Background: The connection between corticotherapy and neuropsychiatric symptoms is
widely known, being one of the first questions
we need to assess when presenting with first
episode psychiatric symptoms or confusional
state.
Aims: To date, data on cases related to inhaled
corticotherapy and neuropsychiatric effects is
scarce. In this paper we describe a rare case in
a young woman.
Methods: The clinical case presented led us
to try to understand the data published on the
subject in order to discuss it in greater length.
Results and Conclusions: We present and
discuss a 27-year-old patient’s case, with no
previous psychiatric disease, who was admitted to our Psychiatric ward after the onset of
severe acute behavioural disturbance characterized by aggressiveness, visual and auditory
hallucinatory activity, misidentification and
altered conscience status. It was later found
that seven days earlier she had been prescribed
inhaled corticotherapy for a minor respiratory
infection. A few days after corticotherapy withdrawal, the clinical symptoms improved significantly.info:eu-repo/semantics/publishedVersio

Monteiro, J

Mota, D

Ribeiro, L

Santos, M

Venâncio, A

English

Repositório do Hospital Prof. Doutor Fernando Fonseca

Revista do Serviço de Psiquiatria do Hospital Prof. Doutor Fernando Fonseca, EPEwww.psilogos.com Junho 2017 • Vol. 15 • N.º 1114open-accessCaso Clínico / Case Report* Serviço de Psiquiatria e Saúde Mental do Centro Hospitalar de Vila Nova de Gaia/Espinho;  mcm.dos.santos@gmail.com.Recebido / Received:  24/01/2017 • Aceite / Accepted:  22/02/2018.ABSTRACTBackground: The connection between corti-cotherapy and neuropsychiatric symptoms is widely known, being one of the first questions we need to assess when presenting with first episode psychiatric symptoms or confusional state. Aims: To date, data on cases related to inhaled corticotherapy and neuropsychiatric effects is scarce. In this paper we describe a rare case in a young woman.Methods: The clinical case presented led us to try to understand the data published on the subject in order to discuss it in greater length.Results and Conclusions: We present and discuss a 27-year-old patient’s case, with no previous psychiatric disease, who was admit-ted to our Psychiatric ward after the onset of severe acute behavioural disturbance charac-terized by aggressiveness, visual and auditory hallucinatory activity, misidentification and altered conscience status. It was later found that seven days earlier she had been prescribed inhaled corticotherapy for a minor respiratory infection. A few days after corticotherapy wi-thdrawal, the clinical symptoms improved sig-nificantly. Key-Words: Delirium; Steroids; Inhaled The-rapeutics; Iatrogenic; Side Effects.RESUMOIntrodução: A relação entre corticoterapia e sintomas neuropsiquiátricos é sobeja-mente conhecida, sendo uma das primeiras questões a colocar face a uma apresentação inaugural com sintomas psiquiátricos ou estado confusional.Objetivos: A apresentação de um quadro de Delirium secundário à administração de terapêutica corticoide inalada é aqui descri-ta pela primeira vez num paciente jovem. Métodos: O caso clínico aqui apresentado levou-nos a tentar entender os dados publi-cados sobre o assunto no sentido de melhor o compreender e discutir.Resultados e Conclusões: Apresentamos e discutimos o caso de uma doente de 27 anos, sem história de doença psiquiátrica, internada após episódio agudo de alteração grave de comportamento com heteroagres-sividade, atividade alucinatória auditiva e visual, falsos reconhecimentos e alteração do estado de consciência. Retrospetivamente Acute Confusional State after Inhaled CorticotherapyEstado Confusional Agudo após Corticoterapia InaladaMário Marques dos Santos* , Diana Malheiro Mota*, Ângela Venâncio*, Lúcia Ribeiro*, José Monteiro*Revista do Serviço de Psiquiatria do Hospital Prof. Doutor Fernando Fonseca, EPEwww.psilogos.com Junho 2017 • Vol. 15 • N.º 1115PsiLogos • pp 114-119Acute Confusional State after Inhaled Corticotherapypode-se apurar inicio de terapêutica corti-coide na forma inalada há 7 dias por um quadro infecioso respiratório. Após retirada dos corticoides ocorreu melhoria significati-va do quadro ao fim de poucos dias. Palavras-Chave: Delirium; Corticoides; Nebulizadores e Vaporizadores; Iatrogenia; Efeitos Colaterais e Reações Adversas Rela-cionadas com Fármacos.CASE PRESENTATIONThe patient is a 27-year-old single female, living with her foster parents. She has com-pleted 12 years of school and is currently em-ployed at a woodwork shop. She was presen-ted at the Emergency Room (ER) of her local hospital after a preceding two-day behaviou-ral disturbance. The patient had become agi-tated at home, destroying her belongings in her own room where she had locked herself in, afraid of her own parents, presumably be-cause of hallucinatory activity and misiden-tifications. From her background we could only point out a history of syphilis in her infancy (without any current laboratory or clinical features), no regular prescription drugs and this was her first contact with mental health services.She had been prescribed inhaled corticothe-rapy - salmeterol and fluticasone propiona-te 250/50 mcg/dose every twelve hours - for flu-like symptoms (cough and malaise). For about seven days she overused it, taking it about once per hour.A state of fluctuating consciousness, disorga-nized speech sometimes incomprehensible, irritability and restlessness, developed pro-gressively over the eight days since she had begun the steroids. At that time she presented with psychomotor agitation with heteroag-gressiveness, visual and auditory hallucina-tions and misidentification - she believed she saw her grandparents in her parent’s bodies. The next day she was evaluated at the ER for these behavioural symptoms. She was given 1g acetaminophen intravenous (IV), fluids and a new dosage of 1mg inhaled budesonide for her persisting cough before she was evaluated by Neurology and Psychiatry.The laboratory and imaging study was per-formed with complete blood count, basic bio-chemistry, chest x-ray and head computed to-mography scan (CT) – with no clinical signs D1 D7 D8 D9 D11 D18• Inhaled Corticotherapy• Confusional State• Behavorial changes• Visual and auditory hallucinations• Misidentifi-cation• ER• Inhaled Budesonide• Olanzapine• Psychiatric Ward Admission• Clinical DischargeFigure 1. Timeline.Revista do Serviço de Psiquiatria do Hospital Prof. Doutor Fernando Fonseca, EPEwww.psilogos.com Junho 2017 • Vol. 15 • N.º 1116Mário Marques dos Santos, Diana Malheiro Mota, Ângela Venâncio, Lúcia Ribeiro, José Monteiro PsiLogos • pp 114-119of a cause for the presenting complaints. The patient also performed a urine test for abusive drug consumption which turned out negative for all the substances searched. Therefore, the attending physicians felt that an adequate ex-clusion of organic disease had been performed and requested a psychiatric evaluation.Attending to the presenting behavioural changes with aggressiveness, attention and consciousness disorders, hallucinatory acti-vity and misidentification, she was voluntary admitted to a psychiatric ward for further clinical investigation and treatment. The patient stopped using inhaled corticotherapy and was started on an atypical antipsychotic (olanzapine 10 mg per day). From this point on, the hallucinatory activity and misidenti-fications ceased.As an inpatient she completed the laboratory tests with virological and syphilis markers, thyroid function tests, B12 vitamin and folic acid dosing. All of these were also innocent except for a minor folic acid deficit. After dis-charge the patient underwent a psychological assessment which determined a minor intel-lectual impairment.During her stay at our inpatient unit she maintained a generally calm and orderly behaviour, a healthy interaction with health care professionals and other patients, notwi-thstanding a puerile posture. Initially she was a little restless but she was able to focus and maintain attention, always awake and was fully oriented to self, as well as time and space, without any behaviour that would suggest she was experiencing delusional or hallucinatory activity. The insight into the hallucinatory phenomena previous to her admission was addressed but, probably due to her cultural background and her intellectual disability, full insight was not achieved. The patient was discharged home, seven days after admission, with a clinical diag-nosis of acute hyperactive delirium indu-ced by propionate of fluticasone (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition2). She was maintained on olanzapine 10 mg/day until her first outpatient appointment a month later. By that time, she presented complaints of somnolence and weight gain, without any psychiatric symptoms so it was decided to discontinue olanzapine. The patient was also advised to abstain from the use of any type of corticotherapy as it is known that after an episode of neuropsychiatric illness induced by corticotherapy, the risk of recurrence is present with new usage3.DISCUSSION AND CONCLUSIONSThe case here reported refers to a 27-year-old woman, with no previous psychiatric history, presenting an acute episode (around two days evolution) of aggressiveness, agitation, fluc-tuating consciousness, visual and auditory hallucinatory activity and misidentification.After an organic screening with blood tests and head CT scan, a psychiatric aetiology was assumed despite several clues to a possible organic origin (first episode, acute presenta-tion, altered mental status, visual hallucina-tions, misidentification and recent infection). After a careful revision of the case, it came to our attention that the patient had recently started inhaled therapeutics for a minor res-piratory infection - salmeterol and fluticaso-Revista do Serviço de Psiquiatria do Hospital Prof. Doutor Fernando Fonseca, EPEwww.psilogos.com Junho 2017 • Vol. 15 • N.º 1117PsiLogos • pp 114-119Acute Confusional State after Inhaled Corticotherapyne propionate 250/50 mcg/dose every twelve hours – and also that she had been using it in a much higher dose than prescribed. Currently, it is widely known that steroid the-rapy is associated with delirium, depression, mania, psychosis and cognitive impairment4. A study of 261272 patients on steroid thera-py, matched by gender and age with patients with the same types of medical disease, but no corticotherapy, were accessed for diffe-rent neuropsychiatric presentations during a three-month period revealing a 5.14 Odds Ratio (IC 95% - 4.54 a 5,82) for delirium, confusion or maze3. Only recently did we start to understand the mechanisms un-derlying these neuropsychiatric symptoms. Cortisol is the end product of the hypothala-mic-pituitary-adrenal (HPA) axis and it has two different receptors widely distributed in the brain especially in the hypothalamus, pi-tuitary gland and hippocampus– mineralo-corticoid and glucocorticoid – the first being implicated in appraisal processes and the on-set of stress reactions and the second in ter-minating the stress response3,4. There seems to be a connection between steroid responses in the brain and other neurotransmitter sys-tems1, namely the dopamine, acetylcholine and also the serotoninergic system which is strongly implicated in mood, cognition and behaviour4. Synthetic steroids preferentially activate glucocorticoid receptors while also depleting (by means of negative feedback) the adrenal cortisol secretion. Therefore, an extreme imbalance between glucocorticoid receptors and mineralocorticoid receptors caused by the exogenous steroid can cause cognitive impairment, disturbed emotions and other neuropsychiatric manifestations3. There is evidence that, in prolonged high do-sages, various forms of neural damage can also explain these symptoms3. There is still much to be known about these mechanisms as they appear to be complex and unpredic-table.Inhalatory use is generally associated with a small systemic dosage, but in this case, it seems that higher doses reached the lung tis-sue (and the gastro-intestinal tract by unin-tentional swallowing) and the bloodstream as consequence of an excessive intake. This is very important as the risk for neuropsychia-tric disturbances is associated with the dosa-ge of corticotherapy3.The clinical improvement about three days after corticoid withdrawal supports the hypothesis of an iatrogenic cause. Likewise, the clinical deterioration after a dosage of budesonide at the ER makes this hypothesis very likely. However, this was also the mo-ment when an atypical antipsychotic drug was started. Using the Naranjo Scale – a sca-le used to access the likelihood of an adver-se reaction being associated with a specific drug – a probable association was stablished (6 out of 13)6. The previous infection history may also have been a risk factor for a con-fusional state. The other drug used – salme-terol - is a long acting beta-2 agonist used as a bronchodilator; we found no evidence to associate its use to psychiatric disturbances or confusional syndromes.Confusional states usually present with psy-chiatric-like symptoms, but the presentation of altered mental status, even a hyperactive one, together with the patient’s recent clini-Revista do Serviço de Psiquiatria do Hospital Prof. Doutor Fernando Fonseca, EPEwww.psilogos.com Junho 2017 • Vol. 15 • N.º 1118Mário Marques dos Santos, Diana Malheiro Mota, Ângela Venâncio, Lúcia Ribeiro, José Monteiro PsiLogos • pp 114-119cal history should have raised the possibility of a non-psychiatric cause for her symptoms. The screening for organic causes of beha-vioural changes should be made whilst com-pleting the patient’s medical history, together with a physical examination and directed auxiliary study. There are several factors associated with confusional states7: patients characteristics such as age, gender, isolation, alcohol and tobacco use; chronic disease as cardiac or respiratory disease or cognitive impairment; environment issues such as ad-mission through the ER, physical restraint, absence of time markers; acute disease with fever, sedation, and changes in food intake. This case highlights the clinical significance of obtaining a careful medical history, espe-cially in a person with no apparent previous psychiatric history presenting with sudden and acute behavioural disturbance. When presented with a case of delirium, the main strategy should be to identify the causing or underlying factors in order to remove them. In this case, the interruption of the inhaled corticotherapy seems to have been crucial for the clinical outcome. Trea-ting behavioural changes, secondary to a confusional state should be made with low dosage haloperidol or an atypical antipsyco-tic7. These two options seem to have similar outcomes, except in the need for higher do-ses where haloperidol shows increased ex-trapyramidal symptoms. These drugs aim to reduce any risks for the patient and others, mechanical restraint should be used as a last resort and only for the shortest time possible.The connection between oral corticotherapy and neuropsychiatric symptoms has already been established3, however, in this case the use of inhaled corticotherapy seems to have caused a confusional state. Therefore, espe-cially in patients with risk factors for con-fusional states, it seems important that this connection should be considered.Conflicting Interests / Conflitos de Interesse:The authors have declared no competing interests exist. Os autores declaram não ter nenhum conflito de interesses relativamente ao presente artigo Funding / Fontes de Financiamento:The authors have declared no external funding was received for this study.  Não existiram fontes externas de financiamento para a realização deste artigo. References / Bibliografia1. Moss JM, Kemp DW, Brown JN. Combination of Inhaled Corticosteroid and Bronchodilator-In-duced Delirium in an Elderly Patient With Lung Disease. J Pharm Pract. 2014;27(1):79-83.2. Diagnostic and statistical manual of mental disorders: DSM-5. Arlington, VA: American Psy-chiatric Publishing, 2013.3. Judd LL, Schettler PJ, Scherwood Brown ES, Wolkowitz OM, Sternberg EM, Bender BG et al. Adverse Consequences of Glucocor-ticoid Medication: Psychological, Cogniti-ve, and Behavioral Effects. Am J Psychiatry. 2014;171(10):1045-51.4. Kusljic, S, Manias E, Gogos A. Corticosteroid--induced psychiatric disturbances: It is time for pharmacists to take notice. Res Social Adm Pharm. 2016;12(2):355-360.Revista do Serviço de Psiquiatria do Hospital Prof. Doutor Fernando Fonseca, EPEwww.psilogos.com Junho 2017 • Vol. 15 • N.º 1119PsiLogos • pp 114-119Acute Confusional State after Inhaled Corticotherapy5. Fardet L, Petersen I, Nazareth I. Suicidal Beha-vior and Severe Neuropsychiatric Disorders Following Glucocorticoid Therapy in Primary Care. Am J Psychiatry. 2012;169(5):491-7.6. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-45.7. Field RR, Wall MH. Delirium: Past, Present, and Future. Semin Cardiothorac Vasc Anesth. 2013;17(3):170-9. 

Estado Confusional Agudo após Corticoterapia Inalada

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Estado Confusional Agudo após Corticoterapia Inalada

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