Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia.

Schizophrenia is a severe mental illness that has its onset in late adolescence or early adulthood and is associated with significant dysfunction across multiple domains. The pathogenesis of schizophrenia remains unknown, but physiologic understanding of the illness has been driven by the dopamine hypothesis. However, acetylcholine (ACh) clearly plays a role with mixed results regarding effect on psychosis. Selective muscarinic M1 and M4 agonists, such as xanomeline, originally developed to aid in cognitive loss with Alzheimer's, showed promise in proof-of-concept study in 20 patients with schizophrenia. Unfortunately, tolerability problems made muscarinic agonists impractical in either condition. However, coadministration of trospium, a lipophobic, non-selective muscarinic antagonist previously used for the treatment of overactive bladder, with xanomeline resulted in a significant reduction of cholinergic adverse effects. A recent randomized, placebo-controlled study of the antipsychotic effects of this combination in 182 patients with acute psychosis revealed improved tolerability with 80% of subjects staying to the end of the 5 weeks study. At the end of the trial, the treatment group saw a -17.4 change in the positive and negative symptom scale (PANSS) score from baseline compared to a -5.9 change in the placebo arm (P < 0.001). Furthermore, the negative symptom subscore, was also superior in the active arm (P < 0.001). These early studies are exciting because they suggest that the cholinergic system may be recruited to treat a severe and disabling disorder with suboptimal treatment options. Xanomeline-trospium combination is currently in phase III studies.

Psychiatric Comorbidities and Risk of Somatic Symptom Disorders in Posttraumatic Stress Disorder: A Cross-Sectional Inpatient Study.

ABSTRACT: Nearly 90% of Americans are exposed to a traumatic event at some point in their lives, and over 8% of those individuals will develop posttraumatic stress disorder (PTSD). Our study examined the demographic differences and psychiatric comorbidities in inpatients with PTSD with and without somatic symptom disorders (SSDs), using data from the Nationwide Inpatient Sample for 2018 and 2019. Our sample included 12,760 adult patients with a primary diagnosis of PTSD, which was further subdivided based on a codiagnosis of SSD. We used a logistic regression model to determine the odds ratio (OR) of association for SSD and identify demographic predictors and comorbid risk factors in inpatients with PTSD. The prevalence of SSD in inpatients with PTSD was 0.43%, and it was more commonly seen in women and Caucasians. Personality disorders (OR, 5.55; p < 0.001) and anxiety disorders (OR, 1.93; p = 0.018) were found to increase the likelihood of codiagnoses of SSD in inpatients with PTSD. These findings support the need for a systematic, modular approach that includes evidence-based interventions to treat at-risk populations.

Frontotemporal Dementia: Dilemma in Discrimination From Similarly Presenting Neurological and Psychiatric Conditions.

Frontotemporal dementia (FTD) is the most common cause of neurocognitive decline, second to Alzheimer's disease (AD) and Lewy body dementia. Its presence offers a unique challenge to physicians trying to detect cognitive deficits, as it not only arises in middle age but also can be misdiagnosed as a primary psychiatric disorder. The following case describes the clinical course of a 50-year-old male with a recent history of sporadic visual and auditory hallucinations, followed by a gradual decline in cognitive function including declining memory, apathy and behavioral disinhibition, and social functioning, which are suggestive of FTD-type. Apart from the gradual decline of his cognitive function, the patient had multiple clinical encounters, during which he was misdiagnosed with schizophrenia. Furthermore, the report showcases the handful of conditions that FTD can be misdiagnosed and discusses the thorough clinical/psychological examination and investigations to be done to arrive at FTD.

Diagnostic Dilemma and Management Difficulties in a Young Patient With Psychosis and Benign Chorea: A Case Report and Review of the Literature.

Psychosis presents with hallucinations, delusions, disorganized speech, abnormal psychomotor behavior, and negative symptoms. It most commonly appears in the setting of schizophrenia, although it could also appear in bipolar disorder, major depression, post-traumatic stress disorder (PTSD) and even in medical conditions and substance use. In young people, the diagnosis of psychosis can present as a challenge due to the overlap of psychotic conditions and other emotional, behavioral, and developmental disorders. In this case report, we present the case of a 19-year-old female with a history of bipolar disorder, oppositional defiant disorder (ODD), depression, anxiety, PTSD, and schizophrenia-spectrum disorder who was admitted to an inpatient psychiatric facility after presenting with acute onset of confusion.