Neuropsychiatric effects of caffeine

Anthony P. Winston, Elizabeth Hardwick and Neema Jaberi

http://apt.rcpsych.org/cgi/content/full/11/6/432

Anthony Winston is a consultant in eating disorders with South Warwickshire Primary Care Trust (Eating Disorders Unit, Woodleigh Beeches Centre, Warwick Hospital, Lakin Road, Warwick CV34 5BW, UK. E-mail: Anthony.Winston@SWarkPCT.nhs.uk) and an honorary senior lecturer in psychiatry at the University of Warwick. Elizabeth Hardwick is a specialist registrar in general adult psychiatry on the West Midlands rotation and Neema Jaberi is a graduate medical student at the University of Warwick.

Caffeine is the most widely used psychoactive drug in the world. It is found in more than 60 known species of plants, and dietary sources include coffee, tea, cocoa beverages, chocolate and soft drinks. Coffee was consumed in Arabia in the 13th century and was introduced into Europe in the early 17th century. Tea was probably drunk in China before the birth of Christ and was brought to Europe in the 16th century. Most dietary caffeine is still consumed as tea and coffee, and the latter accounts for 55% of per capita intake in the UK (Scott et al, 1989). Despite (or perhaps because of) its ubiquity, caffeine is rarely thought of as a problematic drug. Doctors do not often ask patients about its use and enquiry into caffeine consumption is not usually included in psychiatric assessment.

On average, a cup of brewed coffee contains 100 mg of caffeine, compared with 75 mg for instant coffee and 50 mg for tea (Food Standards Agency, 2001); a can of Coca Cola contains 30 mg. Increasingly, stimulant drinks such as Red Bull (80 mg of caffeine per can) are being marketed to the public, and sales have increased dramatically since they first became available in 1987 (Finnegan, 2003). Pharmaceutical caffeine may be bought over the counter (for example as ProPlus tablets) and is also contained in numerous proprietary analgesics, cold and ’flu remedies, diet pills and diuretics; Anadin Extra, for example, contains 90 mg of caffeine per dose. In the UK, mean caffeine consumption is estimated at 359 mg/day (Scott et al, 1989).

Effects and diagnostic classification

The primary effect of caffeine is to relieve fatigue and enhance mental performance. Excessive ingestion leads to a state of intoxication known as caffeinism, which is characterised by restlessness, agitation, excitement, rambling thought and speech, and insomnia. These symptoms clearly overlap with those of many psychiatric disorders. The potential harmful effects of caffeine have long been recognised. As long ago as 1900, the Journal of the American Medical Association reported a conference on ‘Coffee as a beverage: its deleterious effects on the nervous system’, at which a contributor complained that ‘most physicians had given the subject little if any attention’. Another contributor asserted that coffee could cause a variety of symptoms, including depression, irritability, insomnia, tremulousness, loss of appetite and ‘frequent eructations of gas’ (JAMA, 2001).

Four caffeine-related syndromes are recognised in DSM–IV (American Psychiatric Association, 1994): caffeine intoxication; caffeine-induced anxiety disorder; caffeine-induced sleep disorder; and caffeine-related disorder not otherwise specified. Caffeine withdrawal is included in the Appendix to DSM–IV under ‘Criteria sets and axes provided for further study’. The ICD–10 (World Health Organization, 1992) is less specific. It recognises ‘Mental and behavioural disorders due to use of other stimulants, including caffeine’ (F15), which are then sub-classified in the same way as other substance use disorders (acute intoxication, harmful use, dependence syndrome, withdrawal state, etc.). However, there is no specific guidance on diagnosing problems due to caffeine misuse, and the diagnostic criteria are the same as for other substance use disorders. The prevalence of the various caffeine-related syndromes is uncertain.

Despite this formal recognition, caffeine generally receives little attention from psychiatrists. For example, the New Oxford Textbook of Psychiatry (Gelder et al, 2003) does not discuss caffeine misuse, although caffeine is mentioned briefly as a cause of insomnia. Consequently, psychiatrists rarely enquire about caffeine intake when assessing patients. This may lead to a failure to identify caffeine-related problems and offer appropriate interventions.

This article describes the clinical effects of caffeine consumption in a variety of psychiatric disorders and offers some guidance on assessing and managing caffeine-related problems.

Psychological effects

The psychological effects of caffeine are biphasic. Low doses produce stimulation, which is often perceived as desirable, whereas high doses can cause the unpleasant effects of caffeinism (Daly & Fredholm, 1998). Caffeine increases alertness, reduces fatigue and can elevate mood (Leinart & Huber, 1966; Rogers & Dernoncourt, 1997; Smith, 2002). Normal consumption improves performance on tasks that require alertness, such as simulated driving tasks (Smith, 2002). The effect on more complex cognitive tasks is less clear, although there is evidence to suggest that high consumption is associated with better performance, especially in older people (Smith, 2002).

Adverse effects

Caffeine has a number of adverse effects on the gastrointestinal tract. It relaxes the lower oesophageal sphincter and can predispose to gastro-oesophageal reflux disease. It also causes gastric hypersecretion, which is associated with susceptibility to ulceration. It increases the rate of gastric emptying and the acidic gastric contents therefore pass more rapidly into the duodenum; this can lead to inflammation of the duodenal mucosa (Boekema et al, 1999).

The diuretic action of caffeine is well known. The public is often advised to abstain from consuming caffeine in situations where dehydration may be significant, such as long-haul flights. A recent review (Maughan & Griffin, 2003) concluded that single doses of caffeine such as those found in commonly consumed beverages have little or no diuretic action, although large doses (>250 mg) do.

Caffeine may precipitate sinus tachycardia but does not increase the risk of cardiac arrhythmias, except perhaps at very high dose (Katan & Schouten, 2005). It can trigger migraine in susceptible individuals (Goadsby, 2003). Excessive use of caffeine-containing analgesics has been linked to analgesic nephropathy (De Broe et al, 2003). Caffeine may also be harmful in pregnancy; intakes above 300 mg/day may be associated with low birth weight and miscarriage (Food Standards Agency, 2001; Parazzini et al, 2005). The UK Food Standards Agency has recommended that pregnant women should limit their intake to less than this amount, which is equivalent to four average-sized cups or three average-sized mugs of instant coffee or six average-sized cups of tea (Food Standards Agency, 2001).

Dependence and withdrawal

affeine acts as a reinforcing agent in both humans and animals (Griffiths & Munford, 1995), although its effect is less powerful than that of stimulants such as cocaine and amphetamine (Daly & Fredholm, 1998). The reinforcing effect is thought to be due to both pleasurable stimulatory effects and unpleasant withdrawal symptoms (Daly & Fredholm, 1998). Caffeine differs from classical drugs of misuse in causing dopamine release in the prefrontal cortex rather than the nucleus accumbens, which is the principal area involved in reward and addiction (Nehlig, 1999).

Withdrawal symptoms have been reported in both humans and animals (Schuh & Griffiths, 1997; Griffiths & Woodson, 1998). Well-recognised symptoms include headache, irritability, sleeplessness, confusion, nausea, anxiety, restlessness and tremor, palpitations and raised blood pressure (Finnegan, 2003). They typically start slowly, are at their worst at 1–2 days, and recede within a few days. They are rapidly relieved by intake of caffeine, suggesting that they are genuine withdrawal symptoms. Tolerance has been reported to the effects of caffeine on the respiratory and cardiovascular systems, but there is little tolerance to its effect on sleep or mood (Daly & Fredholm, 1998).

Data on the prevalence of withdrawal symptoms are inconsistent, with a range of 11% or less to 100% (Dews et al, 2002). One study found that 7.5% of the population may experience adverse effects following either caffeine consumption or withdrawal (Scott et al, 1989). In another study (Dews et al, 1999), 11% of caffeine consumers reported withdrawal symptoms. Among regular caffeine users, only 0.9% of males and 5.5% of females reported withdrawal symptoms significant enough to interfere with normal activities. Withdrawal symptoms appear to be more common in teenagers: in one sample, 77.8% reported withdrawal symptoms and 41.7% tolerance (Bernstein et al, 2002).

Overall, clinically significant withdrawal symptoms seem to be relatively uncommon in the general population (Dews et al, 1999). It has been suggested that there is a definable caffeine dependence syndrome, on the basis that some adults meet the DSM–IV criteria for substance dependence (Strain et al, 1994). However, many studies of caffeine withdrawal have methodological limitations (Smith, 2002) and the status of caffeine as a drug of dependence remains controversial.