Antidepressant use and the risk of seizure: a meta-analysis of observational studies.

PURPOSE: The association between antidepressant use and the risk of seizures remains controversial. Therefore, this meta-analysis examined whether antidepressant use affects the risk of seizures. METHODS: To identify relevant observational studies, we conducted systematic searches in PubMed and Embase of studies published through May 2023. Random-effects models were used to estimate overall relative risk. RESULTS: Our meta-analysis included eight studies involving 1,709,878 individuals. Our results showed that selective serotonin reuptake inhibitors (SSRI) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.32-1.66; P < 0.001) and selective noradrenalin reuptake inhibitors (SNRI) (OR 1.65, 95% CI 1.24-2.19; P = 0.001), but not tricyclic antidepressants (TCA) (OR 1.27, 95% CI 0.84-1.92; P = 0.249), were associated with an increased risk of seizures. Subgroup analyses revealed an OR of 2.35 (95% CI 1.7, 3.24; P < 0.001) among short-term (< 30 days) antidepressant users. CONCLUSIONS: The findings of this meta-analysis support an increased risk of seizures in new-generation antidepressant users, expanding previous knowledge by demonstrating a more pronounced risk in short-term users.

The safety of benzodiazepines and related drugs during pregnancy: an updated meta-analysis of cohort studies.

PURPOSE: The prevalence of benzodiazepines and related drugs (BZRDs) use during pregnancy increased sharply in recent years. Thus, there are concerns regarding the pregnancy outcomes following exposure to BZRDs. METHODS: Two electronic databases were thoroughly searched to identify related clinical studies published from inception until June 2023. English-language cohort studies with high-quality comparing antenatal BZRDs exposure to an unexposed group on any delivery outcome were included. RESULTS: Ten cohort studies that estimated adverse neonatal outcomes associated with exposure to BZRDs during pregnancy were included. Exposure to BZRDs during pregnancy was associated with an increased risk of congenital malformation [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05-1.13, p < 0.001], heart malformation (OR 1.13, 95% CI 1.04-1.22, p = 0.003), preterm birth (OR 1.45, 95% CI 1.23-1.7, p < 0.001), SGA (OR 1.18, 95% CI 1.08-1.29, P < 0.001), LBW (OR 1.42, 95% CI 1.25-1.6, p = 0.001) or low Apgar score (OR 1.42, 95% CI 1.08-1.87, p = 0.011),compared with no exposure. Further analyses limited to the first trimester exposure yielded consistent results. CONCLUSIONS: Exposure to BZRDs during pregnancy may be associated with several adverse neonatal outcomes. However, we could not rule out the potential indication confounding factor, further studies with high-quality that control for important confounders are still needed to verify our findings.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis.

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring.We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks.Incidence of orofacial clefts.We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66-2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5-6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3-2.8) and CPO (OR 1.48, 95% CI 0.83-2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results.Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Association between irritable bowel syndrome and Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that irritable bowel syndrome (IBS) and Parkinson's disease (PD) share similar pathological mechanisms and risk factors. METHODS: We performed a systematic review and meta-analysis of the evidence for a relationship between IBS and PD. Risk estimates from individual studies were pooled using random-effects models. RESULTS: Six articles involving 58,645 patients with PD were included in our meta-analysis. The overall risk for PD in IBS patients was significantly higher than that in the general population (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.29-1.75; p < .001). Subgroup analysis revealed no significant differences in risk between men (OR = 1.47, 95% CI: 1.3-1.67; p < .001) and women (OR = 1.51, 95% CI: 1.29-1.75; p < .001); however, older (≥65 years) IBS patients (OR = 1.44, 95% CI: 1.3-1.59; p < .001) may be at higher risk for PD than younger (40-64 years) patients (OR = 1.32, 95% CI: 1.05-1.64; p = .017). CONCLUSION: Overall, the PD risk was higher in IBS patients than others, indicating that the intestinal disorder may serve as a warning sign for PD.

The risk of dementia in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Growing evidence indicates that inflammatory bowel disease (IBD) and dementia share similar pathological mechanisms, but no consensus has yet emerged on the effect that IBD and dementia are associated. To explore such a possible correlation, we summarize herein the epidemiological evidence. We subject relevant studies to meta-analysis. METHODS: We comprehensively searched Pubmed and Embase for relevant articles published to Dec 2021. The pooled risk ratio (RR) with the 95% confidence interval (CI) was used to estimate the effect; we calculated the generic inverse variance using a random-effects model. RESULTS: Seven studies involving 65,454 patients with dementia were included in the meta-analysis. The overall risk of dementia in IBD patients was significantly higher than that in the general population (risk ratio [RR], 1.35; 95% confidence interval [CI], 1.08-1.68; P = 0.008). The results of subgroup analyses were consistent with the overall results. The risk of Alzheimer's disease was higher in IBD patients (RR = 2.79, 95% CI = 1.1, 7.04; P < 0.001). CONCLUSIONS: Our results revealed that IBD may be a potential risk indicator for dementia.

Maternal non-steroidal anti-inflammatory drug exposure during pregnancy and risk of miscarriage: a systematic review and meta-analysis.

BACKGROUND: Numerous studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) might be associated with increased risk of miscarriage. However, these results are conflicting and inconclusive. METHODS: We performed this systematic review and meta-analysis to assess the relationship between NSAIDs exposure and risk of miscarriage. A systematic literature search was conducted to identify relevant studies published from the time of database inception until June 2021. RESULTS: A total of ten studies involving 207,341 pregnant women were subjected to meta-analysis. There was no statistically significantly increased risk of miscarriage with the use of NSAIDs during pregnancy (OR = 1.37, 95% CI 0.99-1.88, p = 0.057). However, our findings showed that women exposed to NSAIDs around the time of conception were at increased risk of miscarriage (OR 2.32, 95% CI 1.16-4.66, p = 0.018). Furthermore, no significant association between NSAID use and miscarriage was evident during the first trimester of pregnancy (OR = 1, 95% CI = 0.83-1.2, p = 0.996), possibly attributable to the small sample size. CONCLUSION: Our findings indicate that NSAID exposure around the time of conception might be a risk factor for miscarriage. Further studies are needed to evaluate whether the risk varies by the type, dosage, or timing of NSAID exposure.

ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis.

The effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and disease progression are yet to be investigated. The relationship between ACEI/ARB use and COVID-19 infection was systematically reviewed. To identify relevant studies that met predetermined inclusion criteria, unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted. The search strategy included clinical date published until May 9, 2020. Twelve articles involving more than 19,000 COVID-19 cases were included. To estimate overall risk, random-effects models were adopted. Our results showed that ACEI/ARB exposure was not associated with a higher risk of COVID-19 infection (OR = 0.99; 95 % CI, 0-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure was also not associated with a higher risk of having severe infection (OR = 0.98; 95 % CI, 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95 %CI, 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95 % CI, 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm the concern that ACEI/ARB exposure is harmful in patientswith COVID-19 infection. This study supports the current guidelines that discourage discontinuation of ACEIs or ARBs in COVID-19 patients and the setting of the COVID-19 pandemic.

Infection, antibiotic exposure, and risk of celiac disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: There is evidence of a relationship between infection (and the associated antibiotic exposure) and the risk of celiac disease (CD). This study performed a meta-analysis to investigate this relationship. METHODS: To identify relevant studies, we conducted systematic searches of the PubMed, Embase, and Cochrane databases for articles published up to April 2019. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: The meta-analysis included 19 observational studies (15 on infection and six on antibiotic exposure). Our results showed that any infection was associated with an increased risk of CD later in life (odds ratio, 1.37; 95% CI: 1.2-1.56; P < 0.001). The I2 was 94% (high heterogeneity among studies). Subgroup analyses suggested that the risk of CD is not affected by the type of infectious agent, timing of exposure, and site of infection. Exposure to antibiotics was also associated with new-onset CD (odds ratio, 1.2; 95% CI: 1.04-1.39; P < 0.001). CONCLUSION: Exposure to early infection or antibiotic appears to increase the odds of developing CD, suggesting that intestinal immune or microbiota dysbiosis may play a role in the pathogenesis of CD. These findings may influence clinical management and primary prevention of CD. However, noncausal explanations for these positive associations cannot be excluded.

Attention-deficit/hyperactivity disorder medication and risk of suicide attempt: A meta-analysis of observational studies.

PURPOSE: Epidemiologic findings are inconsistent regarding the association between attention-deficit/hyperactivity disorder (ADHD) medication exposure and suicide attempt in individuals with ADHD. METHODS: A systematic literature search of PubMed, Embase and Cochrane Library up to February 2020 was performed. A meta-analysis was conducted for outcomes in which a summary risk ratio (RR) was calculated when taking heterogeneity into account. RESULTS: Both population-level and within-individual analyzes showed that ADHD medication was associated with lower odds of suicide attempts (RR = 0.76, 95% confidence interval [CI], 0.58-1.00; P = .049 and RR = 0.69; 95% CI, 0.49-0.97; P = .049, respectively). However, the association only existed for participants who were treated with stimulants (RR = 0.72; 95% CI, 0.53-0.99; P = .042 on population-level analysis and RR = 0.75; 95% CI, 0.66-0.84; P < .001 on within-individual analysis). Furthermore, a lower risk of suicide attempts was not observed in subjects who took ADHD medication for 1 to 90 days (RR = 0.91; 95% CI, 0.74-1.13; P = .416 on within-individual analysis). CONCLUSION: The results indicate that non-stimulant treatment is not associated with a higher risk of suicide attempt, but stimulant treatment is associated with a lower risk of suicide attempt.

Meta-analysis found that studies may have overestimated Caesarean section risks for attention-deficit hyperactivity disorder by ignoring confounding factors.

AIM: Epidemiological studies on associations between Caesarean sections (C-sections) and attention-deficit hyperactivity disorder (ADHD) have been inconsistent, and we performed a meta-analysis. METHODS: We systematically searched PubMed and Embase to December 2018 and included nine hospital-based and population registry studies published in 2011-2018. These covered a total study cohort of more than 2.5 million people in eight countries: Australia, Brazil, Denmark, Finland, Germany, Sweden, Turkey and the UK. The analysis provided summary odds ratios (ORs) and 95% confidence intervals (CI) while taking heterogeneity into account. RESULTS: We found that that C-sections were associated with a small increase in the risk of ADHD (OR 1.14, 95% CI 1.11, 1.17, I2 0%) in offspring. In subgroup analyses, the association remained for both infants born after elective C-sections (OR, 1.15, 1.11, 1.19, I2 0%) and emergency C-sections (OR, 1.13, 1.1, 1.17, I2 45.4%). However, these were only marginally significant when we pooled data from siblings from other pregnancies (OR, 1.06, 1.00-1.13, I2 0%), implying that the association was due to confounding. CONCLUSION: The statistically significant association between C-sections and ADHD in children can be partially explained by unmeasured confounding. Further research controlling for important confounders is required before firm conclusions can be drawn.

Maternal and neonatal outcomes after exposure to ADHD medication during pregnancy: A systematic review and meta-analysis.

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) medications are used by increasing numbers of reproductive-age women. The safety of these medications during pregnancy has not been well described. METHODS: A systematic review and meta-analysis was performed to evaluate the adverse maternal and neonatal outcomes associated with exposure to ADHD medication during pregnancy. The PubMed and Embase databases were searched to identify potential studies for inclusion. RESULTS: Eight cohort studies that estimated adverse maternal or neonatal outcomes associated with exposure to ADHD medication during pregnancy were included. Exposure to ADHD medication was associated with an increased risk of neonatal intensive care unit (NICU) admission compared with no exposure at any time (risk ratio (RR) 1.88; 95% confidence interval (CI), 1.7-2.08) and compared with women with exposure either before or after pregnancy (RR 1.38; 95% CI, 1.23-1.54; P < 0.001). Exposure to methylphenidate (MPH) was marginally associated with an increased risk for cardiac malformation (RR 1.27; 95% CI, 0.99-1.63; P = 0.065) compared with no exposure. However, exposure to ADHD medication was not associated with an increased risk for other adverse maternal or neonatal outcomes. This analysis was limited by the small number of studies included and the limited adjustments for the possible confounders in the studies. CONCLUSIONS: Exposure to ADHD medication during pregnancy does not appear to be associated with adverse maternal or neonatal outcomes. Given the few studies included, further larger, prospective studies that control for important confounders are needed to verify our findings.

Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis.

Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.

Use of antipsychotics and risk of myocardial infarction: a systematic review and meta-analysis.

AIM: There is emerging concern that antipsychotics may be associated with an increased risk of myocardial infarction (MI). A previous review identified five observational studies that did not provide an accurate estimate of the association between antipsychotic drug use and MI risk. More recent studies have produced variable results. METHODS: We performed a systematic review and meta-analysis of observational studies to determine whether antipsychotic use affects the risk for MI. Our analysis included all observational studies that compared MI incidence among patients receiving antipsychotics vs. no treatment. RESULTS: Nine observational studies were included in the analysis. The odds for developing MI were 1.88-fold higher (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.39, 2.54) in antipsychotic users compared with individuals who had not taken antipsychotics. Subgroup analyses found an OR of 2.48 (95% CI 1.66, 3.69) among patients with schizophrenia and an OR of 2.64 (95% CI 2.48, 2.81) among short term (<30 days) antipsychotic users. CONCLUSION: The findings of this meta-analysis support an increased risk of MI in antipsychotic drug users. The present systematic review expands previous knowledge by demonstrating an increased and more pronounced risk in short term users.

Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis.

BACKGROUND & AIMS: Selective serotonin reuptake inhibitors (SSRIs) are used to treat various psychiatric disorders. However, there are concerns that SSRIs increase the risk for upper gastrointestinal bleeding (UGIB). METHODS: We performed a systematic review and meta-analysis of controlled observational studies to determine whether SSRI use affects the risk for UGIB. Our analysis included all observational studies that compared UGIB development among patients receiving SSRIs vs no treatment. We calculated pooled odds ratios using random- and fixed-effects models. RESULTS: A total of 22 studies (6 cohort and 16 case-control studies) involving more than 1,073,000 individuals were included in our meta-analysis. In comparing SSRI users with patients who had not taken SSRIs, the odds for developing UGIB were 1.55-fold higher (odds ratio, 1.55; 95% confidence interval, 1.35-1.78). In subgroup analyses, the association was greatest for patients who received concurrent therapy with nonsteroidal anti-inflammatory or antiplatelet drugs; we found no significant increase in the risk of developing UGIB among patients receiving concurrent acid-suppressing drugs. CONCLUSIONS: SSRI use was associated with an almost 2-fold increase in the risk of developing UGIB, especially among patients at high risk for GI bleeding (concurrent use of nonsteroidal anti-inflammatory or antiplatelet drugs). This risk might be reduced significantly by concomitant use of acid-suppressing drugs.

Specific serotonin reuptake inhibitors prevent interferon-α-induced depression in patients with hepatitis C: a meta-analysis.

BACKGROUND & AIMS: Interferon-α (IFN-α)-induced depression is a major complication to treatment of chronic hepatitis C virus (HCV) infection. Specific serotonin reuptake inhibitors (SSRIs) can be used to treat depression, but it is not clear whether they can prevent depression in patients receiving IFN therapy for chronic HCV infection. METHODS: We performed a meta-analysis by searching the Cochrane Library, PubMed, and EMBASE databases through 2013 for published results from randomized, placebo-controlled trials evaluating the utility of SSRIs in preventing IFN-induced depression in HCV patients. We analyzed data from 7 studies with a total of 662 patients. The incidence of IFN-induced major depression and depression severity were defined as primary outcomes. Sustained virologic response, completion of antiviral therapy, and tolerability were considered secondary outcomes. RESULTS: A meta-analysis of IFN-induced major depression revealed that prophylactic SSRIs reduced the risk of depression, compared with placebo (relative risk [RR], 0.56; 95% confidence interval [CI], 0.37-0.84; P = .005). Proportions of patients achieving a sustained virologic response (RR, 1.02; 95% CI, 0.79-1.32; P = .87) and completing antiviral therapy (RR, 0.98; 95% CI, 0.66-1.44; P = .91) were similar between patients given SSRIs and controls. Prophylactic SSRIs were tolerated in patients with HCV during treatment. CONCLUSIONS: On the basis of a meta-analysis of 7 randomized controlled trials, prophylactic administration of SSRIs to patients with HCV significantly lowered the incidence of IFN-induced major depression, compared with placebo, and the SSRIs were well tolerated.

Chinese herbal medicine for carriers of the hepatitis B virus: an updated systematic review and meta-analysis.

More than a third of the world's population is infected with the hepatitis B virus (HBV) and 5% are thought to be HBV carriers, putting them at risk of developing serious liver diseases. The treatment of liver diseases with Chinese herbal medicines (CHM) dates back 2,500 years and the aim of this analysis was to evaluate the efficacy and safety of CHM for HBV carriers compared to Western medicine (WM) or placebo and to summarize the most commonly used herbs. Several databases, such as Pubmed, Embase and the Chinese database CNKI, were used to evaluate randomized, controlled trials (RCTs) focused on CHM treatment for HBV carriers up to 2013. We performed a systematic review and meta-analysis on the herbs and their effect on hepatitis B viral proteins (HBeAg, HBsAg) and HBV DNA. Subgroups were examined based on the study design and pooled risk ratios (RRs) were estimated with 95% confidence intervals (CIs). For the meta-analysis, we focused on 11 out of 52 RCTs (Jadad ≥ 2) and found that CHM was more effective than placebo for HBeAg seroconversion when combined with WM (RR 4.67, 95% CI 1.36-15.98; P = 0.01; P = 39%); Radix Astragali was the most commonly used herb. Those that received CHM were more prone to adverse events; however, they were mild and reversible. The risk of bias was assessed with regards to blinding, incomplete outcome data and publication bias. It should be noted that, due to the poor methodological quality of the studies and the small number of RCTs, the results cannot fully support the use of CHM in the treatment of HBV carriers. To conclude, CHM may be used to treat HBV carriers, but rigorously designed RCTs with long-term follow-ups are required to further evaluate the benefits and safety of CHM.

Renin-angiotensin system inhibitor use and risk of Parkinson's disease: a meta-analysis.

BACKGROUND: Hypertension is a recognized risk factor for Parkinson's disease (PD). The renin-angiotensin system (RAS) inhibitors are widely used to treat hypertension. However, the association of RAS inhibitor use with PD has still been an area of controversy. METHODS: Thus, we conducted a meta-analysis to investigate the relationship between RAS inhibitor use and PD. PUBMED and EMBASE databases were searched for articles published up to Oct 2023. All studies that examined the relationship between RAS inhibitor use and the incidence of PD were included. RESULTS: Seven studies with total 3,495,218 individuals met our inclusion criteria for this meta-analysis. Overall, RAS inhibitor use was associated with a reduction in PD risk (OR = 0.88, 95%CI = 0.79-0.98) compared with the controls. When restricted the analysis to individuals with RAS inhibitor use indication, RAS inhibitor exposure was also associated with a decreased risk of PD (OR = 0.76, 95%CI = 0.62-0.92). Pooled results of cohort studies also did support a protective role of angiotensin converting enzyme inhibitors (ACEIs) (OR = 0.97, 95%CI = 0.89-1.07) users and angiotensin II receptor blockers (ARBs) (OR = 0.8, 95%CI = 0.63-1.02) in PD. CONCLUSION: Overall, RAS inhibitor use as a class is associated with a reduction in PD risk. However, the findings of ACEIs and ARBs may be limited by small sample size. Future well-designed studies considering the classification by inhibitor type, duration, dose, or property of BBB penetration of RAS inhibitors are needed to clarify the contribution of these exposure parameters on the risk of PD.

Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses.

Background: Growing evidence suggests that headache disorders and atopic dermatitis share similar pathological mechanisms and risk factors. The aim of this study was to assess the risk for headache disorders in patients with atopic dermatitis. Methods: We systematically searched the PubMed and Embase databases from inception to December 1, 2023, for observational studies that examined risk of migraine in subjects with atopic dermatitis. Risk estimates from individual studies were pooled using random-effects models. Results: Ten studies with 12,717,747 subjects were included in the meta-analysis. Our results showed that patients with atopic dermatitis were associated with a higher risk of headache disorder (OR, 1.46, 95% CI = 1.36-1.56; P < 0.001; I2 = 98%) or migraine (OR, 1.32, 95% CI = 1.18-1.47; P < 0.001; I2 = 98.9%). Most of the results of the subgroup analyses were consistent with the overall results. Conclusion: The findings of this meta-analysis suggest that atopic dermatitis is a potential risk indicator for headache disorder or migraine. Further studies are still needed to verify our findings due to the substantial heterogeneity in our analyses.

Antidepressant use during pregnancy and the risk for gestational diabetes: a systematic review and meta-analysis.

OBJECTIVE: Antidepressant medications are used by increasing numbers of pregnant women. The evidence on the relationship between antidepressant use during pregnancy and the risk for gestational diabetes mellitus (GDM) is inconsistent. We perform a systematic review and meta-analysis to assess the GDM risk associated with antidepressant exposure during pregnancy. METHODS: We systematically searched the PubMed and EMBASE databases until December 2021. We sought observational studies assessing the association between gestational antidepressant use and GDM. RESULTS: Five observational studies were included in the analysis. Mothers exposed to antidepressants during pregnancy were at a significantly increased risk for GDM (relative risk [RR] 1.20, 95% confidence interval [CI] 1.11-1.30; p < .001). However, after considering confounding by indication, we observed no significant effect of antidepressant use during pregnancy on the risk of GDM (RR 1.13, 95% CI 1-1.28; p = .054; I2 = 0%). Independent of clinical indication, subgroup analysis based on individual antidepressants suggested that the risk was increased by venlafaxine or amitriptyline use, but not by selective serotonin reuptake inhibitors. CONCLUSIONS: The significant association between antidepressant exposure during pregnancy and GDM may be overestimated due to confounding by indication. However, the evidence remains insufficient, particularly for specific drug classes.