Specific Selective Serotonin Reuptake Inhibitors Research Articles

Fluoxetine degrades luminance perceptual thresholds while enhancing motivation and reward sensitivity.

Selective serotonin reuptake inhibitors (SSRIs) increase serotonin activity in the brain. While they are mostly known for their antidepressant properties, they have been shown to improve visual functions in amblyopia and impact cognitive functions ranging from attention to motivation and sensitivity to reward. Yet, a clear understanding of the specific action of serotonin to each of bottom-up sensory and top-down cognitive control components and their interaction is still missing. To address this question, we characterize, in two adult male macaques, the behavioral effects of fluoxetine, a specific SSRI, on visual perception under varying bottom-up (luminosity, distractors) and top-down (uncertainty, reward biases) constraints while they are performing three different visual tasks. We first manipulate target luminosity in a visual detection task, and we show that fluoxetine degrades luminance perceptual thresholds. We then use a target detection task in the presence of spatial distractors, and we show that under fluoxetine, monkeys display both more liberal responses as well as a degraded perceptual spatial resolution. In a last target selection task, involving free choice in the presence of reward biases, we show that monkeys display an increased sensitivity to reward outcome under fluoxetine. In addition, we report that monkeys produce, under fluoxetine, more trials and less aborts, increased pupil size, shorter blink durations, as well as task-dependent changes in reaction times. Overall, while low level vision appears to be degraded by fluoxetine, performances in the visual tasks are maintained under fluoxetine due to enhanced top-down control based on task outcome and reward maximization.

Use of Selective Serotonin Reuptake Inhibitors - Validity of Self-Report versus Plasma Concentrations and Pharmacy Dispensations - A Cross-Sectional Analysis of the Norwegian Women and Cancer Study.

PurposeTo validate self-reported current use of selective serotonin reuptake inhibitors (SSRI) in the Norwegian Women and Cancer study (NOWAC) and to identify factors associated with discordance between data sources.Material and MethodsThis is a cross-sectional record-linkage study comparing SSRI-use derived from four data sources: 1) Specific SSRI questions in the main NOWAC questionnaire, 2) Open questions on medication use in the small questionnaire following blood samples, 3) plasma concentration measurements for a subsample, and 4) pharmacy dispensations from the Norwegian prescription database (NorPD) where current use of SSRI was defined by Legend Time Duration (LTD). Among 105 855 women, aged 46 to 64 years and randomly selected from the general population, 70,191 had data on SSRI-use from both NOWAC and NorPD. Plasma concentration was measured for 93 pairs of self-reported SSRI-users and non-users, with dispensation data available for 68 pairs. Validity was assessed by sensitivity and specificity; agreement was assessed by Cohen’s kappa. Factors associated with discordance between information sources were analyzed by multiple binary logistic regression.ResultsWe found high sensitivity (89.5%) and specificity (98.7%) for the specific questions in the main questionnaire compared with pharmacy dispensations. Measured against plasma concentrations, current SSRI-use defined by open questions and pharmacy dispensations both had high sensitivity (100% and 92.5%, respectively) and specificity (98.6% both). Agreements (kappa) were similarly high for all comparisons (≥0.80). The factors associated with discordance between data sources included poor health, comorbidity, being single and not being in full time work. Education was inversely associated with discordance.ConclusionSelf-reported current use of SSRI from the NOWAC questionnaires is highly valid and, according to plasma concentrations, perhaps even more so than pharmacy dispensations. Factors associated with discordance between information sources should be taken into account in the interpretation of future analyses which include SSRI-use in the NOWAC study.

Safety considerations for prescribing SSRI antidepressants to patients at increased cardiovascular risk

ABSTRACT Introduction With the development of selective serotonin reuptake inhibitors (SSRI), a relatively uncomplicated treatment of depression and a safer alternative to tricyclic antidepressants was introduced. Any medical treatment has potential safety risks, however, and these risks should also be considered when prescribing SSRIs. Areas covered The present review focuses on safety considerations when prescribing SSRIs to patients with previous stroke and myocardial infarction, as depression, and the need for antidepressant treatment, is common in these patients. At the same time, patients with stroke and myocardial infarction may be at increased risk of developing adverse events due to higher age, comorbidity, and co-medication. Specifically, the evidence of the risk of QT prolongation and bleeding versus thrombotic events will be discussed in the present review. Expert opinion No medical treatment comes without risk and SSRIs are no exception. Depression, a common complication after vascular events, is a potentially life-threatening condition in itself and relevant and sufficient treatment is imperative. SSRIs are often the first medical treatment choice in the ambulatory setting, also in patients at increased cardiovascular risk. Relevant comorbidity and co-medication, however, should always be taken into account when initiating treatment and when choosing a specific SSRI.

Urinary selective serotonin reuptake inhibitors across critical windows of pregnancy establishment: a prospective cohort study of fecundability and pregnancy loss

To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss. Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive. Four clinical sites. A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin. Not applicable. Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated. A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug. Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study. NCT00467363.

Effect of escitalopram on Aβ levels and plaque load in an Alzheimer mouse model.

BackgroundSeveral neurotransmitter receptors activate signaling pathways that alter processing of the amyloid precursor protein (APP) into β-amyloid (Aβ). Serotonin signaling through a subset of serotonin receptors suppresses Aβ generation. We proposed that escitalopram, the most specific selective serotonin reuptake inhibitor (SSRI) that inhibits the serotonin transporter SERT, would suppress Aβ levels in mice.ObjectivesWe hypothesized that acute treatment with escitalopram would reduce Aβ generation, which would be reflected chronically with a significant reduction in Aβ plaque load.MethodsWe performed in vivo microdialysis and in vivo 2-photon imaging to assess changes in brain interstitial fluid (ISF) Aβ and Aβ plaque size over time, respectively, in the APP/presenilin 1 mouse model of Alzheimer disease treated with vehicle or escitalopram. We also chronically treated mice with escitalopram to determine the effect on plaques histologically.ResultsEscitalopram acutely reduced ISF Aβ by 25% by increasing α-secretase cleavage of APP. Chronic administration of escitalopram significantly reduced plaque load by 28% and 34% at 2.5 and 5 mg/d, respectively. Escitalopram at 5 mg/kg did not remove existing plaques, but completely arrested individual plaque growth over time.ConclusionsEscitalopram significantly reduced Aβ in mice, similar to previous findings in humans treated with acute dosing of an SSRI.

A meta-analysis of selective serotonin reuptake inhibitors (SSRIs) use during prenatal depression and risk of low birth weight and small for gestational age

BackgroundSelective Serotonin Reuptake Inhibitors (SSRIs) act as the first-line antidepressants prescribed for the treatment of prenatal depression. Evidence from previous studies has suggested that the use of SSRIs treatment for prenatal depression has adversely affected fetal growth. However, these results are inconsistent and inconclusive. MethodsIn this study, we examined whether SSRIs use during pregnancy was related to low birth weight (LBW) and small for gestational age (SGA) using a meta-analysis approach. Relevant studies were retrieved by database searching and selected according to established inclusion criteria. ResultsFifteen articles involved 1,977,446 subjects were identified that tested the relationship between the SSRIs use, LBW and SGA outcomes. Statistical analyses revealed a significant association between SSRIs use and suboptimal fetal growth (RR = 1.45, 95% CI = 1.18 − 1.76, Z = 3.62, p = 0.00 for SGA; RR = 1.38, 95% CI = 1.13 − 1.69, Z = 3.14, p = 0.00 for LBW). LimitationsThese results must be treated with caution as we did not take the confounding factors into account (e.g., trimester SSRIs taken, specific SSRIs prescribed and maternal lifestyle during pregnancy) to elucidate their specific roles in the relationship between SSRIs use during pregnancy and fetal growth. ConclusionOur findings suggested that SSRIs use for prenatal depression is associated with suboptimal fetal growth.

Antipsychotic discontinuation after the initiation of selective serotonin reuptake inhibitors therapy for the treatment of behavioral and psychological symptoms associated with dementia.

Introduction:Antipsychotics are used off label to treat behavioral and psychological symptoms of dementia (BPSD). Due to the emerging data of selective serotonin reuptake inhibitors (SSRIs) for treatment of BPSD, clinicians may choose to use this medication class instead of antipsychotics when pharmacologic therapy is necessary. The objective of this study was to evaluate the prevalence of antipsychotic discontinuation 6 months after SSRI initiation for the treatment of BPSD.Methods:Patients with Alzheimer dementia who were prescribed an antipsychotic and later prescribed an SSRI for BPSD during January 1, 2009, through December 30, 2014, were studied. Exclusion criteria included (1) a dementia diagnosis besides Alzheimer; (2) scheduled benzodiazepines, mood stabilizers, or non-SSRI antidepressant use during the study period; (3) diagnoses of bipolar or psychotic disorders; and (4) diagnosis of delirium during the study period. Patients' age, sex, race, and functional assessment of staging for Alzheimer disease scores were collected. The names, doses, and stop dates of SSRIs and antipsychotics were also recorded.Results:Thirty-six patients were included in the analyses. Overall, antipsychotic use was reduced in 11 patients (30.6%). Ten patients (27.8%) discontinued the antipsychotic, and 1 additional patient had a reduction in dose. When comparing specific SSRIs, 8 (72%) responders were prescribed citalopram, and 15 (60%) nonresponders were prescribed sertraline.Discussion:Approximately 30% of patients with Alzheimer dementia who were prescribed antipsychotics for BPSD were able to discontinue the medication or had a dose reduction after starting SSRI therapy. Most SSRI responders were prescribed citalopram.

Quetiapine XR as add-on to antidepressants in treatment-resistant late-life major depression

ObjectiveTo assess the efficacy and tolerability of quetiapine as add-on to antidepressant agents in treatment-resistant late-life major depression.MethodsA group of 15 patients, 8 male and 7 female, mean age 68.2, evaluated in our department for clinical symptoms that made possible a DSM 5 diagnosis of major depressive disorder, were initiated on quetiapine XR, flexible daily dose 50–300 mg QD. All patients were on treatment with an antidepressant–either a selective serotonin reuptake inhibitor (SSRI) (n = 10), or venlafaxine (n = 5)–for at least 6 weeks and presented no improvement during current treatment administered at therapeutic doses. Patients were assessed using Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression–Severity (CGI-S), Global Assessment of Functioning (GAF), and Columbia Suicide Severity Rating Scale (C-SSRS) every 4 weeks for 3 months.ResultsAfter 12 weeks, patients had a mean improvement in MADRS score of 45.7 ± 2.3%, with a final mean MADRS score of 13.5 (P < 0.01). No variations were registered depending on the specific SSRI or venlafaxine concomitant treatment. Quetiapine XR mean daily dose administered during the study was 125 mg. C-SSRS didn’t registered significant variations in suicidal ideation or behavior throughout the trial. Overall GAF score increased with 22.1 points, and CGI-S decreased with a mean of 1.5 points at week 12 (P < 0.01). Tolerability of add-on quetiapine was very good, no serious adverse event being reported.ConclusionsQuetiapine was efficient and well tolerated in late-life resistant major depression, as add-on to SSRIs or venlafaxine, during the 12 weeks of the trial.

Pharmacy Practice: Exploring the Relationship between SSRIs and Sodium Levels in an Older Adult Population

I was asked to examine the presence of hyponatremia (<130 mEq/L) in older patients (>65 years) taking Selective Serotonin Reuptake Inhibitors (SSRIs) at Moses Cone Hospital. The presence of hyponatremia in older patients using SSRIs indicates potentially inappropriate use according to the STOPP (Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions) and START (Screening Tool to Alert Doctors to Right Treatment) criteria6. This study was done to assess possible risk factors for potentially inappropriate use of SSRIs by older patients at Moses Cone Hospital. Data collected included the patient’s sex, age, sodium level, and the date the sodium level was drawn. Data also included the specific SSRI and the starting date for the SSRI. The study showed no relationship between age, sex, SSRI prescribed and hyponatremia. However, patients that were prescribed an SSRI for less than a year were more at risk for hyponatremia. Therefore, in order to minimize the risk of hyponatremia, additional monitoring may need to be added at SSRI initiation, three months, six months, and one year, especially in patients with other medications that may lower sodium levels.
 Conflict of Interest
 We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.
 
 Type: Student Project

Differential Associations of Specific Selective Serotonin Reuptake Inhibitors With Resting-State Heart Rate and Heart Rate Variability: Implications for Health and Well-Being

Debate has focused on the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressants on heart rate (HR) and HR variability (HRV), both of which are predictors of adverse cardiovascular events. Here, we examine the associations between specific SSRI antidepressants and resting state HR (and HRV) after accounting for a host of potential confounding factors using propensity score techniques. Participants included 10,466 not taking antidepressants, 46 participants taking escitalopram, 86 taking citalopram, 66 taking fluoxetine, 103 taking paroxetine, and 139 taking sertraline. HR and HRV (root mean square of successive squared differences, high frequency) were extracted from 10-minute resting-state ECGs. Analyses including propensity score weighting and matching were conducted using R-statistics to control for potentially confounding variables. Major findings indicated that users of all SSRI medications-except fluoxetine-displayed lower HRV relative to nonusers. Users of paroxetine also displayed significantly lower HRV relative to users of citalopram (Cohen's d = 0.42), fluoxetine (Cohen's d = 0.54), and sertraline (Cohen's d = 0.35), but not escitalopram. Although associations were also observed for HR, these were less robust than those for HRV. Although paroxetine is associated with decreases in HRV relative to nonusers, as well as users of other SSRI medications, fluoxetine was the only medication not to display significant alterations in HR or HRV. These conclusions are limited by the cross-sectional design and nonrandomized nature of medication prescriptions. Findings highlight the importance of focusing on specific medications, rather than more heterogeneous groupings according to antidepressant action, and may have implications for health and well-being for the longer term.

A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults.

Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition. To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014. We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale-Brown Obsessive-Compulsive Scale or its children's version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net ). We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive-behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias. The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents. In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions. The study is registered as PROSPERO CRD42012002441. The National Institute for Health Research Health Technology Assessment programme.

SSRIs and birth defects: can a new statistical approach resolve old controversies?

ABSTRACT FROM: Reefhuis J, Devine O, Friedman JM, et al . Specific SSRI and birth defects: Bayesian analysis to interpret new data in the context of previous reports. BMJ 2015;350:h3190....

Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports

Objective To follow up on previously reported associations between periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects...

Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design

Objective To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular...

Prescription and indication trends of antidepressant drugs in the Netherlands between 1996 and 2012: a dynamic population-based study.

Antidepressant drug use increases worldwide. It is pivotal to closely monitor the use of antidepressants and to determine in what subpopulations the rise is most substantial. In a Dutch primary care database, we aimed to investigate the (sex- and age-specific) prevalence and incidence of antidepressant prescription and to monitor the indication of incident prescriptions over a 17-year period (1996-2012). This study, embedded in the Integrated Primary Care Information database, included all patients aged 10 years or older. Per calendar year, prevalence and incidence of antidepressant drug prescription were calculated by drug class (tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and others), sex, and age. The indication of incident prescriptions (e.g., depression, anxiety, sleep disorders, and neuropathic pain) was determined based on the International Classification of Primary Care codes. In total, 1.49 million patients were included. For all antidepressants together, the prevalence increased over time. However, incident prescription of specific SSRIs decreased from 2000 onward. During the study period, incidence and prevalence were higher in older and female patients. The increase in prevalence and the decrease in incidence were more pronounced in females than that in males. Furthermore, antidepressants were increasingly prescribed for indications such as neuropathic pain and sleep disorders. In Dutch primary care, prevalent prescription of antidepressants continued to increase, but incident prescription of particular SSRIs decreased from 2000 onward. In later years, antidepressants were less frequently prescribed for depression-related indications in incident users.

Leveraging a Critical Care Database: Selective Serotonin Reuptake Inhibitor Use Prior to ICU Admission Is Associated With Increased Hospital Mortality

Observational studies have found an increased risk of adverse effects such as hemorrhage, stroke, and increased mortality in patients taking selective serotonin reuptake inhibitors (SSRIs). The impact of prior use of these medications on outcomes in critically ill patients has not been previously examined. We performed a retrospective study to determine if preadmission use of SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs) is associated with mortality differences in patients admitted to the ICU.The retrospective study used a modifiable data mining technique applied to the publicly available Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) 2.6 database. A total of 14,709 patient records, consisting of 2,471 in the SSRI/SNRI group and 12,238 control subjects, were analyzed. The study outcome was in-hospital mortality.After adjustment for age, Simplified Acute Physiology Score, vasopressor use, ventilator use, and combined Elixhauser score, SSRI/SNRI use was associated with significantly increased in-hospital mortality (OR, 1.19; 95% CI, 1.02-1.40; P=.026). Among patient subgroups, risk was highest in patients with acute coronary syndrome (OR, 1.95; 95% CI, 1.21-3.13; P=.006) and patients admitted to the cardiac surgery recovery unit (OR, 1.51; 95% CI, 1.11-2.04; P=.008). Mortality appeared to vary by specific SSRI, with higher mortalities associated with higher levels of serotonin inhibition.We found significant increases in hospital stay mortality among those patients in the ICU taking SSRI/SNRIs prior to admission as compared with control subjects. Mortality was higher in patients receiving SSRI/SNRI agents that produce greater degrees of serotonin reuptake inhibition. The study serves to demonstrate the potential for the future application of advanced data examination techniques upon detailed (and growing) clinical databases being made available by the digitization of medicine.

A Case of Akathisia induced by Escitalopram: Case Report & Review of Literature

Although cases of Selective Serotonin Reuptake Inhibitor (SSRI) induced akathisia have often been reported in literature, this adverse effect has not adequately been mentioned in major pharmacology textbooks. As a result, SSRIinduced akathisia is very frequently under-recognized. A review of literature showed that almost all frequently used SSRIs such as Fluvoxamine, Fluoxetine, Sertraline, Citalopram have been reported to be causing akathisia. SSRI-induced restless legs syndrome and movement disorders have also been reported. However, Escitalopram-induced akathisia is rare. In our review of literature, we could find only one single case of Escitalopram-induced severe akathisia. And this specific SSRI drug has rarely been implicated with occurrence of restless legs syndrome and extra-pyramidal side-effects like dytonia etc. Here, we present a case of Escitalopram-induced severe akathisia - a 53year old female, who had developed severe akathisia after taking Escitalopram for a few days. According to the Barnes Akathisia Rating Scale (BARS), her Global Clinical Assessment of Akathisia Score was 5 i.e. severe akathisia. As per Naronjo Adverse Drug Reaction Scale the probability of association of this adverse reaction with Escitalopram was 7 (i.e. probable). Her symptoms continued in spite of prompt discontinuation of the drug. But, she improved rapidly with the use of Propranolol and Clonazepam. On the last follow-up, she was free from any symptoms. As new generation antidepressants are rarely associated with extra-pyramidal symptoms, the recognition of such adverse effects requires a high index of suspicion. Early recognition of the symptoms and discontinuation of the offending agent along with supportive therapy like a short course of benzodiazepines, beta-adrenergic antagonists or anticholinergics may rapidly relieve the patient from this distressing symptom.

Use of selective serotonin reuptake inhibitor medications for the treatment of child and adolescent mental illness

Comprehensive clinical management plans for treating depression or anxiety disorders in children and adolescents frequently include the use of selective serotonin reuptake inhibitor (SSRI) medications. This statement reviews empirical data regarding the effectiveness of specific SSRI medications, monitoring guidelines, and potential adverse effects of SSRI use including risk of suicidality. SSRI medications can be effective in treating child and adolescent depression and anxiety disorders. Untreated depressive illness may be more harmful than appropriate use of SSRI medication. Physicians should ensure careful elicitation and documentation of baseline depressive and anxious symptoms before initiating SSRI medication. Following medication initiation, patients should also be closely monitored for potential adverse effects, including suicidal ideation and behaviour.

Antidepressant Use and Risk for Preeclampsia

Prior studies suggest that women who use antidepressants during pregnancy have an increased risk for preeclampsia, yet the comparative safety of specific antidepressants remains unclear. US nationwide Medicaid Analytic eXtract (MAX) data have not been used to study medication safety during pregnancy. We identified 100,942 pregnant women with depression from 2000 to 2007 MAX data. We used pharmacy dispensing records to ascertain exposure to selective serotonin reuptake inhibitor (SSRI), serotonin-norepenephrine reuptake inhibitor (SNRI), tricyclic, bupropion, other antidepressant monotherapy or polytherapy, and specific antidepressants, during the second trimester and first half of the third trimester. Relative risks (RRs) and 95% confidence intervals (CIs) were adjusted for delivery year, preeclampsia risk factors, depression severity proxies, other antidepressant indications, other medications, and healthcare utilization. The risk of preeclampsia was 5.4% among women with depression and no antidepressant exposure. Compared with these women, the risk for preeclampsia was higher among those receiving SNRI (RR: 1.52, 95% CI = 1.26-1.83) and tricyclic monotherapy (RR: 1.62, 95% CI = 1.23-2.12), but not SSRI monotherapy (RR: 1.00, 95% CI = 0.93-1.07) or other antidepressants. Compared with women receiving SSRI monotherapy, preeclampsia risk was higher among women with SNRI (RR: 1.54, 95% CI = 1.28-1.86) and tricyclic (RR: 1.64, 95% CI = 1.25-2.16) monotherapy. None of the specific SSRIs was associated with preeclampsia. The RR with venlafaxine was 1.57 (95% CI = 1.29-1.91) and with amitriptyline 1.72 (95% CI = 1.24-2.40). In this population, SNRIs and tricyclics were associated with a higher risk of preeclampsia than SSRIs.

Antidepressant Treatment During Pregnancy

Antidepressant Treatment During Pregnancy