Pharmacological Treatment Of Depression Research Articles

Dose-response relationship in cognitive behavioral therapy for depression: A nonlinear metaregression analysis.

Evidence on the optimal "dose" of cognitive behavioral therapy (CBT) for treating major depressive disorder is sparse. This analysis aimed to evaluate the dose-response curve in CBT using a nonlinear approach, whereby "dose" was defined as number of treatment sessions. The dose-response curve of CBT was compared to other psychotherapies and pharmacological treatments for depression. A systematic review and metaregression analysis of randomized controlled trials (RCTs) examining the efficacy of CBT in adults with acute depression was conducted. Treatment arms examining other psychosocial or pharmacological interventions were also analyzed. Cubic spline metaregression techniques were used to model nonlinear dose-response curves. Seventy-two studies and 7,377 participants were included. Modeling the dose-response curve between change of depression symptom severity and the number of CBT sessions resulted in a nonlinear curve characterized by a strong improvement in symptom severity from baseline within the first eight sessions. Symptom reduction continues in the further course of the treatment, but at a slower pace. A similar pattern of symptom development was found for other therapies as well, although the prominence of early improvement and overall effect sizes vary across treatment arms. Results imply a general tendency for the strongest alleviation of depressive symptom severity in early stages of CBT treatment, thus, if aiming at symptom alleviation, speak for short CBT interventions. However, these findings have to be discussed in the light of the limited data regarding the sustainability of treatment effects in short-term therapies and effects beyond symptomatic changes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Molecular Mechanisms of Reelin in the Enteric Nervous System and the Microbiota-Gut-Brain Axis: Implications for Depression and Antidepressant Therapy.

Current pharmacological treatments for depression fail to produce adequate remission in a significant proportion of patients. Increasingly, other systems, such as the microbiome-gut-brain axis, are being looked at as putative novel avenues for depression treatment. Dysbiosis and dysregulation along this axis are highly comorbid with the severity of depression symptoms. The endogenous extracellular matrix protein reelin is present in all intestinal layers as well as in myenteric and submucosal ganglia, and its receptors are also present in the gut. Reelin secretion from subepithelial myofibroblasts regulates cellular migration along the crypt-villus axis in the small intestine and colon. Reelin brain expression is downregulated in mood and psychotic disorders, and reelin injections have fast antidepressant-like effects in animal models of depression. This review seeks to discuss the roles of reelin in the gastrointestinal system and propose a putative role for reelin actions in the microbiota-gut-brain axis in the pathogenesis and treatment of depression, primarily reflecting on alterations in gut epithelial cell renewal and in the clustering of serotonin transporters.

Public Interest in Psilocybin and Psychedelic Therapy in the Context of the COVID-19 Pandemic: Google Trends Analysis.

Psychedelic substances have demonstrated promise in the treatment of depression, anxiety, and substance use disorders. Significant media coverage has been dedicated to psychedelic medicine, but it is unclear whether the public associates psilocybin with its potential therapeutic benefits. The COVID-19 pandemic led to an increase in depression, anxiety, and substance abuse in the general population. This study attempts to link increases in interest in these disorders with increases in interest in psilocybin using Google Trends. Weekly interest-over-time Google Trends data for 4 years, from the week of March 11, 2018, to the week of March 6, 2022, were obtained for the following terms: "psilocybin," "psychedelic therapy," "cannabis," "cocaine," "antidepressant," "depression," "anxiety," and "addiction." Important psilocybin-related news and the declaration of the pandemic were noted. Trends data for each of the queried terms were plotted, and multiple regression analysis was performed to determine the slope of the prepandemic and postpandemic data with 95% CIs. Nonparametric Tau-U analysis was performed correcting for baseline trends. Results from this test were used to make inferences about the pre- and postpandemic trends and inferences about the change in overall level of searches between the 2 groups. Tau values for prepandemic data were significant for stable trends, all ranging -0.4 to 0.4. Tau values for postpandemic data showed positive trends for "psilocybin," "psychedelic therapy," and "antidepressant." All other trends remained stable in the range of -0.4 to 0.4. When comparing Tau values for pre- and postpandemic data, overall increases in relative search volume (RSV) were seen for "psilocybin," "psychedelic therapy," and "anxiety," and overall decreases in RSV were seen for "depression," "addiction," and "cocaine." Overall RSVs for "cannabis" and "antidepressant" remained stable as Tau values ranged between -0.4 and 0.4. In the immediate aftermath of the declaration of the pandemic, drop-offs in interest were seen for all terms except for "anxiety" and "cannabis." After the initial shock of a global pandemic, "psilocybin" and "psychedelic therapy" groups demonstrated increases in interest trends and overall RSV. These data suggest that overall interest in "psilocybin" and "psychedelic therapy" increased at higher rates and to higher levels after than before the declaration of the pandemic. This is consistent with our hypothesis that interest increased for these treatments after the pandemic as incidence of depression, anxiety, and addiction increased. However, there may be other drivers of interest for these topics, since interest in antidepressants-the typical pharmacologic treatments for depression and anxiety-followed the expected pattern of drop-off and accelerated interest back to prepandemic levels. Interest in "psilocybin" and "psychedelic therapy" may have also been partially driven by popular culture hype and novelty, explaining why interest increased at a higher rate post pandemic and continued to grow, surpassing prior interest.

Genetic variants used as predictors of response in the pharmacological treatment of depression in the brazilian population

Depression is one of the most frequent mental illnesses in the world and the lack of response to antidepressants are linked to genetic variants. The genetic diversity of Brazilian population may contribute to a variability in the response to these drugs, and this study aimed to assess how genetic variants are clinically and scientifically in the context of therapeutic response to depression in the Brazilian population. This work was carried out through a survey in literature and information obtained from genetic laboratories about the variants used in Brazil as biomarkers of response to antidepressants. Data from scientific studies published since 2000 that evaluated genetic variants that are related to the response to antidepressants in Brazilian populations, in the PubMed, Scielo, Scopus and Web of Science databases were also collected and compared with the international scenario. All laboratories evaluated included variants of CYP2D6 and CYP2C19 genes approved by Food and Drug Administration (FDA) as biomarkers. However, the Brazilian genetic panels include variants that lack proven efficacy in PharmGKB and are not FDA-approved, highlighting the need for more regulation of commercialized tests and further studies on genetic variant analysis for depression treatment in our population. A limited number of Brazilian studies in this field were verified, highlighting the need for more regulation of commercialized tests and further studies on genetic variant for depression treatment in our population.

Patterns in Medication Use for Treatment of Depression in Autistic Spectrum Disorder.

Depression impacts many individuals with autism spectrum disorder (ASD), carrying increased risk of functional impairment, hospitalization, and suicide. Prescribing medication to target depression in patients with ASD occurs despite limited available systematic data describing medication management of depression in this population. The purpose of this study is to discover prescribing patterns for individuals with MDD and ASD during this time period (2004-2012) to inform current and future prescribing practices with historical data. Drawing from a large clinical database describing the prescribing practices in patients with ASD, we identified 166 individuals with ASD (mean age 14.5 ± 8.3 years old) who received medication targeting symptoms of depression. We report prescribing rates for specific drugs, drug treatment duration, and reasons for drug discontinuation when applicable. Sertraline, mirtazapine, and fluoxetine were the three most commonly prescribed medications to treat comorbid depression for this patient population. Among 241 drug starts, 123 (49%) drug treatments were continued at the final reviewed follow-up visit (average treatment duration of ± 0.72 years). The most common reason for discontinuation across all medications prescribed was loss of or lack of effectiveness. This study raises concern that standard of care pharmacological treatments for depression in individuals with ASD may be less effective than in neurotypical populations. There remains a need to develop effective interventions for depression specifically tailored to the needs of individuals with ASD.

Towards Outcome-Driven Patient Subgroups: A Machine Learning Analysis Across Six Depression Treatment Studies

BackgroundMajor depressive disorder (MDD) is a heterogeneous condition; multiple underlying neurobiological and behavioral substrates are associated with treatment response variability. Understanding the sources of this variability and predicting outcomes has been elusive. Machine learning (ML) shows promise in predicting treatment response in MDD, but its application is limited by challenges to the clinical interpretability of ML models, and clinicians often lack confidence in model results. In order to improve the interpretability of ML models in clinical practice, our goal was to demonstrate the derivation of treatment-relevant patient profiles comprised of clinical and demographic information using a novel ML approach. MethodsWe analyzed data from six clinical trials of pharmacological treatment for depression (total n = 5438) using the Differential Prototypes Neural Network (DPNN), a ML model that derives patient prototypes which can be used to derive treatment-relevant patient clusters while learning to generate probabilities for differential treatment response. A model classifying remission and outputting individual remission probabilities for five first-line monotherapies and three combination treatments was trained using clinical and demographic data. Prototypes were evaluated for interpretability by assessing differences in feature distributions (e.g. age, sex, symptom severity) and treatment-specific outcomes. ResultsA 3-prototype model achieved an area under the receiver operating curve of 0.66 and an expected absolute improvement in remission rate for those receiving the best predicted treatment of 6.5% (relative improvement of 15.6%) compared to the population remission rate. We identified three treatment-relevant patient clusters. Cluster A patients tended to be younger, to have increased levels of fatigue, and more severe symptoms. Cluster B patients tended to be older, female, have less severe symptoms, and the highest remission rates. Cluster C patients had more severe symptoms, lower remission rates, more psychomotor agitation, more intense suicidal ideation, and more somatic genital symptoms. ConclusionIt is possible to produce novel treatment-relevant patient profiles using ML models; doing so may improve interpretability of ML models and the quality of precision medicine treatments for MDD.

A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder

ABSTRACTThe pharmacological treatment of depression consists of taking antidepressant drugs for prolonged periods; its modest therapeutic effect can often be associated with significant adverse effects, while its discontinuation can lead to relapses. Psilocybin is today a novel and breakthrough therapy for major depression. It is a natural alkaloid in Psilocybe mushrooms, which are endemic to Mexico. Research on a larger scale is lacking in various populations, including the Mexican people. This proposal contemplates the experimental design of a preclinical (toxicity and pharmacological evaluation of an extract in mice) and clinical study by including the chemical analysis of a species of Psilocybe cubensis mushroom to characterize its main constituents. The clinical study will consider the safety evaluation by exploring tolerated doses of Psilocybe cubensis by measuring pharmacokinetic parameters after oral administration in healthy adults and an open trial on a sample of patients with major depressive disorder to assess the safety and efficacy of fully characterized Psilocybe cubensis in a two-single doses treatment, (with assisted psychotherapy), compared with the traditional care model at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz in Mexico City. This report presents the design of a research project with preclinical and clinical experimental components.

Can music therapy help the elderly with depression?

Depression in elderly people is an ongoing concern, contributing to comorbidities and increasing deaths from suicide. Alternative treatments for the elderly are needed due to risks from polypharmacy and unwanted side effects. Therefore, we considered music therapy and its evidence base as a possible management modality. This study evaluates how music therapy can treat depression in the elderly population, aiming to further investigate the effects that music can have on health. An analysis of over 20 research papers was carried out, looking into a range of topics varying from the monoamine hypothesis of depression to how music can affect multiple comorbidities. A search using accredited platforms, such as PubMed and OVID, was carried out into recent and robust research in this area, to provide a systematic review of the literature. The key papers showed that music was found to have a positive effect on mental aspects of health, as described by a number of psychological theories. Current pharmacological treatments for depression were often not compatible with elderly patients due to unwanted side effects and potentially dangerous results from polypharmacy; therefore, music therapy offered a safer alternative. The results also showed that music therapy can be more favourable than psychological therapy, such as CBT, due to its lower energy and concentration requirements. Depression in the elderly is a serious illness that can lead to reduced quality of life and poor health status. Non-pharmacological treatments need to be identified and music therapy can be an accessible way of doing this, with numerous benefits demonstrated.

Do sociodemographic and clinical factors affect the selection of initial antidepressant treatment for depression in older adults? Results from a nationwide descriptive study in Denmark

BackgroundThe choice of antidepressants for initial pharmacological treatment of depression in older adults and associated patients' characteristics are understudied. We aimed to describe the first selected antidepressant (first-choice) for depression in older adults (≥65 years) and whether patients' sociodemographic and clinical characteristics influence selecting an alternative first-choice (any other antidepressant than the nationally recommended first-choice sertraline) in Denmark. MethodsRegister-based cross-sectional study including all older adults who redeemed their first antidepressant prescription for depression at community pharmacies in Denmark in 2015–2019. We analyzed the effect of patients' characteristics on the first-choice antidepressant selection using multinomial logistic regression. ResultsAmong 34,337 older adults with a first antidepressant-prescription, over two-thirds filled alternative first-choice antidepressants than sertraline (28.9 %): escitalopram or citalopram (30.3 %) or mirtazapine (34.4 %). Socially disadvantaged older adults (e.g., with short educational attainment, being single, or of non-western ethnicity) and clinically vulnerable older adults (e.g., having somatic diagnoses and hospital contacts) were more likely to use alternative first-choice antidepressants. LimitationsInformation on prescribers and in-hospital medications was not included in this study. ConclusionsFurther investigation of the first antidepressant selection and its impact on depression treatment outcomes in older adults is necessary. Moreover, for older patients, national guidelines on depression treatment should be more specific. Article summaryAntidepressant selection for initial pharmacological treatment of depression in older adults can be difficult due to comorbidity, polypharmacy, and age-related changes in pharmacokinetics and pharmacodynamics. Real-world evidence/knowledge on first-choice antidepressant selection and associated user characteristics are rare. This Danish register-based cross-sectional study found over two-thirds of older adults filled alternative antidepressants (primarily escitalopram/citalopram or mirtazapine) than nationally recommended first-choice sertraline for depression treatment and identified wide-ranging sociodemographic and clinical factors influencing the first antidepressant selection.

Patterns and predictors of antidepressant prescribing among adults with cancer and depression in ambulatory care settings in the United States.

Despite depression being a common comorbidity among adults with cancer, limited literature is available regarding pharmacologic depression treatment patterns and predictors in this population. This study aims to examine patterns and predictors of antidepressant prescribing among adults with cancer and depression in ambulatory care settings in the United States (US). This retrospective, cross-sectional study utilized data collected from the 2014 to 2015 National Ambulatory Medical Care Survey (NAMCS). The study sample consisted of adults (age ≥ 18 years) with cancer and depression (unweighted N = 539; weighted N = 11,361,000). A multivariable logistic regression analysis was used to adjust for individual-level factors to identify predictors of antidepressant prescribing. Most patients were adults aged ≥ 65 years, female, and non-Hispanic whites. Thirty-seven percent of the study sample received antidepressant treatment. Multivariable logistic regression analysis revealed that race/ethnicity, physician specialty, and number of medications were significantly associated with receiving antidepressant(s). For example, non-Hispanic whites were two-and-half times more likely to receive an antidepressant [OR 2.43, 95% confidence interval 1.13-5.23] compared to other race/ethnic groups. Every unit increase in the number of prescribed medications increased the likelihood of receiving an antidepressant by 6% (OR 1.06, 95% CI: 1.01-1.11). Among adults with a comorbid cancer and depression diagnosis and a recorded U.S. ambulatory care visit in 2014-2015, 37% received antidepressant treatment. This suggests most patients with cancer and depression do not receive pharmacologic treatment for depression. Future studies are needed to investigate the impact of antidepressant treatment on health outcomes in this patient population.

Factors associated with higher quality of clinical practice guidelines and their recommendations for the pharmacological treatment of depression: a systematic review

ObjectiveThe objective of this study was to assess the quality of clinical practice guidelines (CPGs) for the pharmacological treatment of depression along with their recommendations and factors associated with higher...

Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Depression is one of the main mental disorders. Pharmacological treatment of depression is often associated with delayed effects or insufficient efficacy. Consequently, there is a need to discover new therapeutic methods to cope with depression faster and more effectively. Several lines of evidence indicate that the use of probiotic therapy reduces depressive symptoms. Nonetheless, the exact mechanisms linking the gut microbiota and the central nervous system, as well as the potential mechanisms of action for probiotics, are still not entirely clarified. The aim of this review was to systematically summarize the available knowledge according to PRISMA guidelines on the molecular mechanisms linking probiotics and healthy populations with subclinical depression or anxiety symptoms, as well as depressed patients with or without comorbid somatic illnesses. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated. Twenty records were included. It has been found that probiotic administration is linked to a significant increase in BDNF levels during probiotic treatment compared to the placebo (SMD = 0.37, 95% CI [0.07, 0.68], p = 0.02) when considering the resolution of depressive symptoms in depressed patients with or without comorbid somatic illnesses. CRP levels were significantly lower (SMD = -0.47, 95% CI [0.75, -0.19], p = 0.001), and nitric oxide levels were significantly higher (SMD = 0.97, 95% CI [0.58, 1.36], p < 0.0001) in probiotic-treated patients compared to the placebo, however, only among depressed patients with somatic co-morbidities. There were no significant differences in IL-1β, IL-6, IL-10, TNF-α, and cortisol levels after probiotic administration between the intervention and control groups (all p > 0.05). Firm conclusions on the effectiveness of probiotics and their possible association with inflammatory markers in the healthy population (only with subclinical depressive or anxiety symptoms) cannot be drawn. The advent of clinical trials examining the long-term administration of probiotics could evaluate the long-term effectiveness of probiotics in treating depression and preventing its recurrence.

Health interventions and the unseen impact on equality

Health interventions and the unseen impact on equality

Current Knowledge of the Antidepressant Activity of Chemical Compounds from Crocus sativus L.

Psychotropic effect of Crocus sativus L. (family Iridaceae) biologically active chemical compounds are quite well documented and they can therefore be used in addition to the conventional pharmacological treatment of depression. This systematic review on antidepressant compounds in saffron crocus and their mechanisms of action and side effects is based on publications released between 1995−2022 and data indexed in 15 databases under the following search terms: antidepressant effect, central nervous system, Crocus sativus, cognitive impairement, crocin, crocetin, depression, dopamine, dopaminergic and serotonergic systems, picrocrocin, phytotherapy, neurotransmitters, safranal, saffron, serotonin, and biologically active compounds. The comparative analysis of the publications was based on 414 original research papers. The investigated literature indicates the effectiveness and safety of aqueous and alcoholic extracts and biologically active chemical compounds (alkaloids, anthocyanins, carotenoids, flavonoid, phenolic, saponins, and terpenoids) isolated from various organs (corms, leaves, flower petal, and stigmas) in adjuvant treatment of depression and anxiety. Monoamine reuptake inhibition, N-methyl-d-aspartate (NMDA) receptor antagonism, and gamma-aminobutyric acid (GABA)-α agonism are the main proposed mechanism of the antidepressant action. The antidepressant and neuroprotective effect of extract components is associated with their anti-inflammatory and antioxidant activity. The mechanism of their action, interactions with conventional drugs and other herbal preparations and the safety of use are not fully understood; therefore, further detailed research in this field is necessary. The presented results regarding the application of C. sativus in phytotherapy are promising in terms of the use of herbal preparations to support the treatment of depression. This is particularly important given the steady increase in the incidence of this disease worldwide and social effects.

A Comprehensive Review on Postpartum Depression.

One of the most common psychological effects following childbirth is postpartum depression. Postpartum depression (PPD) has a significant negative impact on the child's emotional, mental as well as intellectual development if left untreated, which can later have long-term complications. Later in life, it also results in the mother developing obsessive-compulsive disorder and anxiety. Many psychological risk factors are linkedwith PPD. The pathophysiology of the development of PPD is explained by different models like biological, psychological, integrated, and evolutionary models, which relate the result of the condition with particular conditions and factors. This article also explains the role of methyldopa as a medication used during pregnancy and the postpartum phase with the development of PPD. There are different mechanisms by which methyldopa causes depression. The large-scale screening of the condition can be done by Edinburgh Postnatal Depression Scale (EPDS). The diagnosis can be made by clinical assessment, simple self-report instruments, and questionnaires provided to mothers. Currently, there has not been any specific treatment for PPD, but selective serotonin reuptake inhibitors (SSRIs) like sertraline are effective in acute management. Venlafaxine and desvenlafaxine are serotonin-norepinephrine reuptake inhibitorsused for the relief of symptoms. The SSRIand tricyclic antidepressants(TCA) used in combination have a prophylactic role in PPD. Nowadays, women prefer psychological therapies, complementary health practices, and neuromodulatory interventions like electroconvulsive therapy more than previous pharmacological treatments of depression.Allopregnanolone drug made into sterile solution brexanoloneleads to a rapid decline of PPD symptoms. PPD is a common and severe disorder that affects many mothers following childbirth but is ignored and not given much importance. Later it affects the child's psychological and intellectual abilities and mother-child bonding. We can easily prevent it by early diagnosis and timely care and management of the mother. Understanding the underlying pathophysiology would also go a long way in preventing and managing the disorder.

Confounding by Indication in Studies of Selective Serotonin Reuptake Inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) are used worldwide as the first-line pharmacological treatment for depression. Although SSRI use can increase the risk of suicide, fractures, and infertility, the nature of these relationships is controversial. This review reports confounding by indication and confounding by severity for SSRI side effects in previously published observational studies. The PubMed and Google Scholar databases were searched for English-language articles published from 2005 to 2022. SSRIs are often prescribed for depressive symptoms, and depression is associated with an increased risk of side effects. Therefore, confounding by indication, whereby patients are selected for a particular treatment depending on their diagnosis or severity of illness, may lead to erroneous treatment conclusions, resulting in an adverse outcome. The side effects of SSRIs that can be considered due to confounding by indication or severity include suicide, fractures, infertility, atrial fibrillation, stroke, autism spectrum disorder, and congenital malformation. When prescribing SSRIs for depression, physicians must consider confounding by indication and severity in the management of side effects. In addition, medication discontinuation should be carefully considered when side effects occur during the treatment.

Risk, Determinants, and Pharmacologic Treatment of Depression Following Acute Ischemic Stroke.

Background and Purpose: We assessed risk and determinants of new-onset depression in acute ischemic stroke (AIS) patients of all ages and no known history of depression. Additionally, we assessed patterns of post-stroke depression (PSD) treatment with pharmacotherapy. Methods: Retrospective cohort study of de-identified Marketscan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Datasets for adults age ≥18years admitted with AIS from July 1, 2016-July 1, 2017. We created Kaplan-Meier curves of cumulative risk of PSD up to 1.5years following index AIS admission. We performed Cox regression to report hazard ratios for determinants of PSD up to 1.5years following AIS. We summarized proportions treated with pharmacotherapy and identified the most commonly prescribed medications. Results: Of 8089 AIS patients, 1059 were diagnosed with PSD. At 1 year, cumulative risk of PSD was 13.4% (standard error .4) and 15.3% (standard error .5) at 1.5years. History of anxiety was most strongly associated with PSD and discharge home least. Among those with PSD, 68.8% were prescribed an antidepressant and 8.4% an antipsychotic. The most commonly prescribed antidepressant was sertraline (28.5%). Conclusions: Among AIS patients of all ages, there is a persistently elevated cumulative risk of new diagnosis of PSD in the 1.5years following AIS. Of the >2/3 treated with an antidepressant, sertraline was most commonly prescribed. Screening and treatment strategies for PSD require further study.

Pharmacological interventions for depression in adults with chronic hepatitis B or C

Pharmacological interventions for depression in adults with chronic hepatitis B or C

Depression in Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a progressive neurodegenerative age-related disorder that affects the central nervous system (CNS) and is characterized by uncontrollable movements such as shaking, stiffness, and loss of balance and coordination. Depression is a common non-motor manifestation of PD, but unfortunately, depression remains unrecognized and often undertreated. The underlying pathophysiology of depression in PD is complicated, and many studies have been conducted to know the exact cause, but the question remains unanswered.In this article, we discuss various pathophysiologies by which depression occurs in PD. The most widely accepted theories are neuroinflammation and monoamine oxidase theory. This article also explored the pharmacological treatment of depression in PD; this involves standard antidepressant therapy such as tricyclic antidepressants (TCA), serotonin-norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), and monoamine oxidase inhibitors (MAO); non-pharmacological treatments such as electroconvulsive therapy (ECT), cognitive-behavioral therapy (CBT) have also been discussed. However, physicians hesitate to prescribe antidepressants to patients with PD due to concerns about harmful drug-drug interactions between antidepressants and antiparkinsonian drugs. Despite the complicated link between PD and depression, the co-administration of antidepressants and antiparkinsonian drugs is safe and beneficial when appropriately managed. However, early recognition and initiation of treatment of depression in PD reduces the longitudinal course and improves the cross-sectional picture. This review article also explored the clinical and diagnostic findings and impact on the quality of life of depression in PD.

The molecular pathophysiology of depression and the new therapeutics.

Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand the molecular pathophysiology of depression, it is still unclear. Current treatments for depression are inadequate for many individuals, because of limited effectiveness, delayed efficacy (usually two weeks), and side effects. Consequently, novel drugs with increased speed of action and effectiveness are required. Ketamine has shown to have rapid, reliable, and long‐lasting antidepressant effects in treatment‐resistant MDD patients and represent a breakthrough therapy for patients with MDD; however, concerns regarding its efficacy, potential misuse, and side effects remain. In this review, we aimed to summarize molecular mechanisms and pharmacological treatments for depression. We focused on the fast antidepressant treatment and clarified the safety, tolerability, and efficacy of ketamine and its metabolites for the MDD treatment, along with a review of the potential pharmacological mechanisms, research challenges, and future clinical prospects.