Blood Test to Predict Schizophrenia Shows Promise

Researchers say they have developed a blood test for schizophrenia.

More than 3 million people in the United States have schizophrenia, a disorder marked by hallucinations and delusions, or a related psychotic illness.

The new test, which is expected to be available later this year from MindX Sciences, identifies markers in the blood that objectively measure a person's risk for schizophrenia, allowing doctors to tailor treatments to their individual biology.

"Schizophrenia is hard to diagnose, especially early on, and matching people to the right treatment from the beginning is very important," said senior study author Dr. Alexander Niculescu, a professor of psychiatry and medical neuroscience at Indiana University School of Medicine in Indianapolis.

"Psychosis usually manifests in young adulthood -- a prime period of life," he explained in a university news release. "Stress and drugs, including marijuana, are precipitating factors on a background of genetic vulnerability. If left unchecked, psychosis leads to accumulating biological damage, social damage and psychological damage."

His team published its research Feb. 8 in the journal Molecular Psychiatry.

For their study, they followed psychiatric patients for more than a decade, identifying biomarkers that predicted high rates of hallucination and delusions, as well as future related hospitalizations. They also examined which biomarkers were targets of existing drugs.

The work builds on previous studies by Niculescu, who is also a staff psychiatrist at the Veterans Administration Medical Center in Indianapolis, and his colleagues over the past two decades.

They have examined blood biomarkers for other psychiatric issues, including anxiety, post-traumatic stress disorder (PTSD), memory disorders and suicide risk.

In general, Niculescu said, the best biomarkers were better predictors than standard scales used to evaluate someone who has hallucinations or delusions.

"Fortunately, biologically some of the existing medications work quite well if initiated early in the right patients," he said. "Social support is also paramount, and once that and medications are in place, psychological support and therapy can help as well."

While Niculescu said there is still much to learn, there is reason for optimism in this era of emerging precision psychiatry.

https://medicine.iu.edu/news/2024/02/psychosis-blood-test

Blood Test to Predict Schizophrenia Shows Promise 

FDA Approves Igalmi (dexmedetomidine) Sublingual Film for Acute Treatment of Agitation Associated with Schizophrenia or Bipolar I or II Disorder in Adults

BioXcel Therapeutics, Inc., a biopharmaceutical company utilizing artificial intelligence (AI) approaches to identify and develop transformative medicines in neuroscience and immuno-oncology,  announced  the U.S. Food and Drug Administration (FDA)   approval of  Igalmi™ (dexmedetomidine) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. Igalmi can be self-administrated by patients under the supervision of a healthcare provider. The Company is prepared to launch Igalmi in the U.S. in the second quarter of 2022.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for healthcare professionals to treat,” said Dr. John Krystal, M.D., the Robert L. McNeil, Jr. Professor of Translational Research and Chair of the Department of Psychiatry at Yale School of Medicine. “The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides healthcare teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option.”

An estimated 7.3 million people in the U.S. are diagnosed with schizophrenia or bipolar disorders. Up to a quarter of these people experience agitation, with episodes that can occur 10 to 17 times annually, totaling up to 25 million agitation episodes for these two patient populations per year. Agitation episodes are associated with a significant burden for patients, caregivers, and the healthcare system.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder-associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, Ph.D., CEO of BioXcel Therapeutics. “With this landmark achievement of our first approved drug, we have taken a monumental step toward our mission of bringing transformative medicines in neuroscience to patients using our AI platform. We are deeply grateful to our clinical trial participants, healthcare providers, researchers, and employees for contributing to this important new therapy. We believe Igalmi has significant market-changing potential, and we are excited to execute on our commercial launch plans in the U.S. this quarter.”

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel group Phase 3 trials evaluating Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The primary endpoint was the mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score assessed at 2 hours following dosing. The key secondary endpoint was the earliest time where efficacy, measured by the change from baseline in PEC score, was statistically separated from placebo. PEC is an investigator-rated instrument for measuring agitation in patients that evaluates five elements associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement.

In both trials, Igalmi met the primary endpoint at two hours after the first dose in patients treated with the 120 mcg and 180 mcg doses, demonstrating statistically significant improvements from baseline. Igalmi also met the key secondary endpoint, demonstrating a rapid onset of action, with statistically significant separation from placebo observed at 20 minutes for both the 180 mcg and 120 mcg doses in SERENITY II and 20 minutes and 30 minutes in SERENITY I, respectively.

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence (drowsiness and feeling sleepy), paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension (low blood pressure) and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi did not exhibit any treatment-related serious adverse effects (SAEs) in Phase 3 studies, it may cause notable side effects including hypotension, orthostatic hypotension and bradycardia, QT interval prolongation, and somnolence.

Data from the pivotal Phase 3 SERENITY II trial evaluating Igalmi in bipolar disorders were published in the Journal of the American Medical Association (JAMA) on February 22, 2022.

About Agitation Associated with Schizophrenia and Bipolar Disorder

Agitation is a common and difficult-to-manage symptom associated with bipolar I or II or schizophrenia. Early identification and prompt intervention to relieve agitation are essential to avoid symptomatic escalation and the emergence of aggression. Expert consensus best-practice guidelines have recommended that agitation should be treated by a combination of behavioral calming techniques, verbal de-escalation, and medications that are voluntarily accepted by patients without coercion. The goal of using medication is to calm the patient so that he or she can be more accurately assessed by clinicians. Medication used in this manner is consistent with current guidelines, which state that the proper endpoint of medication administration is calming without inducing sleep. This approach may help avoid the costly and traumatic use of coercive techniques like physical restraint and seclusion, which may result in admission and prolonged hospitalization.

FDA Approves Secuado (asenapine) Transdermal System for the Treatment of Adults with Schizophrenia

Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical Co., Inc., today announced the U.S. Food and Drug Administration (FDA) has approved Secuado (asenapine see below pic)) transdermal system, the first-and-only transdermal patch formulation for the treatment of adults with schizophrenia.

“As people living with schizophrenia cycle through treatments their therapeutic options narrow, leaving them and their caregivers looking for new treatment options,” said Leslie Citrome, M.D., M.P.H., Clinical Professor of Psychiatry and Behavioral Sciences, New York Medical College. “In addition to offering a new delivery option, transdermal patches can also provide caretakers and healthcare providers with a non-intrusive, visual confirmation that a treatment is being utilized.”

The once-daily transdermal drug delivery system (TDDS) provides sustained concentrations during wear time (24 hours)2 of the atypical antipsychotic drug asenapine, a well-established treatment for schizophrenia. A transdermal patch may help to mitigate some of the challenges patients face with the management of their schizophrenia.2

“There is an enormous unmet need for new types of schizophrenia treatments, and Noven is committed to giving people living with this devastating disease and their family members new options that may help them effectively manage their symptoms,” said Dr. Naruhito Higo, Chairman and Chief Executive Officer, Noven Pharmaceuticals, Inc. “We commend the FDA on the approval of Secuado and look forward to bringing it to market in the U.S. as soon as possible so people living with schizophrenia have a transdermal delivery option for asenapine treatment.”

In the international, Phase 3, double-blind, placebo-controlled study, Secuado achieved the primary endpoint of statistically significant improvement from baseline in the change of the total Positive and Negative Syndrome Scale (PANSS) compared to placebo at week six. Efficacy and safety were assessed during the six-week treatment period in 616 adults living with schizophrenia. Additionally, Secuado demonstrated statistically significant improvement in Clinical Global Impression-Severity (CGI-S) scores, the key secondary endpoint of the Phase 3 study.

The systemic safety profile of Secuado was consistent with what is known for sublingual asenapine.1 The most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain.1

What is Secuado?

Secuado is a prescription medicine used to treat adults with schizophrenia. Secuado is a transdermal system (patch) you apply to your skin. It is not known if Secuado is safe and effective in children less than 18 years of age with schizophrenia.

IMPORTANT SAFETY INFORMATION

Secuado may cause serious side effects, including:

• Increased risk of death in elderly people with dementia-related psychosis. Medicines like Secuado can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Secuado is not approved for the treatment of people with dementia-related psychosis.
• Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death.
• Neuroleptic Malignant Syndrome (NMS): a serious condition that can lead to death. Immediately remove the patch. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following: high fever, confusion, stiff muscles, increased sweating and changes in your breathing, heart rate and blood pressure.
• Uncontrolled body movements (tardive dyskinesia). Secuado may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking Secuado. Tardive dyskinesia may also start after you stop taking Secuado.
• Problems with your metabolism such as:
  • High blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take Secuado.
    Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with Secuado:
    • Feel very thirsty or very hungry
    • Feel sick to your stomach
    • Feel weak or tired
    • Need to urinate more than usual
    • Feel confused, or your breath smells fruity
  • Increased fat levels (cholesterol and triglycerides) in your blood
  • Weight gain. You and your healthcare provider should check your weight regularly during treatment with Secuado.
• Allergic reactions. You may observe rash, decreased blood pressure or a fast heart rate.
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.
• Falls. Secuado may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position, and can slow your thinking which may lead to falls.
• Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with Secuado.
• Irregular heartbeat or a heartbeat that does not feel normal (QT prolongation)
• Increased prolactin levels in your blood (hyperprolactinemia). Your healthcare provider may do blood tests to check your prolactin levels during treatment with Secuado.
• Seizures (convulsions)
• Impaired thinking and motor skills. Use caution when operating heavy machinery when using Secuado.
• Problems controlling your body temperature so that you feel too warm
• Difficulty swallowing
• External heat. Avoid exposing Secuado to direct external heat sources such as hair dryers, heating pads, electric blankets, heated water beds, etc.
• Application site reactions. Increased skin irritation may occur if Secuado is applied for a longer period than instructed or if the same application site is used repeatedly. Use a different application site each day to decrease skin reactions. If skin reactions continue or spread beyond the application site, tell your healthcare provider. Symptoms of application site reactions may include:
• Redness
• Itching
• Irritation
• Pimple-like raised skin
• Pain of the skin
• Swelling
• More 

Ref : https://en.wikipedia.org/wiki/Asenapine

FDA Approves Perseris (risperidone) for Extended-Release Injectable Suspension for the Treatment of Schizophrenia in Adults

In continuation of my update on risperidone

Indivior PLC,   announced that the U.S. Food and Drug Administration (FDA) has approved Perseris, the first once-monthly subcutaneous risperidone-containing, long-acting injectable (LAI) for the treatment of schizophrenia in adults. Clinically relevant levels were reached after the first injection of Perseris without use of a loading dose or any supplemental oral risperidone.

"Treatment adherence is a major challenge in schizophrenia due to the complexity of the disease. It is important to have additional treatment options available to physicians to help them improve their patients' symptom severity," said Maurizio Fava, Executive Vice Chair of the Massachusetts General Hospital (MGH) Department of Psychiatry and Indivior clinical research consultant. "The studies carried out by Indivior suggest that Perseris may offer patients, caregivers and physicians a new once-monthly subcutaneous medication option to treat adults with schizophrenia."

Perseris contains risperidone, a well-established treatment for schizophrenia, and uses the extended-release delivery system to form a subcutaneous (under the skin) depot that provides sustained levels of risperidone over one month. Initial peak risperidone plasma levels occur within 4 to 6 hours of dosing and are due to an initial release of the drug during the depot formation process.

"Schizophrenia is a devastating, chronic and often disabling mental health condition that impacts the lives of people suffering from this illness, their families and caregivers. The approval of Perseris brings us the opportunity to provide adult patients and their healthcare providers with an innovative treatment option that we believe will make a meaningful difference," said Shaun Thaxter, Chief Executive Officer of Indivior. "People with schizophrenia face a complex patient journey that can be hindered by ignorance, apathy and stigma. Indivior is committed to working with stakeholders to reduce the stigma of schizophrenia and expand access to evidence-based treatment."

The efficacy of Perseris was evaluated in a pivotal Phase 3 randomized, double-blind, placebo-controlled, 8-week study of 354 patients (NCT 02109562). Perseris efficacy was demonstrated by an improvement in the primary clinical endpoint, Positive and Negative Syndrome Scale (PANSS) total score at day 57. The improvement in Clinical Global Impression Severity of Illness (CGI-S) was also statistically significant at day 57. Clinical trials of Perseris were designed for the product to be initiated with neither a loading dose nor any supplemental risperidone.

The safety of Perseris was evaluated in 814 adults with schizophrenia who received at least one dose of Perseris during clinical trials. A total of 322 patients were treated with Perseris for at least six months, with 234 of those treated with Perseris for at least 12 months. The systemic safety profile of Perseris was consistent with the known safety profile of oral risperidone. The most common systemic adverse reactions in the pivotal Phase 3 trial (in ≥5% of Perseris patients and greater than twice placebo) were increased weight, sedation/somnolence and musculoskeletal pain. The most common injection site reactions (≥5% of all patients across Perseris and placebo groups) were injection site pain and reddening of the skin.

https://www.drugs.com/history/perseris.html