Use Of Serotonin-norepinephrine Reuptake Inhibitors Research Articles

Serotonin and norepinephrine reuptake inhibitors association with dry mouth in a hospital population.

Xerostomia, or dry mouth, is a condition that results from the reduction or absence of saliva flow secondary to the use of certain medications. The objective of the present study was to analyze the relationship between xerostomia patients and the consumption of serotonin norepinephrine reuptake inhibitors (SNRIs). The University of Florida (UF) Integrated Data (IDR) i2b2, for the period of June 2015 to September 2022, was used based on aggregates of the International Classification of Diseases 10th edition (ICD-10) diagnoses of dry mouth and use of SNRI. MedCalc Software was used to calculate odds ratios. The odds ratio for dry mouth in the SNRI group was 5.95 (95% CI 5.47 to 6.48, P < .0001). The odds ratio for dry mouth in females on SNRI was 5.48 (95% CI 4.97 to 6.02, P < .0001), for males 5.48 (95% CI 4.56 to 6.95), P < .0001), for children 2.87 (95% CI 1.19 to 6.96, P = .0192), and for adults 4.46 (95% CI 4.09 to 4.86, P < .0001). When the different SNRIs were analyzed separately, the odds ratio for dry mouth with the use of venlafaxine was 5.83 (95% CI 5.12 to 6.6, P < .0001), duloxetine 6.97 (95% CI 6.33 to 7.67, P <.0001), desvenlafaxine 5.24 (95% CI 3.65 to 7.52, P < .0001), and milnacipran 9.61 (95% CI 5.66 to 16.31, P < .0001). According to the present study, patients who are taking SNRIs are five-fold more likely to develop dry mouth compared to those not on medications. The results could be informative to medical professionals who prescribe SNRIs and who are not currently aware of the effect they have on salivary production and therefore quality of life, as well as the dental practitioners treating these patients with dry mouth sequalae.

Increased Readmission Rates in Younger Male Patients Due to Suicidal Risk in Newly Diagnosed Depressive Disorders After Initiation of Serotonin Reuptake Inhibitors.

Background Depressive disorders have a prevalence of 322 million people worldwide and are a leading cause of morbidity. These disorders can affect individuals of all ages and can present over time. Due to the diversity in the presentation of depressive disorders, vigilance towards depressive disorders can lead to more timely and effective treatment. Serotonin Selective Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) are the first lines of treatment for these disorders. Moreover, the United States Food and Drug Administration (FDA) issued a black-box warning for several antidepressants, stating an increased risk of suicidality in individuals under 25 years old. However, the placement of this black-box warning has been controversial. In this study, the authors aim to investigate if there is a relationship between the use of SSRI or SNRI on patients with newly diagnosed depressive disorder and hospital readmission due to suicide-related events. Methods For this retrospective cohort study, de-identified data were obtained from the HCA Healthcare database by searching for patients newly diagnosed with depressive disorders and started on SSRIs or SNRIs. Patient data were evaluated for readmissions due to suicide-related events within 90 days of discharge from the hospital and establishing their initial SSRI/SNRI prescription. Results After data was obtained and evaluated via statistical analysis, the variables with statistical significance were: age (p-value = 0.0164) and sex (p-value = 0.0150). These two were significantly associated with the rate of readmission: younger and male patients had an increased risk of readmission due to suicide-related events within 90 days of discharge after starting SSRI, or SNRI, to treat depressive disorders. Conclusion These results support the importance of monitoring patients started on SSRI or SNRI, with particularly careful consideration in depressed young male patients.

Antidepressant medication and risk of cardiovascular disease in posttraumatic stress disorder patients: application of marginal structural models in Korean National Health Insurance Database

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): - National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT Introduction Previous evidence on antidepressant medication and cardiovascular disease (CVD) in posttraumatic stress disorder (PTSD) patients is mixed. We evaluated associations between antidepressant medication and CVD by applying marginal structural model. Methods We gathered medical utilization records of 27,170 patients diagnosed with PTSD in years 2004 - 2018 without prior CVD diagnosis from Korean National Health Insurance Database (NHID). PTSD and CVD were characterized in correspondence of ICD-10 diagnostic codes. We acquired information on antidepressant use from medical utilization records and categorized by medication category: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Discrete-time survival analysis with marginal structural inverse probability weighting was used to test association between antidepressants and CVDs and were compared to results from traditional time-fixed model and simple time-varying model. We calculated cumulative daily defined doses (DDDs) of each antidepressant categories and conducted polynomial splining to test dose response. Results SSRI use was associated with acute coronary syndrome (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.26 - 1.86) and ischemic stroke (HR 1.33, 95% CI 1.08 - 1.63). SNRI use was associated with acute coronary syndrome (HR 1.52, 95% CI 1.09 - 2.12). TCA use was associated with acute coronary syndrome (HR 1.54, 1.21 - 1.96) and ischemic stroke (HR 1.34, 1.06 - 1.70). Polynomial spline showed positive dose-response in association between antidepressant use and CVD. Conclusion Antidepressant use is causally associated with CVD in patients with PTSD. Higher cumulative DDD of antidepressant increases the risk of CVD.

EPH8 Pregnancy Outcomes of Serotonin-Norepinephrine Reuptake Inhibitors (SNRI): Analysis of FDA Adverse Event Reporting System (FAERS) Database (2012-2021)

The use of Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) during pregnancy is a controversial issue as SNRIs can affect the development of the fetus negatively. There is relatively limited information regarding the impact of SNRIs among women during their pregnancy. The objective of the study was to describe the most commonly reported pregnancy adverse events (AEs) related to SNRIs as reported in the FDA Adverse Event Reporting System (FAERS) database.

Association of Periodic Limb Movements With Medication Classes: A Retrospective Cohort Study.

To investigate the association between various medication classes and the periodic limb movement index (PLMI) in a clinical cohort of adults who completed in-laboratory polysomnography. A single, diagnostic, overnight, in-laboratory polysomnogram was completed for 3,488 patients consecutively referred from 2010 to 2015 to determine PLMI. Medication use and medical comorbidities were collected through patient questionnaires. Associations between medication classes and PLMI were ascertained using multivariable ordinal logistic regression models. The median age of the cohort was 56.0 years (48.2% male). After adjusting for age, sex, body mass index, relevant comorbidities, and sleep measures, the use of selective serotonin reuptake inhibitors (SSRIs) (odds ratio [OR] 1.52) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (OR 1.99) was associated with increased PLMI. Conversely, gabapentinoids (OR 0.71), stimulants (OR 0.52), benzodiazepines (OR 0.79), and dopamine agonists (OR 0.38) were associated with decreased PLMI. A non-statistically significant trend for decreased PLMI with neuroleptic use was observed. No significant associations were found between PLMI and the use of antihypertensives, statins, tricyclic antidepressants, bupropion, anticoagulants, antiplatelets, modafinil, and antihistamines. The use of SSRIs and SNRIs was associated with elevated PLMI while the use of gabapentinoids, stimulants, benzodiazepines, and dopamine agonists was associated with decreased PLMI. These results can assist physicians in managing periodic limb movements in sleep (PLMS) and invite further research into the relationship between PLMS and medications with the modulating effects of dose, formulation type, and time of administration. This study provides Class II evidence that SSRIs and SNRIs are associated with elevated PLMI while gabapentinoids, stimulants, benzodiazepines, and dopamine agonists are associated with decreased PLMI.

Association of Type of Antidepressant Initiation with Bleeding Risk in Atrial Fibrillation Patients Taking Oral Anticoagulants.

BackgroundInconsistent evidence suggests that use of certain antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), in patients using oral anticoagulants (OACs) might be associated with an elevated risk of bleeding.ObjectiveThis study aims to investigate the risk of bleeding associated with initiation of different types of antidepressants among atrial fibrillation (AF) patients on OAC therapy.Patients and methodsA total of 30,336 AF patients (mean age 72.2 years; 54% female) on OAC therapy that started antidepressant treatment were identified from the Truven Health Analytics MarketScan Commercial and Medicare Databases for the period 2007–2015. Exposure was defined as filling a prescription for antidepressant, and categorized as SSRI, serotonin/norepinephrine reuptake inhibitors (SNRIs), serotonin reuptake inhibitors (SRIs), tricyclic antidepressants (TCAs), or other antidepressants. The primary outcome was incident hospitalized bleeding. Associations of antidepressant type with bleeding were assessed calculating hazard ratios (HRs) and 95% confidence intervals (CIs) with adjusted Cox models in pairwise propensity score-matched cohorts.ResultsDuring a mean follow-up of 21 months, we identified 1612 bleeding episodes. In pairwise comparisons, SSRI use was associated with an increased risk of bleeding when compared to most other antidepressants (HR 1.22, 95% CI 0.96–1.54 vs SNRI; HR 1.10, 95% CI 0.90–1.35 vs SRI; HR 1.03, 95% CI 0.82–1.30 vs TCA). SNRI use was associated with the lowest bleeding risk. Results did not differ by OAC type, age, and sex.ConclusionsAmong AF patients on OAC initiating antidepressants, risk of bleeding varied across antidepressant type. This information can inform treatment choices among patients receiving OAC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00258-3.

Selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitors and epidemiological characteristics associated with prenatal diagnosis of congenital heart disease.

Identify early pregnancy associations of congenital heart disease (CHD) in a multiethnic cohort. This retrospective observational cohort study compared the general obstetric population to women who gave birth at a referral centre in Australia between 2012 and 2017, after 20 weeks' of gestation, with a pregnancy affected by CHD. We defined mood disorder and anxiety as a history of self-reported or medically diagnosed anxiety, depression, postpartum depression or bipolar disorder. We compared epidemiological factors between 30 842 general obstetric patients and 470 obstetric patients with a foetus affected by CHD. Multivariate analysis showed independent associations between CHD and use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in the first trimester (relative risk [RR] 4.14, 95% CI 2.58-6.65), history of anxiety or mood disorder with no SSRI/SNRI first trimester (RR 2.20, 95% CI 1.77-2.74), folate and/or pregnancy multivitamin use in the first trimester (RR 0.69, 95% CI 0.55-0.87) and increased risk with maternal age >40 years (RR 2.30, 95% CI 1.57-3.38). Our data show maternal mood disorders with and without SSRI or SNRI use, maternal age >40 years and lack of multivitamin/folate use to be independently associated with CHD in pregnancy.

Using nationally representative survey data for external adjustment of unmeasured confounders: An example using the NHANES data.

To evaluate the use of data from population-based surveys such as the National Health and Nutrition Examination Survey (NHANES) for external adjustment for confounders imperfectly measured in health care databases in the United States. Our example study used Medicaid Analytic eXtract (MAX) data to estimate the relative risk (RR) for prenatal serotonin-norepinephrine reuptake inhibitors (SNRIs) exposure and cardiac defects. Smoking and obesity are known confounders poorly captured in databases. NHANES collects information on lifestyle factors, depression, and prescription medications. External adjustment requires information on the prevalence of confounders and their association with SNRI use; which was obtained from the NHANES. It also requires estimates of their association with the outcome, which were based on the literature and allowed us to correct the RR using sensitivity analyses. In MAX, the RR for the association between prenatal SNRI exposure and cardiac defects was 1.51 unadjusted and 1.20 adjusted for measured confounders and restricted to women with depression. In NHANES, among women of childbearing age with depression, the prevalence of smoking was 60.2% (95% Confidence Interval 43.2, 74.3) for SNRI users and 44.1% (39.6, 48.8) for nonusers of antidepressants. The corresponding estimates for obesity were 59.2% (43.2, 74.3) and 40.5% (35.9, 45.0), respectively. If the associations between smoking and obesity with cardiac defects are independent from each other and from other measured confounders, additional adjustment for smoking and obesity would move the RR from 1.20 to around 1.10. National surveys like NHANES are readily available sources of information on potential confounders and they can be used to assess and improve the validity of RR estimates from observational studies missing data on known risk factors.

Antidepressant Use by Class: Association with Major Adverse Cardiac Events in Patients with Coronary Artery Disease

Background: To assess use of antidepressants by class in relation to cardiology practice recommendations, and the association of antidepressant use with the occurrence of major adverse cardiovascular events (MACE) including death. Methods: This is a historical cohort study of all patients who completed cardiac rehabilitation (CR) between 2002 and 2012 in a major CR center. Participants completed the Patient Health Questionnaire (PHQ-9) at the start and end of the program. A linkage system enabled ascertainment of antidepressant use and MACE through 2014. Results: There were 1,694 CR participants, 1,266 (74.7%) of whom completed the PHQ-9 after the program. Depressive symptoms decreased significantly from pre- (4.98 ± 5.20) to postprogram (3.57 ± 4.43) (p < 0.001). Overall, 433 (34.2%) participants were on antidepressants, most often selective serotonin reuptake inhibitors (SSRI; n = 299; 23.6%). The proportion of days covered was approximately 70% for all 4 major antidepressant classes; discontinuation rates ranged from 37.3% for tricyclics to 53.2% for serotonin-norepinephrine reuptake inhibitors (SNRI). Antidepressant use was significantly associated with lower depressive symptoms after CR (before, 7.33 ± 5.94 vs. after, 4.69 ± 4.87; p < 0.001). After a median follow-up of 4.7 years, 264 (20.9%) participants had a MACE. After propensity matching based on pre-CR depressive symptoms among other variables, participants taking tricyclics had significantly more MACE than those not taking tricyclics (HR = 2.46; 95% CI 1.37–4.42), as well as those taking atypicals versus not (HR = 1.59; 95% CI 1.05–2.41) and those on SSRI (HR = 1.45; 95% CI 1.07–1.97). There was no increased risk with use of SNRI (HR = 0.89; 95% CI 0.43–1.82). Conclusion: The use of antidepressants was associated with lower depression, but the use of all antidepressants except SNRI was associated with more adverse events.

Cerebrovascular, Cardiovascular, and Mortality Events in New Users of Selective Serotonin Reuptake Inhibitors and Serotonin Norepinephrine Reuptake Inhibitors: A Propensity Score-Matched Population-Based Study.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are widely prescribed for mood and anxiety disorders. However, it is not clear whether SNRIs are more strongly associated with cardiovascular and cerebrovascular events than SSRIs. This was a propensity score-matched, population-based, cohort study of Manitobans who started an SSRI or SNRI between April 1, 1998, and March 31, 2014. The primary outcome was a composite of acute myocardial infarction (AMI), stroke, or cardiovascular-related hospitalization within 1 year of drug initiation. Each component of the primary outcome and death were analyzed separately in secondary analyses. A total of 225,504 and 54,635 patients initiated treatment on an SSRI and SNRI, respectively. After propensity score matching, a higher risk was observed for the primary outcome among SNRI users (weighted hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21). Secondary analyses showed that the risk of nonfatal stroke was higher among SNRI users (weighted HR, 1.20; 95% CI, 1.08-1.33). The risk of death was higher among SNRI users without mood and/or anxiety disorders (weighted HR, 1.17; 95% CI; 1.03-1.32). No differences were observed in the risk of AMI or fatal stroke between SSRI and SNRI use. New SNRI use was associated with a higher risk of nonfatal stroke relative to SSRI use. Further investigation is warranted regarding the higher risk of death observed in our subgroup analysis among incident SNRI users without mood and/or anxiety disorders.

Use of SSRI and SNRI Antidepressants during Pregnancy: A Population-Based Study from Denmark, Iceland, Norway and Sweden.

BackgroundThe purpose was to describe utilization of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), including trends in prevalence, characteristics of users, drug switching and changes in prescribed doses in a large group of pregnant women across four Nordic countries.MethodsA drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics.ResultsA total of 38 219 (3.3%) pregnancies were exposed to SSRIs and 5 634 (0.5%) to SNRIs. Prevalence of SSRI and SNRI use varied by country (1.8% in Norway to 7.0% in Iceland). Use and prescribed dosages decreased with each passing trimester of pregnancy; prevalence was 2.7% at conception, and 2.1%, 1.7% and 1.3% respectively in 1st, 2nd and 3rd trimester. In 0.6% of pregnancies women filled a prescription before pregnancy and in every trimester. In one third of exposed pregnancies, women were also dispensed anxiolytics, hypnotics or sedatives.ConclusionUse of SSRI and SNRI use during pregnancy varied between the Nordic countries, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women.

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.

Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors for menopausal vasomotor symptoms

Abstract Introduction Some of the most bothersome symptoms associated with menopause are the vasomotor symptoms (VMS), characterized by transient elevations in body temperature associated with a narrowing of the thermoneutral zone and an abnormal firing rate of thermosensitive neurons in the hypothalamus. These VMS have traditionally been treated with hormone replacement therapy (HRT); however, after a trial suggesting an association between HRT and a number of serious adverse events, alternative therapies for VMS are being studied. The purpose of this review is to evaluate the available literature regarding the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for the alleviation of VMS associated with menopause. Methods PubMed and Ovid/MEDLINE keyword searches were conducted. Literature was reviewed for inclusion if it included any SSRI or SNRI for menopausal symptoms published prior to August 31, 2014. Results Seven studies were included in this review article. No articles were found directly comparing HRT to either SSRIs or SNRIs. Multiple agents within these two classes have been studied for VMS in menopausal and postmenopausal women. Discussion Vasomotor symptoms related to the perimenopausal and postmenopausal period can lead to significant physical distress, often requiring medical intervention. Traditional therapies for VMS of menopause have been dominated by the use of HRT. There are conflicting data regarding the use of SSRIs and SNRIs for patients with vasomotor symptoms related to menopause, and these agents may not be ideal for all patients. These agents may be considered as an alternative in patients who have a contraindication or are concerned about using hormonal therapies.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults.

This is an updated version of the original Cochrane review published in 2005 on selective serotonin reuptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards migraine prevention. Another updated review is under development to cover tension-type headache.Migraine is a common disorder. The chronic forms are associated with disability and have a high economic impact. In view of discoveries about the role of serotonin and other neurotransmitters in pain mechanisms, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of migraine. To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic migraine in adults. For the original review, we searched MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), and Headache Quarterly (1990 to 2003). For this update, we applied a revised search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10), MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials. We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older of either sex with migraine. Two authors independently extracted data (migraine frequency, index, intensity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the risk of bias of trials. The primary outcome of this updated review is migraine frequency. The original review included eight studies on migraine. Overall, we now include 11 studies on five SSRIs and one SNRI with a total of 585 participants. Six studies were placebo-controlled, four compared a SSRI or SNRI to amitriptyline, and one was a head-to-head comparison (escitalopram versus venlafaxine). Most studies had methodological or reporting shortcomings (or both): all studies were at unclear risk of selection and reporting bias. Follow-up rarely extended beyond three months. The lack of adequate power of most of the studies is also a major concern.Few studies explored the effect of SSRIs or SNRIs on migraine frequency, the primary endpoint. Two studies with unclear reporting compared SSRIs and SNRIs to placebo, suggesting a lack of evidence for a difference. Two studies compared SSRIs or SNRIs versus amitriptyline and found no evidence for a difference in terms of migraine frequency (standardised mean difference (SMD) 0.04, 95% confidence interval (CI) -0.72 to 0.80; I(2) = 72%), or other secondary outcomes such as migraine intensity and duration.SSRIs or SNRIs were generally more tolerable than tricyclics. However, the two groups did not differ in terms of the number of participants who withdrew due to adverse advents or for other reasons (one study, odds ratio (OR) 0.39, 95% CI 0.10 to 1.50 and OR 0.42, 95% CI 0.13 to 1.34).We did not find studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. antiepileptics and anti-hypertensives). Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine as preventive drugs for migraine. There is no evidence to consider SSRIs or venlafaxine as more effective than placebo or amitriptyline in reducing migraine frequency, intensity, and duration over two to three months of treatment. No reliable information is available at longer-term follow-up. Our conclusion is that the use of SSRIs and SNRIs for migraine prophylaxis is not supported by evidence.

International variation in drug utilization: Antidepressant utilization in North America, Greece, and Ireland

Background: Given significant regional differences globally in healthcare systems, policies, and culture, we examined rates of pharmaceutical utilization among four developed nations using antidepressant drugs as a case example. Materials and Methods: We conducted a population-based cross-sectional time series analysis of antidepressant utilization in Canada, the United States, Greece, and Ireland from January 2007 to September 2011 using data from IMS Healthcare Inc., which tracks over 80% of global prescription sales of over 1.3 million products. We studied 23 antidepressants from five drug classes, namely, 1) serotonin-specific reuptake inhibitors (SSRIs), 2) serotonin-norepinephrine reuptake inhibitors (SNRIs), 3) tricyclic antidepressants (TCAs), 4) monoamine oxidase inhibitors (MAOIs), and 5) 'other' antidepressants. We used time series analysis to examine trends in utilization patterns. Results: Overall antidepressant utilization increased steadily over time for all study regions, although regions differed considerably in the magnitude of antidepressant utilization and the rates of increase. While overall antidepressant utilization rates were similar between Canada (2,876 units per 1,000 population per month) and the United States (2,815 units per 1,000 population per month), these rates were approximately 83% higher than in Greece (1,558 units per 1,000 population per month) and approximately 50% higher than in Ireland (1,898 units per 1,000 population per month). Although the use of SSRIs, SNRIs, and other antidepressants generally increased over time, the use of TCAs and MAOIs generally decreased over time. Utilization of specific drug classes varied widely between regions, ranging from an 80% relative difference in SSRI utilization between the United States and Greece to a nearly 700% difference in the utilization of MAOIs between Canada and the United States. Conclusions: The findings of our study, using antidepressants as the case example, are consistent with previous studies demonstrating significant variation in drug utilization levels internationally. Future studies are needed to document regional variation in light of appropriateness of drug therapies to determine optimal utilization levels for maximal societal benefit.

The Various Care Requirements of Psychotraumatized Subjects: From Linguistic Desert to Therapeutic Perspectives

Background: The cardinal symptoms of posttraumatic stress disorder, which is exhibited as intrusions, avoidance strategies and hypervigilance, are rarely highlighted by psycho traumatized patients when they seek care. Furthermore, the clinical features of posttraumatic stress disorder (PTSD) change over time and vary between patients; thus, a classical description of PTSD that can apply to all patients is more of the exception than the rule. Clinical findings: Many comorbidities affect both the clinical presentation and the development of PTSD. The demand for care is generally expressed via addictive and somatic comorbidities in psycho traumatized subjects: physical bodily injuries are more socially acceptable than psychological injuries. Indeed, the multifaceted nature of PTSD can often mislead clinicians because they tend to focus on the somatic complaints. Psychological comorbidities can also be present, such as depressive and anxiety disorders, dissociative disorders, psychoactive substance use and suicidal behavior. Literature findings: PTSD is favored by a polygenic vulnerability, and a preponderance of susceptibility to neuromodulation implicates various endophenotypes, which explain the different clinical dimensions that are encountered. But no neurobiological study has revealed a biological marker which would apparently and inevitably destine a subject to structure a PTSD in reaction to a stress. In contrast, the psychopathological study discovers afterwards that a particular subject has necessarily built a traumatic repetition syndrome according to the concordance of significant data relating to their history. Conclusion: Although the only FDA-approved drugs for the treatment of PTSD are sertraline and paroxetine, numerous studies have evaluated the use of Serotonin-norepinephrine reuptake inhibitors and atypical antipsychotics. The psychotherapy will thus require active commitment of the subject who far from clearing themselves of the traumatic scene will produce meaning by breaking away from a purely passive position taken at the heart of the tragedy. If the trauma is in essence nonsense, the psychotherapeutic reconstruction will promote this search for a meaning enabling the subject to continue to produce rather than again returning to real death.

Duloxetine-induced Hyponatremia in the Elderly

Hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are recognized as serious side effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). As elderly patients are easily predisposed to hyponatremia due to multiple factors, the use of SSRIs or SNRIs may be more likely to aggravate hyponatremia. We report the case of an elderly patient who developed hyponatremia most likely related to SIADH induced by duloxetine, an SNRI. Symptoms of hyponatremia emerged after treatment initiation and resolved with conservative care following discontinuation of duloxetine. Severe hyponatremia, serum hypoosmolality, urine osmolality, and measurable levels of plasma antidiuretic hormone suggested SIADH. Multiple factors, such as physical comorbidities and conditions, and drug interactions, might be associated with hyponatremia. Older patients receiving SNRIs or SSRIs should be closely monitored for clinical and laboratory evidence of hyponatremia.

Clinical comorbidities, treatment patterns, and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care

Objective:To assess comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or duloxetine (index event) in usual care settings.Methods:Using the LifeLink™ Health Plan Claims Database, patients with FM (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) were identified. Patients initiated on duloxetine were propensity score-matched with patients initiated on pregabalin (n = 826; mean age [standard deviation] of 48.3 [9.3] years for both groups). Prevalence of comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods.Results:Both patient groups had multiple comorbidities and a substantial pain-related and adjuvant medication burden. In the pregabalin group, use of other anticonvulsants decreased significantly (31.6% vs 24.9%), whereas use of serotonin-norepinephrine reuptake inhibitors (SNRIs; 16.5% vs 22.5%) and topical agents (10.1% vs 13.2%) increased in the follow-up period (p < 0.01). In the duloxetine group, there were significant decreases in the use of other SNRIs (13.0% vs 5.7%), selective serotonin reuptake inhibitors (41.3% vs 21.7%), and tricyclic antidepressants (18.8% vs 13.2%), and an increase in the use of anticonvulsants (28.6% vs 40.1%; p < 0.0001). There were significant increases (p < 0.0001) in pharmacy and total healthcare costs in both cohorts, and a significant increase in outpatient costs (p = 0.0084) in the duloxetine cohort from pre-index to follow-up. There were no significant differences in median total healthcare costs between the pregabalin and duloxetine groups in both the pre-index ($10,159 vs $9,556) and follow-up ($11,390 vs $11,746) periods.Limitations:Limitations of this study are typical of those associated with retrospective database analyses.Conclusions:Patients with FM prescribed pregabalin or duloxetine were characterized by a significant comorbidity and pain/adjuvant medication burden. Although healthcare costs increased in both groups, there were no statistically significant differences in direct healthcare costs between the two groups.

Sociodemographic and clinical factors associated with antidepressant type in a national sample of the home health care elderly

Objective The study examined in home health care (HHC) the demographic, functional and clinical factors by antidepressant (AD) type including selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and “Other” ADs such as bupropion and mirtazapine. Method Cross-sectional sample ( N=909) was analyzed from the 2007 National Home Health and Hospice Care Survey that included patients 65 years and older [mean=78.79 years, confidence interval (CI)=77.88–79.69 years] taking one AD. Results Selective serotonin reuptake inhibitors were the most commonly used (63.89%) AD, followed by “Other” ADs (14.29%), TCAs (11.31%) and SNRIs. In a multinomial regression referencing SSRIs, blacks had increased odds of tricyclic use compared to whites [odds ratio (OR)=5.96, CI=1.85–19.19]. Hispanics had decreased odds of “Other” AD (OR=0.13, CI=0.02–0.73) and SNRI use (OR=0.06, CI=0.008–0.45) compared to non-Hispanics. The HHC elderly taking psychotropic medications besides ADs were less likely to use SNRIs (OR=0.31, CI=0.11–0.88) and tricyclics (OR=0.27, CI=0.08–0.87). Advancing age was marginally associated with tricyclic use (OR=1.04, CI=0.99–1.09). Conclusion Race/ethnicity and age differences by AD type — including blacks' increased TCA use, Hispanics' decreased SNRI and “Other” AD use, and older elderly's increased tricyclic use — suggest systematic differences in prescribing practice variations including differences by geography, patient preferences or access to care in the HHC elderly.

Retrospective Evaluation of Clinical Characteristics, Pharmacotherapy and Healthcare Resource Use among Patients Prescribed Pregabalin or Duloxetine for Diabetic Peripheral Neuropathy in Usual Care

To evaluate treatment patterns and costs among patients with painful diabetic peripheral neuropathy (pDPN) newly prescribed pregabalin or duloxetine in usual care settings. Using the PharMetrics® Database, patients with pDPN (ICD-9-CM codes 357.2 or 250.6x) newly prescribed pregabalin or duloxetine were identified. Patients initiated on duloxetine (n=713; mean age 55.4 ± 9.5 years) were propensity score-matched with patients initiated on pregabalin (n=713; mean age 56.3 ± 9.3 years). Prevalence of comorbidities, pain-related pharmacotherapy and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 12 months preceding (pre-index) and following (follow-up) the date of the first pregabalin or duloxetine prescription. Both cohorts had multiple comorbidities and a substantial pain medication burden. Among pregabalin patients, use of other anticonvulsants (35.6% vs. 24.7%) and tricyclic antidepressants significantly decreased (18.2% vs. 13.7%) and serotonin-norepinephrine reuptake inhibitors (SNRIs) increased (7.9 % vs. 12.9%) in the follow-up period; all P values <0.05. Among duloxetine patients, use of other SNRIs (8.7% vs. 5.2%) and selective serotonin reuptake inhibitors decreased significantly (32.1% vs. 18.9%) in the follow-up period, but there were increases for anticonvulsants (42.1% vs. 48.4%), benzodiazepines (25.5% vs. 32%), and sedative/hypnotics (22.6% vs. 25.8%); all P values <0.05. Among pregabalin and duloxetine patients there were increases (P<0.05) in pharmacy, outpatient, and total healthcare costs from the pre-index to the follow-up period. Total medication costs in the follow-up period were significantly higher for duloxetine (median $6,763 [IQR $3,970-$10,914]) relative to pregabalin (median $6,059 [IQR $3,277-$9,865]); P=0.0017. Patients with pDPN prescribed pregabalin and duloxetine were characterized by a substantial comorbidity and pain medication burden. Although there were no differences in total healthcare costs, medication costs were significantly higher in the duloxetine cohort relative to the pregabalin cohort.