Pharmacological Treatment Of Depression Research Articles

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.

Does pharmacological treatment of depression in people with a primary brain tumour bring any benefits? A Cochrane Review summary with commentary.

Persons with primary brain tumour can suffer from depression. Depression may hinder rehabilitation intervention leading to further deterioration of patient's health and functioning. The Cochrane Review aimed to assess the effectiveness and adverse effects of pharmacological treatment of depression in people with a primary brain tumour. A Cochrane Review by Beevers et al. was summarized with comments. The review did not find any eligible studies from the 2090 studies screened which included randomized controlled trials, cohort studies and case-control studies. There is no high-quality evidence as to whether pharmacological treatments for depression in people with primary brain tumours are either effective or harmful.

Antidepressants in epilepsy

IntroductionDepressive disorders are one of the most frequent psychiatric comorbidity in epilepsy and they have a negative impact on the quality of life. Depression often requires antidepressant treatment. However, it is often left untreated in people with epilepsy, in part due to fear that antidepressants could cause seizures.ObjectivesThe goal of this study was to do a review and describe the evidence of the efficacy and safety of pharmacological treatment for depression in epilepsy.MethodsReview of literature sources were obtained through electronic search in PubMed database with special focus in papers published in the last 5 years.ResultsThe existing evidence of the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is still limited and response rate was highly variable. It is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. As the first line of treatment you should consider the use of SSRI or IRSN. The improvement in depressive symptoms ranged from 25% to 82% according to the different studies and depending on the antidepressant administered. A review of the literature indicates that the risk of antidepressant-associated seizures is low although some antidepressants such as amoxapine or bupropion are not recommended.ConclusionsThere are few comparative data to support the choice of antidepressant drug or drug class in terms of efficacy or safety for the treatment of people with epilepsy and depression. It would be important to design controlled trials of antidepressants in large cohorts of participants with epilepsy and clinically significant depression.DisclosureNo significant relationships.

0166 The Role of Vitamin B12 Supplementation in the Association between Depression Symptoms and Daytime Sleepiness

Abstract Introduction A substantial body of literature has demonstrated an association between depression and sleep disturbances. While depressive symptoms are strongly associated with limited sleep duration and quality, high depressive symptomology has been also linked to symptoms of hypersomnolence. Vitamin B12 supplementation is associated with reduced risk of depression and the enhancement of pharmacological treatment for depression, but less is known about the role of vitamin B12 on sleep disturbances associated with depressive symptoms. Thus, our current study examined vitamin B12 intake as a moderator of depression and daytime sleepiness in a national sample of adults. Methods The sample consisted of 5,553 adults who completed the 2017-18 National Health and Nutrition Examination Survey (M age=49.8, SD=18.6; 51.7% female). Participants reported on prescription and nonprescription dietary supplement use in the last 30 days, sleep habits and disorders adapted from the Munich Chronotype Questionnaire, and completed the Patient Health Questionnaire-9 for depression screening. All measures were administered by trained interviewers. A moderation analysis was performed using R statistical programming. The analysis controlled for age, gender, ethnicity, sleep duration, and other B-complex vitamins (e.g., B1, B2, B3, and B6). Results Depressive symptoms were significantly associated with greater daytime sleepiness (b=.06, p <.001). Furthermore, there was a significant interaction between depressive symptoms and vitamin B12 consumption (b=-.002, p=.003, R2=.12). Higher vitamin B12 consumption buffered the relationship between depressive symptoms and daytime sleepiness. In contrast, a stronger positive relationship between depressive symptoms and daytime sleepiness was observed among participants with lower Vitamin B12 consumption. Thus, the findings suggest that consuming vitamin B12 may be beneficial for counteracting daytime sleepiness associated with depression. Conclusion Findings from the current study suggest that vitamin B12 supplementation provides a small, but significant buffering effect on the relationship between depressive symptoms and daytime sleepiness. Although existing pharmacological and behavioral interventions for sleep and depression are clinically effective, vitamin B12 intake may be an additional modifiable behavior that could increase prognosis of treatment. Given the very modest interaction effect, further Support (If Any)

Neuroanatomical, Biochemical, and Functional Modifications in Brain Induced by Treatment with Antidepressants

Depression is a psychosomatic disorder. The pharmacological treatment of depression has been based on the pathophysiology of deficiency in monoamines, mainly serotonin and noradrenaline. All approved antidepressants designed to enhance central monoaminergic tone possess many limitations such as 2 to 5weeks delay in response, a limited clinical efficacy, and severe side effects. Since the pathophysiological aberrations associated to depression go beyond monoamines, the development of better antidepressants would depend on the identification and understanding of new cellular targets. The pharmacological studies of antidepressants, however, indicate the involvement of the blockade of neuronal uptake systems for norepinephrine and serotonin (5-hydroxytryptamine) including receptors for neurotransmitters. Many preclinical studies have suggested that hippocampus containing abundant agonists such as5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG) is critically involved in the mechanism of action of antidepressants. DG being a part of hippocampus possibly contributes to the brain functions such as formation of new sporadic memories. It is reported that antidepressants cause significant alterations in the structure and function of different brain regions in order to finally lead to their therapeutic effects. This review presents an overview of structural changes in the brain during depression; different neurobiological theories and novel drug development; strategy of augmentation with combinatorial therapy; receptors and targets of actions of antidepressants; and involvement of key signaling factors in the regulation of depression, pharmacology, metabolism, and the underlying principles involved in displaying how the application of antidepressants modulates the structure and function of the brain.

Review of pharmacological treatment of depression in patients with primary brain tumour and proposal of modification in management strategy

This brief paper describes the challenges with treatment of depression in brain tumour patients particularly in the absence of any currently accepted guidelines for treating this perculiar subset of patients. The proposal offered here is to move to pharmacologic treatment with other modalities in a methodical pattern only after surgical intervention. This is because simply treating with medications based on physician / patient choice as currently recommended may not achieve optimal results in majority of cases in view of the multiple aetiological factors that interplay. A flowchart treatment plan is presented to guide management in a streamlined fashion.

Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. (“GUIDED”), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian “GAPP-MDD” RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).

Symptom Management in Oncology: Depression and Anxiety.

To describe nursing symptom management of depression and anxiety in patients with cancer. These include journal articles, online resources, and personal experience in providing mental health care to cancer survivors with depression and/or anxiety. Nurses can provide emotional support for patients with cancer and depression or anxiety. Nurses can become aware of nonpharmacologic and pharmacologic treatment for depression and anxiety to help patients decrease their emotional distress. Nurses can also refer patients with cancer to psychiatric professionals and emotional support programs. Nurses do not have to be experts in psychiatry to manage symptoms of depression and anxiety in patients with cancer. Nurses can listen empathically, guide patients in relaxation techniques, and advocate if they need psychotropic medications or psychiatric referrals.

Efficacy in the treatment of depressive disorders

Introduction Depression, being the most disabling disease in the world and presenting high morbidity and mortality, requires an effective treatment to ensure the maintenance of the patients' quality of life. About a third of patients do not respond adequately to antidepressant treatment. New pharmacological therapies are being approached in order to reduce the unfavorable outcomes resulting from this pathology. Objective To develop a systematic review of the literature on the new possibilities of pharmacological treatments for depression in the last four years. Method A systematic review was carried out following the PRISMA protocol (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). We have included studies on the effectiveness of new pharmacological therapies in patients with major depressive disorder and treatment-resistant depression. Results In the treatment of the major depressive disorder (MDD), the use of brexpiprazole 1 mg/day in addition to the usual antidepressant treatment (ADT) resulted in significant improvement in the main symptoms. Already referring to treatments for treatment-resistant depression (TRD): nasal esketamine proved beneficial in the short term, intravenous (IV) ketamine also appears as an effective therapy. Conclusion The use of brexpiprazole 1 mg/day associated with an antidepressant, and the use of lactobacilli represent a new option for those with MDD. In addition, both ketamine, riluzole, and cariprazine appear as new hopes for those who have not yet achieved remission of the depressive disorder with the use of more than two antidepressants

A neural network approach to optimising treatments for depression using data from specialist and community psychiatric services in Australia, New Zealand and Japan.

This study investigated the application of a recurrent neural network for optimising pharmacological treatment for depression. A clinical dataset of 458 participants from specialist and community psychiatric services in Australia, New Zealand and Japan were extracted from an existing custom-built, web-based tool called Psynary . This data, which included baseline and self-completed reviews, was used to train and refine a novel algorithm which was a fully connected network feature extractor and long short-term memory algorithm was firstly trained in isolation and then integrated and annealed using slow learning rates due to the low dimensionality of the data. The accuracy of predicting depression remission before processing patient review data was 49.8%. After processing only 2 reviews, the accuracy was 76.5%. When considering a change in medication, the precision of changing medications was 97.4% and the recall was 71.4% . The medications with predicted best results were antipsychotics (88%) and selective serotonin reuptake inhibitors (87.9%). This is the first study that has created an all-in-one algorithm for optimising treatments for all subtypes of depression. Reducing treatment optimisation time for patients suffering with depression may lead to earlier remission and hence reduce the high levels of disability associated with the condition. Furthermore, in a setting where mental health conditions are increasing strain on mental health services, the utilisation of web-based tools for remote monitoring and machine/deep learning algorithms may assist clinicians in both specialist and primary care in extending specialist mental healthcare to a larger patient community.

Atypical antipsychotics in major depressive disorder

The antipsychotics are used among pharmacological treatment of depression. Atypical antipsychotics have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid, cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects, including hyperglycemia, weight gain, cholesterol levels, and extrapyramidal symptoms. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all second‐generation antipsychotics will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e. produce a depression-like clinical picture). The antidepressant effect appears to be unique to some agents. Also, despite the availability of a large number of antidepressants of different classes, a significant portion of patients do not achieve remission, and treatment resistance is common. This paper reviews the antipsychotics that are effective for the treatment of depressive disorders, and the pharmacological mechanisms of antipsychotics in the treatment of depressive disorders.

The association of depression and anxiety with treatment outcomes in patients with rheumatoid arthritis - a pooled analysis of five randomised controlled trials.

Background:Rheumatoid arthritis (RA) is an inflammatory autoimmune condition associated with an increased risk of developing depression and anxiety. Depression and anxiety are associated with worse outcomes in RA, but the magnitude of the effect of each condition on RA outcomes is unclear. It is also unknown how pharmacological treatment of depression affects RA outcomes.Objective:The primary aim of this study was to investigate the association of comorbid depression and anxiety with remission in patients with RA. Secondary aims were to determine the association between comorbid depression and anxiety on patient-reported outcomes and the relationship between concomitant use of antidepressants and remission in patients with depression.Design:Data from patients with moderate to severe RA were pooled from five randomised controlled trials investigating tocilizumab and conventional synthetic disease-modifying agents.Methods:Remission was defined as a clinical disease activity index (CDAI) of ⩽2.8 and simple disease activity index (SDAI) of ⩽3.3. The association between the time to reach remission and depression and anxiety was analysed using Cox proportional hazard analysis.Results:Individual patient data were available from 5502 subjects, of whom 511 had depression, 236 had anxiety and 387 were using antidepressants. Depression was significantly associated with reduced remission [adjusted HR (95% CI): 0.62 (0.48–0.80), p < 0.001 and adjusted HR (95% CI): 0.59 (0.44–0.79), p < 0.001] using CDAI and SDAI, respectively. Depression was associated with a lower likelihood of achieving more subjective outcomes (⩽1 physician global assessment, ⩽1 patient global assessment) and ⩽1 28-swollen joint count, but not ⩽1 28-tender joint count or C-reactive protein measurement. Treatment with antidepressants did not improve outcomes for patients with depression. Anxiety was not significantly associated with RA remission.Conclusion:Comorbid depression, but not anxiety, was associated with less frequent remission. Concomitant antidepressant use was not associated with improvements in RA outcomes in patients with depression.

Psychological and pharmacological interventions for depression in patients with coronary artery disease.

Psychological and pharmacological interventions for depression in patients with coronary artery disease.

The effects of COVID-19 on the dispensing rates of antidepressants and benzodiazepines in Canada.

BackgroundPopulation studies have shown that rates of depressive and anxious symptoms have increased as a result of COVID‐19. We analyzed trends in the dispensing rates of antidepressants and benzodiazepines in Canada to determine whether the pandemic has caused changes in rates of pharmacological treatment for depression and anxiety.MethodsWe conducted a population‐based, cross‐sectional time‐series analysis of antidepressants and benzodiazepines dispensed monthly by Canadian community pharmacies between January 2017 and December 2020. We used March 2020 as the intervention month to determine if there were any significant changes in the national rate of antidepressant and benzodiazepine tablets dispensed as the result of the COVID‐19 pandemic.ResultsThere was a temporary reduction in the dispensing rate of antidepressants in April 2020 (from 489 tablets per 100 in March 2020 to 356 tablets per 100 in April 2020; p ≤ .0001); however, the rate returned to its previous level by August 2020. There were no detectable deviations in benzodiazepine dispensing after the declaration of the state of emergency in Ontario.ConclusionsDespite the increased reporting of depressive and anxious symptoms during the COVID‐19 pandemic, there have been no changes in the dispensing trends of medications used to treat these disorders. As the pandemic continues to evolve, future research is needed to monitor the prevalence of depression and anxiety, and associated medication use, in the Canadian population.

A Brief, Individualized Exercise Program at Intensities Below the Ventilatory Threshold Exerts Therapeutic Effects for Depression: A Pilot Study.

Due to the fact that existing pharmacological treatments for depression are not ideal, effort has been devoted to the development of complementary, alternative therapies such as physical exercise. The antidepressant effect of exercise is well documented. However, current recommendations and prescriptions of exercise may be too demanding for depressed patients, as some complain about the design of exercise programs and depression is associated with reduced motivation and capacity to exercise. Therefore, appropriately designed, patient-friendly exercise programs may prove critical for the long-term maintenance and therapeutic effects of exercise. In this pilot study, we developed an exercise program based on patients’ individual level of ventilatory threshold (VT), a submaximal index of aerobic capacity measured by Cardiopulmonary Exercise Testing (CPX). Compared to traditional measures, CPX provides more trustable indices of aerobic capacity and more homogenous exercise prescriptions. The main episode of the program consisted of 15–25 min of cycling twice a week at an intensity that approached but never went higher than subjects’ VT (considered low to moderate in intensity). We found that in patients diagnosed with major depressive disorder or persistent depressive disorder (n = 8), the program resulted in a significant reduction in depressive symptoms at week 8, which was maintained at week 16. Meanwhile, patients’ social functioning, quality of life, and cognitive functions improved. Although we used a single arm, non-randomized design, our results suggest that even a brief, low to moderate intensity exercise program may exert therapeutic effects for depression and CPX may be a useful tool for exercise prescriptions.

Is there a place for cellular therapy in depression?

Although efforts have been made to improve the pharmacological treatment of depression, approximately one-third of patients with depression do not respond to conventional therapy using antidepressants. Other potential non-pharmacological therapies have been studied in the last years, including the use of mesenchymal stem cell therapies to treat depression. These therapies are reviewed here since it is clinically relevant to develop innovative therapeutics to treat psychiatric patients. Experimental data corroborate that mesenchymal stem cell therapy could be considered a potential treatment for depression based on its anti-inflammatory and neurotrophic properties. However, some clinical trials involving treatment of depression with stem cells are in progress, but with no published results. These studies and other future clinical investigations will be crucial to define how much mesenchymal stem cells can effectively be used in psychiatric clinics as a strategy for supporting depression treatment.