Therapeutic Effects Of Antidepressants Research Articles

Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.

Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems. Through a comprehensive search in PubMed and Scopus databases, we reviewed 5258 abstracts and identified 36 eligible functional neuroimaging studies on antidepressant effects in major depressive disorder. Activation likelihood estimation was used to investigate regional convergence of the reported foci of antidepressant effects, followed by functional decoding and connectivity mapping of the convergent clusters. Additionally, utilizing group-averaged data from the Human Connectome Project, we assessed convergent resting-state functional connectivity patterns of the reported foci. Next, we compared the convergent circuit with the circuits targeted by transcranial magnetic stimulation therapy. Last, we studied the association of regional and network-level convergence maps with selected neurotransmitter receptors/transporters maps. No regional convergence was found across foci of treatment-associated alterations in functional imaging. Subgroup analysis in the Treated > Untreated contrast revealed a convergent cluster in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. Moreover, we found network-level convergence of the treatment-associated alterations in a circuit more prominent in the frontoparietal areas. This circuit was co-aligned with circuits targeted by "anti-subgenual" and "Beam F3"transcranial magnetic stimulation therapy. We observed no significant correlations between our meta-analytic findings with the maps of neurotransmitter receptors/transporters. Our findings highlight the importance of the frontoparietal network and the left dorsolateral prefrontal cortex in the therapeutic effects of antidepressants, which may relate to their role in improving executive functions and emotional processing.

Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.

Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems. Through a comprehensive search in PubMed and Scopus databases, we reviewed 5,258 abstracts and identified 36 eligible functional neuroimaging studies on antidepressant effects in major depressive disorder. Activation likelihood estimation was used to investigate regional convergence of the reported foci of consistent antidepressant effects, followed by functional decoding and connectivity mapping of the convergent clusters. Additionally, utilizing group-averaged data from the Human Connectome Project, we assessed convergent resting-state functional connectivity patterns of the reported foci. Next, we compared the convergent circuit with the circuits targeted by transcranial magnetic stimulation (TMS) therapy. Last, we studied the association of regional and network-level convergence maps with selected neurotransmitter receptors/transporters maps. No regional convergence was found across foci of treatment-associated alterations in functional imaging. Subgroup analysis across the Treated > Untreated contrast revealed a convergent cluster in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. Moreover, we found network-level convergence of the treatment-associated alterations in a circuit more prominent in the frontoparietal areas. This circuit was co-aligned with circuits targeted by "anti-subgenual" and "Beam F3" TMS therapy. We observed no significant correlations between our meta-analytic findings with the maps of neurotransmitter receptors/transporters. Our findings highlight the importance of the frontoparietal network and the left dorsolateral prefrontal cortex in the therapeutic effects of antidepressants, which may relate to their role in improving executive functions and emotional processing.

Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain.

The serotonergic transmitter system plays fundamental roles in the nervous system in neurotransmission, synaptic plasticity, pathological processes, and therapeutic effects of antidepressants and psychedelics, as well as in the gastrointestinal and circulatory systems. We introduce a novel small molecule fluorescent agent, termed SERTlight, that specifically labels serotonergic neuronal cell bodies, dendrites, and axonal projections as a serotonin transporter (SERT) fluorescent substrate. SERTlight was developed by an iterative molecular design process, based on an aminoethyl-quinolone system, to integrate structural elements that impart SERT substrate activity, sufficient fluorescent brightness, and a broad absence of pharmacological activity, including at serotonin (5-hydroxytryptamine, 5HT) receptors, other G protein-coupled receptors (GPCRs), ion channels, and monoamine transporters. The high labeling selectivity is not achieved by high affinity binding to SERT itself but rather by a sufficient rate of SERT-mediated transport of SERTlight, resulting in accumulation of these molecules in 5HT neurons and yielding a robust and selective optical signal in the mammalian brain. SERTlight provides a stable signal, as it is not released via exocytosis nor by reverse SERT transport induced by 5HT releasers such as MDMA. SERTlight is optically, pharmacologically, and operationally orthogonal to a wide range of genetically encoded sensors, enabling multiplexed imaging. SERTlight enables labeling of distal 5HT axonal projections and simultaneous imaging of the release of endogenous 5HT using the GRAB5HT sensor, providing a new versatile molecular tool for the study of the serotonergic system.

GRP94 in cerebrospinal fluid may contribute to a potential biomarker of depression: Based on proteomics

The present study was designed to investigate potential biomarkers of depression and targets of antidepressants from the perspective of hippocampal endoplasmic reticulum stress (ERS) based on cerebrospinal fluid (CSF) proteomics. Firstly, a six-week depression model was established and treated with fluoxetine (FLX). We found antidepressant-FLX could ameliorate depression-like behaviors and cognition in depressed rats caused by chronic unpredictable mild stress (CUMS). FLX significantly increased neuronal numbers in dentate gyrus (DG) and CA3 regions of hippocampus. CSF proteome data revealed thirty-seven differentially expressed proteins (DEPs) co-regulated by CUMS and FLX, including GRP94 and EIF2α. Results of Gene Oncology (GO) annotation and KEGG pathway enrichment for DEPs mainly included PERK-mediated unfolded protein response, endoplasmic reticulum, and translational initiation. The expression levels of GRP94, p-PERK, p-EIF2α, CHOP and Caspase-12 were increased in hippocampus of CUMS rats, and FLX worked the opposite way. FLX had strong affinity and binding activity with GRP94 protein, and four key proteins on the PERK pathway (PERK, EIF2α, p-EIF2α, CHOP). We proposed that FLX may exert antidepressant effects and neuroprotective action by alleviating excessive activation of the hippocampal PERK pathway and reducing neuronal deficits in depressed rats. PERK, EIF2α, p-EIF2α, and CHOP may be potential targets for antidepressant-FLX. GRP94 in CSF may be a potential biomarker of depression and the therapeutic effects of antidepressants.

Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression

Context Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear. Objective This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats. Materials and methods Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin. Results Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism. Discussion and conclusions This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area.

Increased levels of brain-derived neurotrophic factor in cultures of nervous cells treated with a selective serotonin reuptake inhibitor

Introduction. The effects of antidepressants such as fluoxetine on brain plasticity are associated with increased transcription and signaling of trophic factors such as brain-derived neurotrophic factor (BDNF), which enhances synaptic and neurogenic processes. Objective. To evaluate whether treatment with fluoxetine could increase BDNF levels in retinal cells. Method. To conduct the experiment, retinas were dissected from neonatal rats and cultured in complete culture medium. Next, the cultures designated for the experimental group were treated with 1µM of fluoxetine and maintained for 2, 12, 24, 48, or 72 hours in vitro. The cultures designated for the control group underwent the same protocol, but did not receive the fluoxetine treatment. The levels of BDNF were determined by Western blot analysis, and the data were analyzed by Student's t-test to compare the two groups (control and experimental). Results. The results showed that cultures treated with fluoxetine for 12, 24, and 48 hours had significantly higher levels of BDNF than the control group. Conclusion. The findings suggest that treatment with fluoxetine may have potential therapeutic effects on retinal cells by increasing BDNF levels. This adds to the existing evidence on the role of BDNF in mediating the therapeutic effects of antidepressants and highlights the potential for further research on the use of antidepressants in the treatment of retinal diseases.

Traditional Chinese medicine decoctions and Chinese patent medicines for the treatment of depression: Efficacies and mechanisms.

Depression is a major mental disorder and it is currently recognized as the second-leading cause of disability worldwide. However, the therapeutic effect of antidepressants remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely used for centuries, including commonly-used complementary and alternative medical therapies for depression. Recent clinical trials have been carried out to assess the efficacy and safety of TCM, and to explore the mechanisms of action in relation to the treatment of depression. To summarize frequently used TCM decoctions and Chinese patent medicines (CPM) for treating depression, review their clinical therapeutic effects in treating depressive disorders, consider their possible mechanisms, and characterize the relationships between their efficacy and mechanisms. We performed a computerized literature search using the electronic databases such as PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases, with the keywords "depression", "traditional Chinese medicine decoction", "Chinese patent medicine", "application", "mechanism", and their combinations, from January 1, 2000 to August 8, 2022 (inclusive). A total of 51 papers were identified. We reviewed studies on six each TCM decoctions and CPMs, which demonstrated their significant clinical efficacy for treating depression and examined their mechanisms of action. The anti-depressive effects were related to: 1) increased monoamine neurotransmitter levels, 2) inhibiting hyperactivity of the hypothalamic-pituitary-adrenal axis, 3) regulating hippocampal neurons and neurotrophic factors, 4) regulating immune cytokines, 5) counteracting excitatory amino acid toxicity, and 6) regulating microbe-gut-brain axis function. TCM plays an increasingly important role in the management of depression by enhancing the therapeutic effects and alleviating the side effects of antidepressant chemicals.

Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis.

The neurotrophin brain-derived neurotrophic factor (BDNF) stimulates adult neurogenesis, but also influences structural plasticity and function of serotonergic neurons. Both, BDNF/TrkB signaling and the serotonergic system modulate behavioral responses to stress and can lead to pathological states when dysregulated. The two systems have been shown to mediate the therapeutic effect of antidepressant drugs and to regulate hippocampal neurogenesis. To elucidate the interplay of both systems at cellular and behavioral levels, we generated a transgenic mouse line that overexpresses BDNF in serotonergic neurons in an inducible manner. Besides displaying enhanced hippocampus-dependent contextual learning, transgenic mice were less affected by chronic social defeat stress (CSDS) compared to wild-type animals. In parallel, we observed enhanced serotonergic axonal sprouting in the dentate gyrus and increased neural stem/progenitor cell proliferation, which was uniformly distributed along the dorsoventral axis of the hippocampus. In the forced swim test, BDNF-overexpressing mice behaved similarly as wild-type mice treated with the antidepressant fluoxetine. Our data suggest that BDNF released from serotonergic projections exerts this effect partly by enhancing adult neurogenesis. Furthermore, independently of the genotype, enhanced neurogenesis positively correlated with the social interaction time after the CSDS, a measure for stress resilience.

Therapeutic effects of antidepressants for global improvement and subdomain symptoms of autism spectrum disorder: a systematic review and meta-analysis.

Background:No established pharmacological treatment is available for the core symptoms of autism spectrum disorder (ASD). This study aimed at investigating the efficacy of antidepressants for the core and associated symptoms of ASD.Methods:We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science and ClinicalTrials.gov using the keywords “ASD” and “antidepressants.” We searched from database inception to June 2021 for randomized controlled trials of antidepressant use in patients with ASD. We calculated pooled effect sizes based on a random-effects model.Results:Analysis of 16 studies with 899 participants showed improvements in restricted and repetitive behaviours (effect size = 0.27) and global symptoms (effect size = 1.0) in patients with ASD taking antidepressants versus those taking placebos (p ≤ 0.01). We found no differences between the 2 groups (p ≥ 0.36) in terms of dropout rate (odds ratio [OR] = 1.17) or rate of study discontinuation because of adverse events (OR = 1.05). We also noted improvements in irritability and hyperactivity in the antidepressant group (Hedges g = 0.33 and 0.22, respectively, both p < 0.03). Subgroup analyses showed significant effects of medication type (i.e., clomipramine was better than SSRIs) and age (antidepressants were more effective in adults than in children or adolescents) on both restricted and repetitive behaviours and global improvement (p < 0.05). Meta-regression demonstrated that better therapeutic effects were associated with lower symptom severity and older age.Limitations:The small effect sizes and variations in treatment response that we found warrant further study. Conclusion:Our results supported the effectiveness of antidepressants for global symptoms and symptom subdomains of ASD, with tolerable adverse effects. Low symptom severity and adulthood were associated with better outcomes.

Neurotrophins and Neurotrophic Therapy (Based on the Cerebrolysin Model) in the Treatment of Elderly Patients with Cognitive Disorders and Depression. Part 2

Background: сognitive impairment and late depression, along with dementia, are the most common mental disorders in elderly and senile patients. Currently, more and more attention is being paid to preventive therapeutic approaches in the treatment of these conditions and to the study of drugs with multimodal neuroprotective and neurotrophic properties that contribute to the strengthening of the so-called endogenous system of protection and recovery of the brain, which is a kind of barrier to the incipient neurodegeneration.Objective: to present a review of domestic and foreign modern studies devoted to the study of the multimodal effects of the drug cerebrolysin, which has neurotrophin-like properties, and the results of its use in the treatment of cognitive disorders that do not reach the degree of dementia, as well as late depression.Material and methods: using the keywords “late age, mild cognitive disorders, depression, MCI syndrome, therapy, cerebrolysin”, we searched for scientifi c articles in the MEDLINE and PubMed databases for the period 2000–2020.Conclusion: the data presented in the review showed that cerebrolysin, acting as a multi-target drug, affects multiple molecular mechanisms of the pathogenesis of pre-dementia cognitive disorders and late-age depression. The drug detects a neurotrophin-like effect, improves the processes of neuroplasticity and can help enhance the protection and restoration of the brain under various pathological infl uences. Neurobiological studies and the results of a pilot prospective study indicate the preventive potential of cerebrolysin in preventing the development or slowing the progression of the neurodegenerative process of Alzheimer’s type. In the studies presented in the review, the ability of cerebrolysin to increase the effectiveness of modern antidepressant therapy (with second-generation drugs) in the elderly has been shown, presumably by potentiating the therapeutic effect of antidepressants or by improving their tolerability, which makes it possible to safely use higher doses of antidepressants in the elderly and senile patients.

The effect of physical activity on anhedonia in individuals with depressive symptoms.

The therapeutic effect of antidepressants has been demonstrated for anhedonia in patients with depression. However, antidepressants may cause side-effects, such as cardiovascular dysfunction. Although physical activity has minor side-effects, it may serve as an alternative for improving anhedonia and depression. We sought to investigate whether physical activity reduces the level of anhedonia in individuals with depression. Fifty-six university students with moderate depressive symptoms (Beck Depression Inventory total score > 16) were divided into three training groups: the Running Group (RG, n=19), the Stretching Group (SG, n=19), and the Control Group (n=18). We employed the Monetary Incentive Delay (MID) task and the Temporal Experience of Pleasure Scale (TEPS) to evaluate hedonic capacity. All participants in the RG and SG received 8 weeks of jogging and stretching training, respectively. The RG experienced an increase in the level of arousal during anticipation of a future reward and recalled less negativity towards the loss condition. The SG exhibited enhanced scores on the Anticipatory and Consummatory Pleasure subscales of the TEPS after training. Moreover, in the RG, greater improvements in anticipatory arousal ratings for pleasure and remembered valence ratings for negative affect were associated with longer training duration, lower maximum heart rate, and higher consumed calories during training. To conclude, physical activity is effective in improving anticipatory anhedonia in individuals with depressive symptoms.

Baseline beliefs about medication are associated with outcomes of antidepressants in inpatients with first-diagnosed depression under supervised therapeutic compliance.

The aim of the present study was to explore the effect of baseline beliefs about medication on therapeutic outcomes of antidepressants in inpatients with first-diagnosed depression under supervised therapeutic compliance. Ninety-seven inpatients with first-diagnosed depression were included to collect their baseline demographic data to evaluate the Hamilton depression rating scale (HAMD) scores and the beliefs about medicine questionnaire-specific (BMQ-S) scores at baseline and the end of the eight-week treatment. Additionally, we explored the relationship between inpatients’ medication beliefs and therapeutic effect of antidepressants. The inpatients were divided into remitted depression and unremitted depression groups according to outcomes at the end of the eight-week treatment. There was no significant difference in the baseline HAMD between the two groups (P > 0.050). The scores on the BMQ-S of the unremitted group were significantly lower than those of the remitted group (P < 0.001). The HAMD scores were significantly reduced in both groups after the eight-week treatment (P < 0.001). There was no significant difference in the BMQ-S scores before and after the treatment (P > 0.050). The medication beliefs of the unremitted inpatients after the treatment were still lower than those of the remitted inpatients (P < 0.001). Logistic-regression analysis showed that low BMQ-S scores at the baseline were an independent risk factor for antidepressant efficacy. Beliefs about medication at baseline may be correlated with the therapeutic efficacy in inpatients with first-diagnosed depression under supervised therapeutic compliance.

Preliminary Pharmacogenetic Study to Explore Putative Dopaminergic Mechanisms of Antidepressant Action.

Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable.

Ahi1 regulates the nuclear translocation of glucocorticoid receptor to modulate stress response

Stress activates the nuclear translocation of glucocorticoid receptors (GR) to trigger gene expression. Abnormal GR levels can alter the stress responses in animals and therapeutic effects of antidepressants. Here, we reported that stress-mediated nuclear translocation of GR reduced Ahi1 in the stressed cells and mouse brains. Ahi1 interacts with GR to stabilize each other in the cytoplasm. Importantly, Ahi1 deficiency promotes the degradation of GR in the cytoplasm and reduced the nuclear translocation of GR in response to stress. Genetic depletion of Ahi1 in mice caused hyposensitivity to antidepressants under the stress condition. These findings suggest that AHI1 is an important regulator of GR level and may serve as a therapeutic target for stress-related disorders.

Further characterization of the effect of the prototypical antidepressant imipramine on the microstructure of licking for sucrose.

We previously reported that treatment with the prototypical antidepressant imipramine induced a dose-dependent reduction of the ingestion of a 10% sucrose solution, due to reduction of the licking burst number, thus suggesting reduced motivation and/or increased satiation. Importantly, the experimental sessions were performed in an alternate order, either 1-h or 24-h after imipramine administration. The observation that imipramine effect was more pronounced in the "1-h after-treatment" sessions, i.e. at the time of the brain drug Cmax, led us to suggest that it was likely related to brain drug levels at testing time. However, such an experimental design does not allow to rule out the alternative possibility that the observed effect might be due to post-session administration, as previously observed with memantine. To determine whether imipramine-induced decrease of sucrose ingestion could be observed even in absence of post-session administration, we examined the effect of a daily 22 day treatment with imipramine (5, 10 and 20 mg/kg). In the first half of the treatment period all behavioural tests were performed 1-h after administration. In the second half of the treatment period, tests were performed alternatively either 1-h or 24-h after imipramine administration. The results confirm that imipramine reduces sucrose ingestion due to a reduction of the licking burst number. Most importantly, these results demonstrate that this effect does not require imipramine post-session administration, since it was present before the beginning of post-session administrations. This supports the interpretation of the reduction of sucrose ingestion as a consequence of reduced motivation and/or increased satiation. Thus, these findings, taken together with the results of our previous study, might be relevant in explaining the effects of imipramine in models of drug-seeking and in body weight gain reduction in rats, but not in accounting for the antidepressant therapeutic effect. At variance with the results of our previous study, an increase in burst size was present in the first half of the treatment period, which might be interpreted as a prohedonic effect and/or as a compensatory effect.

Dopamine Multilocus Genetic Profile, Spontaneous Activity of Left Superior Temporal Gyrus, and Early Therapeutic Effect in Major Depressive Disorder.

Objectives: This study aimed to examine the interactive effects of dopamine (DA) pathway gene and disease on spontaneous brain activity and further to explore the relationship between spontaneous brain activity and the early antidepressant therapeutic effect in patients with major depressive disorder (MDD).Methods: A total of 104 patients with MDD and 64 healthy controls (HCs) were recruited. The Hamilton Depression Scale-24 (HAMD-24) was used to measure the depression severity. Both groups were given resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuation (ALFF) was calculated to reflect the spontaneous brain activity based on the rs-fMRI data. After treatment for 2 weeks, depression severity was evaluated again, and HAMD-24 reductive rate was used to measure the therapeutic effect of antidepressants. Multilocus genetic profile scores (MGPS) were used to assess the multi-site cumulative effect of DA pathway gene. The interactive effects of MDD and DA pathway gene on the ALFF of regional brain areas were measured by the multivariate linear regression analysis. Finally, partial correlation analysis (age, sex, education, and illness durations as covariates) was performed to identify the relationship between regional ALFF and therapeutic effect.Results: MDD and DA-MGPS had interactive effects on the left fusiform gyrus (FG_L), right calcarine sulcus (CS_R), left superior temporal gyrus (STG_L), bilateral cerebellum posterior lobe (CPL), bilateral inferior frontal gyrus (IFG), and bilateral superior frontal gyrus (SFG). Partial correlation analysis revealed that the ALFF of STG_L had a significant negative correlation with 2-week HAMD-24 reductive rate (r = −0.211, P = 0.035).Conclusions: The spontaneous activity of STG_L may be a potential biomarker of antidepressant-related early therapeutic effect underlying the influence of DA pathway genes in MDD.

Serotonergic antidepressants for sleep disturbances in perimenopausal and postmenopausal women: a systematic review and meta-analysis.

Although previous meta-analyses mainly focused on the effects of hormonal treatment against menopausal sleep disturbances, the therapeutic role of antidepressants has not been systematically addressed. To study the therapeutic benefit and safety of antidepressants in menopausal sleep disturbances. Randomized controlled trials assessing the therapeutic effects of antidepressants against menopausal sleep problems were identified from the PubMed, Cochrane Library, and Science Direct databases from inception to March 1, 2020. Studies that were clinical trials with placebo controls were included. Subgroup analyses were conducted according to a random effects model. Analysis of seven eligible randomized controlled trials including a total of 1,949 perimenopausal and postmenopausal women showed the effectiveness of serotonergic antidepressants against sleep disturbances despite the small effect size (Hedge g = 0.24, 95% CI = 0.11-0.38). The efficacy remained significantly better than that of placebo for postmenopausal women (Hedge g = 0.25, 95% CI = 0.04-0.45), participants with hot flashes (Hedge g = 0.18, 95% CI = 0.02-0.34), and those without diagnosis of major depressive disorder (Hedge g = 0.23, 95% CI = 0.06-0.40). There was no difference in therapeutic benefit between sedating and nonsedating serotonergic antidepressants. Besides, the dropout rate did not differ between antidepressant and placebo groups. Our results showed that serotonergic antidepressants were effective against sleep disturbances in perimenopausal and postmenopausal women. The efficacy remained significant for women without major depressive disorder. The dropout rates were also comparable between serotonergic antidepressants and placebo groups.

Decreased cortical thickness of left premotor cortex as a treatment predictor in major depressive disorder.

This study aimed to examine the cerebral cortex characteristics (thickness, surface area, and curvature) in patients with major depressive disorder (MDD), and explore whether these cortex characteristics are predictors for the antidepressant therapeutic effect. 105 patients with MDD and 49 healthy controls (HCs) were recruited. Both groups were given magnetic resonance image (MRI) scans at baseline period, and then the cerebral cortex characteristics (thickness, surface area, and curvature) were calculated using the DPABISurf software. The Hamilton Depression Scale-24 (HAMD-24) reductive rate was used to measure antidepressant therapeutic effect and Snaith Hamilton Rating Scale (SHAPS) reduction was performed to assess the change of anhedonia after treatment of 8 weeks. Correlation analysis was performed to identify the relationship between cortex characteristics and antidepressant therapeutic effect in patients with MDD. There were no significant differences in the cortical curvature and surface area between MDD and HC groups, while significant decreases were found in the cortical thickness of inferior frontal cortex (IFC), premotor cortex (PMC), orbital and medial prefrontal cortex (OMPFC) in the left hemisphere of MDD group, comparing with HC group (P < 0.05 for all, corrected by threshold-free cluster enhancement). In MDD group, the cortical thickness of left PMC had significant positive correlations with 8-week HAMD-24 reduction (r = 0.228, P = 0.020) and HAMD-24 reductive rate (r = 0.193, P = 0.048); and a negative correlation with the 8-week SHAPS reduction (r = -0.240, P = 0.018). Decreased cortical thickness in left PMC may be a predictor of therapeutic effect in MDD. Determining the cortical thickness of this region before treatment can provide certain reference value for clinical antidepressant treatment.

Research on the Development of Theme Trends and Changes of Knowledge Structures of Drug Therapy Studies on Major Depressive Disorder Since the 21st Century: A Bibliometric Analysis.

BackgroundAntidepressant treatment is one of the most effective ways of relieving or curing depressive symptoms in patients with major depressive disorder (MDD). Although many studies have explored the efficacy, tolerability, adverse reactions, and functional mechanism of the disease, there has been no systematic evaluation of the relevant results in this field.AimThis paper aims to analyze the theme trends and knowledge structure of drug therapy studies on MDD since the 21st century by employing bibliometric analysis.MethodsLiterature published in PubMed and related to drug therapy studies on MDD were retrieved between 2001 and 2018 in 6-year increments. After extracting major Medical Subject Headings (MeSH) terms/MeSH subheadings, bi-clustering analysis, social network analysis, and strategic diagrams were employed to complete bibliometric analysis.ResultsOverall, 1,577, 2,680, 2,848 relevant research articles were retrieved for the periods during 2001–2006, 2007–2012, and 2013–2018, respectively. In line with strategic diagrams, the main undeveloped and peripheral theme clusters during 2001–2006 were functional mechanisms of antidepressants in pathophysiology, neuroendocrinology and neural biochemistry. These themes were replaced during 2007–2012 by clinical efficacy and influencing factors of antidepressants with or without psychotherapy, mechanisms of adverse reactions of antidepressants, and predictive studies of clinical therapeutic effects of antidepressants based on brain imaging. During 2013–2018 application and evaluation of new antidepressant agents, early identification and prevention of suicide of patients with MDD, as well as genetic- or bio-markers affecting the response and efficacy of antidepressants were the primary themes. Based on social network analyses, emerging hotspots, such as antidepressive agents, second-generation/adverse effects, depressive disorder, major/metabolism, psychotherapy/methods, and brain/drug effects could be identified during 2007–2012 and 2013–2018.ConclusionsThese undeveloped theme clusters and emerging hotspots can be helpful for researchers to clarify the current status of their respective fields and future trends, and to generate novel ideas that may launch new research directions.

Microstructure analysis of sucrose ingestion in the course of chronic treatment with imipramine

The analysis of licking microstructure provides measures which might be interpreted in terms of psychological constructs, such as pleasure and motivation, relevant for the interpretation of the effects of antidepressant drugs. The aim of this study was to characterise the effect of the prototypical antidepressant imipramine on the microstructure of licking for a 10% sucrose solution. In particular, ten 30-min sessions were performed in the course of a daily 21 day treatment with imipramine – 5, 10 and 20 mg/kg/die administered intraperitoneally. To interpret drug effects in relation to the presumed concentration of imipramine and its active metabolite desipramine, the experimental sessions were performed in an alternate order either 1-h or 24-h after imipramine administration. In the sessions performed 1-h after drug administration, the results showed a dose-dependent reduction of sucrose ingestion, accounted for by a reduction of the licking burst number. Moreover, reduced intra-burst lick rate and increased latency to lick were observed with the highest doses. Imipramine effect in the sessions performed 24-h after drug administration was similar but less pronounced. These results are consistent with the hypothesis that the reduction of sucrose ingestion might be due to reduced motivation and/or to a potentiation of satiety signals. These effects appear to be related, at least in part, to brain drug levels at testing time, and do not seem related to the mechanisms underlying the antidepressant therapeutic effect. However, these results might be relevant in explaining the effects of imipramine in models of drug-seeking and on body weight.