The 15 Scariest Mental Disorders of All Time
Imagine having a mental disorder that makes you believe that you are a cow; or another that you’ve somehow become the walking dead. Pretty freaking scary, eh? Well, while relatively rare, these disorders are all too real.
Worldwide, 450 million people suffer from mental illness, with one in four families affected in the United States alone. While some mental disorders, like depression and anxiety, can occur organically, others are the result of brain trauma or other degenerative neurological or mental processes. Look, having any mental illness can be scary, but there are some disorders that are especially terrifying. Below, I’ve described the 15 scariest mental disorders of all time.
‘Alice in Wonderland’ Syndrome
In 1865, English author Lewis Carroll wrote the novel Alice’s Adventures in Wonderland, commonly shortened to ‘Alice in Wonderland.’ Considered to be one of the best examples of the literary nonsense genre, (seriously, who knew they even had a nonsense genre?) it is the tale of an unfortunate young girl named Alice, who falls through a rabbit hole into a subterranean fantasy world populated by odd, anthropomorphic creatures. That’s your vocabulary word for the week… anthropormorphic. Popular belief is that Carroll was tripping when he penned it. Regardless if that’s true or not, what is true is that one of Alice’s more bizarre experiences shares its characteristics with a very scary mental disorder. Also known as Todd Syndrome, ‘Alice in Wonderland’ Syndrome causes one’s surroundings to appear distorted. Remember when Alice suddenly grows taller and then finds she’s too tall for the house she’s standing in? In an eerily similar fashion, people with ‘Alice in Wonderland’ Syndrome will hear sounds either quieter or louder than they actually are, see objects larger or smaller than what they are in reality, and even lose sense of accurate velocity or textures they touch. Described as an LSD trip without the euphoria, this terrifying disorder alters one’s perception of their own body image and proportions. Fortunately, this syndrome is extremely rare, and in most cases affects people in their 20’s who have a brain tumor or history of drug use. If you need yet another reason to not do drugs… well, there ya go.
Alien Hand Syndrome
While most likely familiar from cheesy horror flicks, Alien Hand Syndrome isn’t limited to the fictional world of drive-in B movies. Those with this very scary, but equally rare mental disorder experience a complete loss of control of a hand or limb. The uncontrollable body part takes on a mind and will of its own, causing sufferers’ “alien” limbs to choke themselves or others, rip clothing off, or to viciously scratch themselves, to the point of drawing blood. Alien Hand Syndrome most often appears in patients suffering from Alzheimer’s Disease or Creutzfeldt-Jakob Disease, a degenerative brain disorder that leads to dementia and death, or as a result of brain surgery separating the brain’s two hemispheres. Unfortunately, no cure exists for Alien Hand Syndrome, and those affected by it are often left to keep their hands constantly occupied or use their other hand to control the alien hand. That last one actually sounds even worse- one unaffected arm fighting against the affected arm that’s trying to tear into the person’s own flesh. Yikes.
Also known as Body Integrity Disorder and Amputee Identity Disorder, Apotemnophilia is a neurological disorder characterized by the overwhelming desire to amputate or damage healthy parts of the body. I recall a woman with Apotemnophilia making worldwide news ages ago when she fought with her HMO to cover the amputation of one of her otherwise healthy legs. Good luck; they don’t even cover flu shots. I remember I was pretty shocked that she found a surgeon to agree to do the amputation in the first place, as it seemed to me that might violate that little thing called the Hippocratic Oath us docs took when we got our medical degrees, specifically that part about ‘do no harm’… and sparked a debate about the ethical dilemma of treating or “curing” a psychiatric disorder by creating what is essentially a physical disability. Though not a whole heck of a lot is known about this strangely terrifying disorder, it is believed to be associated with damage to the right parietal lobe of the brain. Because the vast majority of surgeons will not amputate healthy limbs based purely upon patient request, some sufferers of Apotemnophilia feel forced to amputate on their own, which of course is a horrifying scenario. Of those who have convinced a surgeon to amputate the affected limb, most say they are quite happy with their decision even after the fact.
Those who suffer from the very rare- but very scary- mental disorder Boanthropy believe they are cows, and usually even go so far as to behave as such. Sometimes people with Boanthropy are even found in fields with cows, walking on all fours and chewing grass as if they were a true member of the herd. When found in the company of real cows, and doing what real cows do, people with Boanthropy don’t seem to know what they’re doing when they’re doing it. This apparently universal finding has led researchers in the know to believe that this odd mental disorder is brought on by possible post-hypnotic suggestion, or that it is a consequence of dreaming or a sleep disturbance, sort of kin to somnambulism, aka sleepwalking. I can buy the sleepwalking thing. I have a patient that is a lifelong sleepwalker who sleep-eats, sleep-cleans, sleep-cooks, sleep-destroys, sleep-online-shops, sleep-everythings. Some mornings she wakes up to very unpleasant findings of the house in total disarray, electronics dismantled and improperly and ridiculously fashioned together, every piece of furniture moved or a sink full of dishes and pots and pans with dried up food in them. Before setting up prevention measures, she even had single episodes of adult sleep-driving, and even sleep-biking at (eek!) age 9. In the middle of the night, her mother awoke to what she thought was the big garage door opening, and when she went to check, she saw her coasting out of the driveway on her bright yellow bike, heading right toward a very busy highway. She always has zero recall of the events afterwards. If she can do all of that while essentially sleeping, it would be comparatively easy to wander out to a pasture on all fours and stick around to munch on some grass. Curiously, it is believed that Boanthropy is even referred to in the Bible, as King Nebuchadnezzar is described as being “driven from men and did eat grass as oxen.” Or was it King Nemoochadnezzar? No? Okay, moooving on…
Named after Joseph Capgras, a French psychiatrist who was fascinated by the effective illusion of doubles, Capras Delusion is a debilitating mental disorder in which a person believes that the people around them have been replaced by imposters. As if that’s not bad enough, these imposters are usually thought to be planning to harm the sufferer. It really sounds like a bad Tom Cruise movie. Oh, wait; that’s redundant. Anyhoo, in one case, a 74-year-old woman with Capgras Delusion began to believe that her husband had been replaced with an identical looking imposter who was out to hurt her. Fortunately, Capgras Delusion is relatively rare, and is most often seen after trauma to the brain, or in those who have been diagnosed with dementia, schizophrenia, or severe epilepsy.
Like people with Boanthropy, people suffering from Clinical Lycanthropy also believe they are able to turn into animals; but in this case, cows are typically replaced with wolves and werewolves, though occasionally other types of animals are also included. Along with the belief that they can become wolves and werewolves, people with Clinical Lycanthropy also begin to act like the animal, and are often found living or hiding in forests and other wooded areas. Didn’t Tom Cruise play a werewolf in one of his many (vapid) movies? Or was it a vampire? Werewolf, vampire – tomato, potato.
In a case of life imitating art, or life inspiring art, we have Cotard Delusion. In this case, the ‘art’ is zombies, a la The Walking Dead. Oooh, scary! For ages, people have been fascinated by the walking dead. Cotard Delusion is a frightening mental disorder that causes the sufferer to believe that they are literally the walking dead, or in some cases, that they are a ghost, and that their body is decaying and/or they’ve lost all of their internal organs and blood. The feeling of having a rotting body is generally the most prevalent part of the delusion, so it doesn’t come as much of a surprise that most patients with Cotard Delusion also experience severe depression. In some cases, the delusion actually causes sufferers to starve themselves to death. This terrifying disorder was first described in 1880 by neurologist Jules Cotard, but fortunately, Cotard’s Delusion, like good zombie movies, has proven to be extremely rare. The most well-known case of Cotard Delusion actually occurred in Haiti, circa 1980’s, where a man was absolutely convinced that he had previously died of AIDS and was actually sent to hell, and was then damned to forever walk the earth as a zombie in a sort of pennance to atone for his sins.
Diogenes Syndrome is a very exotic name for the mental disorder commonly referred to as simply “hoarding,” and it is one of the most misunderstood mental disorders. Named after the Greek philosopher Diogenes of Sinope (who was, ironically, a minimalist), this syndrome is usually characterized by the overwhelming desire to collect seemingly random items, to which an emotional attachment is rapidly formed. In addition to uncontrollable hoarding, those with Diogenes Syndrome often exhibit extreme self neglect, apathy towards themselves or others, social withdrawal, and no shame for their habits. It is very common among the elderly, those with dementia, and people who have at some point in their lives been abandoned or who have lacked a stable home environment. This is likely because ‘stuff’ never hurts you or leaves you, though most people with the disorder are unlikely to be able to make that connection. Fortunately or unfortunately, depending on how you look at it, this disorder is much more common than some of the others I’ve mentioned here.
Dissociative Identity Disorder
Dissociative Identity Disorder (DID), is the mental disorder that used to be called Multiple Personality Disorder. Another disorder that has inspired a myriad of novels, movies, and television shows, DID is extremely misunderstood. Generally, people who suffer from DID often have 2-3 different identities, but there are more extreme cases where they have double digit numbers of identities. There was a “reality” show a few years ago that centered on a young mother of two that supposedly had like 32 distinct personalities. All of them had names and ranged from a five-year-old child to an old grandpa; and according to her, a few of them were homosexual while the rest were not, so she was required to be bisexual. She claimed that many of the personalities knew everything about all of the others, and they would get mad at or make fun of the others at various times. What’s more, she would “ask” other personalities to come forward so that producers could ask them questions for the camera’s sake, and her voice and mannerisms changed, depending on the different characteristics of the personalities. It was all pretty difficult to buy to be honest, because I’ve seen a lot of people with DID, and none seemed like they were having as much fun with their illness as she did. In true DID cases, sufferers routinely cycle through their personalities, and can remain as one identity for a matter of hours or for as long as multiple years at a time. They can switch identities at any time and without warning, and it’s often nearly impossible to convince someone with DID that they actually have the disorder, and that they need to take medications for it. For all of these reasons, people with Dissociative Identity Disorder are often unable to function appropriately in society or live typical lives, and therefore, many commonly live in psychiatric institutions, where their condition and their requisite medications can be closely monitored.
Most people cringe at the first sniffle indicating a potential cold or illness, especially these days, but not those with Factitious Disorder. This scary mental disorder is characterized by an obsession with being sick. In fact, most people with Factitious Disorder intentionally make themselves ill in order to receive treatment; and this is what makes it different than hypochondria, a condition where people blow mild symptoms into something they aren’t, kind of like if you cough once and automatically think you have covid-19. Sometimes in Factitious Disorder, people will simply pretend to be ill, a ruse which includes elaborate stories, long lists of symptoms, doctor shopping, and jumping from hospital to hospital. Such an obsession with sickness often stems from past trauma or a previous genuinely serious illness. It affects less than .5% of the general population, and while there’s no cure, psychotherapy is often helpful in limiting the disorder.
Imagine craving the taste of a book or wanting to have sex with a car. That’s reality for those affected by Kluver-Bucy Syndrome, a mental disorder typically characterized by memory loss, the desire to eat inedible objects, and sexual attraction to inanimate objects such as automobiles. I’ve seen a television documentary that featured people with strange fetishes, and they had two British guys that were sexually attracted to their cars. They gave them names and described their curves in the same manner that some men describe women. While one guy (supposedly) limited it to “just” caressing his car, the other actually also made out with his car; I’m talking about tongue and everything. Talk about different strokes! Because of the memory loss, not surprisingly, people with Kluver-Bucy Syndrome often have trouble recognizing objects or people that should be familiar. They also exhibit symptoms of Pica, which is the compulsion to eat inedible objects. The same wierd fetish documentary featured two young women that were “addicted” to eating weird stuff; one routinely ate her sofa cushions. She actually pulled the foam apart into bite sized pieces and ate them, many times a day. She became so used to doing so that she would get anxious if she went too long without eating it, so she started having to bring pieces of her sofa with her to work. I’m guessing she didn’t have to worry about co-workers stealing her food. She had started eating the cusions so long ago that she was actually on her second couch. Her family was so concerned about the potential medical ramifications of eating couch cushions that they made her see a gastro doc, who thought he was being punked when he asked why she was there. After imaging studies, she was in fact diagnosed with some intestinal issues and told to stop eating couch cushions, but the desire was too great for her to cease. She’s probably on her fourth couch by now. The other girl actually loved eating powder laundry detergent. She described the taste in the same dreamily excited way a foodie describes a chef’s special dish du jour. This terrifyingly odd mental disorder is difficult to diagnose, and seems to be the result of severe injury to the brain’s temporal lobe. Unfortunately, there is not a cure for Kluver-Bucy Syndrome and sufferers are typically affected for the rest of their lives.
Obsessive Compulsive Disorder
Though it’s widely heard of and often mocked, Obsessive Compulsive Disorder (OCD) is rarely well understood. OCD manifests itself in a variety of ways, but is most often characterized by immense fear and anxiety, which is accompanied by recurring thoughts of worry. It’s only through the repetition of tasks, including the well-known obsession with cleanliness, that sufferers of OCD are able to find relief from such overwhelming feelings. To make matters worse, those with OCD are often entirely aware that their fears are irrational, but that realization alone actually brings about a new cycle of anxiety. OCD affects approximately 1% of the population, and though scientists are unsure of the exact cause, it is thought that chemicals in the brain are a major contributing factor. I’ve discussed OCD and recounted OCD patient stories many times in this blog and in my book, Tales from the Couch.
Paris Syndrome is an extremely odd but temporary mental disorder that causes one to become completely overwhelmed while visiting the city of Paris. Stranger still, it seems to be most common among Japanese travelers. Of the approximately 6 million Japanese visitors to Paris each year, one to two dozen of them experience the overwhelming anxiety, depersonalization, derealization, persecutory ideas, hallucinations, and acute delusions that characterize Paris Syndrome. Despite the seriousness of the symptoms, doctors can only guess as to what causes this rare and temporary affliction. Because most people who experience Paris Syndrome do not have a history of mental illness, the leading thought is that this scary neurological disorder is triggered by the language barrier, physical and mental exhaustion, and the reality of Paris as compared to the idealized version. Slam! I’ll bet the Paris Tourism Board hates to hear about this one! Huh houn, wee wee monsieur.
The Reduplicative Amnesia diagnosis was first used in 1903 by neurologist Arnold Pick, when he described a patient with a diagnosis of what we know today as Alzheimer’s Disease. It is actually very similar to Capgras Syndrome, in that it involves duplicates, but instead of believing that people are duplicates, people with Reduplicative Amnesia believe that a location has been duplicated. This belief manifests itself in many ways, but always includes the sufferer being convinced that a location exists in two places at the same time. Today, it is most often seen in patients with tumors, dementia, brain injury, or other psychiatric disorders.
Stendahl Syndrome is a very unusual psychosomatic illness; but fortunately, it appears to be only temporary. The syndrome occurs when the sufferer is exposed to a large amount of art in one place, or is spending time immersed in another environment characterized by extreme beauty; probably one of those places that “takes your breath away.” Those who experience this scarily weird mental disorder report sudden onset of rapid heartbeat, overwhelming anxiety, confusion, dizziness, and even hallucinations. It actually sounds a lot like a panic attack to moi. Stendahl Syndrome is named after the 19th century French author who described in detail his experience after an 1817 trip to Florence, which is evidently a beautiful place. I have it on good authority that Stendahl Syndrome has never happened to any visitor to Paris, which, oddly enough is Stendahl’s country of origin.
So, we’ve learned a lot today: that there is a nonsense literary genre, that there are a bunch of freaky and frightening mental disorders out there, that some people might need to look up the word anthropormorphic, that illicit drugs are bad for yet another reason, that a lot of terrible B movies are actually based on some pretty obscure mental disorders, that people with Boanthropy probably get a lot of fiber in their diet, that the lives of people with Capras Delusion sound a lot like a bad Tom Cruise movie, that the term “bad Tom Cruise movie” is redundant, that Tom Cruise probably has Clinical Lycanthropy, that Tom Cruise is a tool, oops, sorry, everyone already knew that. We also learned that there is no longer such thing as Multiple Personality Disorder; it is now called Dissociative Identity Disorder, that Kluver-Bucy Syndrome is threatening to couches, and that if you have Kluver-Bucy Syndrome, co-workers will never steal your lunch. We learned that Japanese tourists hate Paris, and that Stendahl Syndrome never happens there. And we learned lots of other cool stuff, but that if you have so much stuff that you can’t walk through your house you likely have Diogenes Syndrome, probably because you have a deep seated knowledge that stuff never hurts you or leaves you.
Please check out my videos on YouTube- better yet, hit that subscribe button, and share them with folks. And as always, my book, Tales from the Couch has lots more information and patient stories on various psychiatric diagnoses and is available on Amazon and in the office. Be well, everyone!Learn More
Caplyta (lumateperone): New for Schizophrenia…and More?
Before we talk about Caplyta (lumateperone), I want to announce that I take no remuneration of any kind from any pharmaceutical or healthcare company. I am providing the following information solely for educational purposes.
Caplyta (lumateperone) has recently been approved by the FDA for the treatment of schizophrenia in adults, and it is expected to be available by prescription by late April 2020. This new drug seems to have a lot of promise, especially for patients who don’t do well on other drugs, or cannot tolerate the side effects of other drugs. This may sound strange, but scientists don’t actually know what the drug’s mechanism of action is, meaning that they don’t know exactly how it works. They have some educated guesses, and I’ll talk about those later. But believe it or not, it’s not that unusual for a drug’s mechanism of action to be partially or poorly understood…it happens frequently.
They’ll figure it all out in time, but what matters right now is that they do know the drug’s efficacy, which is it’s effectiveness, in treating schizophrenia in adults. I think that this will be a vitally important drug, especially for patients who don’t respond to other drugs and/ or cannot tolerate the side effects of other drugs. And I’ll go into that later as well. But first, I want to go over some general information about schizophrenia.
Schizophrenia is a very serious, disabling, and complex mental illness impacting approximately 2.4 million adults in the United States. It is most disabling because there is no for schizophrenia, but there are treatments, and it must be treated and monitored for a lifetime. Like many mental illnesses, it not only severely impacts patients, it also majorly impacts patients’ families. The clinical presentation of schizophrenia is very diverse. Acute episodes can be characterized by psychotic symptoms, such as hallucinations and delusions, and these can be so debilitating that these patients require hospitalization. The disease is chronic and lifelong, and is often accompanied by depression. There can also be a deterioration of social functioning and cognitive abilities. Patients with schizophrenia often discontinue treatment, stop taking their meds, because of major side effects, which can include weight gain, lactation, gynecomastia, and movement disorders. More on these side effects later. For now, suffice it to say that an effective and well tolerated treatment can be game-changing for people living with schizophrenia.
I thought it might be fun to have a little quiz, just to see what you do or don’t know about schizophrenia, all in an effort to educate and de-stigmatize. If you don’t know them now, you will when you finish. I’ll give you the answers and explanations later. No cheating, people!
1) Schizophrenia is the most disabling of all mental illnesses.
2) There are 50 million people with schizophrenia in America.
3) Schizophrenia is often called “split personality disorder.”
4) Psychosis means that a person…
A) Has suffered memory loss
B) Suffers from chronic insomnia
C) Can’t distinguish imagination from reality
D) Has a virus that affects the brain
5) The most common hallucination in schizophrenia is…
A) Visualizing shadows
B) Smelling smoke
C) Feeling cold
D) Hearing voices
6) The first symptoms of schizophrenia can include:
A) Irrational statements
B) Excessive crying
C) Outbursts of anger
D) All of the above
7) Who has more symptoms at the onset of schizophrenia?
8) Many schizophrenics believe that ____ actually eases their symptoms.
Let’s see how many you got right and I’ll explain the correct answers:
1) True/ False: Schizophrenia is the most disabling mental illness.
Correct answer: True
Explanation: Schizophrenia is an incurable, severe, and lifelong disease that is the most disabling of all mental illnesses. Treatments for schizophrenia focus on controlling the symptoms.
2) True/ False: There are 50 million people with schizophrenia in the US. Correct answer: False
Explanation: About 1% of people in the U.S. have schizophrenia, which is just over 2 million people.
3) True/ False: Schizophrenia is often called “split personality disorder”
Correct answer: True
Explanation: Schizophrenia is sometimes confused with other mental illnesses and may be mistakenly referred to as “split personality disorder.” While “schizo” does mean “split,” patients with schizophrenia do not have split personalities. What they do have is psychosis, which is a distorted perception of reality.
4) Psychosis means that a person…
Correct answer: C) Cannot distinguish imagination from reality
Explanation: Experts don’t know what causes schizophrenia. In some people, brain chemistry and brain structure are not normal. Family history may be a factor in some cases. Schizophrenia is never caused by anything a person did, or by any personal weakness, bad choices, or a person’s upbringing.
5) The most common hallucination in schizophrenia is…
Correct answer: D) Hearing voices Explanation: Auditory hallucinations, or “hearing voices” is the most common hallucination in schizophrenia. Voices can seem to be coming from within one’s own mind or externally, as if a person is talking to them. These voices may tell the person with schizophrenia to do things, or they may comment on their behavior. The voices may even talk with one another. It is common for people with schizophrenia to hear voices for a long time before anyone else notices the problem. Other kinds of hallucinations experienced by people with schizophrenia include seeing people or objects that are not there, feeling as if they are being touched by invisible fingers, or smelling odors that no one else can smell.
6) The first symptoms of schizophrenia can include…
Correct answer: All of the above
Explanation: There are numerous early symptoms of schizophrenia. In some cases, family and friends may notice a shift in behavior or sense something is “off” about the person who is schizophrenic. Early signs and symptoms of schizophrenia may include irrational statements, excessive crying or inability to cry, outbursts of anger, social withdrawal, and extreme reactions.
7) Who has more symptoms at the onset of schizophrenia?
Correct answer: Men
Explanation: Schizophrenia affects men and women at equal rates, and symptoms may start suddenly or occur gradually. Men tend to develop schizophrenia slightly earlier, between 16 and 25 years old, while women develop symptoms several years later, in the late 20s to 30s. Schizophrenia symptoms tend to be more severe in men, while women with schizophrenia may have more depressive symptoms and paranoia.
8) Many schizophrenics believe that _______ eases their symptoms.
Correct answer: Smoking
Explanation: Many schizophrenics believe smoking cigarettes eases their symptoms, and up to three times more schizophrenics smoke than in the general population. It is thought that smoking may be a kind of self-medication. The nicotine seems to help with some of the cognitive and sensory symptoms experienced by schizophrenics, and it can ease some of the side effects of medications commonly prescribed. However, it’s important to note that smoking still causes cancer, lung disease, and heart disease.
Now that you probably know a little more about schizophrenia than you did 15 minutes ago, let’s talk about this new drug treatment, Caplyta, generic name lumateperone. Obviously, since it hasn’t been released yet, I haven’t had the opportunity to prescribe it to my patients, but I have been following its development and have read about it extensively. Based on that, I think this drug will be well tolerated, and a valuable drug in the armamentarium for the treatment of schizophrenia. In addition, I think it will be valuable in treating bipolar disorder and could also benefit patients with Alzheimer’s and/ or dementia with agitation.
Let’s talk turkey. Why is it good to have a new option for treating schizophrenia? Here’s where those side effects I mentioned before come in. The current drugs used to treat schizophrenia are chock full of side effects, some of which are stigmatizing and intolerable to patients. So a new drug, a better tolerated one, is a big deal. Older drugs like Olanzapine cause weight gain, metabolic syndromes, insulin resistant diabetes, increased cholesterol, and increased triglycerides. Other drugs like Risperdal are known to cause elevations in prolactin, which causes lactation, milk production in women, and breast enlargement in men, all of which are very unsetteling to patients, to say the least. Another major factor in older antipsychotic drugs like Aripiprazole, Brexpiprazole, and Haloperidol involve what are termed extrapyramidal symptoms, dystonia and tardive dyskinesia. All those fancy words just mean involuntary muscle contractions that can cause repetitive movements like tics, ie grimacing and eye blinking, muscle spasms, and all sorts of uncontrollable muscular movements that people obviously find very uncomfortable and cosmetically disfiguring. These extrapyramidal symptoms are problematic in terms of compliance, meaning that patients don’t take the drugs, they are not not compliant, because while they are already stigmatized by their illness, they are further stigmatized by these side effects of breast enlargement and lactation, and the disfiguring extrapyramidal muscular movements and motor tics the drugs cause.
Caplyta, lumateperone is apparently different. And this is where I’ll explain a little about the mechanism of action, how I believe it works. We know from previous accepted research that the undesirable extrapyramidal motor symptoms like tics and spasms associated with antipsychotic medications are the result of a high affinity for a receptor called the D2 receptor. Having a high affinity for a receptor basically means that a drug likes to bind there, and in doing so, it blocks that receptor. That would be a mechanism: the binding of a drug to a receptor and its subsequent blocking of that receptor. So, the older antipsychotic drugs have a high affinity to, they like to bind to, D2 receptors, blocking them. But this new drug, lumateperone, has low affinity for these receptors, the D2 receptors, so they are left unbound and unblocked. As a result, those stigmatizing involuntary muscle movements and tics are absent. Before I go further, here’s a quick and simplified synopsis on the basics of clinical trials: when drugs are tested in clinical trials, they begin with randomly giving the drug being tested to a certain number of subjects, while giving a placebo (an inactive substance, sometimes called a “sugar” pill) to the other people in the trial. The study is randomized, meaning the people in the study don’t know if they’re being given the drug being tested or the placebo. In most studies, even the people running it and those dispensing the study “medications” don’t know which is which or who’s getting what. That way there is no bias, people just honestly report their symptoms. At the end of the study, when the results are tabulated, the drug company hopes to be able to clearly see the difference between the study drug and the placebo in symptoms and efficacy and whatever other traits they want to look at. Then they use those numbers to report the findings of the testing drug versus the placebo. So for this new schizophrenia drug Caplyta (lumateperone), the reported trial numbers shake out to subjects taking the study drug lumateperone reported having extrapyramidal symptoms/ side effects only 0.4% more than reported by subjects taking the placebo, and that is evidently due to its very low affinity for the D2 receptor, so those D2 receptors are mostly open. D2 receptors blocked= extrapyramidal symptoms, involuntary motor tics. D2 receptors open= no extrapyramidal symptoms. Make sense? This is all very simplified, and there are more receptors and pathways in the body than you would ever want to know…and they all do different things depending on if they are open or blocked, presynaptic or postsynaptic, agonistic or antagonistic, upstream or downstream, activated or inactivated, partially or completely and everything in between. It’s complex stuff…I just want you to have an idea of why drugs cause or don’t cause different side effects, because that’s the name of the game when it comes to efficacy and tolerance of drugs, and that’s what determines patient compliance in taking drugs, and that’s what determines how much their mental illness affects them, and that’s what determines their place in this world. Phew! Get it? It’s a big deal.
So that’s an example of how lumateperone avoids those extrapyramidal side effects. Now you may ask how it works in controlling the hallmark syptoms of schizophrenia: delusions, hallucinations, disorganized speech, and disorganized behavior. That mainly has to do with its effect on another receptor, the Serotonin 5-HT2A receptor. Lumataperone has a high affinity for this receptor; it binds and blocks it. We know that a drug called Pimavanserin does the same thing, and Pimavanserin is used to treat Parkinson’s disease psychosis, so we can correctly infer that blocking and binding the Serotonin 5-HT2A receptor in lumataperone makes it effective as an antipsychotic drug, controlling delusions, hallucinations, disorganized speech, and disorganized behavior associated with schizophrenia. Along those same lines, lumataperone also affects dopamine receptors in a specific pathway called the mesolimbic pathway. That happens to be the pathway that blocks hallucinations, delusions, disorganized speech, and disorganized behavior. This is all good stuff.
What else? Lumataperone has decreased muscarinic receptor activity. When activated, muscarinic receptors cause dry mouth, pupil dilation, blurred vision, constipation, and flushing. Because that activity is decreased, those effects are reduced or absent, so no dry mouth, dilated pupils, blurry vision, constipation, or flushing. It also does not cause or lead to any metabolic syndromes, elevation in cholesterol, significant weight gain, and insulin resistance, another big plus.
Lumataperone has decreased effects on the alpha adrenergic receptor, which causes orthostatic hypotension, meaning a drop in blood pressure upon standing that often leads to a fainting episode. Because of lumataperone’s decreased effects on this receptor, this removes this risk.
Lumataperone also has minimal effects on the endocrine system, and therefore it does not affect prolactin like the older drug Risperdal does, so female patients do not experience lactation and milk production, and men do not get breast enlargement. This is majorly important in drug compliance. Patients are more likely to take the medication if they don’t have to leak milk from existing breasts or grow breasts where they don’t belong.
Lumataperone metabolics and dosing is convenient becuase it does not require titration, meaning patients don’t have to build up to the full dose by taking smaller doses first. Patients start at 42 milligrams, peak plasma level is in 3-4 hours, and it has a half-life of about 13 hours. This is nice, because that means it can be taken just once a day, because the half-life is long enough.
While lumateperone seems to be far superior to the older schizophrenia drugs in nearly every way, there is no such thing as a perfect drug…yet. It does have some possible side effects, including nausea, dizziness, fatigue, and vomiting. But these appear to be fairly insignificant, not affecting quality of life. It has also been shown to cause drowsiness; I think it must have something called a histaminic effect. This is really its most major side effect, with anywhere between 10% and 24% of people to experience drowsiness. But we can turn that frown upside down…we can use this drowsiness to our advantage by dosing it when it’s time to go nite-nite. And since it’s dosed once a day, it works out great.
The last important footprint of Lumateperone has to do with it’s metabolism by the Cytochrome P450 3A4 system (I told you this stuff can get a little complicated). Abbreviated CYP3A4, this is a very important enzyme in the body, mainly found in the liver and the intestine. It oxidizes small foreign organic molecules, such as toxins or drugs, so that they can be removed from the body. Patients taking lumateperone should not take any drug which blocks CYP3A4 enzyme concomitantly. This is really the only contraindication at this time.
So, when we put all of this stuff together, what do we have?
– Caplyta (lumateperone) for schizophrenia
– Dosing: 42 milligrams, once per day, with food, at night if causing drowsiness.
– Works mainly by affecting dopamine, serotonin, and glutamine.
– Binds and blocks Serotonin 5-HT2A receptors, eliminating negative symptoms of schizophrenia: delusions, hallucinations, disorganized thoughts, and disorganized behaviors.
– Low affinity for D2 receptors leaves them unbound and unblocked, eliminating the stigmatizing extrapyramidal symptoms of involuntary muscle movements and tics, dystonia and tardive dyskinesia.
– Minimal endocrine effects, preventing female patients from experiencing lactation, and male patients from breast enlargement, and relieving patients of these stigmatizing side effects.
– Decreased muscarinic receptor activity, eliminating dry mouth, dilated pupils, blurry vision, constipation, and flushing.
– Elimination of metabolic syndromes: no elevated cholesterol, no significant weight gain, no insulin resistance, no diabetes.
– Decreased effects on the alpha adrenergic receptor, eliminating fainting episodes due to orthostatic hypotension.
– Possible side effects: nausea, dizziness, fatigue, and vomiting. But these appear to be fairly insignificant, not affecting quality of life.
– The only significant side effect is drowsiness, 10% to 24%. This can be turned around and used to help insomnia when dosed at night.
– Utilizes CYP3A4: lumateperone is contraindicated in patients taking
drug(s) which block CYP3A4 enzyme.
Essentially, that adds up to getting all the good stuff for treating schizophrenia without getting any of the bad stuff, and all it’s going to cost you is maybe some minor nausea, vomiting, and/ or fatigue, all of which will likely go away after two weeks. You might have some drowsiness, but I see that as a plus, as lots of patients complain of insomnia, and it can be taken only at night due to its once a day dosing.
Schizophrenia for now…what about later? Lumateperone is a weak serotonin transporter pump inhibitor just like SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants are. To simplify the mechanism: serotonin is a happy neurotransmitter regulated by a pump. It’s pumped out, but can be removed by being “uptaken,” if you will, which leads to low serotonin levels commonly found in people with depression. So an SSRI drug, an antidepressant, is given. The SSRI is employed, and the RI, which stands for reuptake inhibitor, stops (inhibits) the reuptake of the serotonin, leaving higher levels of free happy serotonin circulating and thereby increasing mood. It has other antidepressant effects which I think will make it very effective for treating depression and bipolar disorder. And because it has a low affinity for D2 receptors, leaving them open, I think it could control agitation in people with Alzheimer’s and/ or dementia without causing any of those horrible side effects of current antipsychotic medications. When physicians prescribe Caplyta for anything other than schizophrenia, or prescribe any drug for any diagnosis it was not labelled for (ie originally developed for), it is called off-label prescribing, and it is a common practice in psychiatry, as the regulation of receptors and pathways overlap in many different mental illnesses.
In summary, Caplyta (lumateperone) shows a great deal of promise, and I’m looking forward to being able to offer it to my schizophrenia patients that are having compliance issues due to the stigmatizing side effects of current antipsychotic therapeutics. This could be a game changer and a life changer for them. And then once I really see how it’s tolerated, I’ll give great consideration to using it off-label for bipolar depression and to combat agitation in my Alzheimer’s and dementia patients. It could be a much needed breakthrough for them as well.
If you liked this blog, please comment and pass it along. Even posting simple comments and sharing information help reduce the stigma of mental illness…and it’s certainly high time for that. If you’re interested in reading more about the subjects discussed here, and a lot more, check out my book, Tales from the Couch, available in my office or on Amazon.com.Learn More
Delusional disorder is an uncommon psychiatric condition in which patients present with circumscribed symptoms of non-bizarre delusions, but with the absence of prominent hallucinations and no thought disorder, mood disorder, or significant flattening of affect. For the diagnosis to be made, auditory and visual hallucinations cannot be prominent, though olfactory or tactile hallucinations related to the content of the delusion may be present.
To be diagnosed with delusional disorder, the delusion or delusions cannot be due to the effects of a drug, medication, or general medical condition, and delusional disorder cannot be diagnosed in an individual previously diagnosed with schizophrenia. A person with delusional disorder may be high functioning in daily life and may not exhibit odd or bizarre behavior aside from these delusions. The Diagnostic and Statistical Manual of Mental Disorders (DSM) defines six subtypes of the disorder characterized as erotomanic (believes that someone famous is in love with him/her), grandiose (believes that he/she is the greatest, strongest, fastest, most intelligent person ever), jealous (believes that the love partner is cheating on him/her), persecutory (believes that someone is following him/her to do some harm in some way), somatic (believes that he/she has a disease or medical condition), and mixed, i.e., having features of more than one subtypes. Delusions also occur as symptoms of many other mental disorders, especially the other psychotic disorders.
The DSM-IV, and psychologists, generally agree that personal beliefs should be evaluated with great respect to complexity of cultural and religious differences since some cultures have widely accepted beliefs that may be considered delusional in other cultures.Learn More