now that we have finished our discussion of neurotransmitters let's move on to each of the major drug classes the first class we will cover are the antidepressants both because they are among the most widely prescribed class of drugs in all of medicine and because the neurotransmitter profiles are fairly well worked out at this point just as a quick reminder you can use the mnemonic siggy caps to remember the symptoms of depression having at least five of these qualifies the patient for major depressive disorder per DSM standards one thing that students often get tripped up on
on tests is exactly how long the siggy cap symptoms have to occur before they are considered a true major depressive episode I use the mnemonic to blue weeks to remember it the first class of antidepressants we'll cover are known as serotonin specific reuptake inhibitors or SSRIs these work by inhibiting the transporter on the presynaptic neurons that takes serotonin and back up into the cell effectively increasing the amount of serotonin active and available in the synaptic cleft let's quickly review serotonin functions using our head read and Fed mnemonic head refers to the psychological effects including feelings
of satisfaction and decreased impulsivity however this is coupled with a decreased sex drive which can be problematic and indeed is actually the number one reason why people stop taking SSRIs red refers to serotonins effects on platelets remember that SSRIs can occasionally cause prolonged bleeding finally fed refers to the gif X which are prominent side effects who have SSRIs and represent another common reason why people stop taking them one thing the council patients on is how long SSRIs can take to work in multiple studies it has been shown that maximum treatment efficacy is often not reached
until four to six weeks patients can sometimes feel like discontinuing the drug on their own as the side effects like diarrhea or restlessness are immediate while the desired effects can take weeks fluoxetine or prozac was the first and most immediately successful of the SSRIs to be released in the late 1980s prozac is the brand name for fluoxetine and when you can use the information to help us remember some clinically important information about it fluoxetine has one of the longest half-lives of any SSRI why is this important because fluoxetine as well as its metabolite nor fluoxetine
stay in the bloodstream longer it works better for people who aren't great at remembering to take medications regularly however on the other hand because it lingers in the system so long you have to be careful not to switch to another serotonergic drug too fast as the levels can get high and cause serotonin syndrome by focusing on the flu part of fluoxetine it will help us to remember that fluoxetine like the flu generally lasts about one week so when you see fluoxetine think of the flu and the week that he had to spend in bed that
one year that you got it the next drug a popular choice is sertraline or Zoloft the mechanism of this drug is easy to remember as the ser of serotonin is built right into the name saralyn I had a hard time remembering to pair sertraline with zoloft until I started pronouncing it zero trillion in my mind is air trilling zoloft sertraline has harsher GI side effects such as nausea and diarrhea than other SSRIs which has earned at the endearing nickname of squirt Raeleen tell your patients to take it with the meal to help absorption and to
decrease these side effects in addition sertraline is also one of the safer SSRIs for pregnant or breastfeeding women as less of the drug gets into the breast milk so if you use your imagination a little bit the mnemonic squirt Raeleen should work here to paroxetine or paxil is another SSRI and this one is unique in that it is very rapidly absorbed this can result in worse side effects when a patient first begins the drug as a higher amount of the drug gets into the bloodstream in a shorter amount of time it's something to counsel patients
about when you start them on paroxetine to expect some initial side effects before the actual clinical improvement is noticeable also if they are to suddenly stop taking the drug the withdrawal will happen much faster and result in a bad and uncomfortable withdrawal state how to remember this important fact I like to focus on the pair ox part of paroxetine if you played Oregon Trail you'll remember that you moved much faster with a pair of ox and with a single ox one side effect of paroxetine rapid absorption is that it can produce withdrawal symptoms not only
in patients but also in babies born to patients taking paroxetine when they're suddenly withdrawn from the drug when they were born this can at times even result in seizures so be careful about putting someone on haier occitane if they are pregnant the next two SSRIs are basically siblings first we have citalopram or brand-name celexa this drug is generally considered to be a middle-of-the-road SSRI and is considered by some psychiatrists to be an excellent first-line agent due to its overall high tolerability its main benefit is that it is fairly clean in terms of enzyme interactions however
there's some concern about its effect on the QTc interval so at higher doses over 40 milligrams per day for adults and over 20 for the elderly it's a good idea to get yearly EKGs on these patients how to remember this I like to rename this as Alexis to remind me of the car why a car well a car should hopefully remind us to get an electrocardiogram on these patients I even threw in a picture of Alexis electric car s citalopram or lexapro is basically the awesome younger sibling of Celexa it's the S enantiomer of Celexa
which is the pharmacologically active form so a 10 milligram dose of Estela pram is about equivalent to a 20 milligram dose of citalopram even more so than citalopram s citalopram is the cleanest SSRI in terms of enzyme interactions the next SSRI is fluvoxamine otherwise known as luvox fluvoxamine is actually a fairly old antidepressant but in the u.s. it has only been approved for obsessive-compulsive disorder I try to remember the association of fluvoxamine with OCD by pronouncing it luboc with an O C or in the generic form fluvoxamine with o c standing for obsessive-compulsive a quick
note fluvoxamine is not the only SSRI that is helpful for OCD in fact nearly any of the SSRIs seems to have beneficial effects in treating obsessive-compulsive disorder fluvoxamine is just unique in that it is FDA approved for OCD rather than major depression although in all honesty this is not a high-yield fact while serotonin is definitely implicated in the treatment of depression it is not the only neurotransmitter at our disposal each of the mono amines plays a unique role in depression as you recall from our earlier slides serotonin is involved in feelings of satisfaction and anxiety
nor pandaren on the other hand brings increased energy and focus both of which are lost in depression as well each neurotransmitter seems to regulate different parts of the effects of depression how does this work out in clinical practice let's see one drug that boosts both serotonin and norepinephrine is venlafaxine brand-name effexor this is a real take inhibitor for both serotonin and norepinephrine how can I remember this unique mechanism I like to focus on the end sound of been Levac seen to remind me of norepinephrine so how does the norepinephrine impact treatment depending on how the
patient presents you might want to consider venlafaxine over a simple SSRI if your patient's primary symptoms are lack of energy decreased interest and impaired concentration Wendla Faxon may be a preferred choice however with the addition of a new neurotransmitter comes new side-effects one prominent effect of been la vaccine that is not seen in pure SSRIs is hypertension patients started on venlafaxine have about a 50 to 100 percent higher risk of developing hypertension which is likely due to norepinephrine effects on the peripheral vascular system however the vascular effects tend to be short-lived so it's not a
reason not to put someone on it unless if they have a history of hypertension another drug in this class of serotonin and norepinephrine reuptake inhibitors is duloxetine brand-name cymbalta how to remember this dual mechanism focus on the dual part of the duloxetine name that should help remind you of the dual mechanisms that play with dual oxygen in addition to depression treatment duloxetine is often used to help people with chronic pain conditions as it seems to mitigate pain sensation to some degree you can remember this by thinking duh L'Occitane in addition to duloxetine Dolph or dulls
the pain duloxetine another drug that works on both sir tonin and norepinephrine is mirtazapine brand-name Remeron the mechanism here is a little bit different and we won't get into it too much but basically mirtazapine inhibits an intemperate Ori input to the sympathetic nervous system effectively enhancing sympathetic output and counteracting some symptoms of depression from a clinical standpoint you'll run into mirtazapine in nursing homes and cancer clinics why because it seems to have strong effects at increasing appetite which can help guard against the cachexia seen in patients with cancer HIV or simply advanced age I remember
this with the mnemonic meal tazza peen because meal tazza pain makes you want to eat a meal also helpful for these patients mirtazapine tends to decrease nausea in contrast to the standard SSRIs if adding norepinephrine into the mix works then why not try increasing dopamine as well if you'll recall from our dopamine mnemonic drive and attention are crucial functions of dopamine that are lost in depression out of this thought came a drug called boo Pro prion brand-name wellbutrin unlike the antidepressants we've studied so far the appropriate doesn't have significant serotonergic effects instead it works as
magic primarily through dopamine and norepinephrine you can remember this mechanism by focusing on the view part of bupropion and associated with the word butane the word butane should help you link view to DEA and any which stands for dopamine in norepinephrine butane can also help us remember some of the features of Rico beyond the fire from a butane lighter is used to light birthday candles which makes people feel warm and happy you can also think of fire as being hot and steamy to remind yourself that boo pro pion does not have significant sexual side-effects and
finally you can think of using a butane lighter to light a cigarette as bupropion is indicated to help patients stop smoking all this information all packed into a single syllable view that will help you think of a butane and fire so what's the downside to all of this happy feeling sex-crazed cigarette quitting excitement bupropion by virtue of its excitatory properties has a propensity to lower the seizure threshold this is particularly noteworthy when working with patients with bulimia who engage in frequent vomiting as this can cause electrolyte imbalances that help further raise the risk of seizure
for that reason treating a bulimic patient for depression using brute proprio is strongly contraindicated the next drug we will discuss trazadone brand named Ezzor L is unique in several regards first in addition to an antidepressant it is commonly used as a sleeping aid interestingly its effects on sleep work best in patients with depression so it's not exactly an all-purpose sleeping pill even though it's sometimes treated as such secondly its mechanism of action is a bit weird it's both a serotonin antagonist as well as a rehab take inhibitor the mechanism isn't important so don't lose too
much sleep about it one unique feature about trazodone is one of its side effects or an erection lasting several hours this is a medical emergency as blood flow to the engorged organ gets compromised after a while so it's worth counseling your patients about what to do should they experience the side-effect I stole this mnemonic from first aid but you can remember this by thinking trouser bone trazodone trouser bone now we come to the oldest class of antidepressants and some of the first drugs to be officially prescribed for that purpose the tricyclics antidepressants often abbreviated TCA
as you can see tricyclics have incredibly complex binding profiles inhibiting the reuptake of serotonin and norepinephrine while antagonizing acetylcholine and histamine and at the same time inhibiting sodium and calcium ion channels whenever I think about the complexity of tcas I am reminded of a third rule of neurotransmission with great power comes great responsibility the more things you mess with in the brain the higher chances of having an effect but also the higher chance of causing serious side effects despite their age TCAs remains some of the most effective antidepressants but they come with a side effect
profile to match by going through each of the neurotransmitters one by one we can look at the pros and cons of using TCAs as you can guess serotonin and norepinephrine are primarily responsible for the antidepressant actions or tcas the TCS are a very powerful group of antidepressants and are often reserved for treatment-resistant depression which has failed multiple trials of less invasive antidepressant classes such as SSRIs acetylcholine and histamine on the other hand account for more of the TCA side effects by inhibiting acetylcholine you get several prominent antimuscarinic side effects including dry mouth eg eyes blurry
vision constipation urinary retention memory impairment and increased body temperature antagonism of histamine does result in some exogenous sedation and sleepiness while using PCAs finally TCS are now known to work as sodium and calcium channel inhibitors as well this is clinically important and that you could observe some mood stabilization effects however much more likely to be tested on boards is the fact that taking tcas and overdose can cause significant heart and nerve conduction abnormalities due to its effect on ion channels TCA is a notoriously toxic and overdose with a therapeutic index of about seven taking just
seven times the normal amount of the drug could cause death on boards and you should pay close attention to this a widened QRS complex in the context of a suspected overdose is pathognomonic for TCA overdose this is very high yield and not that I'm going to repeat it one more time a widened QRS complex in the context of a suspected overdose is pathognomonic for TCA overdose also high yield is the treatment for TCA overdose sodium bicarbonate how I remember this is to think about a car running over a tricycle it's no contest the car is
going to win every time so from this you can picture a bicarbonate running over a tri cyclic and beating it handily a bicarbonate wins over a tricycle every time putting all of this complexity together is a daunting task but let's see if we can simplify it TCAs act as an agonist at two neurotransmitters an antagonist at another - and an inhibitor of two different ion channels what helps me to remember this is the rhyme trans Chan's and Anne's which conveniently spells out TCA the S at the end of each word indicates the plural or the
fact that there's two transmitters being boosted two channels infected and to antagonize neurotransmitters trans trans and ands quick review question in order to avoid serotonin syndrome you need to have a washout period of usually around two weeks before switching from an SSRI to a tricyclic one necessary has an even longer washout period at five weeks which SSRI is this if you thoughtful Aqsa teen then you would be right fluoxetine with its long half-life requires a longer period of time before starting TCAs to avoid serotonin syndrome this can show up on tests too so make sure
to memorize this now we move on to the first of the tricyclics to be discovered which also happens to be the first antidepressant ever developed imipramine is a prototypical tri cyclic so everything we've talked about thus far applies one thing that sets a member mean apart is that it is sometimes used for management of nocturnal enuresis or bedwetting and children can you guess which neurotransmitter is responsible for its efficacy at helping children hold their bladders if you guessed acetylcholine you be right the anticholinergic effect of imipramine prevents the bladder from contracting thus holding the urine
i remember this by pronouncing amit bromine as I'm peeing Ramin this should help remind you of bedwetting and the fact that I'm peeing Ramin is used for this purpose because of its side-effects it is not to be used as a first-line agent but can be useful in refractory cases another TCA with a specific indication is Clemmie / mean like fluvoxamine clomipramine is only FDA approved for the treatment of OCD in fact clomipramine has been shown in a couple of randomized control trials to be the gold standard for medication treatment of OCD and it was found
to be the most effective option over fluvoxamine and fluoxetine however again due to the high side effect profile of tcas a standard SSRI is probably a good first line with clomipramine being reserved for more severe refractory cases - other commonly prescribed TCAs are amitriptyline and nortriptyline these are again prototypical TCAs but in addition to depression you will also see them being prescribed for people dealing with chronic pain issues such as diabetic peripheral neuropathy chronic low back pain or pelvic pain there are some subtle differences between amitriptyline and nortriptyline but they are beyond the scope of
this lecture we now move on to the third class of antidepressants the monoamine oxidase inhibitors or mao is perhaps to an even greater extent than the tricyclics mao eyes and body the third rule of neuro transition with great power comes great responsibility because they modulate not one not two but three separate mono amines mao eyes are among the most effective of all antidepressants especially in the subtype of depression known as atypical depression however they also have some very severe side effects because of this because of these side effects mao eyes are seen as a last
resort of sorts although with the increased use of ECT in recent years ma eyes have not been used very often because of their rarity we will spend only a few minutes considering them one frequently frequently frequently tested fact about ma eyes is that they are associated with what is known as a hypertensive crisis basically when a patient is on an MAOI and eats food containing tyramine such as aged wine and cheeses the catecholamines can build up to an extent where all the blood vessels constrict leading to incredibly high in dangerous blood pressures how to remember
this clinically significant interaction I like to think about being on Maui the Hawaiian island on a date with Miss Tyra Banks enjoying some fine wines and equally fine cheese's have you formed that mental image yet being on Maui should remind us of Amaya is the drug class Tyra Banks remind us of tyramine the specific molecule that causes the hypertensive crisis in the fine aged wines and cheeses we are enjoying should bring to mind the foods that classically causes interaction there are only two ma eyes that you'll need to remember Selene and phenelzine both are irreversible
inhibitors of monoamine oxidase meaning that the effect lasts until new enzymes can be synthesized what is different between the two is that Sledge alene is selective for the B subtype of ma Li whereas phenelzine is non selective and hits both mao-a and Mao B it's a little confusing but you can remember this using the mnemonics select a lien to remember that Selene is more selective so what's the difference between Mao a and Mao B Mao a degrades all three mono means serotonin norepinephrine and dopamine as well as tyramine as we just discussed whereas Mao B
degrades only dopamine therefore phenelzine which hits both Mao a and Mao B is preferable for the treatment of depression whereas allegedly in which hits only Mao B would be preferable for something like Parkinson's which only involves dopamine as a final slide here's a quick high yield review of the major concepts and mnemonics we have covered in this lecture make sure you know and understand the meaning behind each of these or if not you can rewind and review any relevant parts one last note after going through this presentation hopefully you feel like you have a better
grasp on the psychopharmacology of depressive disorders however it's crucial to recognize when you can apply these principles on your own versus when a patient requires a higher level of care you can remember the criteria for referring out to a psychiatrist using the mnemonic psych md p is for psychosis S is for suicidality Y is for why isn't this working and refers to when a patient has failed multiple attempts at treatment c is for comorbid psychiatric disorders including substance abuse h refers to the highs and lows of bipolar disorder an MD is for monitoring drugs such
as when a patient is on a drug like lithium that requires close to follow-up if the patient meets any of these criteria consider referring out to a psych MD okay that's it for the antidepressants let's take a break
