Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019).

Background and aims: Diabetes-related foot ulcers (DFU) are a persistent healthcare challenge, impacting both patients and healthcare systems, with adverse effects on quality of life and productivity. Our primary aim was to examine the trends in lifetime prevalence of DFU, as well as other micro- and macrovascular complications in the Trøndelag Health Study (HUNT) in Norway. Methods: This study consists of individuals ≥20 years with diabetes participating in the population-based cross-sectional HUNT surveys (1995-2019). Prevalence ratios, comparing the lifetime prevalence of DFU and other relevant micro- and macrovascular complications between the HUNT surveys, were calculated using Poisson regression. Results: The lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 11.0% (9.5-12.7) in HUNT2, 7.5% (6.3-8.8) in HUNT3 and 5.3% (4.4-6.3) in HUNT4. The decrease in DFU prevalence from 1995 to 2019 was observed in both men and women, for all age groups, and for both type 1 and type 2 diabetes. The highest lifetime prevalence of DFU was found among those with type 1 diabetes. The decrease in HbA1c from HUNT2 to HUNT4 did not differ between those with and without a DFU. The prevalence of chronic kidney disease (eGFR <60 mL/min/1.73 m2 (eGFR categories G3-G5)) increased in both individuals with and without a DFU. Conclusion: Results from the HUNT surveys show a substantial decline in the lifetime prevalence of DFU from 1995 to 2019.

Age of onset for increased dose-adjusted serum concentrations of antidepressants and association with sex and genotype: An observational study of 34,777 individuals.

PURPOSE: The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype. METHODS: Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs). RESULTS: A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44‒55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive. CONCLUSION: The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants.

High number of hypoglycaemic episodes identified by CGM among home-dwelling older people with diabetes: an observational study in Norway.

BACKGROUND: A scoping review from 2021 identified a lack of studies on the incidence, prevention and management of hypoglycaemia in home-dwelling older people with diabetes. The aim of this study was to investigate the frequency and duration of hypoglycaemic episodes measured by continuous glucose monitoring (CGM) in older people with diabetes who received home care and who were treated with glucose-lowering medications, and to compare the frequency and duration of hypoglycaemic episodes between subgroups of the study population according to demographic and clinical variables. METHODS: This was an observational study investigating the occurrence of hypoglycaemia in people with diabetes aged ≥ 65 years. Data were collected using blinded continuous glucose monitoring (CGM, iPro2) for 5 consecutive days. Frequency and duration of hypoglycaemic episodes were assessed using a sensor glucose cut-off value of 3.9 mmol/L. A blood sample for measurement of HbA1c and creatinine-based eGFR (CKD-EPI) was obtained during the monitoring period. Demographic and clinical data were collected from electronic patient records. RESULTS: Fifty-six individuals were enrolled (median age 82 years and 52% were men). Of the 36 participants who were treated with insulin, 33% had at least one hypoglycaemic episode during the five-day period. Among 18 participants who neither used insulin nor sulfonylurea, but other glucose-lowering medications, 44% had at least one hypoglycaemicepisode. Of those with hypoglycaemic episodes, 86% lived alone. The median duration of the hypoglycaemia was 1 h and 25 min, ranging from 15 min to 8 h and 50 min. CONCLUSION: This study identified an unacceptably high number of unknown hypoglycaemic episodes among older home-dwelling people with diabetes receiving home care, even among those not using insulin or sulfonylurea. The study provides essential knowledge that can serve as a foundation to improve the treatment and care for this vulnerable patient group. The routines for glucose monitoring and other prevention tasks need to be considered more comprehensively, also, among those treated with glucose-lowering medications other than insulin.

Medication reconciliation-is it possible to speed up without compromising quality? A before-after study in the emergency department.

OBJECTIVE: The aim of this study was to investigate whether it was possible to decrease the time used for medication reconciliation (MR) in the emergency department without compromising quality. A more efficient method will enable more patients to receive MR as early as possible after admission to hospital. METHODS: Potential key factors for improvement of the standard method of MR by clinical pharmacists were identified through an observational period. A revised method was developed, focusing on decreasing time spent on the patient interview by use of a condensed checklist and probing questions based on information from a prescription database. Non-inferior quality (proportion of patients with at least one identified medication discrepancy and number of identified medication discrepancies per patient) of the revised method was evaluated using a before-after study design with 200 individuals in each group. Non-inferiority limit was set at 10%. The Mann-Whitney U test was used for statistical evaluation of the difference in time use per patient in the MR process between the before and after group. RESULTS: Mean age of the included patients was 78 years in both groups. The time used for MR in the after group was 34% shorter (37 min vs 56 min, p<0.0001) compared with the before group. The revised method was shown to be non-inferior compared with the original method with respect to the proportion of patients with at least one identified discrepancy (81%, 95% CI 76% to 86% vs 79%, 95% CI 73% to 84%). Also, non-inferiority was shown for the number of identified discrepancies per patient, where the average number of discrepancies per patient was 1.9 (95% CI 1.7 to 2.1) in both groups. CONCLUSION: This study showed that it was possible to speed up the MR process without compromising its effectiveness in identifying medication discrepancies.

Older people living at home: experiences of healthy ageing.

AIM: The purpose of this study was to investigate how old persons perceived their life to be, how they viewed the ageing process and their need of health care and societal support. BACKGROUND: The purpose of WHO's Healthy Ageing strategy and development of age-friendly environments is to support physiological and psychosocial changes in old persons by facilitating basic needs. Interventions to operationalize these needs in older people living at home are often developed from a professional perspective and to a small extent involves the perceptions, experience and expectations of the older persons. METHOD: This qualitative study has an explorative design using focus group discussions to collect data. In all, 34 persons between 69 and 93 years of age participated in seven group discussions. The interviews were analyzed using inductive manifest content analysis. FINDINGS: The main results suggest that most old persons enjoyed life and wished it to continue for as long as possible. Important was to sustain networks and to feel useful. Unexpected changes were described as threats and the need to use health care services was associated with illness and being dependent. The result is presented in three categories with sub-categories: 'Embracing life', 'Dealing with challenges' and 'Considering the future'.

Documented diabetes care among older people receiving home care services: a cross-sectional study.

BACKGROUND: Home care services plays an important role in diabetes management, and to enable older adults remain home-dwellers. Adequate follow-up and systematic nursing documentation are necessary elements in high quality diabetes care. Therefore, the purpose of this study was to examine the diabetes treatment and management for older persons with diabetes receiving home care services. METHODS: A cross-sectional study was used to assess the diabetes treatment and management in a Norwegian municipality. Demographic (age, sex, living situation) and clinical data (diabetes diagnose, type of glucose lowering treatment, diabetes-related comorbidities, functional status) were collected from electronic home care records. Also, information on diabetes management; i.e. follow-up routines on glycated haemoglobin (HbA1c), self-monitoring of blood glucose, insulin administration and risk factors (blood pressure, body mass index and nutritional status) were registered. HbA1c was measured upon inclusion. Descriptive and inferential statistics were applied in the data analysis. RESULTS: A total of 92 home care records from older home-dwelling persons with diabetes, aged 66-99 years were assessed. Only 52 (57 %) of the individuals had the diabetes diagnosis documented in the home care record. A routine for self-monitoring of blood glucose was documented for 27 (29 %) of the individuals. Only 2 (2 %) had individual target for HbA1c documented and only 3 (3 %) had a documented routine for measuring HbA1c as recommended in international guidelines. Among 30 insulin treated older individuals, a description of the insulin regimen lacked in 4 (13 %) of the home care records. Also, documentation on who performed self-monitoring of blood glucose was unclear or lacking for 5 (17 %) individuals. CONCLUSIONS: The study demonstrates lack of documentation in home care records with respect to diagnosis, treatment goals and routines for monitoring of blood glucose, as well as insufficient documentation on responsibilities of diabetes management among older home-dwelling adults living with diabetes. This indicates that home care services may be suboptimal and a potential threat to patient safety.

Polypharmacy and Potential Drug-Drug Interactions in Home-Dwelling Older People - A Cross-Sectional Study.

BACKGROUND: Risks associated with polypharmacy and drug-drug interactions represent a challenge in drug treatment, especially in older adults. The aim of the present study was to assess the use of prescription and non-prescription drugs and the frequency of potential drug-drug interactions in home-dwelling older individuals. METHODS: A cross-sectional study design was applied. Data were collected during preventive home visits among individuals aged ≥75 in three separate communities of Western Norway. A questionnaire, which was filled out by the individual, their next-of-kin, and the nurse performing the home visit was used for the collection of demographic and clinical data (age, sex, medication use, diagnoses, need of assistance with drug administration). Potential drug-drug interactions were identified electronically by IBM Micromedex Drug Interaction Checking. Point prevalence of potential drug-drug interactions and polypharmacy (≥5 drugs) were calculated. Binary logistic regression analyses were performed to assess factors potentially associated with polypharmacy or potential drug-drug interactions. RESULTS: Among the 233 individuals (mean age 78±3 years, 46% male) included in the study, 43% used ≥5 drugs, 3.4% ≥10 drugs, while 4.3% used no drugs. In 54% of the 197 individuals using two or more drugs, at least one potential drug-drug interaction was detected. Low-dose aspirin and simvastatin were most frequently involved in potential drug-drug interactions. In total, 25% of the individuals reported current use of drugs sold over the counter of which more than 95% were analgesic drugs. Potential drug-drug interactions involving ibuprofen were identified in nine of 11 (82%) individuals using over-the-counter ibuprofen. CONCLUSION: The study revealed a high prevalence of polypharmacy and potential drug-drug interactions with both prescription and non-prescription drugs in older home-dwelling individuals. Close monitoring of the patients at risk of drug-drug interactions, and increased awareness of the potential of over-the-counter drugs to cause drug-drug interactions, is needed.

Continuous glucose monitoring in older people with diabetes receiving home care-a feasibility study.

BACKGROUND: Hypoglycemic incidents in older people can cause severe health problems, enhance general age-related disabilities, and cause frailty. Little is known about incidences of hypoglycemia in older home-dwelling people with diabetes. Thus, the aim of this study was to examine the feasibility of capturing hypoglycemia and issues associated with increased risk of hypoglycemia by use of continuous glucose monitoring (CGM) and standardized questionnaires among older home-dwelling individuals with diabetes type 2 receiving home care. METHODS: CGM with the Ipro2-blinded monitoring system were performed for 5 days in six home-dwelling individuals ≥ 75 years diagnosed with diabetes and receiving home care. Demographic (age, gender, living arrangements) and clinical data (diabetes diagnoses and duration, diabetes medication, documented treatment goal, available glycosylated hemoglobin (HbA1c)) were collected from electronic patient records in home care services. Feasibility (ease of use, quality of data, time spent) of standardized questionnaires to identify the risk of hypoglycemia (the McKellar Risk Assessment Tool), risk of malnutrition (the Mini Nutritional Assessment (MNA)), functional status (the Individual-based Statistics for Nursing and Care Services (IPLOS)), and cognitive status (the Mini Mental Status Exam (MMSE)) was also assessed. Questionnaire data was collected by a study nurse in the individuals' home. RESULTS: The practical use of CGM was satisfactory, with no major remarks about discomfort or technical errors, except for one participant with skin reaction (redness). Collecting data with the McKellar Risk Assessment Tool, MNA and IPLOS worked well according to quality of data, time spent, and ease of use. The MMSE survey required extensive training of personnel to be conducted. CONCLUSION: The feasibility study informs an upcoming study on the incidence and risk factors of hypoglycemia in home-dwelling older individuals. We will ascertain that personnel who will use the MMSE questionnaire to collect cognitive status and skills are familiar with the tool and adequately educated and trained before study start. The use of blinded CGM in this population was well tolerated and can be used "as is" for future studies.

Hypoglycaemia in older home-dwelling people with diabetes- a scoping review.

BACKGROUND: Hypoglycaemia is associated with cognitive and functional decline in older people with diabetes. Identification of individuals at risk and prevention of hypoglycaemia is therefore an important task in the management of diabetes in older home-dwelling individuals. The purpose of this scoping review was to map the literature on hypoglycaemia in home-dwelling older people with diabetes. METHODS: This scoping review included original research articles on hypoglycaemia in older (≥ 65 years) individuals with diabetes from developed countries. A broad search of the databases Cinahl, Embase and Medline was performed in July 2018. The report of the scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews. RESULTS: Our database search identified 577 articles of which 23 were eligible for inclusion. The identified literature was within four areas: 1) incidence of hypoglycaemia in older home-dwelling people with diabetes (11/23 articles), 2) risk factors of hypoglycaemia (9/23), 3) diabetes knowledge and self-management (6/23) and 4) consequences of hypoglycaemia for health care use (6/23). The majority of the literature focused on severe hypoglycaemia and the emergency situation. The literature on diabetes knowledge and management related to preventing adverse events relevant to older home-dwellers, was limited. We found no literature on long-term consequences of hypoglycaemia for the use of home health care services and the older persons' ability to remain home-dwelling. CONCLUSIONS: We identified a lack of studies on prevention and management of hypoglycaemia in the older individuals' homes. Such knowledge is of utmost importance in the current situation where most western countries' governmental policies aim to treat and manage complex health conditions in the patient's home. Future studies addressing hypoglycaemia in older individuals with diabetes are needed in order to tailor interventions aiming to enable them to remain home-dwelling as long as possible.

Factors associated with self-rated health in a Norwegian population of older people participating in a preventive home visit program: a cross-sectional study.

BACKGROUND: Assessing self-rated health by preventive home visits of older people can provide information about the person's well-being, quality of life and risk of developing illness. The aim of this study was to examine associations between self-rated health and factors related to demographics, lifestyle, health conditions and medical diagnoses by older people participating in a preventive home visit program. METHODS: A cross-sectional study including 233 participants (age 75-79) from three municipalities of Western Norway was conducted. Data were collected through preventive home visits performed by six nurses, using a questionnaire including self-rated health assessment and questions and tests related to demographics (e.g. education and housing), lifestyle (e.g. social activities, alcohol and smoking), health conditions (e.g. sensory impairment, pain and limited by disease) and medical diagnoses. Descriptive and inferential statistics including linear block-wise regression model were applied. RESULTS: The block-wise regression model showed that the variables Limited by disease and Pain were negatively associated with self-rated health and Use internet was positively associated. The model had a R2 0.432. The variable that contributed to largest change in the model was Limited by disease (R2 Change; 0.297, p-value< 0.001). CONCLUSIONS: In the present study, being limited by disease and pain were strongly associated with poor self-rated health, indicating that these are important factors to assess during a preventive home visit. Also, digital competence (Use internet) was associated with a better self-rated health, suggesting that it could be useful to ask, inform and motivate for the use of digital tools that may compensate for or improve social support, social contact and access to health -related information.

Use of Antidepressants in Older People during a 10-Year Period: An Observational Study on Prescribed Doses and Serum Levels.

BACKGROUND: According to previous studies, older patients frequently have serum concentrations of antidepressant medication above the recommended reference range. OBJECTIVE: The aim of this study was to investigate whether prescribed doses of antidepressants and the proportion of individuals with serum concentrations above the recommended reference range in older individuals (≥ 65 years) have changed over a 10-year period in Norway. METHODS: Serum concentration measurements and prescribed daily doses of antidepressants in 2007 and 2017 were extracted from a therapeutic drug monitoring (TDM) database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. The database contains routine follow-up serum concentration measurements of psychotropic drugs for patients from all parts of the country. For citalopram, escitalopram, sertraline, mirtazapine and venlafaxine, the differences between 2007 and 2017 in mean prescribed doses and the proportion of patients with at least one serum concentration above the reference range, according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guidelines, were compared. For the proportion of patients with serum concentrations above the recommended reference range, differences between individuals aged 65-79 and ≥ 80 years were also examined. RESULTS: The analyses of prescribed doses included 806 patients from 2007 and 1932 patients from 2017, with 972 and 2441 TDM samples, respectively. Between 2007 and 2017, modest reductions in prescribed daily doses were observed for citalopram (20 vs. 17 mg/day) and escitalopram (11 vs. 10 mg/day), but the proportion of patients with serum concentrations above the recommended reference range was unchanged for both drugs, i.e. 11.5% vs. 12.4% for citalopram and 3.6% vs. 2.9% for escitalopram. For mirtazapine and venlafaxine, prescribed doses were reduced from 28 to 25 mg/day and 150 to 125 mg/day, respectively. A significant reduction in the proportion of individuals with serum concentrations above the recommended reference range was observed for mirtazapine (27.1% vs. 11.5%) and for individuals aged ≥ 80 years using venlafaxine (60.0% vs. 30.0%). For sertraline, no differences in prescribed doses or serum concentrations above the recommended reference range were observed. CONCLUSIONS: Over a 10-year period, prescribed doses of antidepressants have been slightly reduced in older Norwegian patients, but a considerable proportion is still exposed to high serum concentrations of antidepressants.

Prevalence of drug use among adults with intellectual disabilities compared with drug use in the general population.

PURPOSE: Individuals with intellectual disabilities (IDs) have more health problems, a poorer general health, and a shorter life expectancy than individuals in general. High rates of drug use in IDs have been reported. Despite the increasing interest in health problems in individuals with IDs, little is known about their drug use. METHOD: Drug use in a community sample of adults with IDs (N = 593) was compared with dispensed drugs in a time-, age-, and region-matched comparison group of adults in Western Norway (N = 289 325). A logistic regression model was employed by using the main group effect to describe and analyze the differences between the ID sample and the comparison sample and by using the interaction term (group × age) to describe the rate change differences from the reference age (18-30 years) between the two groups. RESULTS: Total drug use in the ID sample was 62% compared with 50% in the reference sample (P = 0.0001). The high prevalence of drugs for the nervous system (ATC N) in the ID sample (50%) explained the difference. From age 51 and over, the increase in the drug use rate for the cardiovascular disease was significantly lower in the ID sample than in the reference sample (P value range: 0.002-0.019). CONCLUSIONS: Adults with IDs use more drugs than adults in general. However, the findings showed lower rates of drug use in the ID sample than in the general population for drugs targeting diseases that are the leading causes of death in individuals with IDs.

Determination of Tacrolimus Concentration and Protein Expression of P-Glycoprotein in Single Human Renal Core Biopsies.

BACKGROUND: Tacrolimus (TAC) is currently the cornerstone of immunosuppressive protocols for renal transplant recipients. Despite therapeutic whole blood monitoring, TAC is associated with nephrotoxicity, and it has been hypothesized that intrarenal accumulation of TAC and/or its metabolites are involved. As TAC is a substrate of P-glycoprotein (P-gp), the expression and activity of this efflux transporter could influence the levels of TAC in renal tissue. The primary aim of this study was to develop and validate a method for quantification of TAC in tissue homogenates from single human renal core biopsies. The secondary aim was to provide measures of P-gp expression and of the demethylated metabolites of TAC in the same renal biopsy. METHODS: Human renal tissue, with and without clinical TAC exposure, was used for method development and validation. Homogenates were prepared with bead-beating, and concentrations of TAC and its demethylated metabolites were analyzed with liquid chromatography tandem mass spectrometry after protein precipitation. A Western blot method was used for semiquantification of P-gp expression in the homogenates. The final methods were applied to renal core biopsies from 2 transplant patients. RESULTS: The TAC assay showed within- and between-run mean accuracy between 99.7% and 107% and coefficients of variation ≤6.7%. Matrix effects were nonsignificant, and samples were stable for 3 months preanalytically when stored at -80°C. TAC concentrations in the renal core biopsies were 62.6 and 43.7 pg/mg tissue. The methods for measurement of desmethyl-TAC and P-gp expression were suitable for semiquantification in homogenates from renal core biopsies. CONCLUSIONS: These methods may be valuable for the elucidation of the pharmacokinetic mechanisms behind TAC-induced nephrotoxicity in renal transplant recipients.

High Tacrolimus Clearance Is a Risk Factor for Acute Rejection in the Early Phase After Renal Transplantation.

BACKGROUND: Patients with high tacrolimus clearance eliminate more drug within a dose interval compared with those with low clearance. Delays in dosing time will result in transient periods of lower concentrations in high versus low clearance patients. Transient subtherapeutic tacrolimus concentrations may induce acute rejection episodes. METHODS: A retrospective study in all renal transplant patients treated with tacrolimus at our center from 2009 to 2013 was conducted. The association between individually estimated tacrolimus clearance (daily tacrolimus dose [mg]/trough concentration [µg/L]) and biopsy-proven acute rejection (BPAR) the first 90 days posttransplantation was investigated. RESULTS: In total, 638 patients treated with oral tacrolimus were included in the analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified into 4 groups per their estimated clearance. The patients in the high clearance group had significantly higher incidence of BPAR (20.6%) with a hazard ratio of 2.39 (95% confidence interval, 1.30-4.40) compared with the low clearance group. Clearance estimate (as a continuous variable) showed a hazard ratio of 2.25 (95% confidence interval, 1.70-2.99) after adjusting for other risk factors. There were no significant differences in neither trough concentrations the first week after transplantation nor time to target trough concentration between patients later experiencing BPAR or not. CONCLUSIONS: High estimated clearance is significantly associated with increased risk of BPAR the first 90 days posttransplantation and may predict an increased risk of rejection in the early phase after renal transplantation.

Psychotropics and weak opioid analgesics in plasma samples of older hip fracture patients - detection frequencies and consistency with drug records.

AIMS: To determine use of psychotropic drugs and weak opioids in hip fracture patients by analysing plasma samples at admission, and compare detected drug frequencies with prescription registry data and drug records. METHODS: Plasma from 250 hip fracture patients aged ≥65 years sampled at hospital admission were analysed by ultra-performance liquid chromatography-tandem mass spectrometry methods for detection of psychotropic drugs and weak opioid analgesics (alcohol also determined). Odds ratios for drugs detected in plasma of hip fracture patients vs. prescription frequencies of the same drugs in an age-, time- and region-matched reference population were calculated. Moreover, recorded and measured drugs were compared. RESULTS: Psychotropic drugs and/or weak opioid analgesics were detected in 158 (63%) of the patients (median age 84 years; 76% females), while alcohol was found in 19 patients (7.6%). The occurrence of diazepam (odds ratio 1.6; 95% confidence interval 1.1-2.4), nitrazepam (2.3; 1.3-4.1), selective serotonin reuptake inhibitors (1.9; 1.3-2.9) and mirtazapine (2.3; 1.2-4.3) was significantly higher in plasma samples of hip fracture patients than in prescription data from the reference population. Poor consistency between recorded and measured drugs was disclosed for z-hypnotics and benzodiazepines; e.g. diazepam was detected in 29 (11.6%), but only recorded in six (2.4%) of the patients. CONCLUSIONS: Plasma analysis shows that use of antidepressants and benzodiazepines in hip fracture patients is significantly more frequent than respective prescription frequencies in the general elderly population. Moreover, consistency between recorded and actual use of psychotropic fall-risk drugs is poor at hospital admission of hip fracture patients.

Therapeutic Drug Monitoring of Selective Serotonin Reuptake Inhibitors in Elderly Patients.

BACKGROUND: Elderly patients are at increased risk for elevated serum concentrations from treatment with selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to examine the use of therapeutic drug monitoring (TDM) of SSRIs in elderly compared with younger patients. METHODS: All serum concentration measurements of SSRIs (escitalopram, citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) performed at our laboratory in 2011 were included. The use of TDM (relative frequency) in older versus younger patients was examined by comparing the use of TDM in patients aged 60 years or older with that in patients younger than 60 years and by evaluating the use of TDM relative to age (age groups in decennials). The number of patients with an SSRI dispensed by prescription in the same region and period (the Norwegian Prescription Database) was used as reference. Additionally, the number of samples above the upper limit of the recommended reference range in patients aged 60 years or older and patients younger than 60 years was evaluated. RESULTS: TDM of an SSRI had been performed in 6333 patients. For all SSRIs, the use of TDM was significantly lower (8.2% versus 10.6% for citalopram, 10.0% versus 13.8% for escitalopram, 8.6% versus 17.0% for fluoxetine, 5.6% versus 10.3% for paroxetine, and 8.1% versus 15.0% for sertraline) in patients aged 60 years or older compared with those younger than 60 years (P < 0.001). There was a gradual decline in the use of TDM with increasing age, with a 3-fold difference between the youngest (10-19) and oldest (90+) patients (P < 0.0001). The percentage of samples above the upper limit of the recommended reference range was 2-fold higher in patients aged 60 years or older (6.7%) compared with patients younger than 60 (3.4%) years (P < 0.0001). CONCLUSIONS: Clinical follow-up of patients with TDM of SSRIs is less frequent in older patients compared with younger patients. This is in contrast to the general guidelines for TDM where patients of advanced age are considered of particular importance to monitor closely.

Impact of genetic variability in CYP2D6, CYP3A5, and ABCB1 on serum concentrations of quetiapine and N-desalkylquetiapine in psychiatric patients.

BACKGROUND: To investigate the impact of genetic variability in CYP2D6, CYP3A5, and ABCB1 on steady-state serum concentrations of quetiapine and the active metabolite, N-desalkylquetiapine, in psychiatric patients. METHODS: Measured serum concentrations of quetiapine and N-desalkylquetiapine from patients with biobanked DNA samples were included retrospectively from a routine therapeutic drug monitoring database. The impact of CYP2D6, CYP3A5, and ABCB1 (345C>T) genotypes on dose-adjusted serum concentrations (C/D ratios) of quetiapine and N-desalkylquetiapine was investigated by multivariate mixed model analysis. RESULTS: In total, 289 patients with 633 serum measurements were included. In the multivariate analysis, mean C/D ratio of N-desalkylquetiapine was estimated to be 33% and 22% higher in inherent CYP2D6 poor metabolizers (P = 0.03) and heterozygous extensive metabolizers (P < 0.001), respectively, compared with inherent extensive metabolizers. The ABCB1 3435C>T polymorphism and CYP3A5 genotype had no significant influence on either of the substances in the present material. CONCLUSIONS: Genetic variability in CYP2D6 contributes to the interindividual variability in steady-state serum concentrations of N-desalkylquetiapine. Although the metabolite exhibits relevant pharmacological activity, the quantitative effect of CYP2D6 genotype on serum concentration of N-desalkylquetiapine is probably of limited clinical relevance for quetiapine treatment.

Impact of age on serum concentrations of venlafaxine and escitalopram in different CYP2D6 and CYP2C19 genotype subgroups.

PURPOSE: The aim of the present study was to investigate the effect of age on venlafaxine and escitalopram serum concentrations in various cytochrome P450 (CYP) 2D6 and CYP2C19 genotype subgroups. METHODS: Serum concentration measurements from CYP-genotyped patients treated with venlafaxine (n = 255) or escitalopram (n = 541) were collected retrospectively from a therapeutic drug monitoring database. Patients were divided into three CYP2D6 (venlafaxine) or CYP2C19 (escitalopram) phenotype subgroups according to inherited genotype, i.e., poor metabolizers (PMs), heterozygous extensive metabolizers (HEMs), and extensive metabolizers (EMs), and subsequently distributed into three age groups, i.e., <40 (control), 40-65, and >65 years. The effect of age on dose-adjusted serum concentrations (i.e., nmol/L/mg/day) of venlafaxine and escitalopram in each of the phenotype subgroups was evaluated by separate multivariate mixed model analyses. RESULTS: In CYP2D6 PMs, the mean dose-adjusted serum concentration of venlafaxine was 8-fold higher in patients >65 years compared with those <40 years (p < 0.001). In comparison, the respective age-related differences in mean dose-adjusted serum concentrations of venlafaxine were much less pronounced in CYP2D6 HEMs and EMs (<2-fold differences between age groups). A similar genotype-related effect of age was not observed for escitalopram (<1.5-fold age differences in all CYP2C19 subgroups). CONCLUSION: This study suggests that the effect of age on serum concentration of venlafaxine is dependent on CYP genotype, in contrast to escitalopram. Thus, to prevent potential side effects, it might be particularly relevant to consider CYP2D6 genotyping prior to initiation of venlafaxine treatment in older patients.