Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).

The antidepressant, sertraline, impacts growth and reproduction in the benthic deposit feeder, Tubifex tubifex.

Among emerging contaminants, pharmaceuticals are considered one of the most pertinent substances that may threaten aquatic ecosystems. Pharmaceuticals are designed to be directed at specific metabolic- and molecular pathways. Thus, they are assumed to be still biologically active when entering the ecosystem and may result in unpremeditated impacts on non-target organisms. One of the most widely used selective serotonin reuptake inhibitors, sertraline (an antidepressant), is regularly found in aquatic environments. However, knowledge about the effects, and in particular, of sediment-associated sertraline in benthic invertebrates is limited. We examined the impacts of chronic exposure (28 d) to sediment-associated sertraline (3.3, 33, 330 µg/g dw sed.) on survival, growth and reproduction in the deposit-feeding oligochaete, Tubifex tubifex. Sertraline significantly decreased T. tubifex survival and growth. Worms exposed to high sertraline concentrations (330 µg/g) had a lower growth rate and reproduction, as indicated by a significantly lower number of cumulated cocoons. Worms exposed to an environmentally relevant concentration (3.3 µg/g) decreased growth but maintained a reproduction rate similar to that of the control. The implications are that adult worms exposed to high sertraline concentrations presumably required more energy for maintenance and detoxification, thereby reducing available energy for reproduction and growth. This represents a trade-off between survival, reproduction and growth. In contrast, T. tubifex exposed to environmentally relevant concentrations allocated more energy to reproduction by slightly increasing the number of cocoons produced and reducing growth. However, the quantity and quality of offspring may be impacted as we observed fewer juveniles in the environmentally relevant treatment than in the control. Overall, the results indicate that sediment-associated sertraline is bioavailable and negatively impacts T. tubifex survival, growth, and reproduction even at environmentally relevant concentrations.

Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer's Disease.

Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living', with the most prevalent type of dementia being Alzheimer's disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-ß protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.

Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants.

BACKGROUND: Sexual dysfunction is a common side effect of Serotonergic antidepressants (SA) treatment, and persists in some patients despite drug discontinuation, a condition termed post-SSRI sexual dysfunction (PSSD). The risk for PSSD is unknown but is thought to be rare and difficult to assess. This study aims to estimate the risk of erectile dysfunction (ED) and PSSD in males treated with SAs. METHODS: A 19-year retrospective cohort analysis was conducted using a computerized database of the largest HMO in Israel. ED was defined by phosphodiesterase-5 inhibitors prescriptions. 12,302 males aged 21-49 met the following criteria: non-smokers, no medical or psychiatric comorbidities or medications associated with ED, no alcohol or substance use. Logistic regression was used for estimation of ED risk in SA-treated subjects compared to non-SA-treated controls, assessed with and without the effects of age, body mass index (BMI), socioeconomic status (SES), depression and anxiety, yielding crude and adjusted odds ratios (cOR and aOR, respectively). RESULTS: SAs were associated with an increased risk for ED (cOR = 3.6, p < 0.000001, 95% CI 2.8-4.8), which remained significant after adjusting for age, SES, BMI, depression and anxiety (aOR = 3.2, p < 0.000001, 95% CI 2.3-4.4). The risk for PSSD was 1 in 216 patients (0.46%) treated with SAs. The prevalence of PSSD was 4.3 per 100,000. CONCLUSIONS: This work offers a first assessment of the small but significant risk of irreversible ED associated with the most commonly prescribed class of antidepressants which should enhance the process of receiving adequate informed consent for therapy.

Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors as adjuncts for postoperative pain management: systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: We conducted a systematic review and meta-analysis to assess effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as adjuncts for postoperative pain management. METHODS: We searched seven databases and two trial registers from inception to February 2021 for RCTs that compared SSRIs or SNRIs with placebo or an active control for postoperative pain management. RESULTS: We included 24 RCTs with 2197 surgical patients (21 trials for SNRIs and three trials for SSRIs). Moderate-quality evidence found that, compared with placebo, SSRIs/SNRIs (majority SNRIs) significantly reduced postoperative pain within 6 h {weighted mean difference (WMD) -0.73 cm on a 10 cm VAS (95% confidence interval [CI]: -1.04 to -0.42)}, 12 h (-0.68 cm [-1.28 to -0.07]), 24 h (-0.68 cm [-1.16 to -0.20]), 48 h (-0.73 cm [-1.22 to -0.23]), 10 days to 1 month (-0.71 cm [-1.11 to -0.31]), 3 months (-0.64 cm [-1.05 to -0.22]), and 6 months (-0.95 cm [-1.64 to -0.25]), and opioid consumption within 24 h (WMD -12 mg [95% CI: -16 to -8]) and 48 h (-10 mg [-15 to -5]), and improved patient satisfaction (WMD 0.49 point on a 1-4 Likert scale [95% CI: 0.09 to 0.89]) without significant increase in adverse events. Selective serotonin reuptake inhibitors tended to be less effective despite non-significant subgroup effects. CONCLUSIONS: Serotonin-norepinephrine reuptake inhibitors as an adjunct to standard perioperative care probably provide small reduction in both acute and chronic postoperative pain and opioid consumption, and small improvement in patient satisfaction without increases in adverse events. The effects of SSRIs are inconclusive because of very limited evidence.

Protective Effect of Escitalopram on Hepatocellular Carcinoma by Inducing Autophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with poor prognosis. Although recent research has indicated that selective serotonin reuptake inhibitors (SSRIs), including escitalopram, have anticancer effects, little is known about the effects of escitalopram on HCC. METHODS: Both in vitro and in vivo studies were conducted to verify the potentials of escitalopram on HCC treatment. To explore whether the effects of escitalopram are clinically consistent with laboratory findings, a nationwide population-based cohort study was also adopted to examine the association between escitalopram and HCC risk. RESULTS: As compared with THLE-3 cells, escitalopram significantly inhibited the proliferation of HepG2 and Huh-7 cells. Specifically, escitalopram significantly induced autophagy in HepG2 and Huh-7 cells by increasing the LC3-II/LC3-I ratio and the expression of ATG-3, ATG-5, ATG-7, and Beclin-1 proteins. Moreover, escitalopram significantly inhibited the growth of xenografted Huh-7 cells in SCID mice that were treated with 12.5 mg/kg escitalopram. Accordingly, the risk of HCC was negatively correlated with escitalopram use. CONCLUSIONS: These findings provided evidence supporting the therapeutic potential of escitalopram for HCC. Both laboratory and nationwide population-based cohort evidence demonstrated the attenuated effects of escitalopram on HCC.

Synergistic Effects of the Combinational Use of Escitalopram Oxalate and 5-Fluorouracil on the Inhibition of Gastric Cancer SNU-1 Cells.

Owing to its high recurrence rate, gastric cancer (GC) is the leading cause of tumor-related deaths worldwide. Besides surgical treatment, chemotherapy is the most commonly used treatment against GC. However, the adverse events associated with chemotherapy use limit its effectiveness in GC treatment. In this study, we investigated the effects of using combinations of low-dose 5-fluorouracil (5-FU; 0.001 and 0.01 mM) with different concentrations of escitalopram oxalate (0.01, 0.02, 0.06, and 0.2 mM) to evaluate whether the assessed combination would have synergistic effects on SNU-1 cell survival. 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.06 mM) administered over 24 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Moreover, 5-FU (0.001 mM) + escitalopram oxalate (0.02 or 0.06 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.02, 0.06, or 0.2 mM) administered over 48 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Compared with controls, SNU-1 cells treated with 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) exhibited significantly increased levels of annexin V staining, reactive oxygen species, cleaved poly (ADP-ribose) polymerase, and caspase-3 proteins. Furthermore, 5-FU (12 mg/kg) + escitalopram oxalate (12.5 mg/kg) significantly attenuated xenograft SNU-1 cell proliferation in nude mice. Our study is the first to report the synergistic effects of the combinational use of low-dose 5-FU and escitalopram oxalate on inhibiting SNU-1 cell proliferation. These findings may be indicative of an alternative option for GC treatment.

Differential serotonin transporter (5-HTT) and 5-HT2 receptor density in limbic and neocortical areas of adults and children with autism spectrum disorders: implications for selective serotonin reuptake inhibitor efficacy.

As selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed medications in autism, we aimed to determine whether targets for SSRIs are differentially affected in three cortical areas in children and adults with autism compared to neurotypical individuals. Utilizing a large cohort of postmortem brain tissue (n = 14-19 per group), saturation ligand binding assays were conducted on sections from the anterior cingulate cortex (ACC), posterior cingulate cortex, and fusiform gyrus (FG). Specific binding to the 5-HT transporter (5-HTT) as well as to 5-HT2 and 1A receptors (5-HT2, 5-HT1A ) was quantified in superficial and deep layers of each region using the ligands [3 H]-citalopram (5-HTT), [3 H]-ketanserin (5-HT2 ), and [3 H]-8-OH-DPAT (5-HT1A ). A Welch's t-test was utilized to compare receptor densities (Bmax ), revealing a statistically significant decrease in 5-HTT within the ACC of the entire autism cohort. There was also a decrease in 5-HT2 receptor density in the ACC in the adult cohort, but not in child postmortem autism cases as compared to controls. Comparing linear regression lines of Bmax values plotted against age, shows a significantly lower intercept for 5-HTT in autism (p = 0.025). 5-HT2 density increases with age in control cases, whereas in autism there is a decrease with age and significantly different slopes between regression lines (p = 0.032). This suggests a deficit in 5-HTT within the ACC in individuals with autism, while decreases in 5-HT2 density are age-dependent. There were no differences in receptor densities in the posterior cingulate cortex or FG in autism and no differences in ligand affinity (KD ) across all regions and ligands examined.

Does the antidepressant sertraline show chronic effects on aquatic invertebrates at environmentally relevant concentrations? A case study with the keystone amphipod, Gammarus locusta.

The increasing use of Sertraline (SER) as antidepressant and its consequent presence in the aquatic environment is raising concern about the chronic effects of this pharmaceutical to aquatic organisms. As the current concentrations of SER in surface waters are typically in the low ng/L range, acute toxicity is unlikely to occur. However, prolonged exposure to low concentrations of SER may lead to sub-lethal effects in aquatic organisms, including alterations in important physiological functions like growth, reproduction, behaviour, and also in key biochemical processes, such as those associated with neurotransmission and redox balance. To test this hypothesis, we selected the amphipod Gammarus locusta, a keystone species used in ecotoxicological hazard assessment. In the present study, juveniles' G. locusta from a permanent laboratory culture were chronically exposed to low concentrations of SER (8-1000 ng/L) in a bioassay that lasted for 48 days, allowing for a life-cycle study including effects on reproduction. At the lowest SER concentrations with environmental relevance (8, 40 and 200 ng/L) we detected no significant changes in key ecological endpoints such as survival, growth, reproduction and movement behaviour, or in any of the biochemical markers analysed. However, at 1000 ng/L SER (a concentration one order of magnitude higher than the levels reported in aquatic environments) females showed a significant increase in movement versus control, whereas no activity changes were observed in males. Overall, these findings indicate that G. locusta females are potentially more susceptible to the chronic effects of SER. Moreover, the current environmental SER concentrations are unlikely to affect amphipod's ecological endpoints because only SER concentrations higher than the levels reported in aquatic environments produced effects on the behaviour of G. locusta females. However, the increasing consumption of SER, highlights the importance of monitoring its chronic risk to the aquatic wildlife.

Effect of Physical Exercise and Acute Escitalopram on the Excitability of Brain Monoamine Neurons: In Vivo Electrophysiological Study in Rats.

Background: The antidepressant effect of physical exercise has been reported in several clinical and animal studies. Since serotonin, norepinephrine, and dopamine play a central role in depression, it is possible that the beneficial effects of physical exercise are mediated via monoamine pathways. This study investigates the effects of voluntary wheel running on the excitability of monoamine neurons. Materials and Methods: Male Sprague-Dawley rats were used in the study. Voluntary wheel running (VWR) rats were housed in individual cages with free access to a running wheel, while control animals were housed in standard laboratory cages. After three weeks, the rats were anesthetized, and in vivo electrophysiological recordings were taken from dorsal raphe nucleus serotonin neurons, locus coeruleus norepinephrine neurons, and ventral tegmental dopamine neurons. Results: VWR stimulated activity in serotonin, but not in norepinephrine or dopamine neurons. Subsequently, acute administration of the selective serotonin reuptake inhibitor escitalopram in control rats led to complete suppression of serotonin neurons; this suppression was reversed by subsequent administration of selective antagonist of serotonin-1A receptors, WAY100135. Escitalopram induced only partial inhibition of serotonin neurons in the VWR rats while WAY100135 increased the firing activity of serotonin neurons above the baseline value. Conclusions: The beneficial effect of physical exercise on mood is mediated, at least in part, via activation of serotonin neurons. Physical exercise can potentiate the response to selective serotonin reuptake inhibitors by increasing the basal firing activity and diminishing selective serotonin reuptake inhibitor-induced inhibition of serotonin neurons.

Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis.

OBJECTIVE: Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning. METHODS: Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5-20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted. RESULTS: TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low. CONCLUSIONS: Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.

Serotonin reuptake inhibitors and breastfeeding: a systematic review.

OBJECTIVE: The postnatal period represents a critical phase for mothers because of physiological hormonal changes, the increase of emotional reactions and a greater susceptibility for the onset/recrudescence of psychiatric disorders. Despite the evidence of an increasing utilization of antidepressant drugs during breastfeeding, there is still few reliable information on the neonatal safety of the selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic reuptake inhibitors (SNRIs) [serotonin reuptake inhibitors (SRIs)] in nursing mothers. The aim of this study is to provide a systematic review on the neonatal safety profile of these drugs during breastfeeding, also assessing the limits of available tools. METHODS: MEDLINE and PubMed databases were searched without any language restrictions by using the following set of keywords: ((SSRIs OR selective serotonin inhibitor reuptake OR SNRIs OR selective serotonin noradrenaline inhibitor reuptake) AND (breastfeeding OR lactation OR breast milk)). A separate search was also performed for each SSRIs (paroxetine, fluvoxamine, fluoxetine, sertraline, citalopram and escitalopram) and SNRIs (venlafaxine and duloxetine). RESULTS: Sertraline and paroxetine show a better neonatal safety profile during breastfeeding as compared with other SRIs. Less data are available for fluvoxamine, escitalopram and duloxetine. Few studies followed up infants breastfeed for assessing the neurodevelopmental outcomes. CONCLUSIONS: Literature review clearly indicates paroxetine and sertraline as the drugs that should be preferred as first line choice in nursing women who need an antidepressant treatment.

Sertraline, citalopram and paroxetine in lactation: passage into breastmilk and infant exposure.

Objectives: This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and Absolute Infant Dose (AID), and to determine actual infant drug exposure through breastfeeding. Subsequently, informed recommendations will be formulated regarding the advisability of breastfeeding in women undergoing treatment with the three most widely used antidepressants. Methods: A pharmacokinetic study in lactating women and their infants using sertraline, citalopram or paroxetine was performed. Paired breastmilk and plasma samples and single point infant plasma samples were collected to determine antidepressant concentrations. An Area Under the Curve (AUC) based approach with the trapezoidal rule was used to calculate M/P ratios and AID for all three antidepressants by combining all measured concentrations for the same dose. Results: Thirty-seven lactating women and their infants participated in this study. 111 paired breastmilk and plasma samples and 37 single point infant plasma samples were collected. Detectable concentrations of sertraline, citalopram and paroxetine were present in all breastmilk samples. For sertraline and citalopram M/P ratio is above one, indicating higher breastmilk than plasma concentrations, however, drug exposure by breastmilk did not lead to detectable plasma drug levels in any of the 15 infants for sertraline, for nine (out of 13) infants for citalopram and for eight (out of nine) infants for paroxetine. Conclusion: Given the well-known benefits of breastfeeding, our findings support breastfeeding of infants by mothers who are taking sertraline, citalopram or paroxetine is safe. Sertraline and paroxetine are the preferred antidepressants during breastfeeding, reaching mostly undetectable infant drug levels.

Reduced Bioavailability of Antidepressants for the Management of Generalized Anxiety Disorder Following Bariatric Surgery: A Case Study.

Bariatric surgery is a commonly performed procedure for patients who have failed to achieve weight loss through medical and lifestyle interventions. However, the altered gastrointestinal anatomy resulting from the surgery can significantly impact the bioavailability of antidepressants in patients with generalized anxiety disorder, potentially leading to uncontrolled anxiety symptoms. This case report describes a patient with generalized anxiety disorder who underwent Roux-en-Y gastric bypass surgery and subsequently experienced increased anxiety symptoms due to poor antidepressant bioavailability. The patient's medication was adjusted to a sublingual formulation, resulting in improved anxiety control and reduced side effects. Healthcare providers should be aware of the potential impact of bariatric surgery on medication absorption and closely monitor patients with generalized anxiety disorder for potential psychiatric medication-related complications postoperatively. The use of alternative routes of administration, such as sublingual medication, may be beneficial in improving drug bioavailability and managing anxiety symptoms. Creating awareness in primary care offices about poor drug absorption and using alternatives such as the sublingual route of administration to achieve optimal systemic delivery requires a multifaceted approach involving education and training for healthcare providers as well as patient education to ensure they are informed and engaged in their own care. By implementing these strategies, primary care providers can improve patient outcomes and prevent unnecessary referrals to specialists.

Antidepressants - The new endocrine disruptors? The case of crustaceans.

Antidepressants are high-volume pharmaceuticals that accumulate to concentrations in the µg·L-1 range in surface waters. The release of peptide hormones via neurosecretory cells appears as a natural target for antidepressants. Here I review research that suggests that antidepressants indeed disrupt endocrine signalling in crustaceans, by acting on the synthesis and release of neurohormones, such as crustacean hyperglycaemic hormone, moult inhibiting hormone and pigment dispersing hormone in decapods, as well as methyl farnesoate in Daphnids. Hence, antidepressants can affect hormonal regulation of physiological functions: increase in energy metabolism and activity, lowered ecdysteroid levels, potentially disrupting moult and somatic growth, reducing colour change capacity and compromising camouflage, as well as induction of male sex determination. Several studies further suggest effects of antidepressants on crustacean reproduction, but the hormonal regulation of these effects remains elusive. All things considered, a body of evidence strongly suggests that antidepressants are endocrine disrupting compounds in crustaceans.

The association of selective serotonin reuptake inhibitors use and stroke in geriatric population.

OBJECTIVES: Selective serotonin reuptake inhibitor (SSRI) exposure has controversial results in increasing the stroke risk. With the risk of stroke increased with age, the safety of SSRI use among older adults attracts much concern. METHODS: We analyzed 28,145 subjects older than 65 years from a subset of a 9-year cohort database from the National Health Insurance Research Database, Taiwan. RESULTS: The survival analysis showed a greater probability of stroke in subjects with SSRI exposure after adjusting other covariates. Compared with other variables, SSRI exposure had the strongest effect (hazard ratio: 2.66, 95% confidence interval: 2.21-3.20). The risk was independent to depression-related stroke risk. CONCLUSIONS: The use of SSRIs independently increases the risk of stroke among older patients. SSRIs are still practically safe to most users, providing precautionary measures are taken.

Citalopram-induced sleep bruxism in a breastfed infant: A case report.

Bruxism associated with antidepressant use is an under-recognized phenomenon. The use of citalopram has gained wide acceptance in the treatment of depression and anxiety disorders; however, the consumption of this medication during lactation and pregnancy has not been carefully characterized. There are limited studies about its side effects in the breastfeeding period. Here, we report a rare case of citalopram-induced sleep bruxism in a 9-month-old female breastfed infant whose mother used SSRI agent citaloporm for her anxiety disorder. Within 2 weeks of initiating her citalopram treatment, with a starting dose of 10 mg/day, the patient reported sleep bruxism in her infant. Thorough examinations of the infant were performed and no abnormal finding was reported. After ruling out other possible causes, the new-onset bruxism symptoms were attributed to the mother's recent use of citalopram, which was discontinued thereafter. The infant's symptoms of bruxism disappeared following the discontinuation of the medication by her mother. These findings and similar reports could draw more attention to bruxism or other possible symptoms in breastfed infants of mothers consuming psychotropic medications.

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.

Chronic exposure of female mice to selective serotonin reuptake inhibitors during lactation induces vocal behavior deficits in pre-weaned offspring.

Developmental factors for autism spectrum disorders (ASDs) have been an ongoing debate despite an increasing number of reports on genetic factors. Recent studies have suggested maternal intake of selective serotonin reuptake inhibitors (SSRIs) as a possible developmental factor elevating the risk for ASD in offspring. Here, we show that maternal exposure of mice to an SSRI, Fluoxetine (FLX), induces abnormal ultrasonic vocalizations (USVs), an indicator of ASD-related behavior. We tested the effect of FLX intake during pregnancy, lactation, or both. We found that the lactation and both conditions decreased the number of USVs emitted by offspring pups. An index for assessing the syllables' frequency modulation revealed that highly modulated syllables appeared to be inhibited only in both conditions. Furthermore, we found that the number of serotonergic neurons at adulthood was reduced in the progeny of mice treated with FLX in all conditions. In addition, maternal exposure to FLX through pregnancy and lactation induced a high death rate of early post-natal pups. These suggest that the maternal exposure to SSRIs affects early development of offsprings as well as the serotonergic system. Focusing on vocal communication, our results indicate that intake of an SSRI during lactation increases the risk of abnormal USVs in pups, and provides potential insights into the development of ASD.

Repurposing Antidepressants and Phenothiazine Antipsychotics as Efflux Pump Inhibitors in Cancer and Infectious Diseases.

Multidrug resistance (MDR) is a major obstacle in the therapy of infectious diseases and cancer. One of the major mechanisms of MDR is the overexpression of efflux pumps (EPs) that are responsible for extruding antimicrobial and anticancer agents. EPs have additional roles of detoxification that may aid the development of bacterial infection and the progression of cancer. Therefore, targeting EPs may be an attractive strategy to treat bacterial infections and cancer. The development and discovery of a new drug require a long timeline and may come with high development costs. A potential alternative to reduce the time and costs of drug development is to repurpose already existing drugs. Antidepressants and antipsychotic agents are widely used in clinical practice in the treatment of psychiatric disorders and some somatic diseases. Antidepressants and antipsychotics have demonstrated various beneficial activities that may be utilized in the treatment of infections and cancer. This review aims to provide a brief overview of antibacterial and anticancer effects of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and phenothiazine antipsychotics, while focusing on EPs. However, it should be noted that the antimicrobial activity of a traditionally non-antibiotic drug may have clinical implications regarding dysbiosis and bacterial MDR.