Caplyta(lumateperone):NEW Treatment Schizoprenia and Bipolar Disorder

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.
A)   True
B)   False

2) There are 50 million people with schizophrenia in America.
A)   True
B)   False

3) Schizophrenia is often called “split personality disorder.”
A)   True
B)   False

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?
A)   Men
B)   Women
C)   Children
D)   Elderly

8) Many schizophrenics believe that ____ actually eases their symptoms.
A)   Silence
B)   Eating
C)   Screaming
D)   Smoking

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. 

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Drugs with Bizarre Side Affects

You’re in your favorite recliner watching the game, and then comes a “word from our sponsors.” You may not bet on the game, but you can bet there’ll be a commercial for a pharmaceutical drug during that break. For today’s purposes, I’ll refer to a fantasy medication named ‘Druguall.’ The Druguall commercial shows a couple at the beach, walking hand in hand along the shore as the announcer explains the indications for Druguall, ending with the requisite side effect statement “…Druguall may be habit forming, and has been shown to cause an inability to make a left turn, an impulse to chew toenails, and a compulsion to repeatedly beat your head against a wall. If symptoms worsen or become problematic, contact your physician immediately. If you are allergic to Druguall, do not take Druguall.” Duh! That last one always kills me. Does the American public need to be told to not take a drug they’re allergic to? Apparently so, because pharma companies have been held liable for idiots taking their drug (despite being allergic to it) in numbers sufficient enough to spend the extra commercial time and money to make the statement to cover their corporate posteriors. But enough of the woes of big pharma. What am I writing about today? Side effects! Every drug’s got ‘em, and they range from comical to serious…even downright deadly. The point of this is so that you’ll ask your doctor when he or she starts you on a new med, especially if you’re already taking other meds…you need to know if they’ll play nice together. 

Here’s the ugly truth that your doctor probably doesn’t want you to know. When it comes to taking most drugs, it’s a crap shoot. He or she can know the side effects, but there’s no way to predict if you’ll experience any of those side effects, what they may be, and if they will have a minor/major affect on your life. When it comes to prescribing, there’s a lot of ‘throw this out there and see if it sticks’ going on. Granted, good physicians know the published side effects of the drugs they prescribe. I certainly do. But even though I know these drugs inside and out, there’s still some trial and error, because everyone reacts to different medications differently. If you’ve ever seen the PDR, the Physician’s Desk Reference, it is chockablock full of side effects. And it’s big enough to be used as a weapon. Nowadays it’s really just for show…everyone just checks the internet. Anyway, when a drug is tried in humans, everything that happens is noted. If the test subject happens to fart ten minutes after taking a trial medication, that medication is labeled with a side effect of flatulence, even though the guy probably just had broccoli for dinner. So if you look at any given drug, there are multitudes of side effects. Today, I want to talk about some of the weirder and wilder ones. 

Lots of medications get a bad rap for having yucky and unpleasant side effects, and most have earned them. Almost every drug on the market has side effects of upset stomach, dizziness, and headache. Borrrring!!! Instead, I want to look at some not-so-common side effects. The big note here is that just because a certain medication can cause a certain side effect doesn’t mean it will cause that side effect.

Hallucinations happen when you sense something that’s not actually there. I’m talking little green men here, people. But hallucinations can be seen, felt, heard, and even smelled. They are some freaky and frightening side effects. Most people associate them with illegal psychadelic drugs like shrooms and acid, but prescription drugs can also cause hallucinations. The sleep aid eszopiclone and a common medication for depression called escitalopram have been known to cause hallucinations. Even a drug to treat malaria called mefloquine can cause hallucinations. I’ve seen more cases of people hallucinating than I could ever count and ordered lots of four-point restraints. I’ve seen super heroes with broken bones they received learning that they actually  couldn’t fly from multi-story buildings. I’ve seen lots of people who say they’re God, and lots who say they’re Satan, but no proof from any of them. 

Now we’ll go from freaky to funny. There are plenty of meds that will turn your urine different colors. Even some non-drug food items can do it…beets can turn it pink, asparagus can turn it green (and stinky!) and carrots can turn it bright yellow. As for meds that change pee color, every woman probably knows that pyridium for UTIs makes it bright Tang orange. Even OTC Azo will do that too. But can you imagine seeing your urine turn green or bright blue? This can be a side effect of taking the antidepressant amitriptyline or the common pain reliever indomethacin. An antibiotic called metronidazole can even cause your urine to turn black. That would freak me out. The anesthetic drug propofol can also make your urine turn blue. Michael Jackson could’ve told you about that one. Well, if he weren’t dead from abusing it.    

Big word alert for the Scrabble set: anosmia; the loss of smell. This side effect actually has a huge impact on a patient’s life, because the loss of smell goes along with the loss of taste, so patients have no desire to eat, and that becomes a problem. Sometimes patients even have to be put on IV feeds. Some examples of drugs that can cause this side effect include the blood pressure drug enalapril, the antipsychotic drugs chlorpromazine and prochlorperazine, and the antibiotic metronidazole. And just a side note, prolonged use of OTC decongestants like Sudafed can also cause loss of smell.

Sexual side effects are always of interest to patients. The most common sexual side effect is the loss of the ability to either perform during sex or the ability to enjoy sex. The usual culprits of these types of sexual side effects are certain drugs that treat depression. These medications are called selective serotonin reuptake inhibitors (SSRIs), and they include common drugs like Prozac (fluoxetine), Celexa (citalopram), and Zoloft (sertraline). I always consider this side effect when choosing what to prescribe. I find that men aren’t willing to trade mental health for sexual satisfaction, but interestingly, women are more willing to do so. 

On the flip side of the sexual side effect coin is priaprism, which is a painful, permanent erection. A variety of medications can lead to this condition, one which patients who’ve experienced it will never forget. This unfortunate side effect lasts for more than four to six hours and may be caused by antidepressants like trazodone, fluoxetine, sertraline and lithium. An anti-anxiety medication called vistaril and the blood thinner coumadin are also known offenders. Priapism due to a medication side effect (as opposed to from taking a little blue pill) often goes away without treatment, though putting ice packs on the affected area might help speed up recovery. Cringing.

This one sort of goes along with the above discussion. There are several medications that cause the side effects of unusual urges for sex and gambling, though hopefully not at the same time. Common culprits include Requip, which is a medication for restless legs, and the antidepressant Abilify. These meds may cause uncontrollable urges to gamble, binge eat, shop, and have sex. Interestingly, a Parkinson’s medication called carbidopa/levodopa also carries a warning of intense urges for gambling and sex. I’ve had cases where men don’t want to leave their homes because they want to masturbate, as well as cases where they’re caught masterbating in public. As for the gambling…I’ve had patients lose a lot of money gambling in casinos, betting on horses, and even at the dog track. The sexual and/or gambling compulsions just drive them.

It’s common knowledge that drugs affect dreams, but not always in a good way. Medications that affect neurotransmitters in the brain commonly cause bad dreams and nightmares. The Alzheimer’s medications donepezil and rivastigmine, as well as the Parkinson’s medication amantadine, are all reported to cause vivid dreams, often being of a sexual nature. Nightmares are also a commonly reported adverse effect of blood pressure medications called beta-blockers. These include propranolol, atenolol and labetalol. There are also reports of steroids like methylprednisolone and prednisone causing nightmares. Varenicline, the medication often prescribed to help people stop smoking, is known to cause dreams that are super strange and very vivid. Not only does varenecline cause bad vivd dreams, I’ve seen patienta think it’s okay to stab themselves repeatedly or to kill themselves. Varenicline is a scary strange drug. Even stranger? The prescription sleep aid zolpidem doesn’t keep many users sleeping in bed. In fact, many who take it have been known to get up at night and go for a drive, maybe talk on the phone, or even have sex…all without remembering anything in the morning. You can ask Elon Musk about zolpidem. He tweeted that he was going for an IPO for $423 a share after taking it. His advisors had a fit the next morning, but he found it amusing and shrugged it off. But Roseanne Barr wasn’t laughing when she lost her eponymous show after a discriminating tweet. She apologized, but the damage was done. Maybe she should’ve called Elon for help.

Another big word for the Scrabble set: Akathisia. The word comes from the Greek for “inability to sit,” so this side effect invokes feelings of unease and an inner restlessness.  Unfortunately, this is another adverse reaction that folks who experience it never forget. They describe it as wanting to crawl out of their skin. The triggers for this horrible sensation are the anti-nausea medications prochlorperazine and metoclopramide, as well as some SSRI antidepressants, and an anti-anxiety medication called buspirone. Thankfully, this terrible feeling goes away when the medication wears off.

What if taking a medication made you pack on the pounds? How about if it caused you to gain 20 plus pounds in only three months? Some people who take the medication olanzapine for bipolar disorder have done just that. Some common medications used to treat depression, like paroxetine, can also cause unintended weight gain. Weight gain is enough to cause depression in and of itself, so I’m always cognizant of that when I prescribe. Other drugs that can pack on the pounds include steroids, birth control pills, hormone replacement therapies, and some diabetes medications. The bottom line on that is that if you must take one of these drugs, you also must watch what you eat.

File this under the creepy side effect column. And yet another big word for the Scrabble set: Onycholysis. This is the medical term to describe when nails separate from the nail bed. You may not think that’s so bad, but trust and believe that patients who experience it do, and you would too if you had it. It can be super painful and may result in infections under the nails. Believe it or not, there are quite a few meds that can cause this: acne treatments tetracycline and fluoroquinolone, antibiotics like ciprofloxacin and levofloxacin, oral contraceptives, and some chemotherapy medications…all may cause your nails to separate from the nail beds. 

Visual disturbances can also be a side effect of certain meds. These disturbances can include blind spots, distorted vision, blurred vision, or halos around lights. Medications that can affect your vision include antihistamines, high blood pressure medications, and medications taken for malaria or tuberculosis. For men on the little blue pill, a truly weird and whacky side effect can be tinting of the vision, as through tinted glasses. And of course it tints the vision blue. I wonder if that might be a promotional idea…to see blue like their little pill. 

Most people are familiar with the hair loss that goes along with some types of cancer treatments, but there are also several other common medications that cause hair loss, including blood thinners, birth control pills, antidepressants, and medication used to treat gout. But hair growth can also be a drug side effect. Women may experience unwanted hair growth from steroid medications and from the drug danazol, which is used to treat endometriosis.

Have you ever torn a tendon? It isn’t always just from a sports injury. Believe it or not, a common medication used to treat urinary tract infections could cause you to rupture your Achilles tendon. The U.S. Food and Drug Administration (FDA) has issued a warning for just that for the class of antibiotics called fluoroquinolones. According to the FDA, pain, swelling, and tears of tendons in the heel, shoulder, and hand are more likely to occur when taking these drugs. Common medications in this class include the often prescribed antibiotics ciprofloxacin and levofloxacin. So maybe it’s best to warm the bench when you’re taking these antibiotics. 

All jokes aside on this one. No list of side effects would be complete without mentioning side effects causing birth defects. Obviously, birth defects are a very serious medication side effect, and this is why pregnant women are told not to take any drugs before checking with their doctor first. Types of drugs that can cause birth defects include high dose vitamin A, some blood pressure medications, and some antibiotics. Two drugs that are especially dangerous and potentially fatal for developing babies are Accutane (isotretinoin) and Thalomid (thalidomide). Accutane is used to treat severe acne and Thalomid is used to treat a type of white blood cell cancer. When pregnant, all side effects are serious. But pregnant or not, isotretinoin is a nasty, scary, dangerous drug. It’s used most commonly by dermatologists for severe acne. I’ve heard of patients flying planes into buildings, thinking they’re invincible and jumping from buildings, and just acting in an exceedingly dangerous way. It’s like they’re without fear.

Rather than a condition, this one is about a drug called Interferon. Interferon is used to treat certain cancers, leukemias, and Hodgkin’s Disease. I’ve seen some pretty bizarre things with Interferon. People become suicidal, openly so. They’ll talk about suicide like it’s an acceptable option. Sometimes they cut themselves and make themselves bleed. It’s very odd and very scary. Interferon can also cause bizarre thoughts, and people become psychotic. Also, they can have anosmia. Remember that? That’s the loss of smell that I discussed above. Interferon can be useful in cancer treatments, but people have to be closely monitored for side effects.

I’ve saved the weirdest of the weird, the most bizarre side effect I’ve ever seen, for last. At the time, I was in medical school but working in the ER. What I saw looked straight out of The Exorcist. The side effect is called an extra-pyramidal oculogyric crisis. Oculo- refers to eyes, which fix upward and to the side during the crisis. In severe attacks, there can also be involvement of the head and neck and structures within the neck. There are several drugs that cause it, and the crises or attacks can happen in varying degrees, from minor reactions to major emergencies requiring intubation for airway control. Oculogyric reactions are caused by neuroleptic drugs,  antipsychotics, antiemetics (anti-nausea drugs), and antidepressants. Cases involving other drugs have been reported, including methylphenidate and carbamazepine. In this case, the patient’s head was turned sideways and backward at an impossible angle, with her eyes fixed very strongly to the opposite side. Her face was frozen in a grimace and her neck was so flexed that she was unable to speak and her airway was compromised. She needed to be intubated for airway support, but doctors were unable to straighten her neck to insert the tube. They were considering a tracheostomy, making a hole in her throat, to buy some time because they didn’t know what was happening.  Because she was unable to speak, she couldn’t tell the ER doctor that she had taken an antiemetic, a medication for nausea, which had caused the episode. The doctors were puzzled as to what was happening because of how extreme the episode was, and several were gathered around her bed in the ER. A nurse just happened to stick her head in the room to see what the commotion was, and she mentioned in passing that she had seen something similar in someone who had taken compazine. At that word, compazine, the patient snapped her fingers and pointed at the nurse; the doctors asked if she had taken compazine and she snapped her fingers again and the mystery was solved. They gave her IV Benadryl and five minutes later her neck and eyes relaxed to midline and in another five minutes, she was able to speak. I’ve seen oculogyric crises since, but none like that. The whole Exorcist thing is the craziest side effect I’ve ever seen, but I will forever remember extra-pyramidal oculogyric crises.

After working in psychiatry for the past 30 years, I’ve seen time and time again that when you put a drug in the human body, you don’t know what you’re going to get. It’s like Forrest Gump’s box of chocolates,  but not as tasty. For more patient stories, be sure to read my book Tales from the Couch, available on Amazon.com.

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How To Know If Someone Is Schizophrenic

A man named Eugene Bleuler coined the term schizophrenia. If you break the word down to its parts, “schizo” and “phrenia,” it literally means split personality. But that’s not what schizophrenia is. There are so many misconceptions about schizophrenia that I want to explain more about it.  

Schizophrenia is a psychotic disorder, a severe and often debilitating brain and behavior disorder. It  affects how a person thinks, feels, and acts, because they have breaks from reality. Basically, that means they have hallucinations and delusions, and can have trouble telling the difference between reality and fantasy. Their thought processes, behavior, and speech can become disorganized. Disorganized basically means abnormal. Disorganized speech is generally gurgly speech, it makes no sense. Disorganized behavior is basically a decline in daily functioning. This can range from a person not taking care of their hygeine, not bathing or brushing their teeth, to catatonia, where they are unable to move at all. They freeze and look like a statue, and this is called posturing. There can be something called “waxy flexibility” which is where their body can be placed in any shape in a fixed position, like a wax figure, hence the name. Disorganized thinking is basically when someone cannot “think straight.” They are unable to connect thoughts into logical sequences, so their thoughts become disorganized and fragmented. They often have unpredictable or inappropriate emotional responses, and hear imaginary voices and believe others are reading their minds, controlling their thoughts, or plotting to harm them. These are delusions and hallucinations; the two are very different. A delusion is a false fixed belief, often involving thoughts of others monitoring or threatening them or reading their thoughts. The most common type of delusion is a paranoid delusion. “The CIA is tracking me,”  “The FBI is coming to get me,” “My neighbor is watching me.”  These are common delusions in people with schizophrenia. Hallucinations cause a patient to hear, see, feel or smell something that is not there. The most common type of hallucination is an auditory hallucination, meaning the person hears something not actually there. These auditory hallucinations can be dangerous if they are what are called “command hallucinations,” because they can tell the person to kill themselves or someone else. Obviously, this is not good, and must be taken very seriously. Anytime you have someone experiencing hallucinations, it is in your best interest to explore these with a mental health practicioner to find out what they are and take appropriate measures. 

Schizophrenia can be cyclical. There can be remission and relapse cycles; a person can get better, worse, and then better again repeatedly over time.
As a result, people with schizophrenia suffer from symptoms either continuously or intermittently throughout their entire lives, and they are often severely stigmatized by people who do not understand the disease. Contrary to popular belief, people with schizophrenia do not have “split” personalities or multiple personalities, and as long as they receive appropriate treatment and are compliant with medications, most pose no threat to others. However, the symptoms are sometimes so terrifying to those experiencing them that they can become agitated, withdrawn, and depressed. Sadly, people with schizophrenia attempt suicide more often than people in the general population, and it is estimated that up to 10 percent of people with schizophrenia will complete a suicidal act at some point within the first 10 years of the illness. This is particularly true in young men with schizophrenia. While schizophrenia is a chronic disorder, it can be treated with medication and psychological counseling, and this can substantially improve the lives of people with the condition.

Schizophrenia can have very different symptoms in different people. The way the disease manifests itself and progresses in a person depends on the age of onset and the severity and duration of symptoms, which are categorized as positive, negative, and cognitive. Positive symptoms don’t mean symptoms that are good, they mean symptoms or actions which are added to the person’s behavior. Examples of positive symptoms are delusions and hallucinations, and these can be severe or mild. Negative symptoms don’t mean they are especially bad, they mean symptoms or actions which are taken away from the person’s behavior. They reflect a loss of functioning in areas such as emotion or motivation. Examples of negative symptoms are loss of motivation, aimlessness, poverty of speech, a blunted or flat affect, and inability to express emotion or find pleasure in life.  They often lead to social withdrawl and apathy, and can be mistaken for laziness or depression. Cognitive symptoms involve problems with attention and memory, especially in planning and organizing to achieve a goal. These cognitive deficits are often the most disabling for patients trying to lead a normal life, as they make it very difficult to keep up with peers in the big wide world. All three types of symptoms- positive, negative, and cognitive- reflect problems in brain function. 

Schizophrenia affects men and women equally. Symptoms such as hallucinations and delusions usually start between the ages of 16 and 30, though men tend to experience schizophrenia symptoms earlier than women. Schizophrenia rarely occurs in children, but awareness of childhood onset schizophrenia is increasing in the psychiatric community. It can be difficult to diagnose schizophrenia in teens. This is because the first signs can include behaviors commonly exhibited by normal teenagers, such as a change in friends, a drop in grades, sleep problems, and irritability. Despite this, there are a combination of factors that can predict schizophrenia in up to 80 percent of youth who are at high risk of developing the illness. These factors include isolation, withdrawing from others, an increase in unusual thoughts, paranoia and unusual suspicions, and a family history of psychosis. 

Currently, schizophrenia is diagnosed by the presence of symptoms or their precursors for a proscribed period of time. There must be at least six months of deteriorating function where the illness is present. Additionally, two or more positive symptoms, such as hallucinations, delusions, and/or disorganized speech, as well as negative symptoms, must be significant and last for at least one month to make a diagnosis. In some cases, only one symptom is required for diagnosis if the delusions are bizarre enough or if dangerous auditory command hallucinations are present, or if there are two or more voices “conversing.” Social or occupational problems can also be taken into account in diagnosis. 

What causes schizophrenia is still unknown. Scientists are working to understand the genetic and environmental mechanisms that combine to cause schizophrenia. It is not purely genetic, because one of a pair of identical twins may have it while the other does not. In terms of environmental issues, when a baby is in utero, it can be exposed to bacteria, viruses, environmental toxins, poisons, and contaminants, which may also play a role. Trauma at birth and decreased oxygenation may play a role. Some psychological and social issues may also contribute. Sexual abuse, physical abuse, a neglectful family, a stressful life, parents that have died, people raised or living in rough urban areas, and people who move from their home country- are more prone to schizophrenia. As more is discovered about chemical circuitry and structure of the brains of people with the disease, better diagnostic tools and early intervention techniques can be developed. This is crucial for schizophrenia, as it is believed that with every psychotic episode, increased damage is done to the brain. It doesn’t go back to it’s previous place. Speaking of the brain, their can be some differences in the schizophrenic brain. In general, but not always, people with schizophrenia may have less intracranial volume, which basically means their brains are small. They have less white matter and their grey matter decreases over time. There is an increase in ventricular volume, meaning that the ventricles that house the brain get larger, but the actual brain itself gets smaller. 

As mentioned before, schizophrenia can be cyclical, with periods of remission and relapse, but no cure exists for schizophrenia. However, it is treatable and manageable with medication and behavioral therapy, especially if diagnosed early and treated continuously. Those with acute symptoms, severe delusions or hallucinations, suicidal thoughts, or the inability to care for themselves may require hospitalization. Schizophrenia treatments typically include antipsychotic drugs as the primary medication to reduce the symptoms of schizophrenia. They relieve the positive schizophrenia symptoms by impacting the brain’s neurotransmitters. Other treatments for schizophrenia include cognitive and behavioral therapy that can then help “retrain” the brain. These approaches improve communication and motivation, and can teach coping mechanisms so that individuals with schizophrenia may attend school, hold down a job, and socialize properly. Obviously, patients who are compliant with medications and therapy do better than those who are not. Social networks and family member support have also been shown to be helpful.

Unfortunately, there are sad cases, people that for whatever reason(s) don’t do well. Life is difficult for them. You may have seen them, wandering the streets aimlessly, making bizarre movements, having an argument with someone who is not there. It is very hard to treat these people who are socially withdrawn. They’re going nowhere in life. They usually live in an assisted living facility, if they’re lucky. Many live on the street. They are sedentary. They usually neglect their hygiene. They don’t eat a healthy diet. They chain smoke cigarettes. Believe it or not, nicotine may be helpful for the treatment of schizophrenia. It sort of calms them down. They drink soda and eat sugary foods. They eat too much and very poorly. They’re prone to developing diabetes because the treatments, the medications, on top of the smoking and the sedentary lifestyle can cause coronary artery disease, diabetes, and fatty liver. They do not live healthy lives due to their illness.

In general, schizophrenics live an abbreviated life, about 20 years less than the norm. The most common issues are delusional beliefs and command hallucinations to kill themselves. Disorganized behavior in public may result in them being victims of crime. They usually have violent ends because they are victims of crime.  Substance abuse is often rampant in schizophrenics seeking an escape from the chaos inside their heads. Non-compliance with treatment is another factor. Also, the much higher incidence of smoking cigarettes, poor diet, poor exercise habits, and poor self-care contribute. All of these separately or together in some form or fashion is what usually causes their longevity to be dramatically decreased.

But with full compliance, patients can have a good life. There are famous people with schizophrenia. John Nash, the Nobel Prize winning mathematician. The great author Jack Kerouac. Peter Green, guitarist for Fleetwood Mac. Syd Barrett founder and member of Pink Floyd, and Beach Boy Brian Wilson.

For case studies of schizophrenia as well as other psychiatric diagnoses, check out my book, Tales from the Couch,

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