Selective Serotonin Reuptake Inhibitor Antidepressants Research Articles

Selective dorsal neurotomy in the treatment of premature ejaculation: A protocol for systematic review and meta-analysis.

Introduction:Premature ejaculation (PE) affects 8% to 30% of adult men worldwide. Recently, the incidence of PE is on the rise. A series of prior studies suggested that the incidence of PE is related to various biological factors as low testosterone, low serum vitamin D, diabetes, lower urinary tract symptoms, and other psychological factors. At present, the major treatments include selective serotonin reuptake inhibitors antidepressants (dapoxetine, paroxetine), topical anesthetics, phosphodiesterase-5 inhibitor, circumcision, and selective dorsal neurotomy (SDN). The previous study found that SDN is effective for PE.Methods and analysis:The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of selective dorsal penile neurotomy for patients with PE will be included. The outcome includes intravaginal ejaculation latency time and Chinese Index of Sexual Function for Premature Ejaculation-5. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions.Results:The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on June 30th of 2021.Conclusion:SDN can effectively prolong IELT, but its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the SDN treatment in patients with PE.Ethics and dissemination:Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences.Protocol registration number:INPLASY202070084

Risk factors for fatal drowning in a Greek region: a retrospective case–control study

BackgroundFatal drowning is one of the leading causes of unintentional injury mortality worldwide and a persistent public health concern in Greece. While several pathologic and sociodemographic contributing factors have been...

Bleeding risk from antidepressants in patients with atrial fibrillation

Although selective serotonin reuptake inhibitor (SSRI) antidepressants have a generally favorable safety profile, their use has been associated with abnormal coagulation and hemostasis, with literature reports of increased bleeding in some patients. This could increase the risk of bleeding in patients who have cardiovascular diseases such as atrial fibrillation, who are often prescribed anticoagulants for prophylaxis against stroke and SSRIs for depressive symptoms.

Efficacy of microsurgical varicocelectomy in the treatment of premature ejaculation: A protocol for systematic review and meta-analysis.

Introduction:Premature ejaculation (PE) is the most common type of sexual disorder among men which comprises a great of problems. Varicocele is defined as the dilation of the pampiniform venous plexus draining the testicle. At present, selective serotonin reuptake inhibitors antidepressants, topical anesthetics, tramadol, phosphodiesterase type 5 inhibitors are the common alternative strategy to improve PE. However, these therapeutic measures have several shortcomings and side effects. Recently, the correlation between varicocele and PE has attracted the attention of some researchers. A few studies consider microsurgical varicocelectomy can be a new remedy for PE. But it is still absent enough a great deal of convincing evidence. The study will assess the effectiveness and safety of the microsurgical varicocelectomy treatment in PE patients.Methods and analysis:Electronic databases including English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be searched from their inception to December 2020 to recognize related studies. All the randomized controlled trials of microsurgical varicocelectomy for the management of PE patients will be included. The potential outcome will include intravaginal ejaculation latency time, Chinese index of sexual function for premature ejaculation-5, visual analogue score, premature ejaculation diagnostic tool, success treatment rate, serum testosterone levels. We will conduct this study strictly according to the Cochrane Handbook for systematic reviews of interventions.Results:The current study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings in the February 28, 2021.Conclusion:This systematic review will provide more evidence to assess whether microsurgical varicocelectomy is an effective intervention for patients with PE. The results will be published in a public issue journal and offer the urologists and andrologists help to make clinical decisions.Ethics and dissemination:Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences.Protocol registration number:INPLASY202060058

CYP2C19 Allele Frequencies in Over 2.2 Million Direct-to-Consumer Genetics Research Participants and the Potential Implication for Prescriptions in a Large Health System.

Understanding the prevalence of clinically relevant pharmacogenetic variants using large unselected populations is critical for gauging the potential clinical impact of widespread preemptive pharmacogenetic testing. To this end, we assessed the frequencies and ethnic distribution of the three most common CYP2C19 alleles (*2, *3, and *17) in 2.29 million direct‐to‐consumer genetics research participants (23andMe, Sunnyvale, CA). The overall frequencies of *2, *3, and *17 were 15.2%, 0.3%, and 20.4%, respectively, but varied by ethnicity. The most common variant diplotypes were *1/*17 at 26% and *1/*2 at 19.4%. The less common *2/*17, *17/*17, and *2/*2 genotypes occurred at 6.0%, 4.4%, and 2.5%, respectively. Overall, 58.3% of participants had at least one increased‐function or no‐function CYP2C19 allele. To better understand how this high frequency might impact a real patient population, we examined the prescription rates (Rx) of high‐pharmacogenetic‐risk medications metabolized by CYP2C19 using the University of California at San Francisco (UCSF) health system’s anonymized database of over 1.25 million patients. Between 2012 and 2019, a total of 151,068 UCSF patients (15.8%) representing 5 self‐reported ethnicities were prescribed one or more high‐pharmacogenetic‐risk CYP2C19 medications: proton pump inhibitors (145,243 Rx), three selective serotonin reuptake inhibitor antidepressants (54,463 Rx), clopidogrel (14,376 Rx), and voriconazole (2,303 Rx).

The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors.

α1‐adrenoceptor antagonists are widely used for hypertension (eg, doxazosin) and benign prostatic hypertrophy (BPH, eg, tamsulosin). Some antidepressants and antipsychotics have been reported to have α1 affinity. This study examined 101 clinical drugs and laboratory compounds to build a comprehensive understanding of α1‐adrenoceptor subtype affinity and selectivity. [3H]prazosin whole‐cell binding was conducted in CHO cells stably expressing either the full‐length human α1A, α1B, or α1D‐adrenoceptor. As expected, doxazosin was a high‐affinity nonselective α1‐antagonist although other compounds (eg, cyclazosin, 3‐MPPI, and ARC239) had higher affinities. Several highly α1A‐selective antagonists were confirmed (SNAP5089 had over 1700‐fold α1A selectivity). Despite all compounds demonstrating α1 affinity, only BMY7378 had α1D selectivity and no α1B‐selective compounds were identified. Phenoxybenzamine (used in pheochromocytoma) and dibenamine had two‐component‐binding inhibition curves at all three receptors. Incubation with sodium thiosulfate abolished the high‐affinity component suggesting this part is receptor mediated. Drugs used for hypertension and BPH had very similar α1A/α1B/α1D‐adrenoceptor pharmacological profiles. Selective serotonin reuptake inhibitors (antidepressants) had poor α1‐adrenoceptor affinity. Several tricyclic antidepressants (eg, amitriptyline) and antipsychotics (eg, chlorpromazine and risperidone) had high α1‐adrenoceptor affinities, similar to, or higher than, α blockers prescribed for hypertension and BPH, whereas others had poor α1 affinity (eg, protriptyline, sulpiride, amisulpiride, and olanzapine). The addition of α blockers for the management of hypertension or BPH in people already taking tricyclic antidepressants and certain antipsychotics may not be beneficial. Awareness of the α‐blocking potential of different antipsychotics may affect the choice of drug for those with delirium where additional hypotension (eg, in sepsis) may be detrimental.

Proteomics Profiling of MDD, Suicide and SSRI Treatment in the Human Hippocampus

One person dies due to suicide every 40 seconds globally. Major depressive disorder (MDD) is projected to become the leading disease burden globally by 2030. The pathogenesis of depression and suicide is unclear and there is a high non-response rate to the most used selective serotonin reuptake inhibitors antidepressants (SSRI).

PMS2 RETROSPECTIVE ANALYSIS TO DETERMINE THE INCREASED RISK OF DEVELOPING OSTEOPOROSIS IN PATIENTS DIAGNOSED WITH DEPRESSION AND/OR PRESCRIBED ANTIDEPRESSANTS

The purpose of this study was to investigate the increased risk of developing osteoporosis due to depression and/or antidepressants in older adults. Using open health claims and prescription data (2015 Q4 to 2019 Q3) female (F) [median age 66 years] and male (M) [median age 67 years] patients between ages of 55 to 85 and 65 to 85 years were classified into the following cohorts for both genders (C)- C1: Depression with antidepressants-Selective serotonin Reuptake Inhibitors (SSRIs) or Tricyclic Antidepressants (TCAs), C2: Depression with antidepressants- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) or Monoamine Oxidase inhibitors (MAOIs), C3: Only depression (no antidepressants), C4: No depression and not on antidepressants. We observed an increased risk of osteoporosis in patients diagnosed with depression and not prescribed anti-depressants among both genders [C3 vs C4 - Odds ratio-OR (F)- 1.370254, OR (M)- 1.81021, p <.001]. We also identified a further increased risk of osteoporosis with those receiving anti-depressants and some variation in specific antidepressant categories between genders. Female patients prescribed [SSRI (p =.002) or TCA (p <.001) or SNRI (p=.008) or TCA and SSRI (p <.001)] had increased incidence of osteoporosis versus C3 or C4. Occurrence of Osteoporosis in patients prescribed TCA was higher compared to SSRI as shown by logistic regression coefficients of 0.1746993 (C1) and 0.0563853, respectively. Male patients prescribed SNRI’s (OR- 1.295335, p <.001) showed a significant risk in developing osteoporosis compared to untreated/controls. Incidence of osteoporosis was higher in older adults diagnosed with depression and increased further with antidepressants compared to only depression/no depression and not on antidepressants. We recommend adjusting current screening guidelines to reflect this increased risk. We also recommend consideration for more frequent monitoring and greater diligence in screening for osteoporosis in this vulnerable patient population.

Pronounced Inter-Individual Variation in Plasma Cortisol Response to Fluoxetine Hydrochloride in the Pig.

Animal welfare assessment requires measures for positive affective state. Pharmacological agents that manipulate affective state can be used to evaluate novel biomarkers for affective state assessment. However, to validate that an agent has modified brain function, a reliable indicator is required. Circulating cortisol has been used as a reporter for effective delivery of the antidepressant selective serotonin reuptake inhibitor (SSRI) fluoxetine hydrochloride to the brain in humans and sheep. Here, we tested cortisol as a reporter for effective delivery of fluoxetine hydrochloride to the pig brain. We hypothesized that following administration of SSRI, innervation of the serotonergic reward pathway would result in activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased circulating cortisol levels. Large White-Landrace gilts received either a single intravenous dose of 100 mg fluoxetine hydrochloride suspended in 10 mL saline (n = 4), or 10 mL saline alone (n = 4). Blood samples were collected every 15 min for one hour prior to, and six hours post-treatment. The interaction of treatment x time on mean plasma cortisol levels between 15-165 min post-treatment was significant (p = 0.048) with highest cortisol concentrations of SSRI treated pigs versus controls (+ 98%) at 135 min post-treatment. However, individual cortisol profiles after SSRI treatment revealed high inter-individual variation in response. We conclude that, while combined data imply that plasma cortisol may be a readout for SSRI efficacy, inter-individual variation in SSRI response may preclude application of this approach in the pig. Given the current limited sample size, further research to confirm these findings is needed.

Augmenting usual care SSRIs with cognitive behavioral therapy for insomnia to improve depression outcomes in youth: Design of a randomized controlled efficacy-effectiveness trial

ImportanceExtant treatments for youth depression are only modestly effective. Alternative approaches are needed to improve health outcomes. A novel approach to improve depression outcomes is suggested by epidemiological studies finding that insomnia often predates and may contribute to depression risk. We test whether treating insomnia among youth starting a new course of SSRI antidepressants improves depression outcomes. This paper describes our study design. Design2-arm randomized controlled efficacy-effectiveness trial. SettingA large non-profit health maintenance organization. Participants165 adolescents aged 12–19 with research-confirmed depression and insomnia diagnoses, starting a new episode of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment prescribed by their usual care provider. InterventionsTwo sleep interventions, each 6–7 sessions, both overlaying “treatment as usual” (TAU) SSRIs: a sleep hygiene (SH) attention control condition, and cognitive-behavioral therapy for insomnia (CBTI). Conclusions and relevanceIf CBT-I improved sleep is shown to improve depression-related outcomes, this may provide an additional, easily tolerated intervention for an important public health target.Trial Registration: clinicaltrials.gov, NCT02290496, https://clinicaltrials.gov/ct2/show/NCT02290496.

Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression

ABSTRACT Up to 10% of women use selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy and postpartum. Recent evidence suggests that SSRIs are capable of altering the gut microbiota. However, the interaction between maternal depression and SSRI use on bacterial community composition and the availability of microbiota-derived metabolites during pregnancy and lactation is not clear. We studied this using a rat model relevant to depression, where adult females with a genetic vulnerability and stressed as pups show depressive-like behaviors. Throughout pregnancy and lactation, females received the SSRI fluoxetine or vehicle. High-resolution 16S ribosomal RNA marker gene sequencing and targeted metabolomic analysis were used to assess the fecal microbiome and metabolite availability, respectively. Not surprisingly, we found that pregnancy and lactation segregate in terms of fecal microbiome diversity and composition, accompanied by changes in metabolite availability. However, we also showed that fluoxetine treatment altered important features of this transition from pregnancy to lactation most clearly in previously stressed dams, with lower fecal amino acid concentrations. Amino acid concentrations, in turn, correlated negatively with the relative abundance of bacterial taxa such as Prevotella and Bacteroides. Our study demonstrates an important relationship between antidepressant use during the perinatal period and maternal fecal metabolite availability in a rat model relevant to depression, possibly through parallel changes in the gut microbiome. Since microbial metabolites contribute to homeostasis and development, insults to the maternal microbiome by SSRIs might have health consequences for mother and offspring.

Association Between Period 3 Gene Polymorphisms and Adverse Effects of Antidepressants for Major Depressive Disorder.

Aims: Circadian rhythm genes including Period 3 (Per3) are associated with major depressive disorder (MDD) and have an effect on the patient's response to selective serotonin reuptake inhibitor (SSRI) antidepressants. The aim of this study was to identify possible associations between three single nucleotide polymorphisms (SNPs) of Per3 (rs10746473, rs228697, and rs228729), the MDD symptoms, and adverse effects of SSRIs. Materials and Methods: A total of 600 MDD patients who had been treated with SSRIs were enrolled. The 17-item Hamilton Rating Scale for Depression (HAMD17) was used to evaluate symptoms and treatment efficacy. In addition, the Treatment Emergent Symptom Scale/UKU Consumer Satisfaction Rating Scale (TESS/UKU) was used to assess adverse effects. The Per3 locus was genotyped by PCR and DNA sequencing. Results: The Per3 rs228697 CC genotype was associated with a higher sleep factor score when compared with the CG genotype (F = 4.027, p = 0.046). In addition, the rs228729 TC genotype was associated with a greater risk of suffering from excitement/agitation (p = 0.002, OR [odds ratio] = 4.049), akathisia (p = 0.014, OR = 4.905) and weight loss (p = 0.041, OR = 2.287) when compared with the CC genotype. Finally, the rs10746473 AA genotype patients were more likely to suffer from dizziness (p = 0.042, OR = 0.362) and the GA genotype patients from tachycardia (p = 0.015, OR = 0.340) when compared with those with GG genotype. Conclusion: The Per3 gene variants in patients can predict adverse effects of SSRIs and drug compliance.

Bones of Contention: A Comprehensive Literature Review of Non-SSRI Antidepressant Use and Bone Health.

Osteoporotic fractures are associated with major morbidity and mortality, particularly among older age groups. In recent decades, selective serotonin reuptake inhibitors (SSRI) antidepressants have been linked to reduced bone mineral density and increased risk of fragility fracture. However, up to one-third of antidepressant prescriptions are for classes other than SSRIs. Older patients, who are particularly vulnerable to osteoporosis and its clinical and psychosocial consequences, may be prescribed non-SSRI antidepressants preferentially because of increasing awareness of the risks SSRIs pose to bone health. However, to date, the skeletal effects of non-SSRI antidepressants have not been comprehensively reviewed. In this article, we collate and review the available data and discuss the findings. Based on the current literature, we tentatively suggest that tricyclic antidepressants may increase the risk of fracture via mechanisms other than a direct effect on bone mineral density. The risk is apparently confined to current users only and is greatest in the earliest stage of treatment, diminishing thereafter. There is, as yet, insufficient data to conclusively determine the effects of other antidepressant classes on bone. Judicious prescribing of antidepressants among higher risk groups necessitates a thorough review of the individual's risk factors for osteoporosis as well as attention to their falls risk. Further longitudinal, rigorously controlled studies are needed to answer some of the remaining questions on the effects of non-SSRI antidepressants on bone and the mechanisms by which they are exerted.

Antidepressant effect of the interaction of fluoxetine with granisetron.

Selective serotonin reuptake inhibitors (SSRIs) may produce digestive side effects such as nausea and vomiting, diarrhoea and decreased appetite. These side effects are determined by the increase in serotonin availability at 5-HT3 receptors. Granisetron, a serotonin 5-HT3 receptor antagonist, is expected to antagonize the digestive adverse effects of serotonin reuptake inhibitors, but the question is to what extent granisetron influences the antidepressant effect of these substances. The aim of this study was to determine the dose of fluoxetine that has an antidepressant effect in the Porsolt test, and the interaction between fluoxetine and granisetron with respect to the antidepressant effect in this test. In experiment 1, fluoxetine was antidepressant only at 20 mg/kg body weight (bw). In experiment 2, granisetron 1 mg/kg bw had a statistically significant antidepressant effect vs. control. Fluoxetine 20 mg/kg bw associated with a small dose of granisetron (0.1 mg/kg bw) produced a significant antidepressant effect vs. control. This shows that low doses of granisetron associated to fluoxetine might produce a significant antidepressant effect, suggesting a potentiation between these two drugs used in sub-effective antidepressant doses. In conclusion, in our experimental conditions, we can assume that granisetron in low doses could be used to combat intestinal transit disorders produced by SSRI antidepressants. These low doses are preferred, because they increase the antidepressant effect of these SSRIs.

Research and development of κ opioid receptor agonists and δ opioid receptor agonists.

Delta opioid delta receptor (DOP) agonists were expected to be analgesics and many researchers tried to develop the SNC80 derivatives. However, the derivatives were dropped at the stage of early clinical trials because of undesirable side effects and weak analgesia. On the other hand, DOP agonists have been proposed as attractive candidates for the novel psychotropic drugs. We recently succeeded in synthesizing a novel selective DOP agonist KNT-127. KNT-127 produced neither catalepsy nor convulsive effects. We have demonstrated that KNT-127 has potent anxiolytic-like effect in rat models of innate anxiety. This anxiolytic-like effect was independent from known adverse effect of benzodiazepine, such as memory impairment, motor coordination deficits, and ethanol interactions. We have also demonstrated that KNT-127 showed potent and rapid antidepressant-like effects in rat models of depression. This antidepressant-like effect was independent from known adverse effect of selective serotonin reuptake inhibitor (SSRI), such as digestive symptoms. Therefore, we propose that DOP should be considered as an attractive target for the development of novel psychotropic drugs, without producing the adverse effects associated with benzodiazepine anxiolytics and SSRI antidepressants. Very recently, we developed another delta agonist NC-2800 with a different structure. NC-2800 is now in the preclinical stage using the CiCLE fund supported by AMED (Japanese Agency for Medical Research and Development).

Results rebut claim that antidepressants lack efficacy for nonsevere depression

A post hoc analysis using individual patient data to evaluate the effects of selective serotonin reuptake inhibitor (SSRI) antidepressants has found that when using the core depression measures of the Hamilton Depression Rating Scale (HDRS), SSRIs are as effective for nonsevere depression as they are for severe depression. These results contradict those of other analyses that have based their findings on all 17 measures of the HDRS, including those for symptoms that are not present to a great degree in patients with nonsevere depression. Study results were published online July 11 in The Lancet Psychiatry.

Post-SSRI sexual dysfunction & other enduring sexual dysfunctions.

Enduring sexual difficulties following treatment with selective serotonin reuptake inhibitor antidepressants have been reported to regulators since 1991, but it was only in 2006 that a formal post-SSRI sexual dysfunction syndrome was reported. The clinical, research and regulatory implications of this syndrome are considerable and researchers using epidemiological methods are well placed to map out the contours of the problem and perhaps pinpoint possible treatments.

Levomilnacipran: More of the Same?

The primary objective of this narrative review is to provide clinicians an in-depth analysis of the mechanism of action, pharmacokinetics, toxicology, and efficacy of levomilnacipran. We propose that unlike selective serotonin reuptake inhibitors (SSRIs), or even their precursor serotonin-norepinephrine reuptake inhibitors (SNRIs), levomilnacipran demonstrates a potentially unique ability to alleviate the fatigue symptom cluster of major depressive disorder (MDD). A literature review was completed in PubMed using the MeSH term levomilnacipran. Inclusion criteria were English-language only, randomized controlled trials and systematic reviews published through March 2019. Analyses using product labels and anecdotal or uncontrolled reports of clinical applications were excluded. Only published data from short-term and long-term trials were analyzed. The search resulted in 73 articles. The evidence-based review comprises a total of 31 articles. The data analyzed suggest that levomilnacipran has evidence in the treatment of MDD. More specifically, data suggest that levomilnacipran may be unique among SSRI and SNRI antidepressants in its ability to improve the fatigue symptom cluster in MDD. Further investigations are warranted into levomilnacipran's potentially unique ability to alleviate the fatigue symptom cluster of MDD. Future head-to-head studies and studies that assess for clinically relevant improvements in fatigue are needed.

Trastornos de ansiedad

Anxiety disordersAnxiety is a common adaptive answer to conditions considered threats. When clinical criteria of intensity, frequency and functional decline of the patients are exceeded, anxiety becomes a disorder. Among them are panic disorders, agoraphobia and generalized anxiety disorder. Due their effectiveness, tolerability and lack of tolerance and dependence, selective serotonin reuptake inhibitor (SSRI) antidepressants or serotonin and norepinephrine reuptake inhibitors (SNRI) are the first-line treatment. Conversely, benzodiazepines, although frequently used for the treatment of acute control of anxiety, are not indicated for long-term management of anxiety.

Managing Depression with Bupleurum chinense Herbal Formula: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehensive systematic review and meta-analysis of BC formula for MDD. Design: Randomized controlled trials were retrieved from English and Chinese databases, from their inceptions to March 2019. Included studies compared BC formula alone or as integrative medicine to selective serotonin reuptake inhibitor (SSRI) antidepressants. Studies included adults 18-65 years of age. People with other types of depression or physical comorbidities, such as poststroke depression, bipolar, and other mental or physical disorders, were excluded. Meta-analysis was performed using STATA software. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: Thirty studies compared BC formula to antidepressants and 25 studies compared BC formula plus antidepressants to antidepressants alone. BC formula was more effective than antidepressants at improving depression severity measured on the Hamilton Rating Scale for Depression (HRSD) (standardized mean difference [SMD] -0.35, 95% confidence interval [CI] -0.52 to -0.18, I2 = 81.2%). Integrative use of BC formula plus SSRIs was also superior to SSRIs alone at improving HRSD scores (SMD -1.03, 95% CI -1.43 to -0.62, I2 = 94.2%). However, heterogeneity of the included studies was high and quality was low. The total number and severity of adverse events in the BC formula groups were less than that in the antidepressant groups. Conclusions: BC formula alone or given as integrative medicine with antidepressants reduced depression severity. However, the evidence is low quality and at risk of bias. Well-designed studies are needed to validate the results we identified in this review.