Abúzus návykových látek je u pacientů se schizofrenií zhruba 3× častější oproti obecné populaci. Jedná se o vzájemně komplikující vztah s řadou nepříznivých důsledků včetně zhoršené adherence a častějších relapsů. Nejužší vztah k onemocnění schizofrenií má kanabis. Farmakoterapie duální poruchy (DD) je v centru pozornosti také proto, že užívání silných antagonistů D2 receptoru může situaci ještě zhoršovat, jak naznačují preklinická i klinická pozorování. Doporučené postupy nejsou v případě DD jednoznačné: uvádějí atypická antipsychotika, klozapin nebo parciální agonisty. Nově se ukazuje významná role D3 receptoru, který má jinou funkci i distribuci než D2 receptor a je zapojen v patofyziologii schizofrenie i abúzu nebo závislosti. Z antipsychotik má silnou afinitu k D3 receptoru parciální agonista kariprazin; prokázal antiadiktivní efekt v animálních studiích, v humánní studii redukoval aktivaci v okruhu odměny a v první observační studii u pacientů se schizofrenií významně snížil abúzus kanabisu. Výsledky ukazují na možný vývoj farmakoterapie duální poruchy, potřebné jsou však další kontrolované studie.
Substance abuse in patients with schizophrenia is approximately 3times more prevalent compared to general population. The relationship is mutually complicating and it has number of adverse consequences including worsening adherence and increased number of relapses. Among the abused substances cannabis has most intimate relationship to schizophrenia. Pharmacotherapy of dual disorder (DD) is in the spotlight also because the use of strong D2 receptor antagonists can even worsen the situation as both preclinical and clinical observations suggest. Guidelines for treatment of DD are not clear-cut generally; atypical antipsychotics, clozapine or partial agonists are recommended. Recently the significant role of D3 receptor has emerged. It has different function and distribution compared to D2 receptor and it is involved both in pathophysiology of schizophrenia and of substance use disorders. Within the group of antipsychotics, the partial agonist cariprazine has strong affinity to D3 receptor. Its anti-addictive effect has been proven in animal studies. In human studies, it reduced activation in reward circuitry and in the first observational study in patients with schizophrenia it reduced cannabis use significantly. The results show possible development of pharmacotherapy of dual disorder, however, further controlled studies are needed.
BACKGROUND: A detailed understanding of alterations in olanzapine pharmacokinetics during acute inflammatory states, associated with infections, remains lacking. This study aimed to investigate the impact of endotoxemia on the pharmacokinetics of olanzapine and desmethylolanzapine (DMO) in mice. METHODS: C57BL/6N mice received an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) or saline (controls), followed 24 hours later by single oral or intravenous doses of olanzapine or intravenous DMO. Concentrations and unbound fractions of olanzapine and DMO were measured in the plasma and brain homogenates. RESULTS: In LPS-injected mice, the area under the concentration-time curve (AUCs) for olanzapine increased 3.8-fold in the plasma and 5.2-fold in brain homogenates, in consequence of a higher absolute bioavailability of olanzapine (+200%), a lower plasma clearance (-34%), and a higher brain penetration ratio for the unbound drug relative to controls (Kp,uu,brain 6.2 vs. 4.1). LPS attenuated the hepatic mRNA expression of cytochrome P450 1A2 and the metabolism of olanzapine to DMO. However, the AUC of plasma DMO increased by 140% due to a 4.8-fold decrease in the plasma clearance of DMO. The brain penetration of DMO was minimal (Kp,uu,brain ≤ 0.051). The LPS-injected mice exhibited a downregulation of the hepatic and ileal mRNA expression of P-glycoprotein (Abcb1a), whereas the expression of Abcb1a and Abcb1b in the brain was upregulated. CONCLUSIONS: Endotoxemia notably increases olanzapine concentrations in the plasma and brain following oral administration in mice. Further studies should clarify whether altered pharmacokinetics results in adverse effects in acutely infected patients taking oral olanzapine.
- MeSH
- Antipsychotic Agents * pharmacokinetics blood administration & dosage MeSH
- Administration, Oral MeSH
- Benzodiazepines * pharmacokinetics blood administration & dosage MeSH
- Endotoxemia * metabolism chemically induced MeSH
- Lipopolysaccharides MeSH
- Brain * metabolism drug effects MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Olanzapine pharmacokinetics MeSH
- Inflammation * chemically induced metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is more complex than that of pulmonary infection, and neuropsychiatric symptoms play a role in this complexity. In this paper, we present the case of a 29-year-old schizophrenic patient who suffered from neuroleptic malignant syndrome (NMS) that developed during coronavirus disease 2019 (COVID-19) infection, with an emphasis on the possible connection between these two conditions. Additionally, we provide an overview of published NMS cases in patients with COVID-19 or after vaccination against SARS-CoV-2. CASE PRESENTATION: A 29-year-old patient treated for schizophrenia, treated with paliperidone palmitate (150 mg every four weeks) and cariprazine (6 mg daily), was admitted to the hospital for agitation and aggressivity; shortly after arrival at the hospital, laryngospasm and hypoxia occurred. The patient tested positive for SARS-CoV-2, and later, he developed pneumonia. During hospitalization, olanzapine (20 mg daily) was added to his regimen. However, due to continuing restlessness, haloperidol was administered (20 mg over the course of one day). A few days later, neuroleptic malignant syndrome occurred. He was treated with bromocriptine (15 mg daily) and clonazepam (2 mg daily) and recovered. CONCLUSIONS: As SARS-CoV-2 is known to interact with angiotensin-converting enzyme 2 and DOPA-decarboxylase is known to be coexpressed with this receptor, we hypothesized that COVID-19 infection might play a substantial role in the development of NMS.
- MeSH
- Antipsychotic Agents therapeutic use adverse effects MeSH
- COVID-19 * complications virology MeSH
- Adult MeSH
- Humans MeSH
- Neuroleptic Malignant Syndrome * diagnosis drug therapy virology MeSH
- Olanzapine therapeutic use MeSH
- SARS-CoV-2 * pathogenicity MeSH
- Schizophrenia * drug therapy complications MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Review MeSH
BACKGROUND: Schizophrenia is a serious mental illness, the pharmacological treatment of which comprises primarily the use of antipsychotics. However, non-adherence to their use and its reliable determination present a serious clinical and economic problem. This study aimed to determine therapeutic adherence in outpatients with schizophrenia spectrum disorders by combining short-term electronic monitoring of dispenser opening with the measurement of antipsychotic blood concentrations. METHODS: A total of 55 patients underwent a week-long electronic monitoring of dispenser opening and measurement of blood concentrations before and after monitoring. Patients who correctly opened the dispenser at least in 80% of scheduled time points during the weekly interval and, at the same time, did not show a change in blood concentration of the antipsychotic by more than 30% in any direction, were considered adherent. RESULTS: 69.1% of the patients met the adherence criteria, which was less than that determined by the Drug Attitude Inventory (DAI-10), the Visual Analogue Scale (VAS), and the Clinician Rating Scale (CRS). 7.3% of the patients took less than 80% of the prescribed doses and a change in blood concentrations of the antipsychotic by more than 30% was detected in 25.4% of the patients. In 70.9% of patients, the detected concentrations were within the recommended therapeutic reference interval. The groups of adherent and non-adherent patients did not differ statistically significantly in the severity of their illness as determined by the Clinical Global Impression (CGI), the Personal and Social Performance scale (PSP), and the Positive and Negative Syndrome Scale (PANSS). CONCLUSIONS: The combined method of evaluating adherence in schizophrenia patients confirmed the results determined by other methods. The benefits of this approach are described in the paper.
- MeSH
- Medication Adherence * psychology MeSH
- Antipsychotic Agents * blood therapeutic use MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Drug Monitoring * methods MeSH
- Prospective Studies MeSH
- Schizophrenia * drug therapy blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Identifying biological markers to guide treatment decisions in first-episode psychosis (FEP) is essential for improving patient outcomes. This longitudinal study investigated DNA methylation (DNAm) patterns and DNAm-derived cell-type proportions (CTP) in blood and associated them with response to risperidone treatment, a second-generation antipsychotic drug, in antipsychotic-naïve FEP patients. We also explored longitudinal changes in DNAm associated with risperidone treatment. We profiled DNAm in 114 individuals before (anFEP) and after two months of risperidone treatment using microarrays. The main results were compared with 115 healthy controls and validated in an independent cohort of subjects with schizophrenia (n = 26) with one-month follow-up data. We identified 302 differentially methylated positions (DMPs) associated with treatment response, measured by changes in the Positive and Negative Syndrome Scale score, of which 16 were validated in the independent cohort. Sixteen differentially methylated regions (DMRs) were associated with response, with one (in SIPA1L3) being validated. A decrease in B-cell proportions was correlated with symptom improvement in both cohorts. Additionally, four DMPs associated with risperidone treatment were identified: two related to the psychotic state and two specifically to risperidone treatment. DNAm-derived CTP showed alterations in anFEP compared with controls, particularly in the neutrophil-to-lymphocyte ratio, which normalized after treatment. These findings suggest that DNAm, particularly in B-cells, may be a promising marker for monitoring response to risperidone treatment in schizophrenia. Our longitudinal study revealed novel and known genes that may be regulated by risperidone and could be used as response markers to improve prognosis in schizophrenia and FEP.
- MeSH
- Antipsychotic Agents * therapeutic use MeSH
- Adult MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- DNA Methylation * drug effects MeSH
- Adolescent MeSH
- Young Adult MeSH
- Psychotic Disorders * drug therapy genetics blood MeSH
- Risperidone * therapeutic use pharmacology MeSH
- Schizophrenia * drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The European Medicines Agency has recommended a series of restrictions on the use of sodium valproate (valproate) following research linking its exposure in utero to adverse congenital and neurodevelopmental effects in offspring. Recent research has highlighted a potential increased risk of neurodevelopmental disorders in children born to males taking valproate prior to conception. Clinicians and patients require guidance regarding suitable alternatives. AIM: To provide an overview of suitable alternatives to valproate in the management of bipolar disorder. METHOD: A narrative review was conducted. Only medications with an established evidence base in managing different phases of bipolar disorder and endorsed within clinical practice guidelines were considered. Eligible guidelines included those (i) where recommendations were informed by a formal guideline development process and (ii) published in English within the last 15 years. REPROTOX® was chosen as the primary information source regarding reproductive safety of alternative medications. RESULTS: Of all second-generation antipsychotics, quetiapine should be considered a first-line alternative to valproate. Lithium has been associated with an increased risk of cardiac malformations, especially Ebstein anomaly, following in utero exposure. However, given its robust efficacy as an antimanic agent and the absolute risk of cardiac abnormalities being low, it's use can still be considered in individuals of child-bearing potential with appropriate monitoring. Carbamazepine treatment should be avoided due to concerns for teratogenicity. Although considered safe in pregnancy, lamotrigine is largely effective at preventing relapse of bipolar depression. Thus, lamotrigine offers limited clinical utility as an alternative to valproate. CONCLUSION: Specific recommendations are made regarding alternatives to valproate in managing bipolar disorder.
- MeSH
- Antimanic Agents * adverse effects therapeutic use MeSH
- Antipsychotic Agents * adverse effects therapeutic use MeSH
- Bipolar Disorder * drug therapy MeSH
- Valproic Acid * adverse effects therapeutic use MeSH
- Humans MeSH
- Disease Management * MeSH
- Pregnancy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Comparative Study MeSH
- Geographicals
- Europe MeSH
Článek se soustředí na farmakoterapii farmakorezistentní schizofrenie. Nejprve je uvedena definice farmakorezistentní schizofrenie a způsoby vyloučení pseudorezistence. Detailněji jsou rozebrány možnosti léčby, tj. změna stávající léčby, augmentace a kombinace antipsychotik. Na závěr je krátce zmíněna perspektivní léčba.
The paper is focused on pharmacotherapy of treatment-resistant schizophrenia and exclusion of pseudoresistance. The treatment options including switch, augmentation and combination of antipsychotics are described. Finally, perspective substances are briefly mentioned.
- MeSH
- Antipsychotic Agents MeSH
- Clozapine therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Drug Resistance * MeSH
- Humans MeSH
- Schizophrenia, Treatment-Resistant * drug therapy MeSH
- Drug Synergism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Antipsychotic Agents * administration & dosage therapeutic use MeSH
- Aripiprazole administration & dosage therapeutic use MeSH
- Adult MeSH
- Administration, Intravenous MeSH
- Congresses as Topic MeSH
- Middle Aged MeSH
- Humans MeSH
- Drug Monitoring MeSH
- Schizophrenia * drug therapy MeSH
- Patient Satisfaction * MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Keywords
- kariprazin, duální porucha,
- MeSH
- Antipsychotic Agents administration & dosage therapeutic use MeSH
- Adult MeSH
- Drug Therapy, Combination MeSH
- Comorbidity MeSH
- Humans MeSH
- Piperazines administration & dosage therapeutic use MeSH
- Substance-Related Disorders * drug therapy MeSH
- Schizophrenia * drug therapy complications MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Gynekomastie je benigní zvětšení prsní žlázy u mužů, které může mít významný psychologický dopad, zejména u dětí a adolescentů. Tento článek se zabývá farmakologicky indukovanou gynekomastií a nejčastějšími léky, které mohou přispět k jejímu vzniku. V rámci naší analýzy jsme identifikovali a přezkoumali relevantní studie a kazuistiky publikované v databázi PubMed, které se zabývají různými aspekty gynekomastie u dětských pacientů. Důležitým krokem v prevenci gynekomastie je informovanost zdravotnického personálu, rodičů a pacientů o potenciálních rizicích spojených s užíváním určitých léků. Je nevyhnutelné, aby při předepisovaní léčby byly zohledněny veškeré možné vedlejší účinky, a aby se provedlo důkladné zhodnocení poměru přínosů a rizik. Mimo jiné se doporučuje provádět pravidelné kontroly a hodnocení pacientů, kteří užívají rizikové léky, aby bylo možné včas identifikovat a řešit případné příznaky gynekomastie. Tento článek zdůrazňuje potřebu zvýšené pozornosti k vybraným lékům, které jsou nejčastěji uváděny v odborné literatuře, a multidisciplinární přístup k léčbě. Informovanost o farmakologických rizicích a podpora ze strany zdravotnických odborníků jsou klíčové pro prevenci a zvládnutí tohoto stavu, ale také pro psychologickou pohodu dětských pacientů trpících touto diagnózou.
Gynecomastia is a benign enlargement of breast tissue in males that can have significant psychological impacts, especially in children and adolescents. This article focuses on pharmacologically induced gynecomastia and the most common medications that may contribute to its development. In our analysis, we identified and examined relevant studies and case reports published in the PubMed database that discuss various aspects of gynecomastia in pediatric patients. An important step in the prevention of gynecomastia is the awareness of healthcare professionals, parents, and patients regarding the potential risks associated with the use of certain medications. It is essential that all possible side effects are considered when prescribing treatment and that a thorough assessment of the benefits and risks is conducted. Additionally, it is recommended to carry out regular check-ups and evaluations of patients who are taking high-risk medications to identify and address any symptoms of gynecomastia in a timely manner. This article emphasizes the need for increased attention to selected medications commonly cited in the scientific literature and a multidisciplinary approach to treatment. Awareness of pharmacological risks and support from healthcare professionals are crucial for the prevention and management of this condition, as well as for the psychological well-being of pediatric patients suffering from this diagnosis.
- MeSH
- Anticonvulsants pharmacology adverse effects MeSH
- Antipsychotic Agents pharmacology adverse effects MeSH
- Child MeSH
- Gynecomastia * etiology MeSH
- Isoniazid pharmacology adverse effects MeSH
- Humans MeSH
- Metoclopramide pharmacology adverse effects MeSH
- Drug-Related Side Effects and Adverse Reactions * drug therapy MeSH
- Omeprazole pharmacology adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
