psychological dependence as other drugs of abuse. Few coffee or tea drinkers report loss of control over caffeine intake, or significant difficulty in reducing or stopping consumption of beverages and food items containing caffeine.
• The symptoms of caffeine intoxication are easy to confuse with those of an anxiety disorder.

The DSM-TR-IV states that it is unclear as of 2000 whether the tolerance, withdrawal symptoms, and "some aspects of dependence on caffeine" seen in some people who drink large amounts of coffee "are associated with clinically significant impairment that meets the criteria for Substance Abuse or Substance Dependence." On the other hand, a research team at Johns Hopkins regards caffeine as a model drug for understanding substance abuse and dependence. The team maintains that 9%–30% of caffeine consumers in the United States may be caffeine-dependent according to DSM criteria for substance dependency.

Description

Pharmacological aspects of caffeine

An outline of the effects of caffeine on the central nervous system (CNS) and other organ systems of the body may be helpful in understanding its potential for physical dependence. When a person drinks a beverage containing caffeine (or eats coffee-flavored ice cream), the caffeine is absorbed from the digestive tract without being broken down. It is rapidly distributed throughout the tissues of the body by means of the bloodstream. If a pregnant woman drinks a cup of coffee or tea, the caffeine in the drink will cross the placental barrier and enter the baby's bloodstream.

When the caffeine reaches the brain , it increases the secretion of norepinephrine, a neurotransmitter that is associated with the so-called fight or flight stress response. The rise in norepinephrine levels and the increased activity of the neurons, or nerve cells, in many other areas of the brain helps to explain why the symptoms of caffeine intoxication resemble the symptoms of a panic attack .

The effects of caffeine are thought to occur as a result of competitive antagonism at adenosine receptors. Adenosine is a water-soluble compound of adenine and ribose; it functions to modulate the activities of nerve cells and produces a mild sedative effect when it activates certain types of adenosine receptors. Caffeine competes with adenosine to bind at these receptors and counteracts the sedative effects of the adenosine. If the person stops drinking coffee, the adenosine has no competition for activating its usual receptors and may produce a sedative effect that is experienced as fatigue or drowsiness.

Caffeine content of food items and OTC preparations

The caffeine content of various food items and medications is as follows:

• Brewed coffee, 8-oz cup: 135–150 mg
• Instant coffee, 8-oz cup: 95 mg
• Powdered cappuccino beverage, 8-oz cup: 45–60 mg
• Tea brewed from leaves or bag, 8-oz cup: 50 mg
• Iced tea from mix, 8-oz glass: 25–45 mg
• Snapple iced tea, 8-oz glass: 21 mg
• Mountain Dew, 8-oz glass: 38 mg
• Dr. Pepper, 8-oz. glass: 28 mg
• Diet cola, 8-oz glass: 31 mg
• Root beer, 8-oz glass: 16 mg
• Coffee ice cream, 8-oz serving: 60–85 mg
• Coffee yogurt, 8-oz serving: 45 mg.
• Dark chocolate candy bar, 1.5 oz: 31 mg
• NoDoz, regular strength, 1 tablet: 100 mg
• NoDoz, maximum strength, 1 tablet: 200 mg
• Excedrin, 2 tablets: 130 mg

Caffeine can produce a range of physical symptoms following ingestion of as little as 100 mg, although amounts of 250 mg or higher are usually needed to produce symptoms that meet the criteria of caffeine intoxication.

Caffeine intoxication

To meet DSM-IV-TR criteria for caffeine intoxication, a person must develop five or more of the twelve symptoms listed below; the symptoms must cause significant distress or impair the person's social or occupational functioning; and the symptoms must not be caused by a medical disorder or better accounted for by an anxiety disorder or other mental disorder.

Because people develop tolerance to caffeine fairly quickly with habitual use, caffeine intoxication is most likely to occur in those who consume caffeine infrequently or who have recently increased their intake significantly.

Caffeine-induced anxiety and sleep disorders

DSM-IV-TR criteria for caffeine-induced anxiety and sleep disorders specify that the symptoms of anxiety and insomnia respectively must be more severe than the symptoms associated with caffeine intoxication. In addition, the anxiety or insomnia must be severe enough to require separate clinical attention.

Causes and symptoms

Causes

The immediate cause of caffeine intoxication and other caffeine-related disorders is consumption of an amount of caffeine sufficient to produce the symptoms specified by DSM-IV-TR as criteria for the disorder. The precise amount of caffeine necessary to produce symptoms varies from person to person depending on body size and degree of tolerance to caffeine. Tolerance of the stimulating effects of caffeine builds up rapidly in humans; mild withdrawal symptoms have been reported in persons who were drinking as little as one to two cups of coffee per day.

Some people may find it easier than others to consume large doses of caffeine because they are insensitive to its taste. Caffeine tastes bitter to most adults, which may serve to limit their consumption of coffee and other caffeinated beverages. Slightly more than 30% of the American population, however, has an inherited inability to taste caffeine.

Symptoms

The symptoms of caffeine intoxication include:

• restlessness
• nervousness
• excitement
• insomnia
• flushed face
• diuresis (increased urinary output)
• gastrointestinal disturbance
• muscle twitching
• talking or thinking in a rambling manner
• tachycardia (speeded-up heartbeat) or disturbances of heart rhythm
• periods of inexhaustibility
• psychomotor agitation

People have reported ringing in the ears or seeing flashes of light at doses of caffeine above 250 mg. Profuse sweating and diarrhea have also been reported. Doses of caffeine higher than 10 g may produce respiratory failure, seizures , and eventually death.

Side effects and complications

High short-term consumption of caffeine can produce or worsen gastrointestinal problems, occasionally leading to peptic ulcers or hematemesis (vomiting blood).

In addition to the symptoms produced by high short-term doses, long-term consumption of caffeine has been associated with fertility problems and with bone loss in women leading to osteoporosis in old age. Some studies have found that pregnant women who consume more than 150 mg per day of caffeine have an increased risk of miscarriage and low birth weight babies, but the findings are complicated by the fact that most women who drink large amounts of coffee during pregnancy are also heavy smokers. Some researchers believe that long-term consumption of caffeine is implicated in cardiovascular diseases, but acknowledge that further research is required.

On the other hand, moderate doses of caffeine improve athletic performance as well as alertness. Caffeine in small doses can relieve tension headaches, and one study found that a combination of ibuprofen and caffeine was more effective in relieving tension headaches than either ibuprofen alone or a placebo. Coffee consumption also appears to lower the risk of alcoholic and nonalcoholic cirrhosis of the liver.

Coffee is the most abundant source of caffeine, although caffeine is also found in tea, cocoa, and cola beverages as well as in over-the-counter and prescription medications for pain relief.

(Patrik Giardino/ CORBIS. Photo reproduced by permission.)

Drug interactions

Caffeine is often combined with aspirin or acetaminophen in over-the-counter and prescription analgesics (pain relievers). It can also be combined with ibuprofen. On the other hand, certain groups of drugs should not be combined with caffeine or taken with beverages containing caffeine. Oral contraceptives, cimetidine (Tagamet), mexiletine (Mexitil), and disulfiram (Antabuse) interfere with the breakdown of caffeine in the body. Caffeine interferes with the body's absorption of iron, and with drugs that regulate heart rhythm, including quinidine and propranolol (Inderal). Caffeine may produce serious side effects when taken together with monoamine oxidase inhibitors or with certain decongestant medications.

Combinations of ephedra and caffeine have been used in weight-loss programs because they produce greater weight loss than can be achieved by caloric restriction alone. Major studies were underway as of 2001 at Harvard and Vanderbilt to determine the safety of these regimens.

Practitioners of homeopathy have traditionally advised patients not to drink beverages containing caffeine in the belief that caffeine "antidotes" homeopathic remedies. Contemporary homeopaths disagree on the antidoting effects of caffeine, observing that homeopathy is used widely and effectively in Europe and that Europeans tend to drink strong espresso coffee more frequently than Americans.

Demographics

The general population of the United States has a high level of caffeine consumption, with an average intake of 200 mg per day. About 85% of the population uses caffeine in any given year. Among adults in the United States, about 30% consume 500 mg or more each day. These figures are lower, however, than the figures for Sweden, the United Kingdom, and other parts of Europe, where the average daily consumption of caffeine is 400 mg or higher. In developing countries, the average consumption of caffeine is much lower— about 50 mg per day.

In the United States, levels of caffeine consumption among all races and ethnic groups are related to age, with usage beginning in the late teens and rising until the early 30s. Caffeine consumption tapers off in adults over 40 and decreases in adults over 65. Caffeine intake is higher among males than among females in North America.

The prevalence of caffeine-related disorders in the United States is not known as of 2002.

Diagnosis

Diagnosis of a caffeine-related disorder is usually based on the patient's recent history, a physical examination, or laboratory analysis of body fluids. In addition to medical evidence, the examiner will rule out other mental disorders, particularly manic episodes, generalized anxiety disorder , panic disorder , amphetamine intoxication, or withdrawal from sedatives, tranquilizers, sleep medications, or nicotine. All of these disorders or syndromes may produce symptoms resembling those of caffeine intoxication. In most cases, the temporal relationship of the symptoms to high levels of caffeine intake establishes the diagnosis.

In some cases, the examiner may consider the possibility of depression during the differential diagnosis, as many people with depression and eating disorders self-medicate with caffeine.

Treatments

Treatment of caffeine-related disorders involves lowering consumption levels or abstaining from beverages containing caffeine. Some people experience mild withdrawal symptoms that include headaches, irritability, and occasionally nausea, but these usually resolve quickly.

Caffeine consumption has the advantage of having relatively weak (compared to alcohol or cigarettes) social reinforcement , in the sense that one can easily choose a noncaffeinated or decaffeinated beverage in a restaurant or at a party without attracting comment. Thus physical dependence on caffeine is less complicated by the social factors that reinforce nicotine and other drug habits.

Prognosis

With the exception of acute episodes of caffeinism, people recover from caffeine intoxication without great difficulty.

Prevention

Prevention of caffeine-related disorders requires awareness of the caffeine content of caffeinated beverages, OTC drugs, and other sources of caffeine; monitoring one's daily intake; and substituting decaffeinated coffee, tea, or soft drinks for the caffeinated versions of these beverages.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition, text revised. Washington, DC: American Psychiatric Association, 2000.

"Anxiety Due to a Physical Disorder or a Substance." Section 15, Chapter 187. In The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Murray, Michael, ND, and Joseph Pizzorno, ND. Encyclopedia of Natural Medicine. Rocklin, CA: Prima Publishing, 1991.

O'Brien, Charles P. "Drug Addiction and Drug Abuse." Chapter 24 in Goodman & Gilman's The Pharmacological Basis of Therapeutics, edited by J. G. Hardman and L. E. Limbird. 9th edition. New York and St. Louis, MO: McGraw-Hill, 1996.

Pelletier, Kenneth R., MD. "Naturopathic Medicine." Chapter 7, in The Best Alternative Medicine. New York: Simon & Schuster, 2002.

PERIODICALS

Breslin, P. A. S., C. D. Tharp, D. R. Reed. "Selective Taste Blindness to Caffeine and Sucrose Octa Acetate: Novel Bimodal Taste Distributions Unrelated to PROP and PTC." American Journal of Human Genetics 69 (October 2001): 507.

"Caffeine Toxicity from Cola Consumption." Internal Medicine Journal 31 (2001): 317–318.

Corrao, G. "Coffee, Caffeine, and the Risk of Liver Cirrhosis." Annals of Epidemiology 11 (October 2001): 458–465.

De Valck, E., R. Cluydts. "Slow-Release Caffeine as a Countermeasure to Driver Sleepiness Induced by Partial Sleep Deprivation." Journal of Sleep Research 10 (September 2001): 203–209.

Diamond, S., T. K. Balm, F. G. Freitag. "Ibuprofen Plus Caffeine in the Treatment of Tension-Type Headache." Clinical Pharmacology and Therapeutics 68 (2000): 312–319.

Griffiths, R. R., and A. L. Chausmer. "Caffeine as a Model Drug of Dependence: Recent Developments in Understanding Caffeine Withdrawal, the Caffeine Dependence Syndrome, and Caffeine Negative Reinforcement." Nihon Shinkei Seishin Yakurigaku Zasshi 20 (November 2000): 223–231.

MacFadyen, L., D. Eadie, T. McGowan. "Community Pharmacists' Experience of Over-the-Counter Medicine Misuse in Scotland." Journal of Research in Social Health 121 (September 2001): 185–192.

Preboth, Monica. "Effect of Caffeine on Exercise Performance." American Family Physician 61 (May 2000): 628.

Rapurl, P. B., J. C. Gallagher, H. K. Kinyarnu, and others. "Caffeine Intake Increases the Rate of Bone Loss in Elderly Women and Interacts with Vitamin D Receptor Genotypes." American Journal of Clinical Nutrition 74 (2001): 694–700.

Rumpler, William, James Seale, Beverly Clevidence, and others. "Oolong Tea Increases Metabolic Rate and Fat Oxidation in Men." Journal of Nutrition 131 (November 2001): 2848–2852.

Sardao, V. A., P. J. Oliveira, A. J. Moreno. "Caffeine Enhances the Calcium-Dependent Cardiac Mitochondrial Permeability Transition: Relevance for Caffeine Toxicity." Toxicology and Applied Pharmacology 179 (February 2002): 50–56.

ORGANIZATIONS

American College of Sports Medicine. P. O. Box 1440, Indianapolis, IN 46206-1440. (317) 637-9200.

American Dietetic Association. (800) 877-1600. <www.eatright.org> .

Center for Science in the Public Interest (CSPI). <www.cspinet.org> .

Rebecca J. Frey, Ph.D.