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Purpose: This study compares the risks of arrhythmia among patients with depression receiving selective serotonin reuptake inhibitors (SSRIs) and those receiving other classes of antidepressants and among patients with depression receiving citalopram-escitalopram and those receiving other SSRIs., Methods: This retrospective cohort study used data from the 2000-2011 National Health Insurance Research Database in Taiwan. Patients with depression who were new antidepressant users were included in the study sample. Propensity score matching was used to balance the covariates between the comparison groups. Crude incidence rates were generated by Poisson regressions, and Cox proportional hazards regression models were used to assess the rates of arrhythmia among SSRI users and nonusers of SSRI antidepressants as well as between citalopram-escitalopram users and users of other SSRIs., Findings: Neither SSRI (hazard ratio [HR] = 0.95; 95% CI, 0.83-1.08) nor citalopram-escitalopram (HR = 1.20; 95% CI, 0.95-1.51) exposure was associated with a risk of arrhythmia compared with other, newer non-SSRI antidepressants or noncitalopram SSRIs. An increase in mortality was, however, observed among citalopram-escitalopram users (HR = 1.21; 95% CI, 1.08-1.31)., Implications: Citalopram, escitalopram, and other SSRIs were not associated with an elevated risk of arrhythmia compared with each other or with non-SSRI antidepressants. Nevertheless, citalopram and escitalopram were associated with an increase in mortality risk compared with other SSRIs and deserve further investigation., (Copyright © 2019. Published by Elsevier Inc.)

Antidepressants are frequently prescribed in first episode schizophrenia (FES) patients for negative symptoms or for subsyndromal depressive symptoms, but therapeutic benefit has not been established, despite evidence of efficacy in later-stage schizophrenia. We conducted a 52 week, placebo-controlled add-on trial of citalopram in patients with FES who did not meet criteria for major depression to determine whether maintenance therapy with citalopram would improve outcomes by preventing or improving negative and depressive symptoms. Primary outcomes were negative symptoms measured by the Scale for Assessment of Negative Symptoms and depressive symptoms measured by the Calgary Depression Scale for Schizophrenia; both were analyzed by an intent-to-treat, mixed effects, area-under-the-curve analysis to assess the cumulative effects of symptom improvement and symptom prevention over a one-year period. Ninety-five patients were randomized and 52 (54%) completed the trial. Negative symptoms were reduced with citalopram compared to placebo (p = .04); the effect size of citalopram versus placebo was 0.32 for participants with a duration of untreated psychosis (DUP) of <18 weeks (median split) and 0.52 with a DUP >18 weeks. Rates of new-onset depression did not differ between groups; improvement in depressive symptoms was greater with placebo than citalopram (p = .02). Sexual side effects were more common with citalopram, but overall treatment-emergent side effects were not increased compared to placebo. In conclusion, citalopram may reduce levels of negative symptoms, particularly in patients with longer DUP, but we found no evidence of benefit for subsyndromal depressive symptoms., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Neurocardiogenic syncope (NCS) is a common form of syncope. Although selective serotonin reuptake inhibitors and other medications have been used to treat NCS with variable success, there is no consensus regarding a first-line therapy., Study Question: To assess the effects of citalopram in NCS and to examine the effect of diagnostic use of the head-up tilt table (HUTT) versus empirical diagnosis on patient outcome., Study Design: A retrospective case series of 1000 consecutive patients who were diagnosed with NCS and treated with citalopram., Measures and Outcomes: The primary outcome measure was well-being score (WS) recorded at each outpatient visit., Results: After excluding patients who had other comorbidities, were taking daily medication, or did not attend a follow-up visit within 1 month after treatment initiation, data from 186 patients were included. Thirty-five patients were diagnosed empirically, and 151 patients were diagnosed with the HUTT. All 186 patients were followed up within 1 month (early follow-up); of these, 92 patients attended a second follow-up after 1 month (late follow-up). The early follow-up group showed a significant improvement in mean WS (7.35 vs. 4.46, P < 0.001) and only 5 patients discontinued therapy because of intolerability. The late follow-up group also showed significant improvements in mean WS at the early follow-up (7.42 vs. 4.43, P < 0.001) and late follow-up (7.42 vs. 4.26, P < 0.001). Of 186 patients who were treated with citalopram, only 11 reported the development of undesirable side effects. There was no significant difference in the outcome of patients who were diagnosed empirically versus those who were diagnosed with the HUTT., Conclusions: Citalopram seems to have desirable effects on NCS and patient well-being. Diagnostic use of the HUTT is useful for confirming diagnoses of NCS but is not likely to improve patient outcome.

Background: Senile depression patients in China usually present with a higher risk of coronary heart disease that may trigger cardiac death. Selective serotonin reuptake inhibitors (SSRIs) were the most prescribed antidepressants in China; the cardiovascular safety of SSRIs when used in Chinese senile depression patients has not been evaluated., Methods: A network of meta-analysis was conducted to fill the objectives. PubMed, Embase databases, and 2 Chinese language electronic databases WANFANG and CNKI were searched for the related articles. The primary outcome of the present study was the number of cardiovascular reactions when each SSRI drug was used among senile depression patients in China. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated within pairwise and network meta-analysis., Results: Fifteen trials were identified, including 1432 patients; the network meta-analysis showed that Chinese senile depression patients treated by Escitalopram were associated with a lower risk of cardiovascular reaction (CDR) than Paroxetine (ORs 0.37, 95% CI 0.14-0.37). Escitalopram also exhibited distinct advantages compared with other SSRIs. The rank of SSRIs with respect to cardiovascular safety was Escitalopram > Sertraline > Citalopram > Paroxetine > Fluoxetine, respectively., Conclusion: Escitalopram exhibited distinct advantages compared with other SSRIs, while Fluoxetine had the biggest cardiovascular reaction probability.

Background: Although the US Food and Drug Administration (FDA) recommended upper limits for citalopram dosing in older adults due to risk of corrected-QT (QTc) prolongation, which was adopted, and extended to escitalopram by Health Canada, the scientific basis is unclear. The objective of this study was to assess the relationship between citalopram/escitalopram dosages and QTc interval in a real-world geriatric setting., Methods: We reviewed electronic health records at a university-affiliated geriatric health care center, over a 7-year period, to identify patients prescribed citalopram and escitalopram, who had an ECG within 90 days of initiation or dosage change. Linear regression analyses were conducted to assess the relationship between antidepressant dosage and QTc interval., Results: 137 patients were identified (citalopram=97, escitalopram=40). No association was found between citalopram, escitalopram and QTc, in unadjusted or adjusted analyses. Among covariates, older age was significantly associated with QTc prolongation in the escitalopram group., Limitations: Limitations to the current study include its retrospective design and the small sample size., Conclusions: These data do not support the FDA or Health Canada's recommended maximum dosages of citalopram or escitalopram in the elderly. Therefore, for patients already on higher doses of these medications, the risk of QTc prolongation may not always outweigh the risk of dose lowering, such as relapse. Until larger prospective studies become available, the decision to comply or not with these federal agencies' recommendations should be weighed on an individual basis, taking into consideration all potential risk factors., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To guide clinicians in selecting the "next line" selective serotonin reuptake inhibitor (SSRI) for adolescents with treatment-resistant major depressive disorder, we sought to compare response rates among SSRIs in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study and to jointly model tolerability and efficacy for the specific SSRI comparisons. Methods: Efficacy and tolerability data for paroxetine, citalopram, and fluoxetine were extracted from the TORDIA study. Using a joint bivariate normal likelihood for response and tolerability (based on the maximum implied variance from the 95% credible intervals previously reported for the three SSRIs), a Monte Carlo pseudorandom sample (100,000 draws) was obtained, from which credible intervals, means, posterior tail probabilities, etc. were determined. Joint null hypotheses of no difference in efficacy and tolerability were then evaluated with regard to superiority of each SSRI over the others. Results: No significant differences in response were observed for citalopram compared with fluoxetine ( p  = 0.247) or for fluoxetine compared with paroxetine ( p  = 0.110), although citalopram trended toward being superior to paroxetine (mean difference: 0.2, p  = 0.055). For efficacy-tolerability models, citalopram and fluoxetine were superior to paroxetine ( p  = 0.029 and p  = 0.022, respectively) but did not differ between each other ( p  = 0.146). Conclusions: Joint efficacy-tolerability models suggest that citalopram and fluoxetine were statistically significantly superior to paroxetine while citalopram trended toward superiority over paroxetine in the efficacy model. These findings provide a more granular and practical evidence base for clinicians faced with treatment sequencing decisions in adolescents with SSRI-resistant depression.

Background: We report on the serotonin syndrome after an alcohol intake in a patient with major depressive disorder treated with escitalopram and clomipramine., Case: A 26-year-old male patient with major depressive disorder had been stable on the treatment with escitalopram (20 mg/d) and clomipramine (50 mg/d) for 4 months. He had rarely taken alcohol, especially never with medication. One night after taking these drugs with a can of beer, he developed agitation, disorientation, myoclonus, hyperreflexia, tremor, tachycardia, diaphoresis, and hypertension, fulfilling the criteria for the serotonin syndrome. It was considered that the serotonin syndrome in the present case might be induced by alcohol's pharmacodynamic interaction with escitalopram and clomipramine leading to decreased clearance of extracellular serotonin in the brain and/or pharmacokinetic interaction with clomipramine leading to increased clomipramine levels., Conclusions: The present case report suggests that there may be an interaction between alcohol and antidepressants resulting in the serotonin syndrome, and clinicians should be aware of this possibility.

Although pharmaceuticals are recognized as a major threat to aquatic ecosystems worldwide, little is known about their ecological effect on aquatic biota and ecosystems. Drug-induced behaviour changes could have a substantial impact on consumer-resource interactions influencing stability of the community and ecosystem. We combined laboratory experiments and functional response modelling to investigate effects of real wastewater treatment plant (WWTP) effluent, as well as environmentally relevant concentrations of the antidepressants citalopram and opioid pain medication tramadol, on trophic interactions. Our biological system consisted of dragonfly Aeshna cyanea larvae as predator of common carp Cyprinus carpio fry. Exposure to WWTP effluent significantly increased A. cyanea maximum feeding rate, while those parameters in tramadol and citalopram-exposed larvae were significantly lower from unexposed control group. This suggested the potential of all tested pollutants to have an effect on consumer-resource equilibrium in aquatic ecosystems. While WWTP effluent strengthened interaction strength (IS) of consumer-resource interaction dynamics making the food web more vulnerable to fluctuation and destabilization, tramadol and citalopram could inhibit the potential oscillations of the consumer-resource system by weakening the IS. Similar studies to reveal the potential of pervasive pharmaceuticals to change of consumer-resource interactions dynamics are needed, especially when real WWTP effluent consisting of mixture of various pharmaceuticals displayed very different effect from single compounds tested., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Individuals receiving maintenance hemodialysis may be particularly susceptible to the lethal cardiac consequences of drug-induced QT prolongation because they have a substantial cardiovascular disease burden and high level of polypharmacy, as well as recurrent exposure to electrolyte shifts during dialysis. Electrophysiologic data indicate that among the selective serotonin reuptake inhibitors (SSRIs), citalopram and escitalopram prolong the QT interval to the greatest extent. However, the relative cardiac safety of SSRIs in the hemodialysis population is unknown., Methods: In this retrospective cohort study, we used data from a cohort of Medicare beneficiaries receiving hemodialysis included in the US Renal Data System registry (2007-2014). We used a new-user design to compare the 1-year risk of sudden cardiac death among hemodialysis patients initiating SSRIs with a higher potential for prolonging the QT interval (citalopram, escitalopram) versus the risk among those initiating SSRIs with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, sertraline). We estimated adjusted hazard ratios using inverse probability of treatment weighted survival models. Nonsudden cardiac death was treated as a competing event., Results: The study included 30,932 (47.1%) hemodialysis patients who initiated SSRIs with higher QT-prolonging potential and 34,722 (52.9%) who initiated SSRIs with lower QT-prolonging potential. Initiation of an SSRI with higher versus lower QT-prolonging potential was associated with higher risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31). This association was more pronounced among elderly individuals, females, patients with conduction disorders, and those treated with other non-SSRI QT-prolonging medications., Conclusions: The heterogeneous QT-prolonging potential of SSRIs may differentially affect cardiac outcomes in the hemodialysis population., (Copyright © 2019 by the American Society of Nephrology.)

Introduction: Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is associated with incidence of adverse events, such as constipation, diarrhea, dry mouth, headache, insomnia, and sexual dysfunction (SDys). Escitalopram (ESC), an effective and safe selective serotonin reuptake inhibitor with good tolerability, was used in this study. In this study, we investigated the prospective effect of Pycnogenol (PYC), an antioxidant, anti-inflammatory, and vasodilator agent, on ESC-induced SDys., Methods: This was a randomized, parallel, open-label study. Seventy-two outpatients of both genders with depression were randomized into two groups as follows: 37 patients from the ESC + PYC group took 50 mg of PYC per day for 4 months in ESC co-treatment, and 35 subjects from the ESC group took ESC only. Five patients dropped out and were excluded from the analysis. The participants were examined every month (visits 1-4)., Results: ESC use led to improvement of depressive symptoms and severity scored by standardized psychiatric tests. PYC co-treatment resulted in attenuation of SDys beginning at 1 month of treatment and continuing for two consecutive months. Furthermore, an increase in heart rate in the PYC group was registered., Conclusions: We propose that PYC-mediated SDys attenuation is based on its ability to improve endothelial functions by its antioxidant, anti-inflammatory, vasodilatory, and anticoagulant action. We assume that the action of PYC on heart rate is in accordance with the aforementioned vasodilatory action of PYC and consequent baroreflex-mediated heart rate response. PYC co-treatment reduced ESC-induced SDys and elevated heart rate.

Background Citalopram and escitalopram can both induce dose-dependent QT prolongation. The risk of arrhythmia may be increased with concomitant use of other drugs that induce QT prolongation. Objective To evaluate the prevalence and impact of pharmacist interventions on the combination of citalopram or escitalopram with other drugs that induce QT prolongation. Setting A French hospital with 517 computerized beds. Method All cardiac adverse drug reactions (ADRs) related to citalopram or escitalopram reported to the French pharmacovigilance database (FPDB) were analyzed. Then, over a 6-month period, all computerized prescriptions including citalopram or escitalopram and drug-drug interactions (DDI) were analyzed by pharmacists using a computerized provider order entry system (DXCare ® , Medasys). Results Only 27 cardiac ADRs related to citalopram or escitalopram were reported in the database. Among the 57,857 prescriptions and 2116 contraindicated DDIs (3.7 %) that were analyzed. 444 DDIs (0.8 %) were considered to be clinically relevant by pharmacists and physicians and 168 (i.e., approximately 30 %) were related to a combination including citalopram or escitalopram. Most of the prescriptions related to DDIs including citalopram or escitalopram were discontinued in response to a pharmacist intervention when initiated during the hospital stay. Conclusion A high number of hospital prescriptions including citalopram or escitalopram with another QT-prolonging drug occurred, highlighting the importance of involvement of clinical pharmacists in prevention of potential ADRs related to such contraindications.

Background: Major depressive disorder (MDD) is a prevalent and disabling disorder that can lead to heavy individual, familial, and societal burdens. Although pharmaceutical interventions still play an essential role in therapeutic measures, limitations, including effects that are delayed for weeks, are noteworthy. Antidepressants with rapid efficacy and acceptable tolerance have been investigated for many years; rapid antidepressant effects and promising clinical applications have been obtained with intravenous and oral scopolamine. This study aims to evaluate the efficacy of repeated intramuscular scopolamine as an add-on treatment to escitalopram., Methods: This is a single-center, saline-controlled, double-blind, three-armed, randomized trial. Sixty-six participants diagnosed with MDD will be recruited at Beijing Anding Hospital and randomly assigned to one of three groups: a high-dose intramuscular scopolamine augmentation group; a low-dose intramuscular scopolamine augmentation group; and a placebo control group. Our primary endpoint is improvement in the 17-Item Hamilton Rating Scale for Depression (HRSD17) score from the baseline (at least a 20% reduction). Prespecified secondary endpoints include response rates and remission rates as well as changes in the total or subscale scores between the baseline and week 4., Discussion: This study will provide the first insight regarding the rapid antidepressant efficacy and tolerability of an intramuscular scopolamine add-on to the usual treatment in Chinese MDD patients. The first discussion concerns whether augmentation can accelerate early antidepressant efficacy. A pilot study of intramuscular scopolamine is performed. The limitations of this study include its small sample size and it being a single-center study, suggesting the need for further confirmation with trials enrolling larger populations., Ethics and Dissemination: The study protocol and all related materials have been approved by the Institutional Ethics Committee of the Beijing Anding Hospital (No. 2016-106, Beijing, China). The findings will be disseminated through peer-reviewed journals and at national and international conferences., Trial Registration: ClinicalTrials.gov, NCT03131050 . Registered on 18 April 2017.

Introduction: Serotonin affects several brain functions including cognition. The serotonin transporter (SERT) regulates brain serotonin levels through reuptake into neurons. The gene encoding this transporter, the SERT gene, has several functional polymorphisms affecting the number of transporters and thereby the serotonin levels. SERT gene expression may be important for cognition and selective serotonin reuptake inhibitors (SSRI) may improve cognition post stroke. We therefore examined the association between SERT genotypes, cognitive function and early treatment with the SSRI citalopram among non-depressed Caucasian stroke patients., Patients and Methods: SERT gene polymorphisms in 270 non-depressed first-ever acute ischemic stroke patients randomized to citalopram, n = 130, or placebo, n = 140, were investigated. Patients were genotyped for a length polymorphism (L = long and S = short allele) and a single nucleotide polymorphism (A/G substitution) dividing the L-allele into LA and LG. According to these genotypes, patients were further grouped according to low (S/S, LG/S and LG/LG), medium (S/LA and LG/LA), or high functional gene expression (LALA). Cognition was measured by the Symbol Digit Modalities Test (SDMT) at 1 and 6 months. Mean SDMT scores according to genotype and randomization groups were compared using multiple logistic regression adjusting for age, stroke severity, premorbid functional status, and vascular risk factors including smoking, hypertension, and diabetes., Results: Stratified by genotype groups, there were no statistically significant differences in SDMT scores between randomization groups. Placebo-treated patients with low SERT expression genotypes, however, tended to have lower mean SDMT scores (at 1 month: 30.2, SD 10.8) compared to citalopram-treated patients (33.6, SD 13.7). Within the placebo group, the low genotype expression patients had significantly lower adjusted mean SDMT scores at 1 month compared to the high genotype expression patients (adjusted mean difference of -6 points, CI -12.0 to -0.05). We found similar results at 6 months, although not statistically significant. The genotype expression was not associated with SDMT scores among citalopram-treated patients., Conclusion: There was no difference in cognition between citalopram and placebo-treated patients according to the genotype group. Our results indicate, however, that low expression SERT genotype may contribute to reduced cognitive function post stroke as placebo-treated patients with low SERT expression tended to score lower on the SDMT. The significant difference in SDMT scores between low and high expression patients was present only in the placebo-treated group, thereby warranting further exploration of the potential effect of early citalopram treatment on cognitive functioning. Our results are preliminary and need replication in larger-scale studies., (© 2019 S. Karger AG, Basel.)

Objectives: This study aimed to investigate whether social support deficit has moderating effects on depressive and cardiac outcomes in an antidepressant trial for depressed patients with acute coronary syndrome as a secondary analysis using Escitalopram for DEPression in acute coronary syndrome study (ClinicalTrial.gov registry number: NCT00419471)., Methods: In total, 217 acute coronary syndrome patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition depressive disorders were randomized into two groups that received escitalopram (N = 108) or placebo (N = 109) for 24 weeks. Social support deficit was evaluated by validated scales at study entry. Depressive outcomes were measured using the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the Beck Depression Inventory. Cardiac outcomes included echocardiography (left ventricular ejection fraction and wall motion scores), electrocardiography (heart rate, PR interval, QRS duration, and QTc duration), and laboratory test results (troponin I and creatine kinase-MB)., Results: A higher social support deficit at baseline was significantly associated with less improvement in Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, Beck Depression Inventory scores, and serum troponin I levels after adjustment for corresponding baseline scores, covariates associated with social support deficit at baseline, and treatment status. The strength of these associations was more prominent in the placebo group compared to the escitalopram group., Conclusions: Evaluation of social support deficit in depressed acute coronary syndrome is important, and particularly during the acute phase, depressed acute coronary syndrome patients with social support deficit should be treated more carefully to improve treatment outcomes, given that social support deficit was predictive of poorer depressive and cardiac outcomes during the 24-week treatment period. Acute coronary syndrome patients with social support deficit should be treated more carefully to improve treatment outcomes.

Background: Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants., Methods: We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index., Results: We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk., Conclusions: The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.

Serotonin is implicated in multiple executive functions including goal-directed learning, cognitive flexibility, response inhibition and emotional regulation. These functions are impaired in several psychiatric disorders, such as depression and obsessive-compulsive disorder. We tested the cognitive effects of the selective serotonin reuptake inhibitor escitalopram, using an acute and clinically relevant dose (20 mg), in 66 healthy male and female volunteers in a double-blind, placebo-controlled study. Participants performed a cognitive test battery including a probabilistic and reversal learning task, the CANTAB intra-dimensional/extra-dimensional shift test of cognitive flexibility, a response inhibition task with interleaved stop-signal and No-Go trials and tasks measuring emotional processing. We showed that acute escitalopram administration impaired learning and cognitive flexibility, but improved the ability to inhibit responses in stop-signal trials while leaving unaffected acute emotional processing. Our findings suggest a dissociation of effects of acute escitalopram on cognitive functions, possibly mediated by differential modulation of brain serotonin levels in distinct functional neural circuits.

Objective: To objectively evaluate the efficacy and safety of citalopram versus other antidepressant drugs in poststroke depression (PSD) treatment., Methods: We searched randomized controlled trials (RCTs) that compared citalopram with other Selective serotonin reuptake inhibitors (SSRIs) and Serotonin norepinephrine reuptake inhibitor (SNRIs) on PSD treatment. The methodological quality of RCTs was assessed according to the Cochrane risk of bias tool. Meta-analysis was conducted using RevMan 5.3 software with standard mean difference (SMD) or Relative risk (RR) and their 95% confidence interval (CI)., Results: A total of 20 studies involving 1485 patients were included .The RR of efficacy index compared to other SSRIs was 1.04 [95% CI: .98-1.09, P = .17], and to SNRIs was 1.01 [95% CI: .93-1.09, P = .83]. The RR of cure index compared to other SSRIs was .99 [95% CI: .82-1.19, P = .88], and to SNRIs was .95 [95% CI: .71-1.27, P = .74]. Significant decreases on Hamilton Depression Scale scores were observed in favor of citalopram when compared to other SSRIs after 4-, 6-week treatment [SMD = -.44, 95% CI: -.85 to -.03, P = .03; SMD = -.50, 95% CI: -.98 to -.02, P = .04], and no significant difference was found with SNRIs in any week [P > .05]. The rate of adverse effects also showed no significant difference between citalopram and other antidepressants [P > .05]., Conclusions: This meta-analysis indicates that the efficacy of citalopram is similar to that of other SSRIs and SNRIs, but citalopram takes action faster than other SSRIs. The adverse effects of citalopram have no significant difference compared to other antidepressants and those adverse effects are less and mild., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The aim of the present study was to determine the relationship between the polymorphisms of -1438A/G and 102T/C in the 5-HT2A receptor (HTR2A) gene and nausea/vomiting as a side effect induced by sertraline (SERT) or citalopram (CIT) in patients with major depressive disorder., Methods: A total of 128 patients were enrolled, 63 patients received CIT, whereas 65 patients were treated with SERT. Nausea/vomiting were assessed with the UKU Side-effects Rating Scale at baseline and at the end of the second and fourth weeks. Polymerase chain reaction-restriction fragment length polymorphism technique was employed to determine genetic differences., Results: We have found that, in the patients treated with CIT, there was a nominally significant difference in the genotypic distribution associated with -1438A/G polymorphism between patients with and without nausea (X 2  = 6.15, p = 0.041). Moreover, logistic regression analysis revealed a significant association between nausea/vomiting as a side effect and -1438A/G polymorphism. That is, patients with the G allele were at a higher risk for developing nausea/vomiting (p = 0.044, odds ratio = 2.213). The 102T/C polymorphism in the HTR2A gene had no significant effect on the nausea/vomiting as a side effect among participants treated with either CIT or SERT., Conclusion: The present study suggests the association of the HTR2A gene -1438A/G polymorphism with nausea/vomiting as a side effect related to CIT treatment., (© 2018 John Wiley & Sons, Ltd.)

Background: To assess the risk of headache associated with commonly prescribed antidepressant medications and to examine the impact of medication class, pharmacodynamics and dosage on risk of headache., Methods: We searched PubMed to identify all randomized, double-blind, placebo-controlled trials examining the efficacy of second generation antidepressant medications in the treatment of adults with depression, anxiety or obsessive-compulsive disorders. We used a fixed-effect meta-analysis to examine the pooled risk ratio of headache reported as a side-effect in adults treated with second generation antidepressants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of medication type, class, dosage, indication, and receptor affinity profile on the measured risk of headache., Results: SSRIs were associated with a significantly increased risk of headache (RR = 1.06, 95%CI = 1.00-1.13, z = 2.0, p = 0.045) when compared to placebo. There was no significant difference (test for subgroup differences χ 2  = 2.2, df = 1, p = 0.14) in the risk of headache between SSRIs and SNRIs (RR = 0.97, 95%CI = 0.88-1.06, p = 0.63). There was no significant difference in the relative risk of headache with second generation antidepressants based on diagnostic indication, pharmacological properties and dosage of medications. The only antidepressants that were found to be significantly associated with increased risk of headache compared to placebo were bupropion (RR = 1.22, 95%CI = 1.06-1.41, z = 2.73, p = 0.006) and escitalopram (RR = 1.18, 95%CI = 1.01-1.37, z = 2.11, p = 0.04)., Limitations: The small number of studies that examined side effects within fixed-dose trials may have limited the power to examine the association between medication dosing and risk of headache. Additionally, reporting bias could potentially occur non-randomly across agents and therefore effect meta-analysis results., Conclusions: Headaches reported after the initiation of second generation antidepressant medications are more likely to be coincidental than a treatment-emergent side effect of these medications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It has been suggested that the superiority of antidepressants over placebo in controlled trials is merely a consequence of side effects enhancing the expectation of improvement by making the patient realize that he/she is not on placebo. We explored this hypothesis in a patient-level post hoc-analysis including all industry-sponsored, Food and Drug Administration-registered placebo-controlled trials of citalopram or paroxetine in adult major depression that used the Hamilton Depression Rating Scale (HDRS) and included a week 6 symptom assessment (n=15). The primary analyses, which compared completers on active treatment without early adverse events to completers on placebo (with or without adverse events) with respect to reduction in the HDRS depressed mood item showed larger symptom reduction in patients given active treatment, the effect sizes being 0.48 for citalopram and 0.33 for paroxetine. In actively treated subjects reporting early adverse events, who also outperformed those given placebo, the severity of the adverse events did not predict response. Several sensitivity analyses, for example, including (i) those using change of the sum of all HDRS-17 items as effect parameter, (ii) those excluding all subjects with adverse events (that is, also those on placebo) and (iii) those based on the intention-to-treat population, were all in line with the primary analyses. The finding that both paroxetine and citalopram are clearly superior to placebo also when not producing adverse events, as well as the lack of association between adverse event severity and response, argue against the theory that antidepressants outperform placebo solely or largely because of their side effects.

Objectives: To evaluate national trends in electrocardiogram (EKG) monitoring in Veterans Affairs (VA) beneficiaries prescribed high-dose citalopram before and after the 2011-12 Food and Drug Administration (FDA) safety warnings., Design: Interrupted time-series analyses., Setting: National VA healthcare system data linked to Medicare data for veterans dually eligible for VA and Medicare services., Participants: Adult VA outpatients prescribed citalopram or sertraline from February 2010 to September 2013 (N=1,068,816)., Measurements: EKG monitoring for VA outpatients prescribed high-dose citalopram (>40 mg/d aged ≤60, >20 mg/d aged >60) or sertraline., Results: For individuals prescribed high-dose citalopram, EKG monitoring increased from 9.0% before the start of the first FDA warning to a peak of 12.6% for individuals aged 18 to 60 and from 14.0% to 19.4% for individuals aged 61 to 100. However, following the second FDA warning in 2012, EKG monitoring declined, returning to prewarning levels in both age groups. EKG monitoring did not increase in individuals with a history of previous cardiac risk factors prescribed high-dose citalopram in either age group., Conclusions: EKG frequency did not significantly change in individuals with cardiac risk factors at greatest potential risk for QT prolongation. Lack of responsiveness to the FDA warnings may be due to many factors, including lack of clarity about which individuals should undergo EKG monitoring, provider substitution of alternative antidepressants for citalopram, conflicting evidence regarding risk for adverse cardiac events with high-dose citalopram use, and lack of provider knowledge regarding the warnings., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Cytochrome (CYP) P450 enzymes have a primary role in antidepressant metabolism and variants in these polymorphic genes are targets for pharmacogenetic investigation. This is the first meta-analysis to investigate how CYP2C19 polymorphisms predict citalopram/escitalopram efficacy and side effects. CYP2C19 metabolic phenotypes comprise poor metabolizers (PM), intermediate and intermediate+ metabolizers (IM; IM+), extensive and extensive+ metabolizers (EM [wild type]; EM+) and ultra-rapid metabolizers (UM) defined by the two most common CYP2C19 functional polymorphisms (rs4244285 and rs12248560) in Caucasians. These polymorphisms were genotyped or imputed from genome-wide data in four samples treated with citalopram or escitalopram (GENDEP, STAR*D, GenPod, PGRN-AMPS). Treatment efficacy was assessed by standardized percentage symptom improvement and by remission. Side effect data were available at weeks 2-4, 6 and 9 in three samples. A fixed-effects meta-analysis was performed using EM as the reference group. Analysis of 2558 patients for efficacy and 2037 patients for side effects showed that PMs had higher symptom improvement (SMD = 0.43, CI = 0.19-0.66) and higher remission rates (OR = 1.55, CI = 1.23-1.96) compared to EMs. At weeks 2-4, PMs showed higher risk of gastro-intestinal (OR = 1.26, CI = 1.08-1.47), neurological (OR = 1.28, CI = 1.07-1.53) and sexual side effects (OR = 1.52, CI = 1.23-1.87; week 6 values were similar). No difference was seen at week 9 or in total side effect burden. PMs did not have higher risk of dropout at week 4 compared to EMs. Antidepressant dose was not different among CYP2C19 groups. CYP2C19 polymorphisms may provide helpful information for guiding citalopram/escitalopram treatment, despite PMs being relatively rare among Caucasians (∼2%)., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

Background: Antidepressant withdrawal manic states are intriguing and under-recognized phenomena. The associated patho-physiological pathways are ill defined and the inclusion of the phenomena in the bipolar spectrum disorders is questionable. This study aims to update a review on antidepressant discontinuation manic states published in 2008 and to look for hints alluding to bipolar disorder in the affected published cases and in the literature. It also reviews the different hypotheses proposed to explain discontinuation mania., Methods: We searched Pubmed using the key words: 'antidepressant withdrawal' or 'antidepressant discontinuation' plus 'mania' or 'hypomania' from January 2008 until January 2018., Results: Five new eligible reports were identified since the last review in 2008, involving the antidepressants Amitriptyline, Fluoxetine, Escitalopram and Mirtazapine. Hypotheses involve the implication of Catecholamines, Acetylcholine and Serotonin in the pathophysiology of this paradoxical phenomenon. Careful analysis of the total 29 cases revealed psychiatric histories in favor of a bipolar spectrum disorder in 12 individuals while five were already known to have bipolar disorder., Limitations: This review is based on case reports with associated recall bias, and lack of in-depth description at times., Conclusions: Antidepressant discontinuation manic or hypomanic states do not occur randomly. An individual susceptibility to bipolar disorder must be considered., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Treatment of severely symptomatic patients with generalized anxiety disorder (GAD) raises particular concerns for clinicians. This 12-week double-blind study evaluated the efficacy of agomelatine (25-50 mg/day) in the treatment of patients with severe GAD, using escitalopram (10-20 mg) as active comparator. The primary outcome measure was the change from baseline of the total score on the Hamilton Anxiety scale (HAM-A) at week 12. Secondary outcome measures included rate of response to treatment (at least 50% score reduction from baseline) in the HAM-A psychic and somatic anxiety sub-scores, Clinical Global Impression severity and change scores, the Toronto Hospital Alertness Test, the Snaith-Hamilton Pleasure Scale, and the Leeds Sleep Evaluation Questionnaire Scores. Sixty one clinical centers (Australia, Canada, Czech Republic, Finland, Germany, Hungary, Poland, Russia, Slovakia) participated from April 2013 to February 2015. Patient characteristics and demographic data were comparable between treatment groups. Both treatments were associated with a clinically significant decrease in HAM-A total score at week 12; the non-inferiority of agomelatine versus escitalopram was not demonstrated (E(SE) = -0.91(0.69), 95%CI = [-2.26, 0.44], p = 0.195). At week 12, the response rate was 60.9% in the agomelatine group, and 64.8% in the escitalopram group. In both treatment arms, HAM-A psychic and somatic anxiety scores decreased, alertness and sleep parameters improved, and ability to experience pleasure increased. In these secondary outcome measures, there were no significant differences between the treatment groups. Agomelatine was well-tolerated, with a lower incidence of adverse events than escitalopram. Agomelatine and escitalopram are efficacious in treating GAD patients with severe symptoms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study., Methods: A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, calendar time, and age through density-based sampling. Rate ratios were computed using conditional logistic regression adjusting for other covariates., Results: We identified 3,838 subjects with EPSs compared with 38,380 age-matched control subjects. Rate ratios with respect to EPSs were as follows: duloxetine, 5.68 (95% confidence interval [CI], 4.29-7.53); mirtazapine, 3.78 (95% CI, 1.71-8.32); citalopram, 3.47 (95% CI, 2.68-4.50); escitalopram, 3.23 (95% CI, 2.44-4.26); paroxetine, 3.07 (95% CI, 2.15-4.40); sertraline, 2.57 (95% CI, 2.02-3.28); venlafaxine, 2.37 (95% CI, 1.71-3.29); bupropion, 2.31 (95% CI, 1.67-3.21); and fluoxetine, 2.03 (95% CI, 1.48-2.78)., Conclusions: This observational study demonstrates a harmful association between the incidence of Parkinson disease or associated EPSs and use of the antidepressants duloxetine, mirtazapine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, bupropion, and fluoxetine.

Objective: The present placebo-controlled study evaluated the efficacy and safety of 8 weeks of treatment with tianeptine 25-50 mg/d in elderly patients suffering from major depressive disorder (MDD) according to DSM-IV-TR. Escitalopram 5-10 mg/d was used as an active comparator., Methods: Elderly outpatients aged at least 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD were recruited by psychiatrists in 44 clinical centers in 10 countries from October 2013 to January 2016. Patients were randomly assigned to receive tianeptine (n = 105), placebo (n = 107), or escitalopram (n = 99) for 8 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇) total score., Results: Tianeptine improved depressive symptoms, as evaluated by the HDRS₁₇ total score in terms of absolute change from baseline (week 0) to week 8 (placebo-tianeptine difference [SE] of 3.84 [0.85] points, P < .001, using a last-observation-carried-forward approach) and response to treatment (tianeptine: 46.7%; placebo: 34.0%, estimate [SE] = 12.70% [6.70], P = .06). A sensitivity analysis using a mixed model for repeated measures confirmed the main results on HDRS total s​core. The placebo-tianeptine difference (SE) was 0.66 (0.15) for Clinical Global Impressions-Severity of Illness (95% CI, 0.37 to 0.96; P < .001) and 0.57 (0.14) for Clinical Global Impressions- Improvement (95% CI, 0.30 to 0.83; P < .001). Positive results were also obtained with the active control escitalopram (HDRS₁₇ total score placebo-escitalopram difference of 4.09 ± 0.86 points, P < .001), therefore validating the sensitivity of the studied population. Tianeptine was well tolerated, with only minimal differences in tolerability from placebo., Conclusions: The present study provides robust evidence that an 8-week treatment period with tianeptine 25-50 mg is efficacious and well tolerated in depressed patients aged 65 years or older., Trial Registration: EudraCT identifier: 2012-005612-26​., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

This paper describes a patient who presented with mania with psychotic features in the context of concomitant use of S-adenosyl-L-methionine (SAMe) and selective serotonin reuptake inhibitor (SSRI). The aim of this case report is to provide medical practitioners with a greater awareness of the possibility of a psychotic episode and/or mania manifesting with concurrent use of SAMe and SSRI., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

As the number of patients receiving a left ventricular assist device increases, physicians must always keep in mind that several conditions can present with non-specific symptoms, such as fever, tachypnoea and confusion. We herein report the case of a left ventricular assist device patient who developed a life-threatening condition with acute hyperthermia, confusion and extremities' clonus and muscle spasms. The patient was diagnosed with serotonin syndrome, attributed to the coadministration of 2 commonly prescribed medications (citalopram and omeprazole). This case highlights that a significant proportion of left ventricular assist device patients is treated with serotonergic agents that may predispose them to the appearance of serotonin syndrome, a potentially life-threatening condition.

Objective: The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population., Method: A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped patients 10-30 hours after drug intake were collected retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo. The patients were divided into subgroups based on CYP2C19 genotype: those carrying inactive (CYP2C19Null) and gain-of-function (CYP2C19*17) variant alleles. The between-subgroup differences in escitalopram exposure (endpoint: dose-harmonized serum concentration) and therapeutic failure (endpoint: switching to another antidepressant within 1 year after the last escitalopram measurement) were evaluated by multivariate mixed model and chi-square analysis, respectively., Results: Compared with the CYP2C19*1/*1 group, escitalopram serum concentrations were significantly increased 3.3-fold in the CYP2C19Null/Null group, 1.6-fold in the CYP2C19*Null/*1 group, and 1.4-fold in the CYP2C19Null/*17 group, whereas escitalopram serum concentrations were significantly decreased by 10% in the CYP2C19*1/*17 group and 20% in the CYP1C19*17/*17 group. In comparison to the CYP2C19*1/*1 group, switches from escitalopram to another antidepressant within 1 year were 3.3, 1.6, and 3.0 times more frequent among the CYP2C19Null/Null, CYP2C19*1/*17, and CYP1C19*17/*17 groups, respectively., Conclusions: The CYP2C19 genotype had a substantial impact on exposure and therapeutic failure of escitalopram, as measured by switching of antidepressant therapy. The results support the potential clinical utility of CYP2C19 genotyping for individualization of escitalopram therapy.

Selective serotonin re-uptake inhibitors are pharmaceuticals used to treat a range of psychological disorders. They are frequently found in surface waters in populated areas. In recent years, they have been shown to affect the behaviour of various aquatic organisms in a way that can have ecological effects. In this study, we exposed zebrafish of both sexes to nominally 0.00, 0.15 and 1.50 µg L -1 Escitalopram in flow-through tanks for three weeks. Subsequently, ten swimming behaviour parameters were quantified using high-resolution video tracking. There were noticeable gender differences in the behaviour responses to Escitalopram. Female fish exposed to 1.50 µg L -1 Escitalopram had a lower maximum swimming velocity, stopped less often and exhibited increased boldness (reduced thigmotaxis) compared to controls. Male fish exposed to 1.50 µg L -1 had a lower maximum swimming velocity compared to control fish. At the end of exposures, both length and weight of the females exposed to 1.50 µg L -1 Escitalopram were significantly less than the group of control fish. In addition, males exposed to 1.50 µg L -1 Escitalopram were significantly shorter than control fish. The behaviour, weight and body length of the fish exposed to nominally 0.15 µg L -1 was not significantly different from control fish in either sex. The results of this study demonstrate that Escitalopram can affect subtle but ecologically important aspects of fish behaviour and lends further credibility to the assumption that Escitalopram is an environmentally active pharmaceutical.

Objective: In 2011-2012 the U.S. Food and Drug Administration (FDA) issued safety announcements cautioning providers against prescribing high doses of citalopram given concerns for QT prolongation. The authors evaluated Veterans Affairs (VA) national trends in citalopram use and dose compared with alternative antidepressants after the FDA warnings., Methods: Time series analyses estimated the effect of the FDA warnings on citalopram and other antidepressant across three periods: before the first FDA warning in August 2011, after the 2011 FDA warning until the second warning in March 2012, and after the 2012 FDA warning. In a National VA health system, adult VA outpatients prescribed citalopram or alternative antidepressants from February 2010 to September 2013 were studied. Outpatient use of high-dose citalopram (>40 or >20 mg daily in adults aged > 60 years) including the proportion of patients prescribed citalopram and difference between study periods., Results: Between the first and second FDA warnings, among patients aged 18-60, high-dose citalopram use decreased by 2.0% per month (p < 0.001) and by 1.9% per month (p < 0.001) for older adults. After the second FDA warning in 2012, 30.7% of older patients remained on doses higher than the newly recommended dose of 20 mg. Reductions in overall use of citalopram were accompanied by significant increases in prescriptions of alternative antidepressants, with sertraline most widely prescribed., Conclusion: Although trends in high-dose citalopram use declined after the 2011-2012 FDA warnings, roughly one-third of older adults still remained on higher than recommended doses. Concomitant increases in sertraline and other antidepressant prescriptions suggest potential substitution of these medications for citalopram., (Copyright © 2017 American Association for Geriatric Psychiatry. All rights reserved.)

Background: Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved., Objectives: The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated., Materials and Methods: All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis., Results: No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T-2677T-3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22-4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29-4.87; P=0.007). In other groups, no statistically significant associations were observed., Conclusion: Our results suggest that female citalopram users with ABCB1 1236T-2677T-3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance of sex-based segregation in pharmacogenetics studies.

Background: Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications., Objective: We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients., Methods: In this nonsystematic review, we aimed to carefully and intensively identify new articles by utilizing a structured PubMed search from 2012-present., Results: QT prolongation remains an imperfect, though well-established marker of risk for TdP. Among antidepressant medications, citalopram does appear to prolong the QT interval more than other selective serotonin reuptake inhibitors, though the clinical significance of this prolongation remains unclear. Escitalopram appears to prolong the QT interval to a lesser extent. Haloperidol carries a risk for QT prolongation, but the assertion that intravenous haloperidol is inherently riskier may be confounded by its primary use in medically ill populations. Among atypical antipsychotic agents, ziprasidone-and possibly iloperidone-is associated with the greatest QT prolongation, whereas aripiprazole appears safest from this standpoint., Conclusions: The evidence for clinically meaningful QT prolongation with most classes of psychiatric agents remains minimal. The most important risk-reducing intervention clinicians can make is undertaking a careful analysis of other QT risk factors when prescribing psychiatric medications., (Copyright © 2017 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Prospective studies have not identified a viable pharmacologic strategy for secondary prevention of posttraumatic stress disorder (PTSD). The authors examined whether preventive intervention via early and short-term administration of a selective serotonin reuptake inhibitor (SSRI), within 1 month of exposure to a traumatic event (before diagnosis of PTSD could be made), may reduce the severity of PTSD symptoms according to DSM-IV at 13 months' follow-up., Methods: Over 25,000 screening calls to patients referred to an emergency department for a traumatic event performed between June 2006 and December 2008 yielded 353 participants who were recruited within the month following a traumatic event . Participants were randomly assigned in a double-blind design to escitalopram (n = 176) or placebo (n = 177). The per-protocol analysis comprised 198 participants (escitalopram, n = 102; placebo, n = 96) who received treatment for 12 to 24 weeks and were available for follow-up at week 56., Results: The primary outcome measure, the Clinician Administered PTSD Scale (CAPS), revealed no prevention effect. However, a secondary outcome, the Pittsburgh Sleep Quality Inventory (PSQI), showed better results for the SSRI group than for the placebo group. For a subset of participants who experienced intentional trauma (missile attacks, rape, or physical assault; n = 50), the prevention effect was found on both primary and secondary measures (CAPS, PSQI and measures of depression and global illness severity)., Conclusions: Early and short-term administration of escitalopram was not shown to prevent PTSD, although it did improve sleep quality. In a subgroup of participants who experienced intentional trauma, however, this early-treatment approach may be effective as secondary prevention. This large study is the first to investigate the preventive effect of early administration of escitalopram on PTSD. It highlights the relevance of the type of trauma (intentional vs unintentional) to the outcome., Trial Registration: ClinicalTrials.gov identifier: NCT00300313​​., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

In 2011/2012, the US Food and Drug Administration issued a warning about the effect of citalopram on the QT interval and decreased its dosing. Further studies addressing this issue have been published since then. The authors were interested to know whether or not the studies have furnished new information that could modify or further specify the FDA-issued recommendations. After analyzing the most relevant studies, the authors concluded that even papers published within the last 5 years confirmed that, of the SSRI class of drugs, citalopram prolongs the QT interval most significantly. While the QT interval prolongation in young and otherwise healthy individuals is small and treatment with citalopram relatively safe, in elderly comorbid patients with polypharmacy, use of even currently recommended doses may result in significant QT interval prolongation. Hence, the decision about future therapy will depend on the degree of risk of each individual patient. Judging by the most recent data, citalopram is not more effective compared with the other SSRIs. As a result, therapy with citalopram will presumably show a declining trend, particularly in elderly patients.Key words: citalopram - escitalopram - QT interval - SSRI.

Background: There is evidence for an association between major depressive disorder (MDD) and both inflammatory and phosphodiesterase (PDE) pathways. This study aimed to evaluate the adjunct role of the PDE inhibitor pentoxifylline (PTX), a compound with anti-inflammatory properties, in the treatment of adult patients with MDD., Methods: This was a prospective, 12-week, double-blind study of parallel groups. Eighty adult outpatients who met the DSM-IV criteria for MDD participated in the trial. Patients were required to have a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 18. Patients were allocated randomly: 40 received escitalopram 20 mg/day plus placebo while the other 40 received escitalopram 20 mg/day plus PTX (400 mg b.i.d.). Patients were assessed by a psychiatrist at baseline, and 4, 8, and 12 weeks after the medication had been started. The serum levels of TNF-α, IL-6, IL-10, BDNF, 8-OHdG, and serotonin were measured at baseline and after therapy., Results: After 8 and 12 weeks, the PTX group showed a statistically significantly greater improvement in HAM-D score compared to the control group (least squares mean difference [LSMD] -3.29, p = 0.000 and LSMD -3.49, p = 0.000, respectively). Moreover, the PTX group showed a statistically significantly greater reduction in the serum levels of TNF-α, IL-6, IL-10, and 8-OHdG along with a statistically significant increase in the levels of BDNF and serotonin in comparison with the control group after the treatment., Conclusion: The findings of this study suggest that PTX could be a promising adjunct to antidepressants in the treatment of MDD patients., (© 2018 S. Karger AG, Basel.)

The aim of this study was to quantify the risk of hair loss with different antidepressants. A retrospective cohort study design using a large health claims database in the USA from 2006 to 2014 was utilized. A cohort of new user and mutually exclusive users of fluoxetine, fluvoxamine, sertraline, citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion were followed to the first diagnosis of alopecia. The cohort was comprised of 1 025 140 new users of fluoxetine, fluvoxamine, sertraline, citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, desvenlafaxine, and bupropion, with sertraline the most commonly prescribed (N=190 227) and fluvoxamine (N=3010) the least prescribed. Compared with bupropion, all other antidepressants had a lower risk of hair loss, with fluoxetine and paroxetine having the lowest risk [hazard ratio (HR)=0.68, 95% confidence interval (CI): 0.63-0.74, HR=0.68, 95% CI: 0.62-0.74, respectively] and fluvoxamine having the highest risk (HR=0.93, 95% CI: 0.64-1.37). Compared with fluoxetine, bupropion had the highest risk of hair loss (HR=1.46, 95% CI: 1.35-1.58, number needed to harm=242 for 2 years) and paroxetine had the lowest risk (HR=0.99, 95% CI: 0.90-1.09). The results of this large population-based cohort study suggest an increase in the risk of hair loss with bupropion compared with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, whereas paroxetine had the lowest risk.

Neonatal abstinence syndrome (NAS) due to prenatally exposure to citalopram can develop during the first days of life even with low dose of drug exposure. Supportive management is the first choice but phenobarbital can be used in treatment of this syndrome. Breastfeeding should not be interrupted. These neonates should be followed both for NAS and neurodevelopmental outcome. In this article, we reported a newborn with NAS due to citalopram exposure with a lower dose than previously reported in the literature, during the last six months of pregnancy. Phenobarbital was used because of non-pharmacological treatment failure., (Sociedad Argentina de Pediatría.)

Electroconvulsive therapy (ECT) is rarely, if ever, considered for the treatment of severe anorexia nervosa (AN) or other eating disorders comorbid with an affective illness. Mood disorders are common in these patients, and psychotropic medications, although frequently used, have limited evidence of benefit in AN or copresenting depressive symptoms. Even when the illness is life threatening, ECT as a treatment may be overlooked. We present a case of an adolescent girl with severe AN and comorbid major depressive disorder with suicidality. This patient failed multiple medication trials but went on to experience complete remission from both the symptoms of her AN and major depressive disorder after undergoing a course of bilateral ECT. Electroconvulsive therapy may prove to be a fast and effective treatment strategy for mood disorders and suicidality in the setting of comorbid AN in adolescents.

Despite safety concerns raised by the European Medicines Agency (EMA), evidence supporting QT-lengthening effects of escitalopram is far to be conclusive. We aimed to evaluate the relationship between escitalopram plasma levels (Escit-PL) and corrected QT-interval length (QTc-length) in 91 outpatients recruited from a hospital setting. Fifteen patients had an abnormally prolonged QTc-interval, and 3 had QTc-intervals ≥500 ms. No correlation between Escit-PL and QTc-length was found (r = 0.08; p = 0.45). Linear/logistic regression analyses were also conducted taking into account potential confounders such as age, gender, personal history of heart disease, medication load and concomitant use of antipsychotic/tricyclic antidepressants. Escit-PL did not predict either QTc-length or abnormally prolonged QTc-interval. Only antipsychotics/tricyclics use (adjusted β = 0.26, SE = 9.1; p = 0.01) was an independent predictor of QTc-length (R 2  = 0.096, F = 4.68, df = 2,88; p = 0.01). Only antipsychotics/tricyclics use (OR 3.56 [95% CI 1.01-12.52]; p < 0.05) and medication load (OR 1.32 [95% CI 1.06-1.64]; p < 0.01) were significantly associated with an increased risk of abnormally prolonged QTc-interval (Omnibus test χ 2  = 9.5, df = 2; p < 0.01). Our study did not find a significant relationship between Escit-PL and QTc-length even when recognized modulating factors of the QT-interval were controlled for. Concomitant use of other potentially arrhythmogenic agents may help to explain the apparent link between escitalopram and QT prolongation previously suggested. The advisability of maintaining the EMA warning is once again called into question.