Comparative analysis of psychiatric medications and their association with falls and fractures: A systematic review and network meta-analysis.

An association between psychiatric medications and falls and fractures in people taking them has been demonstrated, but which class or medication leads to the greatest risk of falls or fractures should be further investigated. The aim of this study was to compare and rank the magnitude of risk of falls and fractures due to different psychiatric medications. Eight databases were searched for this meta-analysis and evaluated using a frequency-based network meta-analysis. The results included a total of 28 papers with 14 medications from 5 major classes, involving 3,467,314 patients. The results showed that atypical antipsychotics were the class of medications with the highest risk of falls, and typical antipsychotics were the class of medications with the highest risk of resulting in fractures. Quetiapine ranked first in the category of 13 medications associated with risk of falls, and class Z drugs ranked first in the category of 6 medications associated with risk of fractures. The available evidence suggests that atypical antipsychotics and typical antipsychotics may be the drugs with the highest risk of falls and fractures, respectively. Quetiapine may be the medication with the highest risk of falls, and class Z drugs may be the medication with the highest risk of fractures.

Unravelling psychoactive substances and their metabolites and transformation products: High-Resolution Mass Spectrometry approaches for comprehensive target and suspect screening in wastewater.

Untangling the consumption rates of psychiatric drugs and their metabolites/ transformation products-(TPs) through wastewater gains attention lately. However, the potential environmental impact caused by their release remains ambiguous. As it follows, the monitoring of this class of pharmaceuticals as well as the evaluation of their potential toxicity is a matter of high concern. In the light of the above, here, wastewater samples, were collected in a 1-year and a half sampling campaign (2020-2021) and were further subjected to solid phase extraction. A Q Exactive Focus Orbitrap mass analyzer was employed for the analysis of the samples. For the data curation, except of the monitoring of targets, a comprehensive suspect screening workflow was developed and slightly optimized based on a lab made HRMS database for the investigation of legally or illegally prescribed psychiatric drugs and their relevant metabolites/TPs in influents and effluents. Carbamazepine and amisulpride were quantified at the highest mean concentrations 243 and 225 ng/L respectively, in influents. In effluents, the highest mean concentrations were calculated for carbamazepine (180 ng/L) and venlafaxine (117 ng/L). The implementation of suspect screening approach enhanced the comprehensiveness of analysis by detecting 29 compounds not included in the target list. O-Desmethylvenlafaxine was the predominant metabolite in influents presenting a mean concentration equal to 87 ng/L while the same pattern was also noticed in effluents where the mean concentration was up to 91 ng/L. From the group of suspect compounds for which no analytical standards were available, the predominant compounds with detection frequency 100 % were norephedrine and codeine in influents while in effluents, oxazepam was detected in 81 % of the analyzed samples. Finally, in silico and mathematical tools were employed for the assessment of the risk posed to environmental systems. Most of the detected compounds present high risk in all trophic levels.

Pharmacokinetics and Pharmacodynamics: A Comprehensive Analysis of the Absorption, Distribution, Metabolism, and Excretion of Psychiatric Drugs.

The two main classifications of antidepressant medications are selective norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs). Out of the available choices, selective serotonin reuptake inhibitors (SSRIs) have emerged as the most commonly prescribed option. The class demonstrates a greater degree of diversity in its structural characteristics in contrast to its neurochemical effects. Nevertheless, it is important to acknowledge that the chemical composition of a drug within this specific class does not carry substantial significance in the selection process. A comprehensive analysis of the pharmacodynamic and pharmacodynamic properties of antidepressant drugs proves advantageous for clinicians and managed care providers responsible for selecting preferred selective serotonin reuptake inhibitors (SSRIs) from a roster of authorized medications. The physicochemical characteristics, which possess considerable significance, are frequently disregarded except during the drug development stage. Pharmacodynamic properties refer to the physiological and biochemical effects that drugs exert on the human body. It is noteworthy that the inclusion of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in a comprehensive depression management protocol may demonstrate enhanced effectiveness in clinical environments as opposed to controlled trials.

Pharmaceutical Residues in Edible Oysters along the Coasts of the East and South China Seas and Associated Health Risks to Humans and Wildlife.

The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.

Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients.

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU). Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05). Discussion: This study underlines the importance to consider phenoconversion when looking at a patient's genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.

Therapeutic Drug Monitoring (TDM) Implementation in Public Hospitals in Greece in 2003 and 2021: A Comparative Analysis of TDM Evolution over the Years.

Therapeutic drug monitoring (TDM) is the clinical practice of measuring drug concentrations. TDM can be used to determine treatment efficacy and to prevent the occurrence or reduce the risk of drug-induced side effects, being, thus, a tool of personalized medicine. Drugs for which TDM is applied should have a narrow therapeutic range and exhibit both significant pharmacokinetic variability and a predefined target concentration range. The aim of our study was to assess the current status of TDM in Greek public hospitals and estimate its progress over the last 20 years. All Greek public hospitals were contacted to provide data and details on the clinical uptake of TDM in Greece for the years 2003 and 2021 through a structured questionnaire. Data from 113 out of 132 Greek hospitals were collected in 2003, whereas for 2021, we have collected data from 98 out of 122 hospitals. Among these, in 2003 and 2021, 64 and 51 hospitals, respectively, performed TDM. Antiepileptics and antibiotics were the most common drug categories monitored in both years. The total number of drug measurement assays decreased from 2003 to 2021 (153,313 ± 7794 vs. 90,065 ± 5698; p = 0.043). In direct comparisons between hospitals where TDM was performed both in 2003 and 2021 (n = 35), the mean number of measurements was found to decrease for most drugs, including carbamazepine (198.8 ± 46.6 vs. 46.6 ± 10.1, p < 0.001), phenytoin (253.6 ± 59 vs. 120 ± 34.3; p = 0.001), amikacin (147.3 ± 65.2 vs. 91.1 ± 71.4; p = 0.033), digoxin (783.2 ± 226.70 vs. 165.9 ± 28.9; p < 0.001), and theophylline (71.5 ± 28.7 vs. 11.9 ± 6.4; p = 0.004). Only for vancomycin, a significant increase in measurements was recorded (206.1 ± 96.1 vs. 789.1 ± 282.8; p = 0.012). In conclusion, our findings show that TDM clinical implementation is losing ground in Greek hospitals. Efforts and initiatives to reverse this trend are urgently needed.

Environmental concerns and bioaccumulation of psychiatric drugs in water bodies - Conventional versus biocatalytic systems of mitigation.

The COVID-19 pandemic has brought increments in market sales and prescription of medicines commonly used to treat mental health disorders, such as depression, anxiety, stress, and related problems. The increasing use of these drugs, named psychiatric drugs, has led to their persistence in aquatic systems (bioaccumulation), since they are recalcitrant to conventional physical and chemical treatments typically used in wastewater treatment plants. An emerging environmental concern caused by the bioaccumulation of psychiatric drugs has been attributed to the potential ecological and toxicological risk that these medicines might have over human health, animals, and plants. Thus, by the application of biocatalysis-assisted techniques, it is possible to efficiently remove psychiatric drugs from water. Biocatalysis, is a widely employed and highly efficient process implemented in the biotransformation of a wide range of contaminants, since it has important differences in terms of catalytic behavior, compared to common treatment techniques, including photodegradation, Fenton, and thermal treatments, among others. Moreover, it is noticed the importance to monitor transformation products of degradation and biodegradation, since according to the applied removal technique, different toxic transformation products have been reported to appear after the application of physical and chemical procedures. In addition, this work deals with the discussion of differences existing between high- and low-income countries, according to their environmental regulations regarding waste management policies, especially waste of the drug industry.

Risk factor analysis of omicron patients with mental health problems in the Fangcang shelter hospital based on psychiatric drug intervention during the COVID-19 pandemic in Shanghai, China.

Backgrounds: The widespread coronavirus disease 2019 (COVID-19) outbreak impacted the mental health of infected patients admitted to Fangcang shelter hospital a large-scale, temporary structure converted from existing public venues to isolate patients with mild or moderate symptoms of COVID-19 infection. Objective: This study aimed to investigate the risk factors of the infected patients from a new pharmacological perspective based on psychiatric drug consumption rather than questionnaires for the first time. Methods: We summarised the medical information and analysed the prevalence proportion, characteristics, and the related risk factors of omicron variants infected patients in the Fangcang Shelter Hospital of the National Exhibition and Convention Center (Shanghai) from 9 April 2022 to 31 May 2022. Results: In this study, 6,218 individuals at 3.57% of all admitted patients in the Fangcang shelter were collected suffering from mental health problems in severe conditions including schizophrenia, depression, insomnia, and anxiety who needed psychiatric drug intervention. In the group, 97.44% experienced their first prescription of psychiatric drugs and had no diagnosed historical psychiatric diseases. Further analysis indicated that female sex, no vaccination, older age, longer hospitalization time, and more comorbidities were independent risk factors for the drug-intervened patients. Conclusion: This is the first study to analyse the mental health problems of omicron variants infected patients hospitalised in Fangcang shelter hospitals. The research demonstrated the necessity of potential mental and psychological service development in Fangcang shelters during the COVID-19 pandemic and other public emergency responses.

Occurrence and removal of psychiatric pharmaceuticals in the Tehran South Municipal Wastewater Treatment Plant.

Psychiatric drugs released by humans in wastewater have received more attention because of their potential risks for aquatic organisms. In this study, the occurrence of the two most common groups of psychiatric drugs (sedatives-hypnotics-anxiolytics and antidepressants) were evaluated in the Tehran South Municipal Wastewater Treatment Plant. All the target sedatives-hypnotics-anxiolytics (alprazolam, phenobarbital, and thioridazine) and antidepressants (fluoxetine, citalopram, sertraline, and venlafaxine) were observed in influent and secondary clarification (SC) effluent. Thioridazine (164.25 ± 218.74 ng/L) and citalopram (672.53 ± 938.56 ng/L) had the highest mean concentrations in the influent, while alprazolam (5.09 ± 2.33 ng/L) and citalopram (776.97 ± 1088.01 ng/L) had the highest concentrations in the SC effluent. The higher concentrations of the psychiatric drugs, except thioridazine, were detected in the SC effluent compared to the concentrations in the influent. The increased drugs concentrations, with negative removal efficiencies, were more distinctive in the cold season samples. Psychiatric drugs processed in the chlorination unit followed a completely different pattern compared to the drugs in the biological treatment unit. All the drugs' concentrations, except thioridazine, decreased in the chlorination unit, ranging between 27 ± 14% for alprazolam and 75 ± 10% for citalopram. However, the mean concentrations of the detected drugs were as follows: sertraline (11.96 ± 11.62 ng/L) and venlafaxine (184.94 ± 219.74 ng/L) which could cause environmental and ecological concerns.

Designing Flexible Longitudinal Regimens: Supporting Clinician Planning for Discontinuation of Psychiatric Drugs.

Clinical decision support tools have typically focused on one-time support for diagnosis or prognosis, but have the ability to support providers in longitudinal planning of patient care regimens amidst infrastructural challenges. We explore an opportunity for technology support for discontinuing antidepressants, where clinical guidelines increasingly recommend gradual discontinuation over abruptly stopping to avoid withdrawal symptoms, but providers have varying levels of experience and diverse strategies for supporting patients through discontinuation. We conducted two studies with 12 providers, identifying providers' needs in developing discontinuation plans and deriving design guidelines. We then iteratively designed and implemented AT Planner, instantiating the guidelines by projecting taper schedules and providing flexibility for adjustment. Provider feedback on AT Planner highlighted that discontinuation plans required balancing interpersonal and infrastructural constraints and surfaced the need for different technological support based on clinical experience. We discuss the benefits and challenges of incorporating flexibility and advice into clinical planning tools.

Consumption of Psychiatric Drugs in Primary Care during the COVID-19 Pandemic.

BACKGROUND: The main objective of this research was to analyze whether there were changes in the use of antidepressants, anxiolytics, and hypnotic-sedative drugs, in the context of primary health care, during the COVID-19 pandemic compared to the pre-pandemic period. We further sought to study consumption in vulnerable population groups. METHODS: A cross-sectional observational study was performed in a primary health district of Spain. The data were obtained from the Andalusian Public Health System database, for the pre-COVID-19 period, from March 2019 to February 2020, and for the COVID-19 period, from March 2020 to February 2021. Univariant and bivariant analyses were performed. The effect size was measured using the Rosenthal test. RESULTS: While the total number of medical prescriptions decreased by 2.5% in the COVID-19 period, the prescriptions of psychiatric drugs increased by 6.1%. The increase in the dose consumption per 1000 inhabitants (DHD) was highest for anxiolytics (7.2%), followed by hypnotic-sedatives (5.6%) and antidepressants (3.7%). The consumption of antidepressants, anxiolytics, and sedative-hypnotic drugs was higher in women, older people, and rural areas and lower in areas with social transformation needs, with these differences being statistically significant. CONCLUSIONS: The consumption of psychiatric drugs has increased over the COVID-19 pandemic, especially in women, older people, and rural areas. Thus, we should reflect on the adequate use of these drugs.

Reevaluation of adverse drug reactions of psychiatric drugs under the chinese drug volume-based procurement policy.

BACKGROUND: The "4 + 7" volume-based procurement is a "large group purchase" led by the Chinese government, with the aim of reducing the price of medicines by trading volume for price. Although the "4 + 7" drugs had passed the national consistency evaluation, the adverse drug reactions need to be further evaluated to ensure the safety of the "4 + 7" drugs with low prices. We aimed to analyze the occurrence characteristics and related influencing factors of adverse reactions of psychiatric drugs under the chinese drug volume-based procurement policy(4 + 7 policy), and provide references for clinical medication. METHODS: 137 cases of adverse drug reactions of four psychotropic drugs reported under the "4 + 7" policy in Wuxi Mental Health Center in 2020 were collected. The gender and age of patients, related "4 + 7" drugs, involving organs / systems, clinical manifestations, distribution of new / serious adverse reactions, clinic outcomes were analyzed. RESULTS: Among the 137 cases of adverse drug reactions, the incidence of adverse drug reactions was the highest in patients aged 61-70 (25.38%). Mainly involved 4 "4 + 7" psychiatric drugs, of which olanzapine tablets caused the most adverse reactions (54, 39.24%). The adverse reactions mainly involved the digestive system, nervous system, cardiovascular system, blood and lymphatic system, among which the digestive system was the most common (61, 44.53%). A total of 8 cases (6.16%) of new and 26 cases of serious adverse reactions were reported, all of which led to the prolongation of disease course. Except for the transient side effects, most of that were improved or cured with no death, disability or teratogenicity after stopping or reducing the dose with symptomatic treatment. CONCLUSION: Since more and more drugs will be included in "4 + 7" for clinic, clinical pharmacists should strengthen the publicity and training of the knowledge of "4 + 7" drugs, strengthen the monitoring of adverse drug reactions, and provide timely feedback to the clinic, in order to achieve early prevention, early identification, timely diagnosis and reasonable intervention of the adverse drug reactions under the context of "4 + 7" policy.

Status of Medications Prescribed for Psychiatric Disorders in Korean Pediatric and Adolescent Patients.

While mental health services for children are increasing, few psychiatric drugs have been approved for such use. We analyzed claim data from 19,557 South Korean pediatric and adolescent patients (<20 years) who were diagnosed with schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, attention deficit-hyperactivity disorder (ADHD), or a tic disorder. Among these diseases, depressive episodes were the most common, followed by an anxiety disorder, ADHD, bipolar disorder, tic disorder, and schizophrenia. For each disease, prescriptions were categorized as full-label (approved indication with pediatric dosing in the package insert (PI)), partial-label (approved indication without pediatric dosing in the PI), and contraindication (contraindicated for the specific pediatric age in the PI). For schizophrenia, major depressive disorder, and anxiety disorder, more than 50% of the patients were prescribed partial-labeled medications. Additionally, more than 5% of patients with major depressive disorder were prescribed medications that were contraindicated for their age group. Our findings reveal that children with full-labeled psychiatric conditions are commonly administered drugs that are not explicitly approved for either their disease state or age, including off-label and unlicensed drugs. To use pharmaceuticals more safely, expanding drug indications using real-world data are needed.

Comparison of potential psychiatric drug interactions in six drug interaction database programs: A replication study after 2 years of updates.

OBJECTIVE: Drug interaction database programs are a fundamental clinical tool. In 2018, we compared the category of potential drug-drug interaction (DDI) provided by six drug interaction database programs for 100 drug interaction pairs including psychiatric drugs, and found the category often differed. This study replicated the comparison in 2020 after 2 years of updates to all six drug interaction database programs. METHODS: The 100 drug pairs included 94 different drugs: 67 pairs with a psychiatric and non-psychiatric drug, and 33 pairs with two psychiatric drugs. The assigned category of potential DDI for the drug pairs was compared using percent agreement and Fleiss kappa statistic of interrater reliability. RESULTS: Despite 67 updates involving 46 of the 100 drug pairs, differences remained. The overall percent agreement among the six drug interaction database programs for the category of potential DDI was 67%. The interrater agreement results did not change. The Fleiss kappa overall interrater agreement was fair. The kappa agreement for a drug pair with any severe category rating was substantial, and the kappa agreement for a drug pair with any major category rating was fair. CONCLUSIONS: Physicians should be aware of the inconsistency among drug interaction database programs in the category of potential DDI for drug pairs including psychiatric drugs. Additionally, the category of potential DDI for a drug pair may change over time. This study highlights the importance of ongoing international efforts to standardize methods used to define and classify potential DDI.

What have we learned in the past year? A study on pharmacy purchases of psychiatric drugs from wholesalers in the days prior to the first and second COVID-19 lockdowns in Germany.

No study has yet investigated how the second coronavirus disease (COVID-19) lockdown has impacted the consumption of psychiatric medications in Germany. Therefore, the goal of this study was to analyze weekly pharmacy purchases of psychiatric drugs from wholesalers in this country in 2019 and 2020 using data from the IMS RPM® (Regional Pharmaceutical Market) Weekly Database. The outcome was the number of pharmacy purchases of psychiatric drugs per week from wholesalers between Calendar Week 2 and Calendar Week 52 in 2019 and 2020. Calendar Weeks 12 and 51 in 2020 corresponded to the days prior to the first and second German COVID-19 lockdowns, respectively. Descriptively, compared with 2019, the number of weekly pharmacy purchases of psychiatric drugs increased by 32% between Calendar Weeks 2-11 and Calendar Week 12 in 2020, while there was a 9% increase between Calendar Weeks 13-50 and Calendar Week 51 that same year. Overall, the relative increase in the weekly pharmacy purchases of psychiatric drugs from wholesalers was less pronounced before the second COVID-19 lockdown in Germany than before the first. Further studies are warranted to identify factors (e.g., decreases in panic buying) that may have contributed to this decreasing trend.

EMA and FDA psychiatric drug trial guidelines: assessment of guideline development and trial design recommendations.

AIMS: The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) produce guidelines for the design of pivotal psychiatric drug trials used in new drug applications. It is unknown who are involved in the guideline development and what specific trial design recommendations they give. METHODS: Cross-sectional study of EMA Clinical Efficacy and Safety Guidelines and FDA Guidance Documents. Study outcomes: (1) guideline committee members and declared conflicts of interest; (2) guideline development and organisation of commenting phases; (3) categorisation of stakeholders who comment on draft and final guidelines according to conflicts of interest ('industry', 'not-industry but with industry-related conflicts', 'independent', 'unclear'); and (4) trial design recommendations (trial duration, psychiatric comorbidity, 'enriched design', efficacy outcomes, comparator choice). Protocol registration https://doi.org/10.1101/2020.01.22.20018499 (27 January 2020). RESULTS: We included 13 EMA and five FDA guidelines covering 15 psychiatric indications. Eleven months after submission, the EMA had not processed our request regarding committee member disclosures. FDA offices draft the Guidance Documents, but the Agency is not in possession of employee conflicts of interest declarations because FDA employees generally may not hold financial interests (although some employees may hold interests up to $15,000). The EMA and FDA guideline development phases are similar; drafts and final versions are publicly announced and everybody can submit comments. Seventy stakeholders commented on ten guidelines: 38 (54%) 'industry', 18 (26%) 'not-industry but with industry-related conflicts', six (9%) 'independent' and eight (11%) 'unclear'. They submitted 1014 comments: 640 (68%) 'industry', 243 (26%) 'not-industry but with industry-related conflicts', 44 (5%) 'independent' and 20 (2%) 'unclear' (67 could not be assigned to a specific stakeholder). The recommended designs were generally for trials of short duration; with restricted trial populations; allowing previous exposure to the drug; and often recommending rating scale efficacy outcomes. EMA mainly recommended three arm designs (both placebo and active comparators), whereas FDA mainly recommended placebo-controlled designs. There were also other important differences and FDA's recommendations regarding the exclusion of psychiatric comorbidity seemed less restrictive. CONCLUSIONS: The EMA and FDA clinical research guidelines for psychiatric pivotal trials recommend designs that tend to have limited generalisability. Independent and non-conflicted stakeholders are underrepresented in the guideline development. It seems warranted with more active involvement of scientists and independent organisations without conflicts of interest in the guideline development process.

Refocusing the Use of Psychiatric Drugs for Treatment of Gastrointestinal Cancers.

Gastrointestinal cancers (GICs) are the most common human tumors worldwide. Treatments have limited effects, and increasing global cancer burden makes it necessary to investigate alternative strategies such as drug repurposing. Interestingly, it has been found that psychiatric drugs (PDs) are promising as a new generation of cancer chemotherapies due to their anti-neoplastic properties. This review compiles the state of the art about how PDs have been redirected for cancer therapeutics in GICs. PDs, especially anti-psychotics, anti-depressants and anti-epileptic drugs, have shown effects on cell viability, cell growth, inhibition of proliferation (cell cycle arrest), apoptosis promotion by caspases activation or cytochrome C release, production of reactive oxygen species (ROS) and nuclear fragmentation over esophageal, gastric, colorectal, liver and pancreatic cancers. Additionally, PDs can inhibit neovascularization, invasion and metastasis in a dose-dependent manner. Moreover, they can induce chemosensibilization to 5-fluorouracil and cisplatin and can act synergistically with anti-neoplastic drugs such as gemcitabine, paclitaxel and oxaliplatin. All anti-cancer activities are given by activation or inhibition of pathways such as HDAC1/PTEN/Akt, EGFR/ErbB2/ErbB3, and PI3K/Akt; PI3K-AK-mTOR, HDAC1/PTEN/Akt; Wnt/ß-catenin. Further investigations and clinical trials are needed to elucidate all molecular mechanisms involved on anti-cancer activities as well as adverse effects on patients.

[Mental health in Spain and differences by sex, and by autonomous communities]. / Salud mental en España y diferencias por sexo y por comunidades autónomas.

OBJECTIVE: To describe the evolution of psychological distress in the adult Spanish population in 2006, 2011 and 2017. To study the mental health status of the population in 2017 analyzing the prevalence of psychological distress, prescription of psychiatric drugs, diagnosis and self-perceived health, in Spain and in the autonomous regions, and differentiating between men and women. METHOD: Cross-sectional study, using data from the 2006, 2011 and 2017 National Health Surveys in Spain. VARIABLES: psychological distress (GHQ-12), self-perceived health, mental disorder diagnosis, prescription of psychiatric drugs, sex and autonomous community. The frequencies, percentages and confidence intervals at 95% were calculated. The statistical significance level for the chi-square test was p <0.05. RESULTS: The prevalence of psychological distress in Spain was 22.2% in 2006, 22.1% in 2011 and 19.1% in 2017. With the exception of Cantabria in 2011, in all cases the prevalence of psychological distress was higher in women than men. In 2017, most of the autonomous communities showed prevalence of diagnosis and poor self-perceived health near the Spanish average (15.4% and 33.6%, respectively). The Spanish average of tranquilizer prescription was 9.2%. The highest prevalence was found in Galicia while the lowest was found in Cantabria (overall population and men) and Ceuta and Melilla (women). The Spanish average of antidepressant prescription was 3.6%. The highest prevalence was found in Asturias (overall population and women) and in Galicia (men), while the lowest was found in Ceuta and Melilla. CONCLUSIONS: Psychological distress is a prevalent phenomenon although its prevalence in Spain has decreased slightly. There are big differences in the prescription of psychiatric drugs between each autonomous community. Women showed poorer outcomes on each mental health indicator analyzed.

Factors associated with common mental disorders and use of psychiatric drugs in cancer outpatients.

BACKGROUND: Considering the high incidence of cancer in Brazil and worldwide, the high prevalence and relevance of Common Mental Disorders (CMD) in the treatment of cancer patients, and the use of psychiatric drugs without reliably proven effectiveness, studies that contemplate this topic are needed to understand and provide rationale for the treatment of CMD in these individuals. OBJECTIVES: This study identified prevalence and factors associated with Common Mental Disorders (CMD) and psychotropic use in cancer outpatients. METHOD: This is a cross-sectional study with descriptive correlational design. It was developed in the chemotherapy sector of a hospital specialized in cancer. The tools used were: Self Reporting Questionnaire (SRQ-20) and structured questionnaires. FINDINGS: Among 403 respondents, CMD prevalence was 31.5% and psychotropic use was 25.8%. CMD were associated with gender, education, family income, psychotropic use and cancer surgery. Psychotropic use was associated with gender, employment status, cancer surgery, treatment period and other physical health conditions. Logistic regressions showed CMD were associated with gender and other physical health conditions; psychotropic use was associated with gender, employment status and other conditions.