Review article 179

Caffeine-induced psychiatric manifestations: a review Hee Ryung Wang, Young Sup Woo and Won-Myong Bahk The association between caffeine consumption and various psychiatric manifestations has long been observed. We present two cases that show the ability of caffeine to induce psychotic and manic symptoms, and we also review the extant literature on caffeine-induced psychiatric manifestations. On the basis of our own and others’ findings, we suggest that caffeine may be related to not only de-novo psychotic or mood symptoms but also to aggravation of pre-existing psychotic or mood disorders. We therefore suggest that caffeine consumption among patients with mood or psychotic symptoms should be assessed carefully in clinical practice as part of routine psychiatric evaluations.

Introduction Caffeine is one of the most commonly consumed psychoactive substances. The association between caffeine consumption and the development or aggravation of psychotic or mood symptoms has long been observed (Hedges et al., 2009; Cerimele et al., 2010; Tibrewal and Dhillon, 2011). Despite this observed association and despite the frequent use of caffeine by many psychiatric patients, very few studies have evaluated the effects of caffeine use on the development and aggravation of psychiatric symptoms, and clinical psychiatrists often underestimate or do not consider these effects. So far, the precise incidence and clinical characteristics of caffeine-induced psychiatric manifestation are not well-known, and the efficacy of various treatments for caffeine-induced psychiatric manifestation has not been well evaluated nor documented. In this article, we describe two interesting cases who presented with de-novo manic symptoms and who experienced psychotic exacerbation after excessive caffeine consumption. We also review the previous literature on caffeine-induced psychiatric manifestations among populations with or without previous psychiatric disorders.


Mr A, a 32-year-old man, was diagnosed with paranoid schizophrenia in 2005. Over the last 3 years, he has been stable, with attenuated persecutory delusion and intermittently occurring auditory hallucinations two or three times per week. During this 3-year period, he has been taking oral olanzapine (20 mg/day) and haloperidol (10 mg/ day) for his residual psychotic symptoms. Mr A had been a habitual coffee drinker, typically consuming one cup of coffee per day. He had experienced acute psychotic aggravation preceded by increased caffeine consumption of three

Int Clin Psychopharmacol 30:179–182 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. International Clinical Psychopharmacology 2015, 30:179–182 Keywords: caffeine, mania, psychiatric manifestations, psychosis Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea Correspondence to Won-Myong Bahk, MD, PhD, Department of Psychiatry, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10, 63 (yuksam)-ro, Yeongdeungpo-gu, Seoul 150-713, Korea Tel: + 82 2 3779 1250; fax: + 82 2 780 6577; e-mail: [email protected] Received 15 January 2015 Accepted 12 March 2015

or four cups of coffee per day (207–276 mg of caffeine/day) for 3 weeks. After an increase in oral olanzapine to 25 mg/ day for 3 weeks, combined with continued haloperidol at 10 mg/day, Mr A’s aggravated psychotic symptoms did not improve. He was instructed to discontinue coffee consumption, but the psychotropic medications were not adjusted. Following his discontinuation of coffee consumption, his psychotic symptoms improved gradually over the next 2 weeks. Mr A had no auditory hallucinations and presented only with attenuated paranoid ideation. Since the initial caffeine elimination, he has abstained from coffee and has not presented with psychotic aggravation. Mr B, a 32-year-old man, had no history of psychiatric disorders. He was a habitual coffee drinker and occasionally consumed energy drinks. He presented with manic symptoms, including talkativeness, elated mood, engaging in a buying spree, decreased need for sleep, and increased activity with abrupt onset over the course of a week. These manic symptoms were preceded by excessive daily consumption of energy drinks (three to five cans, 187.5–312.5 mg of caffeine/day) and coffee (seven to nine cups, 350–450 mg of caffeine/day) (a total of 537.5–762.5 mg of caffeine/day) for 2 weeks. Mr B reported that he consumed these large amounts of caffeine to increase his productivity at work. He was admitted to the closed ward of a Psychiatric Department and his symptoms were managed with olanzapine (10 mg/day) and valproic acid (800 mg/day). During hospitalization, Mr B did not have the opportunity to consume caffeine and his manic symptoms started to improve over 7 days. After 3 weeks, his manic symptoms had disappeared and he was discharged symptom free. Following his discharge, he decided to discontinue psychiatric medication and abstain from coffee or energy drinks. After 1 year, however, he resumed

0268-1315 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

DOI: 10.1097/YIC.0000000000000076

180 International Clinical Psychopharmacology 2015, Vol 30 No 4

the consumption of caffeinated beverages including coffee and energy drinks, again because of work pressures. Caffeine consumption was increased gradually to an average of three to five cups of coffee plus three to five cans of energy drinks every day. After about 2 weeks of heavy caffeine consumption, Mr B began to experience maniclike symptoms similar to those he had experienced during his previous episode. He was readmitted to the closed ward and symptoms were managed with aripiprazole (20 mg/ day) and valproic acid (750 mg/day). After 3 days of hospitalization, his manic symptoms began to improve, and at 3 weeks following admission, he was discharged with no symptoms. Mr B was diagnosed with caffeine-induced mood disorder with manic features, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR) criteria.

Influence of caffeine on psychotic symptoms

Previous reports have suggested that caffeine could contribute toward psychosis. Hedges et al. (2009) reported the case of an otherwise healthy individual who presented with psychosis after long, heavy caffeine consumption. Before presenting with psychotic symptoms, he had increased his caffeine intake to up to 10–36 cups/day. Without any modification of his psychotropic medication, and by simply halving his caffeine intake, his paranoid symptoms disappeared over 3 weeks (Hedges et al., 2009). Tibrewal and Dhillon (2011) reported the case of a 52-year-old man with schizophrenia who showed aggravated psychotic symptoms after a few weeks of increased coffee consumption (up to 20–25 cups of coffee/ day). The addition of olanzapine for the control of acute psychotic symptoms was ineffective, but after restricting caffeine consumption without further adjustment of psychotropic medications, his psychotic symptoms disappeared over 10 days (Tibrewal and Dhillon, 2011). Cerimele et al. (2010) reported a similar case in which a 43-year-old man with schizophrenia showed aggravated psychotic symptoms after daily consumption of up to 8–10 cans of energy drinks (3629–4536 mg of caffeine/day) for 8 weeks. In this case, by simply quitting energy drinks, and without the addition of psychotropic medication, his psychotic symptoms improved after 10 days. In addition, Menkes (2011) reported transient psychosis after a single dose of heavy energy drink consumption (600 mg/day of caffeine) that lasted only for several hours. Lucas et al. (1990) carried out a double-blind placebo-controlled study to investigate the effect of caffeine doses that are often consumed regularly (10 mg/kg) on changes in symptoms among patients with schizophrenia and found that these non-uncommon doses of caffeine could exacerbate their psychotic and manic symptoms. In our case, Mr A also consumed relatively low doses of caffeine (2.52–3.37 mg/ kg). Even though we cannot determine whether increased caffeine consumption caused Mr A’s aggravated psychotic symptoms, the close temporal relationship between the

onset and offset of aggravated symptoms and consumption or discontinuation of coffee consumption suggests that caffeine, even at low doses, could exacerbate psychotic symptoms in vulnerable patients with known schizophrenia. Influence of caffeine on mood symptoms

Previous reports have suggested that caffeine may contribute toward the development of manic symptoms. Similar to Mr B in our case, Ogawa and Ueki (2003) reported the case of a 43-year-old patient without a history of mood disorder who developed manic symptoms following a few weeks of excessive coffee consumption (up to 20 cups/day, 1320 mg of caffeine/day). After admission, the patient was instructed to quit coffee consumption and was treated with antipsychotics, following which, his mood symptoms disappeared over 2 weeks (Ogawa and Ueki, 2003). In addition to de-novo manic occurrence, there are several previous reports that showed relapse or aggravation of manic episodes among patients with known bipolar disorders. For instance, Rizkallah et al. (2011) reported two cases that showed manic relapse after excessive consumption of energy drinks. Machado-Vieira et al. (2001) also reported the case of a patient with bipolar spectrum disorder who experienced a manic episode after excessive consumption of energy drinks. In addition, in a case presented by Dratcu et al. (2007), the authors suggested that caffeine could be a cause of treatment-refractory bipolar disorder. Although it is difficult to establish increased caffeine consumption as a cause of the initial manic occurrence and subsequent relapse of our second case, Mr B, there was a temporal relationship between increased caffeine consumption and the onset of manic symptoms in both in the first and in the second episodes. This, together with the evidence presented above, may indicate that Mr B’s increased caffeine intake influenced the onset of his manic symptoms. In contrast to manic symptoms, evidence on the relationship between depression and caffeine consumption is still conflicting. Previous reports have indicated that caffeine has positive effects on mood or energy states (Lara, 2010), and that caffeine consumption is associated with decreased risk of depression (Smith, 2009). However, contrasting reports have suggested that caffeine may instead induce depressed mood. For instance, Hedges et al. (2009) reported a case that showed depressive mood after long, heavy caffeine consumption, and Rizkallah et al. (2011) also reported the case of a patient with known bipolar disorder who experienced depressive relapse after excessive consumption of energy drinks. It is thus still unclear as to whether individuals consume more caffeine to self-medicate their depressive symptoms or whether excessive caffeine consumption itself leads to depressed mood. It is also unknown whether different doses of caffeine consumption may be differentially related to different mood states (e.g. mild to

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Caffeine-induced psychiatric manifestations Wang et al. 181

moderate doses of caffeine may induce positive mood, whereas excessive doses may cause irritable or depressed mood). Influence of caffeine on panic attack or anxiety symptoms

Previous reports suggested a positive association between anxiety or panic symptoms and caffeine (Winstead, 1976; Greden et al., 1978; Gilliland and Andress, 1981). Charney et al. (1985) compared the effects of oral caffeine administration (10 mg/kg) on healthy controls and patients with panic disorder and agoraphobia with panic attacks. They found that caffeine led to a significant increase in anxiety, fear, nervousness, and restlessness among patients with panic disorder or panic attacks. Klein et al. (1991) reported that a single oral dose (480 mg) of caffeine induced panic attacks in 50% of patients with panic disorder. Stahl (2000) reported that a caffeine dose equivalent to four to six cups of coffee induced panic attacks in many patients with panic disorder, but not in most healthy controls. Nardi et al. (2008) investigated the effects of a caffeine challenge test on the induction of panic attacks and anxiety symptoms among patients with panic disorder, their healthy first-degree relatives, and normal controls. They found that patients with panic disorder and their relatives were more sensitive to a caffeine challenge than healthy controls (Nardi et al., 2008).

Discussion Caffeine acts as a competitive antagonist of the adenosine A1 and A2A receptors and affects dopamine activity in the mesolimbic dopamine pathway. This modulated transmission of dopaminergic signaling could underlie the effects of caffeine on behavior, perception, and thought processes (Hedges et al., 2009), including psychiatric manifestations such as mood or psychotic symptoms (Lucas et al., 1990). Caffeine also affects norepinephrine release by antagonizing the actions of adenosine, which inhibits synaptic transmission by inhibiting the release of neurotransmitters such as norepinerphine at various central and peripheral synapses (Snyder and Sklar, 1984). Thus, increased levels of norepinephrine and caffeine may work synergistically in inducing panic or anxiety symptoms (Stahl, 2000; Snyder and Sklar, 1984; Charney et al., 1985). Here, we will discuss the implications and limitations of the described literature and will conclude by suggesting avenues for further research. In terms of the influence of caffeine on psychosis, on reviewing the literature, we found that most of the cases that reported aggravated psychotic symptoms or presented with de-novo psychosis were men. However, the limited evidence means that we cannot determine whether being male is a risk factor for caffeine-induced psychosis. In terms of the specific caffeine consumption conditions, a wide

range of caffeine doses seemed to cause psychotic symptoms (from 200 to 4600 mg of caffeine/day), and the duration of increased caffeine consumption preceding the development of psychotic symptoms also varied from a few weeks to several months or years. This variability might reflect individual variations of each individual’s vulnerability to psychiatric symptoms, underlying medical or psychiatric condition, current smoking or alcohol consumption state, and physical sensitivity to caffeine metabolism. Nonetheless, what we can gained from this review is the knowledge that, among vulnerable individuals, even low doses of caffeine may cause psychotic symptoms or relapse. Thus, when evaluating patients with psychotic conditions, their caffeine consumption should also be investigated. In terms of the influence of caffeine on mood symptoms, the fact that two cases (Mr B and Ogawa’s case) developed de-novo manic symptoms after consumption of 500–1300 mg of caffeine/day for 2–4 weeks suggests an association between excessive caffeine intake and the occurrence of de-novo manic symptoms. It has been similarly shown that caffeine may contribute toward the relapse of mood episodes among known bipolar patients. In terms of recovery from caffeine-induced psychiatric symptoms, most of the cases described remission within a few weeks or a month. This finding suggests that if psychiatric symptoms should occur during increased caffeine intake and persist for more than a month after quitting or reducing caffeine intake, these symptoms are more likely to be primary psychiatric symptoms rather than those that are secondary to caffeine consumption. Interestingly, some cases described in this review experienced a remission of initial symptoms after quitting or reducing caffeine intake, followed by a subsequent recurrence of symptoms after resuming excessive caffeine consumption. These findings thus more strongly support the hypothesis that caffeine consumption and the occurrence of psychiatric symptoms are associated, and highlight the importance of abstaining from caffeine intake after initial symptom remission. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) describes caffeine-related disorders, including caffeine intoxication, caffeine withdrawal, caffeine-induced anxiety disorder, and caffeineinduced sleep disorder (American Psychiatric Association, 2013). Considering the evidence that has emerged from previous studies, we suggest that the addition of ‘caffeine-induced psychotic or mood disorder’ to the diagnostic category of caffeine-related disorders should be seriously considered. Despite the increase in the literature on caffeine-induced psychiatric manifestations, in clinical practice, it is still not possible to identify the causal relationship between caffeine consumption and the development of psychiatric symptoms, particularly when a person/patient presents with new-onset psychiatric symptoms. It is also difficult to predict who

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182 International Clinical Psychopharmacology 2015, Vol 30 No 4

will be vulnerable to the manifestation of psychiatric symptoms when consuming high doses of caffeine. However, this review has high clinical relevance, in that it suggests that caffeine consumption among patients with mood or psychotic symptoms needs to be assessed thoroughly in clinical practice as part of routine psychiatric evaluation. Finally, in terms of treatment strategies for caffeine-induced psychiatric manifestations, the evidence remains too limited to establish clinical recommendations. In some cases, such symptoms showed remission without adjusting or adding psychotropic medication, whereas in other cases, symptoms were managed with various new psychotropic medications. So far, there have been no methodical investigations into the efficacy of various strategies for treating caffeine-induced psychiatric manifestation, and future studies should thus aim to address this gap in the knowledge.

Acknowledgements Conflicts of interest

There are no conflicts of interest.

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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Caffeine-induced psychiatric manifestations: a review.

The association between caffeine consumption and various psychiatric manifestations has long been observed. We present two cases that show the ability...
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