Tag: mentalhealth

Disgraced Crypto King Sam Bankman And The Selegiline Patch 

There has been a lot of news recently about Sam Bankman, the onetime billionaire turned supervillain. At its peak, his company FTX had an in-house performance coach and psychiatrist named George K. Lerner. It’s unclear how many FTX employees Dr. Lerner treated but he did admit to treating some for ADHD and stated “the rate of ADHD at FTX was in line with most tech companies” whatever that means. I’m not here to debate the practices of the good doctor, but Bankman was known to talk publicly about experimenting with focus-enhancing medications. The main medications he allegedly used to become limitless were stimulants such as Adderall and the more interesting one to me and the topic of this week’s video the selegiline patch.

We are going to discuss selegiline in depth and try to understand why a medication primarily used to treat Parkinson’s may be useful for enhancing focus, creativity, and productivity in the fast-paced world of cryptocurrency. 

What is Selegiline?

Although many may not have heard of this medication, it’s actually a very old concept in psychiatry. A common “pimping” question in psychiatry residency is what was the first antidepressant medication? Most residents will say it was the tricyclic antidepressants which isn’t a bad guess but it’s not correct. The correct answer is the monoamine oxidase inhibitors (MAOIs) specifically iproniazid a failed treatment for tuberculosis. In 1952 researcher noted that patients receiving this medication became unusually happy, this was shocking considering the medication did nothing for their tuberculosis.

Transdermal selegiline is a tissue selective MAOI (MAO-A and MAO-B inhibitor in the brain) and a relatively selective MAO-B inhibitor in the gut. This is an important point, and I will explain more about it as we move through this topic. 

How Do MAOIs Work?

We are speaking about the transdermal selegiline patch here but there is also an oral version that is not approved for major depressive disorder and is a selective MAO-B inhibitor. 

The transdermal patch acts in the brain as an irreversible inhibitor of both MAO-A and MAO-B which are enzymes responsible for breaking down norepinephrine, serotonin, and dopamine which in turn will boost the noradrenergic, serotonergic, and dopaminergic neurotransmission. 

In lay terms this medication increases the availability of all three major neurotransmitters so that more serotonin, norepinephrine, and dopamine is available to act on post synaptic receptors affecting changes in cells and circuits involved in depression. 

FDA Approvals for Selegiline

This is a little complicated because news outlets have stated the medication is only used for Parkinson’s disease which is true if we are talking about the oral tablets. The transdermal patch is FDA approved for major depressive disorder. 

Off label use includes the treatment of treatment resistant depression, panic disorder, social anxiety (which MAOIs are usually superior at treating), treatment resistant anxiety, and Alzheimer’s disease. 

How to Dose Selegiline

The transdermal patch comes in various doses: 

  • 6 mg/24 hours
  • 9 mg/24 hours
  • 12 mg/24 hours 

The initial dose for depression is 6 mg/24 hours and it can be increased by 3 mg/24 hours every 2 weeks to a maximum dose of 12 mg/24 hours. Dietary modification to restrict tyramine from food sources is not required for the 6 mg/24hr patch but at higher doses the same food restrictions are required as other oral MAOIs such as phenelzine. This will be important for our next discussion on side effects. 

Side Effects of Selegiline

Before starting the medication, the patient should be aware of the potential for increased blood pressure. 

Notable Side effects include 

  • Skin reactions at the site of application (the location of the patch should be rotated daily) 
  • Headaches
  • Dry mouth 
  • Diarrhea
  • Insomnia
  • Sedation
  • Possible weight gain 

Serious side effects include: 

  • Hypertensive Crisis 
  • Seizure
  • Induction of manic episodes in bipolar disorder 

Contraindications when combined with:

  • Meperidine
  • Another MAOI 
  • SSRIs, SNRIs, TCAs, tramadol 
  • Dextromethorphan
  • St. John’s wort 
  • Methadone
  • History of Pheochromocytoma 
  • Elective surgery 
  • Proven allergy to selegiline 

The Dreaded Tyramine Reaction 

I believe that MAOIs might be the most effective of the antidepressants because of their ability to affect all three major neurotransmitter circuits, but they are rarely used clinically. In most residency training programs, we are not taught to use these medications. The main barrier is the dietary restrictions and risk for hypertensive crisis if the diet is not followed. 

This diet should be started a week or so before staring the medication. It allows the patient time to get accustomed to the dietary recommendations before being on the medication when the stakes are higher. The diet must be followed for 2 weeks after stopping the MAOI as it can take time for the MAO enzymes to regenerate due to irreversible inhibition. 

Tyramine is an amino acid that is found in some foods, and it helps to regulate blood pressure. MAOIs are responsible for breaking this amino acid down so it’s inactive and unable to causes an increase in blood pressure. When you block MAO excess tyramine will be available to affect blood pressure. 

Ingestion of a high tyramine meal is generally considered to be any meal with 40 mg or more in the fasted state. For the low dose transdermal patch 6 mg/24 hours studies show that 200-400 mg of tyramine in the fasted state is required for a hypertensive response. In general, at low doses dietary modification is not required. If the dose is increased to 12 mg/24 hours than 70-100 mg of tyramine is required for a hypertensive response. Although dietary modification may not be required at higher doses, it’s safer to avoid tyramine rich foods once the selegiline dose is increased and to be cautious at lower doses as well. 

Low Tyramine Diet Principles

When a patient is on an MAOI diet they should only eat things that are fresh. This goes for food that are stored as well as the storage process may affect the tyramine content. The patient should avoid foods that are beyond their expiration date and avoid fruits and vegetables that are overly ripe. Some cheeses are allowed in the diet, but all aged cheese should be avoided. The same can be said for meat products, fresh meats are fine, but aged or spoiled meats should be avoided. 

Fermented products need to be avoided when MAOIs are being used. This goes for all fermented products without exception. 

Chinese food and some other eastern foods should be avoided because they contain soy, shrimp paste, tofu, and soy sauces all of which are high in tyramine. 

Fava and other broad beans should be avoided this includes Italian green beans. 

Foods to Avoid

  • Matured or aged cheeses (cheddar, and blue examples) 
  • Meats: fermented or dry sausages (pepperoni, salami), aged, cured, unrefrigerated, pickled, smoked meats 
  • Caviar, dried, pickled, or smoked fish 
  • Overripe avocados, fava beans, sauerkraut, fermented soya bean, and soya bean paste 
  • Overripe fruits: canned figs, banana peel, orange pulp 
  • Beverages: chianti, sherry, liquors, all tap beers, unfiltered beer containing yeast 
  • Soy products: soy sauce, tofu 
  • Other: miso soup, yeast vitamin supplements, packaged soups 

Foods That are Allowed

  • Cheeses: cream cheese, ricotta, fresh cottage cheese, mozzarella, processed cheese slices like American cheese 
  • Milk Products: yogurt, sour cream, and ice cream 
  • Meat: fresh packaged or processed meat e.g. hot dogs 
  • Beverages: coffee, tea, soda, up to a maximum of 2 drinks either 12 oz of canned or bottled beer or 4 oz of red/white wine. 
  • Soy products: soy milk 
  • Other foods: chocolate in moderation and monosodium glutamate in moderation 

Onset of Action

The therapeutic effect is usually not immediate and still requires 2-4 weeks or longer once an adequate dose is reached. 

Augmentation

For expert psychopharmacologist Only: 

  • You may consider a stimulant such as d-amphetamine, or methylphenidate while watching for increased blood pressure, suicidal ideation, and activation of bipolar disorder) 
  • Lithium
  • Seconded generation dopamine blocking medication 
  • Mood stabilizing anticonvulsant 

Advantages to using MAOIs

  • May be effective in treatment resistant depression 
  • May improve atypical depressive symptoms such as hypersomnia and hyperphagia 
  • Lower risk for weight gain and sexual side effects 

Why Would Selegiline Improve Cognitive function?

Selegiline will increase dopamine and more dopamine in the prefrontal cortex theoretically will enhance cognitive function. A lot of the research on MAOIs and cognitive enhancement come from studies in neurodegenerative disorders such as Alzheimer’s disease. While promising as reported in several articles it does not appear that proper randomized controlled trials were ever conducted. If you watch my videos than you should know the risk of assuming that something that should theoretically work will also work clinically. This is the story of many medications in psychiatry. We also cannot extrapolate that to healthy individuals who do not have neurodegenerative disorders.

Selegiline is metabolized to l-amphetamine, and l-methamphetamine which are well known stimulants that may improve symptoms of attention deficit hyperactivity disorder (ADHD). Again, this is theoretical and has never been proven but based on the metabolism of the medication it makes sense that it may enhance cognition in those with ADHD or even healthy individuals. 

People often forget that depression itself is a major reason for cognitive problems. Depression in elderly patients is sometimes referred to as pseudodementia because it can look like the individuals has substantial cognitive deficits in severe cases. It’s possible that the improvement in depressive symptoms is responsible for the enhanced cognitive function. 

Conclusion

I think this is a good discussion because it highlights an often-forgotten class of medication in modern psychiatry that can be utilized for patients who have failed other medication options. Many psychiatrists are untrained or too scared to use these medications clinically. As far as cognitive enhancement and finding that limitless pill, I do not think this is it. While it may theoretically improve cognitive function it’s never been proven in randomized controlled trials. I would say the evidence supporting this idea is weak and may even be dangerous given the risk for hypertensive crisis. 

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The Best Antipsychotic Medication in The World 

Introduction:

I’ve said it before in previous videos, older medications are more effective and newer medications have fewer side effects. 

The advent of SSRIs in the late 1980’s and early 1990’s was largely driven by safety and not efficacy. The same is true for antipsychotic medications. This may be the reason most people haven’t even heard about Clozapine (brand name Clozaril). 

Efficacy

Clozapine is the single most effective antipsychotic available, and it works in treatment resistant schizophrenia where no other medication is proven to be effective. 

The results speak for themselves, 30% of previously treatment resistant patients experience symptom reduction within 6 weeks and that number jumps to 60% after 6 months of treatment. 

Clozapine has a slew of additional benefits including mood stabilizing prosperities (it can be used in bipolar disorder), reduction in psychogenic polydipsia and the hyponatremia associated with it, reduction in hostility and aggression, reduction in the risk of suicidal ideation, improvement in substance use, and it may even help patients quit smoking a difficult task in schizophrenia. 

So why are most schizophrenic patients not on this medication if it’s so great? 

Side effects, side effect, side effects

-Sedation: feeling tired this can largely be mitigated by dosing the medication at night before bedtime. 

-Tachycardia: It’s worth getting an EKG in patients with preexisting heart conditions or those at high risk due to hypertension and hyperlipidemia 

-Sialorrhea: excessive saliva production leading to drooling, no one wants this 

-Dizziness

-Constipation: this should be addressed immediately if a patient complains about it as it can lead to serious complications. In many cases Senna and Colace will do the trick

-Orthostatic hypotension 

-Weight gain 

Serious and potentially fatal Side effects include: 

-Agranulocytosis: decreased absolute neutrophil count which can result in increased risk for serious infection and the reason everyone on the medication gets weekly blood draws for the first 6 months 

-Seizures: clozapine is known to lower the seizure threshold 

-Myocarditis: inflammation of the heart usually due to a viral infection 

The risk for agranulocytosis is highest when starting treatment, usually during the first year of treatment (0.8%) and the maximum risk is between 4 and 18 weeks (when 77% of cases occur), although it can still occur at any point in the treatment.

Agranulocytosis

Monitoring is thus very important, and each patient must be registered in the Risk Evaluation and Mitigation strategy (REMS) data base before starting the medication. 

A CBC with differential must be drawn to calculate the absolute neutrophil count prior to starting treatment and then weekly for the first 6 months. Then monitoring continues every 2 weeks for the next 6 months and finally monthly after the first year of treatment. 

If agranulocytosis occurs stopping clozapine allows majority of cases to recover within 14 days. 

Now that we know that this medication is very effective but comes with a high side effect burden a natural next question might be why does the medication work? 

Mechanism of Action

Clozapine has very low affinity for the D2 receptors which is unique as most other antipsychotics will bind strongly to D2 receptors. Clozapine had far greater D1 and D4 binding affinity, blocking both receptors. 

Clozapine also has significant activity at other neurotransmitter sites. It blocks alpha receptors which may be the reason for orthostatic hypotension. It blocks histamine H1 receptors resulting in sedation and weight gain. It blocks 5-HT2A serotonin receptors and is highly anticholinergic resulting in constipation and urinary retention. 

It has two unique properties; it influences the glutamate system by altering NMDA receptor sensitivity and increases the release of brain derived neurotrophic factor BDNF. 

Metabolism And Drug Interactions

Clozapine is primarily metabolized by CYP450 1A2 and 3A4 and cigarette smoking will cause a reduction in clozapine levels due to induction of CYP 1A2. 

Before Starting the Medication

Before starting clozapine, the ANC must be above 1,500. If neutropenia develops treatment will depend on the severity of the drop. 

Mild Neutropenia: ANC 1,000-1,499, you would continue treatment and check an ANC three times weekly until it reaches 1,500. 

Moderate Neutropenia: ANC between 500 and 999, stop treatment and check the ANC daily until it reaches 1,000 then 3 times weekly until it reaches 1,500 then weekly for 4 weeks before returning to the patients prior monitoring schedule. 

Severe Neutropenia: ANC less than 500, stop treatment and check an ANC daily until it’s 1,000 then 3 times weekly until it’s 1,500. The patient should not be rechallenged without a hematology consult and clear benefits that outweigh the risks. 

Dosing

Clozapine can be started at 12.5 to 25 mg at bedtime. The dose can be increased 25 mg/day inpatient and 25 mg per week in the outpatient setting as tolerated. 

You can overlap prior treatment with another antipsychotic and tapper the old medication once clozapine dose reaches 100 mg or more. 

Plasma Levels

Clozapine dose should be based on serum levels, with a target blood level of 200 to 300 ng/ml. If there are still symptoms present the target serum level is 450 ng/ml. There are no benefits to serum levels above 900 ng/ml. 

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Hey Doc, What’s Psychogenic Polydipsia?

This is one of the interesting occurrences that can present on the medical floors, emergency rooms, or inpatient units. 

A patient comes in with an established diagnosis of schizophrenia and is currently taking ziprasidone. The person is constantly asking for glasses of water and drinking water excessively throughout the day. 

You might be thinking what is the harm in drinking water, isn’t staying hydrated a healthy behavior? 

…But you order a basic metabolic panel and find the persons sodium is 125 mEq/L. 

Now the panic sets in, it’s time to worry and the patient continues to complain of feeling thirsty and is noted to be urinating frequently. 

There are a few possibilities for the persons behavior, but we need to consider psychogenic polydipsia or primary polydipsia. This was first described in the 1930s in patients with schizophrenia who drank water excessively resulting in low serum sodium levels. 

The cause is unknown, but these patients may have an acquired defect in the hypothalamic thirst regulation. Medications have also been associated with worsening of psychogenic polydipsia. It’s thought to be related to the anticholinergic effects of many of these medications. Examples include carbamazepine, chlorpromazine, oxcarbazepine, haloperidol, and valproate. 

Psychogenic polydipsia (PP) is common, and it’s usually associated with schizophrenia but can occur in other psychotic, mood, and anxiety disorders. Some users of MDMA also develop PP. 

PP is a primary problem where the patient is drinking too much water. This results in a dilution of the blood and thus a low sodium level (defined as < 135 mEq/L) and low serum osmolality. The urine will also be dilute < 100 mOsmol/kg with low urine sodium. 

Two other potential places where we can see polyuria are in cases of hyperglycemia from uncontrolled diabetes and nephrogenic diabetes insipidus. The key distinction in the first case is hyperglycemia. The water is drawn out by osmotic diuresis secondary to excess glucose in the urine. The key labs here are a fasting glucose and a urine analysis which should show hyperglycemia and glucose in the urine. In nephrogenic diabetes insipidus the brain secretes ADH just fine, but the kidney does not respond to it. The urine will be dilute, but the serum sodium level will be high not low separating it from psychogenic polydipsia.

Treatment includes fluid restriction to 1000-1500 mL/day, this can be difficult to enforce even on an inpatient unit. The person may need to be watched because sources like the bathroom sink or even toilet may be used to consume more water. This is usually enough of a treatment, but should the sodium remain low you can add sodium chloride tablets 1-3 grams daily. 

In severe cases where the sodium drops below 120 the person can have a seizure. In these cases, it’s best to handle the fluid replenishment on the medical floor with 3% saline. 

You must be careful not to correct the sodium too rapidly as it can result in the dreaded central pontine myelinolysis which can result in quadriparesis. That’s why we correct the sodium at a rate of no more than 10 mmol/L/24 h or 0.5 mEQ/L/h 

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Everything You Need to Know About Trintellix (Vortioxetine)

Introduction:

Vortioxetine is sold under the brand name Trintellix, and Brintellix and it’s approved for use in major depressive disorder. The name was changed to Trintellix in the U.S. due to confusion with Brillinta an anti-platelet medication. It was studied in generalized anxiety disorder (GAD) at lower doses, but the quality of the evidence is poor and does not appear to improve symptoms or quality of life in patients with GAD. 

I want to make a quick point before going into the details about the medication. When I say the effect size is moderate and Vortioxetine does not perform better than other options for depression, I’m not saying in an individual case that it may not outperform other antidepressants that the person has tried in the past. It very well might for that individual. I’m talking about on average in large sample sizes, Vortioxetine does not outperform other medications according to the current literature. It’s also not a go to medication for treatment resistant depression, the literature does not support this either.

The one place Vortioxetine does seem to stand out is cognitive function. Multiple studies have shown this medication to improve cognitive dysfunction associated with depression. It also appears to improve cognitive function in geriatric depression but failed to show any benefit in neurocognitive disorders like Alzheimer’s disease. It was also looked at as a potential treatment for attention deficit hyperactivity disorder (ADHD) but failed to show an adequate benefit in trials. 

Mechanism of Action and Receptor Targets

This medication falls into a class known as serotonin modulators and stimulators. It is thought to work by several different mechanisms:

-Serotonin reuptake inhibitor

-5-HT1A agonist (may diminish sexual side effects) 

-5-HT1B partial agonist 

-5-HT1D, 5-HT3 (may enhance noradrenergic and cholinergic activity that improves cognition while reducing nausea), and 5-HT7 antagonist (pro-cognitive and antidepressant effects) 

The most robust action is on serotonin reuptake and 5-HT3 antagonism, while the other interactions are considered minor. 

Target Affinity Ki (nM)Action 
SERT1.6Inhibition 
NET113Inhibition 
5-HT1A 15Agonist 
5-HT1B33Partial agonist 
5-HT1D 54Antagonist 
5-HT2C180 
5-HT3A3.7Antagonist 
5-HT719Antagonist 

Metabolism

Vortioxetine is metabolized by CYP2D6, 3A4/5, 2C19, 2C9, 2A6, 2C8 and 2B6, the half-life is 66 hours and it’s dosed one time per day. Reduction is dosing may be needed for patients taking strong CYP2D6 inhibitors (e.g. bupropion).

Dosing:

-5-20 mg/day 

-Tablets come as 5 mg, 10 mg, and 20 mg 

-The initial dose for depression is 10 mg which can be increased as needed to a maximum dose of 20 mg daily. 

-For GAD does were kept lower 5-10 mg/day range 

-Can be taken with or without food 

-It can be stopped without a tapper 

Side Effect:

Common side effects include nausea, vomiting, constipation, sexual dysfunction, weight gain is unusual but possible. Nausea and sexual dysfunction were the most common side effects; all other side effects were reported in less than 10% of cases. 

Sexual dysfunction was found in both the plebe group and the treatment arm. The incidence was 14-20% for placebo and 16-34% for those in the treatment arm.

Rare life-threatening side effects include seizures, induction of mania and suicidal ideation. 

Avoid using tramadol as it can increase the risk of seizure, and do not combine with MAOIs as this can result in serotonin syndrome. 

It’s generally not recommended in pregnancy. 

Conclusion

While this medication may be helpful for some individuals there is no evidence to support its use in treatment resistant depression or other disorders outside of the primary indication major depressive disorder. There does seem to be a benefit for patients who have significant cognitive dysfunction as a result of depression and maybe that is where this medication best fits into a treatment plan. The main side effects are nausea and sexual dysfunction which are common with all antidepressant options. You must also consider the cost of the medication in comparison to duloxetine which outperformed Vortioxetine in some clinical trials.

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Malingering In Psychiatry

  • Let’s first define malingering, this is the production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives. 
  • Not all lying involves secondary gain, but ALL malingering does involve secondary gain 
  • Common secondary gains include avoiding military service, avoiding work, financial incentives, avoiding legal actions, and obtaining controlled substances 
  • Feigning mental illness is not the same as malingering because the reason behind the false production of symptoms is not assumed with feigning symptoms. 
  • Factitious disorder is the voluntary production of symptoms, but this is with the goal of assuming the sick role or role of a patient, it’s not done for secondary gain. 

Consider malingering when….

-Rare symptoms are present 

-Improbable symptoms are being reported

-Rare combination of symptoms are present

-Reported Vs observed symptoms are not congruent

Malingered Depression:

-25-30% of patients who claimed major depression in civil litigation were probably malingering

-Pay careful attention to facial expressions 

-Pay careful attention to motor function, psychomotor retardation is an important observable sign

-If appetite changes are reported look for actual objective weight change 

-symptoms opposite of depression 

-blaming others for everything is not the way guilt typically presents in depression, this is externalizing and not taking personal responsibnility

Malingered Psychosis: 

-Often in true psychosis people can describe the voice/s, is it loud, soft, male, female, you have some experience of what you heard. When you ask a malingering patient about a voice, they should have some ability to describe what they are hearing, if not consider malingering.

-If you are suspicious, begin with open ended questions, ask them to describe things in their own words. 

-Genuine AH are in words or sentences, drug Hallucinations usually occur as unformed noises.

-The location of the voice inside the head or outside is no longer a good predictor of malingering 

-Many times the content of voices are derogatory in nature

-Other signs of malingered psychosis include Vague or inaudible auditory hallucinations, AH not associated with delusions (86% of AH have an associated delusion), no strategies to diminish voices 76% of patients have some coping strategy to diminish the voices. They claim that all instructions are obeyed, the hallucinations are visual alone, seeing little people or giant people for example.

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   Why It’s Important to Thrive and Not Just Survive

We Spend a significant amount of time as doctors monitoring for adverse outcomes. 

We use the absence of disease as an indicator of health. 

But the mere absence of disease is not enough to proclaim good health. 

If we only monitor for the absence of disease, we miss the things that are most important in our patients’ daily lives. 

The things I’ve found to be most important in my life, and often lacking in my patient’s lives are…

Being happy, having a sense of purpose and meaning, and having good relationships which are sometimes ignored if overt signs and symptoms of disease are not present. 

Being “well” is a state of complete mental, physical, and social wellbeing. 

Having a purpose in life is associated with reduced mortality risk, so is life satisfaction. Things like loneliness and social isolation are associated with increased mortality.

When these needs are met people not only live longer but they live with intention. 

Let’s Look beyond the absence disease 

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Guide To Viewing My Content

If you are new to the blog and my social media content, we should start with a brief introduction. 

My name is Dr. Garrett Rossi, I’m a medical doctor who specializes in adult psychiatry. I’m board certified by the American Board of Psychiatry and Neurology. I’ve practiced in multiple settings including inpatient, outpatient, partial care, assertive community treatment teams, and I provide ECT services.

I make mental health content on multiple social media platforms and each one has a specific style and type of content. 

Shrinks In Sneakers YouTube Click Here

This is where you can find the deep dives on mental health topics including medication reviews, psychiatric diagnosis, and various other topics. Videos can range anywhere from 5-20 minutes and time stamps are available in the descriptions for longer content. 

Shrinks In Sneakers Instagram Click Here:

This is where you can find shorter videos and posts on mental health topics. The focus on Instagram is more on mental health advocacy, and myths about psychiatry and mental illness. The content here is shorter but still has a lot of educational value. 

Shrinks In Sneakers LinkedIn:

This is where you can find more information about my professional activities. I have information about my advocacy work, professional memberships, publications, and is another good place to follow my work. I make frequent posts here as well. 

Shrinks In Sneakers Twitter: 

Here I’m not very active and haven’t spent much time but I do update blog posts and other relevant information here as well. 

If you have a question or want to get in touch with me, I am most active on YouTube, LinkedIn, and Instagram. 

We are building a community where empathy is a central part of the content. The goal is to make psychiatry more accessible, provide education, and reduce stigma associated with mental health treatment. 

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How to Manage Aggression with Psychopharmacology in an Inpatient Setting

I’m very careful about the content I consume and the resources I use to grow as a psychiatrist.

When I endorse something like The Psychiatry & Psychotherapy Podcast, you know it’s something I personally use and trust. 


I had the opportunity to work with Dr. Puder on a recent episode How to manage aggression with psychopharmacology in an inpatient setting. Unfortunately, I got caught up taking care of patients on my inpatient service on the day of the recording and did not get to talk with Dr. Puder and Dr. Cummings.

I would encourage you to listen to all the episodes, but my personal favorites are the ones with Dr. Cummings. He has a wealth of knowledge and I’ve learned some amazing clinical pearls that I apply in my daily practice. 

Check out the episode, you will not be disappointed

https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-145-how-to-manage-aggression-with-psychopharmacology-in-an-inpatient-setting

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What is Aphasia?

Aphasia is an inability to comprehend or formulate language usually due to damage to specific brain regions responsible for these processes. 

There are two important points here to note: 

1. Aphasia is the consequence of another brain disorder such as stroke, brain tumor, traumatic brain injury, viral infections like HSV or neurovegetative process (think dementia here). 

2. There are different types of aphasias, most notably they can be broken down into expressive and receptive aphasia

To be diagnosed the person must have significant impairment in one or more of the following

1. Auditory comprehension

2. Verbal expression

3. Reading and writing

4. Functional communication

About 2 million people are affected by this disorder in the U.S. and strokes account for most of the documented cases. 

One of the most common presentations is anomic aphasias where individuals have word retrieval failures and cannot express the words they want to say (usually nouns and verbs). Some level of this is seen in all types of aphasia.

There can be many other presentations including: 

-inability to comprehend language 

-inability to pronounce words

-inability to speak spontaneously

-inability to read 

-inability to write 

The two most common examples: 

Receptive aphasia (Wernicke’s):

This is a fluent aphasia where the person can speak in sentences but there is no meaning, unnecessary words, and possibly the creation of new words called neologisms. 

-They have poor auditory and reading comprehension.

-There is fluent but nonsensical written or oral expression.

-Since thy do not comprehend language well they are often unaware of their mistakes. 

-The area of the brain affected is well known and established it’s the left temporal lobe as indicated in the picture. 

Expressive aphasia: Broca’s 

-These individuals will speak in short, meaningful phrases with great effort. It will be noticeable how much effort they are putting into speaking. 

-They are usually able to understand the speech of others and are aware of the difficulties they are having leading to frustration. 

-The location of the brain injury is well established, damage to the frontal lobe causes this presentation 

Primary progressive aphasia 

-This is a form of dementia 

-Characterized by gradual loss of language functioning while other cognitive domains such as personality and memory are mostly preserved 

-It usually starts with sudden word finding difficulties and progresses to reduced ability to form grammatically correct sentences, and impaired comprehension 

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New Treatment for Acute Agitation

The FDA has approved dexmedetomidine sublingual film for the treatment of agitation associated with schizophrenia or Bipolar I/II disorder in adults.  

When agitation and aggression are severe, swift resolution of the situation is required.

Introduction:

Since the advent of chlorpromazine in the 1950’s pharmacological intervention has been a mainstay in these acute situations. In many cases the combination of haloperidol, lorazepam, and diphenhydramine, the so called B-52 are administered intramuscularly when quick resolution of agitation is required for the safety of the person and staff. 

But what happens when these methods fail to provide adequate relief and person remains agitated?

There are few options available outside of the dopamine blocking medications and benzodiazepines. 

I’ve been in situations as an early career psychiatrist where I’ve had to treat severe agitation that is unresponsive to the traditional methods of treating agitation. 

After multiple medications failed to adequately treat the agitation, I called the medical floor to transfer the person for a Dexmedetomidine (precedex) drip. This is a medication I’ve seen work well in the ICU setting with agitated delirium. 

But drips are complicated to use and require careful monitoring on the medical floor. I was thinking it would be great if there was an option that did not require IV placement or transfer to the medical floor. 

Mechanism of Action:

Recent studies have looked at sublingual Dexmedetomidine as a potential new treatment for agitation. 

Dexmedetomidine is an alpha-2 noradrenergic agonist approved by the FDA for IV sedation and analgesia and limitted to 24 hours. It induces sleep by activating alpha-2 presynaptic receptors reducing norepinephrine release. Both sedation and awakening are rapid, and the medication is safe but does require monitoring of blood pressure and heart rate. 

Phase 3 Clinical Trial Results:

A phase 3 clinical trial of 120 micrograms and 180 micrograms of sublingual dexmedetomidine was compared to placebo in patients with bipolar disorder. They used the excited portion (PEC) of the PANSS to measure efficacy and found a response beginning at 20 minutes and continuing to 120 minutes at both doses. 90% of participants in the 180 microgram and 76% in the 120 microgram groups achieved a response. No significant adverse events occurred in the treatment groups.  

Hsiao JK. Sublingual Dexmedetomidine as a Potential New Treatment for Agitation. JAMA. 2022;327(8):723–725. doi:10.1001/jama.2021.21313

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