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.

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.

More than half of patients with opioid use disorder for chronic non-cancer pain (CNCP) reduced their dose through a progressive opioid withdrawal supported by a rotation to buprenorphine and/or tramadol. The aim of this research is to analyse the long-term effectiveness of opioid deprescription taking into account the impact of sex and pharmacogenetics on the inter-individual variability. A cross-sectional study was carried out from October 2019 to June 2020 on CNCP patients who had previously undergone an opioid deprescription ( n = 119 patients). Demographic, clinical (pain, relief and adverse events) and therapeutic (analgesic use) outcomes were collected. Effectiveness (< 50 mg per day of morphine equivalent daily dose without any aberrant opioid use behaviour) and safety (number of side-effects) were analysed in relation to sex differences and pharmacogenetic markers impact [ OPRM1 genotype (rs1799971) and CYP2D6 phenotypes]. Long-term opioid deprescription was achieved in 49 % of the patients with an increase in pain relief and a reduction of adverse events. CYP2D6 poor metabolizers showed the lowest long-term opioid doses. Here, women showed a higher degree of opioid deprescription, but increased use of tramadol and neuromodulators, as well as an increased number of adverse events. Long-term deprescription was successful in half of the cases. Understanding sex and gender interaction plus a genetic impact could help to design more individualized strategies for opioid deprescription.

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.