Risk of stress cardiomyopathy associated with selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors: a real-world pharmacovigilance analysis.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are reported to cause stress cardiomyopathy (SC). This study evaluated the association between SSRI/SNRI use and the occurrence of cardiomyopathy in the publicly available U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionate analysis and likelihood ratio tests were used to identify risk associated with SSRIs or SNRIs and the incidence of SC, using data from between from 2012 to 2022 acquired from the FAERS database. The study identified 132 individual case safety reports (ICSRs) of SC associated with SSRIs or SNRIs. Venlafaxine (48%) and fluoxetine (27%) were the most common antidepressants of the ICSRs. Approximately 80% of SC cases were reported in females, with individuals aged 45-65 years identified as a high-risk population. Both venlafaxine (ratio-scale information component [RSIC] 2.54, 95% CI 2.06-3.04) and fluoxetine (RSIC 3.20, 95% CI 2.31-4.47) were associated with SC, with likelihood ratio estimates of 3.55 (p = 0.02) for venlafaxine and 4.82 (p = 0.008) for fluoxetine. The median time to cardiomyopathy onset was 20 days, with hospitalization reported in 48.33% of patients. Venlafaxine and fluoxetine were associated with SC risk, particularly in middle-aged women. Caution should be exercised when using SSRIs or SNRIs combined with other serotonergic medications.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) patients are frequently exposed to antidepressant medications (ADMs). Norepinephrine (NE) and serotonin (5HT) systems have a role in levodopa-induced dyskinesias (LID) pathophysiology. METHODS: We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up. RESULTS: LID prevalence (according to MDS UPDRS score 4.1 ≥ 1) was 16% (42/251); these patients were more likely women (p = 0.01), had higher motor (p < 0.001) and depression scores (p = 0.01) and lower putaminal DAT binding ratio (p = 0.01). LID were associated with the exposure time to L-DOPA (2.2 ± 1.07 vs 2.6 ± 0.9, p = 0.02) and to the exposure to ADMs, in particular to SNRI (4.8% vs 21.4%, p < 0.001). The latter persisted after correcting for significant covariates (e.g., disease duration, cognitive status, motor impairment, depression, dopaminergic denervation). A similar difference in LID prevalence in PD patients exposed vs non-exposed to SNRI was observed on matched data by the real-world TriNetX repository (22% vs 13%, p < 0.001). DISCUSSION: This study supports the presence of an effect of SNRI on LID priming in patients with early PD. Independent prospective cohort studies are warranted to further verify such association.

Hyponatremia-associated hospital visits are not reduced by early electrolyte testing in older adults starting antidepressants.

BACKGROUND: Clinical practice guidelines recommend early serum electrolyte monitoring when starting antidepressants in older adults due to the increased risk of hyponatremia. It is unclear whether this monitoring improves outcomes. METHODS: Population-based, retrospective cohort study of Ontario adults aged ≥66 years who initiated therapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) between April 1, 2013, and January 31, 2020. The index date was the date of the first such prescription, and the exposure of interest was serum electrolyte measurement during the subsequent 7 days. The primary outcome was any emergency department or hospital admission with hyponatremia within 8-60 days of antidepressant initiation. Poisson regression models compared individuals who had versus did not have their serum electrolytes tested in the week following SSRI/SNRI initiation, weighting by propensity score-based overlap weights. RESULTS: Among the 420,085 patients aged ≥66 years initiating treatment with an SSRI/SNRI, 26,808 (6.4%) had serum electrolytes measured in the subsequent 7 days and 6109 (1.5%) subsequently presented to hospital with hyponatremia. The time from drug initiation to hospitalization varied (median 29, interquartile range [IQR] 17-44 days), and the median sodium concentration measured in the community (136, IQR 133-138 mmol/L) was marginally higher than those at the time of hospitalization (132, IQR 130-134 mmol/L). Patients who underwent electrolyte testing in the week following SSRI/SNRI treatment were more likely to attend an emergency department (ED) or hospital with hyponatremia within 8-60 days relative to those who did not (relative risk = 2.31, 95% confidence interval: 2.16-2.46). CONCLUSIONS: Testing serum electrolytes in the week after starting an SSRI/SNRI is not associated with a reduced risk of a hospital visit with hyponatremia. These findings do not support current guidelines recommending routine electrolyte monitoring.

Serotonin norepinephrine reuptake inhibitors in managing neuropathic pain following spinal and non-spinal surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: While serotonin norepinephrine reuptake inhibitors (SNRIs) offer promise in managing Post-surgical neuropathic pain (PSNP), uncertainties remain. This study aims to evaluate the effectiveness and adverse events of SNRIs in managing PSNP. METHODS: Systematic searches of PubMed, Embase, and Cochrane databases up to January 1st 2023 identified randomized controlled trials (RCTs) comparing SNRIs to placebo for PSNP. The primary outcome measures were pain at rest and adverse events post-surgery. Subgroup analyses were conducted based on surgical type and specific SNRIs. RESULTS: A total of 19 RCTs, encompassing 1440 participants (719 in the SNRI group vs 721 in the placebo group), met the inclusion criteria and were included. The pooled results demonstrated that pain scores were significantly lower in patients treated with SNRIs at 2 hours (MD:-0.26; 95%CI: -0.47 to -0.04; p=0.02), 6 hours (MD:-0.68; 95%CI: -1.01 to -0.34; p<0.0001), 24 hours (MD:-0.54; 95%CI: -0.99 to -0.09; p=0.02), and 48 hours (MD:-0.66; 95%CI: -1.23 to -0.10; p=0.02) post-surgery. In terms of adverse events, dizziness (OR:2.53; 95%CI: 1.34-4.78; p=0.004) and dry mouth (OR:2.21; 95%CI: 1.25-3.92; p=0.007) were significantly higher in the SNRIs group. Subgroup analysis showed that SNRI was found to significantly lower the 24-hour pain score after spinal surgery (MD:-0.45; 95%CI: -0.84 to -0.05; p=0.03). Duloxetine (MD:-0.63; 95%CI: -1.15 to -0.11; p=0.02) had a significant effect in lowering the 24-hour pain score at rest compared to placebo, whereas venlafaxine did not. CONCLUSIONS: SNRIs yielded considerable pain score reductions across multiple post-surgical intervals, although accompanied by an increased incidence of dizziness and dry mouth.

Risk of abnormal uterine bleeding associated with high-affinity compared with low-affinity serotonin and norepinephrine reuptake inhibitors.

BACKGROUND: Concerns have been raised about the potential association between selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of abnormal uterine bleeding (AUB), which may be influenced by the affinity of SSRIs/SNRIs for serotonin transporter. Thus, we assessed whether SSRIs/SNRIs with high-affinity for serotonin transporter are associated with AUB compared to SSRIs/SNRIs with low-affinity in non-pregnant women. METHODS: Using the UK Clinical Practice Research Datalink, we identified a cohort of women aged 15-24 years, newly prescribed a high- or low-affinity SSRI/SNRI between 1990 and 2019. Confounding was addressed using standardized morbidity ratio weighting. We used weighted Cox proportional hazards models to estimate the hazard ratio (HR) and 95 % confidence interval (CI) of AUB associated with high-affinity compared with low-affinity SSRIs/SNRIs. We assessed the risk of anemia as a secondary outcome. RESULTS: The cohort included 156,307 users of high-affinity SSRIs/SNRIs and 102,631 users of low-affinity SSRIs/SNRIs. High-affinity SSRIs/SNRIs were not associated with an increased risk of AUB compared with low-affinity SSRIs/SNRIs (incidence rates: 46.3 versus 42.4 per 1000 person-years, respectively; HR 1.01, 95 % CI 0.93-1.09). Duration of use, age, and comorbidities did not modify the risk. However, high-affinity SSRIs/SNRIs were associated with an increased risk of anemia (HR 1.29, 95 % CI 1.04-1.61) compared with low-affinity SSRIs/SNRIs. LIMITATIONS: Residual confounding may still be present. CONCLUSIONS: The risk of AUB did not differ between high- and low-affinity SSRIs/SNRIs. However, the potential risk of anemia suggests the need for monitoring and further investigation of the risk of AUB with these medications.

Concurrent administration of serotonergic antidepressants and ozanimod in participants with relapsing multiple sclerosis from the open-label extension DAYBREAK trial.

BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.

BACKGROUND: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown. METHODS: In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI. The primary end point was remission, defined as a score of 10 or less on the Montgomery-Åsberg Depression Rating Scale (MADRS), at week 8 (scores range from 0 to 60, with higher scores indicating more severe depression). The key secondary end point was no relapse through week 32 after remission at week 8. All patients were included in the analysis; patients who discontinued the trial treatment were considered as having had an unfavorable outcome (i.e., they were grouped with patients who did not have remission or who had a relapse). Analyses of the primary and key secondary end points were adjusted for age and number of treatment failures. RESULTS: Overall, 336 patients were assigned to the esketamine group and 340 to the quetiapine group. More patients in the esketamine group than in the quetiapine group had remission at week 8 (91 of 336 patients [27.1%] vs. 60 of 340 patients [17.6%]; P = 0.003) and had no relapse through week 32 after remission at week 8 (73 of 336 patients [21.7%] vs. 48 of 340 patients [14.1%]). Over 32 weeks of follow-up, the percentage of patients with remission, the percentage of patients with a treatment response, and the change in the MADRS score from baseline favored esketamine nasal spray. The adverse events were consistent with the established safety profiles of the trial treatments. CONCLUSIONS: In patients with treatment-resistant depression, esketamine nasal spray plus an SSRI or SNRI was superior to extended-release quetiapine plus an SSRI or SNRI with respect to remission at week 8. (Funded by Janssen EMEA; ESCAPE-TRD ClinicalTrials.gov number, NCT04338321.).

Risk of Hypertensive Disorders of Pregnancy in Women Treated With Serotonin-Norepinephrine Reuptake Inhibitors: A Comparative Study Using the EFEMERIS Database.

Background: Among antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs) are particularly expected to increase the risk of hypertensive disorders of pregnancy (HDP) with regard to their biological mechanism. We aimed to evaluate the association between prenatal exposure to SNRI and HDP.Methods: In EFEMERIS, a French database including pregnant women covered by the French Health Insurance System of Haute-Garonne (2004-2019), we compared the incidence of HDP among women exposed to SNRI monotherapy during the first trimester of pregnancy to the incidence among 2 control groups: (1) women exposed to selective serotonin reuptake inhibitor (SSRI) monotherapy during the first trimester and (2) women not exposed to antidepressants during pregnancy. We conducted crude and also multivariate logistic regressions.Results: Of the 156,133 pregnancies, 143,391 were included in the study population, including 210 (0.1%) in the SNRI group, 1,316 (0.9%) in the SSRI group, and 141,865 (98.9%) in the unexposed group. After adjustment for depression severity and other mental conditions, the risk of HDP was significantly higher among women exposed to SNRIs (n = 20; 9.5%) compared to women exposed to SSRIs (n = 72; 5.5%; adjusted odds ratio [aOR] [95% CI] = 2.32 [1.28-4.20]) and to unexposed women (n = 6,224; 4.4%; aOR [95% CI] = 1.89 [1.13-3.18]).Conclusion: This study indicated an increased risk of HDP in women treated with SNRIs versus women treated with SSRIs.

Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.

Head-To-Head Comparison of Vortioxetine Versus Desvenlafaxine in Patients With Major Depressive Disorder With Partial Response to SSRI Therapy: Results of the VIVRE Study.

Objective: To compare the efficacy of vortioxetine and the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine in patients with major depressive disorder (MDD) experiencing partial response to initial treatment with a selective serotonin reuptake inhibitor (SSRI).Methods: This randomized, double-blind, active-controlled, parallel-group, 8-week study of vortioxetine (10 or 20 mg/d; n = 309) versus desvenlafaxine (50 mg/d: n = 293) was conducted from June 2020 to February 2022 in adults with a DSM-5 diagnosis of MDD who experienced partial response to SSRI monotherapy. The primary endpoint was mean change from baseline to week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Differences between groups were analyzed using mixed models for repeated measures.Results: Non-inferiority of vortioxetine versus desvenlafaxine was established in terms of mean change from baseline to week 8 in MADRS total score; however, a numeric advantage was observed in favor of vortioxetine (difference, -0.47 MADRS points [95% CI, -1.61 to 0.67]; P = .420). At week 8, significantly more vortioxetine-treated than desvenlafaxine-treated patients had achieved symptomatic and functional remission (ie, Clinical Global Impressions-Severity of Illness scale [CGI-S] score ≤ 2) (32.5% vs 24.8%, respectively; odds ratio = 1.48 [95% CI, 1.03 to 2.15]; P = .034). Vortioxetine-treated patients also experienced significantly greater improvements in daily and social functioning assessed by the Functioning Assessment Short Test (P = .009 and .045 vs desvenlafaxine, respectively) and reported significantly greater satisfaction with their medication assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire (P = .044). Treatment-emergent adverse events (TEAEs) were reported in 46.1% and 39.6% of patients in the vortioxetine and desvenlafaxine groups, respectively; these were mostly mild or moderate in intensity (> 98% of all TEAEs in each group).Conclusions: Compared with the SNRI desvenlafaxine, vortioxetine was associated with significantly higher rates of CGI-S remission, better daily and social functioning, and greater treatment satisfaction in patients with MDD and partial response to SSRIs. These findings support the use of vortioxetine before SNRIs in the treatment algorithm in patients with MDD.Trial Registration: ClinicalTrials.gov Identifier: NCT04448431.

The pathophysiology of Post SSRI Sexual Dysfunction - Lessons from a case study.

BACKGROUND: Although Post-SSRI Sexual Dysfunction (PSSD) has finally been recognized by the European Medicines Agency as a medical condition that can outlast discontinuation of SSRI and SNRI antidepressants, this condition is still largely unknown by patients, doctors, and researchers, and hence, poorly understood, underdiagnosed, and undertreated. OBJECTIVE: Becoming familiar with the symptomatology of PSSD and understanding the underlying mechanisms and treatment options. METHOD: We applied a design thinking approach to innovation to 1) provide insights into the medical condition as well as the personal needs and pains of a targeted patient; and 2) generate ideas for new solutions from the perspective of this particular patient. These insights and ideas informed a literature search on the potential pathophysiological mechanisms that could underlie the patient's symptoms. RESULTS: The 55-year-old male patient developed symptoms of low libido, delayed ejaculation, erectile dysfunction, 'brain zaps', overactive bladder and urinary inconsistency after discontinuation of the SNRI venlafaxine. In many of these symptoms a dysregulation in serotonergic activity has been implicated, with an important role of 5-HT1A receptor downregulation and possible downstream effects on neurosteroid and oxytocin systems. CONCLUSIONS: The clinical presentation and development of symptoms are suggestive of PSSD but need further clinical elaboration. Further knowledge of post-treatment changes in serotonergic - and possibly noradrenergic - mechanisms is required to improve our understanding of the clinical complaints and to inform appropriate treatment regimes.

[TREATMENT OF SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SSRIS AND SNRIS) DURING PREGNANCY AND LACTATION].

INTRODUCTION: Women are more likely to develop depression during the perinatal period than at any other time in their lives. Studies from recent years raise significant concerns regarding the potential of a depressive disorder in the pregnant mother to cause adverse obstetric results for the mother and the newborn. As antidepressants can penetrate the placenta to different degrees, concern has been raised regarding their teratogenic potential. In recent years various inconsistent and ambiguous reports specifying mild risks to the fetus and newborn from exposure to serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) during pregnancy have been published. This paper provides a review of current medical knowledge regarding the pharmacological treatment with common antidepressants such as SSRIs and SNRIs in pregnant women. Based on this review we also present treatment and follow-up recommendations of the major published guidelines for the treatment of serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs) during pregnancy for the medical care providers.

SSRI/SNRI -induced Hyponatremia: A Case Series of 26 Patients in a Single Institution from 2018 to 2020.

Antidepressant medications are widely used by patients with depression or a depressive disorder. In spite of a generally favorable safety profile of selective serotonin reuptake inhibitors or serotonin - norepinephrine reuptake inhibitors (SSRI/SNRI), several cases of a possible connection between SSRI/SNRI and hyponatremia have been reported. To describe the clinical characteristics of patients with hyponatremia after SSRI/SNRI exposure, and to examine the association between SSRI/SNRI exposure and the presence of hyponatremia in a Chinese population. A retrospective single-center case series study. We performed a retrospective evaluation of inpatients with SSRI/SNRI-induced hyponatremia from a single institution in China between 2018 and 2020. Clinical data were obtained through review of medical records. Patients who met the initial inclusion criteria but did not develop hyponatremia acted as controls. The study was approved by the Clinical Research Ethics Board of Beijing Hospital (Beijing, P.R. China). We identified 26 patients with SSRI/SNRI-induced hyponatremia. The incidence rate of hyponatremia was 1.34% (26/1937) in the study population. The mean age at diagnosis was 72.58 (±12.84) years, with a male: female ratio of 1:1.42. The duration between SSRI/SNRI exposure and the onset of hyponatremia was 7.65 (±4.88) days. The minimum serum sodium level was 2328.23 (±107.25) mg/dL in the study group. Seventeen patients (65.38%) received sodium supplements. Four patients (15.38%) switched to another antidepressant. Fifteen patients (57.69%) recovered by the time of discharge. There were significant differences in serum potassium, serum magnesium and serum creatinine level between the two groups (p < 0.05). The rate of use of sertraline was significantly higher in the study group compared with the control group (p < 0.05). This pattern was not found in other SSRI/SNRI (p > 0.05). The results of our study show that SSRI/SNRI exposure, in addition to hyponatremia, may also affect the level of serum potassium, serum magnesium and serum creatinine. A history of hyponatremia and exposure to SSRI/SNRI may be potential risk factors for the development of hyponatremia. Future prospective studies are needed to validate these findings.

Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews.

OBJECTIVE: To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition. DESIGN: Overview of systematic reviews. DATA SOURCES: PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to 20 June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews comparing any antidepressant with placebo for any pain condition in adults. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data. The main outcome measure was pain; for headache disorders it was frequency of headaches. Continuous pain outcomes were converted into a scale of 0 (no pain) to 100 (worst pain) and were presented as mean differences (95% confidence intervals). Dichotomous outcomes were presented as risk ratios (95% confidence intervals). Data were extracted from the time point closest to the end of treatment. When end of treatment was too variable across trials in a review, data were extracted from the outcome or time point with the largest number of trials and participants. Secondary outcomes were safety and tolerability (withdrawals because of adverse events). Findings were classified from each comparison as efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the grading of recommendations assessment, development, and evaluation framework. RESULTS: 26 reviews (156 unique trials and >25 000 participants) were included. These reviews reported on the efficacy of eight antidepressant classes covering 22 pain conditions (42 distinct comparisons). No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. 11 comparisons (nine conditions) were found where antidepressants were efficacious, four with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain (mean difference -5.3, 95% confidence interval -7.3 to -3.3), postoperative pain (-7.3, -12.9 to -1.7), neuropathic pain (-6.8, -8.7 to -4.8), and fibromyalgia (risk ratio 1.4, 95% confidence interval 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons). CONCLUSIONS: Evidence of efficacy of antidepressants was found in 11 of the 42 comparisons included in this overview of systematic reviews-seven of the 11 comparisons investigated the efficacy of SNRIs. For the other 31 comparisons, antidepressants were either inefficacious or evidence on efficacy was inconclusive. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain conditions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022311073.

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

OBJECTIVES: Xerostomia, or dry mouth, is a condition that results from the reduction or absence of saliva flow secondary to the use of certain medications. The objective of the present study was to analyze the relationship between xerostomia patients and the consumption of serotonin norepinephrine reuptake inhibitors (SNRIs). METHOD AND MATERIALS: The University of Florida (UF) Integrated Data (IDR) i2b2, for the period of June 2015 to September 2022, was used based on aggregates of the International Classification of Diseases 10th edition (ICD-10) diagnoses of dry mouth and use of SNRI. MedCalc Software was used to calculate odds ratios. RESULTS: The odds ratio for dry mouth in the SNRI group was 5.95 (95% CI 5.47 to 6.48, P < .0001). The odds ratio for dry mouth in females on SNRI was 5.48 (95% CI 4.97 to 6.02, P < .0001), for males 5.48 (95% CI 4.56 to 6.95), P < .0001), for children 2.87 (95% CI 1.19 to 6.96, P = .0192), and for adults 4.46 (95% CI 4.09 to 4.86, P < .0001). When the different SNRIs were analyzed separately, the odds ratio for dry mouth with the use of venlafaxine was 5.83 (95% CI 5.12 to 6.6, P < .0001), duloxetine 6.97 (95% CI 6.33 to 7.67, P <.0001), desvenlafaxine 5.24 (95% CI 3.65 to 7.52, P < .0001), and milnacipran 9.61 (95% CI 5.66 to 16.31, P < .0001). CONCLUSION: According to the present study, patients who are taking SNRIs are five-fold more likely to develop dry mouth compared to those not on medications. The results could be informative to medical professionals who prescribe SNRIs and who are not currently aware of the effect they have on salivary production and therefore quality of life, as well as the dental practitioners treating these patients with dry mouth sequalae. (Quintessence Int 2023;54:150-154; doi: 10.3290/j.qi.b3704403).

Risk of Poor Neonatal Adaptation Syndrome Among Infants Exposed to Second-Generation Atypical Antipsychotics Compared to Antidepressants: Results From the National Pregnancy Registry for Psychiatric Medications.

Objective: While poor neonatal adaptation syndrome (PNAS) has been particularly well described among infants exposed to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), this is not the case for second-generation antipsychotics (SGAs). In 2011, the US Food and Drug Administration (FDA) issued a drug safety warning regarding fetal antipsychotic exposure and risk for PNAS and extrapyramidal symptoms (EPS). The primary objective of this study was to examine the risk for PNAS among infants exposed to SGAs compared to SSRI/SNRI-exposed infants, leveraging the prospective, longitudinal design of the National Pregnancy Registry for Psychiatric Medications (NPRPM).Methods: The NPRPM is a prospective pharmacovigilance program in which pregnant women, aged 18-45 years, are enrolled and followed prospectively. Medical records were systematically reviewed and data abstracted using a checklist of PNAS and EPS symptoms specifically outlined in the FDA drug safety warning. The two study groups included infants exposed to an SGA during pregnancy and infants exposed to an SSRI/SNRI during pregnancy. The primary outcome was the presence of at least one or more PNAS symptoms during the first month of life. Other neonatal outcomes following exposure to the medication of interest, including preterm birth, neonatal intensive care unit (NICU) admission, rates of EPS, and whether infants were discharged home with their mothers, are also reported.Results: Of the 2,145 women enrolled in this study as of December 16, 2020, a total of 373 women and their infants (n = 384) were eligible for inclusion (n = 193 SGA-exposed infants and 191 SSRI/SNRI-exposed infants). Among SGA-exposed infants, 32.6% (63/193) experienced at least 1 PNAS sign compared to 34.6% of infants (66/191) in the SSRI/SNRI-exposed group. The majority of infants in each group showed no symptoms of PNAS. No differences were observed between the two groups with respect to rates of preterm birth, NICU admission, prevalence of EPS, and timing of infants being discharged home with their mothers.Conclusions: PNAS symptomatology was comparable among infants exposed prenatally to an SGA or to an SSRI/SNRI. These preliminary findings provide an estimated risk of PNAS among infants exposed to SGAs of roughly 30%. Interestingly, these findings are also consistent with estimates in the literature of PNAS in SSRI/SNRI-exposed infants, suggesting a possible common pathway underlying this phenomenon.Trial Registration: ClinicalTrials.gov identifier: NCT01246765.

Onset of Transient Sadness Following the Concomitant Use of a Triptan and Selective Serotonin Reuptake Inhibitor/Serotonin Norepinephrine Reuptake Inhibitors Therapy: A Case Report.

Background: Migraine and depression have a bi-directional, positive association. The likelihood of these conditions being comorbidities is high, thus, the possibility of concomitant use of an antidepressant and a triptan is also increased. Case Presentation: We present a case of a 39-year-old female with a history of migraine with aura and depression who had brief episodes of exacerbated depressive symptoms following oral administration of sumatriptan 100 mg daily as needed while taking various selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) medications on different occasions. The patient experienced 30-minute episodes of sweating and subjective increase in temperature approximately 2-3 hours after administration of sumatriptan 100 mg. This was followed by a transient exacerbation of sadness described by the patient as unhappiness, hopelessness, and tearfulness, which lasted 1 to 2 hours. To date, there are no other published case reports that have described this particular presentation. Several studies have reported possible serotonin syndrome as a result of the combination. Current evidence and known pharmacological actions of SSRIs/SNRIs and triptans are not well-defined enough to explain how one can experience episodic worsening depression. Conclusion: This case illustrates that clinicians should consider other potential adverse effects of the combined use of triptans and SSRIs/SNRIs beyond serotonin syndrome.

Association between selective serotonin and serotonin-noradrenaline reuptake inhibitor therapy and hematuria.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are used as first-line treatment for many psychiatric diseases, especially major depressive disorder. However, an important side effect of these drugs is the risk of bleeding due to platelet dysfunction. The aim of this study was to determine the frequency of hematuria in patients using SSRI/SNRIs and to compare with a control group. METHODS: This study included patients who were followed up and treated with SSRI/SNRI in the psychiatric outpatient clinic of the Antalya Medical Park Hospital between 1 January 2021 and 31 March 2021 and a control group comprising patients who presented to the medical check-up outpatient clinic between the same dates. Complete urinalysis was performed for all patients and the results were compared between the groups. RESULTS: Each group included 100 patients with a female/male ratio of 1. The mean age was 41.45 ± 13.47 (16-74) years in the study group and 40.51 ± 13.75 (20-70) years in the control group (p = 0.519). Mean duration of SSRI/SNRI use in the study group was 13.35 ± 1.32 (1-64) months. The prevalence of hematuria was 17% in the SSRI/SNRI group and 6% in the control group (p = 0.015). All cases of hematuria were microscopic hematuria. CONCLUSION: Hematuria is significantly more common in patients receiving SSRI/SNRI treatment. The use of SSRI/SNRI should also be taken into account when investigating the etiology of hematuria.

Depression and antidepressant treatment in the development of hypertensive disorders of pregnancy: Results from a prospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy are associated with longer term cardiovascular risk. Understanding if depression or antidepressant use in pregnancy is associated with HDP is important in identifying those potentially vulnerable to poorer health in later life. This study examines if depression and antidepressants are associated with HDP. METHODS: In all, 815 pregnant women were recruited within an Australian pregnancy cohort study at less than 20 weeks of pregnancy, all undertook the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and were assigned to four groups for this paper: those with unmedicated depression meeting criteria for current depression (n = 97), those taking selective serotonin reuptake inhibitors in early pregnancy (n = 101), those taking serotonin and noradrenaline reuptake inhibitors in early pregnancy (n = 31), and those without depression or taking antidepressant medication (control; n = 586). Women were then assessed again following birth. Hypertensive disorders of pregnancy were diagnosed according to the Society of Obstetric Medicine in Australia and New Zealand Guidelines. RESULTS: Use of serotonin and noradrenaline reuptake inhibitors (SNRIs) (adjusted risk ratio = 9.10, 95% confidence interval = [3.82, 21.67]) and unmedicated depression (adjusted risk ratio = 3.11, 95% confidence interval = [1.32, 7.35]) were independently associated with significantly higher risk for developing hypertensive disorders of pregnancy compared to controls. Selective serotonin reuptake inhibitors (SSRIs) use did not confer any increased risk. Higher doses of SNRIs, but not selective serotonin reuptake inhibitors, were associated with significantly higher risk for developing HDP (adjusted risk ratio = 4.83, 95% confidence interval = [1.50, 15.58]). CONCLUSIONS: Our findings suggest that those with depression in pregnancy and/or on an serotonin and noradrenaline reuptake inhibitor should have closer surveillance for the development of hypertensive disorders of pregnancy. These findings support treatment of depression in pregnancy, however, also the consideration of class of antidepressant.