Interventions to prevent and treat delirium: An umbrella review of randomized controlled trials.

Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of this umbrella review is to synthesize and grade all preventative and therapeutic interventions for delirium. We searched five databases from database inception up to March 15th, 2023 and we included meta-analyses of randomized controlled trials (RCTs) to decrease the risk of/the severity of delirium. From 1959 records after deduplication, we included 59 systematic reviews with meta-analyses, providing 110 meta-analytic estimates across populations, interventions, outcomes, settings, and age groups (485 unique RCTs, 172,045 participants). In surgery setting, for preventing delirium, high GRADE evidence supported dexmedetomidine (RR=0.53; 95%CI: 0.46-0.67, k=13, N=3988) and comprehensive geriatric assessment (OR=0.46; 95%CI=0.32-0.67, k=3, N=496) in older adults, dexmedetomidine in adults (RR=0.33, 95%CI=0.24-0.45, k=7, N=1974), A2-adrenergic agonists after induction of anesthesia (OR= 0.28, 95%CI= 0.19-0.40, k=10, N=669) in children. High certainty evidence did not support melatonergic agents in older adults for delirium prevention. Moderate certainty supported the effect of dexmedetomidine in adults and children (k=4), various non-pharmacological interventions in adults and older people (k=4), second-generation antipsychotics in adults and mixed age groups (k=3), EEG-guided anesthesia in adults (k=2), mixed pharmacological interventions (k=1), five other specific pharmacological interventions in children (k=1 each). In conclusion, our work indicates that effective treatments to prevent delirium differ across populations, settings, and age groups. Results inform future guidelines to prevent or treat delirium, accounting for safety and costs of interventions. More research is needed in non-surgical settings.

Investigating the relationship between DNA methylation, genetic variation, and suicide attempt in bipolar disorder.

Individuals with bipolar disorder are at increased risk for suicide, and this can be influenced by a range of biological, clinical, and environmental risk factors. Biological components associated with suicide include DNA modifications that lead to changes in gene expression. Common genetic variation and DNA methylation changes are some of the most frequent types of DNA findings associated with an increased risk for suicidal behavior. Importantly, the interplay between genetic predisposition and DNA methylation patterns is becoming more prevalent in genetic studies. We hypothesized that DNA methylation patterns in specific loci already genetically associated with suicide would be altered in individuals with bipolar disorder and a history of suicide attempt. To test this hypothesis, we searched the literature to identify common genetic variants (N=34) previously associated with suicidal thoughts and behaviors in individuals with bipolar disorder. We then created a customized sequencing panel that covered our chosen genomic loci. We profiled DNA methylation patterns from blood samples collected from bipolar disorder participants with suicidal behavior (N=55) and without suicidal behavior (N=51). We identified seven differentially methylated CpG sites and five differentially methylated regions between the two groups. Additionally, we found that DNA methylation changes in MIF and CACNA1C were associated with lethality or number of suicide attempts. Finally, we identified three meQTLs in SIRT1 , IMPA2 , and INPP1 . This study illustrates that DNA methylation is altered in individuals with bipolar disorder and a history of suicide attempts in regions known to harbor suicide-related variants.

Development of an anxiety disorder following an emergency department visit due to cannabis use: a population-based cohort study.

Background: There is ongoing uncertainty about whether cannabis use increases the risk of developing an anxiety disorder. In this study we estimated the risk of having an incident healthcare visit for an anxiety disorder following an emergency department (ED) visit for cannabis use and explored factors associated with increased risk. Methods: We used health administrative data to perform a population-based cohort study of all individuals aged 10-105 years with no previous healthcare visits for anxiety disorders in Ontario, Canada, between January 2008 and March 2019. We compared the risk of having an incident healthcare visit for an anxiety disorder in the ED or hospital (primary analysis) or additionally in an outpatient setting (secondary analysis) for individuals with an incident ED visit for cannabis to members of the general population using cumulative incidence functions and cause-specific hazard models adjusted for relevant confounders. Findings: Our study included 12,099,144 individuals aged 10-105 without prior care for an anxiety disorder in the ED or hospital, of which 34,822 (0.29%) had an incident ED visit due to cannabis. Within 3-years of an incident ED visit due to cannabis, 12.3% (n = 4294) of individuals had an incident ED visit or hospitalization for an anxiety disorder-a 3.7-fold (adjusted Hazard Ratio [aHR] 3.69 95% CI 3.57-3.82) increased risk relative to the general population (1.2%). In secondary analysis, further excluding individuals with prior outpatient care for anxiety disorders, 23.6% of individuals with an ED visit due to cannabis had an incident outpatient visit, ED visit, or hospitalization for an anxiety disorder within 3-years compared to 5.6% of individuals in the general population (aHR 3.88 95% CI 3.77-2.99). The risk of having an incident healthcare visit for an anxiety disorder was higher in individuals with ED visits for cannabis use compared to the general population across all age and sex strata. However, younger males with ED visits for cannabis use (aHR 5.67 95% CI 5.19-6.21) had a greater risk relative to the general population than younger women with cannabis use (aHR 3.22 95% CI 2.95-3.52). Interpretation: ED visits for cannabis use were associated with an increased risk of having an incident healthcare visit for an anxiety disorder, particularly in young males. These findings have important clinical and policy implications given the increasing use of cannabis over time and trend towards legalization of cannabis. Funding: Canadian Institutes for Health Research.

Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder.

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical classifier in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.

Cardiology professionals' views of social robots in augmenting heart failure patient care.

Aims: Social robots are arriving to the modern healthcare system. Whether patients with heart failure, a prevalent chronic disease with high health and human costs would derive benefit from a social robot intervention has not been investigated empirically. Diverse healthcare provider's perspectives are needed to develop an acceptable and feasible social robot intervention to be adopted for the clinical benefit of patients with heart failure. Using a qualitative research design, this study investigated healthcare providers' perspectives of social robot use in heart failure patient care. Methods and results: Interdisciplinary healthcare providers from a tertiary care cardiac hospital completed a structured individual interview and a supplemental questionnaire. The framework method was used to analyse the qualitative data. Respondents (n = 22; saturation was reached with this sample; 77% female; 52% physicians) were open to using social robots to augment their practice, particularly with collecting pertinent data and providing patient and family education and self-management prompts, but with limited responsibility for direct patient care. Prior to implementation, providers required robust evidence of: value-added beyond current remote patient monitoring devices, patient and healthcare provider partnerships, streamlined integration into existing practice, and capability of supporting precision medicine goals. Respondents were concerned that social robots did not address and masked broader systemic issues of healthcare access and equity. Conclusion: The adoption of social robots is a viable option to assist in the care of patients with heart failure, albeit in a restricted capacity. The results inform the development of a social robotic intervention for patients with heart failure, including improving social robot efficiencies and increasing their uptake, while protecting patients' and providers' best interest.

Physical activity, suicidal ideation, suicide attempt and death among individuals with mental or other medical disorders: A systematic review of observational studies.

A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the association between physical activity and suicidal ideation, attempts, and deaths has not been systematically appraised in clinical samples. We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, EMBASE, and PsycINFO for observational studies investigating the influence of physical activity on suicidal behavior up to December 6, 2023. Of 116 eligible full-text studies, seven (n = 141691) were included. Depression was the most frequently studied mental condition (43%, k = 3), followed by chronic pain as the most common other medical condition (29%, k = 2). Two case-control studies examined suicide attempts and found an association between physical activity and a reduced frequency of such attempts. However, in studies examining suicidal ideation (k = 3) or suicide deaths (k = 2), no consistent associations with physical activity were observed. Overall, our systematic review found that physical activity may be linked to a lower frequency of suicide attempts in non-prospective studies involving individuals with mental disorders.

Association of bariatric surgery with indicated and unintended outcomes: An umbrella review and meta-analysis for risk-benefit assessment.

Bariatric surgery can cause numerous functional changes to recipients, some of which are unintended. However, a systematic evaluation of wide-angled health benefits and risks following bariatric surgery has not been conducted. We systematically evaluated published systematic reviews of randomized controlled trials and observational studies reporting the association between bariatric surgery and health outcomes. We performed subgroup analyses by surgery type and sensitivity analysis, excluding gastric band. Thirty systematic reviews and 82 meta-analyzed health outcomes were included in this review. A total of 66 (80%) health outcomes were significantly associated with bariatric surgery, of which 10 were adverse outcomes, including suicide, fracture, gastroesophageal reflux after sleeve gastrectomy, and neonatal morbidities. The other 56 outcomes were health benefits including new-onset diabetes mellitus (DM) (odds ratio [OR] = 0.39; 95% confidence interval [CI] = 0.19-0.79), hypertension (OR = 0.36; 95% CI = 0.33-0.40), dyslipidemia (OR = 0.33; 95% CI = 0.14-0.81), cancers (OR = 0.65; 95% CI = 0.53-0.80), cardiovascular diseases (CVDs), and women's health. Surgery is associated with reductions in all-cause mortality and death due to cancer, DM, and CVD. Bariatric surgery has both beneficial and harmful effects on a broader than expected array of patients' health outcomes. An expansion of the indication for bariatric surgery could be discussed to include a broader population with metabolic vulnerabilities.

Validation of a youth suicide risk calculator in an adult sample with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) conveys the highest risk of suicide of all mental disorders. We sought to externally validate a risk calculator (RC) of suicide attempts developed in youth with BD from the Course and Outcome of Bipolar Youth (COBY) study in an adult sample. METHODS: A prospective cohort of adults with BD from the National Institute of Mental Health Collaborative Depression Study (CDS; N = 427; mean (+/- SD) age at intake (36 +/- 13 years)) was secondarily analyzed to validate the COBY RC for one-year risk of suicide attempts/deaths. Nine of the ten predictor variables from the COBY RC were available in the CDS and used: age, age of mood disorder onset, first and second (partial) degree family history of suicide, history of psychotic symptoms, substance use disorder, prior suicide attempt, socioeconomic status, and non-suicidal self-injury (prospectively, incompletely at baseline). RESULTS: Over a mean (SD) follow-up of 19 (10) years, 29 % of the CDS sample attempted suicide. The RC predicted suicide attempts/deaths over one-year follow-up with an area under the receiver operating characteristic curve (AUC) of 0.78 (95 % CI 0.75-0.80). The RC performed slightly better in those with a younger age of mood disorder onset. LIMITATIONS: Clinical samples may limit generalizability; the RC does not assess more acute suicide risk. CONCLUSIONS: One-year risk of suicide attempts/deaths can be predicted with acceptable accuracy in youth and adults with BD, comparable to commonly used RCs to predict cardiovascular risk. This RC may help identify higher-risk individuals with BD for personalized treatment and research. https://cobysuicideattemptsrc.shinyapps.io/Shiny.

Mortality in adolescents and young adults following a first presentation to the emergency department for alcohol.

BACKGROUND AND METHODS: We conducted a population-based, retrospective cohort study of first-time emergency department (ED) visits in adolescents and young adults (AYA) due to alcohol and compared mortality to AYA with nonalcohol ED visits between 2009 and 2015 using standardized all-cause mortality ratios (age, sex, income, and rurality). We described the cause of death for AYA and examined the association between clinical factors and mortality rates in the alcohol cohort using proportional hazard models. RESULTS: A total of 71,776 AYA had a first-time ED visit due to alcohol (56.1% male, mean age 20.7 years) between 2009 and 2015, representing 3.3% of the 2,166,838 AYA with an ED visit in this time period. At 1 year, there were 2396 deaths, 248 (10.3%) following an ED visit related to alcohol. First-time alcohol ED visits were associated with a threefold higher risk in mortality at 1 year (0.35% vs. 0.10%, adjusted hazard ratio [aHR] 3.07, 95% confidence interval [CI] 2.69-3.51). Mortality was associated with age 25-29 years (aHR 3.88, 95% CI 2.56-5.86), being male (aHR 1.98, 95% CI 1.49-2.62), having a history of mental health or substance use (aHR 3.22, 95% CI 1.64-6.32), cause of visit being withdrawal/dependence (aHR 2.81, 95% CI 1.96-4.02), and having recurrent ED visits (aHR 1.97, 95% CI 1.27-3.05). Trauma (42.7%), followed by poisonings from drugs other than opioids (38.3%), and alcohol (28.6%) were the most common contributing causes of death. CONCLUSION: Incident ED visits due to alcohol in AYA are associated with a high risk of 1-year mortality, especially in young adults, those with concurrent mental health or substance use disorders, and those with a more severe initial presentation. These findings may help inform the need and urgency for follow-up care in this population.

Influence of pulmonary rehabilitation on symptoms of anxiety and depression in interstitial lung disease: A systematic review of randomized controlled trials.

BACKGROUND: Interstitial lung diseases (ILDs) cause fibrosis of lung parenchyma, leading to impaired quality of life, dyspnea, and functional decline. Individuals with ILD experience a high prevalence of anxiety and depression. Recent research has demonstrated pulmonary rehabilitation (PR) alleviates symptoms of anxiety and depression in those with COPD. RESEARCH QUESTION: What is the influence of PR on symptoms of anxiety and depression in individuals with ILD? STUDY DESIGN: We conducted a PRISMA-2020-compliant systematic review of randomized controlled trials (RCTs) investigating PR's effect on anxiety and depression in patients with ILD. We searched MEDLINE, EMBASE, Cochrane, and PsycINFO from inception until April 3, 2023. A narrative synthesis was conducted where a quantitative approach was not feasible. RESULTS: Five RCTs (n = 281) were included. Idiopathic pulmonary fibrosis (IPF) was the most common type of ILD (k = 3). One study reported clinically-significant improvements in symptoms of anxiety among patients with IPF, and two studies for symptoms of depression among patients with sarcoidosis. Dropout rates were similar between intervention and control groups. All studies were at a high risk of bias. INTERPRETATION: Pulmonary rehabilitation is not detrimental to anxiety or depression for patients with ILD, and may improve symptoms of anxiety in IPF and depression in sarcoidosis. However, no conclusion can be drawn from available evidence, which is limited by heterogeneous populations/interventions, sample sizes and unexpectedly low prevalences of clinically-significant anxiety or depression. Further adequately powered RCTs that focus on anxiety and depressive symptoms as primary outcomes are needed.

Transition to Schizophrenia Spectrum Disorder Following Emergency Department Visits Due to Substance Use With and Without Psychosis.

Importance: Episodes of substance-induced psychosis are associated with increased risk of developing a schizophrenia spectrum disorder. However, there are limited data on the transition risk for substance use without psychosis. Objectives: To quantify the risk of transition to schizophrenia spectrum disorder following an incident emergency department (ED) visit for (1) substance-induced psychosis and (2) substance use without psychosis and to explore factors associated with transition. Design, Settings, and Participants: A population-based retrospective cohort study (January 2008 to March 2022) of all individuals, aged 14 to 65 years, in Ontario, Canada, with no history of a psychotic disorder. Individuals with incident ED visits for substance use with and without psychosis were compared with members of the general population. Main Outcomes and Measures: Transition to schizophrenia spectrum disorder using a chart-validated algorithm. Associations between ED visits for substance use and subsequent transition were estimated using cause-specific hazard models. Results: The study included 9 844 497 individuals, aged 14 to 65 years (mean [SD] age, 40.2 [14.7] years; 50.2% female) without a history of psychosis. There were 407 737 individuals with an incident ED visit for substance use, of which 13 784 (3.4%) ED visits were for substance-induced psychosis. Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio [aHR], 163.2; 95% CI, 156.1-170.5) increased risk of transitioning, relative to the general population (3-year risk, 18.5% vs 0.1%). Individuals with an ED visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%), but incurred more than 3 times the absolute number of transitions (9969 vs 3029). Cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2). Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger compared with older individuals, particularly for cannabis use. Conclusions and Relevance: The findings of this cohort study suggest that ED visits for substance use were associated with an increased risk of developing a schizophrenia spectrum disorder. Although substance-induced psychoses had a greater relative transition risk, substance use without psychosis was far more prevalent and resulted in a greater absolute number of transitions. Several factors were associated with higher transition risk, with implications for counseling and early intervention.

Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder.

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at > 700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold-changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical predictor in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.

Cerebellar morphological differences and associations with extrinsic factors in bipolar disorder type I.

BACKGROUND: The neural underpinnings of bipolar disorder (BD) remain poorly understood. The cerebellum is ideally positioned to modulate emotional regulation circuitry yet has been understudied in BD. Literature suggests differences in cerebellar activity and metabolism in BD, however findings on structural differences remain contradictory. Potential reasons include combining BD subtypes, small sample sizes, and potential moderators such as genetics, adverse childhood experiences (ACEs), and pharmacotherapy. METHODS: We collected 3 T MRI scans from participants with (N = 131) and without (N = 81) BD type I, as well as blood and questionnaires. We assessed differences in cerebellar volumes and explored potentially influential factors. RESULTS: The cerebellar cortex was smaller bilaterally in participants with BD. Polygenic propensity score did not predict any cerebellar volumes, suggesting that non-genetic factors may have greater influence on the cerebellar volume difference we observed in BD. Proportionate cerebellar white matter volumes appeared larger with more ACEs, but this may result from reduced ICV. Time from onset and symptom burden were not associated with cerebellar volumes. Finally, taking sedatives was associated with larger cerebellar white matter and non-significantly larger cortical volume. LIMITATIONS: This study was cross-sectional, limiting interpretation of possible mechanisms. Most of our participants were White, which could limit the generalizability. Additionally, we did not account for potential polypharmacy interactions. CONCLUSIONS: These findings suggest that external factors, such as sedatives and childhood experiences, may influence cerebellum structure in BD and may mask underlying differences. Accounting for such variables may be critical for consistent findings in future studies.

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder.

BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Functional connectivity of the cerebellar vermis in bipolar disorder and associations with mood.

Purpose: Studies of the neural underpinnings of bipolar type I disorder have focused on the emotional control network. However, there is also growing evidence for cerebellar involvement, including abnormal structure, function, and metabolism. Here, we sought to assess functional connectivity of the cerebellar vermis with the cerebrum in bipolar disorder and to assess whether connectivity might depend on mood. Methods: This cross-sectional study enrolled 128 participants with bipolar type I disorder and 83 control comparison participants who completed a 3 T magnetic resonance imaging (MRI) study, which included anatomical as well as resting state Blood Oxygenation Level Dependent (BOLD) imaging. Functional connectivity of the cerebellar vermis to all other brain regions was assessed. Based on quality control metrics of the fMRI data, 109 participants with bipolar disorder and 79 controls were included in the statistical analysis comparing connectivity of the vermis. In addition, the data was explored for the potential impacts of mood, symptom burden, and medication in those with bipolar disorder. Results: Functional connectivity between the cerebellar vermis and the cerebrum was found to be aberrant in bipolar disorder. The connectivity of the vermis was found to be greater in bipolar disorder to regions involved in motor control and emotion (trending), while reduced connectivity was observed to a region associated with language production. In the participants with bipolar disorder, past depression symptom burden affected connectivity; however, no effects of medication were observed. Functional connectivity between the cerebellar vermis and all other regions revealed an inverse association with current mood ratings. Conclusion: Together the findings may suggest that the cerebellum plays a compensatory role in bipolar disorder. The proximity of the cerebellar vermis to the skull may make this region a potential target for treatment with transcranial magnetic stimulation.

Impact of antidepressant use on the autonomic nervous system: A meta-analysis and systematic review.

Changes in cardiac autonomic nervous system (ANS) regulation observed in psychiatric disorders may be mitigated by antidepressants. We meta-analyzed and systematically reviewed studies examining antidepressants' effects on ANS outcomes, including heart rate variability (HRV). We conducted a PRISMA/MOOSE-compliant search of PubMed and Scopus until March 28th, 2022. We included randomized placebo-controlled trials (RCTs) and pre-post studies, regardless of diagnosis. We pooled results in random-effects meta-analyses, pooling homogeneous study designs and outcomes. We conducted sensitivity analyses and assessed quality of included studies. Thirty studies could be meta-analyzed. Selective serotonin reuptake inhibitors (SSRIs) were significantly associated with a reduction in the square root of the mean-squared difference between successive R-R intervals (RMSSD) (SMD= -0.48) and skin conductance response (SMD= -0.55) in RCTs and with a significant increase in RMSSD in pre-post studies (SMD=0.27). In pre-post studies, tricyclic antidepressants (TCAs) were associated with a significant decrease in several HRV outcomes while agomelatine was associated with a significant increase in high frequency power (SMD= 0.14). In conclusion, SSRIs reduce skin conductance response but have no or inconclusive effects on other ANS outcomes, depending on study design. TCAs reduce markers of parasympathetic function while agomelatine might have the opposite effect. Studies are needed to investigate the impact of SSRIs on the recovery of cardiac ANS regulation after acute myocardial infarction, and the effects of newer antidepressants.