Drug-Associated Liver Injury Related to Antipsychotics: Exploratory Analysis of Pharmacovigilance Data.

BACKGROUND: Drug-associated liver injury is one of the most common causes for acute liver failure and market withdrawal of approved drugs. In addition, the potential for hepatotoxicity related to specific substances has to be considered in psychopharmacotherapy. However, systematic evaluations of hepatotoxicity related to antipsychotics are limited. METHODS: We conducted an exploratory case/non-case study and evaluated pharmacovigilance data from VigiBase related to 30 antipsychotics marketed in the European Union. Reporting odds ratios were calculated for antipsychotics associated with the Standardized Medical Dictionary of Regulatory Activities queries "Drug-related hepatic disorders-comprehensive search" (DRHD-CS) and "Drug-related hepatic disorders-severe events only" (DRHD-SEO). RESULTS: We found several signals for drug-associated liver injury including signals for severe events: 17 of 30 antipsychotics were associated with DRHD-CS and 10 of 30 antipsychotics with DRHD-SEO. Amisulpride, fluphenazine, levomepromazine, loxapine, olanzapine, perazine, perphenazine, pipamperone, sulpiride, and thioridazine were associated with both, DRHD-CS and DRHD-SEO. No association with fatal outcomes was detected. CONCLUSIONS: Several common antipsychotics are associated with hepatotoxicity, partly also with severe hepatotoxicity. Our data do not allow to account for patient-related risk factors for drug-associated liver injury. This should be addressed in further studies.

Psychological Distress, Fear and Coping Strategies During the Second and Third Waves of the COVID-19 Pandemic in Southern Germany.

Background: The COVID-19 pandemic has imposed enormous psychological discomfort and fear across the globe, including Germany. Objectives: To assess the levels of COVID-19 associated psychological distress and fear amongst Southern German population, and to identify their coping strategies. Methods: A cross-sectional survey using an online questionnaire was conducted in healthcare and community settings in the region of Ulm, Southern Germany. Assessment inventories were the Kessler Psychological Distress Scale (K-10), the Brief Resilient Coping Scale (BRCS), and the Fear of COVID-19 Scale (FCV-19S), which were valid and reliable tools. Results: A total of 474 Individuals participated in the study. The mean age was 33.6 years, and 327 (69%) were females. Most participants (n = 381, 80.4%) had high levels of psychological distress, whereas only 5.1% had high levels of fear, and two-thirds of participants showed higher levels of coping. Moderate to very high levels of psychological distress were associated with being female, living alone, distress due to employment changes, experiencing financial impact, having multiple co-morbidities, being a smoker, increased alcohol use over the previous 6 months, contact with COVID-19 cases and healthcare providers for COVID-19-related stress. Individuals who were ≥60 years, lived with non-family members, had co-morbidities and visited a healthcare provider had higher levels of fear. Higher levels of education and income showed better coping amongst participants. Conclusion: Psychological distress was very high during the COVID-19 pandemic in Germany and associated with low levels of coping. This study identified vulnerable groups of people, who should be given priorities for addressing their health and wellbeing in future crisis periods.

Harmonization of summaries of product characteristics (SmPCs) of drugs with the same active ingredients: an evaluation of SmPCs of the most frequently prescribed active substances.

PURPOSE: In aut-idem or generic substitution, discrepancies between summaries of product characteristics (SmPCs) referring to the same active substance (AS) may cause difficulties regarding informed consent and medical liability. The qualitative and quantitative characteristics of such discrepancies are insufficiently studied, impeding harmonization of same-substance SmPCs and compromising safe drug treatment. METHODS: SmPCs of the one hundred most frequently prescribed ASs in Germany were analyzed for discrepancies in the presentation of indications (Inds) and contraindications (CInds). Inclusion and exclusion criteria of drugs/SmPCs were chosen according to the standards of the aut-idem substitution in Germany. RESULTS: According to the study protocol, we identified 1486 drugs, of which 1426 SmPCs could be obtained. 41% respectively 65% of the ASs had same-substance SmPCs that differed from the respective reference SmPC in the number of listed Inds respectively CInds. The number of listed Inds/CInds varied considerably between same-substance SmPCs with maximum ranges in Inds of 7 in amoxicillin, and in CInds of 11 in lisinopril. Many ASs had large proportions (> 50%) of associated same-substance SmPCs that differed from the respective reference SmPC. A considerable proportion of ASs had same-substance SmPCs with formal and content-related differences other than the discrepancy in the number of Inds/CInds. CONCLUSION: This evaluation of same-substance SmPCs shows a clear lack of harmonization of same-substance SmPCs. Considering that generic substitution has become the rule and that physicians usually do not know which drug the patient receives in the pharmacy, these discrepancies raise several questions, that require a separate legal evaluation.

Risk of Bleeding Associated With Antidepressants: Impact of Causality Assessment and Competition Bias on Signal Detection.

Introduction: Until now, methods of pharmacovigilance as disproportionality analysis were not capable of proving the otherwise well-established increased bleeding risk related to antidepressants (ADs). As bleeding events with ADs often occur in combination with antithrombotics, they might not be considered causative of, but merely "linked" with, the bleeding event. Therefore, we hypothesized that the causality assessment of bleeding events in association with ADs and the competitive impact of antithrombotics are factors contributing to the non-findings of previous pharmacovigilance studies. Methods: We performed a case/non-case study based on data from VigiBaseTM and calculated reporting odds ratios (RORs) for 25 ADs. We used individual case safety reports (ICSRs) that were differently categorized in the database regarding their type of association between drug and event. Furthermore, we investigated the competitive impact of antithrombotics by comparing RORs with and without ICSRs related to antithrombotics. Results: Analysis of ICSRs that were categorized as causally associated resulted in the detection of only two signals (citalopram and escitalopram; upper gastrointestinal bleeding). Analysis of ICSRs irrespective of the type of association resulted in the detection of signals in 8 out of 25 ADs (regarding bleeding, in general, gastrointestinal bleeding and upper gastrointestinal bleeding). Consideration of ICSRs associated with antithrombotics as competitive substances did not have a major impact on signal detection in our analysis. Conclusion: Categorization of the type of association between drug and event affects the results of quantitative signal detection. Causality assessment seems to play a major role in signal detection, probably particularly concerning rare, unknown, or clinically insignificant adverse drug reactions. ADs appear to significantly increase the bleeding risk, even independent of antithrombotic comedication.

The Impact of Serotonin Transporter Binding Affinity on the Risk of Bleeding Related to Antidepressants.

PURPOSE/BACKGROUND: The alleged primary mechanism underlying bleeding events associated with antidepressants is inhibition of serotonin uptake in platelets resulting in reduced platelet aggregability and activity, and prolonged bleeding time. There is some evidence that a substance's degree of serotonin reuptake inhibition in terms of its binding affinity to the serotonin transporter (SERT) affects the magnitude of bleeding risk increase. METHODS/PROCEDURE: To test this hypothesis, we performed data mining in the worldwide largest pharmacovigilance database (VigiBase) and conducted pharmacodynamically informed quantitative signal detection. Reporting odds ratios related to the standardized Medical Dictionary of Regulatory Activities query term "haemorrhages" and 24 antidepressants were calculated, and SERT binding affinities (pKi) were obtained and correlated (Pearson correlation). FINDINGS/RESULTS: A strong and statistically significant correlation between substance-related reporting odds ratios and SERT binding affinities was found (r = 0.63; 95% confidence interval, 0.30-0.82; P = 0.00097). IMPLICATIONS/CONCLUSIONS: Our findings strengthen the hypothesis that inhibition of serotonin uptake contributes to the antidepressant-related bleeding risk and suggest an association between the degree of the SERT binding affinity and the bleeding risk. This supports the preferential use of antidepressants with low or no SERT binding affinity in depressed patients at risk of bleeding.

Risk of Bleeding Associated with Antidepressant Drugs: The Competitive Impact of Antithrombotics in Quantitative Signal Detection.

BACKGROUND: To date, disproportionality analysis has been unable to demonstrate the increased bleeding risk associated with antidepressant drugs, especially selective serotonin reuptake inhibitors. OBJECTIVE: We hypothesised that a potential signal for an increased bleeding risk may be mitigated by the effects of agents other than antidepressant drugs that are strongly associated with haemorrhages, especially antithrombotics. In addition, we investigated if the use of more specific search terms of the Medical Dictionary for Regulatory Activities facilitates the detection of signals. METHODS: Pharmacovigilance data from the Uppsala Monitoring Centre were used to calculate substance-specific reporting odds ratios (RORs) for all types of bleeding and gastrointestinal bleeding. Reporting odds ratios were calculated with and without antithrombotic comedication. RESULTS: Regarding any type of bleeding, no signals were found in association with antidepressant drugs. Concerning upper gastrointestinal bleeding, signals were found related to citalopram (ROR: 1.56 [95% confidence interval 1.11-2.20]) and escitalopram (ROR: 1.52 [95% confidence interval 1.03-2.25]). After removal of reports related to antithrombotics, these signals could no longer be detected, but a new signal related to St. John's Wort associated with haemorrhages was found (ROR: 1.50 [95% confidence interval 1.21-1.86]). CONCLUSIONS: Antithrombotics seem unlikely to have a major impact on the detection of the bleeding risk of antidepressant drugs. The different categorisation of adverse drug reactions regarding the strength of a causal relationship between a drug and an event in the database may be relevant for this negative finding.

Arrhythmias related to antipsychotics and antidepressants: an analysis of the summaries of product characteristics of original products approved in Germany.

PURPOSE: Most psychiatric drugs, such as antidepressants (AD) and antipsychotics (AP), may cause cardiac adverse events (CAE). We used summaries of product characteristics (SmPC) for assessing the likelihood of AD and AP to cause CAE. METHODS: We identified all original medicinal products (OMP) of AD and AP approved in Germany. We searched for their SmPCs using the online services of PharmaNet.Bund, Gelbe liste®, Rote Liste®, Fachinfo-Service®, and via manufacturer contact. We extracted frequencies of reported CAE (QT prolongation, Torsade de Pointes tachycardia, and ventricular arrhythmia) and performed a risk assessment. RESULTS: We obtained the SmPCs of 24 AD and 26 AP identified as OMP. Comparably high reported frequencies regarding QT prolongation were found for Invega® (paliperidone), Serdolect® (sertindole) (≥ 1/100 and < 1/10), and Zoloft® (sertraline) (≥ 1/10.000 and < 1/1000); regarding Torsade de Pointes tachycardia were found for Serdolect® (≥ 1/1000 to < 1/100), Zoloft®, and Trevilor® (venlafaxine) (≥ 1/10.000 and < 1/1000); regarding ventricular tachycardia for Solian® (amisulpride), Xomolix® (droperidol), Zyprexa® (olanzapine), and Trevilor® (≥ 1/10.000 and < 1/1000). CONCLUSION: The risk and frequency of CAE, as reported in the SmPCs, varied significantly among substances and between groups. There are more reports for AP than AD. The AP with the most frequently reported CAE (QT prolongation and Torsade de Pointes tachycardia) was Serdolect®; for AD, Zoloft® (QT prolongation, Torsade de Pointes tachycardia) and Trevilor® (Torsade de Pointes tachycardia and ventricular tachycardia) carried a higher cardiac risk.

Corrigendum: Risk of Bleeding Associated With Antidepressants: Impact of Causality Assessment and Competition Bias on Signal Detection.

[This corrects the article DOI: 10.3389/fpsyt.2021.727687.].

Short Imagery Rescripting Intervention to Treat Emotionally Dysregulated Behavior in Borderline Personality Disorder: An Exploratory Study.

BACKGROUND: Current research on borderline personality disorder report an association between emotionally dysregulated behaviors and intrusive mental imagery depicting similar scenes. Imagery rescripting techniques have proven effective in reducing intrusive mental imagery in numerous contexts. We developed a two session-short intervention in which intrusive mental images are identified, analyzed, and modified for daily rehearsal at home. This study aimed to reduce the negative emotions and cognitions associated with self-injurious behaviors by replacing unhealthy imagery with more adaptive content. METHODS: Seven females diagnosed with borderline personality disorder who reported intrusive mental imagery of dysregulated behaviors were recruited for participation. Each participant engaged in two individualized treatment sessions and daily homework requiring the rehearsal of modified imagery. Emotion regulation strategies, borderline symptom severity, and depressiveness were assessed before and after treatment. RESULTS: Acceptance was positive, as no patient dropped out from treatment. Symptom exacerbation was not observed. Borderline symptom reduction was noted and indicia of emotional dysregulation and negative affect declined. LIMITATIONS: The generalizability of results is limited by the small sample size and the absence of a control group. Conclusions: This new two-session short intervention was shown to decrease the emotionally dysregulated behaviors that accompany negative feelings in females with borderline personality disorder.

[Use of summaries of product characteristics (SmPC) among family doctors and pharmacists in the context of the aut-idem regulation: Results of an exploratory cross-sectional survey]. / Nutzung von Fachinformationen bei Hausärzten und Apothekern im Zusammenhang der Aut-idem-Regelung: Ergebnisse einer explorativen Querschnittsbefragung.

INTRODUCTION: Summaries of product characteristics (SmPC) of same-substance medications may feature content-related differences. This may cause difficulties regarding informed consent in the case of prescriptions of drugs in the context of the aut-idem regulation. A survey among family doctors (FD) and pharmacists (PH) was conducted in order to evaluate the usage behaviour of SmPCs, sources used to obtain information about drugs and the awareness of the existence of differences between SmPCs of same-substance medications. METHODS: An exploratory/non-representative, questionnaire- and telephone-based, semi-structured cross-sectional survey was performed (June to August 2018). RESULTS: Participation rate of FD and PH was 29.8 % (34/114) and 73.0 % (73/100), respectively. In the previous month, all PH and 82.4 % of FD said that they had used a SmPC at least once (p=0.001). FD used SmPCs 6.4±4.9 and PH 65.0±52.5 times a month (p<0.001). In both occupational groups SmPCs were used most frequently to obtain information about dosing and/or type of application (FD: 97.1 %; PH: 98.6 %) and contraindications (97.1 % and 86.3 %, resp.). In both samples, the internet was the most frequently used drug information source (FD: 97.1 %; PH: 98.6 %), followed by the Rote/Gelbe Liste (97.1 % and 71.2 %, resp.) and the SmPCs of the original product (52.9 % and 65.8 %, resp.) or generic drug (52.9 % and 61.6 %, resp.). Only 32.4 % of the FD vs. 79.5 % of PH believed that differences might exist between SmPCs of same-substance medications (p<0.001). FD stated that they never (11.8 %) or rarely (85.3 %) use SmPCs for informed consent. It was indicated that the aut-idem substitution is excluded in 10.3 %±5.0 (FD) and 9.6 %±6,1 (PH) of issued or received prescriptions. DISCUSSION: The results of the present survey indicate a low utilization rate of SmPCs by FD and little awareness of the existing differences of SmPCs of same-substance medications in this occupational group. Both aspects may impede proper information of patients, particularly in cases of aut-idem prescriptions of substances for which many same-substance medications with different SmPCs are available. CONCLUSION: Physicians should use SmPCs regularly and keep themselves informed about differences between SmPCs of same-substance medications.

Comparison of International Therapy Guidelines with Regard to the Treatment of Malignant Catatonia.

OBJECTIVE: Malignant catatonia (MC) is an extremely rare, life-threatening disorder. It is characterized by catatonic symptoms accompanied by autonomic instability, hyperthermia, and changes in laboratory values. In many cases, MC is not recognized as such. Evidence-based guidelines are essential to ensure quality of treatment, but what do current national and international guidelines recommend? METHOD: Online search for international guidelines from English-, French-, Italian-, and German-speaking countries whose medical care meets high standards addressing the treatment of MC. These were analyzed and compared regarding statements on MC, recommendations, and strength of scientific evidence. RESULTS: Fifteen of the identified guidelines were included. Only 5 of 15 comment on the treatment of MC. As for other rare diseases, no detailed recommendations are available. Suggested therapies are limited to benzodiazepines and electroconvulsive therapy. Levels of evidence and grades of recommendation are predominantly low. CONCLUSION: Many international guidelines do not mention MC. It is not possible to derive a clear algorithm for the treatment of MC from most current guidelines. A thorough update of most guidelines appears to be necessary. Lack of awareness and knowledge of MC among physicians and medical professionals might lead to inadequate or delayed care, worsened outcome, or death.

Retinal single-layer analysis with optical coherence tomography (OCT) in schizophrenia spectrum disorder.

BACKGROUND: Volume reductions in brain structures of patients with schizophrenia spectrum disorder (SSD) have repeatedly been found in voxel-based morphometry MRI studies. Hence, an underlying neurodegenerative etiological component of SSD is currently being discussed. In recent years, the imaging method of optical coherence tomography (OCT) has shown its potential in evaluating structural changes in the retina in patients with confirmed neurodegenerative disorders, providing a window into the brain. METHODS: Twenty-six patients with schizophrenia or schizoaffective disorder and 23 age- and sex-matched healthy controls were examined with the Heidelberg Spectralis OCT system to derive a single-layer analysis of both retinas. The segmentation of retinal layers was manually corrected to minimize artifacts and software imprecisions. RESULTS: Compared to the control group, SSD patients showed reduced thickness and volume measurements for nearly all retinal layers, and these differences reached significance for macular volume, macular thickness, retinal nerve fiber layer (RNFL) and inner nucleiform layer (INL). Furthermore, a significant correlation between the duration of illness and the total volume of the RNFL was found. CONCLUSION: Our OCT measurements demonstrate reduced single retinal layer thickness in patients with SSD. In the context of the MRI volume changes, our results provide further evidence that structural changes seen in the brain of patients are also observable in the retina, potentially allowing further insights into the different components of the nervous system that are altered in this highly etiologically complex disorder.

[Different number of contraindications between summaries of product characteristics (SmPC) of drugs with the same active ingredients - an analysis of data from SmPCs of neuropsychiatric drugs]. / Unterschiedliche Anzahl von Kontraindikationen zwischen Fachinformationen wirkstoffgleicher Arzneimittel ­ eine Analyse von Daten aus Fachinformationen von neuropsychiatrischen Arzneimitteln.

OBJECTIVE: In the case of prescriptions of pharmaceuticals in the context of the aut-idem-regulation the physician frequently does not know, which same-substance medication is dispensed in the pharmacy; the contemplable same-substance medications may differ in numerous features which raises questions regarding the obligation to give information and medical liability for medical malpractice. Currently, systematic evaluations regarding differences between summaries of product characteristics (SmPCs) of same-substance medications are missing. To determine size and type of those differences SmPCs of most (neuro)psychiatric drugs that are approved in Germany were evaluated regarding the number of listed contraindications (CI). METHODS: Basis for the selection of substances was the Anatomical Therapeutic Chemical (ATC) Classification System (group ATC N Nervous System). Substances that are approved in Germany for the treatment of mental disorders according to ICD-10 F were included. Brand-name medications and SmPCs were searched by means of further in- and exclusion criteria via the online services of PharmNet.Bund, Gelbe Liste, Rote Liste®/Fachinfo-Service® and communication with the manufacturer. RESULTS: N = 941 SmPCs (=116 substances) were evaluated. Considering only the group of SmPCs with > 1 brand-name medication (n = 78; 67.2 %) differences in the number of CIs were found in more than the half of substances (N = 43; 55.1 %). Considering indication groups most groups of SmPCs of same-substance medications with differences in the numbers of CIs were found in - considering only substances with > 1 brand-name medication - hypnotics and sedatives (77.8 %), anxiolytics (75.0 %), drugs for treatment of substance use disorders (66.7 %), antidepressants (61,9 %), anticonvulsant drugs and mood stabilizers (53.8 %), followed by antipsychotics (41.2 %), antidementia-drugs (20.0 %), and psychostimulants (0 %). Largest ranges regarding the number of CIs were found in the SmPCs of morphine (14), amitriptyline (8), chlorprothixene (6), lorazepam (6) and citalopram (4). CONCLUSION(S): In numerous (neuro-)psychopharmacologic substances differences exists between the SmPCs of the associated same-substance medications regarding the number of CIs. Due to the outstanding evaluation of content aspects of these differences and legal evaluation the relevance of this result for clinical practice is not yet clear.

Treatment of the Neuroleptic Malignant Syndrome in International Therapy Guidelines: A Comparative Analysis.

INTRODUCTION: The neuroleptic malignant syndrome (NMS) is a potentially life-threatening condition associated to the use of antipsychotics. Since it requires rapid and efficient medical care, high-quality treatment guidelines should be available. In this article, we analyzed and compared different international therapy guidelines for the treatment of schizophrenia, in which NMS treatment recommendations might be contained. METHODS: We performed an Internet-based search for schizophrenia guidelines via the website of the respective medical society. Guidelines in English, French, Italian, and German from countries whose medical care meets high standards were selected for further analysis and comparison of the NMS treatment recommendations (if present), and their underlying evidence. RESULTS: The NMS is mentioned in 12 of 14 guidelines. Only 9 report concrete therapy recommendations (benzodiazepines/dantrolene/bromocriptine/amantadine/intensive care and/or electroconvulsive therapy (ECT)), however, with high heterogeneity. Only 5 guidelines included all possible drug therapy options and ECT, but with differing combination strategies, dosages, application forms, and combinability of options. The level of evidence of the different recommendations was estimated as low. DISCUSSION: One-third of the selected guidelines do not report any NMS therapy recommendations. Most guidelines mentioning the NMS do not provide therapy recommendations that include all relevant treatment options. The results show a very high heterogeneity, and the recommendations and statements are of low-evidence levels. The lack of knowledge about the NMS and its treatment may delay the onset of therapy, impair the quality of treatment, and lead to a worse outcome or death.

Relation of Promoter Methylation of the Oxytocin Gene to Stressful Life Events and Depression Severity.

Oxytocin (OT) is a neuropeptide associated with trauma, sociality, and depression. Despite the widely accepted assumption of OT playing a role in the etiology of mood and anxiety disorders, associations between stressful life events, depression, and epigenetic regulation of the gene coding for OT (OXT) have not yet been investigated. We therefore aimed to examine the interrelations of stressful life events, depression severity, and methylation of the promoter region of OXT in a sample of N = 146 inpatients suffering from major depression. We found significant negative associations of stressful life events with mean methylation status as well as with methylation status of single CpG sites in the promoter region of OXT. There was no association between depression severity and OXT methylation. However, there were significant sex differences in methylation status of OXT with women showing higher methylation rates than men, putatively suggesting that in depression OXT is less activated in females compared to males. These results speak against an association of OXT methylation and depression severity, but support the assumption of a dysregulation of the OT system due to life stress. Our findings further emphasize the importance of including sex as an important factor in the investigation of the interrelations between OXT, stress, and depression.

Intranasal Pregabalin Administration: A Review of the Literature and the Worldwide Spontaneous Reporting System of Adverse Drug Reactions.

BACKGROUND: It is repeatedly reported that pregabalin (PRG) and gabapentin feature a potential for abuse/misuse, predominantly in patients with former or active substance use disorder. The most common route of use is oral, though reports of sublingual, intravenous, rectal, and smoking administration also exist. A narrative review was performed to provide an overview of current knowledge about nasal PRG use. METHODS: A narrative review of the currently available literature of nasal PRG use was performed by searching the MEDLINE, EMBASE, and Web of Science databases. The abstracts and articles identified were reviewed and examined for relevance. Secondly, a request regarding reports of cases of nasal PRG administration was performed in the worldwide spontaneous reporting system of adverse drug reactions of the European Medicines Agency (EMA, EudraVigilance database). RESULTS: The literature search resulted in two reported cases of nasal PRG use. In the analysis of the EMA-database, 13 reported cases of nasal PRG use (11 male (two not specified), mean age of users = 34.2 years (four not specified)) were found. In two cases fatalities occurred related to PRG nasal use. CONCLUSIONS: Even if only little evidence can be found in current literature, the potential for misuse/abuse of PRG via nasal route might be of particular importance in the near future in PRG users who misuse it. Physicians should be aware of these alternative routes of administration.

Takotsubo Cardiomyopathy With Inconspicuous Initial Electrocardiogram: A Potentially Serious Cardiac Pathology Related to Emotional Stress.

Introduction: Takotsubo cardiomyopathy (TCM) is frequently associated with emotional or physical stress. Thus, patients with TCM might present primarily at a psychiatric clinic. Appropriate diagnosis and therapy may thus be delayed. Case report: A 43-year-old female patient presented as an emergency to the psychiatric outpatient clinic after experiencing severe work-related bullying. On admission, she complained of acute left thoracic chest pain as well as depressed mood, low energy, anhedonia, generalized anxiety, and sleep difficulties, present for several weeks. The initial electrocardiogram (ECG) was unremarkable; serum troponin levels, however, were markedly elevated. The patient was transferred to the department of cardiology. Via cardiac catheterization and MRI, an acute coronary syndrome was excluded and apical ballooning and left ventricular dysfunction, compatible with TCM, was found. Conclusion: Patients with acute psychopathology, recent emotional or physical stress, and acute cardiothoracic symptoms should receive immediate cardiological investigations. As the ECG may be normal in patients with TCM, concurrent measurement of the troponin serum level is recommended. Psychiatrists should consider TCM in patients who report recent stressful events accompanied by cardiothoracic symptoms.