Ketamine offers promising new therapeutic options for difficult-to-treat depression. The efficacy of treatment response, including ketamine, has been intricately linked to EEG measures of vigilance. This research investigated the interplay between intravenous ketamine and alterations in brain arousal, quantified through EEG vigilance assessments in two distinct cohorts of depressed patients (original dataset: n = 24; testing dataset: n = 24). Clinical response was defined as a decrease from baseline of >33% on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 h after infusion. EEG recordings were obtained pre-, start-, end- and 24 h post- infusion, and the resting EEG was automatically scored using the Vigilance Algorithm Leipzig (VIGALL). Relative to placebo (sodium chloride 0.9%), ketamine increased the amount of low-vigilance stage B1 at end-infusion. This increase in B1 was positively related to serum concentrations of ketamine, but not to norketamine, and was independent of clinical response. In contrast, treatment responders showed a distinct EEG pattern characterized by a decrease in high-vigilance stage A1 and an increase in low-vigilance B2/3, regardless of whether placebo or ketamine had been given. Furthermore, pretreatment EEG differed between responders and non-responders with responders showing a higher percentage of stage A1 (53% vs. 21%). The logistic regression fitted on the percent of A1 stages was able to predict treatment outcomes in the testing dataset with an area under the ROC curve of 0.7. Ketamine affects EEG vigilance in a distinct pattern observed only in responders. Consequently, the percentage of pretreatment stage A1 shows significant potential as a predictive biomarker of treatment response.Clinical Trials Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000952-17/CZ Registration number: EudraCT Number: 2013-000952-17.
- MeSH
- bdění MeSH
- depresivní porucha unipolární * farmakoterapie MeSH
- elektroencefalografie MeSH
- ketamin * farmakologie terapeutické užití MeSH
- lidé MeSH
- mozek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
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.
- 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
Heroin users in opioid agonist treatment (OAT) show markedly reduced heroin consumption, less crime and a lower mortality rate. However, the extent of long-term OAT participation over subsequent treatment episodes remains unclear. We analysed the annual proportion of patients in treatment (at least 1 day) since the start of first OAT in 4 European regions: Barcelona (BA) 1996-2012: 8,602 patients; Czech -Republic (CZ) 2000-2014: 4,377 patients; Netherlands (NL) 1994-2014: 33,235 patients, Zurich (ZU) 1992-2015: 11,795. We estimated the long-term decline of treatment need due to mortality or abstinence and also a "nuisance" short-term decline until the equilibrium level of cycling in and out of OAT is reached to obtain the adjusted treatment participation value. The adjusted treatment participation was around 50% (BA: 47.4-51.4%; CZ: 49.8-53.9%; NL: 52.3-54.0%; ZU: 46.4-49.3%), and the annual decline of treatment need was close to 4%. Non-nationals (NL patients with a migrant background) showed substantial lower adjusted treatment participation (rate ratio BA: 0.059-0.343; NL: 0.710-0.751; ZU: 0.681-0.797; CZ: n.a.). Our method may provide a policy-relevant indicator of long-term provision, quality and access to OAT following first treatment.
- MeSH
- databáze faktografické trendy MeSH
- dospělí MeSH
- emigranti a imigranti * MeSH
- lidé středního věku MeSH
- lidé MeSH
- opiátová substituční terapie metody trendy MeSH
- opioidní analgetika aplikace a dávkování MeSH
- poruchy spojené s užíváním opiátů diagnóza epidemiologie terapie MeSH
- rozvrh dávkování léků MeSH
- výsledek terapie MeSH
- zapojení pacienta metody trendy MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Nizozemsko epidemiologie MeSH
- Španělsko epidemiologie MeSH
- Švýcarsko epidemiologie MeSH
Somatic illness is frequently associated with depression and anxiety and major depression significantly increases risk of severe medical conditions, e.g. cardiovascular illness. One of the most frequent comorbidities is that of depression and pain. Alterations in noradrenergic and serotonergic neurotransmissions in the central nervous system have been implicated in the joint pathophysiology of depression and chronic pain. Antidepressants, alone or in combination with psychotherapy, are an effective treatment option in such cases. The newer dual action antidepressants (milnacipran, venlafaxine, duloxetine) acting specifically on both noradrenergic and serotonergic neurotransmitter systems are presumably more reliable in pain management. So far, the most extensively studied drug has been duloxetine. Twelve randomized placebo-controlled trials with the total number of 4,108 patients suffering from pain associated with major depressive disorder suggested consistent analgesic efficacy of duloxetine, especially in fibromyalgia and peripheral neuropathic pain.
- MeSH
- antidepresiva škodlivé účinky terapeutické užití MeSH
- bolest farmakoterapie patofyziologie psychologie MeSH
- chronická nemoc MeSH
- cyklohexanoly škodlivé účinky terapeutické užití MeSH
- cyklopropany škodlivé účinky terapeutické užití MeSH
- depresivní porucha unipolární farmakoterapie patofyziologie psychologie MeSH
- fibromyalgie farmakoterapie patofyziologie psychologie MeSH
- klinické zkoušky jako téma MeSH
- kombinovaná farmakoterapie MeSH
- kombinovaná terapie MeSH
- komorbidita MeSH
- lidé MeSH
- metafyzické vztahy mezi duší a tělem účinky léků fyziologie MeSH
- mozek účinky léků patofyziologie MeSH
- noradrenalin metabolismus MeSH
- psychoterapie MeSH
- serotonin metabolismus MeSH
- thiofeny škodlivé účinky terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
