Hello, people! Last week, we finished up our discussion on the darker side of OCD and talked about the most difficult subtype to deal with, the pure hell of pure obsession OCD, aka Pure O. As promised, we’re back this week with a new topic, N-acetyl Cysteine, or NAC. NAC is an amino acid used by the body to build antioxidants. Antioxidants are vitamins, minerals, and other nutrients that protect and repair the body’s cells from damage, usually referred to as oxidative stress. Historically, NAC has been used mainly in emergency rooms to treat people who overdose on acetaminophen… I’ve ordered it innumerable times for this very purpose. These days, it can be purchased as a supplement OTC, and new studies have begun investigating its effectiveness as both a stand-alone and adjunctive treatment for depressed mood associated with depression, bipolar disorder, schizophrenia, OCD, and trichotillomania, as well as abuse and dependence on nicotine, Cannabis, and cocaine. And it has shown some promising results.
Before we get to that, let’s talk about some things NAC does in the body.
1. NAC is essential for making the body’s most powerful antioxidant, glutathione. Along with two other amino acids- glutamine and glycine- NAC is needed to make and replenish glutathione, which helps neutralize free radicals that can cause oxidative stress- damage to cells and tissues in your body. It’s essential for immune health and for fighting cellular damage, and some researchers believe it may even contribute to longevity. Its antioxidant properties are also important for combatting numerous other ailments caused by oxidative stress, such as heart disease, infertility, and some psychiatric conditions. More on those later.
2. NAC helps detoxify the body to prevent or diminish kidney and liver damage, helping to prevent deleterious side effects of drugs and environmental toxins. This is why doctors regularly give intravenous NAC to people with acetaminophen overdose. It’s usually organ failure that gets you in acetaminophen overdose, and NAC helps to prevent or reduce damage to the kidneys and liver, increasing the chances of survival. NAC also has applications for other liver diseases due to its antioxidant and anti-inflammatory benefits.
3. NAC helps regulate levels of glutamate, the most important neurotransmitter in your brain, and this may improve some psych disorders and addictive behavior. While glutamate is required for normal brain function, excess glutamate paired with glutathione depletion can cause brain damage. This state- excess glutamate with glutathione depletion- is commonly seen in certain psych disorders; specifically, it’s thought to contribute to bipolar disorder, schizophrenia, obsessive-compulsive disorder, and addictive behavior.
For people with bipolar disease and depression, NAC may help decrease symptoms and improve overall ability to function, and research suggests that it may also play a role in treating moderate to severe OCD. In addition, an animal study implied that NAC may minimize the so-called negative effects of schizophrenia, such as social withdrawal, apathy, and reduced attention span. NAC supplements can also help decrease withdrawal symptoms and prevent relapse in cocaine addicts, and preliminary studies show that NAC may decrease marijuana and nicotine use and cravings. Many of these disorders currently have limited or ineffective treatment options, so NAC may be an effective option for individuals with these conditions. More on this in a moment.
4. NAC can help relieve symptoms of respiratory conditions by acting as an antioxidant and expectorant, loosening mucus in the air passageways. As an antioxidant, NAC helps replenish glutathione levels in your lungs, and reduces inflammation in the bronchial tubes and lung tissue. People with chronic obstructive pulmonary disease (COPD) experience long-term oxidative damage and inflammation of lung tissue, which causes airways to constrict, leading to shortness of breath and coughing. NAC supplements have been used to improve these COPD symptoms, leading to fewer exacerbations and less overall lung decline. In a one-year study, 600 mg of NAC twice a day significantly improved lung function and symptoms in people with stable COPD. But those with chronic bronchitis can also benefit from NAC. Bronchitis is the term for when the mucous membranes in your lungs’ bronchial passageways become inflamed, restricting airflow to the lungs. Not much fun. By thinning the mucus in the bronchial tubes, while also boosting glutathione levels, NAC may help decrease the severity and frequency of wheezing and coughing in respiratory attacks. In addition to relieving COPD and bronchitis, NAC may improve other lung and respiratory tract conditions like cystic fibrosis, asthma, and pulmonary fibrosis, as well as symptoms of garden variety nasal and sinus congestion due to allergies or infections. Ultimately, NAC’s antioxidant and expectorant capacity can improve lung function in everyone by decreasing inflammation and breaking up and clearing out mucus.
5. NAC boosts brain health by regulating glutamate and replenishing glutathione. The neurotransmitter glutamate is involved in a broad range of learning, behavior, and memory actions, while the antioxidant glutathione helps reduce oxidative damage to brain cells associated with aging. Glutamate levels are subject to the three bears law: you need some, but too much isn’t good, as it’s an excitatory neurotransmitter. Because NAC helps regulate glutamate levels and replenish glutathione, it may benefit those with brain and memory ailments. The neurological disorder Alzheimer’s disease slows down a person’s learning and memory capacity, and animal studies suggest that NAC may slow the loss of cognitive ability in people with it. Another brain condition, Parkinson’s disease, is characterized by the deterioration of cells that generate the neurotransmitter dopamine. Oxidative damage to cells, and a decrease in antioxidant ability, contribute to this disease, and NAC supplements appear to improve dopamine function as well as disease symptoms, such as tremor.
6. NAC may improve fertility in both men and women. Approximately 15% of all couples trying to conceive are affected by infertility, and in nearly half of these cases, male infertility is the main contributing factor. Many male infertility issues increase when antioxidant levels are insufficient to combat free radical formation in the male reproductive system, leading to oxidative stress and cell death, culminating in reduced fertility. In some cases, NAC has been shown to combat this, improving male fertility. One condition that contributes to male infertility is varicocele. This is when veins inside the scrotum become enlarged due to free radical damage; surgery is currently the primary treatment. In one study, 35 men with varicocele were given 600 mg of NAC per day for three months post-surgery. The combination of surgery and NAC supplement improved semen integrity and partner pregnancy rate by 22% as compared to the control group with surgery alone. Another study in 468 men with infertility found that supplementing with 600 mg of NAC and 200 mcg of selenium for 26 weeks improved semen quality. Researchers suggested that this combined NAC/ selenium supplement should be considered as a treatment option for male infertility. In addition, NAC may improve fertility in women with polycystic ovary syndrome (PCOS) by inducing or augmenting the ovulation cycle which is altered by the condition.
7. NAC may stabilize blood sugar by decreasing inflammation in fat cells. High blood sugar and obesity contribute to inflammation in fat tissue. This can lead to damage or destruction of insulin receptors, which puts you at a much higher risk of type 2 diabetes. When insulin receptors are intact and healthy, they properly remove sugar from your blood, keeping levels within normal limits. When the insulin receptors are damaged, blood sugar levels are more difficult to control. Animal studies show that NAC may stabilize blood sugar by decreasing inflammation in fat cells, keeping receptors happy, and thereby improving insulin resistance. That said, human research on NAC is needed to confirm these effects on blood sugar control.
8. NAC may reduce heart disease risk by preventing oxidative damage. Oxidative damage is caused by free radicals, and this type of damage to heart tissue often leads to heart disease, causing strokes, heart attacks, and other serious cardiovascular conditions.
NAC may reduce heart disease risk by reducing oxidative damage to tissues in the heart. It has also been shown to increase nitric oxide production, which helps veins dilate, improving blood flow. This expedites circulation and blood transit back to your heart, and this can lower the risk of heart attack. Interestingly, a test-tube study showed that when combined with green tea, another well recognized antioxidant, NAC appears to reduce damage from oxidized “bad” LDL cholesterol, another bigtime contributor to heart disease.
9. NAC and its ability to boost glutathione levels appears to increase immune function, boosting immune health. Research on certain diseases associated with NAC and glutathione deficiency suggests that immune function might be improved, and potentially even restored, by supplementing with NAC.
This has been studied mostly in people with human immunodeficiency virus (HIV). In two studies, supplementing with NAC resulted in a significant increase in immune function, with an almost complete restoration of natural killer cells, the main patrol cells. High levels of NAC in the body may also suppress HIV-1 reproduction. A test-tube study indicated that in other immune-compromised situations, such as the flu, NAC may hamper the virus’s ability to replicate; this could potentially reduce the symptoms and lifespan of the associated viral illness. Other test-tube studies have similarly linked NAC to cancer cell death and blocked cancer cell replication. Great news, but more human studies are needed.
This is a short blog, but that’s a good place to stop for this week. Next week, we’ll talk about how NAC may alleviate the symptoms of multiple psychiatric disorders, as well as reduce addictive behavior; and we’ll talk about some preliminary study findings as well. I hope you enjoyed this blog and found it to be interesting and educational. Please feel free to share it with family and friends. Be sure to check out my YouTube channel with all of my videos, and I’d appreciate it if you would like, subscribe, leave comments, and share those vids! As always, my book Tales from the Couch has more educational topics and patient stories, and is available in office and on Amazon.
Thank you and be well people!
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
A Coronavirus PSA
Before we get to this next blog on suicide, I must say something related to Coronavirus transmission, because I’m tired of yelling it at my television when I see people doing it or talking about it, how “safe” it is. What is it? It’s “elbow love,” bumping elbows with someone to say hello, goodbye, good job, whassup, whatever. Think about this, people: during this viral outbreak, what have we been asking people to do when they sneeze or cough? Ideally, to do so in a tissue, but that’s not realistic, it rarely happens, so we ask them to sneeze or cough into their bent arm, at the elbow. Get the picture? The droplets they expell during that sneeze or cough are deposited everywhere surrounding that area, including the part you bump, so if your “bumpee” has Coronavirus, even if they have no symptoms, you, the “bumper” get those bijillions of virions on your elbow, and you can take them home with you. Then maybe your spouse or partner welcomes you home by putting their hands on your arms to give you a kiss… and now half a bijillion virions may be on one of their hands, just waiting to be deposited everywhere. Bottom line: for as long as this virus is around, use your words, not your body, to say whassup. So pass this knowledge on…not the virus.
Suicide is always a very difficult topic for every family, and in thirty years as a psychiatrist, it’s never gotten much easier to broach this subject. What motivated me to write this blog is a recent conversation I had with the father of one of my young patients, a fourteen-year-old named Collin, who in fact had just made what I believed was a half-hearted suicide attempt; the proverbial ‘cry for help.’ Understand that half-hearted does not mean it’s totally safe to blow it off, but we’ll get to an explanation about that later. His father, Lawrence, who prefers to be called Law, was a single parent, a widower after metastatic melanoma devastated the family of three about eighteen months before. Shortly after the mother, Sharon, passed away, Law brought Collin to my office. It was clear from the first appointment that Collin was depressed, and had been for some time. Psychotherapy was difficult with him, and it took about five appointments to establish more than a tenuous relationship and for him to begin to open up to me. I had tried him on a couple of medications, but they never seemed to do the job. I strongly suspected that it was due to a compliance issue. Actually, I’m certain that it was. He just didn’t take them regularly or as directed. That always mystifies me, patients who are miserable, anxious and depressed, but they take their meds haphazardly, at best; meds that could turn their worlds around…not because they’re inconvenient, and not because of side effects, just because. So, the tenuous connection made for less than optimal psychotherapy sessions, and that, combined with the absence of appropriate meds, put Collin on a path that led here, my office, 22 hours after his attempt. I was a little shocked by his attempt, but very shocked at how effectively, how deeply, he was able to hide the monumental amount of pain that he had obviously been feeling. His father Law looked exhausted, shellshocked, and was having such difficulty talking about it for a number of reasons, but he told me that one of the main reasons was shame. He was ashamed that Collin was so ill, and even ashamed that he was ashamed of it. He was ashamed that he could do nothing to help him, and ashamed that he had possibly caused or contributed to his son’s illness. I told him repeatedly and in several different ways that I understood, that his feelings weren’t unusual among parents of children like Collin, that he absolutely was helping him, and that while mental illness does have a familial component, he was not responsible in any way for his sons illness or attempt. Unfortunately, I don’t think he really heard a word I said. In my experience, suicidal ideation, thoughts of suicide, suicide attempts, and the actual act of suicide affects everyone it touches in a way that no other psychiatric illness does. But in this situation, I think Law was thinking about what his life would be like if Collin tried again and succeeded. It would be very sad, alone, and lonely.
Facts and Figures
Suicide is the 10th leading cause of death in the United States, claiming 47,173 lives in 2019. Montana and Alaska have the highest suicide rates, which is interesting because both of those states have very high gun ownership rates. Believe it or not, New Jersey is the lowest. I have no clue why that would be the case. There were 1.4 million suicide attempts last year in the US. Men are 3.54 times more likely than women to commit suicide. Of all the suicides in the United States last year, 69.67% were white men; they don’t seem to be doing so well. The most common way to commit suicide is by firearm, at about 50%; suffocation is 27.7%, poisoning is 13.9%, and other would be the rest, things like jumping from a tall building or bridge, laying on train tracks or jumping in front of a subway car or a bus. Among US citizens, depression affects 20 to 25% of the population, so at any given point, 20% of the population is a bit more prone to suicide, as obvi people must first be depressed (chronically or acutely) before attempting suicide. There are 24 suicide attempts for every 1 completed suicide. The most disturbing statistic is that suicide rates are up 30% in the past 16 years, with a marked increase in adolescent suicides, and suicide is now the second leading cause of death in people ages 10 to 24.
You would think the US would have the highest suicide rates in the world, but in fact, Russia, China, and Japan are all higher.
Suicide Risk Factors
What are some factors that may put someone at higher risk of suicide?
– Family history of completed suicide in first-degree relatives
– Adverse childhood experiences, ie parental loss, emotional/ physical/ sexual abuse
– Negative life situations, ie loss of a business, financial issues, job loss
– Psychosocial stressors, ie death of loved one, separation, divorce, or breakup of relationship, isolation
– Acute and chronic health issues, illness and/ or incapacity, ie stroke, paralysis, mental illness, diagnoses of conditions like HIV or cancer, chronic pain syndromes
But, understand there’s no rule that someone must have one or more of these factors in order to be suicidal.
Mental Illness and Suicidality
In order to make a thorough suicide risk assessment, mental illness must be considered. There seem to be 6 mental health diagnoses that people who successfully complete suicide have in common:
– Bipolar disorder
– Schizoaffective disorder
– Post-traumatic stress disorder
– Substance abuse
Suicidal ideation refers to the thoughts that a person may have about suicide, or committing suicide. Suicidal ideation must be assessed when it is expressed, as it plays an important role in developing a complete suicide risk assessment. Assessing suicidal ideation includes:
– Determining the extent of the person’s preoccupation with thoughts of suicide, ie continuous? Intermittent? If so, how often?
– Specific plans; if they exist or not; if yes, how detailed or thought out?
– Person’s reason(s) or motivation(s) to attempt suicide
Assessment of Suicide Risk
Assessing suicide risk includes the full examination/ assessment of:
– The degree of planning
– The potential or perceived lethality of the specific suicide method being considered, ie gun versus overdose versus hanging
– Whether the person has access to the means to carry out the suicide plan, ie a gun, the pills, rope
– Access to the place to commit
– Note: presence, timing, content
– Person’s reason(s) to commit suicide; motivated only by wish to die; highly varied; ie overwhelming emotions, deep philosophical belief
– Person’s motivation(s) to commit suicide; not motivated only by wish to die; motivated to end suffering, ie from physical pain, terminal illness
– Person’s motivation(s) to live, not commit suicide
What is a Suicide Plan?
A suicide plan may be written or kept in someone’s head; it generally includes the following elements:
– Timing of the suicide event
– Access to the method and setting of suicide event
– Actions taken toward carrying out the plan, ie obtaining gun, poison, rope; seeking/ choosing/ inspecting a setting; rehearsing the plan
The more detailed and specific the suicide plan, the greater the level of risk. The presence of a suicide note suggests more premeditation and typically greater suicidal intent, so an assessment would definitely include an exploration of the timing and content of any suicide note, as well as a thorough discussion of its meaning with its author.
I spent years teaching suicide assessment to other physicians, medical students, nurses, therapists, you name it. It all seems super complicated when you look at all the above factors written out, but as I always taught, it becomes clearer when you put it into practice. What are we doing when we embark on a suicide assessment? We’re determining suicidality, the likelihood that someone will committ suicide. You’re deciding how dangerous someone is to themselves using the factors discussed above. You’re either looking at how lethal they could be, how lethal they are at this time, or how lethal they wereduring a previous episode of suicidal ideation or previous suicide attempt.
When we put this all into practice, we look at statements and actions to determine how dangerous a person is. Did someone say, ‘if so and so does this, I’ll kill myself’ or, did someone act but just scratched their wrist? Those would be low level lethality, and they would not be very dangerous. Did someone buy a gun, load the ammunition, learn how to shoot it, go to the place where they planned to kill themselves at the time they planned, and then practice putting the gun to their head…essesntially a dry run? That would be the most lethal; that person would be the most dangerous. Those are the two poles of lethality and danger, but there are variant degrees and many shades of gray, so you really have to discuss it very thoroughly with each individual.
Let’s say a 15-year-old is in the office after taking a big handful of pills in a suicide attempt. I ask him if he realized that taking those pills could have actually killed him, and he says no. He’s not that lethal, not that dangerous, because even though his means (pill overdose) was lethal, he didn’t know it was, so lacking that knowledge mitigates the risk, making him less dangerous. Example: acetominophen is actually extremely lethal. People who truly overdose on it don’t die immediately, but it shuts down the liver, killing them two days later. A person that takes a bunch of it thinking it’s a harmless over the counter drug is not that dangerous, because even though their method was lethal, they didn’t know it. In a similar manner, I’ve had people mix benzos with alcohol, which is another very lethal method. It’s a very successful way to kill yourself, but a lot of people don’t realize it, so it’s not that lethal to them. In the reverse case, people who know about combining alcohol and benzodiazepines, who know how dangerous it is, are dangerous, highly lethal to themselves.
People who play with guns, like Russian Roulette-type stuff; or people who intentionally try asphyxiating or suffocating themselves, as for sexual pleasure; or people who tie a rope to a rafter and then test their weight…these people are very dangerous, very lethal, very scary to psychiatrists.
Where someone attempts suicide is also very telling, very instructive in determining their lethality, how suicidal, how dangerous they are. If they do it in a place where there is no chance of being found, of being interrupted, they are very suicidal, very dangerous. Contrast that to doing it in a place where there are people walking by, or in a house where someone is, or could be coming home, then they are not as suicidal, not as dangerous. As an exaple, let’s say someone leaves their car running in a garage when they know that no one will be around for 2 days. That is very dangerous, they are very suicidal. If someone takes an opiate overdose at night when everyone’s in bed so they won’t find them for many hours, they are dangerous. If someone takes the overdose during the day, when people are awake at home, they are less dangerous.
A change in somone’s behaviors and/ or outlook can also help determine lethality. When people start giving away their possessions, that is a sign that they are very lethal, very dangerous. Another factor that can be informative is if an unnatural calm comes over them, and they say that they have no more problems, and everything is great. That is an indicator of serious lethality, major danger. These people have a sense of ease because they know that they’ll be dead very soon, and they don’t have to worry about things anymore. These are ominous signs.
Giving information about an attempt also informs a person’s level of lethality. If someone makes a statement of intent to commit suicide, they are not very dangerous. For example, a spouse saying ‘if you leave me, I’ll kill myself’ or ‘you broke my heart, I can’t live without you, I’m going to kill myself’ those statements alone do not indicate a very dangerous person. Not telling anyone and hiding when they plan to attempt is much more dangerous. There are many cases when people don’t come out and tell, but they aren’t being very secretive, intentionally or not, possibly even subconsciously. They leave clues, almost giving people a road map. This is very common, and these people are typically discovered. The discovery can either totally abort the act before it’s attempted, or can abort after the attempt, but in enough time to get the person help. This is why for every 1 “successfully” completed suicide, there are 24 failed suicide attempts. Similarly, someone who says ‘if this thing (interview, event) goes my way, I’ll be good, but if it doesn’t, I swear I’ll kill myself’ is not that dangerous, not very suicidal, because they’re bargaining, which means they’re still living in the real world. But, someone who does not want to negotiate, doesn’t care to affect things one way or another, may not be living in the real world, and they’re dangerous, they may be high risk to enter the world of the dead.
There are a couple other things to be considered in assessing risk of suicide, determining how dangerous someone might be. If someone is impaired, using drugs and/ or alcohol when they attempt or consider suicide, and if they are not suicidal when they’re clean and sober, they are generally not that suicidal, not that dangerous, they just have a drug or alcohol problem. When they get clean and sober for good, the risk is essentially zero, barring anything else. In a similar way, if someone is suffering from a mental illness when they attempt or consider suicide, but when you correct that mental illness they are not suicidal, they are not a huge danger.
So during suicide risk assessment, you can be looking at someone having a nebulous thought and/ or making a statement that a lot of people may have or make, and you know that they’re not very dangerous; or looking all the way to the opposite side, someone who thinks about it, formulates a thorough plan, picks the place and time, aquires all the things needed to commit the act, writes a suicide letter, and practices the complete act soup to nuts, and you know that they are very, very dangerous. And all the shades in between.
So that’s my primer on suicidal thinking and assessing suicide risk. There are lots of factors to keep in mind, and sometimes it’s a little like reading minds, but you get more proficient as the years go by…it’s easier to tell when someone is misleading or being honest and open. If you enjoy a humorous approach to character studies in all sorts of diagnoses, you would enjoy my book, Tales from the Couch, available on Amazon. I mean, most of you are isolating, sheltering in place anyway, right? Might as well entertain yourself! Check it out. – Dr. Mark AgrestiLearn More
Element 3: Better for Batteries or Brains…or Beverages???
Think back to chemistry class, when you studied the periodic table of the elements. You may remember it as being just a confusing jumble of letters and numbers. But our daily lives would be very different without element number 3. It’s a key component in the batteries that power our smartphones, laptops, and even fancy-schmancy Teslas. But that same element also happens to be one of the most effective treatments ever discovered for bipolar disorder and mania, as well as other mental illnesses like depression, schizophrenia, and eating disorders. It is especially effective for treating suicidal ideation. Through the years it’s also been used to treat anemia, headaches, alcoholism, epilepsy, and diabetes. But it’s very scary, because it has some serious and potentially lethal short and long term side effects, and there is a very narrow window between the dose where it’s effective and the dose where it’s deadly. It’s so scary that I literally have only one patient out of my entire practice on it. The element I’m talking about is lithium. Let’s consider the good, the bad, and the ugly of lithium.
The good: it’s effective as all get out. I would call it one of the most effective drugs in the treatment of mania. It treats the high of the manic episode, the irritability, the agitation, disorganization, hallucinations, delusions, rapid speech, insomnia, racing thoughts, grandiosity, and impulsivity of mania. It prevents the mood cycling of bipolar, and it also treats the suicidality associated with mania and depression.
The bad: it has a nasty side effect profile. It causes a host of issues. Sedation is a big one. It makes people tired and causes obvious mental slowing. I say obvious because it becomes obvious to everyone. The person appears dull and medicated. It slows the mind down. Thoughts don’t process at normal speed, and speech and reactions are slow. It also affects kidney function, causing frequent urination, as well as nausea and diarrhea. It also can be very disabling because lithium commonly causes fine tremor. When all of the side effects are looked at together, they can easily be mistaken for alcoholism or drug abuse, so it can affect people’s opinions at work and have other huge social and personal consequences. It can cause a great deal of weight gain, as well as disfiguring acne on the face and back, as well as psoriasis, red scaly patches of skin on the body. On top of all of that, it can also affect the heart, potentially causing sick sinus syndrome, which is an arrhythmia where the heart’s natrual pacemeker, the sinus node, doesn’t work properly.
As for the ugly; let’s just say that lithium wouldn’t be winning any molecular beauty pageants… it is uuuu-uuu-gly! Lithium can cause nephrogenic diabetes insipidus and interstitial nephritis. Those are big words that simply mean it shuts the kidneys down. Like dunzo down. Patients on long term lithium therapy regularly have chronic renal failure. One of my patients that used to be on lithium is currently on a kidney transplant list. Another ugly component of lithium is that it shuts down the thyroid. You kind of need your thyroid to maintain metabolic processes in your body. It’s pretty important…without it, you become ill with all sorts of terrible issues and you must take another drug to kick it back into gear.
There are other issues with taking lithium. There are some commonly used medications that don’t play well with it. You cannot take diuretics, and you can’t take NSAIDs ibuprofen or naproxen for pain, because these can cause dangerously high levels. Lithium is unusual in that it has that small window of operation I mentioned. You have to have levels checked to make sure they’re between 0.6 and 1.2 mEq/L. If you get toxic by taking thiazide diuretics or NSAIDs or by getting dehydrated, lithium can cause permanent brain damage, nausea, vomiting, diarrhea, and death. So, it is extremely problematic in that it has that narrow window between efficacy and death. In addition, certain drugs lower lithium levels. A big one is caffeine; people have to be very careful with caffeine intake. Even drinking too much water can lower lithium levels, because you can literally dilute it in your system.
All things considered, I say lithium is a last line drug. Yes, it works, but it’s like using a sledgehammer to nail a one penny nail into the wall…there’s going to be collateral damage to the structure of the wall. As good as the good is, the bad is too bad and the ugly too ugly. There are so many other drugs now to try first. Lamotrigine, oxcarbazepine, valproic acid, lurasidone, aripiprazole, and quetiapine to name some. Some psychiatrists would argue with me because these other choices may not be as effective, but they won’t cause the mental slowing, acne, tremor, frquent urination, kidney failure, and hypothyroidism. I treat a patient as a whole, I don’t treat just the mental illness. If my treatment of the mental illness damages or destroys other parts of a patient’s life, is that proper treatment? I say no, but some physicians say yes. It’s a philosophical issue, a quality of life issue, that won’t be solved until somebody develops a drug that works as well but without the terrible side effects. As I mentioned above, I have only one patient in my entire practice on lithium, and I’m currently trying to get him off of it. Why? Well, he’s experiencing sedation, cognitive slowing, frequent urination, tremor, nausea, acne, and weight gain; surprise, surprise…it is making his life miserable. So we’ll continue to try other drugs and hopefully find some success elsewhere.
We’ve talked about the use of lithium in batteries and in brains, but in beverages? Believe it or not, it’s true.
Lithium was once a key ingredient in 7 Up soda. This is a 7 Up ad in a 1948 issue of Ladies’ Home Journal magazine. Look how happy everybody is, and notice all the open bottles of liquid lithium everywhere. The father is like “These crazy kids, drinking all this 7 Up. They’re going to drive me to the poor house!” And the son is like “It’s okay, dad! Have another sip of your 7 Up!” And the daughter is like “Wheeee! I LOVE 7 Up!” And the mom is like “I hope I have enough 7 Up to keep me from murdering my entire family.” And the tagline just kills me… “You like it- it likes you!”
7 Up debuted in 1929, and before 7 Up became it’s name, it was called “Bib-Label Lithiated Lemon-Lime Soda,” (really catchy name) and its original ingredients included a “healthy dose” of lithium citrate. Apparently there were more than 500 lemon-lime soft drinks on the market at the time, which is yet another fact that blows my mind. Anyway, to make their product stand out, Cadbury Beverages North America touted in their ads the “positive health effects” of the lithium in the soda, which interestingly was released just a few months before the 1929 stock market crash and the onset of the Great Depression….things that make you go hmmm….Apparently the recipe had some appeal, because in the 1940s, 7 Up was the third best-selling soft drink in the world. But alas, somebody got wise, and lithium was removed from the recipe in 1950. Just a little fun fact: there is a precedent for the addition of “pharmacologically active” ingredients in soft drinks. Coca Cola added a lot of coca leaves (from which cocaine is derived) to it’s original 1886 formulation, giving it it’s name. Another fun fact: the guy that formulated it was an alcoholic and opium addict who was looking for a cure for his affliction. Evidently it contained a great deal of the cocaine molecule, a fact that undoubtedly led to it’s popularity in those olden days. I’m sure lots of folks were bummed out when it was removed from the formulation in 1903. Didn’t matter to the formulator/owner, because he’d been found dead long before on his office floor with an opium stick in his hand.
For more interesting stories on psychiatric conditions and the medications that treat them, check out my book, Tales from the Couch, available in my office or on Amazon.Learn More