BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.

• Klíčová slova
• Multiple sclerosis, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, sphingosine 1-phosphate receptor modulators,
• MeSH
• antidepresiva škodlivé účinky   MeSH
• indany * MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu * škodlivé účinky   MeSH
• lidé MeSH
• oxadiazoly * MeSH
• roztroušená skleróza * chemicky indukované   MeSH
• selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky   MeSH
• serotonin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• indany * MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu * MeSH
• oxadiazoly * MeSH
• ozanimod MeSH Prohlížeč
• selektivní inhibitory zpětného vychytávání serotoninu MeSH
• serotonin MeSH

Our goal was to determine if venlafaxine has a negative effect on bone metabolism. Rats were divided into three groups. The sham-operated control group (SHAM), the control group after orchidectomy (ORX), and the experimental group after orchidectomy received venlafaxine (VEN ORX) in standard laboratory diet (SLD) for 12 weeks. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I (P1NP), bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 (BMP-2) were examined in bone homogenate. The femurs were used for biomechanical testing. Compared to the ORX group we found lower BMD in the diaphysis area of the femur in the VEN ORX group, suggesting a preferential effect on cortical bone. Of the bone metabolism markers, there was significant decrease (ORX control group versus VEN ORX experimental group) in BALP levels and increase in sclerostin and CTX-I levels, suggesting a decrease in osteoid synthesis and increased bone resorption. The results suggest that the prolonged use of venlafaxine may have a negative effect on bone metabolism. Further studies are warranted to establish whether venlafaxine may have a clinically significant adverse effect on bone.

• Klíčová slova
• BALP, Bone mineral density, CTX-I, SNRI, Venlafaxine,
• MeSH
• absorpční fotometrie MeSH
• alkalická fosfatasa metabolismus   MeSH
• bederní obratle diagnostické zobrazování   účinky léků   MeSH
• biologické markery metabolismus   MeSH
• biomechanika MeSH
• femur diagnostické zobrazování   účinky léků   MeSH
• genetické markery MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu toxicita   MeSH
• kolagen typu I metabolismus   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   účinky záření   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetické proteiny metabolismus   MeSH
• kostní morfogenetický protein 2 metabolismus   MeSH
• lidé MeSH
• orchiektomie * MeSH
• osteoprotegerin metabolismus   MeSH
• peptidové fragmenty metabolismus   MeSH
• peptidy metabolismus   MeSH
• potkani Wistar MeSH
• prokolagen metabolismus   MeSH
• remodelace kosti účinky léků   MeSH
• tibie účinky léků   metabolismus   MeSH
• venlafaxin hydrochlorid toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• biologické markery MeSH
• Bmp2 protein, rat MeSH Prohlížeč
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• genetické markery MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu MeSH
• kolagen typu I MeSH
• kostní morfogenetické proteiny MeSH
• kostní morfogenetický protein 2 MeSH
• osteoprotegerin MeSH
• peptidové fragmenty MeSH
• peptidy MeSH
• procollagen Type I N-terminal peptide MeSH Prohlížeč
• prokolagen MeSH
• Sost protein, rat MeSH Prohlížeč
• Tnfrsf11b protein, rat MeSH Prohlížeč
• venlafaxin hydrochlorid MeSH

• MeSH
• hepatocelulární karcinom * epidemiologie   MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu * MeSH
• kohortové studie MeSH
• lidé MeSH
• nádory jater * chemicky indukované   epidemiologie   MeSH
• selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• systematický přehled MeSH
• Názvy látek
• inhibitory zpětného vychytávání serotoninu a noradrenalinu * MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH

BACKGROUND: The study evaluated the effectiveness of EEG alpha 1, alpha 2 and theta power, along with prefrontal theta cordance (PFC), frontal and occipital alpha 1, alpha 2 asymmetry (FAA1/2, OAA1/2) at baseline and their changes at week 1 in predicting response to antidepressants. METHOD: Resting-state EEG data were recorded from 103 depressive patients that were treated in average for 5.1 ± 0.9 weeks with SSRIs (n = 57) and SNRIs (n = 46). RESULTS: Fifty-five percent of patients (n = 56) responded to treatment (i.e.reduction of Montgomery-Åsberg Depression Rating Scale score ≥ 50%) and 45% (n = 47) of treated subjects did not reach positive treatment outcome. No differences in EEG baseline alpha and theta power or changes at week 1 for prefrontal, frontal, central, temporal and occipital regions were found between responders and non-responders. Both groups showed no differences at baseline PFC, FAA1/2 and OAA1/2 as well as change of FAA1/2 at week 1. The only parameters associated with treatment outcome were decrease of PFC in responders and increase of OAA1/2 at week 1 in non-responders. There was no influence of the used antidepressant classes on the results. The PFC change at week 1 (PFCC) (area under curve-AUC = 0.75) showed only a numerically higher predictive ability than OAA change in alpha 1 (OAA1C, AUC = 0.64)/alpha 2 (OAA2C, AUC = 0.63). A combined model, where OAA1C was added to PFCC (AUC = 0.79), did not significantly improve response prediction. CONCLUSION: Besides PFCC, we found that OAA1C/OAA2C might be another candidate for EEG predictors of antidepressant response.

• Klíčová slova
• Alpha asymmetry, Antidepressants, Depressive disorder, Prediction of treatment outcome, Prefrontal theta cordance, QEEG,
• MeSH
• alfa rytmus EEG * účinky léků   fyziologie   MeSH
• antidepresiva farmakologie   MeSH
• depresivní poruchy * farmakoterapie   patofyziologie   MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• hodnocení výsledků zdravotní péče * MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prefrontální mozková kůra * účinky léků   patofyziologie   MeSH
• prognóza MeSH
• selektivní inhibitory zpětného vychytávání serotoninu farmakologie   MeSH
• theta rytmus EEG * účinky léků   fyziologie   MeSH
• týlní lalok * účinky léků   patofyziologie   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
• Názvy látek
• antidepresiva MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH

Although pharmaceuticals are recognized as a major threat to aquatic ecosystems worldwide, little is known about their ecological effect on aquatic biota and ecosystems. Drug-induced behaviour changes could have a substantial impact on consumer-resource interactions influencing stability of the community and ecosystem. We combined laboratory experiments and functional response modelling to investigate effects of real wastewater treatment plant (WWTP) effluent, as well as environmentally relevant concentrations of the antidepressants citalopram and opioid pain medication tramadol, on trophic interactions. Our biological system consisted of dragonfly Aeshna cyanea larvae as predator of common carp Cyprinus carpio fry. Exposure to WWTP effluent significantly increased A. cyanea maximum feeding rate, while those parameters in tramadol and citalopram-exposed larvae were significantly lower from unexposed control group. This suggested the potential of all tested pollutants to have an effect on consumer-resource equilibrium in aquatic ecosystems. While WWTP effluent strengthened interaction strength (IS) of consumer-resource interaction dynamics making the food web more vulnerable to fluctuation and destabilization, tramadol and citalopram could inhibit the potential oscillations of the consumer-resource system by weakening the IS. Similar studies to reveal the potential of pervasive pharmaceuticals to change of consumer-resource interactions dynamics are needed, especially when real WWTP effluent consisting of mixture of various pharmaceuticals displayed very different effect from single compounds tested.

• Klíčová slova
• Citalopram, Functional response, Maximum feeding rate, Predator-prey interaction, Tramadol, WWTP,
• MeSH
• biologické modely MeSH
• chemické látky znečišťující vodu škodlivé účinky   MeSH
• citalopram škodlivé účinky   MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu škodlivé účinky   MeSH
• kapři fyziologie   MeSH
• nymfa účinky léků   růst a vývoj   fyziologie   MeSH
• odpadní voda analýza   MeSH
• potravní řetězec MeSH
• predátorské chování účinky léků   MeSH
• selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky   MeSH
• tramadol škodlivé účinky   MeSH
• učení vyhýbat se účinky léků   MeSH
• vážky účinky léků   růst a vývoj   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• citalopram MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu MeSH
• odpadní voda MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH
• tramadol MeSH

BACKGROUND: Isolated REM sleep without atonia (RSWA) as a main polysomnograhic feature of REM sleep behaviour disorder (RBD) is thought to be a prodromal or subclinical state of the disease. RSWA/RBD occurence in psychiatric population is much more frequent than in general population but its associated factors are still not known. METHODS: We invited 88 psychiatry in-patients to undervent video-polysomnography. The visual scoring was focused on RSWA in submentales and flexores digitales superficiales muscles. This parametr was subsequently correlated mainly with age/gender, their medication and mental status. RESULTS: The RWSA was mostly still in normal range despite the fact, that selected psychiatry patients (≤ 50 years) were taking several classes of psychoactive medication. 3,6% had convincingly RBD, although 35.7% reported rare lifetime occurence of dream-enacting behaviour and 62.8% sporadic nightmares. We found correlation between RSWA and SNRI medication class (p = 0.015), specifically venlafaxine (p = 0.029) as well as quetiapine (p = 0.030). Another significant associated factors were current anxiety (p < 0.001) and depressive symptoms (p = 0.05), but we found no relation between RSWA and given diagnosis. CONLUCIONS: Isolated RSWA in younger psychiatry patients might be a result of multiple factors, including medication and current mental status but these factors are in most cases not sufficient to manifest RBD.

• Klíčová slova
• Antidepressants, Antipsychotics, Anxiety, Depression, Psychiatric patients, REM sleep behaviour disorder, REM sleep without atonia,
• MeSH
• lidé MeSH
• polysomnografie MeSH
• porucha chování v REM spánku * MeSH
• spánek REM * MeSH
• svalová hypotonie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Ovarian suppression or ovarian ablation used in treatment of breast carcinoma results in temporary or permanent menopause and associated menopausal symptoms - most frequently vasomotoric symptoms (hot flashes, sweats), vaginal atrophy, sleep disturbances. Patients can also experience frequent decrease in bone density (osteopenia, osteoporosis), mood swings or depression, less frequently cardiac toxicity. Managements of these symptoms is complex. As hormonal replacement therapy (estrogens or combined estrogen/gestagen therapy) is contraindicated in women with breast carcinoma, other available options include non-hormonal pharmacological or non-pharmacological methods or their combinations. Women should be advised about cooling techniques and how to avoid known triggers; these measures should be combined with other non-pharmacological and pharmacological intervention. Non-pharmacological methods include the use of acupuncture or cognitive behavioral therapy. Some tips to help stay cool and decrease hot flashes - avoid hot beverages, spicy food, limit coffee or alcohol intake, dress in layers of clothing that can be removed if necessary. Pharmacological options include most frequently antidepressants - SSRI (selective serotonin reuptake inhibitor), SNRI (serotonin norepinephrin reuptake inhibitor), or alternatively gabapentin or pregabali. A very promising drug is paroxetine with a lot of clinical trials. Only this drug has FDA approval for the indication of hot flashes. Paroxetine can lead to disproportional changes in plasma levels of drug in CYP2D6 metabolism and thus it is not suitable for combination of paroxetine with tamoxifen. Several studies demonstrated the effectiveness of the newer generation of SSRI - citalopram, escitalopram, sertralin and duloxetin in ameliorating hot flashes. Venlafaxine in dose 75 or 150 mg has been associated with a 61% reduction in hot flashes frequency if compared to 27% reduction with placebo. Medroxyprogesterone acetate and megestrol acetate were investigated especially in patients with breast cancer history and both drugs demonstrate an effect in hot flashes treatment. Management of vaginal atrophy is challenging. Vaginal dryness/atrophy can be relieved with use of topical lubricants/gels or possibly in highly symptomatic patients with short term use of topical estrogens. As these symptoms require highly complex management, multidisciplinary approach is recommended.Key words: breast cancer - postmenopause - ovarian suppression - postmenopausal osteoporosis - therapyThis work was supported by grant of the Czech Ministry of Health - RVO (MOÚ, 00209805).The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 20. 7. 2016Accepted: 10. 8. 2016.

• MeSH
• ablace * MeSH
• antitumorózní látky hormonální terapeutické užití   MeSH
• lidé MeSH
• menopauza * MeSH
• nádory prsu * MeSH
• návaly MeSH
• ovarektomie MeSH
• ovarium * účinky léků   účinky záření   chirurgie   MeSH
• předčasná menopauza MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH
• tamoxifen terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky hormonální MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH
• tamoxifen MeSH

In today's modern society, it seems to be more and more challenging to cope with life stresses. The effect of psychological stress on emotional and physical health can be devastating, and increased stress is associated with increased rates of heart attack, hypertension, obesity, addiction, anxiety and depression. This review focuses on the possibility of an influence of psychological stress on the metabolism of selected antidepressants (TCAs, SSRIs, SNRIs, SARIs, NDRIs a MMAs) and anxiolytics (benzodiazepines and azapirone), as patients treated with antidepressants and/or anxiolytics can still suffer from psychological stress. Emphasis is placed on the drug metabolism mediated by the enzymes of Phase I, typically cytochromes P450 (CYPs), which are the major enzymes involved in drug metabolism, as the majority of psychoactive substances are metabolized by numerous CYPs (such as CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2A6, CYP2D6, CYP3A4). As the data on the effect of stress on human enzymes are extremely rare, modulation of the efficacy and even regulation of the biotransformation pathways of drugs by psychological stress can be expected to play a significant role, as there is increasing evidence that stress can alter drug metabolism, hence there is a risk of less effective drug metabolism and increased side effects.

• Klíčová slova
• antidepressants, anxiolytics, cytochrome P450, drug metabolism, psychological stress,
• MeSH
• antidepresiva metabolismus   MeSH
• anxiolytika * metabolismus   MeSH
• biotransformace MeSH
• jaterní mikrozomy metabolismus   MeSH
• lidé MeSH
• psychický stres MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antidepresiva MeSH
• anxiolytika * MeSH
• systém (enzymů) cytochromů P-450 MeSH

Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb serotonin homeostasis in the fetoplacental unit by inhibiting serotonin transporter (SERT) and organic cation transporter 3 (OCT3) in the maternal- and fetal-facing placental membranes, respectively. Paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and venlafaxine were tested in situ (rat term placenta perfusion) and ex vivo (uptake studies in membrane vesicles isolated from healthy human term placenta). All tested antidepressants significantly inhibited SERT- and OCT3-mediated serotonin uptake in a dose-dependent manner. Calculated half-maximal inhibitory concentrations (IC50) were in the range of therapeutic plasma concentrations. Using in vitro and in situ models, we further showed that the placental efflux transporters did not compromise mother-to-fetus transport of antidepressants. Collectively, we suggest that antidepressants have the potential to affect serotonin levels in the placenta or fetus when administered at therapeutic doses. Interestingly, the effect of antidepressants on serotonin homeostasis in rat placenta was sex dependent. As accurate fetal programming requires optimal serotonin levels in the fetoplacental unit throughout gestation, inhibition of SERT-/OCT3-mediated serotonin uptake may help explain the poor outcomes of antidepressant use in pregnancy.

• Klíčová slova
• antidepressants, fetal programming, placenta, pregnancy, serotonin, transport,
• Publikační typ
• časopisecké články MeSH