LETTER
Low-Dose Caffeine May
Exacerbate Psychotic
Symptoms in People With
Schizophrenia
To the Editor: Caffeine is a commonly
used psychoactive drug worldwide,
and current data point out high intake
of caffeine in some people with
schizophrenia.1 The popularity of
caffeine is due to its stimulant prop-
erties, which might cause mental
and behavioral effects. Caffeine could
alter dopamine transmission that
is secondary to antagonism of
adenosine receptors and has been
reported to induce psychotic symptoms
after large intake of caffeine (at least
10 mg/kg) in persons with2 and
without3 schizophrenia. We report
a case of worsening psychosis in
a 49-year-old man with schizophrenia
being treated with flupenthixol
decanoate injections after consuming
relative low dose of caffeine. The
psychosis resolved after ceasing caf-
feine intake without changing anti-
psychotic medication.
Case Report
Mr. C is a 49-year-old married, jobless
man with a history of chronic schizo-
phrenia, paranoid type for more than
10 years. The patient had no history
of drug abuse but smoked 20 cigarettes
per day for more than 20 years. He
was managed with flupenthixol
decanoate injections by medical staff at
the dose of 40 mg every 2 weeks. Prior
to this presentation, the patient started
to drink about four cans of coffee
daily for 2 weeks and soon developed
paranoia, delusion of reference, and
agitation. Because of the potential
homicidal risk, he was hospitalized,
and his consumption of caffeine was
J Neuropsychiatry Clin Neurosci 26:2, Spring 2014
halted. Surprisingly, without being
prescribed new psychotropic agents,
the patient’s symptoms improved
gradually. Finally, he was discharged
50 days later and received regular
follow-up appointments. He discon-
tinued caffeine intake under the rec-
ommendation of the physician, and no
apparent delusion or hallucination
was noted thereafter.
Discussion
In contrast to previous case reports
that describe the occurrence of
psychosis after heavy ingestion of
caffeine,2,3 we reported a case of
psychosis consumed relative low dose
of caffeine. The patient drank about
four cups of coffee a day, and each
contained 150 mg of caffeine per cup.
The patient weighed 71 kg and,
therefore, consumed less than
8.5 mg/kg/day of caffeine, which is
slightly higher than average intake
between schizophrenia smokers
(4.164.0 mg/kg/day).4 The patient in
our case received regular depot injec-
tions, therefore, poor adherence to
medicine could be ruled out. No known
drug-drug interaction was noted
between caffeine and flupenthixol.
Moreover, no any precipitating factor
that could worsen psychotic symp-
toms was mentioned prior to this
admission. Notably, the patient im-
proved upon ceasing caffeine intake,
and no apparent positive symptoms
was present.
In humans, there are four types of
adenosine receptors. Caffeine functions
as a competitive antagonist at the
adenosine A1 and A2A receptors and
increases dopaminergic effects in the
striatum.5 Through this mechanism,
caffeine modulates the mesolimbic
dopamine pathway that may be
related to its psychotomimetic effect.1
Caffeine is widely used in our society,
but little consideration has been
given to its indirect effects on
dopamine transmission leading to
psychosis exacerbation. Prior case
reports mentioned that high-dose
caffeine can worsen psychotic symp-
toms in people with schizophrenia.2
Clinicians might consider the effect of
caffeine consumption while evaluat-
ing psychotic patients, even though
the consumption dose is low.
The authors report no financial rela-
tionships with commercial interests.
Po-Jui Peng, M.D.
Dept. of Psychiatry, Beitou Branch,
Tri-Service General Hospital,
National Defense Medical Center,
Taipei, Taiwan
Kuo-Tung Chiang, M.D.
Dept. of Psychiatry, Beitou Armed
Forces Hospital, Taipei, Taiwan
Chih-Sung Liang, M.D.
Dept. of Psychiatry, Beitou Branch,
Tri-Service General Hospital,
National Defense Medical Center,
Taipei, Taiwan
Send correspondence to Dr. Peng;
e-mail: yippee0611@gmail.com
References
1. Hughes JR, McHugh P, Holtzman S:
Caffeine and schizophrenia. Psychiatr Serv
1998; 49:1415–1417
2. Cerimele JM, Stern AP, Jutras-Aswad D:
Psychosis following excessive ingestion of
energy drinks in a patient with schizophrenia.
Am J Psychiatry 2010; 167:353
3. Hedges DW, Woon FL, Hoopes SP:
Caffeine-induced psychosis. CNS Spectr
2009; 14:127–129
4. Gurpegui M, Aguilar MC, Martínez-Ortega
JM, et al: Fewer but heavier caffeine
consumers in schizophrenia: a case-control
study. Schizophr Res 2006; 86:276–283
5. Fisone G, Borgkvist A, Usiello A: Caffeine as
a psychomotor stimulant: mechanism of
action. Cell Mol Life Sci 2004; 61:857–872
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