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Diagnostic challenge: bipolar affective disorder--manic episode with psychotic symptoms versus psychotic disorder induced by caffeine-containing substances.


Caffeine is a widely used psychoactive substance; when consumed in excess, it may contribute to the emergence of certain symptoms, and even of heterogeneous psychiatric disorders (1). Caffeine can determine anxiety symptoms in normal individuals, especially in vulnerable patients, like those with pre-existing anxiety disorders. At the same time, caffeine abuse is associated with depressive symptoms and with genuine psychotic symptoms, either in the context of apparent mental health, or aggravating a pre-existing psychiatric pathology, most frequently concerning disorders with psychotic elements (1, 2). As a competitive adenosine antagonist, caffeine affects dopamine synaptic transmission and has been reported to worsen psychosis in people with schizophrenia or with other mental disorders and to cause psychosis in otherwise healthy people (3).

The preference for caffeine containing energy drinks is related to its psycho-stimulating properties: caffeine promotes cognitive excitation and it fights against fatigue. The likelihood of experience adverse somatic or mental effects of this substance indissolubly depends on the amount ingested, on individual vulnerability, and on the pre-existence of a general or mental medical disorder, worsened by caffeine intake (1, 3).

The addiction syndrome represents a group of physio-pathological, behavioural, and cognitive phenomena, where the use of a psychoactive substance becomes a priority for the individual, compared to other previously valued behaviours. It is possible to identify the psychoactive substance/s that the patient abuses based on his own reports, on the toxicological test, on the presence of a psychoactive substance in the patient's possession, as well as on clinical signs and symptoms pointing towards the intake of a certain drug and on information received from the legal representatives. From the ICD-10 perspective, the dependence diagnostic is set when there is a cluster of behavioural, cognitive, and physiological phenomena that develop after repeated substance use and that typically include a strong desire to take the drug, difficulties in controlling and persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state. (4)

The psychotic disorder phenomena occur during or following psychoactive substance use. The disorder is characterized by hallucinations (typically auditory, but often in more than one sensory modality), perceptual distortions, delusions (often of a paranoid or persecutory nature), psychomotor disturbances (excitement or stupor), and an abnormal affect, which may range from intense fear to ecstasy. The sensorium is usually clear, but some degree of clouding of consciousness, though not severe confusion, may be present. Partial remission is attained within a month and total remission within six months (4).

On the other hand, bipolar affective disorder is characterized by two or more episodes in which the patient's mood and activity levels are significantly disturbed, this disturbance consisting, on some occasions, of an elevation of mood and increased energy and activity (hypomania or mania) and on others of a lowering of mood and decreased energy and activity (depression).

Repeated episodes of hypomania or mania are only classified as bipolar. The diagnostic of manic episode with psychotic symptoms within bipolar affective disorder requires the presence of at least one affective episode in the past, as well as the presence of all criteria for mania with psychotic symptoms, affectively congruent or incongruent (4).


A patient aged 55, on his first psychiatric admission, without somatic conditions with chronic evolution; he never suffered any surgical intervention. He came to the ER room of the Psychiatric Clinic, accompanied by his legal representatives, for a psychotic symptomatology with sudden onset; apparently, he seemed in good health.

In terms of socio-familial and professional insertion, the patient is married, he has two major children, he lives in a flat in the city, with his wife, he is legally employed (he is a long distance driver). His own statements and those of his family show that he had no notable adjustment or integration difficulties at home or at work.

The patient declared that, though he had never been admitted to a psychiatric clinic before, there had been well-delimited times in the past when he had felt hopeless with no good reason, more irascible and irritable than in general. During those times, he believed that nothing he did was good enough; on the other hand, he also went through periods (even more numerous than the first ones) of mental wellbeing without extrinsic reasons for the exacerbation of affective tonality. He stated that, despite these mood extremes, he did not record significant decreases in global functioning; he did not experience any setbacks in his professions because of his mood.

At the same time, the patient mentioned his abuse of caffeine containing energy drinks: "they kept me awake and I was able to drive for many kilometres a day; they made me feel full of energy; I thought I could move mountains. I have been on leave for a week now, but I have not been able to give up on energy drinks". Anamnesis reveals that the abuse of caffeine containing energy drinks had been lasting for one year and a half and that it had worsened in the recent months, because "I felt no effect after two energy drinks, as I used to have before, so I got to five of them a day". The patient denies having consumed any alcoholic beverages or other types of psychoactive substances; in addition, he states that he is not a smoker.

In the triage section of the Psychiatric Clinic, the patient manifests great anxiety caused by the context of xenopathic phenomena with sudden onset; he is easily distractible, communicative, and cooperative; however, he is highly suspicious of the examiner; he presents elements of mental fading and he is slightly incoherent in his speech. He is partially aware of his psychiatric troubles.

Both, the family and the patient, state that they came to the Psychiatric Clinic because of his psychomotor agitation, irritability, irascibility, dramatic reduction of braking capacity, clear signs of delirium and hallucinations (including vivid visual and auditory hallucinations), delusional ideations of reference, of chase and of prejudice, grandeur ideation, reduced tolerance to minor frustrations, and seemingly unjustified hetero-aggressive manifestations. The patient's behaviour changed drastically, two days prior to his admission to the clinic.

In terms of family medical history, the patient does not have first-degree relatives with a diagnosed psychiatric pathology; his mother suffers from insulin-requiring type I diabetes, while his father passed away from a colon neoplasm. He recorded no pathological episodes throughout the evolution.

The objective clinical examination of the systems did not show pathological alterations. His lab tests results ranged within normal parameters and his toxicological screen did not show the use of another psychoactive substance. The electroencephalogram and the BESA did not show any epileptic focus. The CT scan also ranged within normal parameters. Therefore, the organic origin of the psychiatric symptomatology exhibited by the patient was ruled out.

The psychological examination showed an unstable emotional configuration, including impulsive-explosive manifestations (with positive hyperthymic elements, as well as delusional and hallucination elements).

During the psychiatric evaluation, following his admission to the psychiatric section with closed doors, considering that the patient is a danger to himself and to the others, he exhibits psychomotor agitation and he is partially cooperative, and communicative. He is obviously preoccupied with his appearance. His expression is mobile, his face is expressive; he makes ample gestures in concordance with the affective tonality; he intermittently initiates eye contact with the interlocutor. His voice has average tonality, increased intensity, affective modulation; the patient observes partially the reciprocity of the dialogue.

The patient reports the presence of complex visual hallucinations ("there were people outside my window and they wanted to enter the house") and of complex auditory hallucinations ("somebody is calling my name; I can hear it loud and clear, but I fail to recognize the voice"). The flow of ideas has an accelerated rhythm, ideas are chaotic; he features delusional ideations of reference, of chase and of prejudice (without bizarre character), as well as grandeur ideas. The patient is logorrheic, his speech is incoherent, with egophiliac tendencies and a marked concern for the xenopathic elements (visual and auditory hallucinations). He also manifests voluntary and spontaneous hypoprosexia, with selective hyperprosexia elements concerning the delirious themes and the visual and auditory hallucinations, all of which make him extremely distractible. Consequently, he shows clear fixing hypomnesia caused by attention deficit disorder; however, the evoking memory is intact.

He also shows elevated mood accompanied, however, by irritability, irascibility, weak control of impulses, reduced tolerance to minor frustrations, decrease in personal efficiency in the context of his grandiosity. The instinctual behaviour is exacerbated on all levels, included an increase in appetite, erotomanic elements, and hetero-aggressiveness with self-protective purpose developed in the context of delusional ideas and hallucinations with persecution and prejudice content. The patient also reports reduced need of sleep. He has good spatial and temporal orientation, but he shows vague elements of unreality. The patient is partially aware of his psychiatric troubles, because he states, "I have not recognized myself these past few days".

Considering the set of psychiatric symptoms and signs, the patient has difficulties in his family relation; he has experienced conflicting situations with the wife, motivated by the delirium context.


When he was first admitted to the clinic, the context of having consumed caffeine containing energy drinks and the seemingly related psychotic symptoms led toward setting the diagnostic of caffeine induced psychotic disorder (F 15.5, according to ICD-10 criteria) (4). However, subsequent anamnesis and the data collected from the family suggested the existence of a bipolar affective disorder in current manic episode, with psychotic symptoms. I do mention, however, that the patient reported affective episodes that were not attested medically and that attained remission within variable periods, without psychotropic medication. Therefore, the diagnostic considers a possible worsening of the manic episode with psychotic symptoms, in the context of energy drinks abuse.

The differential diagnostic ruled out schizophrenia, personality disorders, disorders related to the use and abuse of other psychoactive substances, depression, anxious spectrum disorders, and adult ADHD.

However, the diagnostic upon release was the same as the one upon admission, in order to have an expectative type of approach, considering that therapy with antipsychotics would have been the solution for both diagnostics.


After admission, the patient was given an intramuscular Diazepam injection, as well as 500 mg of valproate and glucose intravenous infusion 5 %. Blood pressure dropped to 90/60 mmHg after administering benzodiazepine. The patient became agitated from a psychomotor perspective once he was taken to the reserve and he began being aggressive toward the other patients. The patient was held mechanically, for his own protection, considering that we responded to benzodiazepine.

On the day following the admission, therapy per se began and it included as follows: Quetiapine XR 300 mg/day, in the evening, increased dosage for two days, up to 600 mg/day in the evening, valproate 1000 mg/day, administered in two phases. Because the therapeutic response was partial, the dosage of Quetiapine XR was increased to 800 mg/day, in the evening, administered once a day. For this dosage, Quetiapine XR had a high degree of receptor occupancy (>70 %) for D2, H1, and 5-HT2A, considering that the emergence of the antipsychotic effect requires an occupancy degree of over 60 % for D2 receptors (5).

The evolution was gradually favourable; the patient was released after three weeks of psychiatric hold, as maintenance treatment, the pharmacological therapy initiated during the hospitalization was preserved. No notable adverse effects to the medication emerged; the patient tolerated it properly. Upon release, the patient was recommended to avoid all psychoactive substances and to benefit from the mentally protective family setting; the follow-up was scheduled after two weeks. The patient's evolution at the two-week follow-up was good; hallucinations and delusional ideas ceased. Currently, the patient's mood is euthymic, and he controls his impulses effectively. Taking into account the particularities of the case, the prognosis is favourable in the context of good therapeutic compliance and if the patient observes the hygiene and diet recommendations made when he was released. The patient requires medical assistance and careful re-assessment, in order to confirm the effectiveness of the treatment.


Considering the particularities of this case, especially the good pre-morbid functioning of the patient, the apparent abuse of caffeine containing energy drinks temporarily associated with intense psychotic symptoms, and the reports of the patient (affective episodes that were not attested medically and that attained remission within variable periods, without psychotropic medication) led to the diagnostic dilemma. Considering the case overlapping with the criteria of caffeine induced psychotic disorder (both the symptoms and their timing, in the context of abuse of caffeine containing energy drinks), the patient's diagnostic upon release was maintained. However, there is still the possibility of a manic episode worsened by caffeine intake, part of a bipolar affective disorder, with the sine qua non condition that the patient actually experienced at least one affective episode in the past. Though the psycho-pharmacological therapeutic management includes the same types of drugs, the long-term prognosis may be different. The confirmation of bipolar affective disorder may require, under certain circumstances, for the patient to continue the treatment a la longue. In this case, the option concerns the expectative and periodical examination of the patient, in order to set a definitive diagnostic.

Ilinca UNTU--M.D., Ph. D. Student, "Socola" Institute of Psychiatry, Iasi, Romania

Dorina DONCIU--M.D., "Socola" Institute of Psychiatry, Iasi, Romania

Vasile CHIRITA--Professor, M.D., Ph. D., Senior Psychiatrist, Honorary Member of Romanian Academy, "Socola" Institute of Psychiatry, Iasi, Romania

ROXANA CHIRITA--Professor, M.D., Ph. D., "Socola" Institute of Psychiatry, Iasi, Romania


The authors declare that they have no potential conflicts of interest to disclose.


(1.) Broderick, P., Benjamin, A. B. Caffeine and psychiatric symptoms: a review. University of Oklahoma, USA. The Journal of the Oklahoma State Medical Association .2004. 97(12):538-542.

(2.) Seifert, S. M., Seifert, S. A., Schaechter, J. L., Bronstein, A. C., Benson, B. E., Hershorin, E. R., Arheart, K. L., Franco, V. I., Lipshultz, S. E. An analysis of energy-drink toxicity in the National Poison Data System. Clin Toxicol (Phila) .2013.

(3.) Dawson, W., Hedges, Fu Lye Woon, Hoopes, Scott P. (2009). Caffeine-Induced Psychosis. CNS Spectrums, 14, pp 127-131 doi:10.1017/S1092852900020101.

(4.) ICD-10. Clasificarea tulburarilor mentale si de comportament. All Publishing House, Bucharest. 1998. pp. 94-98, 138-145.

(5.) Sthal, S. M. Stahl's essential psychopharmacology--neuroscientific basis and practical applications. Fourth edition. Cambridge University Press. 2013.


VASILE CHIRITA "SOCOLA" INSTITUTE OF PSYCHIATRY No. 36 Bucium, zip code 700282, Iasi, Romania


Submission: May, 07th, 2015

Acceptance: May, 25th, 2015
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Title Annotation:Case Reports
Author:Untu, Ilinca; Donciu, Dorina; Chirita, Vasile; Chirita, Roxana
Publication:Bulletin of Integrative Psychiatry
Article Type:Report
Date:Jun 1, 2015
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