Caffeine-Related Psychiatric Disorders



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.

Although many beverages contain caffeine, coffee is a staple form of caffeine consumption. Researchers studying coffee’s complex chemistry have identified both health promoting and inhibiting factors. Aside from enhancing cognitive ability, coffee consumption appears to inversely correlate with diabetes, certain types of cancer lines, and possibly Alzheimer disease. Conversely, coffee can increase cholesterol levels.[1]

Case study

Brenda arrived at the doctor’s office a full hour early. The receptionist greeted Brenda and then handed her the typical questionnaires for new patients. Brenda nervously filled out the forms and squirmed uncomfortably in her seat. Finally, the receptionist invited Brenda to meet with the doctor. The doctor began the interview with an open-ended question that granted Brenda the opportunity to rapidly discuss a several month period of anxiety, depression, insomnia, and restlessness. Through the course of the interview, the doctor learned that Brenda had started college 6 months ago and was struggling to keep up. As her grades slipped, Brenda redoubled her efforts by studying more. Unfortunately, fatigue set in and made her less attentive.

The doctor asked a few screening questions about nutrition and substance abuse that revealed an interesting trend. Brenda recognized the ill effects of fatigue and sought a remedy. While some students might turn to more potent and illicit drugs, Brenda chose caffeine instead. She carefully read labels and soon discovered an energy drink with the highest level of caffeine. The energy drink did the trick, at least for a brief period. Brenda soon found that 6 energy drinks in the evening kept her awake and relatively alert. The caffeine excess came at a cost though, measured in terms of persisting insomnia, nervousness, and mood fluctuations. Those symptoms actually worsened her test performance leading a friend to suggest she visit a doctor.


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:

The average daily consumption of caffeine among Americans is 219 mg.[2] 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.



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.[3, 4]


Research suggests that caffeine consumption is not correlated with breast cancer.[5]

Emerging research suggests that coffee, with its putative antioxidant activity, may reduce the risk of developing prostate cancer.[6]


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).[7]

DSM-IV-TR criteria for caffeine intoxication include the following:

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.

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 or 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.[8]

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.[9]

Severe depression is correlated with high blood-caffeine levels. People with panic disorders are at increased risk of precipitating an anxiety attack after caffeine use.[10]

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.


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.[11]

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 include a careful assessment of beverage consumption.

Caffeine would not produce perceptual problems such as hallucinations.

Caffeine consumption does not produce alterations in thinking, such as delusions.

Caffeine consumption does not cause disorientation, memory problems, mental confusion, impairment in judgment, or problems with abstract thinking.

The Mental Status Examination should include a safety assessment, addressing any potential risk of suicide or homicide. Caffeine by itself would not raise safety concerns, but the associated mood disorders could.


Caffeine principally functions as a mild neurostimulant through adenosine inhibition. Adenosine is an inhibitory neurotransmitter, the effects of which, caffeine blocks. Tolerance to the stimulant effects of caffeine seems to be overcome by daily use, perhaps restoring mood degraded by withdrawal.[12]

A leading theory suggests that caffeine is an adenosine receptor antagonist that particualry blocks 2 major types of adenosine receptors, A1AR and A2AAR.[13]

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.

Laboratory Studies

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.

Medical Care


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


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.


R Gregory Lande, DO, FACN, Clinical Consultant, Army Substance Abuse Program, Department of Psychiatry, Walter Reed Army Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Barry I Liskow, MD, Professor of Psychiatry, Vice Chairman, Psychiatry Department, Director, Psychiatric Residency Program, University of Kansas School of Medicine; Director, Psychiatric Outpatient Clinic, The University of Kansas Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Eduardo Dunayevich, MD, Adjunct Assistant Professor, Department of Psychiatry, University of Cincinnati; Clinical Research Physician, Neuroscience, Lilly Research Laboratories

Disclosure: Nothing to disclose.

Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin

Disclosure: lilly Honoraria Speaking and teaching; Forest Labs None None; Pfizer Grant/research funds Speaking and teaching; Northstar None None; Novartis Grant/research funds research; Pfizer Honoraria Speaking and teaching; Sunovion Speaking and teaching; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research; Merck Honoraria Speaking and teaching

Chief Editor

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA

Disclosure: Nothing to disclose.


  1. Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr. Apr 2011;51(4):363-73. [View Abstract]
  2. 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. [View Abstract]
  3. Lande RG, Labbate LA. Caffeine use and plasma concentrations in psychiatric outpatients. Depress Anxiety. 1998;7(3):130-3. [View Abstract]
  4. 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. [View Abstract]
  5. Fagherazzi G, Touillaud MS, Boutron-Ruault MC, et al. No association between coffee, tea or caffeine consumption and breast cancer risk in a prospective cohort study. Public Health Nutr. Apr 5 2011;1-6. [View Abstract]
  6. Wilson KM, Kasperzyk JL, Rider JR, et al. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst. Jun 8 2011;103(11):876-84. [View Abstract]
  7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). Washington, DC: 2000:212-5, 708-9.
  8. Henderson DC, Borba CP, Daley TB, Boxill R, Nguyen DD, Culhane MA, et al. Dietary intake profile of patients with schizophrenia. Ann Clin Psychiatry. Apr-Jun 2006;18(2):99-105. [View Abstract]
  9. Broderick PJ, Benjamin AB, Dennis LW. Caffeine and psychiatric medication interactions: a review. J Okla State Med Assoc. Aug 2005;98(8):380-4. [View Abstract]
  10. Nardi AE, Valenca AM, Nascimento I, Freire RC, Veras AB, de-Melo-Neto VL, et al. A caffeine challenge test in panic disorder patients, their healthy first-degree relatives, and healthy controls. Depress Anxiety. 2008;25(10):847-53. [View Abstract]
  11. Tunnicliffe JM, Erdman KA, Reimer RA, Lun V, Shearer J. Consumption of dietary caffeine and coffee in physically active populations: physiological interactions. Appl Physiol Nutr Metab. Dec 2008;33(6):1301-10. [View Abstract]
  12. Addicott MA, Laurienti PJ. A comparison of the effects of caffeine following abstinence and normal caffeine use. Psychopharmacology (Berl). Dec 2009;207(3):423-31. [View Abstract]
  13. Xie X, Ramkumar V, Toth LA. Adenosine and dopamine receptor interactions in striatum and caffeine-induced behavioral activation. Comp Med. Dec 2007;57(6):538-45. [View Abstract]
  14. Olsen J, Bech BH. Caffeine intake during pregnancy. BMJ. Nov 3 2008;337:a2316. [View Abstract]
  15. Bakker R, Steegers EA, Obradov A, et al. Maternal caffeine intake from coffee and tea, fetal growth, and the risks of adverse birth outcomes: the Generation R Study. Am J Clin Nutr. Jun 2010;91(6):1691-8. [View Abstract]
  16. Klepacki B. Energy Drinks: A Review Article. Strength and Conditioning Journal. February/2010;32:37.
  17. Higgins JP, Tuttle TD, Higgins CL. Energy beverages: content and safety. Mayo Clin Proc. Nov 2010;85(11):1033-41. [View Abstract]
  18. Seifert SM, Schaechter JL, Hershorin ER, Lipshultz SE. Health effects of energy drinks on children, adolescents, and young adults. Pediatrics. Mar 2011;127(3):511-28. [View Abstract]
  19. McCusker RR, Goldberger BA, Cone EJ. Caffeine content of energy drinks, carbonated sodas, and other beverages. J Anal Toxicol. Mar 2006;30(2):112-4. [View Abstract]
  20. Arria AM, O'Brien MC. The "high" risk of energy drinks. JAMA. Feb 9 2011;305(6):600-1. [View Abstract]
  21. 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. [View Abstract]
  22. Burke LM. Caffeine and sports performance. Appl Physiol Nutr Metab. Dec 2008;33(6):1319-34. [View Abstract]
  23. 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. [View Abstract]
  24. 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. [View Abstract]
  25. Mujika I, Burke LM. Nutrition in team sports. Ann Nutr Metab. 2010;57 Suppl 2:26-35. [View Abstract]
  26. Bishop D. Dietary supplements and team-sport performance. Sports Med. Dec 1 2010;40(12):995-1017. [View Abstract]
  27. Ganio MS, Klau JF, Casa DJ, Armstrong LE, Maresh CM. Effect of caffeine on sport-specific endurance performance: a systematic review. J Strength Cond Res. Jan 2009;23(1):315-24. [View Abstract]
  28. Jenkinson DM, Harbert AJ. Supplements and sports. Am Fam Physician. Nov 1 2008;78(9):1039-46. [View Abstract]
  29. Paton CD, Lowe T, Irvine A. Caffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclists. Eur J Appl Physiol. Dec 2010;110(6):1243-50. [View Abstract]
  30. Lopez-Garcia E, van Dam RM, Li TY, Rodriguez-Artalejo F, Hu FB. The relationship of coffee consumption with mortality. Ann Intern Med. Jun 17 2008;148(12):904-14. [View Abstract]
  31. Geleijnse JM. Habitual coffee consumption and blood pressure: an epidemiological perspective. Vasc Health Risk Manag. 2008;4(5):963-70. [View Abstract]