AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Caffeine is the world's favorite psychoactive substance. Only petroleum exceeds coffee as a globally traded commodity, and commerce and history of the United States are closely linked to tea consumption. Soft drinks now rank as the most popular beverage in the United States, and most contain caffeine. Beverage trade groups estimate the annual per capita soft drink consumption at 56 gallons. Research and worldwide beverage history confirm the safety of moderate caffeine consumption in healthy individuals.

The universal appeal of caffeine is related to its psychostimulant properties. In a healthy person, caffeine promotes cognitive arousal and fights fatigue. These same activating properties can produce symptomatic distress in a small subset of the population. Susceptibility to this symptomatic distress is broadly determined by 3 factors—the dose consumed, individual vulnerability to caffeine, and preexisting medical or psychiatric conditions (mood disorders in particular) that are aggravated by mild psychostimulant use.

Pathophysiology

Caffeine is a xanthine derivative. It acts by pharmacologically stimulating the CNS, heart, voluntary muscles, and gastric acid secretion, and it induces diuresis. Caffeine is rapidly absorbed. Peak plasma levels are achieved in about 1 hour. Caffeine saturates all body tissues and fluids, including breast milk. The half-life of caffeine is 4-6 hours.

The amount of caffeine in coffee and tea varies based on brewing times and methods. General guidelines for beverage caffeine content include the following:

• Brewed coffee (8 oz) - 120 mg
• Instant coffee (8 oz) - 70 mg
• Iced tea (8 oz) - 60 mg
• Hot tea (8 oz) - 60 mg
• Caffeinated soft drink (12 oz) - 50 mg

The average daily consumption of caffeine among Americans is 219 mg.¹ Adults receive nearly three quarters of their daily caffeine from coffee. Children receive one half of their caffeine from soft drinks. Energy drinks represent a fast-growing beverage market. A combination of caffeine and herbal ingredients are touted as providing an energy boost. Energy drinks vary in the amount of caffeine included in their formulations and can range from around 50-300 mg. Although it sounds more exotic in some drinks, guaranine is caffeine. Consumers seeking the activating qualities of caffeine in pill form can find many preparations, the more well known having 200 mg. Individuals worldwide consume about 76 mg of caffeine per day.

Caffeine symptoms appear to be dose-related. Most people experience no behavioral effects with less than 300 mg caffeine. Sleep is more sensitive and can be disrupted by 200 mg caffeine. At doses exceeding 1 g per day, susceptible individuals experience toxic effects.

Frequency

United States

Prevalence rates for caffeine-induced psychiatric disorders have not been well established. Mood disorders and other substance abuses coexist with caffeine disorders. Some studies report 50% comorbidity.^{2, 3}

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

The 4 caffeine-induced psychiatric disorders include caffeine intoxication, caffeine-induced anxiety disorder, caffeine-induced sleep disorder, and caffeine-related disorder not otherwise specified (NOS).

• Diagnostic criteria for the 4 psychiatric disorders are described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR).⁴
• DSM-IV criteria for caffeine intoxication
• • Recent consumption of caffeine, usually in excess of 250 mg (more than 2-3 cups of brewed coffee)
  • Demonstration of 5 or more of the following signs during or shortly after caffeine use:
  • • Restlessness
    • Nervousness
    • Excitement
    • Insomnia
    • Flushed face
    • Diuresis
    • Gastrointestinal disturbance
    • Muscle twitching
    • Rambling flow of thought and speech
    • Tachycardia or cardiac arrhythmia
    • Periods of inexhaustibility
    • Psychomotor agitation
  • The above symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  • The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder, such as an anxiety disorder.
• DSM-IV criteria for caffeine-induced anxiety disorder
• • Prominent anxiety predominates in the clinical picture.
  • There is evidence from the history, physical examination, or laboratory findings suggesting that the anxiety developed within 1 month of caffeine intoxication or withdrawal or that medications containing caffeine are etiologically related to the disturbance.
  • The disturbance is not better accounted for by an anxiety disorder that is not substance-induced.
  • The disturbance does not occur exclusively during the course of a delirium.
  • The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• DSM-IV criteria for caffeine-induced sleep disorder
• • A prominent disturbance in sleep occurs that is sufficiently severe to warrant independent clinical attention.
  • There is evidence from the history, physical examination, or laboratory findings that the sleep disturbance is the direct physiological consequence of caffeine consumption.
  • The disturbance is not better accounted for by another mental disorder.
  • The disturbance does not occur exclusively during the course of a delirium.
  • The disturbance does not meet the criteria for breathing-related sleep disorder or narcolepsy.
  • The sleep disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• DSM-IV criteria for caffeine-related disorder NOS
• • This includes any caffeine disorder other than those previously listed.
  • Symptoms of caffeine withdrawal that are not currently an officially recognized diagnosis are present.
• Caffeine withdrawal is listed in DSM-IV in the appendix, "Criteria Sets and Axes Provided for Further Study." Based on clinical experience, further research, and DSM-IV task force review, the diagnosis may become officially recognized. Symptoms may begin 6-12 hours after stopping or decreasing consumption, peak in 1-2 days, and persist for a week. The research criteria include the following:
• • Prolonged daily use of caffeine
  • Abrupt cessation of caffeine use or reduction in the amount of caffeine used, closely followed by headache and one or more symptoms that include marked fatigue or drowsiness, marked anxiety or depression, and nausea or vomiting.
  • The symptoms in the criteria listed above cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
  • The symptoms are not due to the direct physiologic effects of a general medical condition (eg, migraine, viral illness) and are not better accounted for by another mental disorder.
• Apart from the caffeine-induced psychiatric disorders, clinicians must consider the influence of psychostimulants on other mental disorders.
• • Individuals who abuse other substances commonly consume large quantities of caffeine.
  • People with schizophrenia typically consume large amounts of caffeine.
  • Caffeine may contribute to agitation, irritability, and, possibly, interfere with antipsychotic medications. On the other hand, caffeine can markedly elevate blood levels of antipsychotic medications, increasing the probability of adverse effects. The possible mechanism explaining this finding is that caffeine and antipsychotic medications both compete for metabolism at the hepatic P-450 isoenzyme system. Patients with bipolar disorder are at risk for an exacerbation of manic symptoms when they consume large amounts of caffeine. This is due both to its direct psychostimulant properties and secondary to increase renal excretion of lithium.
  • Severe depression is correlated with high blood-caffeine levels.
  • People with panic disorders may consciously decrease caffeine use.
• Diagnosis of any caffeine-related disorder begins with clinical awareness.
• • Beverage caffeine is such a common component of social activity that its consideration as a psychostimulant often is neglected.
  • Too many clinical histories fail to record caffeine use.
• A complete caffeine history includes doses associated with beverages and medications.
• • Several over-the-counter analgesic, sinus, and weight loss compounds contain caffeine.
  • There are preparations that exploit caffeine's alerting affect. They are marketed as stimulants or "stay-awake" preparations, and they can contain 200 mg of caffeine.

Physical

The observable signs associated with caffeine consumption are dose dependent. For most individuals who consume caffeine in the average range, the physical stigmata will include arousal signs. Expect to see nervousness, elevated heart rate, increased respiratory rate, flushed face, and an exaggerated startle response. Caffeine is a mild diuretic and may contribute to vague gastrointestinal complaints. In rare cases where an individual's dose exceeds 1 g/d, the picture changes. Gross muscle tremors, highly disorganized speech, and possible arrhythmias herald a more sinister outcome.

• Mental Status Examination
• • Many of the effects of caffeine consumption are expressed in behavioral manifestations. The most common is anxiety, with its associated fidgetiness, distractibility, poor eye contact, hesitating speech, and prolonged bursts of energy.
  • Caffeine's effect on mood is complicated and not fully understood. Although initially it may promote some improvement in mood, notably identified by some slight euphoria or focused attention, this pattern may give way to a chronic dysphoria. This mildly depressed state may be a consequence of withdrawal.
  • Any complaint of sleep difficulty should begin with a careful assessment of beverage consumption.
  • Caffeine would not produce perceptual problems such as hallucinations, alterations in thinking (such as delusions, disorientation, memory problems), or raise safety concerns such as suicidal or homicidal tendencies.

Causes

• The means by which caffeine exerts its pharmacologic effects remain uncertain.
• A leading theory suggests that caffeine is an adenosine receptor antagonist.
• Adenosine is an inhibitory neuromodulator affecting norepinephrine, dopamine, and serotonin activity.
• Caffeine's putative antagonism of adenosine would increase those neurotransmitters promoting psychostimulation.
• The same neurotransmitter systems are implicated in the pathophysiology of several psychiatric disorders.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Substance withdrawal disorders

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• A urine drug screen helps exclude symptoms due to illicit drug use. Thyroid studies are also useful.
• Caffeine blood levels can be obtained, but their practical use as a screening tool is limited.

Other Tests

No other specific tests detect caffeine-induced psychiatric disorders. Persons with persistent insomnia, particularly if the history is inconclusive, might benefit from a referral for a sleep study. Cardiac irregularities, whether caffeine induced or not, should be investigated using ECG.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

• Symptoms resolve if caffeine ingestion is discontinued.
• Monitor patient for caffeine withdrawal.
• If caffeine withdrawal develops, supportive reassurance and symptomatic treatment are sufficient. Advise the individual about the expected symptoms of withdrawal, the duration of symptoms, and their benign course. If discomfort persists beyond 2 weeks, the lingering symptoms may be due to a different disorder, requiring further assessment.

Consultations

Treatment may unmask comorbid psychiatric conditions, such as depression. Should these develop, treat accordingly or seek psychiatric consultation.

Diet

If excessive caffeine consumption is either confirmed through the clinical history or strongly suspected of contributing to symptomatic distress, a trial period of caffeine-free beverages should be encouraged. The clinical situation should then be reassessed.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Patient Education

• Every individual entering the medical system should, at some point, receive a nutritional assessment. This can be a brief intervention; however, at least part of the inquiry should seek to understand beverage consumption. This opens the opportunity to address any excessive reliance on a single beverage, be it alcohol, caffeine, or other products.
  
  
  • Clinicians should attempt to quantify each beverage type consumed per day. To assist data collection, the person can be instructed to keep a daily log of all liquids consumed. This can be an instructive lesson for the individual, who might discover, for example, that all liquids consumed in an average day might be caffeinated sodas. This allows the clinician to stress the importance of varying the diet and, most importantly, of adding water in place of other beverages.
  • Individuals should be further instructed to carefully read labels. Many noncola beverages contain caffeine. Certain medications, such as over-the-counter diet pills, cold medications, and analgesics, also contain caffeine.
  • Caffeine consumption during pregnancy is generally safe, according to the Organization of Teratology Information Services, if use is restricted to a moderate range not exceeding 300 mg a day. Caffeine will enter breast milk.⁵
  • Energy drinks are increasingly popular and caffeine is a main ingredient contributing to the sense of arousal. Children and adolescents can consume large amounts of caffeine in pursuit of a "buzz." Even unwitting overconsumption can produce the signs of caffeine intoxication. Parents should encourage children to carefully read the labels and avoid consuming excess amounts of caffeine.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to monitor for comorbid psychiatric conditions

Special Concerns

• Performance enhancement and caffeine
• • Sobe Adrenalin Rush is a popular beverage promising "sustained energy for non-stop living." The filled container weighs less than 9 oz and is a mixture of vitamins, herbals, and caffeine. A sugar-free version has fewer carbohydrates but maintains the 79 mg of caffeine in the traditional sugared mix. Skeptics may conclude that Sobe, and its legions of competitors, is nothing more than a slick marketing of flavored water. Recently published studies suggest otherwise.
  • A randomized, double-blind study compared an energy drink composed of caffeine, glucose, and herbals with a placebo. The authors concluded that a synergy between caffeine and glucose improved cognitive performance and mood. Similar studies found caffeine the most important ingredient responsible for improved performance, decreased fatigue, heightened arousal, and improved mood.
  • The notion that caffeine reduces fatigue and increases arousal has important potential implications. Clinical investigators increasingly examine whether caffeine improves performance on specific activities. The results are encouraging.
  • Performance degradation, a common byproduct of sleep deprivation, is reversed by caffeine consumption. Another group of investigators noted, "that caffeine is an effective strategy to maintain physical performance during an overnight period of sleep loss at levels comparable to the rested state." In a more specific study, the authors found that caffeine improved target detection during shooting but marksmanship did not improve.
  • Athletes recognize the benefits of caffeine. A meta-analysis of 40 published studies confirmed "the ergogenic effects of caffeine, particularly for endurance." Another article expounds on caffeine's ability to improve endurance, particularly with normally exhausting activities. The benefits are not reduced through repeated use of caffeine. The increased endurance from caffeine consumption may partially be mediated by improving respiratory efficiency.
  • The sports world, both athletes and regulators, recognize the potential for abuse. Although ephedrine is illegal, caffeine and the ephedra alkaloids are not. This raises the spectre of the legal use of a performance-enhancing compound. The sports community must eventually grapple with caffeine doping and decide whether its performance benefits create a sufficient competitive advantage that warrants its elimination.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

1. Frary CD, Johnson RK, Wang MQ. Food sources and intakes of caffeine in the diets of persons in the United States. J Am Diet Assoc. Jan 2005;105(1):110-3. [Medline].
2. Lande RG, Labbate LA. Caffeine use and plasma concentrations in psychiatric outpatients. Depress Anxiety. 1998;7(3):130-3. [Medline].
3. Nehlig A. Are we dependent upon coffee and caffeine? A review on human and animal data. Neurosci Biobehav Rev. Mar 1999;23(4):563-76. [Medline].
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). Washington, DC: 2000:212-5, 708-9.
5. Center for the Evaluation of Risks to Human Reproduction: Caffeine. Available at http://cerhr.niehs.nih.gov/common/caffeine.html.
6. Brown SL, Salive ME, Pahor M. Occult caffeine as a source of sleep problems in an older population. J Am Geriatr Soc. Aug 1995;43(8):860-4. [Medline].
7. Daly JW, Fredholm BB. Caffeine--an atypical drug of dependence. Drug Alcohol Depend. Jun-Jul 1998;51(1-2):199-206. [Medline].
8. Dews PB, Curtis GL, Hanford KJ. The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded pilot experiment. J Clin Pharmacol. Dec 1999;39(12):1221-32. [Medline].
9. Doherty M, Smith PM. Effects of caffeine ingestion on exercise testing: a meta-analysis. Int J Sport Nutr Exerc Metab. Dec 2004;14(6):626-46. [Medline].
10. Graham TE. Caffeine and exercise: metabolism, endurance and performance. Sports Med. 2001;31(11):785-807. [Medline].
11. Hays LR, Farabee D, Miller W. Caffeine and nicotine use in an addicted population. J Addict Dis. 1998;17(1):47-54. [Medline].
12. Lamberg L. Brew it or chew it? Military seeks ways to caffeinate [news]. JAMA. Mar 10 1999;281(10):885-6. [Medline].
13. Magkos F, Kavouras SA. Caffeine and ephedrine: physiological, metabolic and performance-enhancing effects. Sports Med. 2004;34(13):871-89. [Medline].
14. McLellan TM, Bell DG, Kamimori GH. Caffeine improves physical performance during 24 h of active wakefulness. Aviat Space Environ Med. Aug 2004;75(8):666-72. [Medline].
15. Mosek A, Korczyn AD. Yom Kippur headache. Neurology. Nov 1995;45(11):1953-5. [Medline].
16. Nehlig A. Does caffeine lead to psychological dependence?. CHEMTECH. 1999;29:30-5.
17. Paluska SA. Caffeine and exercise. Curr Sports Med Rep. Aug 2003;2(4):213-9. [Medline].
18. Porkka-Heiskanen T. Adenosine in sleep and wakefulness. Ann Med. Apr 1999;31(2):125-9. [Medline].
19. Scholey AB, Kennedy DO. Cognitive and physiological effects of an "energy drink": an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions. Psychopharmacology (Berl). Nov 2004;176(3-4):320-30. [Medline].
20. Smit HJ, Cotton JR, Hughes SC, Rogers PJ. Mood and cognitive performance effects of "energy" drink constituents: caffeine, glucose and carbonation. Nutr Neurosci. Jun 2004;7(3):127-39. [Medline].
21. Specterman M, Bhuiya A, Kuppuswamy A, et al. The effect of an energy drink containing glucose and caffeine on human corticospinal excitability. Physiol Behav. Jan 17 2005;83(5):723-8. [Medline].
22. Tikuisis P, Keefe AA, McLellan TM, Kamimori G. Caffeine restores engagement speed but not shooting precision following 22 h of active wakefulness. Aviat Space Environ Med. Sep 2004;75(9):771-6. [Medline].
23. Wesensten NJ, Belenky G, Kautz MA, et al. Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine. Psychopharmacology (Berl). Jan 2002;159(3):238-47. [Medline].

Article Last Updated: Jun 21, 2007