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Transcranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that is receiving increasingly attentionTranscranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that is receiving increasingly attentionfor new clinical applications. Through electromagnetic induction cortical activity can be modulated and therapeuticeffects can be achieved in a variety of psychiatric and neurological conditions. According to the World Health Organization(WHO) depression is the most disabling disease in the world and 350 million people suffer from depression globally. Majordepression is the most common disorder to be treated with TMS and the first mental disorder for which TMS received approvalfrom the US Food and Drug Administration (FDA). We here introduce the basic principles of TMS, discuss the latestdata on safety and side effects, and present various TMS treatment protocols as well as treatment response predictors inmajor depressive disorder.Despite major advances in the treatment of mood disorders, major depression, a common mental disorder, remains a serious public health problem. Electroconvulsive therapy (ECT) regardless of the anesthetic agent used, is the most effective form of treatment in major depression and the gold standard therapy in treatment resistant depression. Ketamine is one of the anesthetic drugs approved by the Αmerican Psychiatric Association Task Force Report for use in ECT. However, it has been used infrequently as an anesthetic in ECT. The initial reports suggested that ketamine has antidepressant properties resulting in rapid antidepressant response when administered in subanesthetic dose (0.5 mg/kg) in slow intravenous injection in patients suffering from depression. In recent trials has been reported that ketamine as the only anesthetic or as an adjunctive to another anesthetic agent may enhance the antidepressant effect of ECT either by increasing efficacy or by producing a rapid antidepressant response. ECT with ketamine may also cause less cognitive side effects. The most notable limitations of these studies are the small number of patients enrolled and several methodological differences (patients characteristics, electrode placements, titration method, anesthetic agent used with ketamine). The results of the clinical trials have been summarized in six meta-analysis and suggest that ketamine when used as a sole anesthetic agent or as an adjunctive anesthetic in ECT may accelerates the antidepressant response but does not augment ECT efficacy. It also does not improve the cognitive profile of the treatment. Larger, double-blind randomized controlled trial are needed for a definite conclusion.Treatment-Resistant Depression (TRD) calls for the development of effective interventions for mood elevation and stabilization. Recently, both ketamine and its S-enantiomer (esketamine) have been investigated with successful clinical trials demonstrating effectiveness in TRD. More specifically, in 2019, intranasally administered esketamine, as opposed to the more effective intravenous ketamine, has been approved by the FDA as a treatment option for TRD. Treatment with esketamine, however, potentially comes with major adverse effects, including risk of psychosis, the possibility of abuse and dependence after repeated use, transient but non-negligible change in blood pressure and the heart rate, and potential toxicity on the urothelium and the liver. These risks are minimized when treatment is kept within the recommended dose range and the drug is administered by experienced medical personnel. Nevertheless, these risks appear to be offset by the effectiveness of esketamine in a wide range of depressive symptoms, such as anhedonia, anxiety, cognitive impairment, suicidality, and general dysfunction. This review highlights the need for more phase 4 clinical studies to evaluate esketamine's performance in real life, including long-term effectiveness and risk studies.Τhe Food and Drug Administration (FDA) approval of the use of S-ketamine in the form of nasal spray for the treatment of treatment-resistant depression, launched a new category of therapeutic agents in psychiatry. garsorasib molecular weight A well-known class of substances, psychedelics, are introduced with a 30-year delay in the treatment of mental disorders. Intravenous ketamine infusion has been studied in the treatment of depression since the 1990s. Here we present the current protocol for the treatment of ketamine infusion in patients with treatment-resistant depression and related clinical information.The lack of utter efficacy and fast action of commonly used antidepressants that selectively target the monoaminergic neurotransmission has led to the exploration of ketamine's actions. Ketamine's antidepressant effect was firstly described in 1973 and nowadays its therapeutic value as a fast- and long- lasting antidepressant has been extensively established. Ketamine is an antagonist of the N-Methyl-D-aspartate receptor (NMDAR) and its main mechanism of action via NMDAR inhibition expressed in GABAergic (gamma-Aminobutyric acid, GABA) interneurons may be relayed to its antidepressant effects. This review aims to describe the pharmacokinetic and pharmacodynamic profile of ketamine when used for treatment-resistant depression. Moreover, ketamine is a racemic mixture consisting of two enantiomers, R- and S- ketamine. We describe the pharmacology of esketamine, along with the guidelines for effective and safe intranasal administration of esketamine. Lastly, this review presents sex differences in preclinical and clinical studies of ketamine and esketamine administration.Major depressive disorder is a serious mental health disorder of high prevalence and the leading cause of disability worldwide. While there are several classes of therapeutic agents with proven antidepressant efficacy, only about 40-60% of patients respond to initial antidepressant monotherapy, and 30-40% of patients may even show resistance to treatment even under optimal antidepressant pharmacotherapy. Despite the existence of international guidelines, there are still no clear and widely accepted treatment algorithms, no established predictive biomarkers of response to treatment, while the management treatment- resistant depression is usually based on clinical experience. The present article offers a brief narrative review of studies published so far on the predictive quality of various blood-based peripheral biomarkers with respect to response to pharmacological, stimulation or behavioral treatment in patients with treatment-resistant depression. To summarize the results, there does not yet appear to be anpatient subgroups, the achievement of higher rates of stable remission, and the development of new precision drugs with minimal side effects.Depression represents the predominant mood pole in bipolar disorder. Bipolar depression typically has a poor response to antidepressant medication, and also involves the risk of polarity shifts, induction of mixed states, and / or rapid cycle induction. The diagnosis of bipolar depression can be delayed by 8 to 10 years. The reason for this delay is mainly the fact that both manic and hypomanic episodes appear lately in the course of the disorder. It is therefore necessary to diagnose this clinical entity as early as possible versus monopolar depression in order to treat it more effectively. This differential diagnosis is based on certain clinical features of bipolar depression, which are often difficult to be distinguished from those of monopolar depression and therefore it is necessary to know specific criteria that differentiate them to some extent qualitatively and / or quantitatively. Such characteristics are daily mood swings, multiple physical complaints, psychomotor retardation, psychotic elements (delusions and perceptual disorders mood congruent or noncongruent), the disturbance of certain bodily functions, including circadian rhythms, sexual desire, appetite, and disorders of sleep architecture. The treatment of bipolar depression is based on the options known from monopolar depression (such as the use of antidepressants, antipsychotics, and certain antiepileptic agents) and their combinations, while in recent years it has been enriched with new pharmaceutical agents and non-pharmacological approaches. New glutaminergic regulators dominate the new pharmacological agents' research, and among them the antidepressant effect of ketamine and esketamine at sub-anesthetic doses is being extensively investigated during recent years. Non-pharmacological approaches include methods such as electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS), sleep deprivation, and phototherapy.Treatment resistant depression is associated with serious and persistent symptomatology, chronic course, reduced quality of life, high rates of comorbidity with medical conditions or other mental disorders, increased indirect health care cost, increased suicidality and risk for hospitalization, negative impact to patients' functioning and occupation and poor treatment outcomes in general. The concept of treatment resistant depression emerged in the 1970s to describe a group of patients suffering from major depressive disorder who failed to reach remission of symptoms after at least two trials with antidepressant (efficient regarding dosage, compliance, and duration). Despite the introduction of many antidepressants over the following years, a large proportion of depressed patients fail to respond to available treatments, and this constitutes a continuing therapeutic challenge.Treatment resistant depression (TRD) is a serious public health problem. It is estimated that around 20- 40% of patients with a major depressive episode (whether monopolar or bipolar) do not exhibit clinical response to the current treatment with antidepressants, that is at least 50% decline in the symptoms scale. Furthermore, about half of the patients with symptom amelioration present residual symptoms which continue to negatively affect their functioning and increase the chance of relapse. Therefore, only 20-40% of patients (36.8% in STAR*D)1 who receive therapy for a major depressive episode for the first time exhibit remission (i.e., at least 70% decrease in symptom severity or HAMD score ≤7/MADRS score ≤10)2 - which is the goal of current treatments. Even when remission is achieved, though, there is often a long way to recovery and to the patient's return to the prior state of occupational and social functioning. Moreover, long-term medical treatment is needed in order to achieve and maintain the above. discussed in this Supplement issue of Psychiatriki.9.In this article, we focus on a biobjective hot strip mill (HSM) scheduling problem arising in the steel industry. Besides the conventional objective regarding penalty costs, we have also considered minimizing the total starting times of rolling operations in order to reduce the energy consumption for slab reheating. The problem is complicated by the inevitable uncertainty in rolling processing times, which means deterministic scheduling models will be ineffective. To obtain robust production schedules with satisfactory performance under all possible conditions, we apply the robust optimization (RO) approach to model and solve the scheduling problem. First, an RO model and an equivalent mixed-integer linear programming model are constructed to describe the HSM scheduling problem with uncertainty. Then, we devise an improved Benders' decomposition algorithm to solve the RO model and obtain exactly optimal solutions. Next, for coping with large-sized instances, a multiobjective particle swarm optimization algorithm with an embedded local search strategy is proposed to handle the biobjective scheduling problem and find the set of Pareto-optimal solutions.