we now come to the mood stabilizers which if you're anything like me will be among the most confusing classes of drugs you will ever study this is because they either have unknown mechanisms of action like lithium or work in multiple areas of the body and thus have unpredictable side effects like the anti-convulsants nevertheless we will venture forward and I will try my best to break it down for you in an easy to understand form just as a quick reminder you can use the pneumonic Dig Fast to remember the symptom of mania having at least three of these qualifies the patient for Mania per DSM standards like major depression the time period is important diagnostically while having two blue weeks is the criteria for major depression in Mania the time period is less in this case one fun week equals a manic episode like psychosis bipolar disorder should be treated by psychiatrist this is largely due to the fact that many of the treatments of bipolar such as lithium require close monitoring as we will discuss soon while this is a review of psychopharmacology not diagnostic this concept is important enough for a quick tangent both medical students and clinicians can have difficulty distinguishing bipolar and borderline as there are many features such as depression hyperactivity impulsivity suicidality and occasional psychotic symptoms that are shared between the two nevertheless learning to differentiate the two diagnoses is of crucial importance why because the treatments for the two are completely different for by polar the main stiff treatment remains pharmacology although therapy may help for borderline however no drugs have shown to be effective at treating the core features of the disorder although some drugs may be used to Target specific symptoms instead a form of therapy known as DBT or dialectic behavioral therapy has been shown to be effective so if you misdiagnose a patient with bipolar or borderline you could waste years trying to help using the wrong treatments so how can we distinguish between the two there are a few core features that are helpful first in bipolar patients changes and mood tend to happen over weeks and months whereas borderline patients can switch between their highs and lows in seconds second second in bipolar disorder episodes tend to occur independently of Life events whereas the mood of patients with borderline disorder is often highly dependent on life events especially interpersonal relationships finally the frequency of the disorders is different with true bipolar being much more rare as low as 1% of the population whereas borderline is up to 10 times more common use these key features to distinguish between the two diagnoses okay now back to the pharmacology of treating bipolar disorders one complicated aspect of treatment is that the management varies depending on what phase of the illness the patient is in chronic management is more straightforward as it always involves mood stabilizers in the acute phase however mood stablers don't work fast enough for management of a manic episode so antis psychotics are often started to bridge the time before mood stabilizers begin working usually about 10 days this is a high yield point and will show up on exams and in the emergency room one might wonder why anti-depressants are not prescribed as part of the picture especially if a patient is in an acute depressive episode this is another high yield point anti-depressants when given to bipolar patients are not only ineffective at treating their depression but they are now thought to induce a shift into manic episodes and create what is called a Rapid Cycling type of bipolar for this reason anti-depressants are to be avoided in patients with known bipolar disorder the first drug we will cover is the oldest mood stabilizer known lithium originally used in 1800s to treat gout lithium was soon noted to have effects on mood and was even incorporated into the soft drink Seven up for a Time much like cocaine used to be an ingredient in Coca-Cola it wasn't until 1949 when it was clearly demonstrated to be a mood stabilizer however that lithium began to be used by the medical community at large for the treatment of bipolar disorder despite various theories the exact mechanism of lithium remains unknown lithium is one of the best studied drugs in terms of Effectiveness for preventing suicide incurrent numbers indicate about a Sevenfold decrease in the risk of suicide for bipolar patients on a therapeutic level of the drug you can see in this graph how the rate of suicide decreases in a way that is directly proportional to lithium drug levels interestingly the anti-suicide effect is independent of its effects on mood there's only one other drug that has been shown to have this much efficacy at preventing suicide can you guess what that is the answer is clopine for patients with schizophrenia so if lithium is so great why is it in the drinking water or at least in the seven up still the problem with lithium is that it pays for its incredible Effectiveness with a harsh side effect profile including a not insignificant risk of death lithium has one of the lowest therapeutic index is known to man meaning that the dose necessary for therapy is uncomfortably close to the dose that will hurt or kill the patient generally the target dose for lithium is 1 to 1.2 which I remember using the neonic lithi 1 the side effects of lithium are varied and widespread but can thankfully be grouped together using the neonic L MN o p l for lithium n for movement or Tremors n for nephrotoxicity o for hypothyroidism and P for pregnancy problems we'll go over each of these one by one as a side effect of lithium intoxication Tremor is incredibly high yield while not specific a Tremor in the context of a patient taking Lithium very likely means that their dose is too high which can show up on Boards N is for nephrotoxicity there's a classic clinical vignette that you are almost guaranteed to encounter on tests and Boards involving an older gentleman who is out mowing the lawn on a hot day moments later he is found passed out in the sun the question generally will ask what medication is he most likely taking since we're in the section about lithium the answer is fairly obvious but let's ask why this relates to the side effect of nephrotoxicity lithium is excreted almost entirely by the kidneys but it is also damaging to the kidneys when concentrated with a 5% rate of renal insufficiency in chronically treated patients in situations where a person gets dehydrated the lithium can concentrate in the tubules and cause significant damage this is especially problematic as lithium can cause nephrogenic diabetes and citus further accelerating the process of dehydration lithium use is also associated with a six-fold increase in the likelihood of developing hypothyroidism which paradoxically can induce mood symptoms which can easily be mistaken for depression the final major side effect of lithium is that it causes major problems to the fetus during the first five weeks of pregnancy most famously fetuses have about a 10 times higher chance of developing Epstein's anomaly which is a congenital cardiac defect involving low implantation of the tricuspid valve you can remember this by packing it into the first three letters of lithium lit t for low implanted tricuspid you may have noticed that all these slides that a high yield box on them hopefully you're getting the idea that lithium side effects are important to know so where does that leave us on lithium basically we have a drug that is one of the few in all of psychopharmacology proven to help prevent suicide which is one of the worst possible outcomes of mental illness it also comes with no small amount of side effects so lithium must be used very responsibly there is a set list of labs that should be drawn on every patient starting lithium and if you know the major side effects they should all be no-brainers take a moment to review them and connect each one to the LMN o pneumonic the next several mood stabilizers that we will cover are all anti-convulsants meaning that they are also used frequently in the treatment of seizur disorders the first valproic acid goes by several names b pro8 vpa d proex depote depine Etc valproic acid Works by at least two mechanisms first it inhibits voltage gated sodium channels which accounts for its anti-convulsant properties however it also works by increasing the amount of Gaba throwing in a bit of a benzo dipine like sedative effect there are two primary considerations you have to make before starting a patient on valproic acid and both are high yield in terms of testable knowledge first boric acid is contraindicated in pregnancy as it is a known teratogen often causing neural tube disorders such as spinabifida you can remember this with the rhyming phrase Val pro at the folate folate deficiency as you recall is itself associated with neural tube defects so you can imagine Val proe eating up all the folate that a mother ingests leaving none for the Fus and causing neural tube defects another dreaded but thankfully rare side effect of Valic acid is hepatic necrosis valporic acid is one of three drugs that can cause this that you'll be expected to know the others being halothane and acetaminophen all of these are important so to help you remember them close your eyes and imagine a butler telling you to have a seat at the dinner table you look at your plate and realize with disgust that liver is being served for dinner so now you have related liver to the phrase have a seat into which is packed the three drugs causing liver necrosis hyane valproic acid and acet aminofen there are other complications of alic acid use including a risk of Trigon ay as well as protein binding interactions with aspirin and warin but those are beyond the scope of this lecture carbamazapine or tegral is another anti-convulsant that is approved for use and bipolar disorder and like valporic acid it acts primarily by inhibiting voltage gated sodium channels and augmenting gabit transmission clinically the three main uses of carbon mapine are trigeminal neuralgia mood stabilization and bipolar disorder and epilepsy carbamazapine is sometimes abbreviated cbz and we can pack its three uses into that acronym C for cranial nerve to remind us that it helps in controlling trigeminal neuralgia B for bipolar disorder and Z for zures while effective for those three conditions it must be noted that carbon mopine like clopine carries a risk of a granulocytosis the risk of mortality is not quite as great as for clopine so use of this drug isn't restricted by a registry in the same way that clopine is but it's something to be aware of and to counsel patients on before starting the drug loten brand named laml is another anti-convulsant mood stabilizer loten is chemically unrelated to the other anti-convulsants and while it does inhibit sodium channels it does not act at The Gabby receptor like other anti compulsin what does this mean clinically it means that Lam motogen is better suited to helping bipolar disorder in a patient presenting with a depressive episode unlike the other anti-convulsants where the Gaba helps to calm patients in the manic phase of the illness not something you're likely to be tested on but helpful for understanding gaba's role in managing Mania a frequently frequently frequently tested point about lamot gen is that one of its most common side effects is a widespread itchy rash occurring in about 5 to 10% of patients this is quite common so patient should be counsel about what to do if they notice any skin changes more seriously these reses can sometimes progress to stev's Johnson syndrome a horrifying dermatologic disease where the epidor literally SS off of the dermis if a patient has signs of mucous membrane involvement you must consider Steven's Johnson syndrome in the differential luckily only about one in a thousand patients will develop this but because of its severity you must know the side effect you can remember the association between skin disorders and LOL by using the pneumonic lit tall finally we'll go over three anti-com olss that are not in fact mood stabilizers so why are Rec covering them because despite a lack of documented efficacy you are likely to see them being used as mood stabilizers on Wards although hopefully not on boards in addition each has some high yield side effects that you will see on boards mostly for neurology so they're worth going over for General Medical knowledge the first of these drugs is oxcarbazepine or tripol which is a close relative of carbon mapine unlike carbamazapine however it has not been demonstrated to reduce mood cycling and bipolar disorder on the plus side oxyc caropine does not carry a risk of a granular cytosis either that's about all you need to know about this drug just be aware that you'll probably see it on Wards and in neurology clinics toymate or Topamax is another anti-convulsant that you will see being used clinically for mood stabilization but similarly to oxcarbazepine it is not FDA approved for this purpose there are several features of the drug that make it particularly appealing for patients however most significant is the weight loss which occurs in more than 10% of patients and can help patients lose anywhere from 5 to 15 pounds this quote side effect is popular among patients yet it must be counterbalanced by the fact that many patients report feelings of mental dulling and in particular word finding difficulty in addition to a greater risk of kidney stones and metabolic acidosis these cognitive effects have earned Topamax the lesson endearing nickname of dopamax I like to think of Topamax as your classic Miss America who likely lost a lot of weight but paid for a bit in the mental compartment this video illustrates the concept of word finding difficulty quite nicely okay recent polls have shown a fifth of Americans can't locate the US on a world map why do you think this is I personally believe that us Americans are unable to do so because uh some people out there in our nation don't have maps and I I believe that our education like such as in South Africa and the Iraq everywhere like such as and I believe that they should our education over here in the US should help the us or should help South Africa and should help the Iraq and the Asian countries so we will be able to build up our future for our children thank you very much South Carolina the final drug that we will cover in this category has also not been approved for treating bipolar disorder as it has yet to produce substantial evidence that it works any better than Placebo nevertheless it is used off label for mood stabilization for a variety of reasons you are more likely to see gabip Penton being used to treat neuropathic pain such as diabetic peripheral neuropathy where it does have more evidence moving on to the next chapter in our psychopharmacology double feuture we will leave the mood stabilizers behind and begin talking about anxiolytics and sedatives which are prescribed for many disorders from general anxiety to panic attacks the pharmacology here is fairly straightforward which would help calm your nerves a bit after having just studied mood stabilizers the majority of anxiolytics increase gaba's effects in some way shape or form so let's take a moment to review Gaba as stated before releasing Gaba often makes the person feel relaxed and sedated physiologically muscles unclench and breathing slows down benzos are all about [Music] relaxing there are two main classes of anxiolytics benzodiazapines and barbiturates they both work on the Gaba receptor but they mechanisms differ somewhat benzo aines increase the frequency at which Gaba channels open while barbituates increase the length of time that the channel stays open you can remember this by thinking of frenzo dapin in barbiturates frenzo for increasing the frequency barbiturate for increased duration not sure how high yield this is clinically but it has shown up on boards before we'll go over the barbituates only very briefly as they have largely fallen out of favor in modern medicine barbit overdoses were directly responsible for The Accidental deaths of Marilyn Monroe Judy Garland and Jimmy Hendrick and their use today in the United States includes physician assisted suicide and Lethal Injections as capital punishment these are not playful drugs and should only be prescribed in the most exceptional cases in contrast the benzo isipin often abbreviated benzos are very commonly used in medicine today compared to barbituates benzos offer a cleaner profile and lower toxicity in overdose they have also proven helpful for the sedating properties and have found uses throughout the medical field from treatment of seizures to relaxing patients before surgical procedure when used on a very short-term basis benzers are some of the most helpful drugs ever discovered yet on a long-term level many problems such as abuse and dependence begin to emerge it's helpful to review the first rule of neurotransmission in the context of benzos as they have some of the most clear-cut states of intoxication and withdrawal all of the sedating and anti-anxiety effects get reversed during the withdrawal phase so cases of rebound anxiety or rebound insomnia are common on these drugs leading to tolerance and sometimes addiction as a quick tip you can recognize the majority of benzo diazines from the syllables a e within the name with almost all ending in aapam one look at this list of benzo diazines should hopefully convince you of that this is an a thing to remember now we will not be covering each benzo opine individually primarily because there are too many of them and they are all fairly similar however there's one clinical distinction to be made between the different BOS and that is in regard to halflife these differences in halflife are clinically significant and account for different indications for each benzo these are the most commonly used medications in each group how to remember which class they belong to we can use the pneumonic short Tom medium cat long divorce unfortunately there is some memorization required so feel free to pause the show if you want to get working on that immediately otherwise feel free to come back later to the list moving away from from benzos there are a few other drugs that are used for anxiety one drug for generalized anxiety disorder that is probably underprescribed is spone or boar it has a complicated neurotransmitter profile which you won't ever be tested on but you'll notice that Gaba is not involved like benzos boost Barone is effective at treating anxiety disorders but in contrast to benzos boost Barone does not cause sedation has no significant withdrawal effects and displays very little addictive potential the serotonin involvement may even make it a better choice for those with coexisting anxiety and depression which is honestly the majority of people with generalized anxiety a large part of the reason why it's not used very often however is because like s eyes the therapeutic effect could take several weeks before kicking in it's something to councel patients on when starting especially if they had taken benzas before and are used to the immediate relief that they can bring a pneumonic to remember the use of boost brone is to think of someone who's always anxious about if they will mess the bus this anxiety about missing the bus can be managed with bus spon now we'll move on to sedatives which are drugs use to help with falling asleep the first one tamasam brand named ril comes from the drug class we just finished studying while all benzos are sedating and can help people get to sleep tamaza Pam is used more frequently for sleep than anxiety and is earned its fair share of nicknames such as Vitamin T tamies Mommy's big helper Etc just remember that tzip Pam is often used for sleep if it helps you can think of someone having a cup of tea before bedtime the next two drugs come from another class the antihistamines which as we discussed in the first lecture have profound sedating properties unlike the other sleeping aids they also available over the counter something to caution patients on however is that antihistamines actually mess with your sleep cycle so while they're helpful for getting to sleep they do not actually provide a good quality of sleep antihistamines are also prone to tolerance and after about 3 days of continued use they perform no better than placebos for Sleep induction nevertheless their low side effect profile and ease of accessibility make them a good inexpensive option for most patients damine brand named Unison has been shown to be the single best antihistamine for treating insomnia another option is Dien hydramine brand named badril while not quite as good as damine at inducing sleep Dien hydramine is a close second and has been used for years as an over-the-counter sleep aid to sedate children and pets before long international flights one popular prescription option for insomnia is zadam brand named Ambien this drug belongs to a class n as non- benzo aine hypnotics which modulate the Gaba receptor but in a way distinct from what benzo aines do to remind me of its function I like to focus on The Zo Part of zadam and think zombie because you look and act like zombie if you don't get enough Z's some common side effects of zadam are interogate Amnesia meaning that you forget everything that happens in the hours after you take zulm as well as some nalism or sleepwalking there are reports of patients taking zulm and then walking around their house making a sandwich or even driving places and media awareness of this has made it common knowledge among patients this unique property has even resulted in the creation of a comic character known as ambient walrus seen above and in the next slide needless to say zulum can have some strange side effects another non- benzoin hypnotic is called asopa clone or Lunesta it's basically just a clone of Zaden you don't need to know too much about it except that it is used for sleep and is preferred over benzo's appearance for this purpose and that's it for those two lectures it's time for another break