Dexmedetomidine for Acute Agitation in Bipolar and Schizophrenia: Worth the Hype?

I recently received a great question about the use of dexmedetomidine for acute agitation. With its recent FDA approval for agitation associated with bipolar disorder and schizophrenia, it’s only natural to wonder: is this the new go-to treatment, or just another overhyped medication?

Let’s start with the obvious. New medications almost always come with a hefty price tag. That cost is only justifiable if they outperform existing options in either efficacy or safety—and in this case, dexmedetomidine falls short on both fronts.

Current data suggest it does not provide superior outcomes when compared to existing, well-established medications like lorazepam, haloperidol, or olanzapine. And it brings along its own baggage: bradycardia, hypotension, and sedation-related complications that can be clinically significant, especially in medically complex patients.

When you combine the high cost with a safety profile that raises some red flags—and no clear advantage in efficacy—it becomes hard to justify widespread use.

For now, I’d place dexmedetomidine in the “hype” category. We already have effective, affordable options with strong track records in managing acute agitation. Until further data prove otherwise, there’s little reason to switch.

Avoid Tianeptine: FDA Alerts Consumers to Risks

The U.S. Food and Drug Administration (FDA) has issued a critical health warning about the growing availability of tianeptine, a dangerous, unapproved substance being sold as a dietary supplement under names like Zaza, Tianna Red, Pegasus, and others.

Commonly referred to as “gas station heroin”, tianeptine mimics opioid-like effects and is being sold in convenience stores, gas stations, smoke shops, and online—posing serious health risks to the public.

⚠️ Why This Matters:

Tianeptine is not approved for any medical use in the U.S. Despite this, it is widely marketed for supposed benefits like mood enhancement, anxiety relief, or cognitive boost. These claims are not supported by clinical evidence, and the risks are significant.

🩺 Serious Health Risks Associated With Tianeptine:

⚠️ Death, particularly when combined with alcohol or other substances

⚠️ Respiratory depression (slow or stopped breathing)

⚠️ Seizures

⚠️ Loss of consciousness

⚠️ Confusion and agitation

⚠️ Opioid-like withdrawal symptoms

🛑 What You Can Do:

Report adverse reactions to the FDA via MedWatch: https://www.fda.gov/medwatch

Avoid any products labeled as containing tianeptine.

Do not trust unregulated supplements marketed for mental clarity or energy.

📌 Quick Summary:

  • Tianeptine = dangerous, unapproved opioid-like drug
  • Sold as a supplement under names like Zaza or Tianna Red
  • Linked to seizures, coma, and death
  • Avoid these products and warn others
  • Report side effects to the FDA MedWatch Program

The Importance of Distinguishing Suicidal Behaviors

This is the subject of a recent discussion I had with a colleague regarding the differences between a suicide attempt and a suicide gesture. Though these terms are sometimes used interchangeably in casual conversation or even in clinical documentation, they carry fundamentally different meanings—both in terms of patient risk and in how we, as clinicians, should respond.

Our conversation emerged from a case involving a patient with borderline personality disorder who presented to the emergency department after ingesting a small quantity of over-the-counter medication. The intent was unclear. Was this a serious attempt to end her life? Or was it a gesture—an act of desperation without the intention to die, but rather to communicate emotional distress?

The question is not academic. Our interpretation of the event determines our risk formulation, our documentation, our treatment planning, and even how we communicate with the patient and their support system. Yet, it is precisely in these gray areas that clinicians often struggle, and where outdated or stigmatizing language can do real harm.

Defining the Terms: Clinical and Functional Differences

suicide attempt refers to an act of self-harm with at least some intent to die. The degree of lethality may vary, but what distinguishes an attempt is that the individual believed the act could result in death and engaged in it with that goal in mind—even if ambivalence was present. The National Institute of Mental Health (NIMH) and the Columbia-Suicide Severity Rating Scale (C-SSRS) define this with some specificity: any potentially self-injurious behavior with non-zerointent to die, regardless of outcome.

In contrast, a suicidal gesture is a behavior that mimics suicidal behavior or appears life-threatening but is typically not intended to be fatal. The function is often communicative or affect-regulating rather than aimed at death. Classic examples include superficial wrist-cutting, ingesting a sub-lethal dose of medication, or tying a noose but not tightening it. These acts often occur in interpersonal contexts and can be seen as efforts to signal pain, elicit help, or assert control in the face of perceived abandonment.

Why the Distinction Matters

It might be tempting to dismiss suicidal gestures as “attention-seeking” or “manipulative,” but this framing is both clinically dangerous and ethically fraught. Individuals who engage in gestures often experience intense psychological suffering, and repeated gestures are a well-established risk factor for future suicide attempts and completed suicide.

From a risk assessment standpoint, gestures should be taken seriously, especially when they become part of a pattern. While the intent to die may not be present in a given gesture, intent can shift quickly, particularly in individuals with mood disorders, personality pathology, or under the influence of substances.

From a treatment perspective, understanding the function of the behavior—whether it is to relieve affective tension, to communicate distress, or to punish oneself—is crucial to tailoring interventions. For instance, dialectical behavior therapy (DBT) explicitly targets self-harm and suicidal gestures as part of its hierarchy of treatment priorities, recognizing the urgency and potential danger of these behaviors even when lethality is low.

Conclusion: Clarify, Don’t Categorize

Ultimately, the conversation with my colleague reminded me that the real clinical challenge is not to label a behavior as a suicide attempt or a gesture, but to understand its meaning in the life of the patient. Both require empathy, structure, and a willingness to engage with complexity. Whether a patient wants to die or wants their suffering to be seen and acknowledged, both deserve serious clinical attention.

By sharpening our definitions and approaching these behaviors with nuance, we can better serve patients in crisis and avoid the pitfalls of assumptions—especially in emotionally charged clinical environments like emergency rooms, inpatient units, or high-acuity outpatient settings.

EMA Warns of Suicidal Ideation from Finasteride

In a significant update to its safety guidance, the European Medicines Agency (EMA) has officially recognized suicidal ideation as a potential side effect of finasteride. The EMA is urging healthcare professionals to advise patients to stop treatment and seek medical help if they experience depressed mood, depression, or suicidal thoughts while taking the drug.

This decision follows a growing number of reports linking finasteride, particularly in younger men using it for androgenic alopecia (male pattern baldness), to neuropsychiatric side effects. While previous warnings have addressed sexual dysfunction, this marks a critical shift in regulatory focus to mental health.

💊 What Is Finasteride?

Finasteride is a 5α-reductase inhibitor used to treat:

  • Benign prostatic hyperplasia (BPH) in a 5 mg daily dose (Proscar)
  • Male pattern baldness (androgenic alopecia) in a 1 mg daily dose (Propecia)

It works by inhibiting the conversion of testosterone to dihydrotestosterone (DHT)—a potent androgen implicated in hair loss and prostate growth.

⚠️ The EMA’s Updated Warning

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) reviewed post-marketing surveillance data and published literature and concluded that:

“There is sufficient evidence to support a causal relationship between finasteride and the risk of suicidal ideation.”

Key recommendations:

  • Suicidal ideation will be added to the drug’s product information as a potential adverse effect.
  • Healthcare professionals should proactively inform patients about this risk.
  • Patients should be advised to discontinue treatment immediately and seek medical advice if they experience changes in mood or mental health.

🧠 Possible Mechanisms Behind Finasteride’s Psychiatric Effects

The exact mechanisms linking finasteride to depression and suicidality remain unclear, but several biological hypotheseshave been proposed:

1. Neurosteroid Depletion

Finasteride inhibits 5α-reductase, which not only converts testosterone to DHT but also helps produce neurosteroids like allopregnanolone and tetrahydrodeoxycorticosterone (THDOC).

  • These neurosteroids have potent GABAergic activity, contributing to anxiolytic and antidepressant effects.
  • Inhibition leads to decreased GABA-A receptor modulation, potentially increasing anxiety, depression, and suicidal thoughts.

2. Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation

Altered steroid metabolism may dysregulate the HPA axis, increasing cortisol levels, a well-known biomarker of depression and suicidal behavior.

3. Persistent Epigenetic Changes

Some animal and human data suggest that finasteride may induce long-lasting changes in gene expression related to stress response and mood regulation, even after discontinuation—supporting the idea of post-finasteride syndrome (PFS).

4. Neuroinflammation

Reduced neurosteroids may increase neuroinflammatory signaling, a growing area of interest in the neurobiology of depression and suicidality.

🧾 Final Thoughts

The EMA’s announcement is a sobering reminder that drugs affecting hormonal pathways can have wide-reaching systemic effects, including on the brain. With better awareness, screening, and patient education, we can minimize harm and support individuals who may be at risk.

Substance-Induced Psychosis vs. Primary Psychosis: Treatment, Prognosis, and the Cannabis Connection

Psychosis can emerge from a range of causes, but distinguishing between substance-induced psychosis (SIP) and primary psychotic disorders like schizophrenia is critical for effective treatment and prognosis. While the clinical presentation often overlaps—hallucinations, delusions, disorganized thinking—the underlying etiology, treatment approach, and long-term outcomes can diverge significantly.

Defining the Two

Substance-Induced Psychosis (SIP) occurs when symptoms of psychosis are directly caused by intoxication with or withdrawal from substances such as cannabis, amphetamines, alcohol, hallucinogens, or synthetic cannabinoids (e.g., spice or K2). The psychosis typically emerges during or shortly after substance use and resolves with abstinence.

Primary Psychosis, on the other hand, refers to psychotic disorders that are not directly attributable to substances or medical conditions. This includes schizophreniaschizoaffective disorder, and brief psychotic disorder, among others.

Treatment: Overlapping Tools, Different Emphasis

1. Acute Management
Both SIP and primary psychosis are often treated with antipsychotic medications during acute episodes. The initial goals are the same: reduce agitation, manage delusions or hallucinations, and ensure safety.

  • Commonly used antipsychotics include risperidone, olanzapine, haloperidol, and quetiapine. In SIP, short-term use is typically sufficient.
  • In cases involving severe agitation or aggression, benzodiazepines (like lorazepam) may be used adjunctively, especially if stimulant intoxication is suspected.

2. Long-Term Strategy

  • SIP: After stabilization, the primary strategy is abstinence from the offending substance and psychosocial support (e.g., CBT, motivational interviewing, relapse prevention).
  • Primary psychosis: Typically requires ongoing antipsychotic treatment, often for life. Psychosocial interventions, supported employment, and cognitive remediation are also central to recovery.

Conversion to Schizophrenia: What’s the Risk?

One of the key concerns with SIP is whether the episode is a harbinger of an underlying primary psychotic disorder.

  • Approximately 20–50% of individuals with substance-induced psychosis later develop a primary psychotic disorder, such as schizophrenia.
  • Amphetamine- and cannabis-induced psychosis carry the highest risk of conversion, particularly when psychosis occurs in adolescence or early adulthood.
  • meta-analysis by Niemi-Pynttäri et al. (2013) found that 46% of people with SIP later developed schizophrenia-spectrum disorders over a follow-up of 8 years.

Predictors of conversion include:

  • Younger age at first psychotic episode
  • Family history of psychotic illness
  • Persistent psychotic symptoms after substance clearance
  • Poor premorbid functioning

Do Antipsychotics Work in SIP?

Antipsychotics reduce acute psychotic symptoms in SIP, but their long-term utility is less clear.

  • Studies show rapid resolution of psychosis within days to weeks in most SIP cases when abstinence is achieved.
  • Long-term antipsychotic treatment does not reduce the conversion rate to schizophrenia in confirmed SIP, suggesting their role should be time-limited unless ongoing symptoms or risk factors emerge.
  • A 2020 review in Psychological Medicine emphasized that monitoring over the 6–12 months post-episode is essential for risk stratification and avoiding premature chronic medication exposure.

Cannabis: A Powerful Catalyst

Cannabis has become the most studied and most controversial substance linked to psychosis. Here’s what the evidence says:

  • Daily cannabis users are 3–5 times more likely to develop a psychotic disorder compared to non-users, especially with high-THC strains (≥10% THC).
  • A 2019 Lancet Psychiatry study by Di Forti et al. showed that strong cannabis use accounts for 12% of new psychosis cases in Amsterdam, and 30% in London.
  • Adolescents who use cannabis, particularly those with a family history of psychosis, are at dramatically increased risk.

Mechanistically, THC may dysregulate the dopamine system in vulnerable brains, tipping the balance toward psychosis. Cannabidiol (CBD), in contrast, may be protective, but commercial cannabis typically contains very little CBD.

Final Thought: Clinicians must balance vigilance and restraint—treating psychosis aggressively when needed but also avoiding unnecessary chronic antipsychotic exposure in what may be a reversible, substance-driven episode.

ARISE Study Phase 3 Results: Understanding Xanomeline’s Setback

What Was the ARISE Study?

The ARISE trial was a Phase 3 clinical study evaluating Cobenfy — a combination of xanomeline (a muscarinic receptor agonist) and trospium chloride (a peripheral anticholinergic) — as an adjunctive treatment for adults with schizophrenia who continued to experience symptoms despite taking an atypical antipsychotic.

What Is a Primary Endpoint, and Why Does It Matter?

In clinical trials, the primary endpoint is the most important outcome researchers are trying to affect — it’s how a drug’s success or failure is officially judged.
In ARISE, the primary endpoint measured the change in symptom severity compared to placebo using a standardized scale for schizophrenia. Meeting this endpoint would have demonstrated clear, statistically significant symptom improvement attributable to Cobenfy.

The Outcome: No Statistically Significant Benefit

According to topline results, Cobenfy did not show a statistically significant improvement compared to placebo when added to atypical antipsychotics. This means the observed difference could have been due to chance and did not meet the pre-set threshold for success.

However, Cobenfy did show a numerical improvement — the group receiving the drug combination performed betterthan placebo in symptom reduction, just not to a statistically convincing degree.

Could Anticholinergic Effects Be to Blame?

One possible explanation for this outcome lies in the mechanism of action of both Cobenfy and many commonly used atypical antipsychotics.

  • Xanomeline is designed to activate muscarinic receptors in the brain (specifically M1 and M4), which may help regulate dopamine and reduce psychosis.
  • But many atypical antipsychotics — like olanzapine, clozapine, and quetiapine — also have anticholinergic properties, meaning they block these same receptors.

This sets up a pharmacological tug-of-war: Cobenfy tries to stimulate muscarinic activity, while the background antipsychotic may be dampening it. This conflict could blunt the therapeutic signal, explaining why the benefit didn’t reach statistical significance.

What This Means for the Future

The failure to meet the primary endpoint is a setback, but not the end of the road. The numerical improvements suggest a potential signal, and with refined trial design — perhaps using background medications with lower anticholinergic load — future studies may better reveal Cobenfy’s potential.

Additionally, this trial underscores the importance of considering mechanism compatibility in combination therapies. It’s not just about adding drugs — it’s about how they interact at the receptor level.

Conclusion

While the ARISE study didn’t deliver the result many hoped for, it raised critical questions that will shape future research. A deeper understanding of anticholinergic burden, drug synergy, and precision pharmacology is essential as we continue the search for more effective treatments for schizophrenia.

Adult ADHD: Current Trends and Emerging Research (2025 Update)

Attention-deficit/hyperactivity disorder (ADHD) has traditionally been seen as a childhood condition — but in recent years, there has been an explosion of interest in ADHD among adults. As awareness grows, so does research. New studies are reshaping how we diagnose, treat, and understand ADHD in the adult population.

1. 🔥 Rising Rates of Adult ADHD Diagnosis

Recent studies show that adult ADHD diagnoses have sharply increased over the past decade. According to a 2023 analysis published in JAMA Psychiatry, the diagnosis rate for adults aged 18–45 rose by more than 80% between 2011 and 2022.

Why the surge?

  • Greater public awareness
  • Better screening tools for adults
  • A cultural shift toward recognizing executive dysfunction in adulthood

However, there are concerns that overdiagnosis is also happening, particularly when ADHD is diagnosed after brief evaluations without thorough history-taking.

2. 🧠 Expanded Understanding of Adult ADHD Symptoms

The symptom profile in adults differs significantly from children. While hyperactivity often fades, issues like emotional dysregulationdisorganization, and executive dysfunction persist.

Recent research emphasizes that adult ADHD often presents as:

  • Chronic procrastination
  • Low frustration tolerance
  • Difficulty managing responsibilities (work, home, finances)
  • Persistent inner restlessness

A 2024 review in The American Journal of Psychiatry noted that emotional impulsivity may actually be a core symptomin adults, not just a secondary feature.

3. 💊 Treatment Shifts: Caution Around Stimulants

While stimulant medications (like amphetamines and methylphenidate) remain the gold standard, new studies highlight the importance of careful prescribing, especially in adults with:

  • Comorbid substance use disorders
  • Cardiovascular risk factors
  • Poor diagnostic workups

Non-stimulant treatments are gaining ground:

  • Atomoxetine (Strattera) remains a mainstay.
  • Viloxazine (Qelbree) was approved for adult ADHD in 2024 and shows promise with lower abuse potential.
  • Bupropion (Wellbutrin) continues to be an important off-label option, especially when depression coexists with ADHD.

According to a 2024 meta-analysis in Lancet Psychiatrynon-stimulants now account for about 30% of new ADHD prescriptions in adults — a significant jump compared to previous years.

4. 🧬 Precision Psychiatry and Biomarkers on the Horizon

Emerging studies are exploring neuroimaging and genetic markers to better understand adult ADHD subtypes.

  • A 2023 study using fMRI found distinct prefrontal cortex dysfunction patterns in adults with ADHD compared to controls.
  • Genetic research continues to implicate genes related to dopamine transmission and synaptic plasticity.

Although these findings are not yet ready for clinical application, the future of ADHD diagnosis may involve biomarkers, moving beyond subjective questionnaires alone.

5. 🌿 Lifestyle Interventions Are Getting More Attention

There’s a growing body of evidence supporting complementary approaches:

  • Cognitive-behavioral therapy (CBT) for ADHD-specific skills
  • Exercise as a way to enhance executive function and mood
  • Mindfulness practices to improve emotional regulation

A 2024 RCT published in Behavior Therapy showed that an 8-week mindfulness-based intervention led to significant improvements in attention and working memory in adults with ADHD — with effect sizes comparable to pharmacotherapy in some cases.

Final Thoughts

Adult ADHD is real, complex, and often misunderstood.
The field is evolving rapidly, with a push toward better diagnosticssafer treatments, and a broader understanding of how ADHD affects life across the lifespan.

As research continues to grow, clinicians are challenged not only to treat ADHD effectively but to do so thoughtfully — avoiding both underdiagnosis and overdiagnosis.

Stay tuned — the future of ADHD care is just getting started.

Natural ADHD Treatments: Evidence-Based Options

The search for natural alternatives to pharmaceutical treatments is a growing trend across many medical conditions, and ADHD is no exception. Although stimulant medications remain the gold standard for ADHD management, boasting large effect sizes, they are not without potential risks and side effects. This raises an important clinical question: are there evidence-based natural options that could serve either as primary therapies or as adjunctive treatments in ADHD? Exploring these alternatives could offer valuable strategies for patients and families seeking safer, well-tolerated interventions.

1. Hirayama et al., 2014 (Phosphatidylserine alone)

  • Population: 36 children (6–12 years) with ADHD
  • Dose: 200 mg/day PS
  • Duration: 15 weeks
  • Main outcomes: ADHD symptoms (teacher ratings), auditory memory

Reported effect:

  • They did not directly report Cohen’s d, but they reported statistically significant differences between PS and placebo groups on ADHD symptom scores.
  • Based on the mean differences and standard deviations reported:

Estimated effect size:
→ Cohen’s d ≈ 0.5–0.6 (moderate effect size)

✅ Interpretation: A medium, meaningful clinical effect, but not huge like you’d expect with stimulants (where d ~0.8–1.2).

2. Manor et al., 2012 (Phosphatidylserine + Omega-3 Fatty Acids)

  • Population: 200 children with ADHD symptoms (formal diagnosis not always required)
  • Dose: 300 mg PS + 120 mg EPA + 80 mg DHA daily
  • Duration: 15 weeks
  • Main outcomes: ADHD symptomatology, impulsivity, emotional regulation

Reported effect:

  • Statistically significant improvements over placebo.
  • Again, they didn’t directly report Cohen’s d, but they provided enough statistical info to estimate.

Estimated effect size:
→ Cohen’s d ≈ 0.3–0.5 depending on the specific symptom cluster.

✅ Interpretation: Small to moderate effect. (Closer to small-to-medium than medium.)

StudyPopulationInterventionKey Outcome
Hirayama 2014ADHD kids (n=36)200 mg PS/dayImproved attention & memory
Manor 2012Kids with ADHD symptoms (n=200)300 mg PS + 200 mg omega-3sReduced impulsivity, improved emotional regulation

🧠 Clinical Bottom Line:

  • Phosphatidylserine alone → moderate effect on ADHD symptoms (especially attention and memory).
  • PS + Omega-3 → small to moderate effect, mainly helping impulsivity and emotional regulation.
  • Better tolerated than traditional ADHD meds but obviously less potent.

👉 They could be considered in mild ADHD cases, in parents preferring “natural” options, or as adjuncts to other therapies.

💊 Methylene Blue: Science-Based Hope or Hype in a Bottle? 💙

As someone who supports thoughtful use of complementary and alternative medicine, I absolutely believe that compounds like SAMe or St. John’s Wort can offer meaningful benefits—when used appropriately and supported by evidence. But with the rise of anti-aging influencers, we’re seeing a familiar pattern: mechanistically promising compounds getting pushed far ahead of the science.

Methylene Blue is a perfect example.

🧬 Mechanistic appeal:

  • Enhances mitochondrial respiration
  • Acts as a redox mediator to reduce oxidative stress
  • May support autophagy and protein homeostasis
  • Studied for cognitive enhancement and neuroprotection

Sounds great on paper—and some early research is encouraging. But…

⚠️ Here’s the caution:

  • Most data is from animal studies or in vitro experiments
  • Human trials for cognitive or anti-aging outcomes are small, inconsistent, and early-stage
  • Long-term safety at “biohacker” doses remains largely untested

Many people are understandably drawn to the promise of longer, healthier lives, but often at the cost of embracing interventions before we truly understand their risks, benefits, or limitations.

Even if the science makes theoretical sense, biology doesn’t always behave the way our models predict.

Let’s stay open—but also skeptical. Not everything that sounds too good to be true ends up being true.

RFK Jr. Claims He’ll Identify the Cause of Autism by September

In a bold statement this week, Robert F. Kennedy Jr. announced that he will reveal the definitive cause of autism by September. Kennedy, a longtime critic of childhood vaccine programs, did not provide specific scientific details or a research plan, but implied that his administration would prioritize transparency and independent investigations into the condition’s origins.

The claim has sparked immediate controversy. Autism is a complex neurodevelopmental condition with a strong genetic foundation and a wide range of potential environmental influences—none of which have yielded a singular, definitive cause. The scientific consensus, built over decades of rigorous research, continues to support a multifactorial model rather than a simplistic explanation.

Many highly intelligent and dedicated scientists have spent years studying autism without identifying a single, unifying cause. One of the recurring issues that arises when politics intersects with science is a resistance to the idea that these are nuanced, multifaceted conditions. It’s not the most satisfying explanation—but it is consistent with the best evidence we have. My fear is that this type of investigation, under political pressure, could prematurely identify a false causal agent—such as vaccines—and reignite a harmful narrative that has already been thoroughly debunked.

Kennedy’s history of promoting vaccine-autism links adds further concern. The CDC, WHO, and a vast body of peer-reviewed research have all concluded there is no credible evidence connecting vaccines to autism. Suggesting otherwise not only undermines public trust in science and medicine—it risks the health of entire communities by fueling vaccine hesitancy.

For families and individuals affected by autism, the promise of discovering its origins is understandably compelling. But it’s critical that we approach that pursuit with scientific integrity, not political expediency.

Powered by WordPress.com.

Up ↑