Shrinks In Sneakers

Tag: treatment resistant schizophrenia

  • 🔍 Suicide & Psychosis: What We Can Learn from Recent Research

    🔍 Suicide & Psychosis: What We Can Learn from Recent Research

    A new study sheds light on suicide risk in patients with psychotic disorders, comparing those with recent-onset schizophrenia or other psychotic disorders to those with longer illness duration. The findings offer critical insights for clinicians and mental health professionals.

    🚨 Key Takeaways:

    📌 Early Illness = Higher Risk: Patients within the first five years of their illness had higher suicide rates, emphasizing the need for intensive early intervention.

    📌 Common Risk Factors: Across both groups, depression, prior suicide attempts, and substance use were major red flags.

    📌 Different Patterns: Those with recent-onset psychosis were more likely to have rapid illness progression, while those with longer illness duration often had chronic distress and social isolation before suicide.

    📌 Missed Opportunities? Many had recent healthcare encounters before suicide, highlighting potential gaps in risk assessment and intervention.

    🛑 What This Means for Us:
    🔹 Early-phase psychosis care should prioritize suicide prevention.
    🔹 Screening for depression, substance use, and prior attempts is essential.
    🔹 More proactive intervention is needed, especially after hospital visits.

    This study reinforces what many frontline clinicians already suspect—suicide prevention in psychosis requires urgent, tailored strategies. How can we improve early detection and support for at-risk patients? Let’s discuss. 👇

  • 🚨 New JAMA Study: Cannabis Legalization & Schizophrenia

    🚨 New JAMA Study: Cannabis Legalization & Schizophrenia

    A groundbreaking study just dropped in JAMA Psychiatry, shedding light on the link between cannabis use disorder (CUD) and schizophrenia following cannabis legalization.

    📊 Key Findings:

    • Higher rates of schizophrenia diagnoses were observed in young men with CUD after legalization.
    • The association was strongest in males aged 18–24, a group already at high risk for schizophrenia onset.
    • No significant changes were found in individuals without CUD, reinforcing concerns about cannabis as a potential trigger in vulnerable populations.

    🧠 What This Means:
    Cannabis legalization doesn’t just increase access—it may be shifting the trajectory of severe mental illness in at-risk groups. While correlation ≠ causation, this study adds weight to the argument that heavy cannabis use isn’t harmless, especially for young people with genetic or neurodevelopmental vulnerabilities.

    ⚖️ Clinical & Policy Implications:

    • Should we rethink cannabis policy in light of these findings?
    • Do we need stronger public health messaging about the psychiatric risks of heavy cannabis use?
    • How can we better screen and intervene early for CUD in young men?

    As psychiatrists, we see these cases firsthand—the young man with new-onset psychosis, the family blindsided, the struggle to regain lost cognitive and social function.

    This study is a wake-up call. Legal ≠ safe for everyone.

    What are your thoughts? Should legalization come with more psychiatric safeguards? Drop your insights below. ⬇️

  • Iclepertin Trial Results: Insights on Schizophrenia Treatment

    Iclepertin Trial Results: Insights on Schizophrenia Treatment

    📢 Update on Schizophrenia Research #MentalHealth #Schizophrenia

    🧠 Iclepertin (BI 425809), initially showing promise in Phase II trials, unfortunately did not meet the primary and key secondary endpoints in the Phase III CONNEX program. Despite this, it was well tolerated, and the safety profile remained consistent.

    🔬 Phase III Results:

    • No statistically significant improvements in cognition or functioning were observed compared to placebo over six months.

    Context: Iclepertin is a glycine transporter 1 (GlyT1) inhibitor, a class of drugs aimed at enhancing the function of the NMDA receptor by increasing glycine levels. This receptor plays a crucial role in cognitive processes, and improving its function was hypothesized to alleviate cognitive impairments in schizophrenia.

    📊 Visual Insights: Below are graphs illustrating the trial data, showing the comparison between Iclepertin and placebo groups across various cognitive assessments.

    🔍 Implications and Next Steps: Although these results are disappointing, they provide valuable insights for future research. The findings highlight the complexity of treating cognitive impairment in schizophrenia and underscore the need for continued exploration of new therapeutic targets and strategies.

    What’s next? Researchers will analyze the data further to identify any subgroups that may have benefited and explore other potential mechanisms to address this unmet medical need.

    💬 Join the Discussion: Have you or someone you know experienced cognitive challenges related to schizophrenia? What are your thoughts on current treatment options? Share your experiences or questions below—let’s foster a supportive community!

    🔔 Stay Updated: Follow us for more updates on ongoing research and join our forums for in-depth discussions on mental health innovations. Together, we can stay informed and connected. #ClinicalTrials #Neuroscience #Breakthrough

  • What HAPPENED to Ulotaront The TAAR-1 Agonist for Schizophrenia?

    What HAPPENED to Ulotaront The TAAR-1 Agonist for Schizophrenia?

    Back in 2019, during my residency, TAAR-1 agonists were hailed as the future of schizophrenia treatment, generating a wave of excitement and high expectations. Fast forward to 2025, and the once-prominent buzz has all but vanished. What happened to this promising class of drugs that once seemed poised to revolutionize the field?

    Ulotaront, an investigational antipsychotic developed by Sumitomo Pharma and Otsuka Pharmaceutical, has recently encountered significant challenges in its clinical development. In July 2023, the drug failed to meet primary endpoints in two Phase III clinical trials aimed at treating acutely psychotic adults with schizophrenia. These studies did not demonstrate a statistically significant improvement over placebo, raising concerns about ulotaront’s efficacy in this patient population.

    Given these setbacks, the timeline for ulotaront’s potential approval by the U.S. Food and Drug Administration (FDA) is now uncertain.Consequently, any previous projections for FDA approval will likely be delayed as the developers reassess their clinical strategy.

    It’s important to note that ulotaront had previously received Breakthrough Therapy Designation from the FDA in 2019 for the treatment of schizophrenia, reflecting initial optimism about its therapeutic potential.

  • Cobenfy: New Insights into Efficacy and Comparative Impact on Schizophrenia Symptoms

    Cobenfy: New Insights into Efficacy and Comparative Impact on Schizophrenia Symptoms

    Overall Efficacy

    • Effect Size: Cobenfy’s overall efficacy on the Positive and Negative Syndrome Scale (PANSS) stands at an effect size of 0.6, which is higher than many established antipsychotics (typically 0.3-0.5). However, clozapine still leads as the gold standard, with effect sizes ranging from 0.76 to 1.0.
    • NNT (Number Needed to Treat): The estimated NNT for Cobenfy is around 4, placing it in the mid-range among antipsychotics, where NNTs often range from 3 to 10.

    Negative Symptom Impact

    • Cobenfy shows a notable efficacy in reducing negative symptoms. It achieves an impressive effect size of 1.18for this symptom domain, which is uncommon among antipsychotics. This improvement in negative symptoms appears to be independent of reductions in positive symptoms, a distinct advantage over traditional agents.
    • The NNT for negative symptoms specifically is around 2, highlighting Cobenfy’s potential as a robust option for patients struggling with these challenging symptoms.

    Onset of Action

    • Rapid Onset: Cobenfy begins to show statistically significant improvements by week 3.
    • Peak Effect: Maximal symptom improvement is typically observed by week 5.

    Conclusion
    Cobenfy offers strong efficacy in schizophrenia, with unique advantages for negative symptoms. While clozapine remains unmatched in treatment-resistant cases, Cobenfy provides a promising option, especially for patients with significant negative symptoms.

  • Family Ties That Bind: When High Expressed Emotion Worsens Schizophrenia

    Family Ties That Bind: When High Expressed Emotion Worsens Schizophrenia

    In psychiatry we are always asking patients about social support. The presence or absence of social support can have a major impact on treatment response and ability to remain well once someone leaves the hospital. This usually includes support from family members and friends. 

    In 1956 the Medical Research Council Social Psychiatry (MRCSP) London conducted a study regarding the readmission of schizophrenic patients. The research revealed that patients who were stabilized symptomatically and functionally inpatient and subsequently discharged to live with their parents or wives were frequently readmitted for relapse of symptoms compared to those who were discharged to a sibling, or non-family environment. While family involvement is generally a protective factor that helps prevent things like suicide, there are some situations where the over involvement of family can complicate matters and even create worse outcomes.

    This usually occurs when a family has high expressed emotion. 

    Expressed emotion (EE) has consistently been shown to predict relapse in schizophrenia as well as other psychiatric disorders. Expressed emotion is a measure of the family environment that is based on how the relatives of a psychiatric patient spontaneously talk about the patient. 

    It measures 3 aspects of the family environment associated with high expressed emotion:

    1. Hostility (outward anger and frustration towards the patient because the family believes they are choosing to not get better) 
    2. Emotional over-involvement (This is where the family tries to solve all the problems for the patient taking away their ability to be self-reliant). 
    3. Critical comments (where the family views the mentally ill patient as lazy or selfish, not appreciating the difficulty of living with mental illness). 

    However, research has shown the following as indications of an environment with low expressed emotion: 

    1.    Positivity: (statements that express appreciation or support for the patient’s behavior and gives verbal and nonverbal reinforcement). 

    2.    Warmth: (kindness, concern and empathy expressed by the caregiver).

    There is such a thing as too much involvement on the part of the families which can lead to complicating family dynamics and exacerbation of an individual’s symptoms of mental illness. Interventions for improving outcomes include reducing contact with high EE caregivers and providing psychoeducation about EE to care givers. Bringing awareness to this behavior may help family members change. 

  • Split or Stick? The Real Impact of Dividing Clozapine Doses

    Split or Stick? The Real Impact of Dividing Clozapine Doses

    This post comes from a recent discussion I had with my resident about the utility of splitting clozapine doses in a recent case we had.

    The evidence on splitting clozapine into multiple daily doses primarily stems from clinical observations and smaller studies rather than extensive, randomized controlled trials (RCTs). Since clozapine has a unique pharmacodynamic and pharmacokinetic profile, standardizing an RCT on dose splitting has been challenging.

    1. Clozapine’s Half-Life and Steady-State Concentration: Clozapine has a long half-life (averaging about 12 hours), meaning steady-state concentrations can be reached without strict multiple dosing. Many patients maintain stable blood levels with once-daily dosing, especially at lower doses.
    2. Dose Splitting and Side Effects: Some smaller studies and clinical observations suggest that splitting doses can help reduce peak plasma levels of clozapine, which can be associated with side effects like sedation, hypotension, and dizziness. In these cases, a split dosing regimen may improve tolerability, particularly in patients who experience significant sedation or orthostatic hypotension with a single daily dose.
    3. Metabolic Side Effects and Compliance: In cases where metabolic side effects are of concern, or in patients who may not tolerate high single doses well, dividing doses could help with tolerability, potentially improving compliance and minimizing adverse effects like sedation or metabolic impact.
    4. Seizure Risk: High plasma peaks with a single large dose may theoretically increase the risk of seizures, especially in patients on higher doses of clozapine. Dividing doses is sometimes recommended as a preventive measure to maintain a more consistent blood level, although robust RCT data supporting this specific benefit is lacking.

    While RCT evidence specifically on clozapine dose-splitting remains limited, clinical judgment, patient tolerance, and monitoring of therapeutic blood levels play essential roles in tailoring dose regimens.