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INTRODUCTION: Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. OBJECTIVE: To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. METHODS: This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. RESULTS: The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. CONCLUSION: A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.
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JUSTIFICATION: Providing care to patients with several conditions and simultaneously taking several medications at home is inexorably growing in developed countries. This trend increases the chances of home caregivers experiencing diverse errors related with medication or care. OBJECTIVE: To determine the effectiveness of four different educational solutions compared to the natural intervention (absence of intervention) to provide a safer care at home by caregivers. METHOD: Prospective, parallel, and mixed research study with two phases. Candidates: Home-based caregivers caring a person with multiple comorbid conditions or polymedication who falls into one of the three profiles of patients defined for the study (oncology, cardiovascular, or pluripathological patients). First phase: Experts first answered an online survey, and then joined together to discuss the design and plan the content of educational solutions directed to caregivers including the identification of medication and home care errors, their causes, consequences, and risk factors. Second phase: The true experiment was performed using an inter- and intrasubject single-factor experimental design (five groups: four experimental groups against the natural intervention (control), with pre- and post-intervention and follow-up measures) with a simple random assignment, to determine the most effective educational solution (n = 350 participants). The participants will be trained on the educational solutions through 360 V, VR, web-based information, or psychoeducation. A group of professionals called the "Gold Standard" will be used to set a performance threshold for the caring or medication activities. The study will be carried out in primary care centers, hospitals, and caregivers' associations in the Valencian Community, Andalusia, Madrid, and Murcia. EXPECTED RESULTS: We expect to identify critical elements of risk management at home for caregivers and to find the most effective and optimal educational solution to reduce errors at home, increasing caregivers' motivation and self-efficacy whilst the impact of gender bias in this activity is reduced. TRIAL REGISTRATION: Clinical Trial NCT05885334.
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The long-term use of psychopharmacology medications in autism spectrum disorder (ASD) hitherto remains controversial due to a lack of evidence about safety and tolerability. In this regard, genotyping the metabolizing enzyme cytochrome P450 (CYP) 2D6, especially its extreme phenotypes, could help to prevent drug-related adverse reactions or adverse events (AEs). There are several medications warranting CYP2D6 screening that are consumed by people with ASD, such as risperidone and aripiprazole to name a few. A naturalistic observational study was carried out in participants with ASD to analyze the influence of the CYP2D6 phenotype in drug tolerability using a local pharmacovigilance system created for this study. In this case, AEs were identified from participants' electronic health records (EHRs) and paper registries. Other variables were collected: socio-demographic information, comorbidities, and psychopharmacology prescriptions (polypharmacy defined as ≥4 simultaneous prescriptions) and doses. The genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number variations. All of these were used to determine theoretical phenotypes of the metabolic profiles: poor (PM); intermediate (IM); normal (NM); and ultra-rapid (UM). Sex differences were analyzed. A total of 71 participants (30 ± 10 years old, 82% male, 45% CYP2D6 NM phenotype (32 participants)) with a median of 3 (IQR 2-4) comorbidities per person, mainly urinary incontinence (32%) and constipation (22%), were included. CYP2D6 UM showed the highest rate of polypharmacy, whilst, IM participants had the highest rates of neurological and psychiatric AEs, even worse if a CYP2D6 inhibitor drug was prescribed simultaneously. CYP2D6 pharmacogenomics and the monitoring of new antipsychotic prescriptions may make a difference in medication safety in adults with ASD. Particularly in those with psychopharmacology polymedication, it can help with AE avoidance and understanding.
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Introduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process. Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0-100 mm), global activity (GAF, 0-100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0-96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed. Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20-123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6-11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = -0.604, p < 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men. Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction.
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BACKGROUND: The visibility of Rare Diseases is a new challenge for society. These diseases are numerous, heterogeneous in nature and distribution, characterized by a high mortality rate but low prevalence, and usually presenting a severe evolution. Adherence to medication studies in rare diseases are uncommon, due to treatment scarcity. OBJECTIVES: The main purpose of this study is to do a meta-analysis, evaluating the level of adherence to medication in the most prevalent rare diseases. METHODS: This work is a systematic review, and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration number: CRD42022372843) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Adherence to treatment in this systematic review and meta-analysis was collected from all studies included, based on the crude numerators and denominators reported, using either the Morisky Medication Adherence Scale 4 or -8. RESULTS: A total of 54 records were identified through database searches, or after screening relevant manuscripts' references. Finally, 18 studies were included in this systematic review and meta-analysis. A total of 1559 participants (54.18% women) aged less than 84 years old were included. Twelve studies used the MMAS-8. In 8 of them, they established the level of adherence to treatment in three categories (low, medium, and high), with the mean prevalence in each of them being 41.4%, 30.4%, and 28.2%, respectively. CONCLUSIONS: The results observed in adherence to treatment in patients with rare diseases show great variability, due to the different aspects involved in the greater or lesser applicability of the medication.
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An increase in life expectancy leads to a greater impact of chronic non-communicable diseases. This is even more remarkable in elder populations, to whom these become main determinants of health status, affecting mental and physical health, quality of life, and autonomy. Disease appearance is closely related to the levels of cellular oxidation, pointing out the importance of including foods in one's diet that can prevent oxidative stress. Previous studies and clinical data suggest that some plant-based products can slow and reduce the cellular degradation associated with aging and age-related diseases. Many plants from one family present several applications that range from the food to the pharmaceutical industry due to their characteristic flavor and scents. The Zingiberaceae family, which includes cardamom, turmeric, and ginger, has bioactive compounds with antioxidant activities. They also have anti-inflammatory, antimicrobial, anticancer, and antiemetic activities and properties that help prevent cardiovascular and neurodegenerative diseases. These products are abundant sources of chemical substances, such as alkaloids, carbohydrates, proteins, phenolic acids, flavonoids, and diarylheptanoids. The main bioactive compounds found in this family (cardamom, turmeric, and ginger) are 1,8-cineole, α-terpinyl acetate, ß-turmerone, and α-zingiberene. The present review gathers evidence surrounding the effects of dietary intake of extracts of the Zingiberaceae family and their underlying mechanisms of action. These extracts could be an adjuvant treatment for oxidative-stress-related pathologies. However, the bioavailability of these compounds needs to be optimized, and further research is needed to determine appropriate concentrations and their antioxidant effects in the body.
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Elettaria , Zingiber officinale , Zingiberaceae , Zingiberaceae/química , Antioxidantes/farmacología , Antioxidantes/metabolismo , Zingiber officinale/química , Curcuma/química , Calidad de Vida , Extractos Vegetales/químicaRESUMEN
Introduction: The WHO considered antibiotic resistance as 1 of the 10 greatest threats to global health in 2019. The inappropriate and indiscriminate use of antibiotics, together with the lack of new therapeutic alternatives, may eradicate their effectiveness in the closest future. Objective: The general objective is to analyze the different causes attributable to patients, providers and pharmacists that could be drivers of irrational use of antibiotics, and responsible for the appearance of bacterial resistance, in community pharmacies. To this end, the different processes or indicators were studied: patients' requests of antibiotics at the pharmacy, their degree of adherence, satisfaction with the prescribed treatment and antibiotics' surplus recycling. Methods: This study was observational, descriptive, and cross-sectional, carried out in 2 pharmacy offices, including 333 participants. At the time of dispensing, first phase, surveys to collect patients', providers' and pharmacists' data were carried out over the counter. The second phase, with the aim of checking adherence, degree of satisfaction and recycling. Results: There were 333 requests for antibiotic regardless prescription availability, 17% of the patients requested an antibiotic without having one. 38% of patients did not have full adherence to antibiotics. Exploring non-adherence reasons, 24% forgot to take the treatment, 2% experienced adverse effects; 8% improved infection symptoms and 21% had problems to follow schedule. Regarding the recycling habits, 57% of patients had leftover treatments at home, but only 11% recycled it. 10% of medical prescriptions were forced by the patient, and significant gender differences were observed in adherence and knowledge of treatment. Conclusion: The results of this study suggested that there may be a significant level of antibiotic inappropriate use locally, potentially related to patients' sex, finding significant deficiencies in prescription by doctors, in the dispensing act carried out in community pharmacies, and finally in patient compliance with treatment.
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Ulcerative colitis, Crohn's disease, rheumatoid arthritis, psoriasis, and lupus erythematosus are some of common inflammatory diseases. These affections are highly disabling and share signals such as inflammatory sequences and immune dysregulation. The use of foods with anti-inflammatory properties such as ginger (Zingiber officinale Roscoe) could improve the quality of life of these patients. Ginger is a plant widely used and known by its bioactive compounds. There is enough evidence to prove that ginger possesses multiple biological activities, especially antioxidant and anti-inflammatory capacities. In this review, we summarize the current knowledge about the bioactive compounds of ginger and their role in the inflammatory process and its signaling pathways. We can conclude that the compounds 6-shoagol, zingerone, and 8-shoagol display promising results in human and animal models, reducing some of the main symptoms of some inflammatory diseases such as arthritis. For lupus, 6-gingerol demonstrated a protective attenuating neutrophil extracellular trap release in response to phosphodiesterase inhibition. Ginger decreases NF-kß in psoriasis, and its short-term administration may be an alternative coadjuvant treatment. Ginger may exert a function of supplementation and protection against cancer. Furthermore, when receiving chemotherapy, ginger may reduce some symptoms of treatment (e.g., nausea).
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Psoriasis , Zingiber officinale , Animales , Humanos , Zingiber officinale/metabolismo , Calidad de Vida , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Alcoholes Grasos/farmacología , Catecoles/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Psoriasis/tratamiento farmacológicoRESUMEN
Despite the large body of research on sex differences in pain, there is a lack of translation to real-world pain management. Our aim was to analyse the sex differences in the analgesic response to oxycodone/naloxone (OXN) and tapentadol (TAP), in comparison with other opioids (OPO) commonly prescribed for chronic non-cancer pain (CNCP). An observational and cross-sectional study was conducted on ambulatory CNCP patients (n = 571). Sociodemographic, clinical (pain intensity, relief, and quality of life), safety (adverse events (AEs), adverse drug reactions), hospital frequentations and pharmacological (morphine equivalent daily dose (MEDD)) variables were collected. Multiple linear regressions were carried out to assess the association between sex and outcomes. Sex differences were observed, with lower female tolerability and higher hospital frequentation, especially in the OXN group (OR AEs report = 2.8 [1.8−4.4], p < 0.001). Here, females showed higher hospital use (23% hospital admission, 30% prescription change, p < 0.05), requiring a higher MEDD (127 ± 103 mg/day, p < 0.05), compared to OXN men. Regardless of the opioid group, CNCP women were significantly older than men (three years), with significantly higher benzodiazepine use (OR = 1.6 [1.1−2.3]), more constipation (OR = 1.34 [0.93−1.90]) and headache (OR = 1.45 [0.99−2.13]) AEs, than men who were more likely to refer sexual dysfunction (OR = 2.77 [1.53−5.01]), and loss of libido (OR = 1.93 [1.22−3.04]). Sex-differences were found related to poorer female drug tolerability and higher hospital resources, even worst in OXN female users. Other differences related to older female ages and benzodiazepine prescription, need to be further analysed from a gender perspective.
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INTRODUCTION: Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug? AREAS COVERED: The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines. EXPERT OPINION: CYP2D6 genotype can influence opioids' pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.
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Analgesia , Analgésicos Opioides , Citocromo P-450 CYP2D6 , Manejo del Dolor , Analgesia/métodos , Analgesia/tendencias , Analgésicos Opioides/metabolismo , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Humanos , Manejo del Dolor/métodos , Manejo del Dolor/tendencias , Farmacogenética , Fenotipo , Medicina de Precisión/métodos , Medicina de Precisión/tendenciasRESUMEN
A good therapeutic alliance is relevant for healthcare providers exposed to patients' suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (n = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40-70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm vs. low scores 80 ± 75 mm, p < 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the health-care providers, they "gained new insight", "felt better", or "felt content with their doctor's treatment". What´s more, patients who affirmed "I benefit from the treatment" experienced increased pain relief (benefit 40 ± 30 vs. non-benefit 19 ± 26 mm, p = 0.010) and improved quality of life (benefit 33 ± 25 vs. non-benefit 18 ± 16 mm, p = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients.
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Dolor Crónico , Alianza Terapéutica , Persona de Mediana Edad , Humanos , Femenino , Masculino , Analgésicos Opioides/efectos adversos , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/inducido químicamente , Calidad de Vida , Estudios TransversalesRESUMEN
Adults with autism spectrum disorder (ASD) and associated intellectual disability (ID) take a high number of different psychotropic drugs simultaneously. Nowadays, little is known about this multidrug pattern efficacy and safety. The present study has endeavored to fill this gap creating a local pharmacovigilance system. A 36-month, retrospective and prospective, observational, and multicenter pharmacovigilance study was carried out in adults with ASD and ID (n = 83). Information regarding ongoing medications (polypharmacy: taking simultaneously >4 drugs; safety profile: adverse events' number, adverse drug reactions' number, and affected system; and observed-to-expected [O/E] ratio using the summary of product characteristics), and current diagnoses were recorded. A median of four ongoing medications per participant was registered, half of the sample was under polypharmacy regimen. Regarding all ongoing medications, 50% were antipsychotic drugs, and 47% of participants had >1 antipsychotic prescribed. In contrast, only 64 adverse events were identified from electronic health records, mostly due to risperidone. Half of them were related either to nervous or metabolic systems, and almost a third were not previously described in the corresponding drug summary of products characteristics. Extrapyramidalism, gynecomastia, hypercholesterolemia, and urinary retention were some AEs that occurred more frequently than expected (O/E ratio > 6 times) according to our data. The highest O/E ratio scores (>120 times) were for hypercholesterolemia and rhabdomyolysis caused by valproic acid. According to the number of adverse events and adverse drug reactions reported in electronic health records locally and nationally by clinicians, we need to increase awareness about medications safety. LAY SUMMARY: A 36-month study in adults with autism, ID, and polypharmacy (>4 drugs) was done to investigate drug safety on everyone. A median of four medications per person was registered, half were antipsychotic drugs, and 47% of participants had >1 antipsychotic medication simultaneously. Only 64 adverse events were identified from electronic health records, mostly due to risperidone. Half of them were related to nervous or metabolic systems and a third were not previously described in the drug information sheet.
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Trastorno del Espectro Autista , Discapacidad Intelectual , Adulto , Trastorno del Espectro Autista/tratamiento farmacológico , Humanos , Masculino , Estudios Prospectivos , Psicotrópicos/uso terapéutico , Estudios RetrospectivosRESUMEN
INTRODUCTION: The association between erectile dysfunction (ED) and cardiovascular disease (CVD) is well known, the latter being an early independent risk factor that can appear up to 5 years before the onset of cardiovascular symptoms. The enzyme endothelial nitric oxide synthase (eNOS) could be implicated in its pathophysiology as an endogenous vasodilator. Our objective was to analyse the influence of variants of the eNOS gene, in the response to treatment of ED, in patients with CVD. METHODOLOGY: Observational, prospective study in patients with ED of the Cardiac Rehabilitation Programme. Demographic variables were collected (International Index of Erectile Function (IIEF), quality of sexual life (mSLQQ), anxiety and depression (HAD), along with cardiovascular risk factors (CVRF). Genetic analysis of polymorphisms T-786C, G894T of the eNOS gene was performed by RT-PCR with TaqMan probe, and the data were analysed using SPSS 25. RESULTS: Patients (n = 35, 60.8 ± 8.44 years) showed a median CVD (IQR 1-3) with severe ED (IIEF-EF of 9.4 ± 6.73 points) and a low perception of their quality of sexual life (-19.4 ± 8.37 points). At the final visit (n = 15), there were 71% responders to treatment with iPDE5, with a significant improvement in their ED (IIEF = 49.4 ± 17.29, IIEF-FE = 18.5 ± 9.60 scores) and of their quality of sexual life (7 ± 12 scores), with a higher percentage of responders among the native homozygous genotypes -786-TT and 864-TT. CONCLUSION: Variants of the NOS3 gene could influence the response to iPDE5. Full analysis of the patient sample will be required to confirm these preliminary results.
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Enfermedades Cardiovasculares/complicaciones , Disfunción Eréctil/genética , Óxido Nítrico Sintasa de Tipo III/genética , Anciano , Disfunción Eréctil/enzimología , Disfunción Eréctil/etiología , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III/metabolismo , Polimorfismo Genético/genética , Estudios Prospectivos , EspañaRESUMEN
The prevalence of personality disorders (PDs) and sexual dysfunction in chronic pain patients is higher than in general population. Our main objective was to analyse the influence of PD in patients with erectile dysfunction and chronic non-cancer pain and their response to andrological treatment. One-hundred one patients were included along 30 months. Pain intensity, quality of life, sexual life quality, anxiety and depression were analysed together with opioid dose. Erectile functioning was measured with the International Index of Erectile Function (IIEF) and PDs with Millon Clinical Multiaxial Inventory (MCMI-III). The mean age was 57 ± 12 years old, with moderate to severe pain, 70% were sexually active and presented moderate to severe ED. PDs were very frequent (31%, cut-off 85 and 84% cut-off 75 scores) mostly anxiety, compulsive, though disorder, somatoform and narcissistic. Self-defeating feature presence was significantly correlated (r = -0.4, 95% CI = -0.605 to -0.145, p = 0.002) with a more severe baseline ED and narcissistic, and a better response to andrological treatment (p = 0.010, d = 1.082). Patients with dysthymia features required significantly higher opioid doses vs. control (238 vs. 102 mg/day, respectively). These findings underline the importance of diagnosing PDs to rigorously treat patients with chronic pain and ED.
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Dolor Crónico , Disfunción Eréctil , Anciano , Analgésicos Opioides/uso terapéutico , Dolor Crónico/complicaciones , Disfunción Eréctil/complicaciones , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Personalidad , Trastornos de la Personalidad/complicaciones , Trastornos de la Personalidad/epidemiología , Estudios Prospectivos , Calidad de VidaRESUMEN
Introduction: People with any psychiatric disorder tend to have difficulties in responding sexually. However,sexual dysfunction (SD) is usually under-recognized, even the tightly hormonal and neuronal common connexions through the brain-sex axis. Multiple sources of resistance to SD assessment and intervention persist. Areas covered: The present review aims to underline the feasibility to introduce SD evaluation in patients with any psychiatric disorders, evaluating the potential mutual benefits of their management. Expert opinion: Women and men living with mental disorders frequently display sexual difficulties; however, some of them consider sexuality as a relevant parameter of their quality of life. In fact, SD as a side effect is a frequent reason for stopping the intake of medication. What is more, a holistic approach integrating sexual function could foster a better understanding of mental pathologies due to a common origin of pathogenesis. This could improve care quality, in keeping with the global tendency toward the development of personalized medicine. Consistently, the integration of SD assessment is highly recommended in mental health, all the more so when a psychotropic drug is prescribed. An expected consequence would be a reconstruction of the healthcare professional's consideration for the sexuality of people experiencing mental disorders.
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Trastornos Mentales/complicaciones , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/etiología , Femenino , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Medicina de Precisión , Psicotrópicos/administración & dosificación , Psicotrópicos/efectos adversos , Calidad de Vida , Disfunciones Sexuales Fisiológicas/diagnóstico , Disfunciones Sexuales Psicológicas/diagnósticoRESUMEN
Nowadays, adults with autism spectrum disorder (ASD) experience several comorbidities whose treatment implies a wide range of psychotropic prescriptions. This study aimed to evaluate medication-related safety, drug-drug interactions, and psychotropics prescription trends. We conducted an observational and multicentric pharmacovigilance study in subjects with ASD and Intellectual disability (ID, n = 83). Clinical information (diagnoses, ongoing medications, comorbidities [multimorbidity ≥ 4 chronic health conditions]) and psychotropic prescriptions (polypharmacy ≥ 4 chronic drugs, daily drug doses, co-prescription) were registered. Ethical approval for this study was obtained. Participants (30±10 years old, 86% men, BMI 27±6 kg/m2) displayed 37% multimorbidity (mean of 3, IQR 2-4), and 57% polypharmacy (13% out of dose recommended range). Most drugs prescribed were psychotropic risperidone which is related to nervous system comorbidities (18% epilepsy, 16% insomnia, and 14% psychotic agitations). Risperidone and quetiapine were co-prescribed in 60% of the cases without any monitoring adverse event routine. The rates of multimorbidity and polypharmacy, among our young adults with ASD and ID, are concerning. Data suggest the need to develop a pharmacovigilance monitoring system to evaluate prescription accuracy, long-term safety of ongoing medications, and the fixed doses in this autistic population with associated ID.
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Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/epidemiología , Discapacidad Intelectual/tratamiento farmacológico , Discapacidad Intelectual/epidemiología , Polifarmacia , Psicotrópicos/uso terapéutico , Adulto , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Masculino , Multimorbilidad , Farmacovigilancia , Fumarato de Quetiapina/uso terapéutico , Risperidona/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVES: The use of opioids to relieve pain is a challenge because of the high variability in dose requirements and tolerance profiles. Among potential modulators are the individual's genetic background and being female. Our aim was to evaluate sex bias and genotype-related influence on opioid titration safety, in chronic low back pain (CLBP), the most frequent chronic noncancer pain. METHODS: A 3-year prospective study was developed in opioid-naive CLBP patients. Data were self-reported by patients (pain [Visual Analogy Scale], adverse events [AEs], and health care resource utilization) and physicians (analgesic prescription, morphine equivalent daily dose, and suspected adverse drug reactions [ADRs]). Outcomes were analyzed as patients with AEs (case) or without (control) together with patients' sex and genotype. Gene variants in OPRM1 (rs1799971), COMT (rs4680), ABCB1 (rs1045642), UGT2B7 (rs12233719 and rs7438135), KCNJ6 (rs2070995 and rs6517442), and CYP3A5*3 (rs776746) were assessed. The hospital ethics committee approved the study, and statistical analyses were performed with R, v.3.2.4. RESULTS: A total of 179 patients were included (64% female, mean pain intensity 73±16 mm), and 90% of them presented at least 1 AE (median of 3 (1 to 6) AEs/patient) with a rate of 5 AEs: 1 ADR without differences due to sex. However, there is a significant delay in referral of female patients (a mean of 6 years) to the Pain Unit, being significantly 3 to 5 times more likely to present sleep or psychiatric disorders. Meanwhile male individuals showed more sexual and reproductive system disorders. Genotypes influenced skin (COMT, G472A-GG) and gastrointestinal (ABCB1, C3435T-CC) related problems. CONCLUSIONS: Sex bias affects female patients resulting in a CLBP diagnostic delay and a different analgesic safety profile. Moreover, the individual's genetic background might be useful to predict certain AEs in opioid-naive patients under an opioid titration procedure. Addressing sex in necessary to resolve inequalities in health care access.
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Dolor Crónico , Dolor de la Región Lumbar , Analgésicos Opioides/efectos adversos , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/genética , Diagnóstico Tardío , Femenino , Genotipo , Humanos , Dolor de la Región Lumbar/tratamiento farmacológico , Dolor de la Región Lumbar/genética , Masculino , Estudios Prospectivos , Receptores Opioides mu/genética , SexismoRESUMEN
Safety data in chronic non-cancer pain (CNCP) with long-term opioid therapy has been poorly studied and can be differently influenced by gender. Furthermore, pharmacogenetics (PGx) could possibly be used to tailor pain medication based on the individual's genetic background. The aim was to assess whether PGx applied to a pharmacovigilance system could help to improve a patient's security profile. A pharmacovigilance data recording system was conducted over 24 months, including genotyping of OPRM1 variants (opioid receptor, A118G) and COMT (enzyme that degrades catecholamines such as norepinephrine, G1947A). Pain intensity (visual analogue scale, VAS), morphine equivalent daily dose (MEDD), adverse events (AEs) and suspected adverse drug reactions (ADRs) were recorded and analysed by gender. The Ethics Committee approved the study and data were analysed with R 3.6.0 software. A total of 748 patients were recruited in the study (67% female, VAS 62 ± 29 mm, MEDD 119 ± 114 mg/day) reporting a median of 6 (3.5-9) AEs/patient. Women presented more nausea, headaches, insomnia, loss of appetite, weight change, depression and dizziness than men. Analysis by genotype demonstrated that PGx influenced the prevalence of vomiting and depression in men, dizziness in women and sexual dysfunction in both. Physicians notified 150 ADRs mostly in females (79%) related to nervous system disorders. PGx applied to a pharmacovigilance recording system provides important information to achieve a better knowledge about AEs in CNCP pharmacological therapy. OPRM1 and COMT polymorphisms were associated with AEs in CNCP patients that differed according to gender.
Asunto(s)
Analgésicos Opioides/efectos adversos , Dolor Crónico/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Manejo del Dolor/métodos , Farmacogenética/métodos , Caracteres Sexuales , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/administración & dosificación , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Polimorfismo de Nucleótido Simple/genética , España/epidemiologíaRESUMEN
PURPOSE: Intellectual disability (ID) and autism spectrum disorder (ASD) are common, co-occurring developmental disorders and are frequently associated with sleep problems. This study aimed to assess the effectiveness and tolerability of agomelatine as a pharmacotherapy for sleep problems in ASD adults with ID. METHOD: A randomised, crossover, triple-blind, placebo-controlled clinical trial, with two three-month periods of treatment starting with either agomelatine or placebo and a washout period of two weeks. Ambulatory circadian monitoring (24 hours/7 days) evaluated total sleep time (TST) as the primary outcome variable. RESULTS: Participants (N=23; 35±12 years old; 83% male) had a median of three (interquartile range (IQR) 1-4) co-morbidities and were taking a median of five (IQR 2-7) prescribed drugs. Before agomelatine or placebo treatment, all subjects presented with insomnia symptoms, including sleep latency (100% abnormal, 55±23 minutes) or TST (55% abnormal, 449±177 minutes), and 66% had circadian rhythm sleep-wake abnormalities with rhythm phase advancements according to the M5 sleep phase marker values. During the three-month agomelatine treatment, night TST significantly increased by a mean of 83 minutes (16% abnormal, 532±121 minutes), together with a phase correction (M5 1:45±2:28 hours vs. 3:15±2:20 hours), improving sleep stability in wrist temperature rhythm (0.43±0.29 vs. 0.52±0.18 AU). Adverse events were mild and transient. CONCLUSIONS: Agomelatine was effective and well tolerated for treating insomnia and circadian rhythm sleep problems present in adults with ASD and ID.
Asunto(s)
Acetamidas/administración & dosificación , Trastorno del Espectro Autista/tratamiento farmacológico , Hipnóticos y Sedantes/administración & dosificación , Discapacidad Intelectual/tratamiento farmacológico , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Acetamidas/efectos adversos , Adulto , Trastorno del Espectro Autista/complicaciones , Ritmo Circadiano , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hipnóticos y Sedantes/efectos adversos , Discapacidad Intelectual/complicaciones , Masculino , Persona de Mediana Edad , Trastornos del Sueño-Vigilia/etiología , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVES: Chronic pain is one of the most common reasons individuals seek medical attention. It is a major issue because of the wide interindividual variability in the analgesic response. This might be partly explained by the presence of variants in genes encoding molecules involved in pharmacodynamics and pharmacokinetics. The aim was to analyze opioid effectiveness in chronic low back pain (CLBP) relief after opioid titration, unveiling the impact of pharmacogenetics. METHODS: The study included 231 opioid-naïve patients from the Spine Unit; age 63 ± 14 years, 64% female, body mass index 29 ± 6 kg/m2 , visual analog scale pain intensity score 73 ± 16 mm. Clinical data were collected at baseline, 3 months after opioid titration, and after 2 to 4 years of follow-up concerning pain (intensity and relief), quality of life, disability, comorbidities, and drug prescription (opioid dose, rotations, and adverse events). The genotype influence of OPRM1, COMT, UGT2B7, ABCB1, KCNJ6, and CYP3A5*3A in analgesic response was analyzed by reverse-transcription polymerase chain reaction genotyping. RESULTS: Patients with the COMT G472A-AA genotype (rs4680) and KCNJ6 A1032G-A allele (rs2070995) CLBP responded differently to opioid titration, with higher pain intensity requiring higher dosing. Furthermore, GG- genotypes of A118G (OPRM1, rs1799971) and A854G (UGT2B7, rs776746) influenced the neuropathic component. After opioid titration, CLBP intensity, neuropathic component, low back pain disability, anxiety, and depression significantly decreased, while quality of life improved. CONCLUSION: Single-nucleotide polymorphisms in genes involved in pain transmission and opioid metabolism might predispose to exaggerated sensitivity and differences in the opioid analgesic effect in patients with CLBP. We encourage clinical trials for their clinical application in chronic pain management.