Nortriptyline

hello dr. ken manda thanks for watching let's talk about Pamela or nortriptyline now this is a tricyclic antidepressant was patented 1962 introduced for the treatment of depression in 1963 Food and Drug Administration approved it in 1964 it's considered a first generation antidepressant it's a relative of amitriptyline and as a matter of fact and the trip Deline that you take is metabolized in the body to nortriptyline going back to the 1950s 1980s we didn't have much in the way of treatment for depression we had the mao inhibitors and the tricyclics antidepressants drugs like nortriptyline but those were largely replaced in the 1980s and 1990s by the SSRIs and SNRIs well in the tricyclics antidepressant family we have drugs that are in common use still we have nortriptyline familar we have a mat rip de lien or elavil imipramine or taut for nill we have an Afrin ill or commit Ramin we also have luteum mil now the drugs are principally prescribed for depression that's what they're indicated for depression while all depression seems to respond to the drugs they seem to work a little bit better in more endogenous depression or we call a melancholic depression these are people who have the depression and markedly diminished interest or pleasure they're slow and flat in the morning they show little emotional expression they sleep badly wake early they have difficult time concentrating they often think about suicide but the drugs are also used to treat ADHD the attention deficit hyperactivity disorder the other drugs that we have available for ADHD are stimulants what nortriptyline might be specially helpful in people who have anxiety and depression related to the ADH remember psychiatric diseases seem to go in pairs or triplets or quadruplets also helpful if you're taking stimulant and it interferes with sleep seems to be more effective in people who have the hyperactivity of the impulsivity than people who have problem with the tension but they're not approved for a pediatric age group drugs are also used off-label for treatment of anxiety and panic and obsessive-compulsive disorder and social anxiety disorders sometimes they're used for PTSD or chronic pain neuropathic pain fibromyalgia they're used to help people stop cigarette smoking used for irritable bowel syndrome and for prevention not the treatment but for the prevention of migraine headaches they're used for Tourette's syndrome or people who pull their hair out a condition of a strike OTO mania women who suffer from interstitial cystitis irritable bladder syndrome people with narcolepsy or a pathologic laughing and crying condition people have chronic hiccups or anorexia nervosa or temporomandibular joint syndrome and in the United Kingdom in England it's used for a period of up to three months for nocturnal bedwetting can be used for insomnia seems to improve sleep in some individuals but in the short term it might disturb the sleep as far as neuropathic pain is concerned now we're talking about neuropathic pain not the typical pain that you get because of damaged tissue like when you bang into a drawer you have osteoarthritis that's different kind of thing we're talking about the neuropathic pain that presents a shooting or burning or stabbing pain the pain that you would get in diabetic neuropathy or post herpetic neuropathy after you have the shingles in neuropathic pain some evidence shows that it seems to be valuable at a relatively modest dose anywhere between 50 and 100 milligrams but studies were small sometimes the dose for neuropathic pain is less than the dose for depression seems to be that nor Tripta liens equivalent to gabapentin or amitriptyline evidence-based guidelines the International Association for the study of pain says hey this is a first-line treatment the Cochrane Collaboration in 2015 reviewed all the evidence and said no it's not the Canadian pain Society in 2017 said well if you're going to use a tricyclic antidepressant for neuropathic pain maybe a secondary amine a drug like either nortriptyline or desipramine seems to be better tolerated in terms of sedation and postural hypotension when you stand up sometimes people get a little bit dizzy because of blood pressure Falls it seems to have less anticholinergic effect doesn't dry your mouth as much doesn't interfere with boughs doesn't interfere with the urination as much compared to the drugs like either a myth Ramin or amitriptyline well it's used for migraine headaches now the interesting story about migraine headaches is 50% by some estimates of people with migraine headaches suffer from either anxiety or depression and it seems that for those individuals that might be specially useful to help prevent the headaches even at a low dose and those of anywhere between 10 and 15 milligrams a day but it's not really well studied it seems that if you're taking it to prevent migraine headaches not to treat but to prevent the migraine headaches it might take as much as six months to show full benefit and people taking the drug for six months seem to do better than people who are taking the drug just for one month for migraine prophylaxis actually the tricyclics antidepressants they aim a trip to lean and in order to clean the second most commonly prescribed medicines after topiramate but you have to realize that we now have all these injectable medicines that costs a heck of a lot more but in spite of the drugs like amethy costing a lot more they don't necessarily provide all that much an increase in benefit compared to the old-fashioned medicines the fact of a drug like nortriptyline seems to be that it has an effect against the adrenergic system against norepinephrine more so than the serotonin now if you look at try cyclic antidepressants they seem to block the serotonin they block the norepinephrine they block a heck of a lot more doesn't help with tinnitus the anxiety of Parkinson's disease might be improved in people who are taking the drug might help with the off periods in Parkinson's disease seems to help a little bit in those people who want to discontinue cigarette smoking seem to be twice as effective as a placebo but it's really only a second-line drug and somewhere between about five and ten percent of the people who are taking the drug for help with discontinuing tobacco smoking just discontinued the drug because they don't like it because they have side effects from the drug the effect by the way is not related to the antidepressant effect and the SSRIs don't seem to be effective in this regard at all now it seems that nortriptyline has a stronger effect on the norepinephrine and it's real take inhibition then serotonin on the other hand am a trip Dolan seems to have an equivalent effect if you take the drug you probably have to take drug one time a day or sometimes two or three or even four times a day you could take it either with food or without food you should make major dose if you're gonna divide the doses major dose before you go to bed and if you find that it keeps you awake or keeps you asleep rather the next morning well maybe you take it a little bit earlier in the day well the tricyclic antidepressants are a novel class of drugs they were found when they were searching for a better antipsychotic medicine after the initial success of the drug mep Rosine Claire magazine seemed to work very well so they modified the phenothiazine ring they put a sulfur in there and they discovered first imipramine that was discovered in 1959 but it didn't help for treating schizophrenia treating the psychosis but it did seem that the people who took the drug had mood elevation matter of fact their mood improved by about fifty percent but in the 1950s in the 1960s there were no clinical criteria established for the diagnosis of depression depression was anything that the physician thought it was unfortunately kind of like the situation we're in now well for severely depressed patients it seems that the tricyclics antidepressants might actually work even better than the SSRIs type of that depression we call melancholia the improvement the remission is more in the patients who are taking the tricyclic antidepressants the melancholia sometimes referred to as atypical depression when people eat a lot sleep a lot they have a leaden feeling there are some black boxes associated with the drug caution that the FDA mandates saying that any antidepressant not just the nortriptyline but all the antidepressants might increase suicidal thinking or behavior especially in adolescents or children or young adults so you have to be very careful prescribing the drug might lead to emergence of suicidal ideations especially if the person takes the drug and then experiences periods of anxiety or agitation of panic attacks insomnia or irritability hostility or impulsivity or even mania or hypomania those situations develop then extra caution is necessary well you shouldn't take the drug within 14 days of taking an MAO inhibitor could lead to the serotonin syndrome we'll tell you about that in a moment shouldn't take it with other tricyclic antidepressants again can lead to the serotonin syndrome you don't take it during a heart attack or during recovery from a heart attack and if you have bipolar disorder shouldn't take it now sometimes people with bipolar disorder present with depression by itself and you can't tell the depression it seems to be pretty much the same so you have to take a detailed family history detailed psychiatric history find out if there's suicide in the family if there's bipolar disorder nortriptyline is not approved for people who have depression associated with bipolar disorder close observation if a person has cardiovascular disease especially because it seems that nortriptyline can produce a very fast heart rate in some individuals and change the conduction time so you have to be careful especially if an individual has a rhythm ia's or history of a heart attack or a stroke and it's not necessary that there's a cause-and-effect relationship but there is some sort of an association and you also have to be careful because the drug is an anticholinergic it interferes with the acetylcholine in the body and that's important in those people who have glaucoma or a history of urinary retention and be careful if you have a history of seizures it could lower the threshold for having another seizure and if you're hyper thyroid or on thyroid replacement might lead to cardiac arrhythmias and it can impair your mental and physical ability that might be required for some sort of hazardous activity so you have to be careful when you start taking the drug if you're operating heavy machinery or driving a car you've got to be careful if you take it with alcohol because of an increased risk of either suicide or overdose now we talked about the serotonin syndrome you can get serotonin syndrome just by taking the nortriptyline by itself or in combination with an SSRI that's prozac or celexa or an SNR I the facts or the triptan that you might use for the treatment of migraine headaches other tricyclic antidepressants shouldn't be combined because of the serotonin syndrome or fenton order if you take lithium or tramadol or tryptophane buspirone or st. John's wort err the mao inhibitors what are the symptoms of the serotonin syndrome the symptoms of serotonin syndrome are quite severe mental status changes agitation hallucinations delirium and coma autonomic instability means your heart rate goes way up your blood pressure's labile goes up and down the problem is associated with dizziness sweating and flushing and alters your body temperature causes some neuromuscular changes leads to tremor and rigidity and maia clonise hyperreflexia in coordination and seizures and gastrointestinal changes like nausea and vomiting and diarrhea in people who have schizophrenia can either activate latent schizophrenia or worse than the psychosis if they're having them if you treat an agitated patient or an overactive patient might lead to even worse / activity or anxiety or agitation gotta be careful about the bipolar disorder because it may precipitate attacks of mania side effects are common and they're relatively mild especially when you compare them to aim a trip to lean and if you start off at a relatively low dose of the drug and then slowly build it up you can develop tolerance and they don't seem to have the severe nature that they would have with you started off at a relatively high dose so that drug can cause some dry mouth and constipation and blurred vision might lead to some sleepiness and make lead to blood pressure falling when you stand up or weakness or drowsiness or dizziness or urinary frequency or paradoxically urinary retention can cause some itch it can some impotence or erectile dysfunction or loss of libido but it does that less than the SSRIs can meet hostility might change the blood sugar a little bit either increase or decrease could meet the weight gain especially in older individuals might lead to confusion or disorientation or impaired coordination other people might notice some nausea vomiting or sweating might lead to mania again in those people who have bipolar disorder some people can find that it dilates their pupil which might be a risk factor if a person has angle closure glaucoma and remember we said that it interferes with the metabolism of acetylcholine will that links it to potentially dementia and that might not be reversible even after you stop taking the drug because the acetylcholine is important in learning and memory now it's associated with more severe and more serious side effects like hypertension arrhythmias and heart block and heart attack and stroke and seizures and extrapyramidal syndrome where a person has rigidity has lack of facial movement tardive dyskinesia the bowels stopped working can interfere with manufacture of the granulocytes that you need to fight infection can even lead to hallucinations when you withdraw from the medicine you can have a relatively minor disorientation syndrome with some nausea and vomiting and maybe some loss of appetite and restlessness can lead to some insomnia or even a headache or generalized malaise or dizziness possibly if you're going to have some surgery might be a good idea because of the potential for arrhythmias to see if you can stop the drug couple days before the surgery it has some interactions it interacts with drugs that have the anticholinergic activity or the sim path of memetic activity like if you pop a sudafed can exaggerate the response to alcohol and if you're taking one of those SSRIs and you decide you want to switch to nortriptyline maybe you're taking Prozac or celexa or paxil or Zoloft well you should wait five weeks five weeks until you take nortriptyline so if you also are taking neurotriptyline and taking a drug that blocks the enzyme that's used to metabolize the nortriptyline that could lead to a pretty high concentration of the nortriptyline in your blood system that might lead the problem so yeah got to be careful especially taking the drug like cimetidine or the antidepressants those are the SSRIs or some drugs that you might take for arrhythmias like with malort ambach or their generic equivalents so if you need to combine the drugs better use relatively low dose and if you stop taking one of those other drugs then you have to make adjustments oftentimes in the dose of the nortriptyline so you begin at a relatively low dose to avoid some of the side effects if you happen to be elderly or if you're an adolescent smaller dose use larger dose and in patients when we do a nap patients might have an antidepressant activity especially if we can monitor the blood level so we want to keep the blood level somewhere between 50 and 150 nanograms per milliliters so in people who are taking relatively higher doses we can monitor how much of the drug is in the system and that can give us a good idea you can take the drug once a day or twice a day or several times a day three times four times a day depending on your particular circumstances the tricyclics antidepressant seem to have a relatively narrow therapeutic index so it's easy to get too much and the likelihood of serious overdose accidental or intentional overdose fairly high and they could result in death so you have to be very careful the problem seems to be related to the sodium channel blockage and that leads to this cardio toxicity so if you overdose oftentimes you overdose on a combination of dry well if you have combination of drugs then it gets complicated if you're taking just the nortriptyline and you overdose well the toxicity can develop relatively quickly with a fall in the blood pressure an arrhythmia is not gonna need to shock and cardiac failure pulmonary edema fluid building up in the lungs seizures and central nervous system depression it shows up as a coma some people become confused or restless or have visual hallucinations or dilated pupils then there is agitation and stupor and dizziness drowsiness muscle rigidity so we treat that appropriately and sometimes it's necessary even to inject some sodium bicarbonate because if we make the blood stream somewhat more alkaline then the free drug binds to protein and becomes less problematic what kind of dose do we use well we start off at a dose at ten twenty five milligrams a day the typical dose the ultimate dose the maintenance dose tends to be about 50 to 75 milligrams a day if a person needs more than a hundred milligrams a day then we should monitor those blood levels Bloods office to make sure they're one taking the drug and to getting the effect of the drug and three that they don't have some sort of an abnormality and metabolizing the drug it's not recommended at a dose of more than 150 milligrams and elderly individuals adolescents probably a dose of maybe thirty to fifty milligrams a day would be tops comes in a variety of strengths comes as capsules ten milligram 25 50 and 75 milligrams even comes as an oral solution we have to be careful about people's ability to metabolize the drug because if a person has some interference with those enzymes necessary to metabolize the drug the drug might build up eight times greater than normal in the system fortunately about 70 to 90 percent of people metabolize the drug normally but when we add other kind of drugs on people with a genetic abnormality they might metabolize either extra fast or extra slowly cause problem if they metabolize it extra rapidly then you don't get the effect extra slowly then you get the toxicity the bioavailability of the drugs back 50% the half-life is anywhere between 16 hours and about two and a half days so again have to be careful it's metabolized mostly in the liver by the 2d6 enzymes mostly goes out in the urine only a little bit goes out in the stool as far as pregnancy and lactation it doesn't really have an established safety record and there's relatively safe but we prefer not to use these kinds of drugs while people are pregnant pediatric groups not really study in seniors monitor for changes in the blood pressure and arrhythmias and the possibility of confusion it also very rarely interferes with the liver function so we do have to be careful and use the lowest dose for the shortest period of time it blocks the norepinephrine and the serotonin reuptake also blocks the histamine and acetylcholine that means it's relatively nonspecific nonspecific means it has more actions but it also means it has more side effects as opposed to say the SSRIs they're pretty specific and what they do with the structure of all of the tricyclic antidepressants pretty much the same just a little change in a molecule or two on the other hand if we look at the SSRIs they're very diverse in their structure they just all happen to work in a similar fashion if we compare nortriptyline say to imipramine another tricyclic antidepressant there's less jitteriness and compared the other tricyclic antidepressants there's less postural hypotension that means when you stand up after you've been sitting a while you don't get the feeling that you're going to faint and you don't tend to fall now how do the tricyclic antidepressants work in comparison to the SSRIs to treat depression well they're about the same all of the drugs are about 20% better than placebo that's not great but that's how they were so fewer than 50% of patients who have depression we're gonna have a satisfactory outcome with first drug prescribed doesn't matter what the first drug prescribed is fewer than 50% going to have a great response it's trial and error approach to the drugs and even with multiple attempts and multiple drugs about 1/3 of the people taking the conventional antidepressants are not going to respond now sometimes it seems that depression may be associate of course with a psychosocial stress that can lead to inflammation in information we can measure sometimes by an increase in the chemical in the bloodstream known as c-reactive protein and it seems that in those people who have an elevated c-reactive protein it seems that we get a better response with the tricyclic antidepressants often time then with the SSRIs but unfortunately the c-reactive protein elevation could be from being overweight or having an infection or some other kind of inflammatory disease rheumatoid arthritis something like that well if you have a heart attack the likelihood of suffering from depresses somewhere between about 15-20 percent and if you suffer from depression after a heart attack your likelihood of mortality might be increased by about two fold so the American Heart Association recommends screening after a heart attack to see if you have depression but they don't specifically recommend the tricyclics antidepressants they don't specifically recommend nortriptyline because of the potential linked to the cardiovascular disease and arrhythmias and by the way about 80% of people who have significant chronic obstructive lung disease seem to suffer from depression and if they take a drug like nortriptyline maybe the depressive symptoms go down but it doesn't really necessarily improve the problem with breathing well nortriptyline is better tolerated and less sedating than amitriptyline has less drying effect on the saliva less problem with the orthostatic hypotension seems to be least problematic as far as drug interactions of all of the tricyclics antidepressant seems to be better in elderly individuals than amitriptyline we can monitor the blood concentration in order to hopefully maintain a relatively safe safe level in body and if a person suffers from depression it seems that the drug works more quickly the name a trip to lean so in the first week about 55% of the patients have some responses opposed to only about 25% with a Matt trip to lean how much does it cost well now that it's generic it's relatively inexpensive you could go buy a month worth 10 milligrams 30 capsules you could get that for cash for anywhere between 12 and 17 dollars and with a coupon from good Rx between four and eight dollars for north tripling fifty milligrams again 30 capsules cost anywhere between 12 and 20 dollars if you have a coupon from good rx for 217 dollars but the shocker is even after all of these years if you want to buy the name-brand product if you want to buy a month worth of Pamela it's gonna cost $1,200 for a month versus four dollars for the generic brand doesn't make any sense that's the craziness of pricing in America well anyway that's the story of nortriptyline or Pamela just try cycling antidepressant used for depression but for a variety of off-label uses including migraine prophylaxis and insomnia and ADHD and neuropathic pain in certain forms of anxiety but currently the SSRIs and the SNRIs are much more popular what's safer in overdose but they're really not more effective at least in terms of treating depression in fact when we talk about treating depression all of the drugs seem to work pretty much the same and unfortunately it's trial and error with again fewer than 50% of patients responding very well to the first drug that is used in treatment and in spite of all of our progress in medicine when it comes to treating depression we're still just in the first chapter of the book anyway thanks for watching if you enjoyed the show please consider subscribing and tell a friend we'll notify you if you're a subscriber when we post new videos I appreciate your interest I'm dr. ken landau [Music] [Music] [Music]

Channel: wellnowdoctor

Views: 7,769

Rating: 4.84127 out of 5

Keywords: Nortriptyline, Pamelor, Amitriptyline, Elavil, TCA, tricyclic antidepressant, antidepressant, ADHD, anxiety, neuropathic pain, migraine prevention, gabapentin, SSRI, MAO inhibitor

Id: Wgagt0nCoM8

Length: 29min 7sec (1747 seconds)

Published: Mon Mar 09 2020