INTRODUCTION: The use of antidepressants in bipolar disorder (BD) remains contentious, in part due to the risk of antidepressant-induced mania (AIM). However, there is no information on the architecture of mood regulation in patients who have experienced AIM. We compared the architecture of mood regulation in euthymic patients with and without a history of AIM. METHODS: Eighty-four euthymic participants were included. Participants rated their mood, anxiety and energy levels daily using an electronic (e-) visual analog scale, for a mean (SD) of 280.8(151.4) days. We analyzed their multivariate time series by computing each variable's auto-correlation, inter-variable cross-correlation, and composite multiscale entropy of mood, anxiety, and energy. Then, we compared the data features of participants with a history of AIM and those without AIM, using analysis of covariance, controlling for age, sex, and current treatment. RESULTS: Based on 18,103 daily observations, participants with AIM showed significantly stronger day-to-day auto-correlation and cross-correlation for mood, anxiety, and energy than those without AIM. The highest cross-correlation in participants with AIM was between mood and energy within the same day (median (IQR), 0.58 (0.27)). The strongest negative cross-correlation in participants with AIM was between mood and anxiety series within the same day (median (IQR), -0.52 (0.34)). CONCLUSION: Patients with a history of AIM have a different underlying mood architecture compared to those without AIM. Their mood, anxiety and energy stay the same from day-to-day; and their anxiety is negatively correlated with their mood.

• Klíčová slova
• antidepressant‐induced mania (AIM), auto‐correlation, bipolar disorder, cross‐correlation, euthymia, mood regulation, time series analysis,
• MeSH
• afekt * účinky léků   MeSH
• antidepresiva * terapeutické užití   škodlivé účinky   MeSH
• bipolární porucha * farmakoterapie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mánie * farmakoterapie   chemicky indukované   MeSH
• psychiatrické posuzovací škály MeSH
• úzkost farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva * MeSH

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

• Klíčová slova
• Europe, PTSD, guidelines, mental health, psychiatry, psychopharmacology,
• MeSH
• antidepresiva terapeutické užití   MeSH
• kognitivně behaviorální terapie * MeSH
• lidé MeSH
• posttraumatická stresová porucha * farmakoterapie   psychologie   MeSH
• psychiatři MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antidepresiva MeSH

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

• Klíčová slova
• diagnosis, evidence-based medicine, guideline, insomnia, treatment,
• MeSH
• antidepresiva terapeutické užití   MeSH
• benzodiazepiny terapeutické užití   MeSH
• dospělí MeSH
• lidé MeSH
• melatonin * terapeutické užití   farmakologie   MeSH
• poruchy iniciace a udržování spánku * terapie   farmakoterapie   MeSH
• spánek MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antidepresiva MeSH
• benzodiazepiny MeSH
• melatonin * MeSH

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; β*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; β*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.

• MeSH
• antidepresiva terapeutické užití   MeSH
• bipolární porucha * farmakoterapie   MeSH
• deprese farmakoterapie   MeSH
• intravenózní podání MeSH
• ketamin * terapeutické užití   MeSH
• lidé MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antidepresiva MeSH
• ketamin * MeSH

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

• MeSH
• antidepresiva * škodlivé účinky   terapeutické užití   MeSH
• deprese nereagující na léčbu * farmakoterapie   psychologie   MeSH
• deprese farmakoterapie   MeSH
• depresivní porucha unipolární * farmakoterapie   psychologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• psilocybin * škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antidepresiva * MeSH
• psilocybin * MeSH

Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression.Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic.Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity.Conclusions: Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key pointsDepression in the working population and depression-related sick leave have a profound economic impact on societyDepression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditionsA wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to workIn terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapyAlthough depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measuresDepression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.

• Klíčová slova
• Absenteeism, depression, functionality, major depressive disorder, return to work, sick leave,
• MeSH
• absentérství * MeSH
• antidepresiva terapeutické užití   MeSH
• deprese terapie   MeSH
• lidé MeSH
• pracovní neschopnost * MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antidepresiva MeSH

BACKGROUND: Symptom manifestations in mood disorders can be subtle. Cumulatively, small imprecisions in measurement can limit our ability to measure treatment response accurately. Logical and statistical consistency checks between item responses (i.e., cross-sectionally) and across administrations (i.e., longitudinally) can contribute to improving measurement fidelity. METHODS: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that assembled flags indicating consistency/inconsistency ratings for the Hamilton Rating Scale for Depression (HAM-D17), a widely-used rating scale in studies of depression. Proposed flags were applied to assessments derived from the NEWMEDS data repository of 95,468 HAM-D administrations from 32 registration trials of antidepressant medications and to Monte Carlo-simulated data as a proxy for applying flags under conditions of known inconsistency. RESULTS: Two types of flags were derived: logical consistency checks and statistical outlier-response pattern checks. Almost thirty percent of the HAMD administrations had at least one logical scoring inconsistency flag. Seven percent had flags judged to suggest that a thorough review of rating is warranted. Almost 22% of the administrations had at least one statistical outlier flag and 7.9% had more than one. Most of the administrations in the Monte Carlo- simulated data raised multiple flags. LIMITATIONS: Flagged ratings may represent less-common presentations of administrations done correctly. CONCLUSIONS: Application of flags to clinical ratings may aid in detecting imprecise measurement. Reviewing and addressing these flags may improve reliability and validity of clinical trial data.

• Klíčová slova
• Careless ratings, Consistency of measurement, HAM-D17, Hamilton Rating Scale for Depression, Inconsistent ratings, NEWMEDS,
• MeSH
• antidepresiva * terapeutické užití   MeSH
• deprese * diagnóza   MeSH
• lidé MeSH
• poruchy nálady farmakoterapie   MeSH
• psychiatrické posuzovací škály MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidepresiva * MeSH

An investigation of inappropriate medication use in treatment of depressivity in institutionalized older adults, based on a nurse-led evaluation of functional status and depressive symptoms in nursing home residents. Methods: A cross-sectional multicenter study was performed using records from 1087 residents cared for in fifteen nursing homes (NHs) in the Czech Republic. Inclusion criteria were being a permanent resident of one of the facilities, being 60 years of age or older, having a Geriatric Depression Scale score of 6 or more, and having a Mini Mental State examination score 10 or more. The final sample for analysis included 317 depressed NH residents. Results: 52 percent of NH residents with depressivity had no antidepressant treatment. Benzodiazepines were the only medication in 16 percent of depressed residents, and were added to antidepressant treatment in 18 percent of residents. Benzodiazepine users had significantly higher GDS scores compared to non-users (p = 0.007). Conclusion: More than half of depressed NH residents remained without antidepressant treatment. Residents inappropriately treated with benzodiazepines were more depressed than residents treated with antidepressants only, or even not treated at all. Cooperation of the interprofessional team in the screening of depressive symptoms has the potential to improve the quality of care.

• Klíčová slova
• benzodiazepines, depression, interprofessional team, nurse, older adults,
• MeSH
• antidepresiva terapeutické užití   MeSH
• benzodiazepiny MeSH
• deprese * farmakoterapie   epidemiologie   MeSH
• pečovatelské domovy * MeSH
• průřezové studie MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidepresiva MeSH
• benzodiazepiny MeSH

BACKGROUND: About every fourth patient with major depressive disorder (MDD) shows evidence of systemic inflammation. Previous studies have shown inflammation-depression associations of multiple serum inflammatory markers and multiple specific depressive symptoms. It remains unclear, however, if these associations extend to genetic/lifetime predisposition to higher inflammatory marker levels and what role metabolic factors such as Body Mass Index (BMI) play. It is also unclear whether inflammation-symptom associations reflect direct or indirect associations, which can be disentangled using network analysis. METHODS: This study examined associations of polygenic risk scores (PRSs) for immuno-metabolic markers (C-reactive protein [CRP], interleukin [IL]-6, IL-10, tumour necrosis factor [TNF]-α, BMI) with seven depressive symptoms in one general population sample, the UK Biobank study (n = 110,010), and two patient samples, the Munich Antidepressant Response Signature (MARS, n = 1058) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D, n = 1143) studies. Network analysis was applied jointly for these samples using fused graphical least absolute shrinkage and selection operator (FGL) estimation as primary analysis and, individually, using unregularized model search estimation. Stability of results was assessed using bootstrapping and three consistency criteria were defined to appraise robustness and replicability of results across estimation methods, network bootstrapping, and samples. RESULTS: Network analysis results displayed to-be-expected PRS-PRS and symptom-symptom associations (termed edges), respectively, that were mostly positive. Using FGL estimation, results further suggested 28, 29, and six PRS-symptom edges in MARS, STAR*D, and UK Biobank samples, respectively. Unregularized model search estimation suggested three PRS-symptom edges in the UK Biobank sample. Applying our consistency criteria to these associations indicated that only the association of higher CRP PRS with greater changes in appetite fulfilled all three criteria. Four additional associations fulfilled at least two consistency criteria; specifically, higher CRP PRS was associated with greater fatigue and reduced anhedonia, higher TNF-α PRS was associated with greater fatigue, and higher BMI PRS with greater changes in appetite and anhedonia. Associations of the BMI PRS with anhedonia, however, showed an inconsistent valence across estimation methods. CONCLUSIONS: Genetic predisposition to higher systemic inflammatory markers are primarily associated with somatic/neurovegetative symptoms of depression such as changes in appetite and fatigue, consistent with previous studies based on circulating levels of inflammatory markers. We extend these findings by providing evidence that associations are direct (using network analysis) and extend to genetic predisposition to immuno-metabolic markers (using PRSs). Our findings can inform selection of patients with inflammation-related symptoms into clinical trials of immune-modulating drugs for MDD.

• Klíčová slova
• Body Mass Index, C-reactive protein, Depression, Depressive symptoms, Inflammation, Interleukin 10, Interleukin 6, Network analysis, Tumour necrosis factor-α,
• MeSH
• antidepresiva terapeutické užití   MeSH
• C-reaktivní protein analýza   MeSH
• deprese * genetika   MeSH
• depresivní porucha unipolární * farmakoterapie   genetika   MeSH
• lidé MeSH
• multifaktoriální dědičnost MeSH
• zánět farmakoterapie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antidepresiva MeSH
• C-reaktivní protein MeSH

OBJECTIVE: Ketamine has been shown to be effective in treatment of episodes of major depressive disorder (MDD). This controlled study aimed to analyse the predictive and discriminative power of heart rate (HR) and heart rate variability (HRV) for ketamine treatment in MDD. METHODS: In 51 patients, HR and HRV were assessed at baseline before and during ketamine infusion and 24 hours post ketamine infusion. Montgomery-Åsberg Depression Rating Scale (MADRS) was used to assess changes of depressive symptoms. A 30% or 50% reduction of symptoms after 24 hours or within 7 days was defined as response. A linear mixed model was used for analysis. RESULTS: Ketamine infusion increased HR and HRV power during and after infusion. Responders to ketamine showed a higher HR during the whole course of investigation, including at baseline with medium effect sizes (Cohen's d = 0.47-0.67). Furthermore, HR and HRV power discriminated between responders and non-responders, while normalized low and high frequencies did not. CONCLUSION: The findings show a predictive value of HR and HRV power for ketamine treatment. This further underlines the importance of the autonomous nervous system (ANS) and its possible malfunctions in MDD. SIGNIFICANCE: The predictive power of HR and HRV markers should be studied in prospective studies. Neurophysiological markers could improve treatment for MDD via optimizing the choice of treatments.

• Klíčová slova
• Electrocardiogram, Heart rate variability, Ketamine, Major Depression, Prediction,
• MeSH
• antidepresiva terapeutické užití   MeSH
• depresivní porucha unipolární farmakoterapie   patofyziologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• ketamin terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• srdeční frekvence fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antidepresiva MeSH
• ketamin MeSH