Psychiatry & Psychotherapy Podcast - The History and Nuances of Bipolar Illness

Episode Date: August 2, 2018

In this episode we discuss: The history of bipolar illness, mood stabilizers, common treatments, psychopharmacology, psychotherapy goals, and more. For paraphrased transcription and blog: go here For more detailed notes by Dr. Cummings, go to my resource page.   By listening to this episode, you can earn 0.75 Psychiatry CME Credits. Link to blog. Link to YouTube video. Join David on Instagram: dr.davidpuder Twitter: @DavidPuder Facebook: DrDavidPuder

Welcome to the Psychiatry and Psychotherapy Podcast, the podcast to help you in your journey towards becoming a wise, empathic, genuine, and connected mental health professional. I'm your host, Dr. David Puter, a psychiatrist who splits his time practicing psychopharmacology, individual and group psychotherapy, medical director of a day treatment program, medical education research, and teaching, residents, and medical students. In this episode, I'm back with Dr. Cummings. Dr. Cummings, welcome back. Thank you very much.

I'm glad to be back with you. Today we're going to be talking about mood stabilizers and bipolar and the history of it and the treatment and kind of the nuance of some of the medications. Whether you're a psychiatrist, an NPA or someone in training, I think this would be very valuable. And if you're a therapist, I think it'll be very valuable to know what are the different medications. We'll talk about some of the side effects, how they would interact potentially with therapy,

with the brain, with brain function. and we'll also talk about the role of therapy within a true bipolar disease. And yeah, so Dr. Cummings, welcome to the show. Thank you very much. Bipolar illness was really first described also by Emil Krepulin, the same man who described schizophrenia in the 19th century. And indeed, the patients he was seeing, he was able to divide into those who had a chronic psychics.

psychotic illness, which without antipsychotics had a pretty uniformly deteriorating course, but then he noticed that there was another major mental illness in which people had episodic disturbances of mood, either elevation of mood and increased energy, decreased need for sleep, often impulsive or sometimes psychotically related behaviors. And on the other pole, people who became also depressed at times became energetic, hypersomnalant in many cases. And the illness he described was then as now cyclic in nature. People would have episodes of either mood elevation or depression separated by variable periods of time of normal functioning. and he indeed described that as manic illness or mania.

And indeed to this day, the DSM identifies bipolar illness primarily by the presence of at least one episode of mood elevation to help distinguish it from unipolar or major depressive disorder. Yes, I think you said a couple of things there that are really insightful. One is that in between episodes, you know, patients are fairly normal. And when they're manic, you know, their mood elevates, their lack of sleep. So they're sleeping, you know, maybe at first four to five hours a night and then three to four and then, you know, not sleeping at all. And one thing I like to say is that every true manic episode will end in three places, death, jail, or hospitalization of some type. Yeah, any other sort of nuance of the diagnosis that you want to throw out there at this point?

Well, there are several important points about bipolar illness. Its initial peak is in the 20s and 30s, although people suspect that many individuals who become bipolar don't initially declare themselves. They often present with a series of recurrent depressive episodes, and then at some point they exhibit a period of mood elevation, meeting the criteria for either hypomania or mania, which then earns them the diagnostic label of bipolar mood disorder. It has evolved into being identified as two types,

type one in which the person has fully evolved mania or mood elevation and fully evolved episodes of depression. And type 2 in which the person may have a milder form of mood elevation, but still has fully evolved periods of depression. Yeah, so full episode you would sometimes, I often see the patients get psychotic. They're rambling. They're talking very fast.

You know, they're connecting the mind calendar with quantum physics. And they're not looking for a psychiatrist. They're looking for a, you know, PhD and physicist to help them save the world. Yes, grandiosity is often very much a part of mania. Although, indeed, historically, some people with bipolar illness have, during episodes of mood elevation before they become disorganized or psychotic, have often been incredibly productive at times. Oh, yeah.

For example, Sir Isaac Newton was thought, in retrospect, to be bipolar. He would withdraw to his apartments in Cambridge, often for months at a time. No one would see him. He wouldn't basically come out. And then he would have a burst of activity. And indeed, he wrote the Principia Mathematica, which created calculus in a period of two weeks, which was characteristic of his sort of periods of great activity and other periods in which he simply was withdrawn and quiescent.

Wow, that's really cool. Yeah, I think that there is that adaptive role of bipolar and that might cause it to be continued to propagate through the genes where it's like if you have a little bit of it, it actually can make you incredibly productive, too much of it, and then not so much, you know? But patients who start to escalate, they also get at times hypersexual,

have multiple partners. And, you know, that can also sort of be a survival advantage of sorts. I don't know if you have any other thoughts on that. Well, indeed, during episodes of mood elevation, at some point, judgment often goes out the window, so to speak. Indeed, when I worked for the Veterans Administration, I had one man who was manic and was at the end of a period of mania.

He was coming back down, presented to the ER, not because of his mania, but because he had met and proposed two five different women, they had all found out about each other, and basically he wanted to be admitted in order to try to save himself. Oh, dear. Oh, dear. Yeah, people,

people sometimes buy all sorts of things that they don't need. I'm not talking about just going to Target or, you know, but I'm talking about like taking out multiple credit cards, buying extra houses, cars, boats. I've had patients burn through tons and tons of money when they're manic. Indeed. And what seems to be underlying this is the limbic system, which is a circuit involving the temporal lobes and structures, which then swings upward into the mammillary bodies,

into the anterior cingulate gyrus, which then projects forward into the frontal lobe. That circuit goes through, in people who are bipolar, periods of hypoactivity or depression, literally depressed metabolic rates, 30 to 40% below normal, And then during periods of mood elevation, there is literally an increase in metabolic activity and instability in that limbic circuit, which in some ways the mood is an element of that. But person's overall activity, sleep wake cycle, circadian rhythms, all of those things that are related to the functioning of the limbic system are disturbed in bipolar illness.

And indeed, there are some models of the illness that suggest that perhaps the core of the pathophysiology is essentially an abnormally regulated biological clock. And most of us, the nerve cells, the neurons that make up the biological clock are very tightly linked to each other in terms of their operation. they literally form two pacemakers or oscillators in a very small structure that sits right on top of the optic chasm called the superoptic nucleus. Normally, all of our circadian rhythms are regulated by this master clock. And in healthy people, it's very difficult to get the two oscillators to separate from each other.

And bipolar people, those oscillators, isolators drift apart relatively easily. Something as simple as loss of sleep during the latter half of the night will cause them to diverge from each other. And when that begins to happen, the overall functioning of the limbic system begins to oscillate in an unstable manner. So people have looked at things like disturbed sleep

as being a very common precipitant of a mood episode. You know, if somebody has a difficult day or a disturbing event and they're genetically vulnerable to being bipolar, well, they may not sleep well that night. And the next night they may not need to sleep as much. And the night after that, they really don't sleep. And then their mood begins to elevate. And another episode is initiated. Yeah. So that's really interesting, especially with all the limbic system kind of coming back.

get in a focus. We talked about that with depression and mood to instability as well. Yeah, any other sort of genetic markers that they found that are linked to bipolar? They have found a number of genetic markers. In fact, the number of genetic foci that have been linked to bipolar illness are right around 100. They overlap in part with schizophrenia, but not entirely. People with bipolar illness have a much more normal brain in terms of development, in terms of the neurons, than do people with schizophrenia.

But there does appear to be an inherent defect in the operation of the elements of the limbic system with this periodic repeating of overactivity and underactivity. plausibly related to the core biological clock. And indeed, the mood stabilizers that we're going to talk about all have an effect in terms of decreasing and stabilizing the activity of the limbic system and tending to push that clock back toward being phase-linked

or operating together as a single oscillator rather than as divergent oscillators. The very first mood stabilizer discovered was lithium. Now, medicine has a history with lithium that predates bipolar illness. Lithium was very popular in the 19th century for the treatment of gout. It does decrease the formation of uric acid crystals, which is thought to be the inflammatory source of gout. And indeed for a while in the 19th century, lithium salts in very low quantities, concentrations became popular in health spas in Europe.

People even bathed in lithium mineral pools, although I'm frankly not sure what that did for them. In the 1940s, a psychiatrist named John Cade served in the war and was a prisoner of war for three years. After the war, he worked in a repatriation hospital in Australia and became fascinated with bipolar illness. Now, at the time, he looked at the earlier history and thought, frankly, that uric acid somehow caused bipolar illness. That turned out to be a wrong hypothesis, but it led him to use lithium urate, which is the most soluble form of uric acid in hamsters to see it. what would happen. And indeed, the hamsters got lethargic and sleepy. In those days, there were not a lot of controls on research. And so he decided to give his lithium compound to 10 patients. Six of them were bipolar. Four of them were schizophrenic. They all became less agitated.

the schizephrinics didn't change all that much, but all of the bipolar patients who were all manic became euthymic, their mood stabilized. Now, frankly, it's amazing to me that he didn't kill any of these people. He gave them gigantic doses of lithium. His initial dose was 1,300 milligrams three times a day. Most of the patients got ill with that. If you give somebody too much lithium, they develop nausea, tremor, diarrhea, and you can make them very seriously ill with the lithium because it has a very narrow therapeutic index.

The distance between therapeutic and toxic is not very far. Optimal for most patients is 0.6 to 1.0 millimoles or millie equivalents per liter. toxicity usually begins at about 1.5 and serious toxicity begins at about 2.0 millimoles per liter. So that's not a huge difference in concentration. Yeah, usual dose, you know, start them at 900 at night or 600 twice a day if they're manic in the hospital and then increase to maybe, you know, 1,500 or 2100. That's probably the max that I've seen, at least at where I practice. I don't know what you guys are doing here at Patton. One of the things we've done is usually we do start most patients at 900 milligrams at night,

obtain a plasma concentration a few five to seven days later and then adjust the dose. Most people are not widely aware of it, but you can actually load lithium, like you can load valproic acid. Cook et al did a study in which, They took the extended release form of lithium and gave people 30 milligrams per kilogram in three doses. On day one, at 4 p.m., 6 p.m. 8 p.m. They divided them that much just to avoid having nausea. Then they measured a lithium level the next morning. If the lithium level was less than one, then they gave them 1,200 milligrams at night of the immediate release.

If it was over 1, they gave them 900 milligrams at night, and then a week later they re-measured the lithium and sort of fine-tuned the dose. Interestingly, none of their patients had any difficulty with adverse effects or toxicity in using that approach. One comment I would make about lithium is essentially it should never be given in divided doses. The kidney is spared by having a long trough period between lithium doses,

and so the renal effects of lithium are minimized if you give it all at bedtime. Yeah, and what are the, I think there's hypertension medication, what is it, that decreases the potential toxicity of it. Yes, if somebody has difficulty, you can use amelioride to decrease nephrogenic diabetes andcipitis. Lithium tends to decrease lithium concentrating, sorry, urine concentrating capacity. So people, almost everyone who takes lithium, their urine output will increase by about 20% and their water intake will correspondingly increased by about 20% to compensate. There are a few people who get much more severe diabetes insipitous.

This is essentially an insensitivity to antidiarrotic hormone in the kidney. That is improved by giving it once a day. So that that's one reason. The other reason, frankly, is that over the course of many years, about 5% of people who take lithium will develop mild to moderate degrees of renal failure, renal insufficiency. That risk is minimized by, one,

keeping the lithium level most of the time under or at 1.0 millimoles per liter and also by giving lithium only once a day. Of what point would you take someone off of lithium? Basically, the best measure for lithium is to measure the estimated delamular filtration rate, the EGFR. If that declines to 50 or less, the person should not take lithium. The other common adverse effect that lithium has is to make the person hypothyroid. Lithium tends to decrease the...

synthesis and the secretion of thyroid hormone. The good news there, though, is that if it makes somebody hypothyroid, these days we can easily replace the thyroid hormone most often with levo-thyroxin, a synthetic analog of the hormone. And frankly, your body doesn't care whether you get your thyroid hormone from your thyroid gland or from a tablet. Any thoughts on psoriasis and lithium? Soriasis is a contraindication to lithium use. It will greatly worsen psoriasis. Also if the person is prone to cystic acne, lithium will typically cause a worsening of cystic

acne. Essentially, one of the effects of lithium is to increase oil secretion in the skin, and that can lead to both increased psoriatic plaques and increased psoriotic plaques and increase cystic acne, which is one of the reasons people began looking for alternatives from 1949 when Cade published his paper until 1970, lithium was the only mood stabilizer on the market, and in the U.S., there weren't really alternatives until the early 1980s. The reason we have other things we use for bipolar illness these days was largely as the result of the work of Robert Post.

He was a psychiatrist who worked at NIMH and was doing an unrelated experiment. He was looking at kindling or increased sensitivity of the limbic system by putting electrodes in to mouse temporal lobes and giving them a one second electrical stimulus each day, once a day. Initially, when you do that, nothing happens. But about day two or three, the mouse will have a complex partial seizure, a temporal lobe seizure, basically. If you keep doing it, pretty soon the mouse will start having spontaneous seizures.

Post looked at that and said, hmm, the nerve cells of the lymphs of the lymphs, limbic system can become more and more sensitive, more and more hyperactive, less and less well-controlled, I can block that effect in terms of seizures with anti-convulsants. He then made a leap in logic and said, well, gee, people with recurrent mood episodes, bipolar patients, I wonder if those mood episodes are acting like the electrical stimulus that is causing kindling in the limbic system. So he said, well, I'll try treating some bipolar patients with an anti-epileptic. The first one he used was carbamazapine tegratol. Tegratol is a very difficult drug to use because it induces its own metabolism, so the

level keeps falling. It also is fairly toxic with respect to the bone marrow. So you have to watch out for loss of white cells, red cells, platelets. So he fairly soon turned to another anti-epileptic valproic acid, which is a branch-chain fatty acid, and found that it was also effective in treating bipolar illness. And indeed, the valproic acid treatment turned out to be more effective if the person was a rapid cycling bipolar patient, having more than four episodes a year,

than was lithium, although lithium remained superior if the person was a classic type 1 bipolar patient. I still prefer lithium. For many patients, it is the best treatment available. For those who can't tolerate lithium or who have become resistant to lithium monotherapy, valproic acid is often the,

alternative or the add-on drug in the case of people who require more than one mood stabilizer. The Valparic itself has a fascinating history. It was originally made in the 19th century and was thought to be an inert

solvent. It was discovered to be an anti-seizure drug when it was being used as a solvent in the 1960s in France as a way to to dissolve what they thought might be anti-seizure medications. And it turned out when they used valproic acid as the placebo, it often outperformed the, quote,'s, drug,

which led them to realize that valproic acid was an anti-epileptic drug. And then, of course, you had posts use of anti-epileptics as mood stabilizers, and indeed psychiatry has pretty much examined every, anti-epileptic introduced sense to see if it had mood stabilizing properties. Some do, some do not. Lomotrogen, for example, limictal, does treat bipolar depression and does stabilize mood cycling but has almost no benefit with respect to mood elevation. In fact, Lamotrogen as a monotherapy may actually cause

switches into mania in some patients. People have looked at topiramate and found that it may have some prophylactic capability, but doesn't seem very effective at all if the person is already manic or depressed. But if their mood is already stable and you're just trying to decrease their cycling, it may have some benefit.

Yeah, I tend to see phalprok acid is problematic, especially for women who want to be pregnant, you know, can cause some pretty severe birth defects. Yes. Valproic acid is very much contraindicated in pregnancy and in young women in general it can be problematic because it can cause polycystic ovary disease. In pregnancy, it causes not only a risk of neural tube defects,

things like spina bifida, it decreases the intellectual capacity of the offspring by about 10 IQ points. And it roughly doubles the risk of autism in the offspring. Yeah, and also for women it causes herstitism and weight gain. Yes. Which, you know, hair and places you don't want it and weight gain, not a winner usually. Which is why people look for alternatives. And indeed, that's one of the reasons that some of the other anti-epileptics have become popular,

usually as adjuncts to lithium. More recently, some of the second-generation antipsychotics have also shown mood-stabilizing properties, albeit, again, usually as an adjunct to a primary or classic mood stabilizer, that includes drugs like aeropiprizole, Brexpryprazol, carriprosine, olanzapine, quatyapine, quatapine in particular is effective in treating bipolar depression, as is lorazodone. Yeah, if someone comes into the inpatient center that I work at,

although I don't work there full time during the week, I sometimes cover in the weekend, And often, you know, zyprexa and lithium can really help someone come out of the mania. You know, you put on zyprexa 10 milligrams at night, lithium 900. And then, you know, it may take three or four days of loading up those medications for them to start sleeping. So that's how you know they're really a true manic patient is, you know, day two or day three or even sometimes day five. even after being on therapeutic doses of these medications. It's like, okay, this person is only sleeping two to three hours a night. That's when we know that this person is like, you know, true manic.

Yeah. Indeed, people with mania are the only group of people I've met who have in some cases a complete lack of sleep and will tell you I feel just wonderful. Everyone else who has insomnia, usually the next day they say, oh my God, I feel terrible. Yeah, they'll be running around the unit, you know, talking to everyone, and, you know, all sorts of different missions depending on their, you know,

story and what they're into. Oh, yeah. Indeed, I helped one of our psychiatrist's practice for their oral board examination back when psychiatry was doing that. and the patient who volunteered was manic, and indeed she came into the room, walked around, shook everyone's hand, said hello, and then announced to the entire group,

I can do a handstand want to see and promptly did a handstand on top of the table. Not the typical social introduction that most people would engage in. Yeah. So, okay, lithium, you have, and then some of the newer ones, Lomictal. I wonder if you can talk a little bit more about Lomictal

because I think it's used often for, you know, borderline per size order, trauma even, mood stabilization, kind of the ups and the downs. I think it has gotten possibly more use than it should because although it does have antidepressant properties

in bipolar illness, it is certainly not a benign drug. I think people initially were attracted to it because there's not a lot of laboratory monitoring involved. The plasma concentrations of Lomotro gene don't correlate very well with its efficacy because it's very rapidly cleared from the blood compartment and taken into tissue. So measuring what's in the blood doesn't tell you very much. It's easy to administer and when you're not using it for seizures, usually it can be dosed all at bedtime. It does carry a risk of Stevens Johnson syndrome, which is severe malignant rash in which

the person winds up looking like a burn victim because their skin literally dies and falls off. It also can cause a lymphohistocytosis, which is very much a similar sort of autoimmune process, but involving the blood vessels and internal organs. Luckily that is rare, but it's also typically a life-threatening response to the drug. The risk of both are increased by titrating the drug too rapidly. They discovered the side effects when they were using the drug initially for seizures, and they were often increasing the dose by 100 milligrams a day, starting at 100,

and by day four, the person was on 400 milligrams, and they wound up with a 9% rate of malignant rash. If you slow down and don't go faster than around 25 to 50 milligrams a week in the titration, the risk is reduced, but it's still not zero. It's probably less than one-half of one percent. But it is a caution. The other caution with the drug, of course, in bipolar patients is it sometimes is not a very good monotherapy because it doesn't provide any protection against mood elevation.

It seems to be effective in treating the depressed phase of the illness but not the manic or hypomanic phase of the illness. What about oxycarbamazepine as a treatment? It has flunked multiple trials as a mood stabilizer. Carbamazepine, which differs from oxcarbasopene only in one bond. In carbamazepine, the bond between carbons 10 and 11, is an epoxide bond in oxcarbasopine, that same bond is an ester bond. It appears, however, that the mood-stabilizing properties of carbamazepine

result from the epoxide metabolite of carbamazepine, and of course oxcarbazepine does not produce that metabolite. Oxcarbazepine can, in some individuals, reduce impulsivity, which seems to be a truism across the anti-epileptic drugs, but it's not an effective bipolar treatment. Do you think it's an effective anti-anxiety or mood stabilizer for people without bipolar? It can be.

I think it has gotten too widely used. There was only one study looking at it in forensic, settings for impulsive or violent patients. It was a self-funded single investigator study, and it's been the only study that was ever produced, never replicated, and suspicious in that the patients were all outpatients, self-recruited via newspaper ad. So its database, even for impulsivity and so forth, is pretty... limited. It does have, I think, some application in that regard, but it is not as good as people

hoped. I think people became enamored of it simply because it was easier to use than carbamazepine, which isn't to say that it's benign. It induces hepatic enzymes. It causes dangerous hyponatremia and about two and a half percent of the people who take it so people can get in trouble. in that way. But for treatment of bipolar illness, it's frankly just not a treatment. Yeah, I've seen it used in the community more for people with, like, anxiety as a sort of an, you know, a different option. But it sounds like you're saying there isn't strong evidence for that.

No, there is not. You know, there haven't been any really good study. identifying it as an anxiolytic. Like most anti-epileptics, it can be sedating and somewhat calming, but you could get the same effect from literally any of the anti-epileptic drugs. Probably safer in that regard would be a gabergic anti-epileptic if someone wanted to go that direction. There are three on the market, Tigabine, pre-gabble, and gabapentin.

I think one of the things that is important to discuss is the cognitive side effects of this kind of group of medications. I'm unaware of any for lithium. I'm aware of some for valproc acid and topamax the most. Yes. Lithium typically causes cognitive impairment only if the plasma concentration is too high, in which case it can cause cognitive.

cognitive impairment and indeed decreased brain function all the way up to coma. If the concentration is high enough, actually lithium, though, used at therapeutic concentrations actually is neurotrophic. It's been used now in some demented patients with modest results. MRI scans, though, will show a thickening of the cortex if you put somebody on lithium. In contrast to that, the anti-epileptic drugs almost universally tend to dull cognitive performance.

And indeed, one of the tip-offs with topiramate that you're giving the person too much is when they start to lose the ability to find nouns. they become anomic. Everything becomes a thing of a jig or what you may call it. At that point, the person is taking too much to a pyramid. Yeah, and I think indiscriminate prescribing of it for migraines and for all sorts of issues is going on from what I've seen.

Patients often come to me in, I can tell that they're having cognitive issues and they're not performing at the sort of the level. that they were prior. And so it's one of my favorite things to do is to try to get them off of that and get them onto something else. They're usually not put on it for bipolar. They're put on it for other reasons. Yeah.

I think that sometimes people over-prescribe medications not adequately appreciating that all of these medications have potential negative effects and they should be used judiciously and cautiously. Yeah. They can provide major benefits. I mean, certainly lithium does. It's a mood stabilizer. It's neurotrophic.

It decreases rates of suicide substantially independent of its mood effects. But it's also a very potentially toxic drug if it's not used well and monitored carefully. Yeah. What do you think about? lithium and suicidality? It's clear that lithium reduces suicidality, and I think that may be its ability

to inhibit impulsivity. I know we talked about impulsivity with respect to the anti-apoleptics and with respect to ox-carbasin, but frankly one of the best anti-impulsivity drugs

in mood disorders in particular is lithium. When they looked at it, suicide rates are substantially lower when people take lithium. And interestingly in the healthy population, when they've done studies in areas with very low concentrations of lithium in the groundwater, rates of suicide and rates of homicide are lower in areas with lithium in the groundwater than in areas that don't have lithium

in the groundwater. The amount people are getting from the groundwater would be roughly the equivalent of taking three milligrams of lithium a day. Which means in the healthy non-bipolar, non-mood-disordered brain, it doesn't take very much lithium to make people somewhat less violent. Yeah, I think they took it out of the water supply in Australia and then the suicide rate went up. I don't know if you've heard of that story. Yeah, I've heard of that one. There was also an excellent study in Greece in which they compared the homicide rates in areas that had lithium in the groundwater versus areas that didn't, as well as suicide rates.

And indeed, I can send you that article to post along with this podcast. Yeah. So this kind of comes to maybe the more practical side of treating a patient. with bipolar outpatient. We've talked a little bit about the inpatient. And I think for inpatient, what I've seen is there's the three classes of medication. The mood stabilizers, where lithium is kind of what I would prefer, but different people have different practices.

And then you have the atypical antipsychotics, which are often kind of added to help bring someone down. And then the third class is the benzodiazepines, which I think barbiturates and was, were used before lithium, right? Yes. Sort of the treatment of bipolar historically. Barbiturates were introduced in 1903. And at the time, they were essentially the only psychiatric medication available.

And so they treated literally everything that involved mood elevation or agitation with the barbiturate. And I think actually when they were the witch trials, back in the middle ages, I was reading that it sounds to me like a lot of the patients were having manic episodes that were sort of diagnosed as being a witch. And they would try to give them something that would cause them to come down, it would cause a normal person to be sedated and they wouldn't be sedated. I don't know if you read that as well. Yes, indeed.

That was one of the tests described in a book called the Malfius Malfiarcher. or the witch's hammer. Right. Now, frankly, most of these tests were designed so that if you were the accused witch, you didn't do very well. For example, one of the tests was being tied up and thrown into a mill pond. If you drowned, you were concluded not to be a witch, but of course you were dead. If you managed to float and you survived, you were concluded to a witch. have done so via witchcraft and in which case they retrieved you from the water and subsequently

burned you. Psychiatry has come a long ways. So outpatients, I really strongly believe, like, if you have a true bipolar episode in the history of a patient, like these patients need to be watched very closely. I think a lot of patients are overdiagnosed of bipolar. They'll come in with a diagnosis of bipolar and I really try to get a good history, both from the family and from the patient of a true manic episode. But if they do have that and you are treating them outpatient, I think it's really helpful to watch them closely for them to have your email or ability to reach out to you and the family to reach out to you if they start to sleep less. That's the first thing that usually happens is irritability or sleeping less. Like they go down to like six hours or five hours,

you know, when they normally sleep eight hours. Indeed, the neurovegetative signs, that is the change in physical activity, the increased energy and the decreased sleep are often more reliable early signs of impending mania than are changes in mood. In part because all of us have some degree of changeability of mood, and that doesn't stand out nearly as clearly as somebody who goes from normally sleeping seven, seven and a half hours a night to now they're sleeping three. and they feel just fine. And then so, you know, the family reaches out to you. And maybe they're on a low dose of lithium. I have several patients like that. And you subsequently, you know, increase the dose a little bit or add, you know, an atypical antipsychotic.

That's normally what I do. And then if that doesn't help a week later, so I'm watching these people fairly closely, that I'll add something at night to help them sleep, like clonopin or that's what I've been doing. recently. I don't know if you have any thoughts, critique on that sort of approach or what you would do differently. No, it's very useful to maintain sleep. And in fact, one of the things that's very important if you have bipolar patients is to teach them that for them sleep hygiene is very important. They should go to bed at the same time every night. They should sleep. For them, it's not a good thing. oh, I'll stay up and watch the late late movie or the talk shows.

That may be a setup for them for the next episode of mood disturbance. So one is they need to practice very good sleep hygiene. If they're having difficulty sleeping, this is a group in which long-term use of one of the Z drugs may be appropriate if they have difficulty maintaining sleep. My own favorite in that group is S-Zopaclone lunesta, because it has a longer half-life. It's half-life is around four to six hours, so it's long enough that the person will actually stay asleep. It also has a broad dose range, 1 milligram to 8 milligrams at night. It's been used to treat primary insomnia and some individuals for up to decades without development of complete tolerance or resulting in any withdrawal. all syndrome if the medication is stopped.

So the patients, when they're doing well, one of the big things I do is I bring the family in, educate them all on what's going on, and then educate the patient and get their total buy-in to taking medications to prevent the episodes in the future, and then get the total buy-in to be ready to increase the medications. Because a lot of times the patients, they like the hypomania. Yes. That feels great. And so they don't really want to add anything.

If at it, you know, the usual is to stop all medications, and that's why you have to like know, you know, which of your patients have this, because you have to watch them very closely for this and the family watches them closely. The other point of education for both the patient and families, for them to realize that the more episodes of illness they have, the more resistant to treatment the illness will become,

That goes back to post and kindling. And the less responsive, the illness will become to medications. The other bad thing that happens when people have more episodes is the cycle tends to become progressively shorter so that if they were initially having an episode every two or three years, that suddenly is down to under a year, and then they may be having multiple episodes per year. And of course, one of the major costs for both families and individuals who are bipolar

is, you know, severe depression or severe mania is incredibly disruptive to the individual's life. Very, very disruptive. I mean, it can destroy their marriage, destroy their job. Really, really cause them large setbacks. Large setbacks. The last point, I think that's important to, kind of introduces like what is the role of like psychotherapy in this and I think um stress influences the the you know the physiologic sort of reaction to stress will promote more episodes of bipolar

or make it easier for them to become manic um very much so I I tend to think that uh the hypothesis that was originally made by Tom Ware at NIH that for many biophers, that for many biophers, bipolar patients, the common pathway into a mood episode is an environmental stressor that causes sleep disturbance, which then sets off the instability that they have innately in their internal clock, and then they're off into a mood episode. So, indeed, teaching the person's good sleep hygiene, teaching them to be better able to cope with stressors. And frankly, the other benefit I see from psychotherapy is people tend to become more self-aware

and may be able themselves to spot earlier changes in their mood and thinking. They're essentially able to recognize an impending episode sooner, which of course allows them and us to intervene before things get out of hand. Yeah. Yeah. I also think there's a good role in exercise and healthy living with these patients. And that's sort of part of the complete package of, hey, let's, you know, do all of these things at once now that you're healthy, now that you're stable, so that we can prevent a future episode and prevent a severe future episode. Because literally the brain in a severe episode of bipolar is being damaged.

Yes. And we want to prevent brain damage. The other caveat I want to make in terms of pharmacology is, and this is something very difficult for psychiatrists not to do. If you have a bipolar depressed patient, do not give them an antidepressant. There are now a host of studies out there suggesting that antidepressants offer little or no benefit with respect to the depression. it serves only to increase the rate of mood cycling and to risk a switch into mania. Yeah, and this is, I think, also where it's very important

to get a really clear diagnosis and to dig a little bit. I had one patient who I saw go manic while on a chemical dependency unit, pacing the halls at night, talking hyperverbal, and we're like, this patient's going manic. So we had to transfer to the psychiatric hospital. When she came back to the CD unit a week later, I asked her about the episode and she didn't remember very much at all. The history, even a week later, was not enough to let me know that this patient had a manic episode.

So looking at hospital records, looking at histories from the family members, I think it's very, very important to get a clear diagnosis early on. Yes. Indeed, in all of medicine and psychiatry, there's no sure way to fail than to treat something the person doesn't have. Yeah. Well, Dr. Cummings, thank you for coming on. Okay, thank you. I think you're taking a vacation for a couple weeks. I am. Actually, I'll be in Scotland for three weeks in July. That's great.

Which is great because July and August are about the only decent weather there is to be had in Scotland. We'll have a great time and bring some, I don't know, what would he bring back from Scotland? Depends on what we find, but it should be a good trip. All right, take care. Thanks.