Matthäus Fellinger, Thomas Waldhör, Benjamin Vyssoki, Michaela Amering, Lisa Leutgeb, Andreas Gschaider, Bernhard Rappert, Daniel König, Gernot Fugger, Philipp Knasmüller, and Andrea Gmeiner
Background Coercive measures such as involuntary psychiatric admission are considered a last resort in the treatment of people with psychiatric disorders. So far, numerous factors have been identified that influence their use. However, the link between a pandemic – in particular, restrictions such as lockdowns – and the use of involuntary psychiatric admission is unclear. Aim To examine the association between COVID-19 lockdowns and involuntary psychiatric admissions in Austria. Method This retrospective exploratory study assessed all involuntary psychiatric admissions and use of mechanical restraint in Austria, except for the federal state of Vorarlberg, between 1 January 2018 and 31 December 2020. Descriptive statistics and regression models were used. Results During the 3-year study period, 40 012 individuals (45.9% females, mean age 51.3 years) had 66 124 involuntary psychiatric admissions for an average of 10.9 days. Mechanical restraint was used during 33.9% of these admissions. In weeks of nationwide COVID-19 lockdowns (2020 v. 2018/2019), involuntary psychiatric admissions were significantly fewer (odds ratio = 0.93, P = 0.0001) but longer (11.6 (s.d.: 16) v. 10.9 (s.d.: 15.8) days). The likelihood of involuntary admission during lockdowns was associated with year (2020 v. 2018–2019; adjusted odds ratio = 0.92; P = 0.0002) but not with sex (P = 0.814), age (P = 0.310), use of mechanical restraint (P = 0.653) or type of ward (P = 0.843). Conclusions Restrictions such as lockdowns affect coercive measures and resulted in fewer but longer involuntary psychiatric admissions during weeks of lockdown in Austria. These results strengthen previous findings that showed the dependence of coercive measures on external factors, highlighting the need to further clarify causality and desired prevention effects when using coercive measures.
Victoria Watzal, Godber Mathis Godbersen, Ana Weidenauer, Matthäus Willeit, Valentin Popper, Michael Treiber, Maximilian Preiss, Dominik Ivkic, Ulrich Rabl, Gernot Fugger, Richard Frey, Christoph Kraus, Dan Rujescu, and Lucie Bartova
The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug-induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare.
Maximilian Preiss, Ulrich Rabl, Valentin Popper, Victoria Watzal, Michael Treiber, Dominik Ivkic, Nicole Praschak-Rieder, Angela Naderi-Heiden, Gernot Fugger, Richard Frey, Dan Rujescu, and Lucie Bartova
The non-benzodiazepine hypnotic zolpidem is frequently administered as a short term psychopharmacotherapy for insomnia. Although it is well-established in a broad clinical routine and often well-tolerated, severe delirium and complex sleep behavior were reported in rare cases. Hereby, it remains unclear whether zolpidem's potential for delirium might be enhanced when combined with further psychopharmacotherapeutics. The present case report portrays a young male Caucasian inpatient with schizoaffective disorder, who was admitted due to severe hyperactive delirium after a single dose of zolpidem 10 mg that was administered in addition to already established psychopharmacotherapy including clozapine 200 mg/day, aripiprazole 15 mg/day and cariprazine 4.5 mg/day. In detail, disorientation, agitation, confabulations, bizarre behavior, and anterograde amnesia occurred shortly after ingestion of zolpidem and gained in intensity within a couple of hours. Once zolpidem was discontinued, the abovementioned symptoms subsided completely and did not reoccur. Since a clear temporal association could be drawn between the intake of zolpidem and the onset of hyperactive delirium, the present clinical experience should serve as a cautionary note for combining potent sedative-hypnotics and substances with anticholinergic properties, even in young adults in a good general condition. Moreover, our case argues for the necessity of further research into the pathomechanism of the interaction potential of non-benzodiazepines as zolpidem, especially with substances exerting anticholinergic properties, which are known for their potential to precipitate delirium. Therefore, the metabolic pathways of the concurrently administered substances should be further taken into account.
Alexander Kautzky, Lucie Bartova, Gernot Fugger, Markus Dold, Daniel Souery, Stuart Montgomery, Joseph Zohar, Julien Mendlewicz, Chiara Fabbri, Alessandro Serretti, Dan Rujescu, and Siegfried Kasper
Subjects
treatment-resistant depression, antidepressant, sold age, Psychiatry, RC435-571
Abstract
Abstract Background Treatment-resistant depression (TRD) is an important clinical challenge and may present differently between age groups. Methods A total of 893 depressed patients recruited within the framework of the European research consortium “Group for the Studies of Resistant Depression” were assessed by generalized linear models regarding age effects (both as numerical and factorial predictors) on treatment outcome, number of lifetime depressive episodes, hospitalization time, and duration of the current episode. Effects of age as numerical predictor on the severity of common depressive symptoms, measured with Montgomery–Åsberg Depression Rating Scale (MADRS) for two-time points, were assessed by linear mixed models, respectively, for patients showing TRD and treatment response. A corrected p threshold of 0.001 was applied. Results Overall symptom load reflected by MADRS (p 4) for these items both before and after treatment (all p ≤ 0.001). Conclusions In this naturalistic sample of severely ill depressed patients, antidepressant treatment protocols were equally effective in addressing TRD in old age. However, specific symptoms such as sadness, appetite, and concentration showed an age-dependent presentation, impacting residual symptoms in severely affected TRD patients and calling for a precision approach by a better integration of age profiles in treatment recommendations.
Gernot Fugger, Thomas Waldhör, Barbara Hinterbuchinger, Nathalie Pruckner, Daniel König, Andrea Gmeiner, Sandra Vyssoki, Benjamin Vyssoki, and Matthäus Fellinger
Subjects
Depression, Gender, Sex, Age, Hospitalization, Length of stay, Psychiatry, RC435-571
Abstract
Abstract Background The prevalence of major depressive disorder (MDD) in women is up to 50% higher as compared to men. However, little is known about discrepancies in health care utilization between depressed female and male patients. Consequently, the aim of the present study was to elucidate gender differences regarding the frequency of hospital admissions and the length of inpatient treatment for MDD across the lifespan. Methods This nationwide, registry-based study analyzed all inpatient admissions in psychiatric hospitals due to recurrent/non-recurrent MDD episodes according to ICD-10 (moderate (F32/33.1), severe (F32/33.2), severe with psychotic features (F32/33.3)) in Austria across 14 years. We calculated weekly admission rates per 100,000 patients by directly age-standardized rates. Results Across 232,289 admissions (63.2% female) the population based admission rates in MDD were significantly higher in women (p
Gernot Fugger, Lucie Bartova, Markus Dold, and Siegfried Kasper
Subjects
General Medicine
Abstract
ZusammenfassungDie unipolare Depression zählt weltweit zu den häufigsten psychischen Erkrankungen und ist mit einer enormen Krankheitslast assoziiert. Trotz Verfügbarkeit von zahlreichen effektiven und gut verträglichen antidepressiv wirksamen Psychopharmakotherapeutika erreicht nur etwa ein Drittel unserer Patientinnen und Patienten auf eine etablierte antidepressive „First-line-Therapie“ eine vollständige Remission. Im Gegensatz dazu spricht ein weiteres Drittel aller Betroffenen auf zwei konsekutive, adäquate antidepressive Therapien mit gleich oder unterschiedlich wirkenden Antidepressiva, die ausreichend hoch dosiert und genügend lange verabreicht wurden, nur unzureichend an und erfüllt somit die Kriterien einer therapieresistenten Depression (TRD). Das Vorhandensein einer TRD stellt für Behandler häufig eine sehr anspruchsvolle, klinische Herausforderung dar. Der folgende Artikel unterstreicht die Wichtigkeit der therapeutischen Beziehung und effektiver, transparenter Kommunikation sowie die absolute Notwendigkeit, das therapeutische Vorgehen strikt nach bestehenden Leitlinien auszurichten, um einen optimalen Therapieerfolg zu gewährleisten. Ein Fallbericht skizziert eine erfolgreiche Anwendung von Esketamin-Nasenspray als höchst effektive neu zugelassene Behandlungsoption.
Introduction Due to favorable antidepressant (AD) efficacy and tolerability, selective-serotonin reuptake inhibitors (SSRIs) are consistently recommended as substances of first choice for the treatment of major depressive disorder (MDD) in international guidelines. However, little is known about the real-world clinical correlates of patients primarily prescribed SSRIs in contrast to those receiving alternative first-line ADs. Methods These secondary analyses are based on a naturalistic, multinational cross-sectional study conducted by the European Group for the Study of Resistant Depression at ten research sites. We compared the socio-demographic and clinical characteristics of 1410 patients with primary MDD, who were either prescribed SSRIs or alternative substances as first-line AD treatment, using chi-squared tests, analyses of covariance, and logistic regression analyses. Results SSRIs were prescribed in 52.1% of MDD patients who showed lower odds for unemployment, current severity of depressive symptoms, melancholic features, suicidality, as well as current inpatient treatment compared to patients receiving alternative first-line ADs. Furthermore, patients prescribed SSRIs less likely received add-on therapies including AD combination and augmentation with antipsychotics, and exhibited a trend towards higher response rates. Conclusion A more favorable socio-demographic and clinical profile associated with SSRIs in contrast to alternative first-line ADs may have guided European psychiatrists’ treatment choice for SSRIs, rather than any relevant pharmacological differences in mechanisms of action of the investigated ADs. Our results must be cautiously interpreted in light of predictable biases resulting from the open treatment selection, the possible allocation of less severely ill patients to SSRIs as well as the cross-sectional study design that does not allow to ascertain any causal conclusions.
Nathalie Pruckner, Alessandro Serretti, Thomas Waldhör, Barbara Hinterbuchinger, Matthäus Fellinger, Daniel König, Benjamin Vyssoki, Gernot Fugger, Sandra Vyssoki, Andrea Gmeiner, Fellinger M., Waldhor T., Serretti A., Hinterbuchinger B., Pruckner N., Konig D., Gmeiner A., Vyssoki S., Vyssoki B., and Fugger G.
Subjects
Male, Bipolar Disorder, Major Depressive Disorder, Seasonal variation, Psychotic depression, Age, Hospitalisation, Sex characteristics, medicine, Humans, In patient, Depressive symptoms, Depressive Disorder, Major, business.industry, Seasonal Affective Disorder, Seasonality, medicine.disease, Mental health, Hospitalization, Psychiatry and Mental health, Clinical Psychology, Psychotic Disorders, Major depressive disorder, Female, business, Demography
Abstract
Background Aside from the concept of seasonal affective disorder, the evidence for a seasonal pattern (SP) of major depressive disorder (MDD) is controversial. Furthermore, the effect of sex and age is still unclear. Methods This is a nationwide, registry-based study assessing all inpatient admissions in mental health hospitals due to MDD episodes according to ICD-10 (moderate (F32/33.1), severe (F32/33.2) and severe with psychotic features (F32/33.3)) in Austria across 14 years. Calculations were based on deviations from expected monthly admissions. Results The sample comprised 231,824 hospitalisations (36.8% men) for MDD. A significant SP (p=0.001) in moderate and severe depressive episodes in both women and men with decreased admission rates in the summer months and December was detected. In psychotic depression a significant SP was only evidenced in women (p = 0.002, men: p = 0.291). Patients older than 55 years had a reduced SP compared to those being younger. Limitations Only anonymised admission data of inpatient treatments were available. Hospitalization rates cannot fully be equated to the occurrence of MDD. Conclusions The current study indicates a seasonal variation in MDD symptoms that may go beyond seasonal affective disorder. Knowledge about the predictability of depressive symptoms in patients should encourage preventive strategies.
Lucie Bartova, Gernot Fugger, Markus Dold, Alexander Kautzky, Giuseppe Fanelli, Raffaella Zanardi, Diego Albani, Ana Weidenauer, Dan Rujescu, Daniel Souery, Julien Mendlewicz, Stuart Montgomery, Joseph Zohar, Chiara Fabbri, Alessandro Serretti, and Siegfried Kasper
Subjects
Psychiatry and Mental health, Clinical Psychology, All institutes and research themes of the Radboud University Medical Center, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Abstract
Contains fulltext : 292377.pdf (Publisher’s version ) (Open Access) BACKGROUND: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are among the most frequently prescribed antidepressants (ADs) for major depressive disorder (MDD), with an increasing trend in the last decade. Given the relative dearth of information regarding rationales for their preferred use as first-line ADs in the broad clinical routine, the present study systematically investigated real-world characteristics of MDD patients prescribed either SNRIs or other AD substances across different countries and treatment settings. METHODS: In the present secondary analyses based on a large European, multi-site, naturalistic and cross-sectional investigation with a retrospective assessment of treatment outcome, we firstly defined the proportion of MDD patients receiving SNRIs as first-line AD psychopharmacotherapy and secondly compared their sociodemographic and clinical characteristics to those patients prescribed alternative first-line ADs during their current major depressive episode (MDE). RESULTS: Within the total sample of 1410 MDD patients, 336 (23.8 %) received first-line SNRIs. Compared to other ADs, SNRIs were significantly associated with inpatient care, suicidality and treatment resistance during the current MDE, and a longer lifetime duration of psychiatric hospitalizations. Moreover, greater severity of depressive symptoms at study entry, higher daily doses of the administered ADs, as well as more frequent prescriptions of psychopharmacotherapeutic add-on strategies in general and antipsychotic augmentation in particular, were significantly related to first-line SNRIs. CONCLUSIONS: Considering the limitations of a cross-sectional and retrospective study design, our data point towards a preferred use of first-line SNRIs in a generally more severely ill MDD patients, although they did not lead to superior treatment outcomes compared to alternative ADs.
Lucie Bartova, Richard Frey, Gernot Fugger, Marleen M. M. Mitschek, Alessandro Serretti, Alexander Kautzky, Laura Mandelli, Daniel Souery, Joseph Zohar, Marius Hienert, Siegfried Kasper, Ana Weidenauer, Julien Mendlewicz, Chiara Fabbri, Markus Dold, Stuart Montgomery, Bartova L., Dold M., Fugger G., Kautzky A., Mitschek M.M.M., Weidenauer A., Hienert M.G., Frey R., Mandelli L., Zohar J., Mendlewicz J., Souery D., Montgomery S., Fabbri C., Serretti A., and Kasper S.
Subjects
Male, medicine.medical_specialty, Disease onset, male depression, 03 medical and health sciences, Depressive Disorder, Treatment-Resistant, 0302 clinical medicine, Disease severity, Thyroid dysfunction, Internal medicine, medicine, gender, sex, Humans, Depression (differential diagnoses), Research Articles, Asthma, Cross-Sectional Studie, Depressive Disorder, Major, major depressive disorder, business.industry, Depression, treatment response, Sex related, medicine.disease, Antidepressive Agents, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Migraine, Major depressive disorder, Antidepressive Agent, Female, business, 030217 neurology & neurosurgery, Human, Research Article
Abstract
Background: Sex-related effects on the evolution and phenotype of major depressive disorder (MDD) were reported previously. Methods: This European multicenter cross-sectional study compared sociodemographic, clinical, and treatment patterns between males and females in a real-world sample of 1410 in- and outpatients with current MDD. Results: Male MDD patients (33.1%) were rather inpatients, suffered from moderate to high suicidality levels, received noradrenergicand specific serotonergic antidepressants (ADs) as first-line AD treatment, generally higher mean AD daily doses, and showed a trend towards a more frequent administration of add-on treatments. Female MDD patients (66.9%) were rather outpatients, experienced lower suicidality levels, comorbid thyroid dysfunction, migraine, asthma, and a trend towards earlier disease onset. Conclusions: The identified divergencies may contribute to the concept of maleand female depressive syndromes and serve as predictors of disease severity and course, as they reflect phenomena that were repeatedly related to treatment-resistant depression (TRD). Especially the greater necessity of inpatient treatment and more complex psychopharmacotherapy in men may reflect increased therapeutic efforts undertaken to treat suicidality and to avoid TRD. Hence, considering sex may guide the diagnostic and treatment processes towards targeting challenging clinical manifestations including comorbidities and suicidality, and prevention of TRD and chronicity.
Jakob Unterholzner, Pia Baldinger-Melich, Lucie Bartova, Valentin Popper, Gernot Fugger, Richard Frey, and A. Strnad
Subjects
Gynecology, medicine.medical_specialty, Political science, medicine, General Medicine
Abstract
ZusammenfassungEinschränkungen der Bewegungsfreiheit psychiatrischer Patienten im Sinne einer mechanischen Fixierung sind in Österreich im Rahmen des Unterbringungsgesetzes zur Abwehr von Selbst- und Fremdgefährdung zulässig, sofern deren Anwendung verhältnismäßig ist. Neben rechtlichen Aspekten sind im Rahmen von Bewegungseinschränkungen auf das Krankenbett ethische Aspekte in Zusammenhang mit einem sorgfältigen klinischen Management unentbehrlich. International gibt es Bestrebungen, Zwangsmaßnahmen dieser Art in der Psychiatrie zu reduzieren. Breiter Konsensus besteht darüber, dass deren Anwendung als Ultima-Ratio-Intervention zu sehen ist, die ausschließlich in Situationen eingesetzt werden soll, die nicht durch gelindere Maßnahmen zu bewältigen sind. Die vorgestellten Fallvignetten aus der psychiatrischen Intermediate Care Station der Wiener Universitätsklinik sollen dies verdeutlichen.
Richard Frey, Gernot Fugger, Lucie Bartova, Siegfried Kasper, Alessandro Serretti, Julien Mendlewicz, Joseph Zohar, Marleen M. M. Mitschek, Daniel Souery, Markus Dold, Stuart Montgomery, Chiara Fabbri, Fugger G., Dold M., Bartova L., Mitschek M.M.M., Souery D., Mendlewicz J., Serretti A., Zohar J., Montgomery S., Fabbri C., Frey R., and Kasper S.
Subjects
Adult, Male, medicine.medical_specialty, AcademicSubjects/MED00415, Migraine Disorders, Comorbidity, Major depressive disorder, Pharmacologie, Serotonin syndrome, Depressive Disorder, Treatment-Resistant, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Internal medicine, Outcome Assessment, Health Care, mental disorders, Prevalence, medicine, Humans, Agomelatine, clinical aspects, migraine, Pharmacology (medical), 030212 general & internal medicine, Depression (differential diagnoses), Pharmacology, Depressive Disorder, Major, AcademicSubjects/SCI01870, business.industry, Brief Report, Middle Aged, medicine.disease, Europe, Psychiatry and Mental health, Migraine, Practice Guidelines as Topic, Antidepressant, Female, clinical aspect, medicine.symptom, business, 030217 neurology & neurosurgery, Psychiatrie, medicine.drug
Abstract
BACKGROUND: The present multicenter study aimed at defining the clinical profile of patients with major depressive disorder (MDD) and comorbid migraine. METHODS: Demographic and clinical information for 1410 MDD patients with vs without concurrent migraine were compared by descriptive statistics, analyses of covariance, and binary logistic regression analyses. RESULTS: The point prevalence rate for comorbid migraine was 13.5% for female and 6.2% for male patients. MDD + migraine patients were significantly younger, heavier, more likely female, of non-Caucasian origin, outpatient, and suffering from asthma. The presence of MDD + migraine resulted in a significantly higher functional disability. First-line antidepressant treatment strategy revealed a trend towards agomelatine. Second-generation antipsychotics were significantly less often administered for augmentation treatment in migraineurs. Overall, MDD + migraine patients tended to respond worse to their pharmacotherapy. CONCLUSION: Treatment guidelines for comorbid depression and migraine are warranted to ensure optimal efficacy and avoid possible pitfalls in psychopharmacotherapy, including serotonin syndrome., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published
Alessandro Serretti, Julien Mendlewicz, Alexander Kautzky, Raffaella Zanardi, Siegfried Kasper, Gernot Fugger, Joseph Zohar, Chiara Fabbri, Daniel Souery, Markus Dold, Giuseppe Fanelli, Stuart Montgomery, Lucie Bartova, Dan Rujescu, Fugger, Gernot, Bartova, Lucie, Dold, Marku, Fabbri, Chiara, Fanelli, Giuseppe, Zanardi, Raffaella, Kautzky, Alexander, Zohar, Joseph, Souery, Daniel, Mendlewicz, Julien, Montgomery, Stuart, Rujescu, Dan, Serretti, Alessandro, and Kasper, Siegfried
Subjects
Male, medicine.medical_specialty, Randomization, Dose, Antimanic Agent, Suicidal risk, Treatment outcome, Antidepressant, Major depressive disorder, Augmentation, Socioeconomic Factor, Benzodiazepines, Depressive Disorder, Treatment-Resistant, All institutes and research themes of the Radboud University Medical Center, Antimanic Agents, Medicine, Humans, Psychiatry, Biological Psychiatry, Depression (differential diagnoses), Pharmacology, Cross-Sectional Studie, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Benzodiazepine, business.industry, Middle Aged, medicine.disease, Antidepressive Agents, Europe, Cross-Sectional Studies, Treatment Outcome, Multicenter study, Socioeconomic Factors, Second-generation antipsychotic, Combination, Antidepressive Agent, Antidepressive Agents, Second-Generation, Female, Drug Therapy, Combination, business, Human
Abstract
About two thirds of the patients with major depressive disorder (MDD) do not sufficiently respond to monotherapy with antidepressants (ADs) which makes them reliant on further treatment approaches. Hereby, combination of different ADs and augmentation with second-generation antipsychotics (SGAs) are widely used and recommended psychopharmacotherapeutic strategies. The present secondary analyses are based on an international, naturalistic, cross-sectional multicenter study conducted by the European Group for the Study of Resistant Depression. Comparing socio-demographic and clinical characteristics of 436 adult MDD patients receiving either SGAs (N = 191, 43.8%) or ADs (N = 245, 56.2%), that were additionally administered to their first-line AD psychopharmacotherapy, we aimed to identify possible trajectories of decision-making for clinicians regarding which treatment option to prefer in individual patients. Our most robust findings represent an association of SGA augmentation with the presence of psychotic symptoms, longer mean duration of lifetime psychiatric hospitalizations, employment of further augmentation strategies with mood-stabilizers and benzodiazepines, and a trend towards higher mean daily dosages of their first-line ADs and current suicidal risk. Treatment outcome was not significantly different between patients receiving either SGA augmentation or AD combination. Being aware of limitations inherent to the cross-sectional study design and the lack of randomization, more severe and rather chronic conditions in MDD seemed to encourage clinicians to choose SGA augmentation over AD combination. The fact that mood-stabilizers and/or benzodiazepines were more frequently co-administered with SGAs may represent a requirement of an overall refined psychopharmacotherapy including additional fast-acting agents with potent AD, tranquilizing and anti-suicidal effects in MDD patients experiencing challenging clinical manifestations. New glutamatergic substances seem to be promising in this regard.
Background Augmentation with second-generation antipsychotics (SGAs) represents an evidence-based psychopharmacotherapeutic strategy recommended in case of insufficient response to the first-line antidepressant (AD) treatment in major depressive disorder (MDD). Comparative evidence regarding efficacy and prescription preferences of the individual SGAs is scarce. Methods In the scope of this European, multi-site, naturalistic cross-sectional investigation with retrospective assessment of treatment outcome, we compared sociodemographic and clinical characteristics of 187 MDD patients receiving either quetiapine (n = 150) or aripiprazole (n = 37) as augmentation of their first-line AD psychopharmacotherapy. Results Comorbid posttraumatic stress disorder and diabetes were significantly associated with aripiprazole augmentation in our primary and post-hoc binary logistic regression analyses. Furthermore, we identified an association between aripiprazole co-administration and the presence of additional psychotic features, higher rates of AD combination treatment, and a longer duration of psychiatric hospitalizations during the lifetime, which, however, lost significance after correcting for multiple comparisons. Regarding treatment outcome, we found a trend of higher response rates and greater reductions in severity of depressive symptoms in MDD patients dispensed quetiapine. Conclusions Factors associated with a more chronic and severe profile of MDD seem to encourage clinicians to choose aripiprazole over quetiapine, that was, however, administered in the majority of our MDD patients, which might reflect the current approval situation allowing to prescribe exclusively quetiapine as on-label augmentation in MDD in Europe. Given the retrospective assessment of treatment response, the markedly smaller proportion of patients receiving aripiprazole augmentation generally showing an unfavorable disease profile, and the partially heterogeneous statistical robustness of our findings, further studies are required to elaborate on our observation and to generate unambiguous recommendations regarding the choice of first-line SGA augmentation in MDD.
Gernot Fugger, Lucie Bartova, Chiara Fabbri, Giuseppe Fanelli, Raffaella Zanardi, Markus Dold, Alexander Kautzky, Dan Rujescu, Daniel Souery, Julien Mendlewicz, Joseph Zohar, Stuart Montgomery, Alessandro Serretti, Siegfried Kasper, Fugger, Gernot, Bartova, Lucie, Fabbri, Chiara, Fanelli, Giuseppe, Zanardi, Raffaella, Dold, Marku, Kautzky, Alexander, Rujescu, Dan, Souery, Daniel, Mendlewicz, Julien, Zohar, Joseph, Montgomery, Stuart, Serretti, Alessandro, and Kasper, Siegfried
Subjects
Depressive Disorder, Major, Mirtazapine, Major depressive disorder, Mianserin, Antidepressive Agents, Tricyclic, Antidepressive Agents, Antidepressant treatment, Psychiatry and Mental health, Clinical Psychology, Noradrenergic and specific serotonergic antidepressant, Phenotype, Humans, Antidepressive Agent, Human
Abstract
Since selective serotonin reuptake inhibitors, that are recommended as first-line antidepressant psychopharmacotherapy for major depressive disorder (MDD), may not be the optimal choice for every patient, antidepressants with different modes of action exerting a distinct set of expectant effects, represent a valuable alternative. Despite the previously observed increased prescription rates of noradrenergic and specific serotonergic antidepressants (NaSSAs) particularly mirtazapine in Europe, the individual profiles of patients primarily prescribed NaSSAs in real-world settings have not been systematically investigated yet. In this secondary analysis based on a European, cross-sectional, naturalistic, multicenter study involving 1410 adult males and females with primary MDD, sociodemographic and clinical variables were compared between patients dispensed NaSSAs and those with alternative first-line antidepressants. Hereby, NaSSAs were administered in 8.6 % of the sample (mirtazapine: n = 114, mianserin: n = 7). We detected associations with older mean age, male sex, unemployment, as well as additional melancholic and catatonic features, inpatient treatment, lower mean daily dosages of the administered antidepressants but higher rates of augmentation with low-potency antipsychotics, and greater mean reductions of depressive symptoms during their current major depressive episodes. Although the study design is unsuitable to draw any causal conclusions, our findings provide a realistic picture of patients eligible for first-line antidepressant treatment with NaSSAs, especially mirtazapine, and underscore the role of this AD substance class in severe MDD. Further, they may represent a promising basis for future systematic research focusing on precision diagnostics and treatment in MDD, that would ideally result in faster responses and better outcomes, especially in the so-called difficult-to-treat conditions including treatment resistant depression.
Richard Frey, Anne Eckert, Anna Höflich, Siegfried Kasper, Rupert Lanzenberger, Thomas Vanicek, Arkadiusz Komorowski, Zoltan Micskei, Sergej Milovic, Gernot Fugger, Georg S. Kranz, and Benjamin Vyssoki
Subjects
Adult, Male, Oncology, medicine.medical_specialty, Bipolar Disorder, medicine.medical_treatment, Stimulation, behavioral disciplines and activities, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Electroconvulsive therapy, Internal medicine, mental disorders, Neuroplasticity, Secondary Prevention, medicine, Humans, In patient, Electroconvulsive Therapy, Depressive symptoms, Depression (differential diagnoses), Aged, Brain-derived neurotrophic factor, brain‐derived neurotrophic factor, Depressive Disorder, unipolar and bipolar affective disorder, business.industry, continuation electroconvulsive therapy, Brain-Derived Neurotrophic Factor, Original Articles, Middle Aged, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, depression, Original Article, Female, business, 030217 neurology & neurosurgery, After treatment
Abstract
Introduction Continuation electroconvulsive therapy (c‐ECT) is highly effective for the prevention of depressive symptom relapse. There is a lack of understanding, about how c‐ECT works in humans, particularly with regard to its effects on brain derived neurotrophic factor (BDNF) concentrations. Here, we aimed to close a gap in the literature by evaluating BDNF levels in patients receiving c‐ECT. Methods We included 13 patients with either unipolar or bipolar depression (mean age ± SD: 55.5 ± 17.1; f/m: 10/3; unipolar/bipolar: 10/3) who received between one and four c‐ECT (average per patient: 2.8). Serum BDNF (sBDNF) levels were assessed before and after each c‐ECT sessions. Clinical assessments were also administered both before and after treatment. Results Our analysis revealed a significant increase in sBDNF after each treatment (c‐ECT 1‐3: P
Despite plenty of effective antidepressant (AD) treatments, the outcome of major depressive disorder (MDD) is often unsatisfactory, probably due to improvable exploitation of available therapies. This European, cross-sectional, naturalistic multicenter study investigated the frequency of additional psychotherapy in terms of a manual-driven psychotherapy (MDP) in 1410 adult in- and outpatients with MDD, who were primarily treated with AD psychopharmacotherapy. Socio-demographic and clinical patterns were compared between patients receiving both treatments and those lacking concomitant MDP. In a total of 1279 MDD patients (90.7%) with known status of additional MDP, those undergoing a psychopharmacotherapy-MDP combination (31.2%) were younger, higher educated, more often employed and less severely ill with lower odds for suicidality as compared to patients receiving exclusively psychopharmacotherapy (68.8%). They experienced an earlier mean age of MDD onset, melancholic features, comorbid asthma and migraine and received lower daily doses of their first-line ADs. While agomelatine was more often established in these patients, MDD patients without MDP received selective serotonin reuptake inhibitors more frequently. These two patient groups did not differ in terms of response, non-response and treatment resistant depression (TRD). Accordingly, the employment of additional MDP could not be related to better treatment outcomes in MDD. The fact that MDP was applied in a minority of patients with rather beneficial socio-demographic and clinical characteristics might reflect inferior accessibility of these psychotherapeutic techniques for socially and economically disadvantaged populations., SCOPUS: ar.j, info:eu-repo/semantics/published
Panagiotis Ferentinos, Stefano Porcelli, Stuart Montgomery, Alessandro Serretti, Julien Mendlewicz, Daniel Souery, Siegfried Kasper, Alexander Kautzky, Lucie Bartova, Dimitris Dikeos, Joseph Zohar, Markus Dold, George N. Papadimitriou, Gernot Fugger, Dold, Marku, Bartova, Lucie, Fugger, Gernot, Kautzky, Alexander, Souery, Daniel, Mendlewicz, Julien, Papadimitriou, George N, Dikeos, Dimitri, Ferentinos, Panagioti, Porcelli, Stefano, Serretti, Alessandro, Zohar, Joseph, Montgomery, Stuart, and Kasper, Siegfried
Subjects
Male, Cross-sectional study, suicidality, Prevalence, Comorbidity, Pharmacologie, Suicidality, Treatment response, Regular Research Articles, Depressive Disorder, Treatment-Resistant, 0302 clinical medicine, Pharmacology (medical), Depression (differential diagnoses), Middle Aged, Antidepressive Agents, 3. Good health, Europe, Psychiatry and Mental health, Suicide, depression, Major depressive disorder, Female, Psychosocial, medicine.medical_specialty, 03 medical and health sciences, medicine, Humans, Augmentation/combination treatment, Psychiatry, Retrospective Studies, Pharmacology, Psychiatric Status Rating Scales, Depressive Disorder, Major, major depressive disorder, business.industry, Hamilton Rating Scale for Depression, treatment response, Retrospective cohort study, medicine.disease, 030227 psychiatry, Editor's Choice, augmentation/combination treatment, Cross-Sectional Studies, Socioeconomic Factors, business, 030217 neurology & neurosurgery, Psychiatrie
Abstract
Background: This European multicenter study aimed to elucidate suicidality in major depressive disorder. Previous surveys suggest a prevalence of suicidality in major depressive disorder of ≥50%, but little is known about the association of different degrees of suicidality with socio-demographic, psychosocial, and clinical characteristics. Methods: We stratified 1410 major depressive disorder patients into 3 categories of suicidality based on the Hamilton Rating Scale for Depression item 3 (suicidality) ratings (0 = no suicidality; 1–2 = mild/moderate suicidality; 3–4 = severe suicidality). Chi-squared tests, analyses of covariance, and Spearman correlation analyses were applied for the data analyses. Results: The prevalence rate of suicidality in major depressive disorder amounted to 46.67% (Hamilton Rating Scale for Depression item 3 score ≥1). 53.33% were allocated into the no, 38.44% into the mild/moderate, and 8.23% into the severe suicidality patient group. Due to the stratification of our major depressive disorder patient sample according to different levels of suicidality, we identified some socio-demographic, psychosocial, and clinical variables differentiating from the patient group without suicidality already in presence of mild/moderate suicidality (depressive symptom severity, treatment resistance, psychotic features, add-on medications in general), whereas others separated only when severe suicidality was manifest (inpatient treatment, augmentation with antipsychotics and benzodiazepines, melancholic features, somatic comorbidities). Conclusions: As even mild/moderate suicidality is associated with a failure of achieving treatment response, adequate recognition of this condition should be ensured in the clinical practice., SCOPUS: ar.j, info:eu-repo/semantics/published
Siegfried Kasper, Rupert Lanzenberger, Markus Dold, Gernot Fugger, and Martin Aigner
Subjects
Fluphenazine, medicine.medical_specialty, Positive and Negative Syndrome Scale, business.industry, medicine.medical_treatment, law.invention, Psychiatry and Mental health, Randomized controlled trial, Tolerability, law, Internal medicine, medicine, Quetiapine, Ziprasidone, Antipsychotic, Literature survey, business, Psychiatry, medicine.drug
Abstract
ObjectivesThis meta-analysis investigates if dose increase of an antipsychotic drug (high-dose treatment, dose escalation) is advantageous for schizophrenic patients who failed to respond adequately to standard-dose treatment with the same antipsychotic.MethodsWithin a systematic literature survey, we identified all randomized controlled trials (RCTs) comparing a dose increase directly to standard-dose continuation treatment in schizophrenic subjects with initial non-response to prospective standard-dose pharmacotherapy with the same antipsychotic. The primary outcome was mean change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes were dichotomous response and attrition rates. Study selection and data extraction were conducted independently by two authors. We calculated effect sizes (Hedges's g and risks ratios) using the Mante–Haenszel random-effects model. Meta-regression analyses were performed to explore the influence of the degree of the dose increase on effect sizes.ResultsFive trials (n = 348) examining quetiapine (n = 2, n = 191), ziprasidone (n = 1, n = 75), haloperidol (n = 1, n = 48), and fluphenazine (n = 1, n = 34) were included. We found no significant between-group differences for the mean PANSS/BPRS total score change, even not when itemized according to the individual antipsychotic agents. There were no between-group differences for response and dropout rates. The non-significant meta-regressions indicate no impact of the different amounts of dose increments on effect sizes.ConclusionsWe found no evidence for the efficacy of a dose escalation after initial non-response to standard-dose pharmacotherapy as general advisable treatment strategy. As the high-dose treatment was not accompanied by significant increased attrition rates, appropriate tolerability and acceptability of this pharmacological option can be assumed.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Introduction The observance of possible somatic and environmental causes is essential to improve safety and efficacy in the treatment of agitated states. Severe agitation is considered a medical emergency requiring immediate psychopharmacologic intervention. Objectives To establish a clinically applicable consensus statement based on evidence- as well as eminence-based medicine with respect to schizophrenia and mania. Methods The recommendations given are based on information from psychopharmacologic treatment studies as well as logistic and practical factors intrinsic to clinical settings. Results Atypical antipsychotics given orally together with Lorazepam are considered the first-line treatment of agitated states in psychotic patients. Adequate communication with the patient is considered essential for effective oral administration. A novel alternative, Loxapine 4.5 mg or 9.1 mg (approved by the EMA 2013), is administered via an inhaler and exerts its sedative effects within 10 minutes. Inhalation may carry the benefit of greater patient acceptance. In contrast, intramuscular administration of antipsychotics is typically perceived by patients to be more invasive and persuasion or coercion may be necessary in severely ill patients. On the other hand, Aripiprazole, Haloperidole, Olanzapine and Ziprasidone show clinical efficacy within 15-30 minutes in psychopharmacologic trials when administered intramuscularly (i.m.). When taking extrapyramidal symptoms, QTc-prolongation and potential for combination with benzodiazepines into account, Aripiprazole i.m. carries the highest recommendation grade. Lorazepam may be administered intravenously. Currently, no antipsychotics are approved for intravenous administration. Conclusion This project gives recommendations which consider risk-benefit ratios and patient compliance.
Background Although discussed controversially, coercive practices during involuntary admission are common in mental health services. The impact of physical restraints on patients has not been sufficiently studied. Aims To investigate the subjective perception of patients during and after physical restraint. Method 47 patients in a psychiatric intermediate care facility experiencing belt fixation were interviewed and filled out self-assessment forms at 4 visits. Results The median duration of restraint was 99 hours. Median VAS scores indicated moderate levels of anxiety. With increasing time span from the fixation, memory regarding this event decreased and patients experienced a regain of self-control. Consistently, 50% perceived high levels of coercion at admission, PTSD could be supposed in 25% of the patients. Conclusion Despite a considerable restraint of freedom, distress related to belt-fixation seems acceptable in our sample. Patients’ disapproval concerning restraint measures seems to diminish with time, probably related to decreasing memory regarding the fixation practice.
ZOLPIDEM, DELIRIUM, CLOZAPINE, SCHIZOAFFECTIVE disorders, YOUNG adults
Abstract
The non-benzodiazepine hypnotic zolpidem is frequently administered as a short term psychopharmacotherapy for insomnia. Although it is well-established in a broad clinical routine and often well-tolerated, severe delirium and complex sleep behavior were reported in rare cases. Hereby, it remains unclear whether zolpidem's potential for delirium might be enhanced when combined with further psychopharmacotherapeutics. The present case report portrays a young male Caucasian inpatient with schizoaffective disorder, who was admitted due to severe hyperactive delirium after a single dose of zolpidem 10mg that was administered in addition to already established psychopharmacotherapy including clozapine 200 mg/day, aripiprazole 15 mg/day and cariprazine 4.5 mg/day. In detail, disorientation, agitation, confabulations, bizarre behavior, and anterograde amnesia occurred shortly after ingestion of zolpidem and gained in intensity within a couple of hours. Once zolpidem was discontinued, the abovementioned symptoms subsided completely and did not reoccur. Since a clear temporal association could be drawn between the intake of zolpidem and the onset of hyperactive delirium, the present clinical experience should serve as a cautionary note for combining potent sedative-hypnotics and substances with anticholinergic properties, even in young adults in a good general condition. Moreover, our case argues for the necessity of further research into the pathomechanism of the interaction potential of non-benzodiazepines as zolpidem, especially with substances exerting anticholinergic properties, which are known for their potential to precipitate delirium. Therefore, the metabolic pathways of the concurrently administered substances should be further taken into account. [ABSTRACT FROM AUTHOR]
PULMONARY fibrosis, LAMOTRIGINE, DRUG side effects, MENTAL depression, DRUG interactions, LENNOX-Gastaut syndrome, ASPIRATION pneumonia
Abstract
The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug- induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare. [ABSTRACT FROM AUTHOR]
Objective: The incidence of thyroid dysfunction (TD) and major depressive disorder (MDD) is increasing year by year in the general population. However, the prevalence and correlates of TD in first-episode drug-naive (FEDN) MDD patients have not been explored. This study sought to fill this gap and examine the association between TD and MDD. Methods: We recruited 1,289 FEDN MDD patients aged 18~45years. A total of 1,289 FEDN MDD outpatients were recruited. Demographical and suicide data were collected for each patient, and lipid profiles, thyroid function, and fasting blood glucose (FBG) levels were measured. The Hamilton Depression Scale 17 (HAMD-17) was assessed for depression. Results: The prevalence of TD in young FEDN MDD patients was 64.86%. Compared with those without TD, patients with TD had longer duration of illness, greater HAMD score, higher BMI, TG, TC, and LDL-C levels, and higher suicide attempt rates, but lower HDL-C and FBG levels. Further logistic regression indicated that duration of illness, HAMD score, TC, HDL-C, BMI, and FBG levels were significantly associated with TD. Limitations: No causal relationship can be drawn due to the cross-sectional design. Conclusion: TD is common in young FEDN MDD patients. So clinicians should monitor thyroid function in patients with MDD. [ABSTRACT FROM AUTHOR]
I JCM i was able to uphold its high standards for published papers due to the outstanding efforts of our reviewers. Regardless of whether the articles they examined were ultimately published, the editors would like to express their appreciation and thank the following reviewers for the time and dedication that they have shown I JCM i : ht Footnotes 1 B Disclaimer/Publisher's Note: b The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). Thanks to the efforts of our reviewers in 2022, the median time to first decision was 20 days and the median time to publication was 41 days. [Extracted from the article]
Background Augmentation with second-generation antipsychotics (SGAs) represents an evidence-based psychopharmacotherapeutic strategy recommended in case of insufficient response to the first-line antidepressant (AD) treatment in major depressive disorder (MDD). Comparative evidence regarding efficacy and prescription preferences of the individual SGAs is scarce. Methods In the scope of this European, multi-site, naturalistic cross-sectional investigation with retrospective assessment of treatment outcome, we compared sociodemographic and clinical characteristics of 187 MDD patients receiving either quetiapine (n = 150) or aripiprazole (n = 37) as augmentation of their first-line AD psychopharmacotherapy. Results Comorbid posttraumatic stress disorder and diabetes were significantly associated with aripiprazole augmentation in our primary and post-hoc binary logistic regression analyses. Furthermore, we identified an association between aripiprazole co-administration and the presence of additional psychotic features, higher rates of AD combination treatment, and a longer duration of psychiatric hospitalizations during the lifetime, which, however, lost significance after correcting for multiple comparisons. Regarding treatment outcome, we found a trend of higher response rates and greater reductions in severity of depressive symptoms in MDD patients dispensed quetiapine. Conclusions Factors associated with a more chronic and severe profile of MDD seem to encourage clinicians to choose aripiprazole over quetiapine, that was, however, administered in the majority of our MDD patients, which might reflect the current approval situation allowing to prescribe exclusively quetiapine as on-label augmentation in MDD in Europe. Given the retrospective assessment of treatment response, the markedly smaller proportion of patients receiving aripiprazole augmentation generally showing an unfavorable disease profile, and the partially heterogeneous statistical robustness of our findings, further studies are required to elaborate on our observation and to generate unambiguous recommendations regarding the choice of first-line SGA augmentation in MDD. [ABSTRACT FROM AUTHOR]
Background The present multicenter study aimed at defining the clinical profile of patients with major depressive disorder (MDD) and comorbid migraine. Methods Demographic and clinical information for 1410 MDD patients with vs without concurrent migraine were compared by descriptive statistics, analyses of covariance, and binary logistic regression analyses. Results The point prevalence rate for comorbid migraine was 13.5% for female and 6.2% for male patients. MDD + migraine patients were significantly younger, heavier, more likely female, of non-Caucasian origin, outpatient, and suffering from asthma. The presence of MDD + migraine resulted in a significantly higher functional disability. First-line antidepressant treatment strategy revealed a trend towards agomelatine. Second-generation antipsychotics were significantly less often administered for augmentation treatment in migraineurs. Overall, MDD + migraine patients tended to respond worse to their pharmacotherapy. Conclusion Treatment guidelines for comorbid depression and migraine are warranted to ensure optimal efficacy and avoid possible pitfalls in psychopharmacotherapy, including serotonin syndrome. [ABSTRACT FROM AUTHOR]
INPATIENT care, LENGTH of stay in hospitals, PSYCHIATRIC hospitals, MENTAL depression, PSYCHOTIC depression, HOSPITAL admission & discharge, MEDICAL care
Abstract
Background: The prevalence of major depressive disorder (MDD) in women is up to 50% higher as compared to men. However, little is known about discrepancies in health care utilization between depressed female and male patients. Consequently, the aim of the present study was to elucidate gender differences regarding the frequency of hospital admissions and the length of inpatient treatment for MDD across the lifespan. Methods: This nationwide, registry-based study analyzed all inpatient admissions in psychiatric hospitals due to recurrent/non-recurrent MDD episodes according to ICD-10 (moderate (F32/33.1), severe (F32/33.2), severe with psychotic features (F32/33.3)) in Austria across 14 years. We calculated weekly admission rates per 100,000 patients by directly age-standardized rates. Results: Across 232,289 admissions (63.2% female) the population based admission rates in MDD were significantly higher in women (p < 0.001). Female to male ratios across subgroups were 1.65 (F32/33.1), 1.58 (F32/33.2), 1.73 (F32/33.3), and peaked around 65 years (ratio ≥ 2 for all subgroups). Length of hospital stay for women was significantly longer in all depression subtypes (p < 0.001). Conclusions: Elevated rates of inpatient treatment in women cannot solely be explained by a higher MDD prevalence and are dependent on age and type of depressive episode. Irrespective of the type and severity of the mood episode, women exhibit longer hospitalisation times. [ABSTRACT FROM AUTHOR]
Background This European multicenter study aimed to elucidate suicidality in major depressive disorder. Previous surveys suggest a prevalence of suicidality in major depressive disorder of ≥50%, but little is known about the association of different degrees of suicidality with socio-demographic, psychosocial, and clinical characteristics. Methods We stratified 1410 major depressive disorder patients into 3 categories of suicidality based on the Hamilton Rating Scale for Depression item 3 (suicidality) ratings (0=no suicidality; 1–2=mild/moderate suicidality; 3–4=severe suicidality). Chi-squared tests, analyses of covariance, and Spearman correlation analyses were applied for the data analyses. Results The prevalence rate of suicidality in major depressive disorder amounted to 46.67% (Hamilton Rating Scale for Depression item 3 score ≥1). 53.33% were allocated into the no, 38.44% into the mild/moderate, and 8.23% into the severe suicidality patient group. Due to the stratification of our major depressive disorder patient sample according to different levels of suicidality, we identified some socio-demographic, psychosocial, and clinical variables differentiating from the patient group without suicidality already in presence of mild/moderate suicidality (depressive symptom severity, treatment resistance, psychotic features, add-on medications in general), whereas others separated only when severe suicidality was manifest (inpatient treatment, augmentation with antipsychotics and benzodiazepines, melancholic features, somatic comorbidities). Conclusions As even mild/moderate suicidality is associated with a failure of achieving treatment response, adequate recognition of this condition should be ensured in the clinical practice. [ABSTRACT FROM AUTHOR]