Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part II: A Review of Fatal Outcomes in US Pharmacovigilance Data and Proposed Changes.

Purpose/background: This is the second part of a 2-part article that proposes improving the United States (US) clozapine package insert. Part II focuses on fatal outcomes and the 5 boxed warnings, 4 specifically for clozapine: severe neutropenia, seizure, orthostatic hypotension and myocarditis, and 1 for all antipsychotics (elderly with dementia).

Methods: US reports to the World Health Organization's global pharmacovigilance database were analyzed from clozapine's introduction to January 15, 2023.

Letter to the FDA Proposing Major Changes in the US Clozapine Package Insert Supported by Clozapine Experts Worldwide. Part I: A Review of the Pharmacokinetic Literature and Proposed Changes.

Purpose/background: Clozapine was approved in the United States (US) using 1989 regulations and knowledge. After 30 years, many sections of the US package insert (PI) are outdated.

Methods: We comprehensively reviewed the literature to propose PI updates.

Pimavanserin treatment increases plasma brain-derived neurotrophic factor levels in rats.

Background: Pimavanserin, a serotonin 5HT-2A receptor inverse agonist is the first-line, FDA-approved treatment of hallucinations and delusions associated with Parkinson's Disease psychosis (PDP), which occurs in up to 50% of PD patients. The neurobiological mechanism underlying the therapeutic effectiveness of Pimavanserin in PDP remains unknown. Several earlier studies have shown that treatment with 5HT-2A antagonists and other drugs acting on the serotonergic system such as SSRIs increase Brain derived neurotrophic factor (BDNF) levels in rodents.

The role of the insula in cognitive impairment of schizophrenia.

Cognitive impairment is one of the core clinical symptom domains of schizophrenia. Research shows that cognitive deficits in this neuropsychiatric syndrome is associated with neurodevelopmental pathology affecting multiple brain regions such as the dorsolateral prefrontal cortex, the hippocampus and the parietal lobe. The insula is a relatively small structure that is highly connected with several brain regions as well as multiple brain networks.

The Association of the Gut Microbiota with Clinical Features in Schizophrenia.

The connection between gut microbiota and schizophrenia has become a fertile area of research. The relationship is bidirectional and quite complex, but is likely to lead to practical clinical applications. For example, commensal microbiota have been shown to produce inflammatory metabolites that can cross the blood-brain barrier-a possible neurobiological precursor of psychosis.

Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study.

Background: A randomized, controlled, phase 3b study (ALPINE) evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) using a 1-day initiation regimen in patients hospitalized for an acute exacerbation of schizophrenia. Paliperidone palmitate (PP) was used as an active control. Exploratory endpoint assessments included severity of illness, positive and negative symptoms, quality of life, caregiver burden, and satisfaction with medication.

Measurement-based care training curriculum in psychiatry residency programs: I: Description of the curriculum and demonstration of implementation.

Background: Recent literature shows that most practicing psychiatrists do not receive training in measurement-based care (MBC). Among the primary barriers to MBC implementation are the lack of formal training and curriculums. We present the first comprehensive MBC curriculum for use in adult psychiatric practice, and describe how the curriculum is adapted and implemented in psychiatry residency training programs.

The effect of antipsychotic medications on white matter integrity in first-episode drug-naïve patients with psychosis: A review of DTI studies.

Background: Psychotic episodes have been associated with damage to both grey matter (GM) and white matter (WM). Although a recent meta-analysis suggest that in long term treatment, first generation antipsychotics (FGA) are associated with progressive reduction in GM, second generation antipsychotics (SGA) seem to have benefits to WM microstructure.

Methods: A search was conducted to identify controlled trials published from January 2000 to January 2021, which assessed WM integrity as measured by DTI in drug-naïve patients with FEP before and after antipsychotic administration.

White matter pathology in patients with borderline personality disorder: A review of controlled DTI studies.

Background: Neuroimaging, especially diffusion tensor imaging (DTI), has emerged as a helpful tool in assessing and characterizing white matter (WM) integrity. The resultant early treatment from early diagnosis is crucial because treatment is often more efficacious. Borderline personality disorder (BPD) is a challenging disorder to diagnose and treat, and has been reported to have various neurobiologic abnormalities.

The effects of yoga on depression and motor function in patients with Parkinson's disease: A review of controlled studies.

Background: Parkinson's disease (PD) is a neurodegenerative/neuropsychiatric disorder characterized by both motor and non-motor symptomology. The reported prevalence of depression in patients with PD is difficult to ascertain due to overlapping somatic symptoms and failure to self-report symptoms. Although antidepressants remain a first-line treatment, they can have adverse effects.

A systematic review of diffusion tensor imaging studies in drug-naïve OCD patients before and after pharmacotherapy.

Background: Obsessive-compulsive disorder (OCD) is difficult to treat. Studies have shown associations of white matter pathology in OCD, as well as various other psychiatric illnesses, using diffusion tensor imaging (DTI). We conducted a systematic review of controlled studies on drugnaïve patients with OCD vs pharmacologically treated patients with OCD to examine whether pharmacotherapy exerts changes on white matter in OCD.

Changes in inflammatory biomarkers before and after SSRI therapy in PTSD: A review.

Background: Selective serotonin reuptake inhibitors (SSRIs) are regarded as the standard pharmacotherapy for the treatment of posttraumatic stress disorder (PTSD). Recent studies indicate that neuroinflammation is associated with PTSD. We conducted a search of the literature to determine if SSRI efficacy is associated with a decrease in inflammation levels.

Low high-density lipoprotein and psychopathology: A review.

Background: An association between the level of total cholesterol and psychopathology has been the focus of numerous studies. Low total cholesterol has been found to be related to depression, personality disorders, and dissociative disorder. High cholesterol has been associated with schizophrenia, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder, and posttraumatic stress disorder.