The 10 Best Psychiatric Medications

Welcome to Back from the Abyss. I'm Dr. Craig Heacock. Today, a solo episode, the first episode of the season, season 4 on psychopharmacology. And this is the 10 best psych meds. Recently, I did a second opinion on a severely, terribly, chronically depressed young woman, probably bipolar spectrum depression, as well as crippling somatic anxiety. And she was only taking an SSRI and an amphetamine stimulant, and she actually has a psychiatric provider. And this, my friends, is not good care. These meds made no sense at all for this young woman, because basically she's taking exactly zero depression meds. And amphetamine stimulants are well known to increase anxiety, particularly body or somatic anxiety. So this and a number of other recent cases and consults led me to think that I've got to do another psychopharmacology episode. And clearly, there's some major confusion out there about how and when to use psych meds appropriately. Now, I love synthesizing and finding the essentials of a complex topic, searching for the parsimonious explanation or understanding. So I thought it would be an interesting challenge to come up with just 10 medications that could effectively treat, say, 95% or more of all psychiatric problems that potentially respond to medication. I originally wanted to limit the list to seven, but this left some critical gaps. So I settled on 10. To make the list, a medication needed to be very effective, generally safe, well tolerated, generic. And if I could come up with a brand name med that was significantly more effective and or safer and or better tolerated than a similar generic, then fine, that med could potentially make the list. But surprise, surprise, no brand name meds made the cut. A one note here about buprenorphine. Now, buprenorphine or suboxone didn't make the list. And let me just give you a heads up why. Buprenorphine, number one, I don't consider it a psychiatric med. I consider it a game changing med, a life saving med, a med that all specialties should consider prescribing. But it's not necessarily a psychiatric med, but just wanted to say, just because it's not on the list, doesn't mean I don't love it. And one could argue it's the most important medication that any of us is prescribing right now, because of the 100,000 more people who are dying of opioids every year. So here we go, the essential 10, the 10 meds with which you can safely and meaningfully treat most mood, anxiety, and psychiatric disorders. The first four medications on the list are primarily for the syndrome of depression. For each med, I'll cover why the med made the list, primary indications, what it does, what to expect, most common side effects, and some clinical pearls about the med. Number one on the list, and these are not necessarily an order of importance, although the first med is my most favorite. And back from the abyss listeners can probably guess what it is. Lomotogene. That's also called lmictal. Why Lomotogene? Again, longtime listeners of the podcast could answer this for me, but for newer listeners, I'll just jump right in. In 1994, an amazing gift came to psychiatry. And that was the introduction of Lomotogene. Now, Lomotogene came on the market for partial seizures and migraines, but like so many other medications, it was found to have this other wonderful use. And Lomotogene is in a class by itself, and it is a depression med. It's not a mood stabilizer. A lot of people call it that. But if you think about a mood stabilizer, by definition, we need to stabilize mood from the bottom and the top, meaning bringing down mania agitation or bringing up dysthymia or depression. And Lomotogene doesn't do anything to prevent or treat mania. So it is actually a depression med. It's anti-depressant. And Lomotogene is really the first powerful anti-depressant that doesn't have sexual side effects or waking, which are two of the awful, awful realities of so many of the powerful depression treatments that we use. So who is Lomotogene appropriate for? What are the indications? Lomotogene is an anti-depressant primarily for people with a depressive syndrome with hypersomnia, oversleeping, and/or seasonal worsening, and/or suspicion of a bipolar spectrum mood disorder. One way to think about Lomotogene, and I think about it like this, Lomotogene is like a climbing rope. So if you're on Lomotogene, you're doing well, you're stable, you're euthymic, and your mood starts to plunge. Lomotogene is like a climbing rope. You don't notice Lomotogene until your mood is starting to plunge, and then you can feel a catch. And I've had many, many patients describe that. Like they woke up on a Tuesday morning and they could feel that like, that doom-dread hopelessness start to settle in, and then poof, went away. And so, and the other reason I like that idea of a climbing rope is that you don't notice the climbing rope until you need it. And the vast majority of people on Lomotogene will say they don't know they're on it, you know, they can't orgasm, they're not gaining weight, they don't have dry mouth, they're not having strange sleep problems or horrible nightmares, they, it's kind of like a sugar pill, except when the depression starts to stir, it's an ugly head, it's there for you to save you. So Lomotogene doesn't have any of the other common side effects that antidepressants do, but it does have one notable side effect, and that is maybe 10% of people get a skin rash. And that's typically benign. There are some very rare kinds of rashes, including Stevens-Johnson and some other truly allergic constitutional rashes you can see with Lomotogene. But for most people, if they get a rash, it's not a big deal. You can restart Lomotogene at a lower dose and start over. And that actually relates to my clinical pearl. I have a lot of people come to me who say, "Oh, I've been on Lomotogene and I got a rash, so I can't be on it." And I always ask them, "Well, did you just have a rash or did you have Stevens-Johnson, which is a potentially life-threatening rash, which starts with blisters in the mucus membranes in the mouth? I'll say, "Did you have that or did you have a rash with a fever or with swollen lymph nodes or flu-like symptoms?" And the vast majority of time, people say, "No, I just had a rash." And so what I tell people is, "Look, you can try Lomotogene again. We'll just go very slow." Instead of starting you at 25 milligrams, maybe we start you at 12.5 or 6.25 and we just titrate very slowly. And that is often very effective. I've had many people come to me that say, "I can't take Lomotogene because of rash." And we just start it slowly, titrate more slowly, and they're on it. And they don't have rash and they get all the benefits of this life-saving climbing rope. Number two on the list, my second favorite med. What would that be, listeners? That would be ketamine. Why ketamine? Again, listeners to this podcast know this, but let me just lay out the evidence. You know, if we only get four meds on my list for depression, we're going to want something really powerful for the hard cases. And the data over the last few years make it look like appropriately does ketamine is as effective for ECT, at least for people under 50-55. And typically has been more effective than TMS, although the new form of TMS that's coming out of Stanford called the SAINT/SAINT TMS, which is an MRI-guided TMS. It's looking like that may be as effective as ketamine and ECT. But really nothing else that we have in psychiatry is such a game changer for super severe patients, medication-wise, as ketamine. And also, ketamine can dial down very severe post-traumatic stress exacerbations, or even people that are just having terrible SI, suicidality. You know, some people will have a symptomatic feature of their depression, they just have this terrible 24/7, like screaming loud in the head, suicidality. And ketamine can just quiet that in a way that maybe only a couple other meds can. And actually, they're lower down the list. We'll talk about that. So it turns out that ketamine is not only often super effective for treatment-resistant depression. It's the treatment of choice for bipolar and mixed depression. Nothing else is nearly as good. It's an amazing treatment for exacerbations of PTSD. And as I've found over the last few years, ketamine is actually a pretty darn good treatment for dysthymia, which is just low-grade depression where people can function. But I call it black and white TV when people are dysthymic, like they can function, they can see their world, but everything is just kind of drained out and lifeless. But ketamine actually is quite effective for that. What does ketamine do? Well, maybe we can kind of tie that in with what to expect. I mean, one of the things we know that ketamine does is that it repotentiates the endorphin receptors. And the endorphin receptors are what allow people to feel soothed, calm, at peace. And so in the four or five, six, seven days after a higher dose ketamine treatment, a psychedelic dose, people often describe very profound sense of calming, of feeling like things are going to be okay. There's a real sense of resourcing. And in resourcing, we mean that people are just more able to handle what's on their plate there at their more resilient selves at their more creative and collaborative and engaged selves. Ketamine can cause a very rapid boost in energy and mood. In fact, such a rapid boost that in people with the vulnerability to bipolar one, they can actually flip into mania. And I've talked about that on the podcast. Ketamine improves deep sleep, slow wave sleep, which is crucial for cognition. And interestingly, one of the predictive factors for ketamine working for treatment resistance and depression is people who have cognitive impairment. And that very well may tie in this improvement in deep sleep with ketamine. And then on more the psyche level, ketamine improves access to the unconscious. And it also potentiates somatic therapy. And somatic therapy is kind of a royal road to trauma therapy. And so that's why, for example, last season in the psychedelic somatic therapy episode with Sajrasvi, he talked about using ketamine as a way to elicit transference and work with the unconscious through this through the body through somatic work. Ketamine is a really well tolerated, the two main side effects, motion sickness, which we can use a scapulamine patch, a motion sickness patch, and/or Zofran on Dancitron. And then hypertension, and this is actually a significant issue for men over 50 in particular. If you have high blood pressure, you know, we're often going to need to think about increasing blood pressure meds or at doing quantity in before a session. But other than motion sickness and potential for blood pressure spike, ketamine is typically really well tolerated. A couple clinical pearls. Ketamine, like ECT, seems to work best and last longest with appropriate meds on board. Now, I have a lot of people come to me saying, you know, I would like to treat my depression or PTSD, but I don't want to be on meds or I want to get off meds. And first couple years, I tried to get people off their meds, but then it became abundantly clear that most people needed to stay on their meds. And then as I read more and more, the ECT has some real kind of clinical parallels with ketamine, that it made more and more sense that ECT is a reboot of the brain, kind of a soft reset. And ketamine, one of its mechanisms, it seems to be a soft reset of the brain that helps meds work better. Okay, the third medication. Now, this was a little tricky because I have ketamine and have lomotrogene, but I needed a med for a very common presentation we see. And this is what we call anxious depression. People say, yeah, I'm kind of 50% anxious, 50% depressed. This is often called unipolar depression. This is depression with insomnia. This is also called major depressive disorder, which as I've spoken at length on other episodes, I think that's not a real diagnosis. That's a waste basket for a whole bunch of things that can cause an anxious depression. But in any case, there are people who show up at our doorstep that need something for anxious depression. And sort of the three, if you will, families or classes and meds that we could use to address that would be the serotonin norepinephrine reuptake inhibitors. That's one. The second one would be the tricyclics. A third option would be the MAO inhibitors. But when we look at safety and tolerability, I think the, and efficacy, I think the SNRIs are on top. And coming out on top of the SNRI family, in my opinion, is Desfamilifaxine, or prestige is the brand name. And the reason is it tends to have the lowest sexual side effects, has the least weight gain. It actually does work quite well for both. I think the serotonergic effects of Desfamilifaxine really dialed down the rumination, obsession, neuroticism and panic that we see in anxious depression. And the adrenergic effects are really where the depression efficacy lies. Most common side effects of Desfamilifaxine would be anxiety and insomnia, which is interesting because Desfamilifaxine is a really good anxiety med, but like so many anxiety meds, they often make anxiety worse before they make it better. Another clinical pearl, as many of you know, the SNRIs like this, like Desfamilifaxine, can actually make bipolar disorder worse and they can trigger rapid cycling. All right. Number four on the list, the fourth depression med. I needed one more med for severe depression. So prior to ketamine, which is kind of hard to believe life before ketamine, but there was life before ketamine. That was like before 2018. When people would show up in my office with crippling depression, severe, disabling, the kind of thing where I think, okay, we're going to maybe have to walk you over to the inpatient unit, kind of the kind of depression where people can't take care of their kids, can't get out of bed. My go-to and I think the go-to of lots and lots of other psychiatrists was Aeropipersol or Abelify brand name. Aeropipersol is an atypical anti-psychiatrist chronic family. That's things like Latuta, leuracidone, ceroqual, cotypene, geodon, supracidone. And these are often very powerful antidepressants, but they have a whole host of side effects, including weight gain and insomnia and diabetes and tremors and on and on and on. But I have to say, there's a subset of people that really need to be on an atypical. And even in my group of people who are doing maintenance ketamine, who are getting a lot of benefit from that. These are folks with chronic treatment-resistant depression, typically bipolar spectrum. Many of them, despite being on the motor gene and getting regular ketamine treatments, many of them also need to be on something like Aeropipersol. And the reason I chose that one instead of, say, leuracidone, Latuta is, Aeropipersol has been around longer. It's generic. You know, I think Rexalti, which is Brexipipersol, and leuracidone, which is Latuta, are probably roughly equally effective, but they're still brand name and they're extremely expensive. And there's no evidence that they're any better. So what are the indications for Aeropipersol? People who are decompensating in the bipolar spectrum, but particularly people with severe bipolar depression or mixed episodes. Abilify can be a real game changer. Even though Aeropipersol is called a quote-unquote anti-psychotic, it's actually not a very good anti-psychotic. It's a much better mood stabilizer and anti-depressant. And this relates to one of the clinical pearls. At low doses, say, under five milligrams, Aeropipersol is a powerful dopamine agonist and is thus very stimulating, elevates mood and can even trigger mania in some people, but has powerful anti-depressant effects. As you go up, say, between five and 15 milligrams, Aeropipersol has sort of mixed agonist antagonist effects at the dopamine II receptor, which gives it more of a mood stabilizing character. And when you go about 15 milligrams, it's more of a D2 blocker and more of a classic anti-psychotic, although Aeropipersol is not a great choice in general for people who are bona fide psychotic or dangerous. It just doesn't have that oomph of some of the more powerful anti-psychotics. And I should say the most common side effect of Aeropipersol, surprise, surprise, is anxiety and agitation, because we're often starting at low dose where it's very stimulating, can get dopamine going. But by the same mechanisms, I think that it can cause mania in some people. It can just get people very, a little too motivation driven, sometimes hypersexual, sometimes spending too much money, so almost like elements of a little bit of mania. We can see that with people with low dose at bill of five. Next on the list, two medications for the syndrome of anxiety. Number five, this was one of my Desert Island meds from a couple years ago, and that would be Essitalopram, Lexapro the brand name. Why Essitalopram? Well, Essitalopram is the best tolerated, most potent SSRI. And we really need an SSRI on the list because there's nothing else like SSRIs for ruminative, obsessional, catastrophizing above the neck anxiety, as well as dialing down neuroticism. So when we're looking at trying to treat obsessive compulsive disorder, disabling rumination, people who are worrying 24/7, overall neuroticism, or people who are just extremely sensitive to what's happening around them, eating disorders other than anorexia, trichotillomania, nothing beats SSRIs, and in particular, nothing beats Essitalopram, because you can really push the dose up to treat people with severe symptoms, and more often than not, you can make it so it's very well tolerated. And one way to think about how Essitalopram works, if you imagine, you know, the monkey mind, the ruminating, catastrophizing part of the brain is the frontal lobe. And the amygdala, which is the fear, anxiety part of the brain lying deep in the midbrain, their pathways to connect the ruminating part of the brain with amygdala. And it seems like one of the things that SSRIs are doing, they are down regulating or dialing down this circuit. So when people have ruminating, catastrophizing, obsessional thoughts, the fear and anxiety doesn't correlate nearly as much, they can have a terrible thought and they don't get that rush of dread and sickness and kind of that positive feedback from the amygdala. And then they're more able to kind of let those thoughts go without the amygdala cranking up the awful somatic and fear part of the thought. So while SSRIs are usually quite well tolerated, there's a major issue with them. And many listeners know about this. And so it turns out that the SSRIs can really squash orgasm. And on my website, I have a video about this. So if you go to the media page on CraigHeecockMD.com, there's a great video with Jenny Schuyler, who's a dear friend of mine in sex therapy. She and I talk about this issue. So if you're interested in sexual side effects and SSRIs, you might want to watch that video. The short of it is, for sure, a significant percentage of people are going to have orgasm issues on SSRIs. That seems to be less common with esoteric pram compared to the other SSRIs, but it's still an issue. What percentage of people, I mean, maybe, maybe half of women or more are going to have orgasm issues on SSRIs, somewhat less with men. Another resource that I really recommend you look at, there's a wonderful book by Emily Nagoski called Come As You Are, and it is arguably the best book on female sexuality. But there's a whole bunch of great information in there on meds and libido and how just to think about this complicated, the complicated relationships between not just medications, but things we take and the way we live our lives and how that can affect desire and arousal and orgasm. So I encourage you to check that out. A clinical pearl for esoteric pram. If you're having someone with severe symptoms, severe OCD, severe body dysmorphia, severe postpartum depression, or other kinds of symptoms that respond well to SSRIs, you're often going to need to push the dose up high. So for esoteric pram, that would be like 30 to 40 milligrams. And that's a dose that pharmacists are going to call you and insurance companies are going to deny it, which is ridiculous because this is a generic, very inexpensive med. But I can't tell you how often when I push the dose up to 30 or 40, I get all this pushback from payers. So what I usually tell people is just use a good rx.coupon and pay cash because it's just not worth fighting the insurance companies over whether we can give people a little more of a very inexpensive generic med. Another interesting clinical pearl, esoteric pram and the other SSRIs has this really cool use for PMS for premenstrual dysphoric disorder. So we think of SSRIs as working in the brain, but they also work peripherally on progesterone and they inhibit the breakdown of progesterone. And it seems like what's happening with PMDD PMS is that in some women who are hormonally very sensitive as their progesterone levels are falling either right before they have their menstrual cycle or right after they have a baby, that can cause really severe decompensation of mood and anxiety. And because esoteric pram and other SSRIs inhibit the metabolism of progesterone, they keep the levels higher so people have a much smoother path through the days leading up to the onset of menses or the postpartum days when progesterone is plunging after the birth of the child. So now we reach number six on the list, which is the second med for the syndrome of anxiety. That would be a benzodiazepine and I chose lorazepam. So originally I was hoping not to have a benzodiazepine on the list because they can be so addictive and so hard to come off of and they can cause a ton of problems. But I think, and I'll describe when, there are many cases in psychiatry where you just got to have a benzone. But why lorazepam? Let me say a little bit more about that. Lorazepam has a medium duration of action, like five, six hours. The shortest acting benzo is alprazolam or ZX and it lasts, you know, hour or two. And people love alprazolam. They ask for it by name. When the people go to pharmacies in Cabo or Porto de Arta, they're going there looking for alprazolam. And that's because alprazolam hits you really hard. It's a very fat soluble. So it's like, bam, a number of my patients in the past have told me that a two milligram alprazolam is like an, quote unquote, elephant gun to the face. One guy said, it just hits you like this. He caught. That doesn't sound good to me. But I guess if you're a benzo connoisseur, some people like that. But alprazolam is fine, like for an hour long MRI or two hour plane flight, but not something you want to be prescribing regularly because not only does it come on really fast and wear off fast, but alprazolam really commonly leads to rebound anxiety as people come off it. And then they have more and then rebound anxieties that came off it. So alprazolam can very quickly lead to cycles of compulsive use dependence and addiction. And then at the other end of the benzodiazepines would be clonazepam, which is very long acting. And in my residency, we were taught to use that ideally because the long acting effect and the thought was that it's less addictive and less dependence. But what I've found over the years is that clonazepam with its very, very, very long half life is a pretty good way to manage some things. But holy hell, when you try to get people off it, it's kind of like trying to get people off methadone because both methadone, which is an opioid, very, very, very long acting opioid and clonazepam, which is a very long acting benzodiazepine, it's like, it's not even like trying to pull off a bandaid, it's like trying to slowly take staples out of someone's 28 inch long wound over like eight months and just slowly tearing out the staple bit by bit just every day. And it's just, it's this endless, endless withdrawal. And so more and more, I've been trying to avoid clonazepam. So lorazepam, which has a midrange four to six hour duration of action, doesn't have nearly the rebound issues that is alprazolam. It's not nearly as sought after by people who are trying to get high. And then it doesn't have that brutal, brutal, endless month taper withdrawal thing that clonazepam has. So why do we need a benza? Well, there's some people that we see that nothing else is going to cut it. I would say people who are having a nervous breakdown. Now, that's not a technical term, but it's actually very accurate. There's some people who are in kind of a fight flight sleep deprived collapse. And what they most need are something like lorazepam so they can get some sleep and calm their nervous system. Or in general, people who are just in kind of sleep crises around grief or mania, you know, you've heard on this podcast, this idea that sleep is the best mood stabilizer. And one of the ways lorazepam can be so valuable is when people come into the office and they're just so wound up and strung out and just, you can just feel like the 5000 RPM coming off them for whatever reason, something like lorazepam can get them sleeping, calm them down, because all the benzodiazepines crank up GABA, which is the primary inhibitory neurotransmitter in the brain. That's like cool water on the sizzling out of control brain. Everything gets dialed down, good and bad, which actually then leads to the most common side effects of benzos. Besides the tolerance independence problems, benzos can really affect cognition and memory. And again, I think that's part of this idea. Like if you turn down all circuits throughout the brain, the good things the brain's doing like helping you think and prioritize and remember all those functions get affected too. Here's an interesting clinical pearl about benzodiazepines, which even a lot of my physician colleagues don't seem to know. The benzodiazepines have very different potency. So here's the benzo potency conversion. This is a little nerdy, but some of you might like it. 0.25 milligrams of clonazepam is the same as 0.5 milligrams of alprazolam, which is the same as one milligram of lorazepam, which is the same as five milligrams of diazepam. So listen to that three times, it'll be a quiz at the end. Okay, next we have three medications for psychosis and mania. Number seven, the first one, one of my Desert Island meds from a couple of years ago. And if you remember that episode, they were all L meds, lamyctolexpro, lithium. And finally now lithium shows its face. Why lithium? Why is it on the list? Well, lithium is the gold standard mood stabilizer. It causes lots of positive changes in the brain. And in fact, some people in psychiatry are saying that lithium is the only, if not one of the only disease modifying meds, meaning that the vast majority of psychiatric meds are trying to dial down symptoms. And while lithium does dial down symptoms, it also causes changes in the brain, which positively affect the outcome of an illness such as bipolar one. So if you or someone you know has bipolar one disorder, manic depression, you really should be on lithium unless there's a good reason why you shouldn't be, because it is the medication of choice for manic depression bipolar one. And it's not just that that lithium is gold standard for bipolar one, but it is one of only three or four meds. It's been consistently shown to dial down suicidal thinking. It's really good to prevent violence and explosive anger. It seems to lengthen people's fuse. It can be used to augment antidepressants. So in a lot in some ways like ketamine, lithium seems to cause a number of just positive changes in the brain, which are helpful for different psychiatric syndromes. Lithium usually takes a week or two to start to work, but when it does, it's both subtle and profound. And you've heard people in this podcast talk about how lithium was the only thing that really ever changed things for them. The most common side effects of lithium by far nausea, so if you take it on empty stomach, it can make you nauseated. And some people are really sensitive to the tremor. You can get a tremor in your hands, especially like when you're writing or using a computer mouse, fine tremor, action tremor, that's usually dose related. So it's also often an indicator that you're right at the therapeutic level of lithium. A clinical pearl related to lithium, it's best tolerated if you dose it all at bedtime and you use immediate release. Okay, number eight on the list, this is the second of three meds for psychosis and mania. This would be Olanzapine, the brand name is Zyprexa. Why Olanzapine? Olanzapine is an outstanding med for psychosis, for agitation, for mania, for severe insomnia. Zyprexa or Olanzapine puts you to sleep. And this is actually critical because so many people who are in psychiatric crisis, whether it's mania or psychosis or quote unquote, nervous breakdown, grief, existential crisis, and on and on. So many people who are in psychiatric crisis can't sleep. And even a lot of very good meds that can be helpful for some of these symptoms don't necessarily help you sleep, but Olanzapine really helpful for sleep. In fact, you could almost, yes, I think you could almost run a psychiatric unit just with Olanzapine. If you gave Olanzapine to everybody that came in the psych unit, I think you would do almost as well as using all the other meds that we give people in a psych unit. So the indications, you know, we think, I think of it as a fire extinguisher. When people's brain is on fire, on fire with mania, horrific insomnia, agitation, Olanzapine can put the fire out. And it does this by blocking the dopamine II receptor, which is implicated in mania and psychosis, and it reestablishes sleep. Again, if sleep is the best mood stabilizer, if we're giving people meds that don't promote sleep, then we're probably going against what people's brains most need, a clinical pearl. If Olanzapine is helpful, the next med on this list is probably going to be even better. And that's because number nine on this list, clozapine, clozapine came first. So it was developed back in the 70s and 80s. And even back then they knew it was an amazing med for mania and psychosis and even treatment resistant depression. But it had a couple scary side effects. It could affect the bone marrow and thus impede the immune system by dialing down a white blood cell called neutrophils. It could cause seizures, it could cause different cardiac problems. So clever scientists back in the 80s thought if we could just tweak the clozapine molecule, maybe we could come up with something that's better than clozapine, but doesn't have this bone marrow risk or seizure risk. And so with a very small tweak of a huge complicated molecule that came up with Olanzapine number seven on the list. And as I said, well, while Olanzapine is a great med, it's not as powerful as clozapine. So they did successfully get rid of the seizure risk and the bone marrow issue, but they dialed down some of the efficacy. So one way you might think of Olanzapine and clozapine on this list is that Olanzapine is a good place to start with mania and psychosis and agitation. But if it's not enough, you can step up to clozapine, which is sort of the big gun. It's the best sleep med on the planet. It's the best antipsychotic on the planet. It's the best mood stabilizer and probably even the best antidepressant. So whether it's for treatment resistant schizophrenia, schizoaffective disorder, bipolar disorder, if you want to pull in the number one most effective med. And again, there are some issues with it. It needs careful monitoring, weekly blood draws for the first six months. It is one of the three or four treatments in psychiatry that can be completely life altering, life changing. The most common side effects with clozapine sedation, as I said, it's the world's best sleep med. It can lower your blood pressure such that you can have what's called orthostasis where if you stand up too quickly, you can get light headed. And it definitely sadly, like a lot of psych meds, it can be a weight gainer and push people towards diabetes. So in my practice, most everybody on clozapine takes metformin. And I'm guessing and this is a clinical pearl, I think, you know, soon when the GLP one agonist like semi-glutide, when those are more accessible, I think our folks on Olanzapine and clozapine and other weight gainer meds will be able to give them those, get the full benefit of the psych med, but then have them on something that can counteract what's really the dreaded most serious long-term side effects of these kind of meds. Okay, number 10 on the list is a stimulant. And much like the benzo, I thought I'd really like to make a list of 10 meds that doesn't have any real addictive meds on it. But we really need a benzo for when the brain's on fire. And I would argue, you know, there is a significant percentage of people who come in our doors as psychiatrists that they need a stimulant. I mean, it's also game changing in terms of helping them function and do their lives. But I do think the choice of stimulant is crucial. So let me back up a minute. When people ask for a stimulant, what are they asking for? They ask for Adderall, they might ask for Dexogen, they ask for Vivants, basically they ask for one of the amphetamine based stimulants. So there's two kinds of stimulants, there's amphetamine based and methylphenidate based. Nobody comes in asking for methylphenidate based. And it's interesting, they are roughly equally effective in most people, the methylphenidate meds and amphetamine meds. But people ask for the amphetamine ones because they feel better, they have more euphoria, they tend to crank up libido, they give you a lot more energy, they're way more abusable. You can sell them for a dollar to $2 a milligram to your friends. You can party on them in a way that you really can't with methylphenidate to the same degree. So, you know, we learn in med school, listen to your patients, try to meet your patients where they are. But I think this is a place where actually, maybe we don't want to meet the patients where they are. Because again, like back to the benzo question, what benzo do people ask for? They want Xanax, they want Alprazolam. Why? Because bam, it hits the brain fast, crosses the blood brain barrier, feels good. It's an elephant gun to the face, if that's your thing. And similarly, when people ask for a stimulant, they want Adderall. But again, because most people, not everyone, but most people respond pretty well to both, I would argue we should always start with methylphenidate and not just methylphenidate, but extended release methylphenidate because that way you don't need to take it multiple times a day. It will come in a time release formulation, so people are less likely to snort it or shoot it. And it's just much safer. And so the indications for a stimulant such as methylphenidate would be things like ADD, ADHD, perhaps sedation from clozapine. I have some of my clozapine patients on a little bit of methylphenidate in the morning, body dysmorphic disorder, possibly geriatric depression. It can be useful in sleep disorders at times. And as I describe it to patients, what we're looking for with methylphenidate is that they can focus, they can stay on track, they can think and plan and prioritize better, not that they're going to feel better or feel more energized or be more motivated or have a better mood. Because a lot of times people come back with Adderall and they'll say, "Well, I tried the methylphenidate, but I like the Adderall better." And to me, that's always a time to ask more, "What do you mean like?" And almost invariably, it's not that they're liking that their executive functioning of their brain is better, or that they're prioritizing more easily or their cognitive speed is improved. No, they mean that they feel better, they feel juiced on the Adderall. So conclusion, when you think stimulant, at least start with methylphenidate extended release. Again, some people might respond better to Vivants or Adderall, but for your patients, short and long-term safety, I think that's a better place to start. Okay, so there's my top 10. I'm going to be super parsimonious, and I'm going to have a new set of desert island meds. So for people who didn't hear that episode, I said, I think it's back in season one or two. If I were a psychiatrist on a desert island and I could only have three meds to treat people, what would I want? At that point, I said, lexaprolemictal and lithium. But now, with a little more thought and a bunch more podcast episodes, my desert island meds would be clozapine. Because clozapine, you can even slice up a teeny bit of it and treat terrible sleep problems, because it's so anticholinergic, you can treat diarrhea with it, you can treat mania and agitation and psychosis, and you can treat severe depression. The second one after clozapine would be ketamine, because anybody with depressive syndromes or trauma syndromes would be possibly a decent candidate for ketamine. And then, of course, limotrigine has to be in there, because that encompasses this whole bucket of people with very endogenous early onset, hard to treat bipolar spectrum depression. And there we go. So if you sail out to a desert island and you see me sitting there like Lucy with my clozapine ketamine, limotrigine, you'll know that you've reached Craig's Desert Island, if you do. Stop by, say hi. Love to chat. (soft music)