Doctor, can I have an extra cup of caffeine? Researchers performed a systematic review of studies of caffeine consumption and clinical symptoms in patients with bipolar disorder.
Ms P is a 52-year-old Caucasian female with bipolar I disorder, most recent episode depressed with psychotic features. Her mood disorder has been stable on ziprasidone, with no psychiatric hospitalizations in the past 5 years. She smokes 2+ packs of cigarettes per day over 30 years. Ms P drinks a large quantity of caffeine daily: she routinely brings a 44-ounce cup of soda with her to clinic visits, and states that she drinks at least 2 of these cups daily. She also has comorbid hypertension and chronic obstructive pulmonary disease, for which she is adherent with medication. At a recent outpatient appointment, Ms P noted that her mood was euthymic, and there was no evidence of psychosis. She reported sleeping 6 to 7 hours per night and denied significant anxiety. Ms P’s psychiatrist regularly provides psychoeducation on reducing her caffeine intake.
Caffeine is the most commonly consumed psychoactive substance worldwide, primarily via tea and coffee. Caffeine is an adenosine A1 and A2A receptor antagonist that increases arousal, reinforcement, and psychomotor activation.1 In the general population, there is evidence for the broad health benefits of caffeine, with evidence that coffee intake may be associated with decreased morbidity and mortality.2 By contrast, psychoeducational programs for patients with bipolar disorder routinely advise reducing or limiting caffeine intake.3-5 However, the evidence for this recommendation has not been systematically reviewed and synthesized.
The Current Study
Accordingly, Frigerio and colleagues6 performed a systematic review of the effects of caffeine consumption on clinical symptoms in patients with bipolar disorder. This review was conducted in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study authors systematically searched PubMed, EMBASE, and PsycINFO for studies that assessed any measure of clinical outcomes and consumption of caffeine in adults with bipolar disorders (BD). They included studies of any design that reported data on at least 1 adult with BD that compared a measure of caffeine use and illness severity (eg, symptoms of mania, depression, psychosis, sleep, anxiety, or suicide). Clinical data were extracted and a risk of bias assessment was performed for each identified study.
From 1678 records, the authors reviewed 25 full text articles for eligibility, of which 17 met inclusion criteria. These 17 studies included 10 case reports, 5 cross-sectional studies, 1 cohort study, and 1 single-arm interventional study. None of the studies used objective, standardized methods to measure caffeine intake, instead relying on self-report.
One cross-sectional study found that patients with (bipolar or unipolar) depression reported more anxiety in response to caffeine compared to controls with no psychiatric illness. Patients with bipolar depression experienced more light-headedness, palpitations, and (perceived) tachycardia in response to a cup of coffee than either controls or patients with unipolar depression. Another cross-sectional study found a positive association between caffeine use and mixed-affective states in patients with BD. Three cross-sectional studies found that in euthymic patients with BD, greater caffeine consumption was associated with worse sleep parameters (including sleep quality and duration). The cohort study reported that patients with BD who drank coffee had more suicidality and a higher frequency of manic episodes than noncoffee drinkers. One case report described a patient with remission of seasonal manic episodes after withdrawing from high caffeine use. There were also 8 case reports of patients who either were consuming high quantities of caffeine or abruptly increased caffeine intake prior to the onset of manic symptoms.
The authors concluded that although there may some relationship between caffeine consumption and symptom severity in patients with BD, the evidence is nonsubstantive given the small number of (noncase report) studies, inconsistent findings, and inadequate consideration of potential confounding factors. The primary limitation of the present review was that the majority of included studies were case reports. Potential mechanisms whereby acute increases in caffeine may precede the onset of manic episodes in patients with BD include direct stimulant effects, modulation of sleep patterns, and/or effects on metabolism of mood stabilizers. However, increased caffeine intake could also be a prodromal sign of impending mania, or a consequence of a manic episode.
The Bottom Line
Further rigorously-designed studies with consideration of potential confounders are needed to determine whether caffeine use impacts long-term prognosis in BD.
Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric TimesTM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.
1. Fredholm BB, Bättig K, Holmén J, et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999;51:83-133.
2. Poole R, Kennedy OJ, Roderick P, et al. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ. 2017;359:j5024.
3. Stafford N, Colom F. Purpose and effectiveness of psychoeducation in patients with bipolar disorder in a bipolar clinic setting. Acta Psychiatr Scand Suppl. 2013;442:11-18.
4. Hospital Clínic Barcelona: Frequently asked questions. Clínic Barc. Accessed 5 July, 2020. https://www.clinicbarcelona.org/en/assistance/diseases/bipolar-disorder/frequently-asked-questions
5. Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30:495-553.
6. Frigerio S, Strawbridge R, Young AH. The impact of caffeine consumption on clinical symptoms in patients with bipolar disorder: a systematic review. Bipolar Disorders. 2021;23:241-251.