Effects of citalopram on blood pressure control in depressive patients with hypertension: A randomized clinical trial.

Introduction: Since there is a bi-directional interaction between hypertension and depression, we aimed to evaluate the effects of citalopram administration in the management of hypertension. Methods: A randomized clinical trial was conducted on 72 patients with concomitant depression and hypertension. The intervention group (n=41) received citalopram 20 mg daily plus anti-hypertensive standard treatment, while the control group (n=31) received only the standard treatment. The study's primary endpoint was in-office blood pressure (BP) measurement at baseline and home BP monitoring in the first and second months after entering the study. Results: There were no significant differences in baseline systolic BP (163.3±19.6 vs.164.2±20.3 mm Hg; P=0.910) and diastolic BP (94.5±13.8 vs. 88.2±14.4; P=0.071). After one month, diastolic BP (82.7±11.7 vs. 77.09±12.2; P=0.023) was significantly higher in the control group compared to the intervention group. Two months after the intervention, systolic BP (133.8±16.5 vs. 124.5±12.4; P=0.009) and diastolic BP (80.7±10.3 vs. 73.7±9.7; P=0.002) were significantly decreased in the intervention group compared to the control group. Conclusion: This study supported the beneficial effects of citalopram in lowering BP in patients with concomitant depression and hypertension.

Timing of selective serotonin reuptake inhibitor use and risk for preterm birth and related adverse events: with a consideration of the COVID-19 pandemic period.

OBJECTIVE: There is uncertainty around the safety of SSRIs for treating depression during pregnancy. Nevertheless, the use of SSRIs has been gradually increasing, especially during the COVID-19 pandemic period. We aimed to (1) characterize maternal depression rate and use of SSRIs in a recent 10-year period, (2) address confounding by indication, as well as socioeconomic and environmental factors, and (3) evaluate associations of the timing of SSRI exposure in pregnancy with risk for preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) infants among women with depression before pregnancy. METHODS: We conducted propensity score-adjusted regression to calculate odds ratios (ORs) of PTB, LBW, and SGA. We accounted for maternal/pregnancy characteristics, comorbidity, depression severity, time of delivery, social vulnerability, and rural residence. RESULTS: There were 50.3% and 40.3% increases in the prevalence rate of prenatal depression and prenatal SSRI prescription rate during the pandemic. We identified women with depression ≤180 days before pregnancy (n = 8406). Women with no SSRI order during pregnancy (n = 3760) constituted the unexposed group. The late SSRI exposure group consisted of women with an SSRI order after the first trimester (n = 3759). The early-only SSRI exposure group consisted of women with SSRI orders only in the first trimester (n = 887). The late SSRI exposure group had an increased risk of PTB of OR = 1.5 ([1.2,1.8]) and LBW of OR = 1.5 ([1.2,2.0]), relative to the unexposed group. Associations between late SSRI exposure and risk of PTB/LBW were similar among a subsample of patients who delivered during the pandemic. CONCLUSIONS: These findings suggest an association between PTB/LBW and SSRI exposure is dependent on exposure timing during pregnancy. Small for gestational age is not associated with SSRI exposure.

Low doses of fluoxetine for the treatment of emotional premenstrual syndrome: a randomized double-blind, placebo-controlled, pilot study.

INTRODUCTION: The neuroactive metabolite of progesterone, allopregnanolone (ALLO), has been implicated in premenstrual syndrome (PMS) physiopathology and preclinical studies suggested that low doses of fluoxetine increase the ALLO brain concentration. OBJECTIVES: To assess which low dose of fluoxetine (2 mg/d, 5 mg/d or 10 mg/d), administered exclusively during the luteal phase of menstrual cycle, has a potential effect for preventing or mitigating emotional PMS symptoms. METHODS: In this randomized, double-blind, placebo-controlled pilot study, we followed 40 women (mean age = 29.7 +/- 7.4 years) with emotional PMS, during two menstrual cycles: cycle 1, without pharmacological intervention; and cycle 2, with pharmacological intervention. Participants took capsules, on average, seven days preceding the likely date of menses. We assessed the severity of PMS symptoms in both cycles using the Daily Record of Severity of Problems scale (DRSP). RESULTS: There was an increase in the DRSP scores during the late luteal phase of cycle 1, confirming the diagnosis of emotional PMS. Low doses of fluoxetine (5 mg/d: 33.5%; 10 mg/d: 48.4%) reduced DRSP total score in the day before menses (day-1) at cycle 2 compared with day-1 at cycle 1. Fluoxetine 10 mg/d had the most consistent decline in emotional PMS symptoms; 70% of the participants reported a reduction greater than 40% in the DRSP score. CONCLUSIONS: Low doses of fluoxetine, which may have no or few effect on the serotonergic system, but may interfere in the progesterone metabolization, seem to have some potential to mitigate emotional PMS symptoms. While the 10 mg/d of fluoxetine had the best performance on reducing emotional PMS symptoms, the 5 mg/d dose also seems to have some effect on emotional PMS symptoms. Further larger studies will help establish the lowest effective dose of flouxetine for PMS treatment.

Intermittent selective serotonin reuptake inhibitors for premenstrual syndromes: A systematic review and meta-analysis of randomised trials.

BACKGROUND: Intermittent (luteal phase) dosing of selective serotonin reuptake inhibitors is one treatment strategy for premenstrual syndromes such as premenstrual dysphoric disorder. This avoids the risk of the antidepressant withdrawal syndrome associated with long-term continuous dosing. AIMS: To compare intermittent dosing to continuous dosing in terms of efficacy and acceptability. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, PubMed and CINAHL for randomised trials of intermittent compared with continuous dosing of selective serotonin reuptake inhibitors in premenstrual syndromes. We extracted response rates, dropout rates and changes in symptom scores. We used random effects meta-analyses to pool study-level data and calculated odds ratio for dichotomous data and standardised mean difference for continuous data. Risk of bias was assessed using the Cochrane risk-of-bias tool. The study was registered with PROSPERO (CRD42020224176). RESULTS: A total of 1841 references were identified, with eight studies being eligible for analysis, consisting of a total of 460 participants. All included studies provided response rates, six provided dropout rates and five provided symptom scores. There was no statistically significant differences between intermittent and continuous dosing in terms of response rate (odds ratio: 1.0, 95% confidence interval (CI): 0.23-4.31, I2 = 71%), dropout rate (odds ratio 1.26, 95% CI: 0.39-4.09, I2 = 33%) or symptom change (standardised mean difference: 0.04, 95% CI: -0.27 to 0.35, I2 = 39%). All studies had a moderate or high risk of bias. CONCLUSION: Since intermittent dosing avoids the potential for withdrawal symptoms, it should be considered more commonly in this patient population.

Selective serotonin reuptake inhibitors and inflammatory bowel disease; Beneficial or malpractice.

IBD, a chronic inflammatory disease, has been manifested as a growing health problem. No Crohn's and Colitis councils have officially ratified anti-depressants as a routine regimen for IBD patients. However, some physicians empirically prescribe them to rectify functional bowel consequences such as pain and alleviate psychiatric comorbidities. On the other side, SSRIs' prescription is accompanied by adverse effects such as sleep disturbances. Prolonged intermittent hypoxia throughout sleep disturbance such as sleep apnea provokes periodic reductions in the partial oxygen pressure gradient in the gut lumen. It promotes gut microbiota to dysbiosis, which induces intestinal inflammation. This phenomenon and evidence representing the higher amount of serotonin associated with Crohn's disease challenged our previous knowledge. Can SSRIs worsen the IBD course? Evidence answered the question with the claim on anti-inflammatory properties (central and peripheral) of SSRIs and illuminated the other substantial elements (compared to serotonin elevation) responsible for IBD pathogenesis. However, later clinical evidence was not all in favor of the benefits of SSRIs. Hence, in this review, the molecular mechanisms and clinical evidence are scrutinized and integrated to clarify the interfering molecular mechanism justifying both supporting and disproving clinical evidence. Biphasic dose-dependent serotonin behavior accompanying SSRI shifting function when used up for the long-term can be assumed as the parameters leading to IBD patients' adverse outcomes. Despite more research being needed to elucidate the effect of SSRI consumption in IBD patients, periodic prescriptions of SSRIs at monthly intervals can be recommended.

The Safety and Efficacy of Fluoxetine for the Treatment of Refractory Primary Monosymptomatic Nocturnal Enuresis in Children: A Randomized Placebo-Controlled Trial.

PURPOSE: We investigated the efficacy and safety of fluoxetine, a selective serotonin reuptake inhibitor, for treating refractory primary monosymptomatic nocturnal enuresis in children. MATERIALS AND METHODS: Children 8-18 years old with severe primary monosymptomatic nocturnal enuresis unresponsive to alarm therapy, desmopressin, and anticholinergics were screened for eligibility. After excluding children with daytime urinary symptoms, constipation, underlying urological, neuropsychiatric, endocrinological, or cardiac conditions, patients were randomly and equally assigned to 10 mg fluoxetine once daily or placebo for 12 weeks. The primary outcome was treatment response according to the International Children's Continence Society terminology. Treatment-related adverse effects and nighttime arousal were secondary outcomes. RESULTS: A total of 150 children were enrolled, of whom 110 (56 in fluoxetine group and 54 in placebo group) with a mean age of 11.8 (SD 2.46) years were finally analyzed. After 4 weeks, 7.1% and 66.1% of the fluoxetine group achieved complete response and partial response (defined as 50%-99% reduction of the number of wet nights), respectively, versus 0% and 16.7% of the placebo group (P < .001). At 12 weeks, complete and partial responses were achieved in 10.7% and 21.4% of the fluoxetine group, respectively (vs 0% and 14.8% of the placebo group, P = .023). Fluoxetine-treated patients had fewer wet nights (4.7 [SD 4.2] fortnightly vs 9.7 [SD 3.5] at 4 weeks, P < .001; 5.7 [SD 4.4] vs 9.9 [SD 3.4] at 8 weeks, P < .001; 7.5 [SD 4.6] vs 9.9 [SD 3.4] at 12 weeks, P = .003). Fluoxetine was associated with improved nighttime arousal (P = .017), and minor and rapidly reversible adverse effects in 5 (8.9%) patients. CONCLUSIONS: Fluoxetine is safe treatment for refractory primary monosymptomatic nocturnal enuresis in children with good initial response that declines at 12 weeks.

The effect of the use of proton pump inhibitors, serotonin uptake inhibitors, antihypertensive, and anti-inflammatory drugs on clinical outcomes of functional dental implants: A retrospective study.

OBJECTIVE: The present retrospective study investigated the effect of chronic intake of proton pump inhibitors, selective serotonin uptake inhibitors, anti-inflammatory, and antihypertensive drugs on the survival of dental implants and on the occurrence of peri-implantitis. MATERIALS AND METHODS: Survival analyses for implant failure and peri-implantitis were performed patient level for each drug subcategory and for risk factors. The HR for each drug was calculated with adjusted models as compared with a control group made of subjects not assuming the specific drug. Multilevel logistic regression was used to explore the influence of implant-level and patient-level variables on the outcomes. RESULTS: A total of 270 subjects receiving 1118 dental implants were included, with a mean follow-up time of 5.19 ± 4.22 years. After 10 years, the survival rate was 86.9% (patient level), and according to survival analysis, 61.3% of subjects were free from peri-implantitis. The use of anti-inflammatory medicines produced a significant effect (p = .04) on peri-implantitis as compared to subjects not using the drug, with a 2.7-year drop in the mean survival time. The HR was slightly above the level of significance in a semiadjusted model (p = .058). The multilevel analysis found a significant effect on the entire sample and not when considering only subjects with implants with more than 1-year follow-up. CONCLUSIONS: We found a possible relationship between anti-inflammatory drug use and the occurrence of peri-implantitis in the examined cohort of patients, and no correlation for the other drugs.

Males and females differ in reported sexual functioning with escitalopram treatment for major depressive disorder: A CAN-BIND-1 study report.

BACKGROUND: Antidepressant use for major depressive disorder (MDD) is frequently associated with sexual dysfunction. AIMS: Cross-sectional and longitudinal relationships between antidepressant treatment outcomes and sexual functioning (SF) were evaluated separately for males and females receiving escitalopram. We further assessed the association between pre- and posttreatment SF. METHODS: In all, 208 of the 211 CAN-BIND-1 trial participants (77 males and 131 females) with MDD and detectable drug blood levels were eligible for the analyses. All received escitalopram (10-20 mg) for 8 weeks. At baseline and Week 8, participants completed the Montgomery-Åsberg Depression Rating Scale (MADRS) and the SexFx scale, which measures sexual satisfaction and SF frequency. Mixed-model repeated measures assessed baseline to Week 8 SF changes among participants with different response/remission statuses. Multiple linear regression analyses examined SF differences between treatment outcomes at Week 8 as well as associations between pretreatment and eventual SF. RESULTS: For both sexes, overall sexual satisfaction improved among responders but not among nonresponders (p < 0.05). For females, overall SF frequency did not change significantly over time regardless of response status. For males, overall SF decreased significantly among nonresponders; orgasm decreased significantly among nonresponders and, to a lesser extent, among responders (p < 0.05). For both sexes, pretreatment SF was significantly associated with SF at Week 8 across all domains (p < 0.05). CONCLUSION: For both sexes, sexual satisfaction improves with response to escitalopram. For females, the response does not correspond to improvements in SF frequency. For males, SF frequency, particularly that of orgasm, declines regardless of response/nonresponse.ClinicalTrials.gov identifier: NCT01655706.

Selective Serotonin Reuptake Inhibitor Promotes Bone-Tendon Interface Healing in a Rotator Cuff Tear Rat Model.

BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) is believed to accelerate wound healing, and thus expected to have a positive effect on rotator cuff repair. We hypothesized that SSRI has a positive effect on the healing of the bone-tendon interface (BTI), and improved rotator cuff tear healing would be confirmed by mechanical strength measurements and histological assessment of the restored tendon. METHODS: The study used 40 adult male Sprague-Dawley wild-type rats. The animals were divided into two groups: group-SSRI, the supraspinatus repair with SSRI injection group, and group-C, conventional supraspinatus repair only without SSRI. Biomechanical and histological analyses were performed 8 weeks after index rotator cuff surgery. RESULTS: The ultimate load (N) was significantly higher in group-SSRI than in group-C (54.8 ± 56.9 Vs 25.1 ± 11.1, p = .031). In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 0.6 ± 0.5, group-SSRI: 1.1 ± 0.6, p = .024), vascularity (group-C: 0.1 ± 0.2, group-SSRI: 0.3 ± 0.4, p = .024) and cellularity (group-C: 1.7 ± 0.4, group-SSRI: 2.0 ± 0.0, p = .023) between the groups. Based on the total score, group-SSRI was significantly better compared with group-C (6.3 ± 2.7 Vs 4.3 ± 1.9, p = .019). CONCLUSION: Our study demonstrated that SSRI could facilitate improved biomechanical and histological outcomes 8 weeks after rotator cuff repair in a rat model. Consequently, SSRI may improve healing after rotator cuff repair.

Pretreatment anxious depression as a predictor of side effect frequency and severity in escitalopram and aripiprazole adjunctive therapy.

OBJECTIVE: To report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects. METHODS: 188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10-20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2-10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate-adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD-7 ≥ 10) and number of side effects. Covariate-adjusted logistic regression and chi-square tests explored the association between anxious depression and specific side effects. RESULTS: For both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p = .010) or had trouble with (IRR = 1.34, p = .026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p < .05). CONCLUSION: Patients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety.

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.

RATIONALE & OBJECTIVES: ± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration's phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. The current standard of care for these disorders involves treatment with psychiatric medications (e.g., selective serotonin reuptake inhibitors), so it will be important to understand drug-drug interactions between MDMA or psilocybin and psychiatric medications. METHODS: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the MEDLINE database via PubMed for publications of human studies in English spanning between the first synthesis of psilocybin (1958) and December 2020. We used 163 search terms containing 22 psychiatric medication classes, 135 specific psychiatric medications, and 6 terms describing MDMA or psilocybin. RESULTS: Forty publications were included in our systematic review: 26 reporting outcomes from randomized controlled studies with healthy adults, 3 epidemiologic studies, and 11 case reports. Publications of studies describe interactions between MDMA (N = 24) or psilocybin (N = 5) and medications from several psychiatric drug classes: adrenergic agents, antipsychotics, anxiolytics, mood stabilizers, NMDA antagonists, psychostimulants, and several classes of antidepressants. We focus our results on pharmacodynamic, physiological, and subjective outcomes of drug-drug interactions. CONCLUSIONS: As MDMA and psilocybin continue to move through the FDA drug development process, this systematic review offers a compilation of existing research on psychiatric drug-drug interactions with MDMA or psilocybin.

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

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

Periodontal status and the efficacy of the first-line treatment of major depressive disorder.

OBJECTIVES: The efficacy of treatment of major depressive disorder (MDD) is not satisfactory. Systemic inflammation may play an important role in MDD pathogenesis and treatment outcomes. Periodontal disease is the systemic inflammatory condition. Its prevalence may be as high as 45%. We aimed to assess the association of periodontal status with the outcome of 3-month first-line treatment of MDD with selective serotonin reuptake inhibitors. MATERIAL AND METHODS: We performed the prospective cohort study during 2018/2019 at Psychiatric Hospital "Sveti Ivan," Croatia, on a consecutive sample of 43 patients. The outcome was the MDD symptoms severity measured using the Hamilton Depression Rating Scale-17. The periodontal status was indicated by the clinical attachment loss (CAL). RESULTS: Baseline periodontal status had a nonlinear significant and clinically relevant association with the MDD treatment outcome (R2 change of the quadratic term = 0.12; p = 0.027). In patients with good baseline periodontal status the severity of MDD symptoms was significantly improved. When the value of CAL was ≥4.44 mm, indicating the worse periodontal status, further increase in baseline CAL was associated with the worsening of MDD treatment outcomes independently of the baseline depression severity and 14 sociodemographic and clinical predictors of treatment outcome. CONCLUSIONS: Periodontal healthcare is accessible, and should be utilize in an integrative, multidisciplinary approach not only for the sake of psychiatric patients' quality of life and prevention of periodontal disease, but for the sake of the outcomes of psychiatric treatment as well.

The Diagnostic Role of Neurophysiological Tests for Premature Ejaculation: A Prospective Multicenter Study.

PURPOSE: Premature ejaculation (PE) is one of the most common male sexual dysfunctions. Local anesthetics (LAs) and dapoxetine are frequently used to treat PE; however, previous studies show variable efficacy. This study aims to determine the efficacy of LAs and dapoxetine using a novel classification based on neurophysiological tests. MATERIALS AND METHODS: This multicenter cohort study enrolled adult men (568) with an intravaginal ejaculatory latency time (IELT) ≤2 minutes. Patients were divided into 4 groups according to the results of neurophysiological tests and assigned different treatments for 12 weeks: 1) penile sensory hyperexcitability type (Sens)-LAs; 2) penile sympathetic hyperexcitability type (Symp)-dapoxetine; 3) mixed type (Mixed)-both LAs and dapoxetine; 4) normal type (Norm)-both LAs and dapoxetine. Self-estimated IELT and patient-reported outcomes were recorded. RESULTS: The total percentage of men achieving IELT >2 minutes and ≥5 minutes after treatment were 82.7% and 76.7%, respectively. For men with abnormal results of neurophysiological tests, 401 (86.6%) had improved IELT >2 minutes after the 12-week treatment course, in which 375 (81.0%) achieved IELT ≥5 minutes. All patient-reported outcome measures improved in each group after 12 weeks of treatment, with greater improvements among those with abnormal neurophysiological tests. CONCLUSIONS: The efficacy of LAs and dapoxetine increased in PE patients with abnormal results of neurophysiological tests. This novel classification of PE using neurophysiological tests could help guide and improve efficacy of PE therapies.

Selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor associated cutaneous adverse drug reactions: A systematic review of case reports and case series.

Anecdotal evidence suggests that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) cause cutaneous adverse drug reactions (CADRs). However, there is limited information on the factors associated with these occurrences. In this study, we aimed to describe the demographic, clinical and pharmacological characteristics associated with CADRs encountered by patients administered SSRIs and/or SNRIs for psychiatric diagnoses and to compare the differences in these factors between severe and non-severe CADRs. A protocol was developed a priori (PROSPERO: CRD42020204830) in line with the PRISMA guidelines. We searched PubMed/Medline, PsycINFO and SCOPUS from inception to October 2020 to identify case reports and/or case series of SSRI and SNRI associated CADRs. Additional cases were obtained from the retrieved articles' bibliography. A total of 141 articles were included in the study, documenting 173 CADRs. Females accounted for 128 (74.0%) of the analysed CADRs. The median age of the cases was 42 IQR (27; 53) with no statistically significant differences in age between males and females (P = 0.542). A total of 157 (90.8%) of the reported CADRs were associated with SSRIs, particularly fluoxetine 68 (39.5%), sertraline 30 (17.4%) and paroxetine 25 (14.5%). Non-severe CADRs and severe CADRs accounted for 23 (13.4%) and 149 (86.6%) reports respectively. No statistically significant differences were observed for gender (P = 0.616), age at onset (P = 0.493) and time to onset (P = 0.105) between non-severe CADRs and SCARs. In conclusion, CADRs following SSRIs and SNRIs disproportionately affect females in the reproductive age group compared to males and are mostly associated with SSRIs.

Rapid response to selective serotonin reuptake inhibitors in post-COVID depression.

The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. After COVID-19, depression was reported in 40% of patients at one-, three-, and six-months follow-up. Emerging literature suggests anti-inflammatory and antiviral properties of antidepressants in the treatment of SARS-CoV-2. We aim to investigate the efficacy of Selective Serotonin Reuptake Inhibitor (SSRI) in treating post-COVID depression. We included 60 patients affected by a major depressive episode and treated with SSRI in the six months following recovery from COVID. The severity of depression was rated at baseline and after four weeks on the Hamilton Depression Rating Scale (HDRS). Response to treatment was considered when the patients achieved a 50% HDRS reduction. To investigate changes of depressive symptomatology over time, repeated measures ANOVAs according to clinical variables were performed. We found that 55 (92%) patients showed a clinical response to antidepressant. Patients showed a significant decrease over time of HDRS score (baseline HDRS = 23.37 ± 3.94, post-treatment HDRS = 6.71±4.41, F = 618.90, p < 0.001), irrespectively of sex, previous psychiatric history, previous history of mood disorder, and SSRI type. This is the first study to explore the SSRI efficacy in post-COVID depression, suggesting rapid antidepressant effects in most patients. SSRIs treatment could contribute to the rapid antidepressant response by directly targeting the neuroinflammation triggered by SARS-CoV-2. We suggest screening psychopathology of COVID-19 survivors to diagnose emergent depression and pharmacologically treat it to reduce the disease burden and related years of life lived with disability.

Trazodone Add-on in COVID-19-related Selective Serotonin Reuptake Inhibitor-resistant Post-traumatic Stress Disorder in Healthcare Workers: Two Case Reports.

COVID-19 represents a significant stress factor for all people worldwide due to several factors, including quarantine, lockdowns, fear of contagion, deaths, and other traumatic events. However, the healthcare workers (HCWs) have paid the higher price of this pandemic in terms of fatalities, contagions, and psychological well-being. Studies suggest that this particular population is at increased risk of developing a severe post-traumatic stress disorder (PTSD). The early diagnosis and timely treatment of PTSD in HCWs may restore well-being and significantly impact health services functioning, reducing burnout, days spent far from work, disrupted personal and team empowerment, and worse job performances. In the present article, we reported on two cases of HCWs directly involved in the treatment of COVID-19 patients who showed selective serotonin reuptake inhibitor-resistant PTSD, which was successfully treated with extended-release trazodone TRZ ContramidⓇ add-on.

Drug-Resistant Hyponatremia after Escitalopram Intake: A Series of Two Case Reports.

The consumption of new selective serotonin reuptake inhibitors (SSRIs) is raising dramatically especially in European countries. It contributes to occurrence of clinically important drug side effects. One of which can be hyponatremia. We present two case reports of 85-year-old and 84-year-old women who developed hyponatremia after escitalopram administration. We hypothesize that in both cases hyponatremia was connected with antidepressants administration. However, due to multiple comorbidities and polypharmacy it is often impossible to establish the exact mechanism of hyponatremia. Moreover, it is crucial to distinguish subtypes of drug-induced syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), such as SSRI-induced SIADH, reset osmostat SIADH, thiazide-associated hyponatremia, thiazide-induced hyponatremia, mineralocorticoid responsive hyponatremia of older adults, in order to properly diagnose and treat geriatric patients. Administration of antidepressants or thiazides should be followed by a regular monitoring of serum sodium level.

Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial.

Background and Purpose: The EFFECTS (Efficacy of Fluoxetine­a Randomised Controlled Trial in Stroke) recently reported that 20 mg fluoxetine once daily for 6 months after acute stroke did not improve functional outcome but reduced depression and increased fractures and hyponatremia at 6 months. The purpose of this predefined secondary analysis was to identify if any effects of fluoxetine were maintained or delayed over 12 months. Methods: EFFECTS was an investigator-led, randomized, placebo-controlled, double-blind, parallel group trial in Sweden that enrolled adult patients with stroke. Patients were randomized to 20 mg oral fluoxetine or matching placebo for 6 months and followed for another 6 months. The primary outcome was functional outcome (modified Rankin Scale), at 6 months. Predefined secondary outcomes for these analyses included the modified Rankin Scale, health status, quality of life, fatigue, mood, and depression at 12 months. Results: One thousand five hundred patients were recruited from 35 centers in Sweden between 2014 and 2019; 750 were allocated fluoxetine and 750 placebo. At 12 months, modified Rankin Scale data were available in 715 (95%) patients allocated fluoxetine and 712 (95%) placebo. The distribution of modified Rankin Scale categories was similar in the 2 groups (adjusted common odds ratio, 0.92 [95% CI, 0.76­1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (interquartile range, 75­100) versus 93 (interquartile range, 82­100); P=0.0021 and communication 93 (interquartile range, 82­100) versus 96 (interquartile range, 86­100); P=0.024 domains of the Stroke Impact Scale compared with placebo. There were no other differences in secondary outcomes. Conclusions: Fluoxetine after acute stroke had no effect on functional outcome at 12 months. Patients allocated fluoxetine scored worse on memory and communication on the Stroke Impact Scale compared with placebo, but this is likely to be due to chance. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02683213.

Evidence-Based Pharmacotherapy of Generalised Anxiety Disorder: Focus on Agomelatine.

Recent network meta-analyses support the use of pharmacotherapy in patients with generalised anxiety disorder (GAD). Compared with placebo, drug treatment can improve symptoms and quality of life, and is more effective in preventing relapse. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are generally considered the first-line agents of choice in GAD, but in some patients, an alternative evidence-based treatment with a different mechanism of action may also be considered (e.g. those with severe GAD, inadequate response, adverse effects and/or contraindications). One example is agomelatine, a melatonin receptor agonist and serotonin 2C (5-HT2C) receptor antagonist, which has been shown to have efficacy that is greater than placebo in patients with GAD, and to have a tolerability profile that compares favourably with that of escitalopram. Both agomelatine and escitalopram are efficacious in treating patients with GAD, including those with severe symptoms. Video Abstract.