Background: clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: we selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together. Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

In modern society, depression is one of the most common mental illness; however, its pathophysiology is not yet fully understood. A great body of evidence suggests that depression causes changes in neuroplasticity in specific regions of the brain which are correlated to symptom severity, negative emotional rumination as well as fear learning. Depression is correlated with atrophy of neurons in the cortical and limbic brain regions that control mood and emotion. Antidepressant therapy can exhibit effects on neuroplasticity and reverse the neuroanatomical changes found in depressed patients. The investigation of fast-acting agents that reverse behavioral and neuronal deficiencies of chronic depression, especially the glutamate receptor antagonist NMDA ketamine, and the cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are of real interest in current research. Actual medication such as serotonin (5-HT) selective reuptake inhibitor (SSRI) antidepressants, require weeks to months of administration before a clear therapeutic response. The current review aimed to underline the negative effects of depression on neuroplasticity and present the current findings on the effects of antidepressant medication.

No abstract

Electroconvulsive therapy (ECT) is a technique that has been used since 1938 to treat several psychiatric disorders as a replacement for chemically induced seizures. Despite its history of stigma, controversy and low accessibility, ECT is found to be beneficial and efficient in severe cases of depression where medication fails to bring results. Titration tables developed over time, based on evidenced-based medicine, have made this treatment technique safe and, in some cases, the first choice of treatment. The aim of the review was to summarize the research conducted on the efficacy of ECT on major depressive disorder and variables studied such as technique, comorbidities and medication as well as the effects and outcomes of this procedure. At the same time, the application and correlations with other psychiatric and neurological disorders, including catatonia, agitation and aggression in individuals with dementia, schizophrenia, and epilepsy were assessed. There are no statistically demonstrated effects due to the fact that a small number of moderate-quality studies have been published; however, the combination of ECT technique with standard medication and care, can improve patient outcome. Furthermore, with regard to ECT, widespread and robust volume changes in both cortical and subcortical regions have been shown. Antidepressant response and volumetric increases appear to be limited by the specific neuroplasticity threshold of each patient.