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BACKGROUND: Global pediatric healthcare reveals significant morbidity and mortality rates linked to respiratory, cardiac, and gastrointestinal disorders in children and newborns, mostly due to the complexity of therapeutic management in pediatrics and neonatology, owing to the lack of suitable dosage forms for these patients, often rendering them "therapeutic orphans". The development and application of pediatric drug formulations encounter numerous challenges, including physiological heterogeneity within age groups, limited profitability for the pharmaceutical industry, and ethical and clinical constraints. Many drugs are used unlicensed or off-label, posing a high risk of toxicity and reduced efficacy. Despite these circumstances, some regulatory changes are being performed, thus thrusting research innovation in this field. DATA SOURCES: Up-to-date peer-reviewed journal articles, books, government and institutional reports, data repositories and databases were used as main data sources. RESULTS: Among the main strategies proposed to address the current pediatric care situation, nanotechnology is specially promising for pediatric respiratory diseases since they offer a non-invasive, versatile, tunable, site-specific drug release. Tissue engineering is in the spotlight as strategy to address pediatric cardiac diseases, together with theragnostic systems. The integration of nanotechnology and theragnostic stands poised to refine and propel nanomedicine approaches, ushering in an era of innovative and personalized drug delivery for pediatric patients. Finally, the intersection of drug repurposing and artificial intelligence tools in pediatric healthcare holds great potential. This promises not only to enhance efficiency in drug development in general, but also in the pediatric field, hopefully boosting clinical trials for this population. CONCLUSIONS: Despite the long road ahead, the deepening of nanotechnology, the evolution of tissue engineering, and the combination of traditional techniques with artificial intelligence are the most recently reported strategies in the specific field of pediatric therapeutics.
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BACKGROUND: The ApoE genotype and neuropsychiatric symptoms (NPS) are known risk factors for cognitive decline in older adults. However, the interaction between these variables is still unclear. The aim of this study was to determine the association between the presence of the ApoE ε4 allele and the occurrence of NPS in older adults without dementia. METHODS: In this cross-sectional investigation we determined the apolipoprotein E (ApoE) genotype of 74 older adults who were either cognitively normal (20.3% / Clinician Dementia Rating Scale (CDR): 0) or had mild cognitive impairment (MCI: 79.7% / CDR: 0.5). We used a comprehensive cognitive assessment protocol, and NPS were estimated by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), Mild Behavioural Impairment-Checklist (MBI-C), Hamilton Rating Scale for Depression (HAM-D), and Apathy Inventory. RESULTS: ApoE ε4 carriers had higher MBI-C total scores than ApoE ε4 noncarriers. Correlations between NPS and ApoE genotype were observed for two NPI-C domains, although in opposite directions: the ApoE ε4 allele was associated with a 1.8 unit decrease in the estimated aberrant motor disturbance score and with a 1.3 unit increase in the estimated appetite/eating disorders score. All fitted models were significant, except for the one fitted for the domain delusions from the NPI-C. Among individuals with amnestic MCI, ε4 carriers presented higher depression score (HAM-D) than noncarriers; in turn, ε4 noncarriers exhibited higher aggression score (NPI-C) than ε4 carriers. CONCLUSIONS: Our analyses showed associations between NPS and the presence of the ApoE ε4 allele in two NPI-C domains, despite the sample size. Furthermore, compared to noncarriers, the presence of the ApoE ε4 correlated positively with appetite/eating disorders and negatively with aberrant motor disturbance domain. Examination of the amnestic MCI group displayed significant, although weak, associations. Therefore, ε4 carriers exhibited higher depression scores according to the HAM-D scale compared to ε4 noncarriers. Conversely, ε4 noncarriers had higher scores in the aggression domain of the NPI-C than ε4 carriers.
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Apolipoproteína E4 , Demência , Idoso , Humanos , Apolipoproteína E4/genética , Apolipoproteínas E , Estudos Transversais , Demência/diagnóstico , Demência/genética , GenótipoRESUMO
Objectives: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. Methods: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. Results: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively. Conclusion: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.
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OBJECTIVES: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. METHODS: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. RESULTS: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen's d values of 0.92 and 1.78, respectively. CONCLUSION: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Lítio/farmacologia , Estudos Transversais , Cognição , Doença de Alzheimer/tratamento farmacológicoRESUMO
Introduction: Transcranial magnetic stimulation (TMS) is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation (TBS) is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is to investigate the efficacy of TBS in geriatric depression. Clinical trial registration: [https://clinicaltrials.gov/ct2/], identifier [NCT04842929].
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Objective: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. Methods: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aβ1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. Results: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. Conclusion: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.
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OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. METHODS: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aß1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. RESULTS: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. CONCLUSION: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.
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Doença de Alzheimer , Disfunção Cognitiva , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Árvores de Decisões , Humanos , Proteínas tau/líquido cefalorraquidianoRESUMO
BACKGROUND: Neuropsychiatric symptoms (NPS) may represent early clinical manifestations of evolving brain diseases. Studies underpin the occurrence of NPS in the context of mild cognitive impairment (MCI) and prodromal Alzheimer's disease, where symptoms referred to as 'mild behavioural impairment' (MBI) have been shown to predict conversion to dementia and to hasten cognitive/functional decline. However, the association between NPS and cerebrovascular risk factors has been poorly investigated, despite the high prevalence of the latter among individuals with MCI. The aim of the present study was to investigate the association between MBI and cerebrovascular risk in a clinical sample of non-demented elders. METHODS: Sixty-five MCI and 15 cognitively unimpaired older adults were cross-sectionally assessed with the Mild Behavioural Impairment Checklist (MBI-C), using the cut-off score > 6.5 to define positive screening. Participants were submitted to the Hachinski Ischaemic Score (HIS) to account for cerebrovascular symptoms, vascular risk, and related comorbidities. Neuroimaging scans (magnetic resonance imaging and/or 18F-fluorodeoxyglucose-positron emission tomography) and apolipoprotein E genotype were obtained. RESULTS: Positive associations were found between total MBI-C scores and increasing number of comorbidities present (0-2 comorbidities), but not with three comorbidities. Two domains of the MBI-C-impulse dyscontrol and social inappropriateness-followed the same trend of the MBI-C total score, with higher scores with the increasing numbers of comorbidities. No significant associations were found between MBI symptoms and HIS or cerebrovascular burden in neuroimaging assessment. CONCLUSION: We found weak associations between MBI-C total score and the presence of comorbidities with cerebrovascular risk, but not with structural or functional neuroimaging abnormalities or HIS. This finding may represent that the presence of comorbidities adds limited risk to the occurrence of MBI in this sample of non-demented elders.
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Doença de Alzheimer , Disfunção Cognitiva , Idoso , Lista de Checagem , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Humanos , Testes NeuropsicológicosRESUMO
BACKGROUND: Decreased cerebrospinal fluid (CSF) concentrations of the amyloid-ß (Aß), along with increased total (T-tau) and phosphorylated tau protein (P-tau), are widely accepted as core biomarkers of Alzheimer's disease (AD) pathology. Nonetheless, there are a few remaining caveats that still preclude the full incorporation of AD biomarkers into clinical practice. OBJECTIVE: To determine the frequency of clinical-biological mismatches in a clinical sample of older adults with varying degrees of cognitive impairment. METHODS: 204 participants were enrolled for a cross-sectional assessment and allocated into diagnostic groups: probable AD (nâ=â60, 29.4%); MCI (nâ=â84, 41.2%); or normal cognition (NC, nâ=â60, 29.4%). CSF concentrations of Aß42, T-tau, and 181Thr-P-tau were determined, and Aß42/P-tau ratio below 9.53 was used as a proxy of AD pathology. The AT(N) classification was further used as a framework to ascertain the biological evidence of AD. RESULTS: The majority (73.7%) of patients in the AD group had the Aß42/P-tau ratio below the cut-off score for AD, as opposed to a smaller proportion in the MCI (42.9%) and NC (23.3%) groups. In the latter, 21 subjects (35%) were classified as A+, 28 (46.7%) as T+, and 23 (38.3%) as Nâ+â. In the AD group, 66.7%of the cases were classified as A+, 78.3%as T+, and 80%as N+. CONCLUSION: Analysis of CSF biomarkers was able to discriminate between AD, MCI, and NC. However, clinical-biological mismatches were observed in a non-negligible proportion of cases.
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Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , FosforilaçãoRESUMO
Introduction: There is a growing awareness about the noxious effects of the 2019 Coronavirus Disease (COVID-19) pandemic on the mental health of the elderly. However, there is limited information from clinically driven research. The objectives of the present study were to examine the magnitude of psychiatric symptoms and to determine their association with caregiver distress, in a cross-section of community-dwelling older adults and a subsample of aging adults with Down syndrome (DS) attending a psychogeriatric service in São Paulo, Brazil. Method: Telephone-based interviews and electronically filled self-assessment questionnaires were used to collect information from patients and caregivers, addressing their impressions and concerns about the pandemic and related effects on the patient's emotional state and behavior. Clinical information was obtained from hospital charts, medical records, and psychometric tests administered through telephone interviews [Hospital Anxiety and Depression Scale (HADS) and Neuropsychiatric Inventory Questionnaire (NPI-Q)]. Results: We included 100 consecutive participants, comprising 71 older adults with psychogeriatric/neurocognitive disorders and 29 aging adults with DS. Higher HADS and NPI-Q scores were significantly associated with caregiver distress (p < 0.05) in both groups. Correlation analyses indicated strong, positive associations between caregiver burden and scores in HADS anxiety (HADS-A) and HADS depression (HADS-D) scales in the subsamples of euploid and DS subjects. Higher NPI-Q scores in the former group were also correlated with caregiver distress, with stronger associations for neuropsychiatric symptoms. Similar findings were observed among DS subjects. ANOVA tests indicated significant associations between NPI-Q scores and caregiver distress among dementia patients, as well as with HADS scores. Similar results were found after multiple linear regressions; as such, among the elderly subsample, higher scores in HADS-A (p = 0.002) and HADS-D (p = 0.001) predict a significant impact on caregiver burden (p < 0.00001, R 2 0.46); taking into consideration caregiver burden as a dependent variable and NPI-Q total score as an independent variable, we obtained significant strong prediction values for either DS (p < 0.00001, R 2 0.95) or elderly adults (p < 0.00001, R 2 0.88). Conclusion: During the COVID-19 pandemic, patients with neurocognitive disorders present with clinically relevant neuropsychiatric symptoms, with significant impact on caregiver distress. Apathy, aberrant motor behavior, sleep disorders, and psychoses were the main psychopathological domains, which had determined caregiver burden worsening.
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The prevalence of Alzheimer's disease (AD), a progressive neurodegenerative disorder, is expected to more than double by 2050. Studies on the pathophysiology of AD have been changing our understanding of this disorder and setting a new scenario for drug development and other therapies. Concepts like the "amyloid cascade" and the "continuum of AD," discussed in this article, are now well established. From updated classifications and recommendations to advances in biomarkers of AD, we aim to critically assess the literature on AD, addressing new definitions and challenges that emerged from recent studies on the subject. Updates on the status of major clinical trials are also given, and future perspectives are discussed.
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Humanos , Encéfalo/patologia , Diagnóstico Precoce , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Biomarcadores , Progressão da DoençaRESUMO
The prevalence of Alzheimer's disease (AD), a progressive neurodegenerative disorder, is expected to more than double by 2050. Studies on the pathophysiology of AD have been changing our understanding of this disorder and setting a new scenario for drug development and other therapies. Concepts like the "amyloid cascade" and the "continuum of AD," discussed in this article, are now well established. From updated classifications and recommendations to advances in biomarkers of AD, we aim to critically assess the literature on AD, addressing new definitions and challenges that emerged from recent studies on the subject. Updates on the status of major clinical trials are also given, and future perspectives are discussed.
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Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Encéfalo/patologia , Diagnóstico Precoce , Biomarcadores , Progressão da Doença , HumanosRESUMO
BACKGROUND: Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. OBJECTIVES: To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. METHOD: Studies were included in the review according to the following criteria: a) clinical trials (placebo-controlled or not) or case reports; b) short- or long-term interventions with antidepressants; c) prescription of newer generation antidepressants as first-line treatment; d) samples of adult or adult-old patients. From a total of 301 articles addressing the association between antidepressants and cardiovascular adverse events as primary or secondary outcomes, we selected 30 controlled clinical trials and 10 case reports. RESULTS: In most clinical studies, the effects of antidepressants on cardiac function are usually computed as secondary outcome variables, however with limited information. Conversely, case reports tend to present more comprehensive sets of clinical and laboratorial parameters, but the generalization of such data is limited by the small number of observations. The occurrence of QTc prolongation (with increased risk of torsade de pointes) has been reported. Aging, higher dosages of antidepressants, drug interaction, and pre-existing cardiovascular comorbidities were found as risk factors for the aforementioned cardiovascular and ECG abnormalities. CONCLUSION: Prescribing antidepressants requires caution given their potential impact on cardiac function, and the clinician should carefully monitor cardiovascular and ECG parameters particularly in cases with underlying heart disease.
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Antidepressivos/efeitos adversos , Coração/efeitos dos fármacos , Síndrome do QT Longo/induzido quimicamente , Transtornos Mentais/tratamento farmacológico , Torsades de Pointes/induzido quimicamente , Relação Dose-Resposta a Droga , Interações Medicamentosas , Eletrocardiografia , Humanos , Síndrome do QT Longo/diagnóstico , Fatores de Risco , Torsades de Pointes/diagnósticoRESUMO
PURPOSE OF REVIEW: The present article addresses intriguing questions related to the clinical intervention in distinct neuropsychiatric syndromes of patients with dementia. RECENT FINDINGS: We reviewed 154 articles published between 2015 and 2016 targeting psychopharmacological and nonpharmacological interventions, and safety-tolerability concerns. We selected 115 articles addressing the purpose of this study. Of these, 33 were chosen because they were dedicated to subtopics: agitation (42), depression (33), apathy (18), sleep disorders/anxiety (8), and psychosis (4). Clinical studies using both pharmacological (70) and nonpharmacological (37) interventions were considered; others were included for theoretical support. Regarding the methodological design, we found double-blind RCTs (17), single-blinded RCTs (4), open-label studies (18), case reports (5), cross-sectional or cohort studies (25), epidemiological papers (2), and expert reviews (44). This observation raises concerns about the overall methodological adequacy of a substantial proportion of studies in this field, which limits the potential of generalization of the findings. Finally, 18 studies were designed to determine safety-tolerability issues of psychotropic medications (6 were discussed). SUMMARY: Effective and well tolerated treatment of neuropsychiatric syndromes in dementia remains a critically unsolved challenge. We understand that this is an extremely important area of research, and critically required to guide clinical decisions in geriatric neuropsychiatry.
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Demência/terapia , Transtornos Neurocognitivos/terapia , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Apatia/efeitos dos fármacos , Terapia Combinada , Estudos Transversais , Demência/diagnóstico , Demência/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Transtorno Depressivo/terapia , Método Duplo-Cego , Humanos , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/psicologia , Sintomas Prodrômicos , Agitação Psicomotora/diagnóstico , Agitação Psicomotora/psicologia , Agitação Psicomotora/terapia , Psicopatologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/terapia , Psicotrópicos/uso terapêuticoRESUMO
ABSTRACT Objetive To identify potential clinical and epidemiological predictors of long-term response to lithium treatment. Methods A total of 40 adult outpatients followed in an university hospital, with confirmed diagnosis of bipolar disorder and with history of lithium use for at least a six months period, had their response to this medication assessed through the use of a standardized instrument. The ALDA scale is based on retrospective clinical data, in our study assessed through a thoroughly reviewed of the medical charts, and is used to evaluate the clinical improvement with the treatment (Criterion A), corrected by the acknowledgement of possible confounding factors, such as duration of the treatment, compliance and concomitant use of additional medications (Criterion B), in order to estimate the response that can be specifically attributable to lithium. Results Our study found an inverse relation between the number of mood episodes with psychotic symptoms and lithium treatment outcome. Conclusion The results reinforce the hypothesis that lithium seems to be less efficacious in patients with bipolar disorder who present psychotic symptoms.
RESUMO Objetivo Identificar potenciais preditores clínicos e epidemiológicos de resposta terapêutica ao uso prolongado de lítio. Métodos Um total de 40 pacientes adultos em tratamento ambulatorial em um hospital universitário, com diagnóstico confirmado de transtorno afetivo bipolar e história de pelo menos seis meses de uso de lítio, teve sua resposta a essa medicação avaliada com a utilização de um instrumento padronizado. A escala ALDA leva em consideração informações clínicas obtidas de forma retrospectiva, em nosso estudo, por meio de minuciosa revisão dos prontuários médicos, para julgar a melhora clínica obtida com o tratamento (Critério A), corrigida pela identificação de possíveis fatores confundidores, tais como duração do tratamento, adesão e uso concomitante de outras drogas (Critério B), de forma a estimar a resposta que pode ser atribuída especificamente ao uso do lítio. Resultados Nosso estudo encontrou uma relação inversa entre o número de episódios de humor com a presença de sintomas psicóticos e o desfecho no tratamento com lítio. Conclusão Esses resultados reforçam a hipótese de que o lítio parece ser menos eficaz em pacientes com transtorno afetivo bipolar que manifestam sintomas psicóticos.
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INTRODUCTION: Thyroid dysfunction has often been associated with several psychiatric manifestations. Previous case reports/series suggest the possible role played by acute alteration of thyroid status in the onset of psychotic symptoms. METHODS: Case report and literature review. RESULTS: A 45-year-old woman with no psychiatric antecedents was brought to the ER with a full-blown psychotic episode, marked by paranoid delusions, which developed gradually over two months. She had been treated elsewhere for hyperthyroidism for five years with methimazole 40 mg/d, with poor compliance. One month before the beginning of the psychotic symptoms, methimazole was raised to 60 mg/d and she started taking it correctly. Five months earlier she had TSH: 0.074 uUI/ml and free T4: 1.3 ng/dl. At admission we found a diffuse thyroid goiter, TSH: 70.9 uUI/ml and free T4: 0.03 ng/dl. Brain CT was normal. We hospitalized her with the diagnosis of a psychosis secondary to hypothyroidism, suspended methimazole, and gave her levothyroxine (up to 75 µg/d) and risperidone (2 mg/d). The patient had a quick remission and was discharged after 15 days. Within one month she had TSH: 0.7 uUI/ml and was completely recovered psychiatrically. She has been well since then, with risperidone in the first 8 months, and without it for 10 months now. CONCLUSION: This case report is a reminder of the necessity of checking thyroid status as part of clinical assessment of psychoses. It also supports the hypothesis that antithyroid drugs may have severe psychiatric consequences, especially when they lead to an acute change of thyroid status.
INTRODUÇÃO: Disfunções tireoidianas têm sido frequentemente associadas a diversas manifestações psiquiátricas. Séries e relatos de caso sugerem o possível papel da alteração aguda do status tireoidiano na vigência dos sintomas psicóticos. MÉTODOS: Relato de caso e revisão de literatura. RESULTADOS: Uma mulher de 45 anos sem antecedentes psiquiátricos foi trazida para Unidade de Emergência Referenciada com episódio psicótico, marcado por delírios paranoides, que se desenvolveram gradualmente nos dois meses anteriores. Ela tinha sido tratada, em outro serviço, por hipertireoidismo durante cinco anos com metimazol 40 mg/d, com aderência ruim. Um mês antes do início dos sintomas psicóticos, o metimazol foi aumentado para 60 mg/d, dose que ela estava tomando corretamente. Cinco meses antes ela tinha TSH: 0,074 uUI/ml e T4 livre: 1,3 ng/dl. Na admissão, encontraram-se aumento difuso da glândula, TSH: 70,9 uUI/ml e T4 livre: 0,03 ng/dl. TC de crânio estava normal. Foi hospitalizada por diagnóstico de psicose secundária ao hipotireoidismo, suspenso o metimazol e introduzidas levotiroxina (até 75 µg/d) e risperidona (2 mg/d). A paciente teve rápida remissão e recebeu alta após 15 dias. Um mês após ela apresentava TSH: 0,7 uUI/ml, com remissão completa da psicose. Ela permaneceu bem, com risperidona nos oito meses seguintes e sem a medicação há 10 meses. CONCLUSÃO: Este relato de caso é um alerta para a necessidade de investigar a função tireoidiana como parte do manejo clínico da psicose. Também reforça a hipótese de que drogas antitireoidianas podem ter graves consequências psiquiátricas, especialmente quando levam à mudança aguda do status tireoidiano.