Personality and psychiatric disorders in chronic pain male affected by erectile dysfunction: prospective and observational study.

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.

Gender based differences, pharmacogenetics and adverse events in chronic pain management.

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.

OPRM1 Gene Interaction with Sleep in Chronic Pain Patients Treated with Opioids.

BACKGROUND: The experience of chronic non-cancer pain (CNCP) is one of the most common reasons individuals seek medical attention. Patients with CNCP frequently experience concomitant sleep-related problems. OBJECTIVES: The aim was to evaluate sleep problems in opioid naïve CNCP patients, before and after opioid titration, analyzing the influence of OPRM1 gene variants. STUDY DESIGN: A prospective, cohort, observational study. SETTING: This study was performed at the Pain Unit of the Alicante University General Hospital. METHODS: Pain and Medical Outcomes Study Sleep questionnaire (MOS-Sleep) were assessed at baseline and 3 months after opioid titration in 231 opioid naïve CNCP patients. Sleep data was compared with a matched-control group (n = 64). Morphine equivalent daily doses, adverse events, and drugs prescribed for pain were also registered. OPRM1 polymorphism rs1799971 was analyzed by RT-PCR. Ethics Committee approved the study and results were analyzed by R software. RESULTS: After 3 months of opioid titration, patients with CNCP (63 ± 14 years, 64% female, VAS 74 ± 17 mm) significantly decreased pain intensity, anxiety and depression, and increased quality of life. Sleep problems were significantly more frequent in females (P = 0.002). Age, quality of life, anxiety, and depression all influenced sleep disturbances and problems indices, which were significantly different from the control group. Furthermore, the OPRM1 118-GG genotype was also associated with significantly lower sleep adequacy, and more sleep problems. LIMITATIONS: Total number of subjects studied was relatively small and most patients were on other non-opioid centrally-acting medications. CONCLUSIONS: Opioids decreased CNCP severity, improving patients' psychological areas, and quality of life. However, patients with OPRM1 118-GG genotype indicated an increase in sleep problems and worsening sleep pattern while taking opioids. KEY WORDS: OPRM1, pharmacogenetics, MOS-Sleep, opioids, chronic noncancer pain, sleep related problems, sleep problem index SLP-6 and SLP-9.

Health benefits of an adverse events reporting system for chronic pain patients using long-term opioids.

BACKGROUND: Safety data from long-term opioid therapy in the real world has been poorly studied in chronic non-cancer pain (CNCP). The aim was to design a pharmacovigilance data recording system and assess whether participation in this recording system improves pain management, enhancing patient's health status. METHODS: A pharmacovigilance data recording system was conducted during 24 months. Data were self-reported by patients (pain, adverse events [AEs] and healthcare resources use) and physicians (morphine equivalent daily dose [MEDD] prescribed and suspected adverse drug reaction [ADRs]). Outcomes from patients with (case) or without (controls) suspected ADRs and cases follow-up were also compared with Spanish Pharmacovigilance System data. RESULTS: A total of 753 patients were recruited in 897 visits. Fentanyl and tramadol were the most prescribed opioids, 89% with concomitant drugs, pregabalin being the one with the most potential drug interactions. Cases presented significantly higher pain intensity (VAS 67 ± 26 vs 59 ± 30 mm, P < 0.05), number of AEs (8 ± 6 vs 5 ± 3 AEs/patient, P < 0.01), polypharmacy related to pain (65% vs 34%, P < 0.01) and MEDD (139 ± 130 vs 106 ± 99 mg/d, P < 0.01) than controls. Furthermore, cases presented significant higher changes in pharmacological pain therapy due to pain, unplanned emergency visits and hospital admission than controls. Physicians notified 168 suspected ADRs mostly related to neurological or psychiatric events and 8% of them were previously unknown. CONCLUSIONS: This data recording system provided important information to achieve a better control of CNCP pharmacological pain therapy, improving patient's health status and reducing costs to the Health System.

Endothelial nitric oxide synthase gene polymorphisms and erectile dysfunction in chronic pain.

OBJECTIVES: To investigate whether endothelial nitric oxide synthase (eNOS) T786C, 4VNTR and G894 T gene polymorphisms could mediate in andrological treatment response in Spaniards. SUBJECT PATIENTS/METHODS: The study participants were Spaniard males with erectile dysfunction (ED) and chronic pain (n = 105) recruited at the Pain Unit. eNOS polymorphisms were genotyped by quantitative polymerase chain reaction using Taqman specific probes. Statistical analyses were carried out using R-3.2.4 software. RESULTS: A total of 69 patients required andrological treatment and 76% of them improved ED upon iPED5 (20%), testosterone (35%) or iPDE5/testosterone treatment (45%); being significantly better in T786C-CC patients. Multivariate regression analysis indicated that age, opioid daily dose and carriage of T786C-C allele influenced the risk and ED severity in Spaniard chronic pain patients. CONCLUSION: T786C polymorphism at eNOS locus appeared to be a major contributor in the variable erectile function iPDE5/testosterone response in Spaniards.

The relationship of salivary testosterone and male sexual dysfunction in opioid-associated androgen deficiency (OPIAD).

BACKGROUND: Opioids are an effective treatment for chronic non-malignant pain (CNP). Long-term use risks and side effects such as opioid-induced androgen deficiency (OPIAD) exist. This could be measured by saliva testosterone (Sal-T). OBJECTIVES: To evaluate OPIAD in long-term opioid use in CNP patients. METHODS: A cross-sectional study included CNP male outpatients under opioid treatment. Total-Testosterone (Total-T), Free-Testosterone (Free-T), Bio-Testosterone (Bio-T) and Sal-T were measured. Correlations were calculated by Spearman's rho (SPSS 20). RESULTS: From 2012 to 2014, 134 from 249 (54%) consecutive male outpatients reported erectile dysfunction (ED), 37% of them related to opioids and 19% evidenced OPIAD. A total of 120 subjects (94 cases and 26 matched-controls) were included. A significantly lower luteinizing hormone, Total-T and Free-T were found, as well as, a significant correlation between Sal-T and Total-T (r = 0.234, p = 0.039), Bio-T (r = 0.241, p = 0.039), IIEF (r = 0.363, p = 0.003) and HAD-anxiety (r = -0.414, p = 0.012) in OPIAD patients. Sal-T levels were significantly lower in patients with severe-moderate ED versus mild ED (p = 0.045) and in patients with severe ED versus moderate-mild ED (p = 0.036). CONCLUSIONS: These data demonstrate the high prevalence of ED in long-term use of opioids, part of this is associated to OPIAD, which can be tested by Sal-T as a non-invasive approach.

Opioids Increase Sexual Dysfunction in Patients With Non-Cancer Pain.

INTRODUCTION: Long-term opioid therapy has been found to have a strong impact on the hypothalamic-pituitary-gonadal axis that can be manifested clinically by sexual dysfunction (SD). This event is rarely reported and thus unnoticed and undertreated. AIM: To analyze the presence of SD in a large group of patients receiving long-term opioids. METHODS: A descriptive, cross-sectional pilot study of sexual health was conducted for 2 years in 750 consecutive ambulatory patients with chronic non-cancer pain (CNP) receiving opioids for at least 12 months. Cases that reported SD and matched controls were included. Standardized questionnaires and medical record reviews were used to assess rates of pain at diagnosis, daily morphine equivalent doses, and opioid adverse effects. MAIN OUTCOME MEASURES: Sexual function was determined by the Female Sexual Function Index (FSFI; scores = 2-36) and the International Index of Erectile Function erectile function domain (IIEF-EF; scores = 1-30). RESULTS: Thirty-three percent of 33% of 750 patients with CNP recorded SD based on their spontaneous notification at the pain unit. Men reported SD significantly more frequently than women (33% vs 25%, respectively, P < .05), although they reported having a regular partner (84% vs 70%, P = .03) and a sexually active life (69% vs 34%, respectively, P = .00) significantly more often. FSFI scores were significantly influenced by sexual activity in lubrication and arousal. IIEF scores were significantly determined by age in satisfaction with sexual intercourse and overall satisfaction. The morphine equivalent dose was significant higher in men than in women (38%; median = 70 mg/d, interquartile range = 43.1-170, 115.5 ± 110.3 mg/d vs median = 60 mg/d, interquartile range = 30-100.6, 76.67 ± 63.79 mg/d, P = .016) at the same mean intensity of pain (P = .54), which correlated to FSFI scores (r = -0.313, P = .01). CONCLUSION: SD is prevalent in patients with CNP and higher in men who received a significantly higher mean opioid dose at the same intensity pain level than women. The morphine equivalent dose was correlated to SD intensity. Evidence-based interventions to support sexual activity and function in CNP are needed.