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Lithium Indications, Mechanism, Monitoring, & Side Effects

Lithium Indications, Mechanism, Monitoring, & Side Effects

Lithium is indicated for a number of things. Most clearly, as a mood stabilizer in bipolar spectrum disorders. It is unique among mood stabilizers in that it is very robustly anti-manic. The medication treats and prevents manic episodes from occurring, providing fairly robust prophylaxis against mood cycling. Lithium is also effective in treating bipolar depression, though not as effectively. Very few of the other mood stabilizers are effective for the depressed pole of bipolar illness.

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Why Lithium is a Great Option for Treating Bipolar, with Dr. Walter A. Brown

This week the Psychiatry and Psychotherapy Podcast is joined by Dr. Walter A. Brown, Clinical Professor Emeritus in the Department of Psychiatry and Human Behavior at Brown University, author of the brand new book “Lithium: A Doctor, a Drug, and a Breakthrough”.  In order to capture the full experience of this week’s episode, I’ve posted a transcript of my interview with Dr. Brown. 

 Dr. Puder: Tell me a little bit about yourself and how you got interested in this topic. 

Dr. Brown: I’ve been a psychiatrist for more than 40 years. A lot of my career has been as a full-time academic, doing research into various features of biological psychiatry, with a particular emphasis on the endocrine system as it applies to psychiatric illness and psychopharmacology.  I am also interested in the history of psychiatry. 

I came across Lithium early in my residency training. I did my first year of residency training in 1968-69. One of my first patients was somebody who was a manic-depressive, what we now call bipolar, and he was very difficult to manage. As I say in the introduction of my book, one of the things he was always trying to do was to leave the locked ward he was on in the hospital in New Haven, and go to Washington to meet with the President; it was my job as a first year resident to stop him from doing that. Several times a week, a group of nurses and I would have to restrain him and he would be injected with a sedative, but none of that really helped the fundamental features of his illness. 

At one point, as I was arriving at the hospital (I used to ride my bicycle to the hospital) I saw this man, who I refer to in the book as Mr. G, taking off across the parking lot and heading for the train station. I intercepted him on my bike and brought him back to the ward, but the people in charge there felt that he was just too difficult to manage and so he was transferred to the local state hospital for long term care. It was two years later that I saw him at one of the outpatient clinics. He was doing fine; he was no longer hospitalized, he was no longer insisting on meeting the President, and his periodic attacks of mania and depression had stopped. I chatted with him briefly and he told me he was on this new drug: Lithium, and clearly, it had really changed his life. After that, I had, like other psychiatrists of that era, many experiences with patients where they were taken off of whatever stuff they were on to treat their manic and depressive attacks and put on Lithium and they did very well.  

I became curious as to how this drug was discovered, how it worked, and I started looking into it. At the same time, one of the things I do in the department of psychiatry at Brown is teaching a seminar on classical papers in psychiatry; papers that change the field. I came across, in the context of that teaching, John Cade’s original report of the use of Lithium in mania. It was gripping for me because Cade was an essentially young, unknown Australian psychiatrist working in 1948 when he did this study in a remote hospital outside of Melbourne, Australia. He had no grants, no collaborators, he had no formal research training and yet he managed to come up with what is arguably the most important discovery in psychiatry; certainly of the 20th century. I was curious as to how this guy, who is still not a household name, managed to come up with something so important basically on his own.  

So I looked into the history of his discovery and what happened afterward. The more I learned about this, the more interesting the story became for me, and so I really decided to write it down. What I started doing was writing a biography of John Cade. There hadn’t been one by that time and I thought: “given the importance of his discovery, it would be good to take a careful look at who this man was”  But as I started to do research about Lithium and how it developed, it became clear that although Cade certainly was the first person to use Lithium in mania and sparked a lot of other research, a good number of other researchers participated in the discovery. They brought important elements to it and finally established Lithium for its main effects, which are to prevent episodes of mania and depression. The book became more than just the story of one man, it became the story of the scientific process, and the scientific discovery and I tried to look at the elements that went into finally getting Lithium established.

Dr. Puder: It was interesting, and it’s a great story, because it gives us that glimpse into the scientific method, the errors of how we develop bias, and how charisma can get in the way of finding the truth. Before we launch into it [Lithium], tell me a little bit about the natural course of bipolar pre-Lithium, pre-medications. 

Dr. Brown: First of all, for untreated Bipolar, roughly 20% of people with the illness with kill themselves. Suicide is very common in manic-depressive illness, particularly during the depressive phase, so 20% of people will end up dead as a result of the illness. The illness does not go away on its own. The usual course [of Bipolar] is that the frequency of the episodes of both mania and depression increase over time. People usually start off with, let’s say one episode of mania every two years, then they’ll change to having one episode every eighteen months, and then one episode a year. These episodes are almost invariably followed or preceded by a very, very severe depression. That’s the typical course, and that was the course of the illness before John Cade made his discovery. There really was no effective treatment other than using electroconvulsive therapy to treat the depressive phase (and sometimes the manic phase), but the alleviation of symptoms didn’t last very long using electroconvulsive treatment.

Dr. Puder: How genetic is Bipolar in your estimation, and what do we know about it at this point? Specifically, I was reading about how you looked at some of the Amish Studies and I think people would love to hear about that. 

Dr. Brown: Let me say upfront: we don’t know what the genes are that underlie manic-depressive illness. But I don’t think that there’s any question at this point that it [Bipolar] is a genetically based illness. It runs in families and there are probably several genes that underlie the disorder.  How do we know that it’s genetic? Probably the family studies that have been done over the last three to four decades have been the most important. The acid test for heredity is the comparison of monozygotic and dizygotic twins and the different concordance rates for the illness for the different types of twins. Concordance means: the likelihood that if one twin has the disease, the other twin will also have it. For manic-depressive illness, the concordance rate for monozygotic twins (those who have identical genetic make-up) is about 60%, but the concordance rate in dizygotic twins (those who don’t share the same genes and come from different eggs) is closer to 10%. That tells us that genetics plays a big role and that the family environment, which is going to be roughly the same if you’re a dizygotic or monozygotic twin, plays very little role in the expression of this illness. The relatives of manic-depressive patients have a 10-20x higher prevalence of manic-depressive illness than the general population; it’s clearly genetically based.

Dr. Puder: What was it like for people [with Bipolar] prior to Lithium? How where they treated? I think it would be interesting to talk a little bit about some of the specific examples of how people were treated; like Rosemary Kennedy, the sister of John Kennedy, who had a lobotomy. When I read that in your book it just broke my heart, because it was so tragic that it had to happen. Tell me a little bit about what life was like and how these people were treated. 

Dr. Brown: People with manic-depressive illness were treated the way people with other serious mental illness were treated up until the mid-20th century. That was whatever was currently in use to treat the seriously mentally ill was used for manic-depressives. In antiquity, way back when, there really were no treatments. People were cared for by their families and kept sometimes in horrendous circumstances If somebody was depressed, they were probably left alone until they got better. Depression, even the severe depression that is part and parcel to manic-depressive illness, actually goes away in most people after a period of six month or so.  But when people were manic, it involved a lot of bizarre behavior, rapid speech, sexual excesses, and physical violence, all kinds of things that created problems for society and the family. These people were sometimes locked in prisons, they were kept in cages in their family homes; basically there was nothing useful that could be done for them. Through the middle-ages, there were various kinds of potions and things we used to treat all kinds of mental illness, including compounds that contained opium (which would sometimes sedate people but really didn’t alleviate the fundamental symptoms of the illness). 

Then in the late 19th century, a number of physical treatments started to come into play. These included malarial treatment of tertiary syphilis. People with tertiary syphilis, or neurosyphilis (which is a horrendous attack on the brain, it’s a degenerative brain disease), made up a large portion of the patients of asylums. Some of these patients had the symptoms of manic-depressive illness, though they didn’t have the classic symptoms that we later learned were characteristic. 

People were treated with malarial fever therapy, which killed the spirochete that caused the illness [syphilis] and some of those people probably had manic-depressive symptoms; that was used at the turn of the 20th century. Other treatments of the era included insulin coma, which was used to treat manic-depressives as well as schizophrenic patients. People were given doses of insulin that brought their blood sugar very low, they would go into a coma, sometimes they’d have seizures, and this went on for days. This was a very dangerous treatment that was thought to be useful in both depression and schizophrenia, but with further study, turned out not to be terribly effective; but it was widely used for a number of years. Deep sleep therapy, which was not dissimilar to insulin coma, was also used. People were given high doses of sedatives and put to sleep for weeks on end, supposedly when they awoke they would lose some of their psychotic symptoms. That didn’t last very long. 

Finally, one of the most notorious treatments, that you have already alluded to was lobotomy, which was discovered by Moniz, a Portuguese neurologist in the 1930s. This involved severing the frontal lobe from the rest of the brain using what was essentially an ice-pick stuck through the orbit of the eye. This was a treatment that supposedly was useful both for severe depression, severe obsessive-compulsive symptoms, and it was certainly used for a number of manic-depressive patients (we now call them Bipolar). It [lobotomy] was very widely used in the 1940s and early 1950s. After several decades, both psychiatrists and neurologists concluded that it was not terribly useful, that people really didn’t know what they were doing to the brain when patients had this procedure. The procedure had a lot of awful side effects including intellectual impairment and socially inappropriate behavior. That’s what happened to Rosemary Kennedy, she became essentially a vegetable as a result of it. That treatment was finally abandoned, although variants of it are sometimes used today. 

The other big change over the years was in the role of asylums. Asylums started out in the Middle Ages as being not very different from jails. In fact, the kinds of people that were sent to the Asylums of those days were both criminals and those that were mentally ill; anyone who was “troubled” in society. In the 19th century, a number of humanitarian changes were brought about in asylums. Patients were treated with what they called “moral treatment”, which meant bringing them in, not chaining them up like they had been previously, giving people good food, a chance to work in gardens and so forth, and there was a feeling that a lot of patients actually recovered as a result of being in these pleasant environments. But on closer scrutiny, it was clear that this kind of so called “moral treatment” really didn’t accomplish much and patients weren’t much better after it, so it was largely abandoned.

Dr. Puder: Why do you think poets have a higher rate of bipolar? You mentioned in your book that 20-40% of poets have bipolar. You also mentioned that writers, artists, and composers have 5-15x higher rate than the general population. What are some of your reflections on that? 

Dr. Brown: It’s clear now, from multiple studies conducted over a long period of time, that there is an association between certain types of creativity and manic-depressive illness. People, particularly poets, but also writers, composers etc. have much higher rates of manic-depressive illness than the general population. The association seems clear, but why it exists, I don’t think anybody really knows. There’s all kinds of speculation that the gene that puts people at risk for manic depressive illness many also separately have something to do with creativity. In fact, family members of people with manic-depressive illness, who don’t have the illness themselves, often score high on measures of creativity. So it seems like there might be some genetic connection between manic depressive illness and creativity. 

It’s also been speculated that the experience of having these very intense moods somehow facilitates the poetic imagination and is somehow related to a person’s ability to perceive the world around them in the kind of special way that poets do so. But nobody really knows for sure what underlies this association.

Dr. Puder: Tell me about the story of John Cade—some of the highlights, and some of the things that were like “ah ha!” moments for you. 

Dr. Brown: One kind of perception of what Cade did is that he was just was lucky; he just sort of stumbled on something and he really didn’t put much thought into it. I think the story is more complicated than that. First of all, he was born into a family where the father was a psychiatrist. His father, when Cade was quite young, joined the Australian expeditionary force to fight in the First World War. He was overseas for a number of years, assigned to an ambulance corp that was like a mobile hospital. When he returned from the World War, the senior Cade was in rough shape; he was not the person he was before he left, he was shattered psychologically. He was unable to work effectively as the general practitioner that he was before the war. So he took a salaried position with the Victoria of Australia Mental Health Service and he became director of several mental hospitals. In those days, the director and his family lived on the grounds of mental hospitals. So John Cade grew up among severely mental ill patients and his son speculated that it gave him a special empathy with these people, a kind of comfort with them, and a desire to help them. Cade attended a very prestigious secondary school called Scotch Academy, and then went on to Melbourne University where he went to medical school. At first, when he graduated from medical school he was going to go into pediatrics, but decided to switch to psychiatry.  

At that time, psychiatry training was not as formalized as it is now, so he worked for a couple of years in various psychiatric hospitals. Then, like his father, he joined the army with the outbreak of the Second World War and he was also assigned to an ambulance division. He shipped out in 1940 to what was then called Malaya [now Malaysia] as a general medical officer in the army, he was not officially a psychiatrist. 

Then in 1941, the Japanese invaded the Malayan peninsula; the war that ensued was a complete disaster for the British and Australian commonwealth forces. Even though the commonwealth forces outnumbered the Japanese 2 to 1, the Japanese were battle hardened and had much better leadership - strategically they did a lot better. The commonwealth generals made a lot of errors. Finally, the commonwealth forces retreated to Singapore, where they made a final last stand and were defeated. About 30,000 of these soldiers were imprisoned in the Changi POW camp, which became notorious, and Cade was among them. He was imprisoned for three and a half years.  

During his imprisonment he underwent severe malnutrition, as did all of the other prisoners, which was the major problem at Changi. The Japanese had not ratified the Geneva Convention, which stated that prisoners had to be fed an adequate diet, so these guys really were grossly underfed. Cade, because of his psychiatric experience, was put in charge of a 12-person psychiatric unit and he was the only doctor there who did that. There he cared for, and did consultations for, POWs who developed psychiatric disturbance. This experience did a number of things for Cade: (1) it convinced him that the needed better treatment for things like depression and (2) a lot of mental illnesses had a biological basis. When he would do autopsies on some of the psychiatrically ill he would find various kinds of brain abnormalities, including hemorrhages and tumors. Clearly the vitamin deficiency diseases he was seeing sometimes had a psychiatric component. 

When Cade returned home, he took a job at a psychiatric hospital run by the Victorian Mental Health Service, and there he decided to start some research looking into the causes of manic-depressive illness. He theorized that, like thyroid disease, manic-depressive illness results from both an excess and a deficit of some normal bodily substance (in the case of the thyroid, thyroid hormone). He was going to look for the toxic substance in manic-depressive patients that caused the illness.  

At this point things get a little bit difficult to follow logically, but he started doing some experiments with guinea pigs where he injected the urine of manic depressive patients and basically judged the toxicity of the urine by how much it took to kill the guinea pig; by his own admission, it was a crude test of toxicity. He found that, in fact, some of the urine from manic-depressive patients seemed to be more toxic than the urine of people with other psychiatric diagnoses and health people. He then began to look for the substance in urine that could be causing the mania and in doing this he went through various constituents of urine. In the context of all of this, he began to inject the guinea pigs with uric acid and Lithium salts because Lithium was very good at bringing uric acid into solution. So he started using Lithium urate and Lithium carbonate to examine the role of uric acid in this toxic urine, and when he injected animals with these Lithium salts he found that they became somewhat tranquilized. The guinea pigs would lie on their backs placidly just looking up at him, not running around and looking startled like they usually would. This somehow gave him the idea to go next door (his laboratory was on the grounds of a psychiatric hospital) and go to the ward with a bunch of severely manic patients and see what Lithium would do for them.  

First he took Lithium in varying doses himself, because there really wasn’t much experience in the [medical] literature using Lithium at the doses he planned to use it in humans. The Lithium didn’t hurt him, although his wife was not happy about the fact that he was experimenting on himself. Then he started giving Lithium to manic patients. The first patient he gave it to had been chronically manic for about five years. Within two weeks of getting Lithium citrate this man was able to leave the ward, ultimately went home and returned a useful occupation. Cade then went on to treat an addition nine patients, all of whom did remarkably well on Lithium, better than they had on any other kind of treatment that was thrown at patients at the time. He wrote up his results in the Medical Journal of Australia, and that was the beginning. 

Dr. Puder: He [Cade] sounds like such an amazing person. I remember one of the quotes you had from one of his speeches about all the different types of science and all the unique interests he had throughout his career and he seemed like such an intelligent person. 

Dr. Brown: What struck me most about how he [Cade] operated was his capacity for unfettered neutral observation. He was very interested in the natural world and I point to several examples in the book. He was very interested in scat of animals. He did his own research on birds and looking to see if the White-backed Magpie and the Black-backed Magpie were different species or varieties of one species. He pointed out to one of his sons that the fact the Gum Emperor Caterpillar Moth produced a feces that was six-sided meant they had a six-sided anus. He was always looking at things and examining them. I think his ability to see the unexpected was somewhat unusual. He certainly didn’t expect to see the guinea pigs that he gave Lithium to to become tranquilized. I think there aren’t a lot of people who trust unexpected observations. As Yogi Berra supposedly said, “If I didn’t believe it, I wouldn’t have seen it.” But Cade believed things that he saw for the first time and I think that cognitive characteristic really facilitated his discovery. 

Dr. Puder: I want to jump ahead a little bit, for the sake of time. There’s a lot more to this story that I’ll leave for people to read about how it [Lithium] when from his discovery to not being widely adopted much later. I wanted to pick your brain a little bit on a statistic that you mentioned; that 50% of people with Bipolar in European and Scandinavian countries receive Lithium, but only 10% in the U.S. I wanted to get your opinion on that and also your thoughts on why that might be the case. 

Dr. Brown: It’s hard to get highly reliable numbers on how many people are taking Lithium because nobody is really tracking it. The pharmaceutical industry is not really interested in what’s going on with Lithium because they can’t patent it and don’t make any money from it.  The best that I could come up with after combing through the literature was this 10% vs. 50%. I think there are two reasons for that. One is that after the 1980s other drugs, particularly Depakote, came out on the market that could also prevent episodes of mania and depression; the drug company that made it promoted it very aggressively. Depakote was heavily marketed and promoted and to some extent took over Lithium’s role as the “gold standard.” The second thing is that Lithium can create serious side effects (I might say that Depakote also has side effects). In order to safely give Lithium to somebody, it has to be given along with the measurement of Lithium blood levels. The reason for this is that the Lithium blood level required for a treatment effect, or a therapeutic effect, is not very far below the Lithium level that will give somebody toxic symptoms. These include tremors and other neurological symptoms such as coma, and people can die from a Lithium overdose.

But once blood levels are monitored, which is not that hard to do, and doesn’t need to be done more than once or twice a year when someone is stable, it works perfectly well. I think the third reason is that historically, in this country, Lithium created trouble. Around 1949, Lithium Chloride, another salt of Lithium, was promoted as a salt substitute for people on low-sodium diets. Lithium Chloride tastes salty, but it doesn’t create problems with Hypertension and Kidney Disease that Sodium Chloride does. People started using it a lot and they were pouring it very liberally on their food. A number of patients, around 1949, got toxic from the use of Lithium salt substitute; some died. The FDA banned Lithium and banned its use in other substances.  People didn’t forget about that, it was a real panic. It didn’t last very long, maybe about a year, all the Lithium was taken off all the shelves in all the pharmacies. People remember that salt substitute debacle and that may have had something to do with its [Lithium’s] slow uptake in the U.S. But I think the primary reason for the fact that Lithium is somewhat underused here [the U.S.], I think is the aggressive marketing of those other drugs.

Dr. Puder: Yeah, I think that’s why I get passionate about this for my audience. There’s no drug rep that’s going to come to your office and promote Lithium. So I think that people who are looking at the science, that are looking at the data, are trying to treat patients according to evidence-based medicine  - we’ve got to keep putting those principles out there. What is your one big take away maybe about the history of Lithium or maybe about the scientific method? 

Dr. Brown: There are a couple, one is that it’s important that whatever institutions that are trying to promote innovative research keep a look out for people who are imaginative, like John Cade, are careful observers who might not necessarily be inclined to write an extensive grant proposal. Sometimes the kind of people who are likely to make important, break-through discoveries are not the kind of people that are necessarily getting funded in this country.  There’s a tremendous concern on the part of the psychiatric establishment and the research establishment over the lack of real innovation, particularly in treatment. 

After Cade’s discovery in 1949, the following decade from 1950-1960, all of the major types of drugs that we use today were discovered, the anti-depressants, antipsychotic drugs were discovered. Since that time there have been many new drugs, different drugs have come on the market, but they really don’t represent a change from those earlier drugs.  Why don’t we have more innovation? Why does the National Institute of Mental Health spend a “gazillion” dollars on all kinds of research, but as the former director of the NIMH said, “it hasn’t really moved a needle with respect to coming up with better treatments for the conditions that plague us.” I think we need to take a look at how me approach innovation. 

Dr. Puder: That makes me think. Writing grants and doing research you have to be very organized. There’s this other side of our human potential, which is people who are highly creative and often are more spontaneous, are high in openness. They’re almost like two different types of people. The kind of person who rises up in research now a days, you have to be highly organized, almost obsessive with how detail oriented you are. Does that make sense? 

Dr. Brown: Yes, absolutely. The other take away, and I think one of the things I try to convey in the book is how different scientists learn from each other. There was a sort of web of information that was created about Lithium and I document how after Cade’s discovery some other Australians looked at Lithium, then a Dane named Mogens Schou went ahead and did some very important studies, people read his papers and added some very important information…. So it [the book] is also an illustration of how scientific discoveries build on each other. 

Dr. Puder: I really appreciated that part of your book. I think it’s a great book, because it really does show the scientific method, I think it also shows the danger of different charismatic leaders who had ideas about what the best treatments were for mental illness, how they utilized their charisma and often good intentions, but were not as scientific minded and open to internal critique as some. I’ve really enjoyed our conversation. I would love to dive into some of the pivotal papers at some other time if you would like to talk about that, I think that it would be a lot of fun. 

Dr. Brown: Sure, that would be great. Thank you for such penetrating questions. 

Special thanks to Dr. Walter A. Brown for the excellent discussion about John Cade and the history of Lithium. If you would like to read more of the story, you can find Dr. Brown’s book, “Lithium: A Doctor, a Drug, and a Breakthrough” here



Frontal Lobe Damage: Treating Patients through Grief, Acceptance and Growth

In this episode of the podcast, I interview Steven Prince, one of my patients who had a rare form of a stroke—in the right orbital frontal cortex. He participated in a psychiatric program that I run. He tells his story of how his function and emotions changed, and how he dealt with it. At the end of the episode, I talk more with Jaeger Ackerman about the science and neurology of his case so other mental health professionals can have a basis for how to think about approaching brain injury.

David Puder, M.D., Jaeger Ackerman

The case of Phineas Gage

The history of the study of frontal lobe damage

Phineas Gage was a railroad construction worker who experienced a massive frontal lobe injury in 1848 in New England. He was efficient, capable, and full of energy prior to his accident. During an explosion at work, a 13 pound iron bar was launched through his face at close range, up through his skull. It entered his left cheek, went through his eye, and came out of the top of his skull, landing 100 feet away. 

Gage was carted to a local doctor where he got out of the cart and walked into the doctor’s office. As the doctor treated him for a few weeks, brain matter and infections, bone particles and tissue were oozing out of his head. Still, Gage survived, with relatively little physical injury after he was healed, with the exception of his left eye.

The main effect of Gage’s injury was in his behavior. He was studied, a medical marvel of survival, and is now reputed to be one of the first, and therefore most important, cases dealing with frontal lobe damage and its effect on behavior. After his accident, Gage was belligerent, fitful and profane. He lost the balance between his emotions and his intellectual ability to function. 

Other symptoms of broad temporal frontal lobe damage can be:

  • Apathy

  •  Depression

    • Anterior (Stuss 1986) and Lateral lobes (Paradiso 1999)

    • Left lesions more likely to lead to depression than right lesions (Rogers 1998)

    • Postmortem neuropathology of depressed patients indicated generalized prefrontal diminution (Cotter 2005)

  • Euphoria (Grafman 1986)

    • Sporadic or recurrent and resembles the affect of the hypomanic state (nervous, irritable, sometimes paranoid)

    • Usually accompanied by compulsive, shallow, childish humor

    • Distractibility and hyperactivity 

  •  Motion and Emotion

    •  Hypokinesia (dorsolateral lesions) (Heilman 1991)

    • Hyperkinesia- aimless/excessive motility (orbitofrontal lesions) (Meyer 1948,)

      • Perseveration (repeating old patterns of behavior even in circumstances that demand change) (Konow 1970)

    • Emotional Lability and disinhibition (orbitofrontal lesions) 

  • Empathy 

    • Large lesions of orbitofrontal/ventromedial cortex impair mainly affective empathic component (Shamay-Tsoory 2004)

    • Inability to interpret and respond to emotional voice or facial expressions (Shaw 2005)

  • Social Behavior

Grief, acceptance and growth

Steven’s story

Steven had five strokes and tinnitus. It was also not physical trauma, and Gage’s was much worse. His decline led him to spend five hours a day researching his health conditions.

He was suffering from anxiety, depression, fear and grief in reaction to his health condition, and Steven did something about it. He came to my outpatient group.  

At his worst, Steven’s tinnitus caused him to lock up the guns in his house so he wouldn’t think of ending his life, and he says he “took xanax like candy.” He felt as if he was mourning and grieving losing who he was. He’d had a successful career previously, but he no longer found the same meaning in his life. 

During his struggles with his mental health, Steven joined the day treatment program that I am the medical director of. When he first came to the program, he didn’t think he would fit in. When he introduced himself on the first day of meetings, he told the others his name, and then described his illness. When the entire room finished introducing themselves, the therapist kindly pointed out that they had all introduced themselves through the lens of their illnesses. “Aren’t you people? Humans? You are not your diagnosis,” the therapist said. Steven said it changed his life to see it that way. 

As he became more comfortable being his “new” self, more comfortable with his emotions and frustrations about his limitations, he became more aware of how he was speaking and thinking about himself. He learned to accept his illness instead of battling it. When he accepted it, he was alright with moving on and being a whole person, just in an entirely different way. He says he became more self confident, healthy, and less stressed. His wife has commented on his increased empathy as well. 

Steven’s diagnosis - Right Side ACA Strokes

After Steven’s stroke, he felt “flooded.” He would become overwhelmed with audio and visual stimulation, which caused him to have to retreat into a dark room for up to 24 hours. 

ACA Stroke/Frontal Lobe Damage symptoms

  1. Accounts for 0.3 to 4.4% of total stroke cases. Males are more commonly affected than females, and most of these strokes occur between the age of 59 and 75. ACA strokes arise on the left hemisphere more commonly than the right. (Kang and Kim 2008, Arboix, Garcia-Eroles et al. 2009)

  2. Most common presentation is motor deficits characteristically involving the contralateral lower extremity; present in 86.3-90% of ACA strokes (Kumral 2002)

  3. Other motor disorders related to ACA infarcts include hypometria, bradykinesia, global akinesia, loss of reciprocal coordination, parkinsonian gait, tremor, dystonia, and motor neglect (Nagaratnam, Davies et al. 1998, Kobayashi, Maki et al. 2011)

  4. Sensory deficits less common; ~25%, and always correlate with weak extremity (Kang 2008)

  5. Abulia (willpower, assertiveness), agitation, motor perseveration, memory impairments, emotional lability, anosognosia are neuropsychological features reported in ACA infarcts (Kang and Kim 2008)

  6. Altered consciousness and speech disorders identified in up to 43.1% of ACA infarcts (Arboix, Garcia-Eroles et al. 2009)

  7. Transcortical motor aphasia and transcortical mixed aphasia (Nagaratnam, Davies et al. 1998, Kumral, Bayulkem et al. 2002)

The main part of the brain that is typically affected by this kind of stroke is the prefrontal cortex region, which makes up 29% of human brain matter. Humans are unique in that the prefrontal cortex is significantly larger than in other species. This region of the brain is responsible for temporal organization, executive memory and executive attention. 

Temporal organization is the most general and characteristic of all prefrontal functions in the primate and enables the organization of actions and thought within the domain of time. This temporal organization facilitates the capacity for elaborate behaviors, speech fluency, higher reasoning, and creative activities.

Executive memory is the idea of taking formed prior experiences and being able to learn from them and make decisions about the future. This ability effectively organizes the present in order to prepare for the future

Executive attention deals with using short term active memory to apply to the immediate here and now. Within executive attention, there are a few main functionalities:

  • The preparatory set is the part of the brain that reconciles sensory cues and coordinates past memories to prepare the body for active response—like a runner gearing up for a race. 

  • Inhibitory interference control enhances contrast to different information. The brain filters out what it needs in the immediate, and is able to dampen down everything else that doesn’t matter. In Steven’s case, this part of his brain was damaged because he had a lack of control over what information was inhibit or processed as important by his brain.

Also in Steven’s case, I opted to focus on increasing his sensorium by lowering his xanax intake to help him increase his executive functioning so he could become more himself. 

The fascinating thing is that the brain can change itself. If you have a loss of movement from a stroke, you want a program that is 5 days per week and really intensive. That’s why partial programs can be helpful to guide the patient in developing the brain in a way that would be most healing for a loss of psychological function. 

The importance of emotional congruency

One of the main things we focus on in the program Steven was part of is implementing the importance of congruence. Congruency is about making sure who you are on the outside reflects who you are on the inside. When people are incongruent, they put undue psychological stress on their personality to perform and feel the need to appease others. Steven adaptively relied on his ability to tell funny stories, and when he felt he could finally just “be” and not “perform” for others to make them feel more comfortable, he felt he could take that part of his personality off. He became more congruent with what his inner state felt like. 

As Steven shed his need to please, he became more assertive. He also learned to handle his tinnitus with self compassion and lower anxiety. Now, he lives with it and it causes him little emotional distress. 

Within the program, doctors helped our patients develop congruence through their writing, drawing and talk therapy. We can often see incongruencies in those different modalities and begin to talk about them. Another way we help them with their mental health is through encouraging them to start doing strength training. 

Moving on

Steven’s passion is now helping connect others who need support through their chronic illnesses. He wanted to find a support group where he lived, but he couldn’t, so he started his own on Facebook. He opened it to more than stroke victims, and he has been successful in creating that group, having guest speakers who are mental health professionals, and building a supportive community within it. He says he wants to bring hope and encouragement to people with chronic illness. 

Watching Steven change and heal has been a pleasure. He has moved through the grief, acceptance, and growth that is possible for many of our patients. 

Treating patients with frontal lobe damage

Other than therapy, I find that optimizing a patient’s sensorium is incredibly important to restore normalcy of life.

You can improve sensorium through improving sleep, diet, and strength training. Also, having meaning and purpose, having friendships and an internal locus of control, can also optimize sensorium.

Consider listening to this one next:

An Introduction to Psychodermatology: “The Mind-Skin Connection” 

On this week’s episode of the podcast, I sat down with Chloé Walker, a 2019 Loma Linda University graduate with a fresh passion and desire to pursue a career in psychodermatology. We had a candid conversation about how planting awareness of the interconnection between mind and skin will equip this specific patient population and medical professionals with the proper tools and resources that empower positive patient response and care outcomes. 


Chloé Walker, MD and David Puder, MD 

What is Psychodermatology? 

At the most basic level, Psychodermatology encompasses the interaction between mind and skin. It is the marriage between the two disciplines of psychiatry and dermatology, uniting both an internal focus on the non-visible disease, as well as an external focus on the visible disease.  This tight interconnection between mind and skin is maintained at the embryological level of the ectoderm throughout life. 

According to this article, although the history of psychodermatology dates back to ancient times, the field has only recently gained popularity in the United States. More specifically, Hippocrates (460-377 BC) reported the relationship between stress and its effects on skin in his writings, citing cases of people who tore their hair out in response to emotional stress.  

Understanding skin disorders through the lens of psychosomatic medicine allows the clinician to reveal the underlying source of suffering, which may be in the form of repressed expressions of anger and hostility. Stating, “In the skin we see not just our internal physical state but all our psychological processes and reactions. Pressure from within and pressure from without reveals itself on the skin.” 

This study concluded that how patients cope with an internally focused emotion plays an integral role in facilitating how the body externally manifests that emotion through the skin in a process clinically referred to as the conversion phenomenon.  Specifically, PTSD was highly and positively correlated with Escape-avoidance (r = 0.52, p < 0.001), as an emotion-focused coping strategy which were in turn associated with Chronic Idiopathic Urticaria (CIU) severity and psychiatric symptom severity. 

How are Psychodermatological Disorders Classified?  

According to this article, while there is no single universally accepted classification system of psychocutaneous disorders, the most widely accepted system, devised by Dr. Koo and Dr. Lee, involves three main categories

1) Psychophysiologic disorders encompasses those skin conditions that are precipitated or exacerbated by the psychological stressor. Examples include acne, alopecia areata, atopic dermatitis, psoriasis, psychogenic purpura, rosacea, seborrheic dermatitis, and urticaria.  

2) Psychiatric disorders with dermatologic symptoms encompass skin conditions that are associated primarily with an underlying psychopathology in which visible skin lesions are self-inflicted by the patient. Examples include body dysmorphic disorder, delusions of parasitosis, eating disorders, factitial dermatitis, neurotic excoriations, obsessive compulsive disorders, and trichotillomania.

3) Dermatologic disorders with psychiatric symptoms encompass those skin conditions that secondarily develop an emotional disorder in which the psychological consequences often outweigh the physical symptoms in severity. Examples include alopecia areata, albinism, chronic eczema, hemangiomas, ichthyosis, psoriasis, rhinophyma, and vitiligo.

As you can see from this classification system alone, there is a significant amount of overlap that exists between categories.  

Direct vs Indirect classification 

A 2019 comprehensive review article suggests that psychiatric disease may have a direct or indirect association to dermatological disease: 

A direct association involves psychiatric disorders that cause the dermatological disorder purely by itself without any secondary influence. This classification includes stress and tactile hallucinations that are not physically visible.

An indirect association involves psychiatric disorders that trigger behaviors causing physically visible skin damage. This includes the skin changes that result from manual scratching due to psychogenic pruritus.

Some psychiatric diseases may have both direct and indirect associations in the development of dermatological diseases. For example, depression is directly associated with psoriasis through an inflammatory mechanism, and is indirectly associated via trichotillomania. 

Temporal classification 

Most dermatologists encounter patients who report a temporal relationship between disease flares and stressful life events. 

Board certified dermatologist and clinical psychologist, Dr. Fried states, “When it comes to treating patients who we suspect may be experiencing skin, hair, or nail problems as a result of stress or other emotional factors, it is helpful to ask them whether their skin seems to look or feel worse when they are stressed.” 

Developmental classification 

Attachment style changes a patient’s connection with their dermatologist and their overall experience of stress. 

In fact, a 2017 European multicentre study found that secure attachment of dermatological outpatients may be a protective factor in the management of stress. Those participants with secure attachment reported stressful life events significantly less often and increased satisfaction with their dermatologist than those with insecure attachment styles.  

The overall important takeaway highlighted in this study is the value of taking a thorough history of present and past psychosocial factors, including stressors and traumas to have a more in-depth understanding of the skin disease at hand preventing parasuicidal behaviors and suicide. Stating that Up to 90% of patients who commit suicide may have a psychiatric disorder (50% MDD; 25% substance abuse and dependence followed by psychotic disorders, PTSD and body dysmorphic disorder). 

Let’s talk about Psychiatric Morbidity in Dermatology.  

According to an article in the Indian Journal of Psychiatry, the incidence of  psychiatric disorders among dermatological patients is estimated at 30 to 60%

Another study conducted in India suggests that recognition alone of psychiatric disorders by a dermatologist is not adequate. Stating that out of 636 patients, 104 (16.4%) had psychiatric consultations and in 97 of them a psychopathology had been diagnosed. The patients with a psychopathology constituted 15.3% of all the patients and 93.3% of those who received a psychiatric consultation. The most prevalent pathology was depression (31 patients 32.0%). The most prevalent dermatological diagnosis of the patients with psychiatric morbidity was chronic urticaria (25 patients, 25.8%). 

This study showed how the emotional burden of skin increases the risk of self-harm and suicide. Questionnaire results including all consultant dermatologists in the British Association of Dermatologists Members Handbook 1996/97 320 reported (78% of the total sample) encounters of  patients with psychological or psychiatric disturbance which they considered to be a consequence of their skin. Eighty-six participants were aware of a total of 178 patients who had attempted suicide associated with their skin disorder.

Unique fears center around acne. This study concludes that “In the long run acne may cause cutaneous as well a psychological scars.” Stating that in a sample of 355 high school students from the city of João Pessoa with an average age of 16, there was a prevalence of 89.3% of acne vulgaris. The most prevalent psychosocial issue was "afraid that acne will never cease," present in 58% of affected youth. 

Another study supports that acne patients have an increased risk of depression and anxiety with anxiety being more common having a direct relationship to impairment of quality of life. 

What is the Best Plan of Approach involving Treatment Modalities? 

Role of the dermatologist

  1. Have a good screening tool such as GAD-7 and PHQ-9

  2. Get a full history including stressors and potential psychological/ developmental aspects. This largely involves motivational interviewing

This article strongly supports the use of  intake PHQ-9 and GAD-7 questionnaires (which are shorter in length, free to use and self-administered) as a practical approach for busy dermatology clinics.  

Outpatient psychiatry and psychotherapy: 

Psychotherapy (including behavioral modification techniques) are first line especially when addressing pediatric psychocutaneous disorders.

  1. Combined treatment will be most effective: 

Treatment is determined based upon the underlying psychopathology

  • OCD: SSRI Fluoxetine, TCA Clomipramine, or N-acetylcysteine which has shown great promise in the treatment of trichotillomania. 

  • Anxiety: SSRIs for Generalized Anxiety Disorder (GAD). 

  • Depression: SSRI Sertraline preferred for melancholic depression or psychomotor slowing; SNRI Venlafaxine for melancholic depression; TCA Doxepin for psychomotor agitation.

  • Psychosis: Atypical antipsychotics are first line with Pimozide as an alternative option

        2)  Exercise, diet, probiotics,  sleep, mindfulness, spirituality (forgiveness)

Intensive Outpatient Programs (IOPs) and Partial day treatment programs

  1. MEND Outpatient Program (Mastering Each New Direction) specific to chronic disease states- meaning, congruence, family conflicts.

Inpatient:

  1. Recommended for actively suicidal patients with a plan.  

ECT/TMS/Ketamine 

  1. Recommended for treatment resistant patients with failed multiple treatments and therapies. 


How does the Skin Respond to Stress?    

This article discusses how stress activates body response systems including the Hypothalamus-pituitary-adrenal axis (HPA), Sympathetic axis (SA),  Cholinergic axis (CA), and neuropeptides and neurotrophins. Acute stress triggers a “fight or flight” response by changes in memory performance, blood flow and energy metabolism. However, long-term stress exposure, the adaptive capacity of the stress response systems is lost due to lack of time for recovery and regeneration of the responsiveness to stress. 

Stress may precipitate the vicious cycle in the pathogenesis of chronic urticaria (longer than six weeks in duration). This article provides insight into the mechanism of how stress facilitates vasodilation and increased vascular permeability also implicated in the pathophysiology of atopic dermatitis, eczema, and psoriasis. Early responses of stress result in the downstream secretion of cortisol and IL-18 which modulate HPA axis inhibition of secreted corticotropin-releasing hormone (CRH). However, cases of chronic exposure ultimately result in low cortisol release, increased production of proinflammatory cytokines and increased production of CRH secondary to hypocortisolism-induced loss of feedback control. Hair follicle keratinocytes, sebocytes, and mast cells also operate within a peripheral HPA axis equivalent to the central HPA axis in the skin secreting CRH and IL-18, as well as expressing CRH-R1 receptors in response to stress all contributing to severely induced cutaneous inflammation. 


Link to full notes and OCD handout: here

An Inside Look At Eating Disorders: Anorexia, Bulimia, & Orthorexia

On this week’s episode of the podcast, I interviewed Sarah Bradley, a competitive runner who has worked her way through a personal struggle with anorexia, bulimia and orthorexia.  

Sarah Bradley and David Puder, MD

What is an eating disorder? 

One of the most important things about anorexia and bulimia is understanding that they are caused by a complex interplay of genetics, epigenetics, early development, and current stressors. They can lead to dangerous outcomes because of how the eating disorder changes both the body and the brain. Many therapists and nutritionists, as you’ll hear in my conversation with Sarah Bradley, don’t treat from multiple angles, and often lack empathy into this condition.

There are three main types of eating disorders we will cover here:

  • Anorexia is the practice of cutting calories to an extreme deficit or refusing to eat. 

  • Bulimia involves purging, or vomiting, the food that has been eaten. 

  • Orthorexia is a fixation and obsession on eating healthy food (like only eating green vegetables with lemon juice). 

Statistics:

  • Anorexia traditionally lasts for an average of eight years.

  • Bulimia traditionally lasts for an average of five years

  • Approximately 46% of anorexia patients fully recover, 33% improve, and 20% remain chronically ill. 

  • Approximately 45% of those with bulimia make a full recovery, 27% improve, and 23% continue to suffer.

Symptoms:

In a future episode, I will go into details like the DSM V diagnosis of anorexia or bulimia. For this episode, we wanted to keep it more practical. 

A patient with anorexia will desire food but choose not to eat it (unlike depression, in which the patient does not desire food). A patient with bulimia vomits their food after consumption, which can cause significant electrolyte abnormalities, seizures, and potential death. 

Treating patients with eating disorders

Having empathy towards someone with eating disorders can be difficult if you are approaching it from your own experience (or lack of experience). If you are not careful, as a psychiatrist or therapist, you can actually make things worse. And if you suggest a certain diet to aid in recovery, you can push a patient into orthorexia. 

The mortality of anorexia and bulimia is considerable, which is why my practice often gets patients into an eating disorder day treatment program.  

In this episode we talked about what not to say. In particular, we talked about not saying things like “you have a great body, why do you want to lose weight?” Or a dietitian who told Bradley, “We will only talk about food, not emotions,” which assumes that eating disorders are a physical, and not emotional, problem.  

When we looked at online chat forums to see how patients experienced their doctors when they discussed their eating disorders, these are some comments we found:

“Went to a dr to try to get referred to an Ed therapist I think last year? My bmi was 15, and I was told by the dr "you obviously don't need help. It's not like you need inpatient. You aren't at a weight that I feel it would be appropriate for me to refer you to someone. If you want to, you can go to the er for a voluntary psych hold." I was so humiliated that I just nodded and left.”

“When my bulimia was at its worst, on the very first appointment, and right in front of my dad, the guy said, "I'm going to put you on Wellbutrin. You don't binge and purge right? Like eat and make yourself throw up." I said no because I was right in front of my dad. So the therapist said, "oh, yeah I didn't think so. You aren't overweight like people with bulimia, because it doesn't cause weight loss. I just have to ask. Also at the very beginning of my ED, my school counsellor dismissed me when I said I was trying to stop eating, because I wasn't a girl, extremely underweight, or actually not eating. I'm still pissed about it.”

“I told my therapist about my starving and then b/p-ing cycle a couple of sessions back, and then she told me after a while "do you still do your vomiting thing?" and I told her, "yeah, but maybe just 2 or 3 times a week now" and she's like "oh okay, at least that's better" and then proceeded to change the topic into something other than my "bad eating habits". Needless to say, I've never been diagnosed and I feel like my disorder isn't real.”

“An actual medical doctor said, after I told her how much weight I had lost by eating almost nothing, "At least you had the weight to lose.  Let's get you on some antidepressants..." Um... ok, yeah, NO. I also told her I thought 88 lbs was a nice weight, I'm 5'2, she said that was much too low.  She then added that when she immigrated to America, she weighed 88 lbs, but she is shorter. Like, WTF??”

Overall, mental health professionals need to do research into understanding the disorder and be empathic when responding to their patients. 

Creating mental separation from the disorder 

Although behaviors associated with the eating disorder are carried out by the patient, the confusion that the disorder is an aspect of their self (rather than a disorder or illness) can make it difficult for them to detach sufficiently from the disorder. Being able to detach from the disorder means that they can evaluate the role of the eating disorder in their life: both the positive and negative aspects.

Here are some good examples from an online eating disorder toolkit to help you, as a therapist, be able to help your patients differentiate between their eating disorder and themselves: 

“We’ve spoken about the ways anorexia can seem like a best friend to you. I wonder if you can see any ways in which the anorexia is making life harder for you?”

“Our job is to give you back some control over the Eating Disorder and keep you healthy no matter what.”

“You are here because the Eating Disorder has gone too far and made staying healthy impossible for you.” 

Eating Disorder Patients’ Interpretations of Therapists’ Bodies

Clients evaluate their therapists’ body size and speculate on their relationship with food. This can determine what impact this might have on the therapeutic process. 

According to this article, three main themes emerged during analysis of how patients feel about their therapists’ bodies: 

1. They automatically look at the therapist’s body. 

2. They believe thinner therapists can help them more than overweight therapists. Still, “healthy looking” was as perceived better able to help than thin or overweight therapists. 

3. The patients were less likely to take advice or help from therapists they viewed as overweight or too thin. 

Delusional thinking with eating disorders:

In patients suffering from anorexia nervosa, disturbances of thought content may vary in severity depending on how much insight is preserved, ranging from obsessions to full-blown delusions. They often can believe food is “poisoned, contaminated, still alive or ready to attack; food may be animalized or described as a poison.” 

They can even believe that their body is “under the influence of external forces, dissolving or being under attack; some patients fear that the contents of their body might spill outside or have a sense of all the body fat going down to their stomach. Delusions of sinfulness may emerge...There are patients who complain about hearing the ‘voice of anorexia’ or a voice that forbids them to eat.”  

Sarah Bradley recounts some of her experiences:

  • “I have major anxiety when being in close proximity to people with obesity while eating: I honestly worry in some nearly magical way, their eating will make me eat and potentially overeat. Often if I am exposed to someone with obesity eating, I cannot eat the rest of the day.”

  • “Not letting myself sit, sleep, or rest for too long out of fear that the lack of energy expenditure will cause automatic weight gain.”

  • “Being incredibly paranoid about the risk of weight gain from psychiatric medications, even if little to no risk exists for a certain drug. Before adhering to my current medications of zoloft, lamictal, and trazodone, I had to have several long conversations with my psychiatrist to get reassurance even though I knew those particular drugs held no serious risk for weight gain. Historically, my paranoia had been so bad, I would lie about taking medication or stop seeing my doctor altogether.”

  • “Thinking about food all day and thinking about my body all day. Literally, having these constant ruminations about what I could or could not eat and how large I must look to the point that I was falling behind in school and couldn’t hold a social conversation for too long.”

Severe clinical cases of eating disorders

Often, in severe/chronic cases of eating disorders, clinicians do not even use psychotherapy until there has been a substantial improvement in nutritional standing and the patient has reached a healthier weight. One’s cognitive functioning is also very low after having entered starvation, and they are often very focused on food beyond a point of interest that comes with an eating disorder, but because the body is crying out for energy.

In these severe cases, sometimes the patient is not willing to make progress and is defiant towards weight gain or diet change, so they may need to be hospitalized. 

Even though this isn’t specific to psychotherapy, it is vital to recovery to reach a healthier diet and body weight (even if someone is overweight who is malnourished and has been starving themselves for rapid weight loss). And so, another big part of how to stop obsessing about food is the ability to achieve a better diet and healthier weight. For some, this means gaining weight. For some, this means maintaining weight. For some, this may mean ceasing binging and/or purging that can result in weight maintenance/weight loss.

What works to help patients with eating disorders?

In Sarah’s experience, here’s how she stopped thinking about food, and therefore is “90% better” after her long-standing eating disorder.:

  • Gaining weight, helped her stop thinking about food. 

  • Finding other passions in life helped her focus future goals and aspirations.

  • Finding a good therapist that understood her and was open to learn about her perspective rather than putting on their own perspective (empathy).

  • Taking and sticking with a medication to treat comorbid depression.  

  • Creating a stronger network of friends.

As therapists, we can help our patients accomplish all of these things through empathic listening and encouraging to move towards healthy connections. 








The Process of Grief

On today’s episode of the podcast, I am interviewing Maris Loeffler, LMFT. We cover different types of grief (acute, complicated, traumatic, etc.), attachment styles in relation to grief, and  some helpful things to consider in caring for a grieving patient as a mental health provider.   

An Overview of Grief 

Joseph Wong (MS3), Tyler Rigdon (MS2), David Puder M.D.

This article complements the above podcast, with some research findings we did not talk about in detail, and is written for mental health professionals to understand some of the research behind grief work.

Grief is the multifaceted response—emotional, behavioral, social—to a loss or major life adjustment (like a divorce, loss of a job, etc.). Bereavement is the process of grieving specific to the loss of affection or bond to a person or animal (Parkes & Prigerson, 2013; Shear, Ghesquiere & Glickman, 2013; Shear, 2015). 

Some of the signs and symptoms of grief are: 

  • somatic symptoms (e.g. choking or tightness in the throat, abdominal pain or feeling of emptiness, chest pain) 

  • physiological changes (e.g. increased heart rate and blood pressure, increased cortisol levels)

  • sleep disruption and changes in mood (e.g. dysphoria, anxiety, depression, anger) 

(Buckley et al., 2012; Lindemann, 1944; O’Connor, Wellisch, Stanton, Olmstead & Irwin, 2012; Shear & Skritskaya, 2012; Shear, 2015; Zisook & Kendler, 2007

Medical and psychiatric complications can also arise due to grief and include:

Acute grief begins after a person has learned of the passing of a loved one (Shear, 2015). During acute grief, a person may experience immense sadness, yearning for the deceased, and persistent thoughts of the decreased (Maciejewski, Zhang, Block & Prigerson, 2007; Shear, 2015). Auditory and visual hallucinations are benign hallucinations commonly found in acute grief and involve the person seeing, talking to or hearing the voice of the deceased (Grimby, 1993). 

The process of grief has long been seen through the lens of Kubler-Ross’ 5 stages of grief (denial, anger, bargaining, depression and acceptance). Now, however, it is now more commonly understood that the process of grief is not as linear or predictable as originally posited by Kubler-Ross, and that there may not even be stages of grief that a person has to pass through in their grieving process (Maciejewski, Zhang, Block & Prigerson, 2007; Stroebe, Schut & Boerner, 2017). 

Most bereaved individuals are able to progress from acute grief to integrated grief, in which the individual has adapted to their grief and is able to once again enjoy daily life and activities (Shear & Mulhare, 2008; Shear, Ghesquiere & Glickman, 2013). About 6 months after the loss of the decreased, negative grief indicators (e.g. disbelief, yearning, anger) are in decline (Maciejewski, Zhang, Block & Prigerson, 2007). Thus, this transition from acute grief to integrated grief means that the individual only experiences grief as a temporary period rather than a prolonged chronic state. However, approximately 10% to 20% of people who lose a romantic partner do not transition from acute grief to integrated grief and instead transition to complicated grief (prolonged grief disorder) where the individual experiences grief for a longer period of time than expected to the point where it causes impairment in daily functioning (Bonanno & Kaltman, 2001; Shear, 2015). 

Complicated grief is more common in parents who have lost children, when the loss of the decreased is sudden or violent (e.g. suicide, homicide, accident), and is less common after an expected loss (e.g. chronic illness) (Meert et al., 2011; Mitchell, Kim, Prigerson & Mortimer, 2005; Nakajima, Masaya, Akemi, & Takako, 2012; van Denderen, de Keijser, Kleen & Boelen, 2015; Young et al., 2012). Complicated grief has been found to be most prevalent in women above 60 years old (Kersting, Brähler, Glaesmer, & Wagner, 2011). 

Complications of complicated grief include:

  •  sleep disturbances

  • suicidal ideation

  • substance use disorders

  • decreased immune function

  • increased risk for cardiovascular disease and cancer (Buckley et al., 2012; Shear, 2015). 

Like acute grief, the symptoms of complicated grief involve intense yearning for the decreased and persistent sadness. In complicated grief, these symptoms are accompanied by the fact that the individual is unable to accept the reality of the death of the deceased, and has intrusive thoughts or images of the deceased, and excessive ruminations and recurring negative emotions (e.g. anger, guilt, bitterness) surrounding the death Shear & Mulhare, 2008; Shear, 2015; Simon, 2012). Individuals with complicated grief commonly avoid situations, events or places that remind them of their loss and are fixated by viewing, touching or smelling momentos left behind by the decreased (Shear, 2015). 

Attachment Styles and Grief 

Attachment theory was first established by Mary Ainsworth in the 1960s and 70s and applied to children with 4 attachment styles in children being classified: 

In the 1980s, attachment theory was extended to adults and 4 attachment styles were also classified: 

The anxious attachment style reflects worry concerning the availability of the attachment figure, while the avoidant attachment style reflects a tendency to keep at arm’s length from attachment figures (Shear & Shair, 2005). 

Secure attachment style is characterized by low anxiety and low avoidance. Anxious-preoccupied is characterized by high anxiety and low avoidance, dismissive-avoidant is characterized by low anxiety and high avoidance and fearful-avoidant is characterized by high anxiety and high avoidance (Shear & Shair, 2005). 

It has been well-documented that bereaved individuals with insecure attachment styles are at risk for increased grief symptoms. Insecure attachment styles have been found to put spouses of terminally ill patients at greater risk for traumatic grief symptoms (Van Doorn, Kasl, Beery, Jacobs & Prigerson, 1998). Individuals with an anxious ambivalent attachment style that lost a close friend or family member in the previous year experienced greater levels of grief and depression, while individuals with an avoidant attachment style experienced greater somatic symptoms in comparison to individuals with secure attachment styles (Fraley and Bonnano, 2004; Wayment & Vierthaler, 2002).

Below are the prototypic behaviors and characteristics of the adult attachment styles with respect to grief. 

Anxious Attachment

Typically occupied with fear of abandonment, exhibits hypervigilance and seeking behaviors. Afraid that their partner might leave them. 

Patients with anxious attachment styles latch onto items or articles of clothing; however, people can normally hold onto momentos as part of the grieving process, so further investigation should be done to differentiate the two. 

Avoidant Attachment

Fearful of intimacy and emotional engagement. Prefers to process things alone. They withdraw with signs of emotional neediness from partner. 

How does this attachment style impact the grieving process and hinder healing? 

  • Have trouble with acknowledging the depth/importance of the relationship. 

  • Don’t like to be vulnerable in the relationship.  

  • Avoid fully looking within themselves and processing their grief response.  

  • By pushing down their emotions, it makes it hard to get through the grief process ,as when you grieve, you need to feel emotions, and it makes it difficult to process emotions if you’re not acknowledging them. 

    • Maris’ approach is to work with the body if they can’t put words to what they’re feeling as part of the grief process. People with avoidant attachment styles have more somatic symptoms (headaches, stomachaches), so putting that into words for them can help them better understand their grief process. 

Disorganized Attachment

Kids with disorganized attachment have no organized way of regaining connection. They later will have higher rates of dissociation. Patients with high amounts of dissociation will need to feel grounded and present to process through things, and learning when someone is dissociating will be helpful to help them progress in their emotional development. I (Dr. Puder) often look for microexpressions in the midst of someone dissociating to help me know what emotions are felt but not being allowed to experience.

Other Considerations 

The following are some of Maris’ considerations that have helped her in approaching a patient with grief. 

  • One of Maris’ grounding principles is centered around, “When I bring a person into the room, I need to understand what they need.” This mindset helps her to just let the client speak their story for the first few sessions, after which she will begin formulating her own ideas about the client’s grieving process. In a non-confrontational manner, she will ask questions like the following to dig deeper. 

    • “I’m noticing that it’s difficult for you to talk about the funeral.” 

    • “It feels like you get angry when you notice how your brother is handling the situation.”

  • Realize a patient’s grief hits them after the funeral service. After the deceased has passed and before the funeral, usually family members and friends gather to give support to the grieving. However, after the funeral, those people are no longer there and the patient is left alone. Consider this timeline when helping the patient through their grieving process. 

  • Sometimes it’s difficult to determine the fine line between supporting a friend with grief and exhausting them with your presence. So what are the things to consider in comforting a friend with grief? 

    • Firstly, it depends on your relationship with the person

    • Second, ask them what would be most helpful for them at the moment

      • Right after a loss, everyone comes around, but sometimes people want to be left alone and it can be exhausting for the person in question to feel overburdened with emotional comfort. 

      • Sometimes it’s valuable to check in and reach out. That alone can make an impact, even if you can’t find the right words to comfort the person.

  • The importance of personally going through therapy cannot be understated in this line of work. Even therapists need therapists, and being a patient can help you become a better therapist by allowing you that first-person perspective. 

  • Some patients may be doing really well with therapy for a period of time, but encounter roadblocks associated with life events without the presence of the decreased (first Christmas or the first anniversary after the loss of their loved one). The patient may need to revisit their grief once again, and that’s perfectly fine—grieving is not linear, nor is it the same for everyone. 

  • Every patient has their own way of talking about and processing their grief. Certain patients may even repeat the process of the passing of the decreased over and over. While it may be repetitive to hear the same thing every session, allowing the patient to talk about their experience helps the patient with their process of grieving.

  • Some patients might feel a lot of guilt towards themselves while grieving. Normalize the feeling of guilt, express the difficulty in feeling things, and help them look at the guilt with less judgement. 

  • Some patients may even feel anger towards the deceased, which they might have difficulty acknowledging or getting it out. It is common for people to remember the decreased in terms of their good aspects or attributes, but that may not always be the case for the patient. Allow them the space and time to express their negative emotions, which may not always be apparent on the surface in their grieving process. 


Maybe at some point, you have thought to yourself that you don’t have the ability to process grief with your patients or that it simply isn’t your strong suit. I hope that some of the points brought up in this podcast will be helpful in your own practice and journey as a mental health provider. 

Connect with Maris Loeffler, LMFT on Instagram, Linked In, Psychology Today



Clozapine for Treatment Resistant Schizophrenia

On today’s episode of the podcast, Dr. Cummings and I talk about clozapine, a medication that treats schizophrenia.

Mikyla Cho B.A., Michael Cummings, M.D., David Puder, M.D.

What is clozapine?

Not only is clozapine the gold standard medication for treatment-resistant schizophrenia, it is also one of the most unique drugs used in psychiatry.

It was synthesized 1958, only eight years after chlorpromazine, the first antipsychotic drug, was created. At that time, researchers tested for antipsychotic properties by taking various compounds and testing to see if lab mice developed dystonia and catalepsy. When researchers tested clozapine, they found that it did not cause dystonia, but instead made the mice sleepy. Because of this, clozapine was almost missed entirely as an antipsychotic medication. Eventually, however, clozapine was found to be more successful than other antipsychotic drugs.

By the 1970s, Austria, Germany, and Finland had produced positive data on clozapine proving its efficacy. However, clozapine was also found to have caused severe neutropenia in sixteen patients in Finland, and even caused the death of eight of those patients. For this reason, clozapine did not enter the United States until it was approved by the FDA in 1989.

Defining “Treatment-Resistant” Schizophrenia

Clozapine was approved largely due to the work of John Kane. In his work, Kane helped define “treatment-resistant” schizophrenia, and ultimately the context in which clozapine has proven benefits. The term “treatment-resistant” can be defined as schizophrenia that has failed to respond to an adequate dosage of two antipsychotic medications given for an adequate duration:

  • The dosage should be a minimum of 600-1000 mg chlorpromazine equivalents.

  • Duration should be a minimum of six weeks.

  • Additionally, patients must have failed a prospective trial of haloperidol 15 mg given daily.

With this definition, Kane and his team found that a patient’s odds of responding to clozapine was 50-60%, whereas the probability of responding to other antipsychotic medications was 0-5% (with an average response of 2%). Today, these rates are essentially unchanged.

In 2017 Howes et al. found similar response rates to clozapine. The team largely followed Kane’s original criteria for treatment-resistant schizophrenia but did not include the failed prospective trial of haloperidol. Additionally, the team measured plasma levels of clozapine to assess patients’ adherence. Ultimately, they found that the odds of responding to clozapine was 40-60% while the odds of responding to other antipsychotics was 7% or less.

In contrast, there have been meta-analyses, including Cochrane, suggesting that clozapine is not more effective than other antipsychotics. However, these studies have failed to strictly define or include “treatment-resistant” schizophrenia criteria. It is likely that schizophrenic patients who were not truly treatment-resistant were included in those studies. In this context, clozapine is not more effective than other antipsychotic medications.

Unique Effects

In addition to being the gold standard for treatment-resistant schizophrenia, clozapine has other unique effects. It has been found to reduce both suicide and violence in patients, independent of the drug’s antipsychotic effects. Criminal behavior is also decreased. Clozapine can also be used to treat psychogenic polydipsia and refractory mixed bipolar states.

Mechanism of Action

Part of the reason that makes clozapine so unique is its mechanism of action. Typically, second generation antipsychotics antagonize dopamine but more selectively than their first generation counterparts. Additionally, atypical antipsychotics antagonize the 5-HT2a receptors, which actually assist with dopamine transduction in the frontal lobe. Although clozapine does have atypical antipsychotic properties, it also works by modulating glutamate signal transduction, particularly in the frontal and temporal lobes. Even at high plasma levels, the concentration of clozapine at the D2 and D3 receptor is only 30-40%. It is the modulation of glutamate that helps stimulate and “awaken” the hypoactive brain of a schizophrenic patient.

Improving glutamate decreases the positive symptoms, improves the negative symptoms, and even helps with cognitive symptoms. Clozapine’s unique mechanism of action may be why Krakowski et al (2006) found that although clozapine, olanzapine, and haloperidol had approximately the same reduction in psychosis for violent schizophrenic patients, clozapine was superior to olanzapine and haloperidol in decreasing violence in the same patients because it significantly mediated the executive function of the frontal lobe.

Other than glutamate, clozapine does affect other key molecules and receptors. The major daily side effects are most likely due to the blockade of the His-1 receptors, and the subsequent sedation may become a dose-limiting side effect for the patient, especially at higher plasma levels of clozapine. Alpha-adrenergic antagonism also contributes to the drug’s side effect profile, such as hypotension. Additionally, although clozapine’s robust and positive effect on glutamate likely overrides much of the drug’s anticholinergic effects, there is still the chance for anticholinergic burden, especially if the patient is taking other anticholinergic medications.

Target Dose and Medication Adherence

It is vital to maintain a therapeutic alliance with a patient on clozapine, as noncompliance is a major factor for treatment failure in schizophrenic patients. For example, the adherence rate for antipsychotic medications in general is less than 40%. This is partially alleviated with long-term injectable agents, but clozapine does not have this option. The only forms of clozapine are tablets, wafers, and liquid agents. Therefore, it is beneficial to schedule regular meetings with patients on clozapine.

One method to assess medication adherence is by checking plasma concentrations and blood levels of clozapine. If patients are adherent, their plasma concentration of clozapine should be fairly consistent. Obtaining blood levels also assures the provider that the current medication dose is optimal, as patients vary in metabolism and absorption rates and other factors, such as smoking and different medications, can also affect hepatic metabolism.

To treat psychosis, the target range of clozapine should be 350-600 ng/mL. If symptoms are not adequately controlled at this level, but patients are tolerating the medication, clozapine can be gradually titrated to approximately 600-1000 ng/mL. After 1000 ng/mL there is a diminishing return of benefits and an increased likelihood of side effects. Rarely, patients will need to go above the 1000 ng/mL level. If the goal is to not treat psychosis but another issue like criminality, then patients will generally respond at much lower doses. For example, in 2014 Brown et al. found that there was a dramatic reduction in violence in seven psychopathic patients with an average clozapine concentration of 171 ng/mL.

Benefits of Clozapine

On-going, uncontrolled psychosis only leads to mental decline. Early in the disease process, patients lose 2% of their brain mass every year for the first five years, and although this decline slows after that point, it never reaches zero. Additionally, although a healthy lifestyle with adequate nutrition and exercise prevents cognitive decline, it is particularly difficult to motivate schizophrenic patients because of the nature of the disease. On average, schizophrenic patients live 20 years less than the general population.

Clozapine helps address both issues. It has been shown to slow the progress of schizophrenia than any other antipsychotic, and it has been shown to prolong a patient’s lifespan. In 2017 Yoshimura et al. found that the efficacy of clozapine begins to decline about 2.8 years after a patient has been shown to be treatment-resistant. This finding along with clozapine’s other benefits create the argument that clozapine should be prescribed sooner rather than later to help patients suffering from treatment-resistant schizophrenia.

You can download an extensive, FREE management summary from the episode here:




The Unspeakable Mind: Stories of Trauma and Healing from the Frontline of PTSD Science

On today’s episode of the podcast, I am interviewing Dr. Shaili Jain. We cover Dr. Jain’s personal interest in PTSD work, moral injury, causes of PTSD, presentation of PTSD and treatment modalities for PTSD.

Joseph Wong (MS3), David Puder M.D.

An overview of PTSD

PTSD, or Post Traumatic Stress Disorder, occurs when someone experiences, or subjectively experiences, a near death or psychologically overwhelming event, and then goes on to develop specific symptoms because of it. Different types of trauma/stressors that can lead to PTSD include sexual violence, combat experience, medical conditions (e.g. myocardial infarction), and natural disasters (e.g. hurricane) (Chivers-Wilson, 2006; Edmondson et. al, 2012; Grieger et al., 2006; Hussain, Weisaeth & Heir, 2011).

It is characterized by:

  • Direct exposure or witnessing of trauma/stressor

  • Presence of intrusive symptoms post-traumatic experience

  • Avoidance of traumatic stimuli

  • Negative changes in mood and cognition

  • Hyper-reactivity

  • Hyper-arousal (APA, 2013).

Here are a few stats about PTSD:

  • In 2017, over 47,000 Americans died by suicide (CDC, 2019). This number has been climbing about 1,000 new cases per year from 31,000 American deaths by suicide in 2000 (CDC, 2019). One contributor to this statistic are people with Post-traumatic stress disorder (PTSD), who are at increased risk of suicide (Wilcox, Storr & Breslau, 2009).


Symptoms and Diagnosis of PTSD

Certain symptoms of PTSD, like negative changes in mood and cognition, can be associated with other conditions, like anxiety, depression, and borderline personality disorder. Using screening tools like PCL-5 can help delineate PTSD from other conditions, although they can come with false positives (more people who are labeled as having PTSD than actually have it). Experienced clinicians can correctly diagnose through detailed history taking. Diagnosing PTSD begins with listening for a history of major trauma, which can take many forms. The patient will usually describe that they felt their sense of normalcy was shattered, and that they felt totally helpless in the face of that traumatic event.

During the first 4 weeks after the trauma, the impact of the trauma should be noted, and the duration of the symptoms should also be observed. The diagnosis of PTSD involves a disturbance of > 1 month with characteristic symptoms such as intrusive nightmares, flashbacks, memories, hypervigilance (APA, 2013). Subtle signs to look for are the patient’s mood states such as shame, guilt, anger, fear, horror, which are particular for PTSD (Hendin & Haas, 1991).

These patients also show a restricted range of emotion (they never show pure happiness, anger or sorrow). Avoidance is another key characteristic of patients with PTSD as they avoid places, people and memories associated with the traumatic event. This avoidance behavior is particularly tricky to deal with as some patients never make it to see a mental health professional.


Complex PTSD

Complex PTSD is a subtype of PTSD with complex symptomatology in response to chronic trauma (Herman, 1992). Usually, the patient has an extensive history of childhood abuse where the patient can’t remember a time when they weren’t being abused. Another example of chronic trauma includes victims of long-term intimate partner violence. In comparison with textbook patients with PTSD, who have a distinct life before and after their traumatic experience, patients with complex PTSD are only familiar with the traumatic experience.

Patients with complex PTSD have issues with emotional regulation, and can range from rageful to regretful in a single session, much like patients with borderline personality disorder. Patients with complex PTSD often get caught up in cycles of re-enactment where they act out in their personal relationships, and even in their therapeutic relationships, in ways that mimic the trauma that they’ve felt. In Dr. Jain’s experience, although patients with complex PTSD exhibit emotional lability, just like borderline personality disorder, she would think a diagnosis would lean more towards borderline personality disorder if the classic symptoms (such as identity issues, self-injury, chronic suicidality and attachment issues) were present (APA 2013).


Dissociative PTSD

Dissociative PTSD is a subtype of PTSD that occurs in 15-30% of PTSD patients, in which the patient not only meets the criteria for PTSD, but also exhibit persistent dissociative symptoms (e.g. depersonalization, derealization) (APA, 2013; Armour, Karstoft & Richardson, 2014).

Derealization is the feeling of detachment from one’s environment, while depersonalization is the feeling of detachment from one’s body, thoughts, perceptions and actions (APA, 2013). Patients often describe the feelings of depersonalization and derealization as “they don’t feel real,” or that “the world around them doesn’t feel real.”

Because patients with the dissociative subtype of PTSD experience these symptoms persistently, their day is often derailed as they don’t live in the present, but in their dissociative world. Patients who have had severe childhood abuse tend to have the dissociative subtype, which is associated with a poorer prognosis. Patients can dissociate in many environments, including the therapy environment, thus grounding techniques such as breathing techniques and anxiety-reducing exercises may be useful to bring patients from their dissociative state.


PTSD Treatments

Therapy and PTSD

The gold-standard treatment for PTSD is psychotherapy, with an emphasis on a strong therapeutic alliance. In her book, Jain Shaili talks about the importance of the story being given a voice. Many times when someone experiences trauma, it has violated the heart of what they find to be sacred and true, and the effects can be that they have experienced things they find completely unspeakable.

When memories remain unspeakable, even unthinkable, they become sticking points that prevent the brain, and person, from being able to move on. Because of this, many people with PTSD are difficult to reach, emotionally. It’s built into the nature of the disorder that they can be avoidant, don’t want to address the trauma, and are often mistrustful.

As a result of this psychosocial stress, patients with PTSD experience many negative emotions such as guilt, shame and remorse as well as increased suicidality (Hendin & Haas, 1991). PTSD thrives when patients hold it in, rather than talking about it, so an important part of treatment is to establish a therapeutic alliance so that the patient feels comfortable sharing their traumatic experience. Another important factor that contributes to healing is connecting the patient’s spiritual beliefs to their moral injury (Currier, Holland & Drescher, 2015).


The Search for Meaning

In the face of trauma, there are some that show resilience by making meaning out of the trauma and catapulting their lives into a direction where trauma is integrated into their lives rather than directing it.

Although not everyone is fortunate enough to arrive at that place by themselves, trauma-focused psychotherapy can add new learning, adjust maladaptive beliefs and help patients re-evaluate their trauma and its impact on their lives so that they can move forward meaningfully.

Medications for PTSD:

  • SSRIs/SNRIs

    • The most well-studied medication class used to treat PTSD and are 1st line due to favourable adverse effect profiles (Asnis, Kohn, Henderson & Brown, 2004).

    • Sertraline and paroxetine are also both FDA-approved for the treatment of PTSD (Asnis, Kohn, Henderson & Brown, 2004). However, in practice, SSRIs and SNRIs are pretty much equivalent, so tailor fit the medication according to the patients needs. For example, many patients with PTSD have chronic pain, so Venlafaxine (Effexor®) would be a good choice.  

    • Fluoxetine, paroxetine, and sertraline have been found to reduce hypervigilance, emotional numbing, and intrusion levels in clinical trials of over 3,000 participants with PTSD with over 60% of participants seeing a reduction in their symptoms (Kapfhammer, 2014). Many patients with PTSD are mistrustful of medication, so developing a good relationship with the patient through the therapeutic alliance can help convince patients that medications and medication adherence are in their best interest. With a strong therapeutic alliance and good medication management, that 60% can be even higher.

  • Mirtazapine

    • Can be used to treat insomnia at lower doses (7.5 mg - 15 mg). Has antidepressant effects at higher doses.

    • We try to avoid polypharmacy. If treating PTSD with medications, only starts with 1 medication at a low dose and see how that works. Patients that suffer from insomnia can improve dramatically after a few weeks of good sleep from such a medication as mirtazapine.

    • For insomnia, Dr. Jain prefers to use non-pharmacological therapy like Cognitive Behavioral Therapy for Insomnia (CBTI) and only uses medication for the short term to get them to the point where therapy like CBTI can treat the root cause of their insomnia.

  • Mood stabilizers

    • Once again, the general approach is to put the patient on SSRIs/SNRIs at a lower dose and move up the dose as needed.

    • In patients that have issues with hostility, aggression, harm to self and don’t improve on SSRIs/SNRIs, we would consider mood stabilizers as a possible treatment.

  • Second generation antipsychotics

    • Used to be popular in the past to give a low dose for patients with PTSD that exhibited hostility and aggression. Unfortunately, risperidone was shown to not be an effective treatment for PTSD and came with many worrying side effects (e.g. metabolic syndrome, fatigue, sleepiness) (Krystal et al., 2011) .

  • Benzodiazepines

    • In the past, patients with PTSD used to be put on benzodiazepines, but it is now known that benzodiazepines are just a band aid rather than a true treatment for PTSD with especially concerning side-effects in the elderly population (i.e. increased risk fall and impaired cognition) (Cumming & Le Conteur, 2003).

    • In 2012, a study involving over 10,000 patients who were prescribed benzodiazepines were found to have 50% increased mortality with long-term use (Kripke, Langer & Kline, 2012).

    • Dr. Jain would only prescribe very-short term prescriptions (5 day supply) for emergencies like horrific flashbacks and dissociative events.

    • PTSD and addiction go hand in hand due to the addictive nature of benzodiazepines, so education is important in teaching patients that there are serious side-effects associated with benzodiazepines (e.g. impairment in cognition and increased fall risk in the elderly) and that other treatment modalities can be helpful in managing their PTSD.

  • Marijuana

    • Although there are many strong personal testimonies and anecdotes concerning the efficacy of marijuana in alleviating the various symptoms of PTSD, there were no high quality randomized clinical trials as of 2016 that have looked at the efficacy of marijuana for PTSD (Wilkinson, Radhakrishnan & D'Souza, 2016).

    • There are clinical trials underway (one in a VA in Arizona) testing CBD for PTSD.

    • 3 things worry about marijuana usage in patients with PTSD

  1. Adverse interactions between psych meds and marijuana are currently unknown and can be dangerous as patients are often taking both their medications and marijuana.

  2. Marijuana impairs driving, attention, memory, IQ, and increases rate of psychosis.  View my prior blog, Youtube and podcast on Marijuana: here

  • Ketamine and MDMA

    • There are currently ongoing studies in the VA, but it’s still too early to tell without seeing the data.


I would highly recommend checking out Dr. Jain’s book:

The Unspeakable Mind: Stories of Trauma and Healing from the Frontline of PTSD Science

Here are several of my prior episodes on PTSD:

How to Help Patients With Sexual Abuse

How to Treat Emotional Trauma

Emotional Shutdown—Understanding Polyvagal Theory



Schizophrenia Differential Diagnosis & DSM5

On today’s episode of the podcast, I am interviewing with Dr. Ariana Cunningham. We cover the DSM5 criteria for schizophrenia and the differential diagnoses for schizophrenia.

Joseph Wong (MS3), Ariana Cunningham, M.D., David Puder M.D.

Diagnosing schizophrenia  

Doctors and therapists need to be able to rule everything else out before they can land on schizophrenia as an official diagnosis. The specific symptoms are known as “first-rank symptoms,” which we will cover later in the article, that will help with diagnosing patients (Schneider, 1959). Eighty-five percent of people with schizophrenia endorse these symptoms, but be wary of jumping to conclusions, because they are not specific to schizophrenia and, in some studies, are also endorsed by bipolar manic patients (Andreasen, 1991).

DSM5 (Diagnostic and Statistical Manual of Mental Disorders 5th ed.)

Schizophrenia is a clinical diagnosis made through observation of the patient and the patient’s history.

  • There must be 2 or more of the characteristic symptoms below (Criterion A) with at least one symptom being items 1, 2 or 3. These symptoms must be present for a significant portion of time during a 1 month period (or less, if successfully treated).

  • The patient must have continuous, persistent signs of disturbance for at least 6 months, which includes the 1 month period of symptoms (or less, if successfully treated) and may include prodromal or residual periods.

    • For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care, are markedly below the level achieved prior to the onset.

    • If the onset is in childhood or adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational achievement.

Criterion A:

A. Positive symptoms (presence of abnormal behavior)

1. Delusions

2. Hallucinations

3. Disorganized speech (eg, frequent derailment or incoherence)

4. Grossly disorganized or catatonic behavior

B. Negative symptoms (absence or disruption of normal behavior)

5. Negative symptoms include affective flattening, alogia, avolition, anhedonia, asociality.

Development, Course and Risk Factors

Psychotic symptoms of schizophrenia typically occur in young adulthood (late teens to mid-30s) (American Psychiatric Association, 2013). About 80% of schizophrenia presents with acute onset, intermittent symptoms and few/no symptoms while about 20% present with insidious onset, continuous symptoms and poorer outcomes (Bleuler, 1978). In terms of age of onset, it has been well documented that males present earlier than females (early to mid 20s for males vs late 20s for females) (Patel, Cherian, Gohil & Atkinson, 2014).

There are two key factors that have been associated with poorer prognosis. Earlier age of onset, which is highly associated with schizophrenia in males, has been well-documented to be associated with a poorer prognosis (Kao & Liu, 2010). The deficit form of schizophrenia (persistent negative symptoms of schizophrenia) have also been shown to be associated with a poorer prognosis (Kirkpatrick, 2008).

The highest risk factors for schizophrenia have been tied to genetic factors such as having an affected immediate family member or being the offspring of an immigrant from certain countries (Torrey, 2012). Molecular genetics have also been used to show that genetic inheritance is highly associated with schizophrenia, although it is not currently known how much genetic variation increases the risk for schizophrenia (Ripke, 2014). Non-genetic risk factors for schizophrenia include infectious causes such as Toxoplasmosis, living in an urban environment, birth seasonality and maternal exposure to influenza (Torrey, 2012).

Although functional recovery is rarer early on in the course of schizophrenia, the good news is that timely and intensive treatment can impact functional recovery early in the illness (Robinson, 2004). Patients who had more intensive intervention showed greater improvement in quality of life, higher functioning in school/work, and less psychopathology (Kane, 2016).

Differential diagnosis

When I see a patient that presents with these symptoms, the first thing I consider is substance use. I check if they had prior urine drug screens in their medical records, physical signs of substance use (e.g. poor dentition, track marks) and history of motor vehicle accidents. Even if history and physical condition do not suggest substance use, it’s common practice to order a urine drug screen on anyone coming into an inpatient psychiatry unit and look at prior drug screens in the medical record.

Other considerations include psychosis due to another medical condition (e.g. Wilson’s disease), personality disorder (long history of passive suicidal intent dating back to adolescence for borderline personality disorder, odd beliefs associated with Cluster A personality disorders, etc.), mania (e.g. rapid talking, grandiosity, decreased need for sleep) or severe depression (long progressive history with eventual psychosis).

For patients manifesting with some, but not all of the symptoms of schizophrenia, here is a list of differential diagnoses. With schizophrenia being a diagnosis of exclusion, it is important to consider all possible diagnoses.

A. Based on timeline of symptoms (American Psychiatric Association, 2013):

  • Brief Psychotic Disorder: Presence of > 1 positive symptom lasting 1 day to 1 month .  

    • Can be precipitated by stressors or have peripartum onset.

  • Schizophreniform: Same diagnostic criteria as schizophrenia, except lasting for at least 1 month, but less than 6 months. May be the start of schizophrenia, but not all patients with schizophreniform go on to be diagnosed with schizophrenia.

    • Social and occupational decline do not need to be present like they do in schizophrenia.


B. Presence of mood disorder features (APA, 2013)

  • Schizoaffective: Meets criteria for schizophrenia as well as major mood disorder (manic episodes or significant depressive episodes that have occurred at different times in the person’s life).

    • Schizoaffective disorder is differentiated by major mood disorder with psychotic features by the presence of > 2 weeks of psychotic symptoms without major mood episode.

  • Bipolar Mood Disorder: Bipolar I: Meets criteria for current or past manic episode that could be preceded or followed by hypomanic or major depressive episodes. Bipolar II: Meets criteria for current or past hypomanic episode and major depressive episode.  

    • Typically, a manic patient will take a few days to fall asleep when they are in an episode even when on significant medications.

  • Major Depressive Disorder Severe with Psychotic Symptoms: Psychotic symptoms (e.g. delusions or hallucinations) exclusively occur during a major depressive or manic episode, which is differentiated by schizoaffective disorder, which is characterized by > 2 weeks of psychotic symptoms with major mood episode.

    • There is a long period of depression leading up to the psychotic symptoms. The patient usually by the time they have psychosis has been depressed for months if not years. The psychosis and depression will not change in 2-3 days like they can in someone hospitalized with borderline personality disorder.  


C. Personality Disorders (APA 2013):

  • Borderline Personality Disorder (Cluster B): Long-standing pattern of unstable interpersonal relationships, impulsive behavior (e.g. sexual or self-harming), and mood instability (e.g. feelings of emptiness, intense dysphoria) .

    • A borderline personality disorder patient will have negative inner “voices” that will lead them to fear they are hearing things, but they can put on a social veneer and appear put together. A schizophrenic patient cannot put on a social veneer when in a disorganized and psychotic state.

    • These patients also have a history of passive suicidality dating back to adolescence.

  • Schizotypal personality (Cluster A): Long-standing pattern of odd or eccentric beliefs and/or perceptual disturbances that do not rise to the level of delusions or hallucinations.

    • Shares many similar symptoms as schizophrenia, but schizotypal personality disorder can be distinguished from schizophrenia as the personality disorder is present before the onset of psychotic symptoms and persists even when the psychotic symptoms vs. a period of persistent psychotic symptoms in schizophrenia.  

  • Schizoid personality (Cluster A): Long-standing pattern of little interest in social relationships or intimacy.

    • Shares similar symptoms as schizophrenia such as flattened affect, but does not present with psychosis.

    • Schizoid personality disorder can be distinguished from schizophrenia as the personality disorder is present before the onset of psychotic symptoms and persists even when the psychotic symptoms vs. a period of persistent psychotic symptoms in schizophrenia.  

D. Other considerations:

  • Substance-induced psychosis: Symptoms occur during intoxication or acute withdrawal and do not persist after the individual is sober.

    • The people who are coming off of methamphetamines typically want to sleep the first few days and are irritable coming off of meth, while people with schizophrenia will talk with you for a bit, and be awake during the day (although sometimes lying in bed doing nothing).  

    • THC has been associated with an increased risk of developing psychosis. A meta-analysis of 18 studies involving 66,816 individuals gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to nonusers (Marconi, 2016).

  • Psychosis due to a general medical condition or medication: Symptoms can occur with other medical conditions such as CVA or TBI, Wilson’s disease, porphyria, or syphilis infection (watch for it in HIV patients) as well as medications (e.g. steroids) and certain dietary supplements.

  • Delusional disorder: One or more delusions (false belief system) that are fixed and persistent, lasting for > 1 month.

    • Can be differentiated from schizophrenia by the lack of other symptoms besides delusions. An exception to this is that patients may have olfactory or tactile hallucinations consistent with the delusion, but they won’t have auditory hallucinations that is most commonly associated with schizophrenia (Chaudhury, 2010; Opjordsmoen, 2014).

    • Functioning is also not impaired compared to schizophrenia.

  • Pervasive developmental disorders: May present with symptoms resembling psychosis or negative symptoms; however, an important factor to consider before diagnosing schizophrenia is the patient’s developmental pattern.

    • For example, for a 3 - 5 year old child, imaginary friends are common for that developmental stage and shouldn’t be instantly labelled as a visual hallucination- so when you listen to their vocabulary consider what age they are even if they look physically much older (Taylor & Mottweiler, 2008).

    • “An additional diagnosis of schizophrenia should only be made in a patient with autism spectrum disorder or communication disorders if psychotic symptoms are present for at least a month” (APA 2013).

For more on schizophrenia check out these other episodes:

Schizophrenia with Dr. Cummings: Controversies, Brain Science, Crime, History, Exercise, Successful Treatment

The History and Use of Antipsychotics with Dr. Cummings  



Do I have Schizophrenia?

On today’s episode of the podcast, Ariana Cunningham and I continue our discussion from the first episode about schizophrenia, focusing on the clinical manifestations of the disease.

Ariana Cunningham, M.D., David Puder, M.D., 

Clinical manifestations 

Many people worry that they have schizophrenia. I receive messages or inquires often of people asking about symptoms and manifestations. If you have those types of questions, or if you’re a mental health professional who needs to brush up on symptoms and medications, this article should help you.

There are many clinical observations of how schizophrenia presents itself. Cognitive impairments usually precede the onset of the main symptoms[1], while social and occupational impairments follow those main symptoms. 

Here are the main symptoms of schizophrenia:

  • Hallucinations: a perception of a sensory process in the absence of an external source. They can be auditory, visual, somatic, olfactory, or gustatory reactions.

  • Most common for men “you are gay”

  • Most common for women “you are a slut or whore”

  • Delusions: having a fixed, false belief. They can be bizarre or non-bizarre and their content can often be categorized as grandiose, paranoid, nihilistic, or erotomanic 

  • Erotomania = an uncommon paranoid delusion that is typified by someone having the delusion that another person is infatuated with them.

  • This is a common symptom, approximately 80% of people with schizophrenia experience delusions.

  • Often we only see this from their changed behavior, they don’t tell us this directly.

  • Disorganization: present in both behavior and speech. 

  • Speech disorganization can be described in the following ways:

  • Tangential speech – The person gets increasingly further off the topic without appropriately answering a question.

  • Circumstantial speech – The person will eventually answer a question, but in a markedly roundabout manner.

  • Derailment – The person suddenly switches topic without any logic or segue.

  • Neologisms – The creation of new, idiosyncratic words.

  • Word salad – Words are thrown together without any sensible meaning.

  • Verbigeration – Seemingly meaningless repetition of words, sentences, or associations

  • To note, the most commonly observed forms of abnormal speech are tangentiality and circumstantiality, while derailment, neologisms, and word salad are considered more severe.

  • Cognitive impairment:

  • Different processing speeds 

  • Verbal learning and memory issues

  • Visual learning and memory issues

  • Reasoning/executive functioning (including attention and working memory) issues

  • Verbal comprehension problems

  • Mood and/or anxiety: mood and anxiety disorders occur at a higher rate in schizophrenic patients than in the general population, and for this reason it is important for providers to . Estimates of the lifetime prevalence of depression in schizophrenia vary widely—from 6 to 75%—based on differing study characteristics including varying definitions of depression, patient settings, and durations of observation (Conus et al, 2010Hausman et al, 2002McRenolds, 2013). There is a higher prevalence of anxiety in patients with early-onset schizophrenia than in patients with later onset. 

  • Suicidality: People with schizophrenia have a higher rate of suicide than the general population. Generally, 5% of 10% of all completed suicides are people with schizophrenia (Hor et al, 2010; Arsenault et al, 2004).

There are also some associated signs we want to make sure you are aware of, even though they aren’t considered central to the diagnosis of schizophrenia:

  • Neurological signs aka “soft signs” include slight impairments of sensory integration and motor coordination (Heinrichs et al, 1988). Some examples of this include: R-L confusion, agraphesthesia (the inability to recognize letters or numbers traced on the skin, usually on the palm of the hand), olfactory dysfunction, astereognosis (the inability to identify familiar objects by touch alone). Be sure if you see one of these symptoms that you consider the possibility that they could be a side effect of medications.

  • Catatonia is another important state sometimes associated we would like you to be familiar with. A helpful tool to use when evaluating a patient is the Busch Francis Catatonia rating scale which lists all the criteria associated with catatonia and 0-3 rating scale for each.

  • Interestingly, another association we see in people with schizophrenia is that there are higher rates of diabetes, hyperlipidemia, and hypertension. In fact the life expectancy is reduced 10-20 years compared with the general population. The main medical mortality is heart disease.

In conclusion

On the podcast episode, we discuss the clinical manifestations of schizophrenia and what you would be looking for when making a diagnosis. The more we understand about this disorder—how the symptoms manifest, in what order they often present, and how to differentiate these signs from adverse drug reactions, and expected comorbidities—the better. Improved understanding of this will improve diagnosis and equip providers to implement treatment sooner, thus improving the prognosis and projected functionality of patients with schizophrenia.

In the next podcast we will be discussing the following topics:

  • How the disease progresses?

  • DSMV definition and diagnostic criteria

  • Differential diagnoses

  • Symptom management:

  • Pharmaceutical

  • Non pharmaceutical

Here are some further episodes on schizophrenia:

How Psychiatric Medications Work with Dr Cummings

Schizophrenia with Dr. Cummings

Schizophrenia in Film and History



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