Use of antidepressants and risk of repeat self-harm in older adults 75+ with nonfatal self-harm: A 1-year prospective national study

Purpose: To assess exposure to antidepressants (AD) before and after nonfatal self-harm (SH) in older adults and to examine 1-year rates and risk factors for subsequent SH. Methods: Longitudinal national register-based retrospective cohort study of Swedish residents aged 75+ (N = 2775) with treatment at hospital or specialist outpatient clinic in connection with SH between January 1, 2006, and December 31, 2013. The cohort was followed for 1 year after the index episode. Exposure to AD was assessed at index and at subsequent SH. Cox regression analysis was used to assess factors associated with 1-year repeat SH. Results: At the index episode, 51% were prevalent AD users; 23% started AD during the following year. Overall 12% of prevalent AD users, 8% of AD nonusers, and 6% of AD new users repeated SH or died by suicide. About two-thirds of these subsequent behaviors occurred within 3 months after the index episode. Men had increased risk of subsequent SH (Hazard ratio [HR] 1.38, 95% CI: 1.09-1.74); older age (>85 years) was associated with a lower risk (HR 0.72, CI 95% 0.55-0.93). Users of AD did not have an increased risk of repeat SH. Conclusions: Half of older adults who self-harmed were prevalent AD users and a further one fourth started an AD within 1 year after the index SH. Antidepressant use was not associated with increased risk of subsequent SH in this high-risk cohort of older adults

Antidepressant Use and Suicide Rates in Adults Aged 75 and Above: A Swedish Nationwide Cohort Study

Background: The treatment of depression is a main strategy for suicide prevention in older adults. We aimed to calculate suicide rates by antidepressant prescription patterns in persons aged ≥ 75 years. A further aim was to estimate the contribution of antidepressants to the change in suicide rates over time. Methods: Swedish residents aged ≥ 75 years (N = 1,401,349) were followed between 2007 and 2014 in a national register-based retrospective cohort study. Biannual suicide rates were calculated for those with selective serotonin reuptake inhibitor (SSRI) single use, mirtazapine single use, single use of other antidepressants and use of ≥ 2 antidepressants. The contribution of antidepressants to the change in biannual suicide rates was analyzed by decomposition analysis. Results: There were 1,277 suicides. About one third of these were on an antidepressant during their last 3 months of life. In the total cohort, the average biannual suicide rate in non-users of antidepressants was 13 per 100,000 person-years. The corresponding figure in users of antidepressants was 34 per 100,000 person-years. These rates were 25, 42 and 65 per 100,000 person-years in users of SSRI, mirtazapine and ≥ 2 antidepressants, respectively. In the total cohort, antidepressant users contributed by 26% to the estimated increase of 7 per 100,000 in biannual suicide rates. In men, biannual suicide rates increased by 11 suicides per 100,000 over the study period; antidepressant users contributed by 25% of the change. In women, those on antidepressant therapy accounted for 29% of the estimated increase of 4.4 per 100,000. Conclusion: Only one third of the oldest Swedish population who died by suicide filled an antidepressant prescription in their last 3 months of life. Higher suicide rates were observed in mirtazapine users compared to those on SSRIs. Users of antidepressants accounted for only one quarter of the increase in the suicide rate. The identification and treatment of suicidal older adults remains an area for prevention efforts.This study was funded by the Swedish Research Council (VR) 2016-01590, the Swedish Research Council for Health, Working Life and Welfare (Forte) 2016-07097, and ALFGBG433511 (Grants to MW). The sponsors had no role in the study design; collection, analysis, and interpretation of the data; writing of the report; or decision to submit the paper for publication. Söderström-König Foundation (to KH, Grant number 844351

Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study

Abstract Purpose Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs. Method Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs. Results Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65-3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls. Conclusion PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls

Disease Burden Attributed to Drug use in the Nordic Countries: a Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2019

The Nordic countries share similarities in many social and welfare domains, but drug policies have varied over time and between countries. We wanted to compare differences in mortality and disease burden attributed to drug use over time. Using results from the Global Burden of Disease (GBD) study, we extracted age-standardized estimates of deaths, DALYs, YLLs and YLDs per 100 000 population for Denmark, Finland, Iceland, Norway, and Sweden during the years 1990 to 2019. Among males, DALY rates in 2019 were highest in Finland and lowest in Iceland. Among females, DALY rates in 2019 were highest in Iceland and lowest in Sweden. Sweden have had the highest increase in burden since 1990, from 252 DALYs to 694 among males, and from 111 to 193 among females. Norway had a peak with highest level of all countries in 2001–2004 and thereafter a strong decline. Denmark have had the most constant burden over time, 566–600 DALYs among males from 1990 to 2010 and 210–240 DALYs among females. Strict drug policies in Nordic countries have not prevented an increase in some countries, so policies need to be reviewed.publishedVersio

Inappropriate prescribing, non-adherence to long-term medications and related morbidities : Pharmacoepidemiological aspects

Background: Inappropriate use of medications (IUM), in particular inappropriate prescribing and non-adherence to prescribed medications, are important causes of drug-related morbidities (DRMs). They are increasing problems with the ageing populations and the growing burden of chronic conditions. However, research is needed on the association of IUMs with DRMs in outpatient settings and in the general population. Aim: The aim of this thesis is to estimate and analyse the burden of potentially inappropriate prescriptions (PIPs) in the elderly and non-adherence to long-term medications among adults across care settings, and to investigate how IUM is associated to DRMs. Methods: A meta-analysis summarised the previous evidence on the percentage of adverse drug reactions (ADRs) associated to IUM across healthcare settings (Study I). From a cohort in the general population, using medical records and register data, the prevalence of PIPs in the elderly and its association with ADRs were estimated retrospectively (Study II). From the same cohort, the factors associated with refill non-adherence to antihypertensive therapy, considering the use of multiple medications, and the association between non-adherence and sub-therapeutic effects (STEs) were investigated (Study III). A survey assessed the refill behaviour to antihypertensive, lipid lowering and oral antidiabetic medications (undersupply, adequate supply and oversupply), and its association with perceived ADRs and STEs (Study IV). Results: IUM was the cause 52% and 45% of ADRs occurring in adult outpatients and inpatients respectively. Across healthcare settings, 46% of the elderly refilled PIPs over a 6-month period; PIPs were considered the cause of 30% of all ADRs; and the elderly who were prescribed PIPs had increased odds to experience ADRs (OR 2.47, 95% CI 1.65-3.69). In total, 35% was nonadherent to the full multidrug therapy and 13% was non-adherent to any medication (complete non-adherence).  Sociodemographic factors (working age and lower income) were associated with non-adherence to any medication, while clinical factors (use of specialised care, use of multiple medications, and being a new user) with non-adherence to the full multidrug therapy. STEs were associated with non-adherence to any medication a month prior to a healthcare visit (OR 3.27, 95% CI 1.27-8.49), but not with long-term measures of non-adherence. Among survey respondents, 22% of the medications were oversupplied and 12% were undersupplied. Inadequate refill behaviour was not associated with reporting ADRs or STEs (p<0.05). Conclusions: A large proportion of ADRs occurring in hospital is caused by IUM, but more knowledge is needed in other settings. PIPs are common in the elderly general population and associated with ADRs. Therefore decreasing PIPs could contribute towards ADR prevention. Considering the use of multiple medications may help to better understand the factors associated with non-adherence to a multidrug therapy for tailoring the interventions to patient needs. Monitoring the adherence prior to a healthcare visit may facilitate interpreting STEs. Yet, the absence of an association between long-term measures of refill non-adherence with clinical and perceived DRMs suggest the need to enhance the knowledge of this association in clinical practice. In summary, this thesis shows a significant potential for improvements of medication use and outcomes

Antidepressants and suicidal behaviour in late life: a prospectivepopulation-based study of use patterns in new users aged 75and above

AbstractPurpose To investigate associations between antidepressantuse patterns and risk of fatal and non-fatal suicidal behavioursin older adults who initiated antidepressant therapy.Method A national population-based cohort study conductedamong Swedish residents aged ? 75 years who initiated antidepressanttreatment. Patients who filled antidepressant prescriptionsbetween January 1, 2007 and December 31, 2013(N = 185,225) were followed until December 31, 2014. Subhazardratios of suicides and suicide attempts associated withuse patterns of antidepressants, adjusting for potential confounderssuch as serious depression were calculated usingthe Fine and Gray regression models.Results During follow-up, 295 suicides and 654 suicide attemptsoccurred. Adjusted sub-hazard ratios (aSHRs) wereincreased for both outcomes in those who switched to anotherantidepressant (aSHR for suicide 2.42, 95% confidence interval1.65 to 3.55, and for attempt 1.76, 1.32 to 2.34). Elevatedsuicide risks were also observed in those who concomitantlyfilled anxiolytics (1.54, 1.20 to 1.96) and hypnotics (2.20,1.69 to 2.85). Similar patterns were observed for the outcomesuicide attempt. Decreased risk of attempt was observedamong those with concomitant use of anti-dementia drugs(0.40, 0.27 to 0.59).Conclusion Switching antidepressants, as well as concomitantuse of anxiolytics or hypnotics, may constitute markersof increased risk of suicidal behaviours in those who initiateantidepressant treatment in very late life. Future researchshould consider indication biases and the clinical characteristicsof patients initiating antidepressant therapy.Keywords Antidepressants . Suicide .Pharmacoepidemiology . Aged . Cohort stud

Use of Psychoactive Medications and Risk of Suicide in Late Life (75+): A Total Population Study

Abstract Background Psychoactive medications play an important role for the mental health and risk of suicidal behaviour in the oldest segment of the population (75+). A better understanding of psychoactive medication use is advocated to prevent suicide in this age group. Purpose We investigated the risk of suicide associated with the use of psychoactive medications in the total population aged ≥ 75 years, with and without exposure to antidepressants. Method A national population-based register study, including all Swedish residents aged ≥ 75 years between 2006 and 2014 (N = 1,413,806). A nested case–control design was used to investigate psychoactive medications associated with suicide among users and non-users of antidepressants. Risk estimates were calculated in adjusted conditional logistic regression models for the entire cohort and by gender. Results Suicide occurred in 1305 persons (907 men and 398 women). Among them, 555 (42.5%) were on an antidepressant at the time of suicide. Adjusted incidence rate ratio (aIRR) for suicide was increased in those who were on hypnotics in the total cohort (aIRR 2.05, 95% confidence interval 1.74 to 2.41), in both users and non-users of antidepressants and for both genders. Elevated suicide risk was observed in those who concomitantly used anxiolytics with antidepressants (1.51, 1.25 to 1.83). Decreased risk of suicide was observed among those who were on anti-dementia drugs, in the total cohort (0.33, 0.21 to 0.52) and in both users and non-users of antidepressants. Use of antipsychotics and mood stabilisers showed no effect on suicide risk. Conclusion Use of hypnotics and concomitant use of anxiolytics with antidepressants was associated with increased risk of late-life suicide. Our findings suggest the need for careful evaluation of the benefit–risk balance of psychoactive medications as well as their availability as a possible suicide means. Future research should consider the indication of use of the psychoactive medications and the severity of psychiatric and medical illnesses of the patients

Authors

Refill adherence and self-reported adverse dru

Refill adherence and self-reported adverse drug reactions and sub-therapeutic effects : a population-based study

PURPOSE: To assess refill adherence to dispensed oral long-term medications among the adult population and to investigate whether the percentages of self-reported adverse drug reactions (ADRs) and sub-therapeutic effects (STEs) differed for medications with adequate refill adherence, oversupply, and undersupply. METHOD: Survey responses on self-reported ADRs and STEs were linked to the Swedish Prescribed Drug Register in a cross-sectional population-based study. Refill adherence to antihypertensive, lipid-lowering, and oral anti-diabetic medications was measured using the continuous measure of medication acquisition (CMA). The percentages of self-reported ADRs and STEs were compared between medications with adequate refill adherence (CMA 0.8-1.2), oversupply (CMA > 1.2), and undersupply (CMA < 0.8). RESULTS: The study included 1827 persons, and the refill adherence was measured for 3014 antihypertensive, 839 lipid lowering, and 253 oral anti-diabetic medications. Overall, 65.7% of the medications had adequate refill adherence, 21.9% oversupply, and 12.4% undersupply. The percentages of self-reported ADRs and STEs were respectively 2.6%, 2.7%, and 2.1% (p > 0.5) for ADRs and 1.1%, 1.6%, and 1.5% (p > 0.5) for STEs. CONCLUSIONS: Adequate refill adherence was found in two thirds of the medication therapies. ADRs and STEs were unexpectedly equally commonly reported for medications with adequate refill adherence, oversupply, and undersupply. These results suggest that a better understanding of patients' refill behaviors and their perceived medication adverse outcomes is needed and should be considered in improving medication management. The impact of individual and healthcare factors that may influence the association between refill adherence and reported medication adverse outcomes should be investigated in future studies. Copyright © 2013 John Wiley & Sons, Ltd

Potentially inappropriate prescribing and adverse drug reactions in the elderly : a population-based study

Purpose Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs. Method Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs. Results Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65–3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls. Conclusion PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls