Rexulti

hello I'm doctor Ken Lander thanks for watching let's talk about wreck salty or wrecks result this is a drug that was approved by the Food and Drug Administration in 2015 it's a second-generation antipsychotics an atypical antipsychotic it's for the treatment of schizophrenia or as an adjunct an add-on medicine for people who have treatment resistant depression now in the second generation antipsychotic family we have drugs that are very well known we have abilify insight present seroquel and the Tuda and geodon and we have in Vega and we have rail are this drug rock salty happens to be manufactured by a Japanese company known as Asuka and they combined their efforts with London back which is company out of Denmark their Co marketing this drug the drug is remarkably similar to abilify question is second-generation a whole lot better than the first generation that's arguable some people when they first came out said hey these have fewer side-effects not so sure about that well let's take a look at the dose if you're gonna take the drug you only have to take it once a day you take it with it without food if you happen to have major depression you can add it to your other antidepressant added either half a milligram per milligram a day then after a week you could increase it two milligrams if you need and even go up to ultimately three milligrams if you have schizophrenia then you would begin a dose of 1 milligram for half of the first week the second half of the first week take 2 milligrams and then beginning week 3 you take 4 milligrams but if you have moderate to severe either liver or kidney impairment the maximum dose you can take for a major depressive disorders 2 milligrams and 3 milligrams if you happen to have schizophrenia it also is important to realize that about one person in eight is born with a defect in one of the drug metabolizing enzymes and if you happen to be among those in tools you have to reduce the dose of the drug by about 50% and if you happen to be taking other drugs other drugs can also affect those drug metabolizing enzymes and turn them down in which case you have to reduce the dose by about 50% if you affect one drug metabolizing enzyme but if you affect two drug metabolizing enzymes you would have to reduce it by about 75% now the 2d6 is impacted by quinine and cymbalta the 3a4 is impacted by clarithromycin and fluconazole and other drugs but on the other hand if you're taking a drug that stimulates those enzymes well then you have to double the dose so if you happen to be taking Saint John's wort of taking rough than--than you have to take more of the drug but then you have to realize that when you stop taking those drugs you got to tell the doctor so that they can appropriately modify the dose that you're taking and you have to avoid grapefruit grapefruit juice you have to avoid severe or injen saw you're taking the medicine because those are going to change some of those drug metabolizing enzymes now schizophrenia is a major market for this drug it's gets Freni affects about two and a half million people these people have hallucinations and delusions they have disorganized thinking trouble organizing their thoughts they have suspiciousness they have mistaken beliefs they feel guilty or anxious they have little desire to be around other people and the drug is okay for those people but the real target is as an add-on for depression depression is a major condition in the country it's diagnosed in about 7% of the people on an annual basis here in the United States 15 million people over age 18 suffer from depression and only about 30 to 40 percent get an adequate amount of relief with the treatment so taking the prozac in the paxil and similar drugs really doesn't get rid of the symptoms that may reduce the symptoms but it doesn't eliminate the symptoms when you have the symptoms that persist while you're taking an antidepressant you've taken one unit - we in fact depressants and you still have the symptoms that's what we call treat a resistant depression now depression isn't just I feel a little bit sad or angry about something no depression is a complex condition and it's associated with finding decreased pleasure and your normal activities or decreased mood or irritability and then you have some unhappiness and low self-esteem and worthlessness feelings and pessimism and hopelessness and guilt so it's a package of more than just I feel depressed now if you suffer from treatment-resistant depression you actually have a depression and now you're under treatment with standard kind of therapy but you're not really getting better what can you do you could increase the dose of the antidepressant maybe it could change the drug maybe you could add another drug maybe you could make a different kind of a antidepressant different class of antidepressant a can MAO inhibitor tricyclic antidepressant maybe it could try some counseling and for some people an anticonvulsant anti epileptic drug could be used or lithium and some people know dose stimulant maybe even thyroid hormone for some people but now the thing that's catching on is the augmentation therapy augmentation therapy with one of these atypical antipsychotics there are nine licensed in the United States but only three have received FDA approval for marketing as treatment for treatment-resistant depression those are abilify and seroquel and a combination of zyprexa and prozac that we call sim backs and now Rick salty there's a question though dude the medicines really provide significant benefit especially when you compared them to the side-effects that they caused the likelihood of a typical muscle movements tardive dyskinesia or weight gain or type 2 diabetes are now we worry about heart attacks and stroke with the medicine so let's look at some of the studies that were done okay let's look at clinically treatment-resistant depression that people have been on therapy for at least eight weeks and they haven't gotten any better taking the lexapro or the paxil or the prozac or that cymbalta or the effexor let's test them with something called the Madras that's a rating scale that we use as 10 item examination 10 item score anywhere between 0 and 60 these people have an average score on entry of about 27 now 175 were divided into two groups two groups each of 175 about one group received a new antidepressant by itself the other group received a new antidepressant and two milligrams of drug salty and the people who received 2 milligram of Uruk salty their score went down by about 8 and a half points as opposed to the people who were taking the antidepressant alone their score went down only about 5 points so there was about a 3 little more than a 3 point difference between the two that sounds very impressive until you stop for a moment and realized that the final score instead of starting off 27 now with the rock salt ii combined with an antidepressant the score was about 19 it was about 22 in the people who were taking the antidepressant alone and the diagnosis of having no depression is a score between 0 and 6 so we haven't reached that so let's take a look at another time and in this trial instead of taking 2 milligrams and their antidepressant now we take the new antidepressant some people take the 1 milligram and some people take the 3 milligram and what do we find again we find the same thing people thinking 3 milligram they had reduced score by about 8 and a half points people who were taking the antidepressant one milligram they had a reduced score by about 7 and a half points people who were taking just the antidepressant alone they had a reduction in their score of about 6 points so when we look at the total score on the mattress score people think antidepressant alone had a score of 20 people who were taking the one in the 3 milligrams in addition to the antidepressant had scores of 18 and 19 and again no depression is 0 to 6 well it might sound like it's statistically significantly better on the other hand at the end of therapy these people were still stuck right at the junction of moderate to mild depression so we haven't eliminated their condition and as a matter of fact the whole reason that the antipsychotics might work as they might make you sedated so you sleep better and the small difference in the score might simply be due to a little better sleep and that's especially a problem because these studies are conducted by the drug companies and you have to take their supposed benefit with the grain of salt but they did another study at the Veterans Hospital Center the Veterans Administration and they did a real study they looked at 35 separate VA hospitals looked at about 1500 people who were resistant to at least one impact to present for 12 weeks and then for the next 36 weeks these people received either an antidepressant a different antidepressant they received wellbutrin or they received wellbutrin in addition to the original antidepressant or they were given abilify and remember abilify and rock salt ii are pretty much the same drug so what was the likelihood of remission no depression at the end of the therapy well it was only about 25-30 percent in the entire group it didn't matter which of the therapies were chosen and if we look at the response so getting somewhat better but not getting completely cured we find that somewhere between 60 and 70 percent of the people fell into that group almost irrespective of which category whether we're switching off to the wellbutrin by itself adding the wellbutrin to the other antidepressant or adding abilify and abilify can be substituted for a Rexall t so if we look at the graphs of how the patients responded you can't see any daylight between them they all see to be about the same now if we look at the white Li hood of improvement in schizophrenia well again we have the test than the tests called the PA NSS and it stands for the positive and negative symptom scale you can have score of as high as 210 or as low as 30 these people had a score of an average of about 95 so on the study they received either 2 milligrams or 4 milligrams or placebo the people receiving the active drug they have a decrease of about 20 points versus about 12 point decrease with the placebo so again we have a decrease with the drug but it's not quite as impressive as it would seem so then let's do another study let's keep some of the people on the people who have responded let's keep them on the drug or switch them off to a placebo and see what happens over a period of time see if the schizophrenia comes back and if we keep the person on Rexall t twenty percent of the time one in five people who seem to have gotten better get worse right while they're taking the drug but if we look at what happens with the placebo half of them are going to have recurrence of the symptoms so for relatively minor improvement let's see what the risks are and the risk are they have a blackbox warning on the drug mac box warning says that there's increased mortality in the elderly patients who have dementia related psychosis if they take the drug in over a period of 10 weeks the risk of death increases by about sixty or seventy percent from their baseline and that's from cardiovascular disease sudden cardiac death or heart failure or infections like pneumonia and they have an increased incidence of suicidal thoughts and behaviors especially if they happen to be less than 24 years of age now the studies only were ongoing for about four months so we don't know exactly whether they're safe after that or what they do to the incidence of suicide so other warnings and precautions well they can increase the risk of cerebral vascular disease in elderly individuals who have psychosis and maybe have dementia these people have increased risk of fatal and non-fatal stroke and transient ischemic attacks mini strokes and they can have an increased incidence of neuroleptic malignant syndrome where the body temperature gets elevated and associated with muscle rigidity and altered mental state and instability of the blood pressure heart rate can sometimes cause muscles to break down the kidneys to stop working and then there's tardive dyskinesia atypical movements typically of the face sometimes of the hands irreversible movements oftentimes involuntary movements the higher the dose the longer you're on the drug the greater the risk is if you happen to have any other kind of disease maybe increases the risk so we want short duration low therapy and we want to reassess to make sure you really need the drug because once the tardive dyskinesia symptoms begin that's a problem it doesn't go away when you stop taking the drug and then there are other kind of problems too metabolic problems so it increases the blood sugar causes diabetes if your blood sugar is normal 9 percent of the time it'll be diabetic and if your blood sugar is borderline about 25 percent of the time it's up in the diabetic range and then there's ketoacidosis in hyperosmolar coma increases that increases your cholesterol increases your triglycerides and increases the body weight short-term because it gained about 6 pounds every year long-term you can have 20-30 percent gain and weight but some of the people going to have a decrease about 10% of people gonna lose about 7 percent or more of their body weight you can have inner restlessness taking the drug 6 to 12 percent of the people gonna have that can increase your core temperature your body temperature even though it doesn't cause nor leptin malignant syndrome it can increase your body temperature still especially if the exercise or if you're dehydrated or if you're taking certain medicines like anticholinergics may be a cost medicine or medicine to dry up the common cold and it was recently learned and labeled label change in 2018 that it might be associated with pathologic gambling and other compulsive behaviors like sexual behavior shopping and eating binge eating other impulsive behaviors the person might not realize that so the caretaker has to be notified and when you stand up it might cause your blood pressure to fall that might cause you to faint especially initiation of therapy or changed in the dose and it's certainly worse more likely to happen if you're dehydrated or you have a history of cardiovascular disease you've had a heart attack you have to be careful of these kind of drugs and because they can cause this orthostatic hypotension that can cause you to be tired and they can also cause you to fall and then if you fall you can break something then you have other kind of issue you have to exert a certain amount of caution if you're driving a car if you have a history of epilepsy this lowers the seizure threshold can cause some Parkinson's like syndromes cause difficulty swallowing cause dystonia especially in young men with spasm of the neck sometime it's so difficult that makes the tightness so that you have difficulty swallowing maybe your tongue protrudes usually at high dose usually relatively soon after you begin the medicine can cause the blood count to decrease especially the white blood count if you're pregnant and you're taking the drug specially in the third trimester might affect the baby so the baby born then with either hypertonia or hypotonia agitated tremor can have respiratory distress and feeding difficulties can recover hours to days or might take prolonged hospitalization so not for women who are pregnant not for women who are breastfeeding the way it works it works on the neurotransmitters like everything else it works on the serotonin and the dopamine and the nor adrenaline sort of works just like abilify now when you compare it to other atypical antipsychotics supposedly it has improved efficacy and tolerability and might not cause quite as much restlessness or quite as my insomnia or maybe it has nothing to do with that it all depends on who you believe chemically what happens is once you take the drug about 95 percent is going to be absorbed gonna be absorbed into the bloodstream maximum in about 4 hours the half-life once it gets in takes about 91 hours to get half of it out its gonna float around the bloodstream bound to proteins it's going to be metabolized and then 25% is gonna be passed out in the or and 50% gonna be passed out in the stool interestingly in female mice not rats but female mice it can increase the incidence of mammary gland adenocarcinoma breast cancer by about 6 fold now Otsuka really had a problem you see they also have the patent on abilify and the patent for abilify expired in October of 2014 and generics came available in April of 2015 so that meant their revenue stream was going to take a big hit so they brought out Rexall T in July of 2015 as a substitute or as a successor to abilify recently they've been spending millions of dollars to advertise the drug and they're focusing on the lucrative market the antidepressant add-on market they talked about a brave phase and unresolved symptoms they anticipate the revenue from the drug is going to be in excess of a billion dollars maybe a billion and a half dollars but how do rating agencies consider the drug well the medical letter which is probably the most quoted research source quoted drug source of information says there's no reason to prescribe Rexall t over generic abilify that's been around much longer and we know it's safe they say also that you have to consider the cost you can buy a month of abilify for less than $25 you know how much a month of Rexel t is going to cost you it's gonna cost somebody more than a $1,100 a month now the Canadian government reviewed the situation as well and the Canadian government they said that for schizophrenia there is not significant enough dad and not sufficient enough data at the 4 milligram dose for long-term maintenance and they said a 2 milligram it's not consistent and actually they said it seems to be pretty much the same as other antipsychotic drugs so they say that the anti-psychotic drugs shouldn't be used for non psychotic depression they said the trials are short they're based on these rating scales and we don't really know how to translate the rating scale to really how the patient is doing and they say that the labeling camouflages the properties shared with the older antipsychotics and then of course there's the problem of the increased risk of death and people who have a dementia so just as an aside in February of 2019 Rick salty failed two trials on mania they were trying to get approval for bipolar disorder for the mania of bipolar disorder which is relatively easy therapy lots of drugs available well they looked at patients who had mania severe enough to require hospitalization so again relatively easy kind of treatment but after therapy the patients didn't seem to improve so the company is excuse was the people who received the placebo did exceptionally well not the case necessarily and now they're trying to get it approved for or studying it for hyperactivity and children attention deficit hyperactivity disorder and they were also hoping to get approval as the first drug for Alzheimer's disease hoping that it would get licensed to treat the agitation of Alzheimer's disease but they did two studies one was positive and one was negative and they have not been able to convince the Food and Drug Administration that it actually improved cognition in these people the Veterans Administration puts up roadblocks to people get the drug because they don't think it really is necessarily any better than the other medicines and Medicaid they say hey try the abilify in the respiratory tracts and seroquel first because these drugs are known quantities and they're relatively inexpensive so if you're going to take Rexall tea for one month of therapy the cost is going to be somewhere between about eleven hundred fifty dollars and twelve hundred twenty dollars with a coupon now they have all sorts of deals so that you can get the drug for less with a copay card but somebody's going to pay a significant amount of money compared to abilify for twenty two bucks seroquel for eleven dollars a month respiratory levantar zyprexa for thirteen dollars a month or remember you could take the rich salty and you can take that for 1,100 to 1,200 dollars a month so where does the drug stand seems to be very unimpressive despite a lot of very slick advertising and heavy promotion the drug company wants to continue the revenue stream obviously after generics of their ability have become available but when we look at the scientific evidence behind it is there any reason to use such an expensive drug does it really provide any significant benefit over what's already on the market already on the generic market for very little money and the answer is no there isn't and if you want to know more about some of these antidepressants or atypical antipsychotics what some of my other shows on them anyway thanks for watching I'm dr. ken landau [Music] [Music] [Music] [Music]

Channel: wellnowdoctor

Views: 19,629

Keywords: Rexulti, Abilify, Zyprexa, Seroquel, Bipolar disorder, Depression, Treatment resistant depression, Schizophrenia, Augmentation therapy, Atypical Antipsychotic, Tardive dyskinesia, Serotonin, Dopamine, Mania

Id: LPkhKLObDwU

Length: 24min 30sec (1470 seconds)

Published: Wed Jun 19 2019