Current Use Of Selective Serotonin Reuptake Inhibitors Research Articles

Use of Selective Serotonin Reuptake Inhibitors - Validity of Self-Report versus Plasma Concentrations and Pharmacy Dispensations - A Cross-Sectional Analysis of the Norwegian Women and Cancer Study.

PurposeTo validate self-reported current use of selective serotonin reuptake inhibitors (SSRI) in the Norwegian Women and Cancer study (NOWAC) and to identify factors associated with discordance between data sources.Material and MethodsThis is a cross-sectional record-linkage study comparing SSRI-use derived from four data sources: 1) Specific SSRI questions in the main NOWAC questionnaire, 2) Open questions on medication use in the small questionnaire following blood samples, 3) plasma concentration measurements for a subsample, and 4) pharmacy dispensations from the Norwegian prescription database (NorPD) where current use of SSRI was defined by Legend Time Duration (LTD). Among 105 855 women, aged 46 to 64 years and randomly selected from the general population, 70,191 had data on SSRI-use from both NOWAC and NorPD. Plasma concentration was measured for 93 pairs of self-reported SSRI-users and non-users, with dispensation data available for 68 pairs. Validity was assessed by sensitivity and specificity; agreement was assessed by Cohen’s kappa. Factors associated with discordance between information sources were analyzed by multiple binary logistic regression.ResultsWe found high sensitivity (89.5%) and specificity (98.7%) for the specific questions in the main questionnaire compared with pharmacy dispensations. Measured against plasma concentrations, current SSRI-use defined by open questions and pharmacy dispensations both had high sensitivity (100% and 92.5%, respectively) and specificity (98.6% both). Agreements (kappa) were similarly high for all comparisons (≥0.80). The factors associated with discordance between data sources included poor health, comorbidity, being single and not being in full time work. Education was inversely associated with discordance.ConclusionSelf-reported current use of SSRI from the NOWAC questionnaires is highly valid and, according to plasma concentrations, perhaps even more so than pharmacy dispensations. Factors associated with discordance between information sources should be taken into account in the interpretation of future analyses which include SSRI-use in the NOWAC study.

Selective Serotonin Reuptake Inhibitors and Risk of Noncardioembolic Ischemic Stroke: A Nested Case-Control Study.

Multiple studies have reported that the use of selective serotonin reuptake inhibitors (SSRIs) is associated with an increased risk of ischemic stroke; however, this finding may be the result of a confounding by indication. We examined the association using different approaches to minimize such potential bias. A nested case-control study was carried out in a Spanish primary health-care database over the study period 2001 to 2015. Cases were patients sustaining an ischemic stroke with no sign of cardioembolic or unusual cause. For each case, up to 5 matched controls (for exact age, sex, and index date) were randomly selected. Antidepressants were divided in 6 pharmacological subgroups according to their mechanism of action. The current use of SSRIs (use within a 30-day window before index date) was compared with nonuse, past use (beyond 365 days) and current use of other antidepressants through a conditional logistic regression model to obtain adjusted odds ratios and 95% CI. Only initiators of SSRIs and other antidepressants were considered. A total of 8296 cases and 37 272 matched controls were included. Of them, 255 (3.07%) were current users of SSRIs among cases and 834 (2.24%) among controls, yielding an adjusted odds ratio of 1.14 (95% CI, 0.97-1.34) as compared with nonusers, 0.94 (95% CI, 0.77-1.13) as compared with past-users and 0.74 (95% CI, 0.58-0.93) as compared with current users of other antidepressants. No relevant differences were found by duration (≤1, >1 year), sex, age (<70, ≥70 years old) and background vascular risk. The use of SSRIs was not associated with an increased risk of noncardioembolic ischemic stroke. On the contrary, as compared with other antidepressants, SSRIs appeared to be protective.

Antidepressants and the Risk of Cardiovascular Events in Elderly Affected by Cardiovascular Disease: A Real-Life Investigation From Italy.

The purpose of this study was to assess the possible relation between use of antidepressant (AD) drugs, that is, tricyclic ADs, selective serotonin reuptake inhibitors (SSRIs), and atypical ADs (AAs), and the risk of hospitalization for cardiovascular (CV) events among older patients with previous CV diseases. A nested case-control study was carried out among patients aged 65 years and older from 5 Italian health care territorial units who were discharged for CV disease during 2008 to 2010. The cohort was composed by 344,747 individuals, and of these, 97,739 (28%) experienced hospital admission for CV events (myocardial infarction, arrhythmia, stroke, heart failure) during follow-up (until 2014) and were included as cases. Up to 5 controls were randomly selected and matched to each. A conditional logistic regression was fitted to estimate the risk of CV events associated with ADs past or current use. A within-patient comparison was performed by the case-crossover design to account the effect of depression. Current users of SSRIs and AAs were at increased risk of CV events with odds ratios of 1.25 (95% confidence interval, 1.21-1.29) and 1.31 (1.25-1.37), respectively. An increased risk of arrhythmia and stroke was associated with current use of SSRIs and AAs, whereas an increased risk of heart failure was detected with current use of any ADs. The results were confirmed by the case-crossover approach. Evidence that AD use is associated with an increased risk of CV events in accordance with specific mechanisms of action among older people with CV disease was added by this study.

Antidepressants and the Risk of Hemorrhagic Stroke in the Elderly: a Nested Case–Control Study

Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed in the elderly due to a more favorable risk profile than other antidepressants (ADs). However, SSRIs are associated with an increased risk of gastrointestinal bleeding, while evidence on the risk of hemorrhagic stroke (HS) is limited. Therefore, we compared the risk of HS associated with the use of ADs in the elderly. Based on data from the German Pharmacoepidemiological Research Database (GePaRD), a case-control study matched on age, sex, and health insurance provider, nested in a cohort of incident users of ADs ≥ 65years of age was performed. Cases were identified from hospital discharge diagnoses, and exposure was identified from outpatient prescriptions. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Based on 4059 cases and 40,590 controls, an increased risk of HS was found in current use of SSRIs (OR 1.39, 95% CI 1.22-1.58), selective serotonin and noradrenaline reuptake inhibitors (1.69, 1.35-2.11), noradrenergic and specific serotonergic ADs (1.44, 1.22-1.69), and noradrenaline reuptake inhibitors (3.81, 1.54-9.43) compared with tri- and tetracyclic antidepressants. An increased risk of HS was seen in patients with a high baseline risk of bleeding and in patients with depression. The risk of HS varied between individual ADs. Our study shows that the use of medications inhibiting serotonin and/or noradrenaline reuptake increases the risk of HS in patients aged 65years and older and that the risk varies across individual ADs.

Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-life investigation from Italy.

The study aimed to fill existing knowledge gaps on the safety of antidepressant drugs (ADs) by estimating the risk of hospitalization for arrhythmia associated with use of selective serotonin reuptake inhibitors (SSRIs) and newer atypical ADs (NAAs) among elderly with previous cardiovascular (CV) events. The cohort was composed by 199,569 individuals aged ≥65years from five Italian healthcare territorial units who were discharged for cardiovascular outcomes in the years 2008-2010. The 17,277 patients who experienced hospital admission for arrhythmia during follow-up were included as cases. Odds of current ADs use among cases (i.e., 14days before hospital admission) was compared with (i) odds of current use of 1:5 matched controls (between-patients case-control) and with (ii) odds of previous use during 1:5 matched control periods (within-patient case-crossover). The risk of arrhythmia associated with ADs current use was modelled fitting a conditional logistic regression. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. Current users of SSRIs and NAAs were at increased risk of arrhythmia with case-control odds ratios (OR) of 1.37 (95% confidence interval, CI 1.18 to 1.58) and 1.41 (1.16 to 1.71) and case-crossover OR of 1.48 (1.20 to 1.81) and 1.72 (1.31 to 2.27). An increased risk of arrhythmia was associated with current use of trazodone (NAA) consistently in case-control and case-crossover designs. Evidence that current use of SSRIs and NAAs is associated to an increased risk of arrhythmia among elderly with CV disease was consistently supplied by two observational approaches.

Association of use of selective serotonin reuptake inhibitors with risk of acute pancreatitis: a case-control study in Taiwan.

Few studies have reported the association of the use of selective serotonin reuptake inhibitors (SSRIs) with acute pancreatitis. We conducted a population-based case-control study to explore this relationship. In this study, 4631 cases with first attack of acute pancreatitis and 4631 controls without acute pancreatitis were selected using a randomly sampled cohort of one million health insurance enrollees from 2000 to 2013. Both cases and controls were aged 20-84years and were matched with sex, age, comorbidities, and index year of diagnosis of acute pancreatitis. Patients with current use of SSRIs were defined as those whose last tablet of SSRIs was noted ≤7days before the date of diagnosis of acute pancreatitis; patients with late use of SSRIs were defined as those whose last tablet of SSRIs was noted ≥8days before the date of diagnosis; and patients with no use of SSRIs were defined as those who were never prescribed SSRIs. The odds ratio (OR) and 95% confidence interval (CI) for acute pancreatitis associated with the use of SSRIs were assessed using multivariate unconditional logistic regression analysis. After adjusting for covariables, multivariate logistic regression analysis revealed that compared with patients with no use of SSRIs, the adjusted OR of acute pancreatitis for those with current use of SSRIs was 1.7 (95% CI, 1.1-2.5), whereas that for patients with late use of SSRIs was 1.0 (95% CI, 0.9-1.2) without statistical significance. Current use of SSRIs is associated with the diagnosis of acute pancreatitis. Therefore, clinicians should consider the possibility of SSRI-associated acute pancreatitis among patients currently taking SSRIs and those presenting with the diagnosis of acute pancreatitis without a definite cause.

Association of Selective Serotonin Reuptake Inhibitors With the Risk for Spontaneous Intracranial Hemorrhage

Selective serotonin reuptake inhibitors (SSRIs) may increase the risk for spontaneous intracranial hemorrhage (ICH), an effect that is in theory linked to the strength of inhibition of serotonin reuptake of an antidepressant. However, whether antidepressants that are strong inhibitors of serotonin reuptake actually increase the risk for ICH and the effect of concomitant use of antithrombotics are unknown. To assess the risk for ICH associated with the use of SSRIs compared with tricyclic antidepressants (TCAs) among new users of antidepressants and according to the relative affinity of the antidepressant for the serotonin transporter and to assess whether concomitant use of antithrombotics modifies this risk. This population-based cohort study included new users of antidepressants 18 years or older from January 1, 1995, to June 30, 2014. More than 650 general practices in the United Kingdom contributing to the Clinical Practice Research Datalink enrolled patients. with use of a nested case-control approach, each case of a first ICH identified during follow-up was matched with as many as 30 control individuals by age, sex, calendar time, and duration of follow-up. Follow-up was completed on October 31, 2014. Current use of SSRIs compared with TCAs and strong compared with weak serotonin reuptake inhibitors. Incidence rate ratios (RRs) of ICH. Among a cohort of 1 363 990 incident users of antidepressants (36.8% male; 63.2% female; mean [SD] age, 47.9 [18.5] years), 3036 cases of ICH were identified during follow-up and matched to 89 702 controls. Current SSRI use was associated with an increased risk for ICH (RR, 1.17; 95% CI, 1.02-1.35) relative to TCAs, highest during the first 30 days of use (RR, 1.44; 95% CI, 1.04-1.99), and translating in very few additional events. Similarly, the risk was increased by 25% with strong inhibitors (RR, 1.25; 95% CI, 1.01-1.54) and highest during the first 30 days of use (RR, 1.68; 95% CI, 0.90-3.12). Concomitant use of anticoagulants may increase the risk substantially (RR, 1.73; 95% CI, 0.89-3.39). The use of SSRIs and more generally of antidepressants with strong inhibition of serotonin reuptake are associated with an increased risk for ICH, particularly in the first 30 days of use and when used concomitantly with oral anticoagulants.

Preadmission use of selective serotonin reuptake inhibitors and short-term mortality in diabetic patients hospitalized due to stroke.

Patients with diabetes have an increased risk of stroke with a poor prognosis. Moreover, diabetic patients are at increased risk of depression and therefore likely to use selective serotonin reuptake inhibitors (SSRIs). We examined whether preadmission SSRI use was associated with increased mortality in diabetic patients hospitalized due to stroke. Population-based medical databases were used to identify all first-time stroke-related hospitalizations and subsequent mortality in diabetic patients in Denmark between 2004 and 2012 (n = 12 620). Based on redeemed prescriptions, SSRI use was categorized as current (new or long term), former or nonuse, and absolute 30-day mortality and mortality rate ratios (MRRs) were computed using Cox regression controlling for confounding factors. Amongst SSRI nonusers, 30-day stroke mortality was 15.8% (10.4% for ischaemic stroke, 41.8% for intracerebral haemorrhage and 27.3% for subarachnoid haemorrhage). Amongst current SSRI users, 30-day stroke mortality was 23.3% (17.1% for ischaemic stroke, 50.7% for intracerebral haemorrhage and 28.6% for subarachnoid haemorrhage). Current SSRI use was associated with increased 30-day stroke mortality compared with nonuse [adjusted MRR 1.3, 95% confidence interval (CI) 1.1-1.5], with the highest risk observed amongst new users (MRR 1.5, 95% CI 1.2-1.8). Overall stroke mortality was driven by increased mortality due to ischaemic stroke, with adjusted MRRs of 1.3 (95% CI 1.1-1.7) for current users and 1.7 (95% CI 1.2-2.4) for new users. Propensity score-matched results were similar and robust across subgroups. In patients with diabetes, preadmission SSRI use was associated with increased mortality following ischaemic stroke, compared with nonuse.

Risk of Seizures Associated with Antidepressant Use in Patients with Depressive Disorder: Follow-up Study with a Nested Case-Control Analysis Using the Clinical Practice Research Datalink.

Antidepressant use has been associated with an increased risk of seizures. Evidence on the association between antidepressant use at therapeutic doses and seizures mainly comes from clinical trials that were not designed to investigate this potential relationship. The objective of this study was to assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders. We conducted a retrospective follow-up study with a nested case-control analysis between 1998 and 2012, using data from the UK-based Clinical Practice Research Datalink (CPRD). We estimated crude incidence rates with 95 % confidence intervals (CIs) of seizures in depressed patients who used selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), 'other antidepressants', no antidepressants, or who had used antidepressants in the past. To adjust for potential confounding, we estimated odds ratios of antidepressant drug use among cases with seizures and matched controls in a nested case-control analysis. Of 151,005 depressed patients, 619 had an incident seizure during follow-up. Incidence rates per 10,000 person-years were 12.44 (95 % CI 10.67-14.21) in SSRI users, 15.44 (95 % CI 8.99-21.89) in SNRI users, 8.33 (95 % CI 4.68-11.98) in TCA users, 9.33 (95 % CI 6.19-12.46) in non-users of antidepressants, and 5.05 (95 % CI 4.49-5.62) in past users of antidepressants. In the case-control analysis, relative risk estimates for seizures were increased in current users of SSRIs (adjusted odds ratio 1.98, 95 % CI 1.48-2.66) and SNRIs (adjusted odds ratio 1.99, 95 % CI 1.20-3.29), but not TCAs (adjusted odds ratio 0.99, 95 % CI 0.63-1.53), compared with non-users. Current use of SSRIs or SNRIs was associated with a twofold increased risk of first-time seizures compared with non-use, while current use of TCAs (mostly low dose) was not associated with seizures. Treatment initiation in SSRI and SNRI users was associated with a higher risk of seizures than longer-term treatment.

Antidepressant use and the risk of suicide: A population-based cohort study

BackgroundThe existing literature provides contradictory evidence on antidepressant use and risk of suicide. Some studies have shown that the use of Selective Serotonin Reuptake Inhibitors (SSRIs) is associated with an increased risk of suicide, especially during the first months of treatment, whereas other studies did not confirm this association. For this reason, our objective was to investigate the association between antidepressant use and risk of suicide in incident antidepressant users in relation to time since starting therapy. MethodsWe conducted a population-based cohort study within the Dutch Integrated Primary Care Information (IPCI) database, in incident users of antidepressant therapy between 1994 and 2012 (n=27,712). Cox proportional hazard models were used to study the association between current use of SSRIs, tricyclic antidepressants (TCA) and other antidepressants and risk of suicide or attempted suicide. ResultsDuring follow-up, a total of 280 incident antidepressant users attempted or committed suicide. Current use of SSRIs (hazard ratio (HR): 0.78, 95% CI: 0.57–1.07), TCAs (HR: 0.82, 95% CI: 0.48–1.42) or other antidepressants (HR: 0.75, 95% CI: 0.47–1.18) was not statistically significantly associated with suicide compared to past use of any of the antidepressants. LimitationsAlthough a large healthcare database was used, the number of reported cases of suicide (attempt) was low. ConclusionsThis study did not indicate an increase in risk of suicide after starting treatment with SSRIs, TCAs or other antidepressants compared with past antidepressant use.

Use of selective serotonin reuptake inhibitors and lifestyle among women of childbearing age: a Danish cross-sectional survey

ObjectiveTo examine the use of selective serotonin reuptake inhibitors (SSRIs) among Danish women of childbearing age according to lifestyle factors.DesignCross-sectional survey.SettingThe Central Denmark Region.Participants4234 women (71.5% of the invited women)...

Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures

Aim Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures. The serotonin transporter (5-HTT) has been located in the bone and may play a role in bone physiology. We assessed the association between antidepressant drug use, categorized in a therapeutical-based way and on basis of their affinity for the 5-HTT, and the risk of both osteoporotic and non-osteoporotic fractures. Methods A case–control study was conducted using the PHARMO RLS. Cases were patients with a first hospital admission for a fracture during the study period. Up to four controls were matched to each case on gender, age, geographical area, and index date. Results We identified 16,717 cases, of whom 59.5% had an osteoporotic fracture, and 61,517 controls. Compared to no use, current use of SSRIs was associated with a statistically significant increased risk of osteoporotic fractures (OR 1.95, 95% CI 1.69–2.26), as was current use of TCAs and non-SSRI/non-TCA antidepressant drugs (ORs 1.37, 95% CI 1.16–1.63 and 1.40, 95% CI 1.06–1.85, respectively). The risk of an osteoporotic fracture was statistically significantly higher for antidepressants with a high affinity for the 5-HTT (OR 1.86, 95% CI 1.63–2.13) compared to antidepressants with a medium or low affinity (OR 1.43, 95% CI 1.19–1.72 (medium) and OR 1.32 95% CI 0.98–1.79 (low) (p < 0.05 for trend). The risk of non-osteoporotic fractures did not show the same trend. Conclusions The extent of affinity for the 5-HTT may contribute to the increased risk of osteoporotic fractures related to antidepressant drug use. The pharmacological mechanism-based classification could to be an appropriate alternative for traditional classification to study the association between the use of antidepressants and the risk of fractures.

Risk of Ischemic Stroke Associated With Antidepressant Drug Use in Elderly Persons

Competing hypotheses have been formulated about a possible association between selective serotonin reuptake inhibitors (SSRIs) and ischemic stroke. However, the relationship between antidepressant drug use and ischemic stroke is still unclear. The aim of the study was to assess the association between the use of different types of antidepressants and the risk of ischemic stroke in elderly outpatients. A population-based, nested, case-control study was conducted in persons 65 years and older in the Integrated Primary Care Information database (1996-2005). Cases were all patients with a validated first ischemic stroke. Controls were matched on year of birth, sex, and index date. Exposure to antidepressants was divided in current, past, and nonuse and further categorized by type (SSRI, tricyclic, and other antidepressants), dose, and duration. Conditional logistic regression was used to compare the risk of ischemic stroke between users of antidepressants and nonusers. Overall, 996 incident ischemic strokes were identified. Current use of SSRIs was associated with a significantly increased risk as compared with nonuse (odds ratio, 1.55; 95% confidence interval, 1.07-2.25) in elderly patients, particularly when used for less than six months. No associations were observed for current use of tricyclic and other antidepressant drugs. To summarize, compared with nonuse, only SSRI use seems to be associated with an increased risk of ischemic stroke in elderly patients, particularly as a short-term effect.

Selective Serotonin Reuptake Inhibitors and the Risk of Cataracts: A Nested Case-Control Study

Older-generation antidepressants have been associated with increasing the risk of cataracts. Although animal studies have alluded to a potential link between selective serotonin reuptake inhibitors (SSRIs) and the development of cataracts, no large population based-study has addressed this potential association. This study sought to quantify the risk of cataracts with SSRIs by conducting a pharmacoepidemiologic study using the linked administrative databases in the province of Quebec, Canada. Nested case-control study. A cohort of subjects who had received a coronary revascularization procedure from 1995 through 2004 in the province of Quebec, Canada. Using an administrative data set, a case-control study was conducted within a cohort of Quebec residents who had received a coronary revascularization procedure from 1995 through 2004. Cases were defined as those with the first diagnosis of a cataract diagnosed by an ophthalmologist. For each case, 10 controls were selected and matched to the cases by index date, age, and cohort entry. Crude and adjusted rate ratios (RRs) and corresponding confidence intervals (CIs) were computed for current use of SSRIs. Rate ratios were adjusted for gender, corticosteroid use, statins, high blood pressure, antihypertensives, and antidiabetics. First International Classification for Disease (Ninth Revision) code for a cataract diagnosed by an ophthalmologist. Eighteen thousand seven hundred eighty-four cases and 187 840 controls met our study inclusion criteria. The adjusted RR for cataracts among current users of SSRIs was 1.15 (95% CI, 1.08-1.23). The risk of cataracts was highest with fluvoxamine (RR, 1.39; 95% CI, 1.07-1.80), followed by venlafaxine (RR, 1.33; 95% CI, 1.14-1.55) and paroxetine for cataract surgery (RR, 1.23; 95% CI, 1.05-1.45). The average time to diagnosis of cataracts while on SSRI therapy was 656 days. A possible association was found between current exposure to SSRIs, especially fluvoxamine and venlafaxine, and a future diagnosis of cataracts. The possibility that this observation may be the result of the effect of smoking, which could not be controlled for in the study, cannot be excluded. Future studies are needed to confirm this association in other populations.

Use of anti-depressants and the risk of fracture of the hip or femur

SummaryAnti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients.IntroductionAnti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use.MethodsA case–control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region.ResultsThe risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (ORadj) 2.35 [95% confidence interval (CI) 1.94–2.84]) and TCAs (ORadj 1.76 [95% CI 1.45–2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from ORadj 1.64 [95% CI 1.14–2.35] for drugs with low 5-HTT inhibition to ORadj 2.31 [95% CI 1.94–2.76] for those with high 5-HTT inhibiting properties.ConclusionCurrent use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

Selective serotonin reuptake inhibitor use and bone mineral density in women with a history of depression

Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for depression. They have been reported to regulate serotonin signalling in bone cells and may influence bone metabolism. This study aimed to investigate the effect of SSRIs on bone mineral density (BMD) in a sample of women with a lifetime history of depression. In this community-based study of 607 women, a history of depression was ascertained using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR research version, non-patient edition. BMD was measured at the posterior-anterior (PA) spine, hip, total body and forearm using dual energy absorptiometry, and medication use and lifestyle factors were self-reported. Among 177 women with a lifetime history of depression, current users of bisphosphonates, glucocorticoids, hormone therapy and antidepressants other than SSRIs were excluded. Of the remaining 128 (median age 51.5 years, range 30-74), 26 (20.3%) reported current SSRI use. After controlling for age, weight, height and smoking history, BMD among SSRI users was 5.6% lower at the femoral neck (P=0.03), 6.2% lower at the trochanter (P=0.04) and 4.4% lower at the mid-forearm (P=0.03) than nonusers. No differences in BMD were detected at other sites. Although the mechanism remains unclear, these observations are consistent with a role for the serotonergic system in regulating bone metabolism.

Association of Low Bone Mineral Density With Selective Serotonin Reuptake Inhibitor Use by Older Men

Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of antidepressants that block the serotonin transporter. Osteoblasts and osteocytes express functional serotonin transporters; serotonin transporter gene disruption in mice results in osteopenia; and SSRI use has been associated with increased risk of hip fracture. To determine whether SSRI use is associated with lower bone mineral density (BMD) in older men and to compare the results for SSRIs with those of other antidepressants, we performed a cross-sectional analysis of data from 5995 men 65 years and older participating in the prospective cohort Osteoporotic Fractures in Men Study. Main outcome measures included medication use; BMD at the femoral neck, greater trochanter, and lumbar spine measured by dual-energy x-ray absorptiometry; and potential covariates. In adjusted analyses, mean BMD among SSRI users (n=160) was 3.9% lower at the total hip and 5.9% lower at the lumbar spine compared with BMD in men reporting no antidepressant use (n=5708 [P=.002 for total hip; P<.001 for lumbar spine]). There was no significant difference among users of trazodone hydrochloride (n=52) or tricyclic antidepressants (n=99) compared with nonusers. Adjusting for variables that could be associated with BMD and/or SSRI use did not significantly alter these results. The observed difference in BMD for SSRIs is similar to that seen with glucocorticoids. In this population of men, BMD was lower among those reporting current SSRI use, but not among users of other antidepressants. Further research is needed to confirm this finding in light of widespread SSRI use and potentially important clinical implications.

Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study

Objective To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between...

Current Use of Selective Serotonin Reuptake Inhibitors and Risk of Acute Myocardial Infarction

It has been suggested that increased platelet activation increases the risk of acute myocardial infarction (AMI) in patients with depression. Selective serotonin reuptake inhibitors (SSRIs) may attenuate platelet activation by serotonin depletion in platelets. Observational studies have shown discrepant results of AMI risk associated with the use of SSRIs. The aim of this study was to evaluate the association of exposure to different groups of antidepressants, including SSRIs, and the risk of AMI. The study also assessed in more detail the influence of timing of the exposure to antidepressants in a general adult population (<90 years of age), with or without diagnosed risk factors for AMI. We conducted a population-based case-control analysis on the UK General Practice Research Database (GPRD). The study included 8688 patients (<90 years of age), with a first-time AMI between 1995 and 2001, and 33 923 controls, who were matched by age, sex, calendar time, and general practice. Conditional logistic regression was used to estimate odds ratios (ORs). Current use of an antidepressant was defined as a supply of the last prescription for an antidepressant that lasted up to the index date or beyond. Recent past use was defined as a supply of the last prescription for an antidepressant that ended 1-29 days before the index date. SSRIs investigated were citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine. Non-SSRIs investigated were amitriptyline, clomipramine, dosulepin, doxepin, imipramine, lofepramine, nefazodone, trazodone and trimipramine. Other antidepressants included were amoxapine, desipramine, lithium, maprotiline, mianserin, moclobemide, nortriptyline and protriptyline. Adjusted ORs (with 95% CI) for the current use of SSRIs, non-SSRIs, or other antidepressants, compared with non-use of antidepressants, were 0.63 (95% CI 0.43, 0.91; p=0.02), 0.92 (95% CI 0.77, 1.09; p=0.32) and 0.59 (95% CI 0.29, 1.20; p=0.14), respectively. The adjusted OR of recent past use of SSRIs compared with non-use of SSRIs was 1.42 (95% CI 1.02, 1.97; p=0.04). The present analysis provides further evidence that the current use of SSRIs is associated with a slightly decreased risk for AMI.

Use of selective serotonin reuptake inhibitors and risk of developing first-time acute myocardial infarction.

Selective serotonin reuptake inhibitors (SSRIs) have been associated with serotonin depletion in platelets, potentially leading to abnormal aggregation and prolonged bleeding time. In view of the importance of serotonin in coronary thrombosis, and decreased platelet serotonin concentrations associated with SSRIs, the present study was performed to test the hypothesis of a decreased risk of acute myocardial infarction (AMI) associated with SSRIs. We conducted a population-based case-control analysis using the UK General Practice Research Database (GPRD). A total of 3319 patients aged 75 years or younger free of clinical conditions predisposing to ischaemic heart disease, with a first-time diagnosis of AMI between 1992 and 1997, and 13 139 controls without AMI matched to cases for age, sex, general practice attended, and calendar time were included. Conditional logistic regression was used to estimate relative risks. Adjusted odds ratios (with 95% CI) for current use of SSRIs, non-SSRIs, or other antidepressants, compared to the group of nonusers of antidepressants were 0.9 (95% CI 0.5,1.8), 0.9 (95% CI 0.7,1.2), and 1.3 (95% CI 0.6,2.8), respectively. As compared with nonuse of SSRIs, current use (regardless of any other antidepressants used) resulted in an adjusted OR of 1.1 (95% CI 0.7,1.6). The current analysis provides evidence that SSRI exposure does not substantially decrease the risk of developing first-time AMI in patients free of factors predisposing to ischaemic heart disease. However, due to relatively small numbers of exposed subjects and the resulting wide confidence intervals, further studies may be needed to document a lack of effect of SSRIs in subjects without pre-existing diseases predisposing to AMI.