Selective Serotonin Reuptake Inhibitors In Patients Research Articles

Antipsychotic medications associated with increased length of hospital stay in autoimmune encephalitis and multiple sclerosis: A retrospective study

BackgroundAntipsychotic medications (APMs) and selective serotonin reuptake inhibitors (SSRIs) are frequently utilized in patients with neuroinflammatory disorders, such as autoimmune encephalitis and multiple sclerosis (MS). This retrospective study investigates how in-hospital treatment with APMs and SSRIs in patients with these neuroinflammatory diseases are associated with differences in hospital length-of-stay (LOS) and mortality. MethodsWe evaluated all the inpatients in the Stanford University Hospital from 2008 to 2023 diagnosed with either non-infectious encephalitis or MS and subdivided them into those who did or did not receive APMs or SSRIs while hospitalized. We then analyzed whether hospital LOS and mortality differed with these medications. ResultsAmong inpatients with non-infectious encephalitis (n = 114), those who were exposed to APMs had a significantly increased mean LOS (11.8 vs 20.9 days, p < 0.01). For inpatients with MS (n = 1095), treatment with an APM was associated with a significant increase in mean LOS (2.8 vs. 7.1, p < 0.00001). When comparing typical to atypical APMs given to subjects with MS, those who received atypical APMs showed a significant increase in LOS (4.3 vs 10.5, p < 0.01), although typical APMs showed significantly increased risk of mortality (p < 0.05). For inpatients with MS and SSRI use, there was a significant increase in mean hospital LOS (3.5 vs 5.3, p < 0.01), with a significant difference found in those who received fluoxetine or citalopram, but not sertraline or escitalopram. Finally, several healthcare disparities were found, including that Black patients were more likely to receive APMs, and those with MS were more likely to receive typical rather than atypical APMs. Conversely, Black patients with MS were less likely to receive SSRI treatment. ConclusionsThere was a statistically significant increase in LOS associated with APM use in non-infectious encephalitis and MS, as well as with SSRI use in MS. These data reflect the importance of these medications in these neuroinflammatory disorders and suggest that further investigation into their risks and benefits would be warranted.

TED-trazodone effectiveness in depression: a naturalistic study of the effeciveness of trazodone in extended release formulation compared to SSRIs in patients with a major depressive disorder.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most often used medications to treat major depressive disorder (MDD). Despite their effectiveness in reducing depressive symptoms, several issues are associated with their use in MDD, such as limited improvement of anhedonia, emergence of emotional blunting, induction or exacerbation of insomnia, and sexual dysfunction. Due to its also devoid of the issues related to treatment noted with SSRIs. The aim of this 12-week non-inferiority naturalistic observation was to compare the effectiveness and tolerability of SSRIs and trazodone in extended release (XR) in MDD. Methods: A total of 186 subjects were recruited, of which 92 received trazodone XR and 94 received SSRIs. Patients were allocated to trazodone XR or SSRIs, according to the attending physician based on clinical evaluation. Assessments at baseline and weeks 2, 4, 8, and 12 were conducted to evaluate the severity of depression (Montgomery-Åsberg Depression Rating Scale, clinician- and patient-rated Quick Inventory of Depressive Symptomatology-the primary endpoints of the study), anhedonia (the Snaith-Hamilton Pleasure Scale), anxiety (the Hamilton Anxiety Rating Scale), insomnia (the Athens Insomnia Scale), and therapeutic effectiveness (the Clinical Global Impression Scale). Results: After 12weeks, trazodone XR was more effective than SSRIs in reducing the severity of depression, anxiety, and insomnia. There was a trend for higher effectiveness of in reduction of anhedonia, which became insignificant after controlling the results for the duration of previous psychiatric treatment as a covariate. The proportion of treatment-responsive subjects in the trazodone XR group compared to SSRIs was comparable or higher. The proportion of patients achieving remission was higher in the trazodone XR arm vs. the SSRI arm. Discussion: In summary, the results indicate that trazodone XR is effective in MDD in the "real-world" setting. Its potential superiority over SSRIs in addressing particular symptomatic dimensions should be verified in future studies.

Abstract 10842: Progression of COVID-19 Severity Among SARS-CoV-2 Positive Patients Prescribed Selective Serotonin Reuptake Inhibitors

Introduction: The clinical spectrum of COVID-19 can range from asymptomatic to severe, with severe resulting in part from an intense inflammatory response. Selective serotonin reuptake inhibitor (SSRI) is the most commonly prescribed class of antidepressants and has anti-inflammatory and anti-platelet effects. Recent studies reported greater survival and lesser COVID severity in patients taking SSRIs, specifically fluoxetine/fluvoxamine. Recently, application was made to the FDA for emergency use of fluvoxamine to prevent severe COVID-19, but it was denied based on insufficient data. Methods: Patients (n=33,088) testing positive for SARS-CoV-2 between March 14, 2020-December 31, 2021 as outpatients were studied. Patients were matched 3:1 by SSRI prescription at the time of a positive test by propensity score (±0.001). Patients were evaluated for COVID-19 hospitalization within 14-days and death within 3-months of positive SARS-CoV-2 test. Results: A total of 8,272 SSRI patients were well-matched to 24,816 no SSRI patients (Table 1). Hospitalization and death were significantly greater in the SSRI group compared to the no SSRI group (Table 1). A total of 2,067 (25.0%) of SSRI patients were taking fluoxetine or fluvoxamine. While attenuated, no SSRI remained associated with a lower 14-day COVID-19 hospitalization risk when compared to fluoxetine or fluvoxamine use, but not with 3-month death (Table 2). Conclusion: This study did not find a lower risk of progression of COVID-19 severity with the use of any SSRI or fluoxetine/fluvoxamine alone. Results from this study support the FDA’s decision to not recommend their use at an early stage of a COVID-19 infection.

Selective serotonin reuptake inhibitors increase risk of upper gastrointestinal bleeding when used with NSAIDs: a systemic review and meta-analysis

The use of selective serotonin reuptake inhibitors (SSRIs) can increase the risk of gastrointestinal (GI) bleeding. Similarly, it is well known that the use of NSAIDs predisposes patients to upper GI bleeding. The aim of this study was to explore if the addition of SSRIs in patients already taking NSAIDs significantly increases their risk for upper GI bleeding. An electronic literature search was conducted using the SCOPUS and MEDLINE databases from inception through September 2020. Cohort and case–control trials that reported patients with upper GI bleeding on NSAIDs with SSRIs, compared to controls on NSAIDs only were included. Newcastle–Ottawa checklist was used to ensure inclusion of high-quality studies. Data was extracted by the lead investigator and cross-checked by the second author. Dichotomous data was pooled to obtain an odds ratio (OR) of the risk of upper GI bleeding in patients on NSAIDs with concomitant SSRI use. The primary endpoint of the study was the risk of upper GI bleeding with SSRIs and NSAIDs compared to NSAIDs alone. A total of 366 citations were reviewed, and 21 were selected for full-text evaluation. 1 cohort and 9 case–control studies were eligible. There was an additional increased risk of upper GI bleeding in patients on NSAIDs with concomitant SSRI use (OR 1.75, 95% CI = 1.32–2.33). In patients already on NSAID therapy, the concomitant use of SSRIs can significantly increase the risk of upper of GI bleeding.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

S639 Selective Serotonin Reuptake Inhibitors Increase Risk of Upper Gastrointestinal Bleeding When Used with NSAIDs: A Systemic Review and Meta-Analysis

Introduction: The use of selective serotonin reuptake inhibitors (SSRIs) can increase the risk of upper gastrointestinal bleeding (UGIB) but reported results are heterogenous. In this study we aimed evaluate the risk of UGIB with SSRIs use in patients on NSAIDs. Methods: A comprehensive literature search was conducted using the SCOPUS and MEDLINE databases from inception through September 2020. Cohort and case-control studies that reported risk of UGIB in patient on NSAIDs with and without SSRIs were included. In phase I, title and abstracts were reviewed for study eligibility. In phase II, full manuscripts of potentially eligible studies were reviewed for eligibility. Newcastle-Ottawa checklist was used for study methodology quality assessment. Data extraction and quality assessment were performed in duplication, and any disagreements were resolved by consensus. The primary outcome was UGIB. Dichotomous data was pooled to calculate an odds ratio (OR) of the risk of UGIB in patients on NSAIDs with concomitant SSRI use. Results: Our search produced a total of 366 citations, and 21 were selected for full-text review. 1 cohort and 9 case-control studies were included in final analysis. On quality assessment scores are reported in Table 1. Use of SSRIs was associated with increased risk of UGIB in patients on NSAIDs with an OR 1.75, 95% CI=1.32-2.33. The number needed to harm for upper GI bleeding with SSRIs in patients on NSAIDs was 12. Conclusion: Moderate to good quality studies report significantly higher risk of UGIB with concomitant SSRIs use with NSAIDs. These observations have important clinical implications in choosing peptic ulcer prophylaxis.Table 1.: Study Methodology Quality Assessment on Newcastle-Ottawa Scale.Figure 1.: Risk of UGIB with and without SSRI Use Footnote: Forest Plot depicting OR of having UGIB with and without SSRI use in patients on NSAIDs.

Does the Loudness Dependence of Auditory Evoked Potential Predict Response to Selective Serotonin Reuptake Inhibitors?: A Meta-analysis.

ObjectiveLoudness of dependence of the auditory evoked potential (LDAEP) is an electroencephalogram-based measure that represents amplitude changes of auditory evoked potentials in primary auditory cortex. Several narrative reviews argued that pre-treatment LDAEP values predict responses to selective serotonin reuptake inhibitors (SSRIs). This study aims to quantify the overall relationship between baseline LDAEP values and treatment response to SSRIs in patients with depression and generalized anxiety disorders, evidenced by clinical symptoms reductions, across multiple studies.MethodsIn our meta-analysis, seven articles with a total sample of 241 patients were included.ResultsOur results showed that stronger baseline LDAEP values predicted favorable response to SSRIs for depression and anxiety, with a moderate effect size.ConclusionThe current results support the idea that LDAEP is a promising biomarker for SSRIs treatment prediction in patients with depression and generalized anxiety disorder.

Which SSRI is safest for patients with CVD and major depressive disorder?

Major depressive disorder is a common mood disorder and presents increased morbidity and mortality risks for patients with comorbid cardiovascular disease (CVD). Selective serotonin reuptake inhibitors (SSRIs) are a cornerstone of treatment for major depressive disorder, given their relative safety and affordability compared with other antidepressant classes, and SSRIs frequently are used in patients with CVD. However, clinicians should carefully weigh safety considerations before prescribing SSRIs in these patients. This article reviews the safety of SSRIs in patients with CVD and discusses SSRI selection.

Predictors of treatment response to pharmacotherapy in patients with persistent postural-perceptual dizziness.

The study aimed to identify the predictors of response to selective serotonin reuptake inhibitors (SSRIs) for 12weeks in patients with persistent postural-perceptual dizziness (PPPD). Short-term treatment responses were studied in 197 outpatients [127 (64.5%) women, mean age ± SD = 51.7 ± 15.9] diagnosed with PPPD. Clinical and self-rated assessments were analyzed at the baseline and at the end of pharmacotherapy for 12weeks. Multivariable logistic regression analysis was used to determine the following variables as the potential predictors of treatment response as measured by scoring in clinical global impression-improvement scale (CGI-I) scores: age, sex, comorbidity, baseline CGI-S score, Beck Depression Inventory-II score, State-Trait Anxiety Inventory score, Dizziness Handicap Inventory score at the baseline, and prescribed doses of antidepressants or benzodiazepines. The overall response rate to pharmacotherapy was 65.0% (128/197). Female sex and greater disease severity at the baseline (higher CGI-S score) were associated with a better response to the pharmacotherapy. Subgroup analyses by sex identified younger age and lower anxiety as the indicators for better outcomes in men, and absence of comorbidities in women. During the initial assessment, the severity of PPPD was associated with depressive symptoms and subjective functional handicap due to dizziness. The response to pharmacotherapy is favorable in PPPD. Sex, age and initial disease severity are the predictors of the response to SSRIs in patients with PPPD.

Association of Serum Biomarker Levels and BDNF Gene Polymorphism with Response to Selective Serotonin Reuptake Inhibitors in Indian Patients with Major Depressive Disorder

Introduction: Depression is a major public health problem. Response to selective serotonin reuptake inhibitor (SSRI) treatment varies considerably between patients. In the context of polygenic diseases like depression, measurement of a panel of biomarkers involved in the pathophysiology of depression might help predict outcome to treatment with SSRIs. Objective: The objective was to establish the relationship between serum biomarker levels and the brain-derived neurotrophic factor (BDNF) val66met polymorphism and response to SSRIs in patients with major depressive disorder. Methods: 50 patients with moderate to severe depression were recruited from the Department of Psychiatry, Sri Ra­machandra Institute of Higher Education and Research. Blood samples were collected, and Hamilton Depression Rating Scale scoring was done at baseline and after 8 weeks of treatment with SSRIs. Baseline and post-treatment levels of high-sensitivity C-reactive protein (hsCRP), BDNF and neuregulin 1β1 (NRG1β1) were analysed using commercially available ELISA kits. Genotyping of the BDNF Val66Met polymorphism was performed using a PCR-RFLP method. Results: Following treatment, there was a significant decrease in the mean hsCRP and NRG1β1 levels and a significant increase in the mean BDNF level. Responders had significantly lower baseline hsCRP and higher baseline BDNF levels when compared to non-responders. Response rates were significantly higher in the Val/Val group when compared to the Val/Met group. Conclusions: Baseline serum levels of hsCRP and BDNF predicted response to SSRIs in major depressive disorder, and Val/Val patients responded better when compared to patients carrying the Met allele.

The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (PT) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N = 865), and in a replication cohort (STAR*D, N = 1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.

Alternate day dTMS combined with SSRIs for chronic treatment resistant depression: A prospective multicenter study

IntroductionChronic treatment resistant depression takes a substantial toll on patients' quality of life and alternative treatment options are limited. This prospective multicenter study evaluated the safety, tolerability and efficacy of four weeks of thrice-a-week deep transcranial magnetic stimulation (dTMS) in combination with selective serotonin reuptake inhibitors (SSRIs). MethodsForty patients who failed to respond during a 16-week double-blind placebo controlled (DBPC) trial of dTMS or sham dTMS as monotherapy were screened and started a treatment of previously tolerable but ineffective SSRI. After ten days of medication, high frequency dTMS was added three times a week for four weeks. ResultsdTMS combined with SSRIs was well tolerated, with only headaches as a related adverse event (n = 4), which did not cause drop outs. Six patients were excluded from analysis: 1 was missing screening data and 5 received less than 10 sessions. Out of 34 patients included in this study, 12 (35.3%) patients remitted (HDRS-21 < 10). No significant differences were found between patients who had received sham or active dTMS in the earlier DBPC multicenter trial. LimitationsThis was a small scale open study of dTMS with SSRIs in patients that failed to respond during a DBPC dTMS trial, although a carryover effect cannot be excluded. Comparative efficacy of dTMS with and without SSRIs and specific dosing and protocol parameters warrant specifically-designed large-scale controlled studies. ConclusionsThrice weekly dTMS at 120% motor threshold(MT), 10 HZ, 3‑s trains, 20‑s intervals, 2400 daily pulses, can augment formerly ineffective SSRI treatment.

Interaction between Monoamine Oxidase B Inhibitors and Selective Serotonin Reuptake Inhibitors

Monoamine oxidase B (MAO-B) inhibitors are used to treat the motor symptoms of Parkinson disease. Depression is commonly associated with Parkinson disease, and selective serotonin reuptake inhibitors (SSRIs) are often used for its management. Tertiary sources warn that the combination of MAO-B inhibitors and SSRIs can result in increased serotonergic effects, leading to serotonin syndrome. To explore the mechanism, clinical significance, and management of this potential drug interaction through a review of the supporting evidence. PubMed, MEDLINE (1946 forward), Embase (1947 forward), PsycINFO (1806 forward), and International Pharmaceutical Abstracts (1970 forward) were searched on February 4, 2017. Studies and case reports describing aspects of the potential interaction between MAO-B inhibitors and SSRIs in patients with Parkinson disease and published in English were identified by both title and abstract. The search identified 8 studies evaluating the potential interaction between SSRIs and the MAO-B inhibitors selegiline and rasagiline. The largest, a retrospective cohort study of 1504 patients with Parkinson disease, found no cases of serotonin syndrome with coadministration of rasagiline and an SSRI. A survey of 63 investigators in the Parkinson Study Group identified 11 potential cases of serotonin syndrome among 4568 patients treated with the combination of selegiline and antidepressants (including SSRIs). In addition, 17 case reports describing the onset of serotonin syndrome with coadministration of an SSRI and either selegiline or rasagiline were identified. Following discontinuation or dose reduction of one or both of the agents, the symptoms of serotonin syndrome gradually resolved in most cases, with none being fatal. According to the literature, serotonin syndrome occurs rarely, and the combination of SSRI and MAO-B inhibitor is well tolerated. Therefore, SSRIs and MAO-B inhibitors can be coadministered, provided that their recommended doses are not exceeded and the SSRI dose is kept at the lower end of the therapeutic range. Among the SSRIs, citalopram and sertraline may be preferred.

Intracerebral Hemorrhage and Outcome After Thrombolysis in Stroke Patients Using Selective Serotonin-Reuptake Inhibitors.

Selective serotonin-reuptake inhibitors (SSRIs) impair platelet function and have been linked to a higher risk of spontaneous intracerebral hemorrhage-an association that may be augmented by oral anticoagulants (OAC). We aimed to assess whether preadmission treatment with SSRIs in patients with acute ischemic stroke is associated with post-thrombolysis symptomatic intracerebral hemorrhage (sICH) and functional outcome. A multicenter retrospective analysis was conducted in prospective registries of patients treated by thrombolysis within 4.5 hours of stroke onset. The association between preadmission treatment with SSRIs and sICH (ECASS II definition [European Cooperative Acute Stroke Study]) or unfavorable 3-month outcome (modified Rankin Scale >2) was assessed by logistic regression, taking into account potential interaction with concomitant use of antithrombotics. Six thousand two hundred forty-two patients were included (mean age, 70.1±14.0 years; median National Institutes of Health Stroke Scale, 9 [5-16]). Preadmission treatment with SSRIs was present in 4.3% (n=266) of patients. Overall, SICH rate was 3.9% (95% confidence interval [CI], 3.5%-4.4%; n=244), and SSRI use was not significantly associated with sICH in unadjusted (odds ratio [OR], 1.28; 95% CI, 0.72-2.27) or adjusted (OR, 1.30; 95% CI, 0.71-2.40) analysis. However, there was a significant interaction of concomitant use of OACs (international normalized ratio <1.7) and SSRI for occurrence of sICH (P=0.01). SICH was significantly more frequent in patients taking both OAC and SSRI (23.1%; 95% CI, 8.2%-50.3%) than in patients taking OAC but not SSRI (adjusted OR, 9.04; 95% CI, 1.95-41.89). Preadmission use of SSRI was associated with unfavorable 3-month outcome (unadjusted OR, 1.90; 95% CI, 1.48-2.46; adjusted OR, 1.59; 95% CI, 1.15-2.19). Preadmission treatment with SSRIs was not significantly associated with an increased risk of post-thrombolysis sICH in this cohort study. However, subgroup analysis suggested an increased risk of sICH in patients taking both SSRI and OAC. Preadmission treatment with SSRIs was associated with unfavorable outcome, which may reflect the prognostic significance of prestroke depression.

An observational study of duloxetine versus SSRI monotherapy in Japanese patients with major depressive disorder: subgroup analyses of treatment effectiveness for pain, depressive symptoms, and quality of life.

ObjectiveTo examine how clinical and demographic patient baseline characteristics influence effectiveness of duloxetine versus selective serotonin reuptake inhibitor (SSRI) treatment, in real-world Japanese clinical settings of patients with major depressive disorder (MDD) and associated painful physical symptoms (PPS).MethodsThis was a multicenter, 12-week, prospective, observational study in patients with MDD (Quick Inventory of Depressive Symptomatology ≥16) and at least moderate PPS (Brief Pain Inventory-Short Form [BPI-SF] average pain ≥3). Patients received duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine). Assessments were made by using BPI-SF average pain, 17-item Hamilton Rating Scale for Depression (HAM-D17), EuroQol 5-dimension questionnaire, Social Adaptation Self-Evaluation Scale, Global Assessment of Functioning, and ability to work. Predefined subgroups included the number of previous episodes of depression (0 vs ≥1), baseline BPI-SF average pain score (≤6 vs >6), baseline HAM-D17 total score (≤18 vs >18), baseline HAM-D17 retardation (≤7 vs >7) and anxiety somatic subscale scores (≤6 vs >6), and age (<65 vs ≥65 years).ResultsTreatment effectiveness was evaluated in 523 patients (duloxetine N=273, SSRIs N=250). Treatment with duloxetine was superior to SSRIs on most outcome measures in patients experiencing their first depressive episode, those with higher baseline PPS levels, and in patients with more severe baseline depression. This was also the case for older patients. In patients with less severe depression, SSRI treatment tended to show more improvements in depression and quality of life measures versus duloxetine treatment.ConclusionThese preplanned subgroup analyses of data from a prospective observational study suggest that, for Japanese MDD patients with PPS, duloxetine is more effective than SSRIs in patients with a first episode of MDD, with more severe depression, or more severe PPS.

Pain Relief in Depressive Disorders: A Meta-Analysis of the Effects of Antidepressants.

Pain is a common symptom in patients with depressive disorders, which, if present, worsens the prognosis. However, there is little empirical knowledge of the therapeutic effects of antidepressants on painful physical symptoms of patients with depressive disorders. Furthermore, tricyclic/tetracyclic antidepressants (TCAs) have not yet been included in existing meta-analyses. A broad, systematic search of PubMed literature on antidepressant drug treatment of patients with depressive disorders with comorbid pain symptoms was carried out. A random-effects meta-analysis has been performed among 3 different groups of drugs for the 2 end points: pain and depression. Fourteen placebo-controlled studies with selective serotonin-noradrenaline reuptake inhibitors (SSNRIs) could be included, with 3 of them also investigating selective serotonin reuptake inhibitors (SSRIs). Three further placebo-controlled SSRI studies were identified, but only 2 placebo-controlled TCA studies.Both SSNRIs and SSRIs, but not TCAs, were significantly superior to placebo as regards their analgesic effects. However, all effects were small. For SSNRIs, there was a strong positive correlation between their effectiveness for pain relief and their positive effect on the mood of the patients. The analgesic effects of SSNRIs and SSRIs in patients with primary depressive disorders can be interpreted as largely equivalent. Because of a lack of placebo-controlled TCA studies, the results for TCAs would be comparable only to those of SSRIs and SSNRIs, if non-placebo-controlled TCA studies were included. The positive correlation found indicates a close relationship of pain relief and antidepressant treatment effects. These results refer merely to patients with primary depressive disorders, not to patients with primary pain disorders. Further studies comparing the effects of different types of antidepressant drugs on pain in depressive patients are warranted.

Pharmacological Modulations of the Serotonergic System in a Cell-Model of Familial Alzheimer's Disease.

Serotonin (5-HT) plays a central role in the integrity of different brain functions. The 5-HT homeostasis is regulated by many factors, including serotonin transporter (SERT), monoamine oxidase enzyme (MAO), and several 5-HT receptors, including the 5-HT1B. There is little knowledge how the dynamics of this system is affected by the amyloid-β (Aβ) burden of Alzheimer's disease (AD) pathology. SH-SY5Y neuroblastoma cells transfected with the amyloid precursor protein (APP) gene containing the Swedish mutations causing familial AD (APPswe), were used as a model to explore the effect of Aβ pathology on 5-HT1B and related molecules including the receptor adaptor protein (p11), SERT and MAOA gene expression, and MAOA activity after treatment with selective serotonin reuptake inhibitor (SSRI) (sertraline), and a 5-HT1B receptor antagonist. Sertraline led more than 70 fold increase of 5-HT1B gene expression (p < 0.001), an increased serotonin turnover in both APPswe and control cells and reduced intracellular serotonin levels by 75% in APPswe cells but not in controls (p > 0.05). Treatment with the 5-HT1B receptor antagonist increased SERT gene-expression in control cells but not in the APPswe cells. 5-HT and 5-HT1B antagonist treatment resulted in different p11 expression patterns in APPswe cells compared to controls. Although MAOA gene expression was not changed by APPswe overexpression, adding 5-HT lead to a significant increase in MAOA gene expression in APPswe but not control cells. These findings suggest that the sensitivity of the 5-HT1B receptor and related systems is affected by APPswe overexpression, with potential relevance for pharmacologic intervention in AD. This may at least partly explain the lack of effect of SSRIs in patients with AD and depression.

Cognitive Function before and during Treatment with Selective Serotonin Reuptake Inhibitors in Patients with Depression or Obsessive-Compulsive Disorder.

Objectives. Identification of adverse effects of selective serotonin reuptake inhibitors (SSRIs) is of great importance due to their extensive use in medicine. Some studies have reported the effects of SSRIs on cognitive functions, but the results are conflicting. This study was designed to assess the effect of these drugs on cognition of patients with depression or obsessive-compulsive disorder (OCD). Methods. Patients with depression or OCD, naïve to therapy, and candidates of receiving one drug from SSRI class, voluntarily, entered this study. Mini-Mental State Examination (MMSE) test was the tool to assess their cognitive functions. MMSE scores of each patient were recorded prior to taking SSRIs and at weeks 3, 5, and 8 of drug therapy. Results. 50 patients met our inclusion criteria, with a baseline mean MMSE score of 23.94. At 3, 5, and 8 weeks of treatment, the mean scores were 22.1, 21.4, and 20.66, respectively. With a p value of <0.0001, the gradual decline was statistically significant. Conclusion. The MMSE scores of our patients showed a gradual decline over the consecutive weeks after taking SSRI drugs. It seems that the use of SSRIs in patients with depression or OCD, can cause cognitive dysfunction in the acute phase of treatment.

Serotonergic antidepressant drugs and L-dopa-induced dyskinesias in Parkinson's disease.

Serotonergic system is believed to play a role in levodopa-induced-dyskinesias pathogenesis, and serotonin transporter has been evaluated as potential target. To retrospectively investigate the potential effect of selective serotonin reuptake inhibitors (SSRIs) during dopaminergic treatment, in the development of dyskinesias in patients with Parkinson's disease (PD). One hundred and thirty-five consecutive patients with PD, with 10-year follow-up since diagnosis. Age at PD onset, duration of levodopa treatment, maximum daily dose, and SSRIs exposure were collected. Risk, latency, and severity of dyskinesias were evaluated comparing patients with and without SSRIs exposure. Forty-nine patients received SSRIs for a variable period, 86 were never treated; no significant difference between the groups was observed (P=0.897) in the prevalence of dyskinesias. Considering latency between PD diagnosis and dyskinesias onset, patients exposed to SSRIs developed dyskinesias later (6.48±1.99 vs 5.70±1.89years, P=0.020). The median dyskinesia severity score was 0 in the exposed group vs 1 in non-exposed patients (P=0.025). Multivariate analysis demonstrated SSRIs exposure as the only independent predictor, protecting from severe dyskinesia. Use of SSRIs in patients with PD did not protect from dyskinesias; however, exposure may delay the onset and reduce the severity, confirming modulation of the serotonergic system as possible antidyskinetic strategy.

Serotonin Reuptake Inhibitor Use, Depression, and Long-Term Outcomes After an Acute Coronary Syndrome: A Prospective Cohort Study

To the editor: In coronary heart disease (CHD) patients, depression is highly prevalent (1). Selective serotonin reuptake inhibitors (SSRIs) are recommended as first-line antidepressant treatments for this population (2,3). While there is a long-standing notion that SSRIs may improve cardiac prognosis by inhibiting platelet aggregation, SSRI use may also worsen prognosis by increasing bleeding (4), or arrhythmia risk (5). Only a few small randomized clinical trials (RCTs) with a total of 801 patients have assessed the efficacy of SSRIs in patients with a cardiac condition (6,7). Although no evidence for harm was detected in two meta-analyses, the follow-up periods for adverse cardiac events in these RCTs did not extend beyond six months, and patient samples were highly selected (i.e. only patients not already receiving antidepressant therapy in usual care were included, and patients with comorbid conditions were excluded). Accordingly, we evaluated, in an observational cohort of patients with acute coronary syndromes (ACS), the association of SSRI and non-SSRI second-generation antidepressant use with the occurrence of cardiac events and mortality across a period of 42 months.