The post COVID-19 healthcare landscape and the use of long-acting injectable antipsychotics for individuals with schizophrenia and bipolar I disorder: the importance of an integrated collaborative-care approach

Background Long-acting injectable antipsychotics (LAIs) are an essential maintenance treatment option for individuals with schizophrenia or bipolar I disorder (BP-I). This report summarizes a roundtable discussion on the impact of COVID-19 on the mental healthcare landscape and use of LAIs for individuals with schizophrenia or BP-I. Methods Ten experts and stakeholders from diverse fields of healthcare participated in a roundtable discussion on the impact of the COVID-19 pandemic, treatment challenges, and gaps in healthcare for individuals with schizophrenia or BP-I, informed by a literature search. Results Individuals with schizophrenia or BP-I are at increased risk of COVID-19 infection and increased risk of mortality after COVID-19 diagnosis. LAI prescriptions decreased early on in the pandemic, driven by a decrease in face-to-face consultations. Mental healthcare services are adapting with increased use of telehealth and home-based treatment. Clinical workflows to provide consistent, in-person LAI services include screening for COVID-19 exposure and infection, minimizing contact, and ensuring mask-wearing by individuals and staff. The importance of continued in-person visits for LAIs needs to be discussed so that staff can share that information with patients, their caregivers, and families. A fully integrated, collaborative-care model is the most important aspect of care for individuals with schizophrenia or BP-I during and after the COVID-19 pandemic. Conclusions The COVID-19 pandemic has highlighted the importance of a fully integrated collaborative-care model to ensure regular, routine healthcare contact and access to prescribed treatments and services for individuals with schizophrenia and BP-I.

Real-world clinical predictors of manic/hypomanic episodes among outpatients with bipolar disorder

Background Bipolar disorder is a mental illness in which manic and depressive states are repeated, causing psychosocial dysfunction. Manic/hypomanic episodes cause problems with interpersonal, social and financial activities, but there is limited evidence regarding the predictors of manic/hypomanic episodes in real-world clinical practice. Methods The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was administered in an observational study that was conducted to accumulate evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics by conducting a retrospective medical record survey. Our study extracted baseline patient characteristics from September to October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. We investigated the presence or absence of manic/hypomanic episodes over the course of one year from baseline to September-October 2017. Results In total, 2231 participants were included in our study, 29.1% of whom had manic/hypomanic episodes over the course of one year from baseline. Binomial logistic regression analysis revealed that the presence of manic/hypomanic episodes was correlated with lower baseline GAF scores, rapid cycling, personality disorder, bipolar I disorder, and a mood state with manic or mixed features. Substance abuse was also a risk factor for manic episodes. There was no significant association between a baseline antidepressant prescription and manic/hypomanic episodes. Conclusions In Japan, 29.1% of outpatients with bipolar disorder had manic/hypomanic episodes over the course of one year. Our study suggested that a low GAF score, rapid cycling, personality disorder, bipolar I disorder, substance abuse, and baseline mood state could be predictors of manic/hypomanic episodes. Based on our findings, an antidepressant prescription is not a predictor of manic/hypomanic episodes.

Peripheral inflammatory markers associated with brain-volume reduction in patients with bipolar I disorder

Background: Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients. Methods: Euthymic patients with bipolar I disorder (BD-I) aged 20 to 45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1, chitinase-3-like protein 1 (also known as YKL-40), fractalkine, soluble tumor necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others. Results: We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus and supramarginal gyrus. A greater number of total lifetime mood episodes was also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes. Conclusions: The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.

Cariprazine Use in Early Psychosis: Three Case Reports

Objective: Cariprazine is a new atypical antipsychotic approved for the acute and maintenance treatment of schizophrenia (1, 2) and for the treatment of manic or mixed episodes associated with bipolar I disorder (1). Recently, cariprazine also got extended FDA-approval for the treatment of depressive episodes in adults with bipolar I disorder (3). The use of low doses of atypical antipsychotics is an essential component of early intervention in psychosis. For its particular performance and tolerability, cariprazine is becoming an important option for the treatment of first-episode psychosis.Method: Three patients experiencing first-episode psychosis (FEP) were successfully treated with cariprazine. Two patients were in their first months of the disease, and the third patient was in his third year after the FEP.Results: The three patients had a diagnosis of non-affective FEP, which includes schizophrenia, delusional disorder, and schizoaffective disorder. One of them was in their third year after the FEP with a predominance of negative symptoms at this stage of the disorder. All the patients were treated with cariprazine with a target dose of 3–4.5 mg/day. The three patients showed improvements in their psychosis, including a decrease in negative symptoms. No significant side effects were reported.Conclusion: Our three case reports indicate that cariprazine is an atypical antipsychotic beneficial in the treatment of early psychosis. Treatment with low doses of cariprazine could be effective and tolerable in this phase of the disorder. Future studies with longer follow-up of FEP patients are recommended to confirm these positive results of cariprazine in the early phases of psychosis.

Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers

A combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine’s unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.