Selective Serotonin Reuptake Inhibitors Intake Research Articles

Functional brain responses to emotional faces after three to five weeks of intake of escitalopram in healthy individuals: a double-blind, placebo-controlled randomised study

Short-term intake of selective serotonin reuptake inhibitors (SSRIs) modulates threat-related amygdala responses in healthy individuals. However, how SSRI intake over a clinically relevant time period modulates threat-related amygdala responses is less clear. In a semi-randomised, double-blind, placebo-controlled study of 64 healthy individuals (SSRI n = 32, placebo n = 32), we examined the effect of 3–5 weeks of SSRI escitalopram (20 mg daily) on brain response to angry, fearful and neutral faces using BOLD fMRI. Data was analysed using a whole-brain region-wise approach extracting standardised effects (i.e., Cohen’s D). The study was conducted at the Copenhagen University Hospital. A priori, we hypothesised that SSRI would attenuate amygdala responses to angry and fearful faces but not to neutral ones. Whether SSRI modulates correlations between amygdala responses to emotional faces and negative mood states was also explored. Compared to placebo, 3–5 weeks of SSRI intake did not significantly affect the amygdala response to angry, fearful, or neutral faces (|Cohen’s D|< 0.2, PFWER = 1). Whole-brain, region-wise analyses revealed significant differences in frontal (|Cohen’s D|< 0.6, PFWER < .01) and occipital regions (|Cohen’s D|< 0.5, PFWER < .01). SSRI did not modulate correlations between amygdala responses to emotional faces and negative mood states. Our findings indicate that a 3–5 week SSRI intake impacts cortical responses to emotional stimuli, an effect possibly involved in SSRI’s therapeutic efficacy.Trial registration Clinical Trials NCT04239339.

Reasons for Discontinuation or Change of Selective Serotonin Reuptake Inhibitors in Online Drug Reviews

Selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed medication class to treat a variety of mental disorders. However, adherence to SSRIs is low, and uncovering the reasons for discontinuation among SSRI users is an important first step to improving medication persistence. To identify the reasons SSRIs are discontinued or changed, as reported by patients and caregivers in online drug reviews. This qualitative study used natural language processing and machine learning to extract mentions of changes in SSRI intake from 667 drug reviews posted on the online health forum WebMD from September 1, 2007, to August 31, 2021. The type of medication change, including discontinuation, switch to another medication, or dose change and the reason for the change were manually annotated. In each instance in which an adverse event was reported, the event was categorized using Medical Dictionary for Regulatory Activities primary system organ class (SOC) codes, and its relative frequency was compared with that in spontaneous reporting systems maintained by the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency. Reasons for SSRI medication change as assessed using SOC codes. In total, 667 reviews posted by 659 patients or caregivers (516 [78%] of patients were female; 410 [62%] 25-54 years of age) were identified that indicated a medication change: 335 posts indicated SSRI discontinuation, 188 posts indicated dose change, and 179 posts indicated switched medications. Most authors 625 (95%) were patients. The most common reason for medication discontinuation or switching was adverse events experienced, and the most common reason for dose change was titration. Both uptitration and downtitration were initiated by either a health care professional or patient. The most common adverse events were classified by SOC codes as psychiatric disorders, including insomnia, loss of libido, and anxiety. Compared with those in regulatory data, psychiatric adverse events, adverse events recorded by investigations (mostly weight gain) and adverse events associated with the reproductive system (mostly erectile dysfunction) were reported disproportionately more often. This qualitative study of online drug reviews found that useful information was provided directly by patients or their caregivers regarding their medication behavior, specifically, information regarding SSRI treatment changes that may inform interventions to improve adherence. These findings suggest that these reported adverse events may be associated with SSRI persistence and that people may feel more inclined to report such events on social media than to clinicians or regulatory agencies.

Selective serotonin reuptake inhibitors as a risk factor for dental implant failure: a retrospective clinical study

The trend in recent decades in Europe and the United States points to an exponential increase in the consumption of antidepressant drugs and, in particular, selective serotonin reuptake inhibitors (SSRIs). This retrospective study aimed to investigate whether there is an association between SSRI intake and dental implant (DI) failure or survival and, secondarily, to investigate the influence of other systemic and local factors. This retrospective cohort study was done in accordance with the the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational studies. A total of 170 patients received 573 DIs between 2014 and 2020.The reported DI failure rate was 6.11% (n = 35 DIs). Of these 18.31% failed in patients treated with SSRIs while 4.38% failed in patients who were not prescribed SSRIs (p < 0.001). Specifically, use of these drugs was associated with a hazard ratio rate of DI failure that was 4.53 times higher (95% CI: 1.93 to 10.61), and in the multivariate analysis, a 3.70 times higher adjusted risk was found. A lower DI survival rate at 90 months’ follow up was also observed in these patients compared with those not taking them (84.30% vs 96%, respectively; p = 0.00014). With the limitations of the present study it can be affirmed that there is a relation between the intake of SSRIs and DI failure, as well as a lower survival rate in these patients.

The attention-emotion interaction in healthy female participants on oral contraceptives during 1-week escitalopram intake.

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebo-controlled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment.

Severe Pulmonary Stenosis in a Newborn with Antenatal Exposure to Selective Serotonin Reuptake Inhibitor Drug: A Case Report

Depression in pregnancy is being recognized as a major contributor to adverse maternal and fetal outcomes. Recent years have seen significant research focused on the development of safe pharmacological methods to treat depression in pregnancy, resulting in the common use of selective serotonin reuptake inhibitors (SSRIs) as a first line of treatment. There have been a few reports of congenital birth defects associated with the consumption of SSRIs during pregnancy, particularly congenital heart defects. Several studies have attempted to evaluate the relationship between SSRI use and congenital heart defects in neonates, but they were inconclusive. In this report, a case where maternal SSRI intake during two consecutive pregnancies was associated with neonatal pulmonary valve stenosis, raising the possibility of a correlation between the usage of a certain SSRI, and a particular congenital heart defect has been described. Keywords: Congenital heart defects, Depression, Pregnancy, Pulmonary valve stenosis, Serotonin uptake inhibitors

Effects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm

Impaired cognitive flexibility represents a widespread symptom in psychiatric disorders, including major depressive disorder (MDD), a disease, characterized by an imbalance of neurotransmitter concentrations. While memory formation is mostly associated with glutamate, also gamma-Aminobutyric acid (GABA) and serotonin show attributions in a complex interplay between neurotransmitter systems. Treatment with selective serotonin reuptake inhibitors (SSRIs) does not solely affect the serotonergic system but shows downstream effects on GABA- and glutamatergic neurotransmission, potentially helping to restore cognitive function via neuroplastic effects. Hence, this study aims to elaborate the effects of associative relearning and SSRI treatment on GABAergic and glutamatergic function within and between five brain regions using magnetic resonance spectroscopy imaging (MRSI).In this study, healthy subjects were randomized into four groups which underwent three weeks of an associative relearning paradigm, with or without emotional connotation, under SSRI (10mg escitalopram) or placebo administration. MRSI measurements, using a spiral-encoded, 3D-GABA-edited MEGA-LASER sequence at 3T, were performed on the first and last day of relearning. Mean GABA+/tCr (GABA+ = GABA + macromolecules; tCr = total creatine) and Glx/tCr (Glx = glutamate + glutamine) ratios were quantified in a ROI-based approach for the hippocampus, insula, putamen, pallidum and thalamus, using LCModel. A total of 66 subjects ((37 female, mean age ± SD = 25.4±4.7) for Glx/tCr and 58 subjects (32 female, mean age ± SD = 25.1±4.7) for GABA+/tCr were included in the final analysis.A significant measurement by region and treatment (SSRI vs placebo) interaction on Glx/tCr ratios was found (pcor=0.017), with post hoc tests confirming differential effects on hippocampus and thalamus (pcor=0.046). Moreover, treatment by time comparison, for each ROI independently, showed a reduction of hippocampal Glx/tCr ratios after SSRI treatment (puncor=0.033). No significant treatment effects on GABA+/tCr ratios or effects of relearning condition on any neurotransmitter ratio could be found.Here, we showed a significant SSRI- and relearning-driven interaction effect of hippocampal and thalamic Glx/tCr levels, suggesting differential behavior based on different serotonin transporter and receptor densities. Moreover, an indication for Glx/tCr adaptions in the hippocampus after three weeks of SSRI treatment could be revealed. Our findings are in line with animal studies reporting glutamate adaptions in the hippocampus following chronic SSRI intake. Due to the complex interplay of serotonin and hippocampal function, involving multiple serotonin receptor subtypes on glutamatergic cells and GABAergic interneurons, the interpretation of underlying neurobiological actions remains challenging.

Perioperative use of selective serotonin reuptake inhibitors is associated to poor postoperative outcome in patients undergoing liver resection

Presenter: Patrick Starlinger MD | Mayo Clinic, Rochester Background: Recently, modification of intra-platelet serotonin levels as therapeutic intervention to promote postoperative liver regeneration was proposed. In this context, we previously showed a bivalent effect of serotonin on liver regeneration and early tumour recurrence. We were able to provide exploratory data on the use of selective serotonin reuptake inhibitors (SSRI) within the previous publications. Yet, this data has to be considered exploratory, as the number of patients under SSRI treatment was extremely low. Accordingly, we aimed to evaluate the use of selective serotonin reuptake inhibitors (SSRI) in a large cohort of patients undergoing liver resection. Methods: In total, 755 patients undergoing liver resection were retrospectively included from our prospectively maintained institutional database. Perioperative intake of SSRI was evaluated and patients were followed up for postoperative liver dysfunction (LD) and morbidity. Results: Within this cohort 75 patients (9.9%) with perioperative SSRI therapy could be identified. Of note, patients treated with SSRI showed a higher incidence of severe morbidity (22.9% - no SSRI vs 31.6% - SSRI, p<0.05) and a significantly increased incidence of liver dysfunction (10.7% - no SSRI vs 23.4% - SSRI, p<0.05). On the other hand, patients receiving SSRI therapy were found to suffer from significantly reduced early tumor recurrences at 6 and 12 months after surgery (6 months: 13.0% - no SSRI vs 22.7% - SSRI, p<0.05; 12 months: 26.3% - no SSRI vs 42.1% - SSRI, p<0.05). Conclusion: Within the present study we present solid data on the influence of SSRI on postoperative clinical outcome. Indeed, perioperative SSRI treatment seems to be associated to development of LD most likely via downregulation of intra-platelet serotonin, which was shown to be central for postoperative liver regeneration. However, SSRI therapy also seems to supressearly tumor recurrences and might therefore reflect an attractive adjuvant therapy in patients after liver resection.

Selective serotonin reuptake inhibitors during pregnancy Do not increase the risk of Hirschsprung disease

PurposeHirschsprung disease (HSCR) is a multifactorial disease. Maternal intake of selective serotonin reuptake inhibitors (SSRI) during early pregnancy has previously been associated with increased risk for HSCR. The aim of this study was to assess the risk for HSCR in newborns after maternal intake of SSRI in a population-based Swedish cohort. MethodsThis was a Swedish nationwide, population-based, case–control cohort study containing all children born in Sweden between 1/12006 and 31/122012. The cases were identified in the Swedish National Patient Register and the controls (five age- and sex-matched controls per case) were randomly selected among children without HSCR in the cohort. Data on maternal SSRI use during pregnancy were collected from the Swedish Prescribed Drug Register. ResultsOut of 775,024 born children during the study period, 150 cases of HSCR (112 males) and 750 controls (560 males) were included. Five (3.3%) mothers of newborns with HSCR had used SSRI during pregnancy compared to 16 (2.1%) mothers of the controls (p = 0.372). The mean age was similar in mothers who had used SSRI compared to those who had not (30.9 (SD +/− 5.1) versus 30.6 (SD +/− 5.0), p = 0.81). ConclusionsThere was no increased risk of HSCR owing to maternal intake of SSRI in this cohort.Level of evidence: Level I.

Does the Intake of Selective Serotonin Reuptake Inhibitors Negatively Affect Dental Implant Osseointegration? A Retrospective Study.

The success of osseointegration is influenced by several factors that affect bone metabolism and by certain systemic medications. Selective serotonin reuptake inhibitors (SSRIs) have been previously suggested to be among these medications. This study aims to investigate the association between systemic intake of SSRIs and failure of osseointegration in patients rehabilitated with dental implants. A retrospective cohort study was conducted, including a total of 2055 osseointegrated dental implants in 631 patients (109 implants in 36 SSRI \users and 1946 in 595 nonusers). Predictor and outcome variables were SSRI intake and osseointegration failure, respectively. The data were analyzed with Mann-Whitney test or Fisher exact test accordingly. Both patient-level and implant-level models were implemented to evaluate the effect of SSRI exposure on the success of osseointegration of dental implants. Median duration of follow-up was 21.5 months (range = 4-56 months) for SSRI users and 23 months (range -60 months) for nonusers ( P = .158). Two of 36 SSRI users had 1 failed implant each; thus, the failure rate was 5.6%. Eleven nonusers also had 1 failed implant each; thus, the failure rate was 1.85%. The difference between the 2 groups failed to reach statistical significance at patient and implant levels ( P = .166, P = .149, respectively). The odds of implant failure were 3.123 times greater for SSRI users compared with nonusers. Patients using SSRIs were found to be 3.005 times more likely to experience early implant failure than nonusers. The results of this study suggest that SSRIs may lead to increase in the rate of osseointegration failure, although not reaching statistical significance.

Is the intake of selective serotonin reuptake inhibitors associated with an increased risk of dental implant failure?

The aim of this retrospective study was to investigate the association between the intake of selective serotonin reuptake inhibitors (SSRIs) and the risk of dental implant failure. Patients were included if they were taking SSRIs only and no other medication, did not present any other systemic condition or compromising habits (bruxism, smoking, snuff), and complied with the use of prophylactic antibiotics for implant surgery. The multivariate generalized estimating equation (GEE) method and multilevel mixed-effects parametric survival analysis were used to test the association between SSRI exposure (predictor variable) and the risk of implant failure (outcome variable), adjusting for several potential confounders (other variables). The total number of implants with information available and meeting the necessary eligibility criteria was 931 (35 failures). These were placed in 300 patients. The implant failure rate was 12.5% for SSRI users and 3.3% for non-users (P=0.007). Kaplan–Meier analysis showed a statistically significant difference in the cumulative survival rate (P<0.001). The multivariate GEE model did not show a statistically significant association between SSRI intake and implant failure (P=0.530), nor did the multilevel model (P=0.125). It is suggested that the intake of SSRIs may not be associated with an increased risk of dental implant failure.

BiteStrip analysis of the effect of fluoxetine and paroxetine on sleep bruxism

ObjectiveThe relationship between sleep bruxism (SB) and selective serotonin reuptake inhibitors (SSRIs) is still under debate because of the lack of well-designed objective studies. The current study investigates possible effects of SSRIs, fluoxetine, and paroxetine on SB in patients with anxiety and depression. Materials and methodsThirty users of SSRIs for treatment of depression or anxiety were enrolled in the study. After clinical and anamnestic examination, 15 fluoxetine and 15 paroxetine users were included. For an objective evaluation of SB, a single-use disposable home screening device, BiteStrip, was used prior to the first SSRI intake and was repeated on the 7th and 15th days. Patients’ self-reported data also were obtained for assessment of patient awareness. ResultsBiteStrip scores were significantly higher on the 7th and 15th days than the first measurement (p<0.01). There was an increase in 26 (86.6%) patients’ bruxism scores on the 7th day. There was also an increase in 27 (90%) patients’ bruxism scores on the 15th day. But according to patients’ self-reports, only 6 patients had an awareness that bruxism symptoms were initiated or exacerbated 15days after starting fluoxetine or paroxetine. ConclusionFluoxetine and paroxetine, SSRIs used for the treatment of anxiety and depression, may initiate or aggravate SB. Clinicians should consider that SSRIs may be the cause of SB when SSRI users are referred to dental clinics for SB symptoms. As there is a shortage of researches on this subject, further studies are necessary to confirm the existence of SSRI-induced SB.

Regional differences in SERT occupancy after acute and prolonged SSRI intake investigated by brain PET

Blocking of the serotonin transporter (SERT) represents the initial mechanism of action of selective serotonin reuptake inhibitors (SSRIs) which can be visualized due to the technical proceedings of SERT occupancy studies. When compared to the striatum, higher SERT occupancy in the midbrain and lower values in the thalamus were reported. This indicates that occupancy might be differently distributed throughout the brain, which is supported by preclinical findings indicating a regionally varying SERT activity and antidepressant drug concentration. The present study therefore aimed to investigate regional SERT occupancies with positron emission tomography and the radioligand [11C]DASB in 19 depressed patients after acute and prolonged intake of oral doses of either 10mg/day escitalopram or 20mg/day citalopram. Compared to the mean occupancy across cortical and subcortical regions, we detected increased SERT occupancies in regions commonly associated with antidepressant response, such as the subgenual cingulate, amygdala and raphe nuclei. When acute and prolonged drug intake was compared, SERT occupancies increased in subcortical areas that are known to be rich in SERT. Moreover, SERT occupancy in subcortical brain areas after prolonged intake of antidepressants was predicted by plasma drug levels. Similarly, baseline SERT binding potential seems to impact SERT occupancy, as regions rich in SERT showed greater binding reduction as well as higher residual binding. These findings suggest a region-specific distribution of SERT blockage by SSRIs and relate the postulated link between treatment response and SERT occupancy to certain brain regions such as the subgenual cingulate cortex.

Unraveling the Association Between SSRI Use and Falls

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression and are also associated with an increased falls risk. However, the biological mechanism underlying accidental falls with SSRI intake has yet to be elucidated. The present experimental study was designed to investigate whether obstacle avoidance skills in long-term (>90 days), senior paroxetine users (61 ± 5.8 years) are affected during gait, simple and challenging postural balance tasks, as well as during manual reaction time tasks. The performance of the paroxetine users was compared with healthy group-matched controls (60 ± 4.8 years). The results demonstrated impaired postural balance in the paroxetine users, especially during one-legged stance or under various dual-task conditions. Although the deficit in one-legged stance could indicate vestibular involvement, this was deemed unlikely because performance of standing on compliant surface with closed eyes remained unaffected. Paroxetine use also failed to affect manual reaction times or obstacle avoidance performance. It is suggested that paroxetine affects attentional capacities particularly in conjunction with balance control. Compared with healthy seniors, long-term senior users of paroxetine seem to be at an increased risk of falling due to impairments in balance control, especially when attention has to be divided between 2 concurrent activities.

Serotonin, pregnancy and increased autism prevalence: Is there a link?

The prevalence of autism, a neurodevelopmental condition resulting from genetic and environmental causes, has increased dramatically during the last decade. Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise. In the rodent model developed by Whitaker-Azmitia and colleagues, hyperserotonemia during fetal development results in a dysfunction of the hypothalamo-pituitary axis, affecting the amygdala as well as pro-social hormone oxytocin regulation. Dysfunction of the amygdala and abnormal oxytocin levels may underlie many clinical features of ASD. Selective serotonin reuptake inhibitors (SSRI) are the most widely used class of antidepressants drugs, and they are not contraindicated during pregnancy. In this paper, we hypothesize that increased serotonemia during pregnancy, including due to SSRI intake, could be one of the causes of the raising prevalence in autism. If our hypothesis is confirmed, it will not only shed light on one of the possible reason for autism prevalence, but also offer new preventive and treatment options.

Maternal Selective Serotonin Reuptake Inhibitor Intake Does Not Seem to Affect Neonatal Platelet Function Tests

Recently, concerns have been raised regarding the potential impairment of neonatal platelet function and the potential risk of bleeding in neonates born to mothers treated with selective serotonin reuptake inhibitors (SSRI). Our aim was to test whether the platelet function of neonates born to SSRI-treated mothers was impaired when compared to non-SSRI-exposed neonates. In a single-center prospective study, platelet function was evaluated using a cone and platelet analyzer (CPA) device and compared between mother-infant pairs as well as normal non-SSRI-exposed infants. Twenty-seven SSRI-exposed and 27 non-SSRI-exposed full-term neonates and their 23 mothers were tested. No correlation was found between SSRI exposure among either neonates or mothers and parameters of surface coverage (SC) and average size (AS), manifesting platelet function as tested by CPA. SC was similar among SSRI-exposed babies as compared to those in the control group, whereas the size of platelet aggregates (AS) was higher among controls. Neither maternal diseases nor SSRI intake were associated with impaired platelet function and lower SC values, nor were any perinatal conditions. None of the babies suffered from bleeding. We conclude that maternal SSRI therapy does not impair whole-blood CPA-tested platelet function of healthy full-term neonates.

Selective serotonin reuptake inhibitors: Their effect on high-intensity exercise performance

Parise G, Bosman MJ, Boecker DR, Barry MJ, Tarnopolsky MA. Selective serotonin reuptake inhibitors: their effect on high-intensity exercise performance. Arch Phys Med Rehabil 2001;82:867-71. Objective: To determine the neuromuscular and performance effects of acute and long-term exposure to selective serotonin reuptake inhibitors (SSRIs). Design: Two randomized, double-blind, crossover studies. Setting: Departments of Kinesiology and Medicine, McMaster University, Hamilton, Ont, Canada. Participants: Eleven healthy, college-aged men in the acute study; 12 healthy, college-aged men in the chronic study. Interventions: In the acute study, subjects were given a placebo and fluoxetine (40mg) 6 hours before testing, in the chronic study, they were given fluoxetine (40mg/d) and an identical placebo for 2 weeks before testing. Main Outcome Measures: Target measures were maximum voluntary contractions (MVCs), evoked peak torque, and percentage of motor unit activation for muscle strength and central drive. Repeated Wingate cycle ergometer tests were used to measure anaerobic power, capacity, and fatigue index. V̇O2max tests (80%, 90%) were used to measure time to exhaustion and cardiorespiratory responses. Results: In the acute study phase, MVC was lower for fluoxetine versus placebo (p =.05) and a slight fatigue resistance was measured in the repeated Wingate tests for the fluoxetine group; however, there were no affects on any other measured variable. In the chronic study phase, minute ventilation was lower for the fluoxetine trial (p <.05); however, there were no treatment affects on any of the other measurements. Conclusion: Acute and chronic SSRI intake does not effect strength or high-intensity exercise performance in young adult men. © 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation