3D-QSAR Design of New Escitalopram Derivatives for the Treatment of Major Depressive Disorders

Antidepressants are psychiatric agents used for the treatment of different types of depression being at present amongst the most commonly prescribed drug, while their effectiveness and adverse effects are the subject of many studies and competing claims. Having studied five QSAR models predicting the biological activities of 18 antidepressants, already approved for clinical treatment, in interaction with the serotonin transporter (SERT), we attempted to establish the membrane ions’ contributions (sodium, potassium, chlorine and calcium) supplied by donor/acceptor hydrogen bond character and electrostatic field to the antidepressant activity. Significant cross-validated correlation q2 (0.5–0.6) and the fitted correlation r2 (0.7–0.82) coefficients were obtained indicating that the models can predict the antidepressant activity of compounds. Moreover, considering the contribution of membrane ions (sodium, potassium and calcium) and hydrogen bond donor character, we have proposed a library of 24 new escitalopram structures, some of them probably with significantly improved antidepressant activity in comparison with the parent compound

Folate Augmentation of Treatment – Evaluation for Depression (FolATED): protocol of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Clinical depression is common, debilitating and treatable; one in four people experience it during their lives. The majority of sufferers are treated in primary care and only half respond well to active treatment. Evidence suggests that folate may be a useful adjunct to antidepressant treatment: 1) patients with depression often have a functional folate deficiency; 2) the severity of such deficiency, indicated by elevated homocysteine, correlates with depression severity, 3) low folate is associated with poor antidepressant response, and 4) folate is required for the synthesis of neurotransmitters implicated in the pathogenesis and treatment of depression.</p> <p>Methods/Design</p> <p>The primary objective of this trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary and secondary care. Secondary objectives are to evaluate the cost-effectiveness of folate augmentation of antidepressant treatment, investigate how the response to antidepressant treatment depends on genetic polymorphisms relevant to folate metabolism and antidepressant response, and explore whether baseline folate status can predict response to antidepressant treatment.</p> <p>Seven hundred and thirty patients will be recruited from North East Wales, North West Wales and Swansea. Patients with moderate to severe depression will be referred to the trial by their GP or Psychiatrist. If patients consent they will be assessed for eligibility and baseline measures will be undertaken.</p> <p>Blood samples will be taken to exclude patients with folate and B12 deficiency. Some of the blood taken will be used to measure homocysteine levels and for genetic analysis (with additional consent). Eligible participants will be randomised to receive 5 mg of folic acid or placebo. Patients with B12 deficiency or folate deficiency will be given appropriate treatment and will be monitored in the 'comprehensive cohort study'. Assessments will be at screening, randomisation and 3 subsequent follow-ups.</p> <p>Discussion</p> <p>If folic acid is shown to improve the efficacy of antidepressants, then it will provide a safe, simple and cheap way of improving the treatment of depression in primary and secondary care.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN37558856</p

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Pharmacotherapy prescribing patterns in the treatment of bipolar disorder in an outpatient population at Tara hospital

A research report submitted to the Faculty of Medicine, University of the Witwatersrand Medical School, in partial fulfilment of the requirements for the Degree Masters of Medicine in the branch of Psychiatry, Johannesburg, August, 2015Introduction Pharmacotherapy is a key component in the management of bipolar disorder. Whilst one might aim for fewer agents, not all patients with bipolar disorder can be stabilized with monotherapy and combination treatment (polypharmacy) is increasingly used to manage patients in clinical practice. Mood stabilizers have traditionally been prescribed as monotherapy, however the use of atypical antipsychotic agents is seen in clinical practice with various such agents approved for such usage. Combination treatment with an antipsychotic, preferably an atypical antipsychotic together with a standard mood stabilizer is also noted in clinical practice as well as recommended by guidelines. Bipolar patients managed in a specialist psychiatric setting have a greater chance of being managed with polypharmacy than in a general practice setting. The use of polypharmacy may also be attributed to receiving treatment in an academic environment. This current study was based on the application of diagnostic criteria and principles of the Diagnostic and Statistical Manual of Mental Disorders version IV TR (DSM IV TR), published by the American Psychiatric Association and The International Classification of Diseases version 10 (ICD 10), published by the World Health Organisation. Aims The study aims to describe the range and frequency of medications used in the management of bipolar bisorder in a specific setting as well as describe the nature and frequency of monotherapy versus polypharmacy use. Hypothesis The study hypothesized that the majority of patients attending the specialist / academic psychiatric outpatient clinic at Tara Hospital would be prescribed polypharmacy and that antipsychotics (typical or atypical) would be prescribed in combination with standard mood stabilizers in the majority of cases. Method The study took the form of a retrospective patient file review. The clinical files were for patients attending the Tara Hospital psychiatric outpatient clinic. The files of every patient who attended the clinic at least once in 2009 were screened and included in the study where the recorded ICD 10 code corresponded with a bipolar disorder subtype or a single manic or hypomanic episode. Where the recording of the ICD 10 code was missing or incomplete further scrutiny of the clinical notes enabled the researcher to establish a diagnosis of bipolar disorder using the ICD 10 and/ or DSM IV TR diagnostic criteria and therefore include the patient file in the study. Other necessary information was obtained by reviewing clinical notes as well as the prescription written on the last patient visit for 2009. Results The study found that the majority of patients (93.8%) were prescribed polypharmacy, with 3.2 the mean number of psychotropic medications prescribed per patient. Lithium was prescribed in 34.3% of patients. Sodium valproate was prescribed in 37.1% of patients. Eighty three point eight percent (83.8%) of the patients were prescribed at least one standard mood stabilizer. The atypical antipsychotics (46.6%) were prescribed more frequently than the typical antipsychotics (16.5%). Lamotrigine (31.8%) was the preferred novel anticonvulsant and the selective serotonin reuptake inhibitors (SSRI’s) were the most commonly prescribed antidepressant (28.9%). Clonazepam (26.8%) was the most frequently prescribed benzodiazepine add-on. The use of combination treatment to manage bipolar disorder was the rule rather than the exception. There was however much variety in the combinations used with no particular combination being prescribed in the majority of patients. Forty seven percent (47%) of the combinations used included a standard mood stabilizer and a typical or atypical antipsychotic. Conclusion The current study provides preliminary data on the prescribing patterns in bipolar disorder in a specialist psychiatric clinic within an academic complex in South Africa. The findings are in keeping with international studies and highlights that polypharmacy and combination treatment in the management of bipolar disorder is the norm in such settings. There is a large variation in clinician practices and much variety seen in the combinations of medications used to treat bipolar disorder despite the availability and use of treatment guidelines. This is perhaps because bipolar disorder is such a complex disorder and that most of the treatment recommendations are based on limited data. Treatment guidelines have emerged in order to attempt to standardize treatment and provide clinicians with algorithms to utilize and apply research findings in daily clinical practice. Further study into the effective prescribing principles for bipolar disorder is necessary

Quality prescribing for antidepressants: guide for improvement 2024 to 2027

The prescribing of antidepressants continues to increase in Scotland, with many people receiving antidepressants for two years or more. This may be appropriate for some individuals, but it is important that ongoing treatment is reviewed regularly and that the risks and benefits of treatment are discussed. Treatment goals should be agreed with individuals, both at the time of initiation and when reviewing medication, and treatment plans should take a holistic approach to management and support. These should include discussions of non-pharmacological and wider community support options where these are available and indicated.This prescribing advice is primarily intended to support and encourage the appropriate use of antidepressants for mental health and physical conditions, as part of the wider treatment options available. It supports appropriate initiation of antidepressants, regular and proactive reviews, reduction and stopping of treatment where it is ineffective or where treatment courses have been completed. Regular person-centred reviews can optimise the care of those receiving antidepressants and minimise avoidable medicine-related harm. These reviews can also support and enable appropriate continuation of antidepressant treatment where this is required, using the 7-Steps person-centred review approach

The clinical effectiveness of evidence-based interventions for depression: A pragmatic trial in routine practice

Abstract BACKGROUND: Controversy persists about how effectively empirically-supported treatments for major depression work in actual clinical practice as well as how patients choose among them. We examined the acute phase effectiveness of cognitive therapy (CT), interpersonal psychotherapy (IPT), and combined psychotherapy-pharmacotherapy (PHT) in a naturalistic setting, allowing patients their choice of treatment. METHODS: The study compared CT (n=63), IPT (n=56), CT-PHT (n=34), and IPT-PHT (n=21) for 174 subjects with major depression in a secondary care mood disorders clinic. Patient preference, rather than randomization, determined treatment selection. The Beck Depression Inventory-II (BDI) was the primary outcome variable. Exclusion criteria were minimal. RESULTS: All treatments were associated with a reduction in depressive symptoms, with a 35% remission rate by week 26. Overall improvement was well within ranges reported in efficacy trials. On average, treatment effects of the different interventions straddled the same range, but moderation analyses revealed that BDI scores dropped faster in the first 16 weeks in patients who received CT alone than patients who received CT and pharmacotherapy, a pattern not found in patients who received IPT (with or without pharmacotherapy). LIMITATIONS: Limitations consist of a modest sample size, choice of treatment was made by participants which may have been influenced by many sources, and the absence of a non-active control group. CONCLUSIONS: This study supports the effectiveness of empirically-supported antidepressant treatments selected by patients in routine settings, and provides an indication that speed of therapeutic response may vary amongst treatments

Major Depressive Disorder as a Condition Negatively Impacting Both Mental and Physical Functioning. What to Do When There Is Treatment Resistance?

The objective of this article is to assess the efficacy and safety of diverse therapeutic strategies for treatment-resistant depression (TRD), encompassing both pharmacological and non-pharmacological interventions. Additionally, the review identifies potential avenues for future research within this domain. The article compares the results of selected studies. We conducted a literature search in November of 2024, using PubMed. Six studies were identified, chosen, and appraised. Among these studies, three are systematic reviews and three are narrative literature reviews. If&nbsp; it comes to treatment efficacy studies have demonstrated the effectiveness of several strategies. Ketamine and esketamine have shown rapid and substantial efficacy in mitigating the symptoms of TRD. Augmentation with aripiprazole and quetiapine has also been found to enhance the response to antidepressant treatment. The combination of olanzapine and fluoxetine is effective for treating TRD, however, it may be associated with metabolic side effects. Augmentation with lithium, triiodothyronine (T3), and lamotrigine shows promising results, though further research is required to fully evaluate their efficacy and safety in TRD management. The management of TRD is associated with several challenges. These include the absence of a standardized definition and grading system, which impedes the comparison of research outcomes. The multifactorial nature of TRD further complicates the development of a universal treatment strategy. Summarizing, there are several treatment strategies available for TRD, however, the most effective approach should be personalized for each patient. Ongoing research is critical to advancing our understanding of TRD and developing more effective therapeutic options