Seroquel

hello dr. ken Lana thanks for watching let's talk about seroquel comes in two forms immediate release and sustained release or extended release there was known as quetiapine it's an atypical antipsychotic developed in 1985 Food and Drug Administration granted marketing approval for the first drug the immediate release form in 1997 went off patent in 2012 the sustained release or extended release form granted marketing approval 2007 off patent 2017 structurally the drug is related to zyprexa and clozapine it's among the top 100 prescription agents used in the United States with about 9 million prescriptions every year for the drug that increased from about 1500 prescriptions in the year 2000 up to a million prescriptions in 2012 to almost 9 million by 2016 and that level has not been matched by any other atypical antipsychotic which is especially of note when you consider that the only approved indications for the drug are for schizophrenia and for bipolar disorder the mania or the depressive episodes and it can be used in treating major depressive disorder when it's added to an antidepressant in other areas of the world for instance in Australia it's also approved for generalized anxiety disorder and treatment resistant depression the dose of the medicine depends on the disorder and depends on the age of the individual so if we're talking about schizophrenia the starting dose for adults would be 300 milligrams increased to between 400 and 800 milligrams for maintenance dose but adolescents between 13 and 17 start off at 50 milligrams and then the doses rapidly escalated to the adult dose Sundays 3 4 & 5 if a person suffers from bipolar mania and is an adult can be treated either with seroquel by its alpha is an adjunct to lithium and valproate dots begin at 300 milligrams and again go to between 400 and 800 milligrams is a maintenance dose but adolescents say between the ages of 10 and 17 they begin in 50 milligrams and go to a maximum of 600 milligrams for bipolar disorder with the depressive episodes will start at 50 milligrams and go to a maximum of 300 milligrams for geriatric patients people over age 65 then the starting doses again very low 50 milligrams titrate slowly especially in people who are debilitated or who are predisposed to low blood pressure after be very careful in the pediatric population because the drug is not approved and doesn't seem to work for people who suffer from bipolar disorder the depressive episodes anyway in diagnosing and treating children treating pediatric population the diagnoses are very complicated so wouldn't be bad to get several opinions people who have liver impairment again start with a relatively small dose comes in multiple different those forms 50 milligram 150 milligrams 200 300 400 milligrams you swallow the medicine whole you don't split it you don't chew it you don't crush it you take it with food or a light meal because it's better absorbed with some fat in the diet if you're taking the extended-release you only take it once a day preferably at night if you're taking the immediate release you have to take two or maybe three pills a day during maintenance therapy periodically you reassess to decide if you really need to continue taking the drug if you stop the drug for any reason for more than a week you have to start on the titration that we just talked about you don't start at maintenance dose all of a sudden if you happen to be taking the immediate release form and you want to switch to the extended release form because you don't want to take the two or three pills a day you just add up all of the pills that you take after milligrams and take as a single shot of the extended-release there's no information unfortunately about switching from one atypical antipsychotic to another or even combining the atypical antipsychotics which is generally thought of as not being such a great idea there's a black box warning especially for elderly people with dementia related psychosis that there's increased mortality that also increase suicidal thoughts and behavior in children and adolescents and young adults on short-term studies so you have to monitor people who are beginning therapy to make certain that they don't become suicidal certainly can interact with a variety of other medicines so for instance if you're taking a medicine that acts to inhibit drug metabolizing enzyme known as 3a4 in the liver you have to reduce the dose of Seroquel by 5/6 so in other words you only take about 16 percent of your dose if you happen to be taking it with ketoconazole with it Reconnaissance IV medicines and then when you stop those medicines then you go back to your regular dose and you have to increase the dose of Medicine fivefold if you happen to be on chronic therapy with say st. John's wort or like the Antonine or tegretol or rifampin and you have to be cautious of taking it with medicines that lower the blood pressure because already the medicine has a tendency to reduce your blood pressure and it can antagonize the effects of levodopa and other medicines that are used to treat Parkinson's disease now it has warnings and precautions saying that you know if you are elderly and you have those dementia related psychoses well there can be about a 60 to 70 percent increase in mortality from cardiovascular disease from heart failure and sudden cardiac death and infections aspiration pneumonia being the most common and it can lead to an increase in cerebral vascular disease in the out really individual stroke and transient ischemic attacks can lead to thoughts suicide even behavior related to suicide worsening of depression can lead emergence of suicidal actions so the family the caregivers have to be notified of persons naked to watch the person especially if the person starts to develop some symptoms that are unusual for them anxiety or panic or agitation or insomnia or hostility or impulsivity or restlessness and doctors should be very careful about the number of pills that they give to people because these pills can be dangerous and overdose who in those people who are susceptible very low number of pills may also cause a condition known as the neuroleptic malignant syndrome it's eventually fatal it causes the body temperature to increase the muscles to become rigid it causes irregularity of the poster the blood pressure causes sweating and arrhythmias can cause muscle breakdown increase in the CPK and the myoglobin and it can cause rhabdomyolysis breakdown as muscle tissues that leads to acute renal failure times it's confused for pneumonia or infections or heatstroke pregnancy there is a problem that if the woman is taking the drug during the third trimester then the fetus or the newborn can demonstrate the extrapyramidal symptoms or withdrawal reactions that's obviously a significant problem but this drug might be better than some of the other drugs that are also used for schizophrenia or for a significant bipolar disorder we don't have any good data regarding the major birth defects or miscarriage rate associated with the drug but we do know that the risks of undiagnosed and untreated major depressive disorder and schizophrenia and bipolar disorder can be significant in pregnant women the drug shouldn't be used for lactation since it is excreted into the breast milk their metabolic changes associated with taking the medicine so it increases the blood sugar can lead to ketoacidosis or hyper Osmo wear comb or even death and people who are susceptible they may develop diabetes and demonstrate an increase in fluid intake increase in the urine output increase in they eat associated with weakness about 12% within 12 weeks are going to go from borderline elevated blood sugar to the diabetic level of blood sugar also alters the lipid level can increase the weights of the cholesterol goes up to more than 240 and the LDL the bad cholesterol goes up to more than 160 and the triglycerides go up to more than 200 that can 20% of the individuals and somewhere up to 20% of the individual is going to gain more than 7 percent of their body weight by the time only two months has gone by of taking the medicine they also can develop a condition on his tardive dyskinesia with potentially irreversible abnormal movements tends to be associated with a longer course and a higher dose but can occur at any dose for even a short period of time and it doesn't even matter if you've stopped the medicine the condition persists will can lead to orthostatic hypotension so you stand up in your blood pressure Falls you become dizzy in your heart rate goes up then you have fainting episodes and you can fall means you have to use a special caution if the person has a history of coronary vascular disease has a heart attack or has had heart failure and people who are predisposed to hypotension seem to be especially at risk so those people who are dehydrated people taking the anti hypertensive medicines and then the medicine just has a tendency to make you sleepy and if you add the sleepiness in the tendency to postural hypotension you can have a significant problem with Falls and fractures and everything else so that's a problem and especially in the pediatric age group we know that children and adolescents have a tendency to develop high blood pressure so this systolic or the upper number goes up more than 20 points in about 5 to 7 percent of the individuals but the lower number the diastolic pressure goes up by more than 10 millimeters mercury and almost half of the people it can even develop a hypertensive crisis while you're taking the medicine it's also associated with a significant decrease in the white blood cell the neutrophils the cells that fight infection person can even develop fatal a granular cytosis where you're not making any of the white cells after caution and use caution and people who have a low white count to begin with or a history of a low white count associated with different kind of medicines you should monitor the person before they start taking the drug and then after a short period of time to make sure the white count is stable dogs can develop cataracts we don't know about people but it's suggested because of lens changes that you have a slit-lamp examination before therapy and about every six months while you're on therapy but even more concerning is the likelihood of what we call QT prolongation that has to do with the electrical activity of the heart and we can measure it on an electrocardiogram now concurrent illnesses and medicines that are known to alter the electrolytes can predispose to this prolonged QT and then if you add the seroquel especially if you're also taking a drug like amiodarone or soda law or any of the other atypical antipsychotics or leave a Quinn or cipro or rifra Meissen or a tricyclic antidepressant like a MIT protein if you're taking quinidine if you're taking a procainamide where you have to be extremely cautious you have to be cautious to make certain that the potassium level isn't to load the magnesium level isn't too low you don't even have a slow heart rate and certainly caution if you have a congenital early prolonged QT if you have history of heart disease heart failure heart muscle disorder if you're an elderly individual all of those predisposed to this situation that can lead to severe cardiac arrhythmias and sudden cardiac death the drug also can cause seizures that we have to use caution especially if the person has a decreased seizure threshold person over age 65 person with a history of seizures person who has Alzheimer's disease and thyroid function is depressed by about 20% in we're around two to five percent of individuals within the first six weeks of taking the drug and then it can lead to hyperprolactinemia that's specially in children where we have a problem where about 10% of girls and about 10 to 15% of boys develop elevated level of prolactin prolactin is a chemical that's made by the brain that tends to cause enlargement of the breast and in young boys that's obviously a significant problem it causes that because it antagonizes the dopamine receptor so when you have elevated prolactin that can lead to production of breast milk it can cause a decrease in reproductive function it can cause a decrease in the production of sex hormones amenorrhea impotence and of course it can lead to a decrease in the bone mineral density and it's estimated that as many as one in three breast cancers are at least in part dependent on prolactin so at least in mice and rats we know that seroquel can increase the incidence of mammary gland adenocarcinoma cancers with mammary gland which is an equivalent cancer at the breast also cause pancreatic islet cell neoplasia in rats don't know that in humans well can lead to cognitive impairment that's a significant problem leads to somnolence and somewhere between a quarter and a half of all of the people who take it and again that can lead to Falls and impaired judgment and thinking it can lead to some problem with motor skills it can lead to problems if you happen to try to drive a car and it can cause problems in body temperature regulation so you have to be especially careful that your body temperature doesn't go up too high especially if you exercise strenuously you're in a hot humid environment you're dehydrated or you're taking an anticholinergic type medicine and in some people it causes dysmotility of the esophagus causes the esophagus not to work right which means the food doesn't go down which means that you have an increased incidence of aspiration and that's a common cause of morbidity and mortality especially in people who have Alzheimer's disease and we know that it has anticholinergic effects and i cholinergic effects can lead to constipation and can lead the urinary tract obstruction and can lead to elevation of intraocular pressure so all things to consider well the standard side effects or somnolence and as I say between a quarter and a half of all of the people dry mouth and about a third of the people leads to dizziness and about 10% of the people and then a significant percent of people are going to have dyspepsia problems with their swallowing indigestion restlessness anxiety or tremor muscle spasms are going to have trouble with their peripheral vision peripheral edema can develop shortness of breath people develop peculiar nightmares or priapism or they get up at night and sleepwalk interestingly even though the medicine was brought on market 1997 it wasn't until 2005 that the Food and Drug Administration without fanfare labeled the drug that well you know when you take this in combination a series of other drugs drugs I just mentioned with the QT syndrome it could be linked to arrhythmias in sudden cardiac death now they don't use the word sudden cardiac death but a low dose it increases the sudden cardiac death rate by about 60% high dose increases it by about three-fold 300% so obviously significant problem and that was only added after a big fight at the Food and Drug Administration can also lead to extra parameter syndrome extrapyramidal syndromes tremor and drooling and cogwheel rigidity and dystonia and spasm to the neck that can lead to some tightness of the throne even difficulty breathing and sticking the tongue out well if you take the seroquel it can interfere and cause a false positive urine test for methadone and for tricyclic antidepressants the Food and Drug Administration has what they call the adverse event reporting system that's voluntary so there's a lot of under reporting and even though things are reported there's not necessarily a cause and reflect no cause an effect but with seroquel with the guitar' pain there have been over 50,000 reports of serious injury and about 10,000 associations with death reported well person has renal impairment you need the slightly reduced dose if you have liver impairment since its extensively metabolized in the liver you have to have a lower dose or stay off of it it's unfortunately used off-label for a significant number of medical disorders ranging from generalized anxiety disorder this simple anxiety or eating disorders like anorexia nervosa anger management and dementia and sleeplessness and SAAM nee it's used for post-traumatic stress disorder personality disorder it's used for autism and behavioral and psychological symptoms that are associated oftentimes with dementia it's used for substance abuse and erectile dysfunction used for poor appetite and off-label if still it's used for borderline personality disorder and the psychoses associated with Parkinson's disease and it's used in conjunction with the SSRIs the selective serotonin reuptake inhibitors for excessive compulsive disorder and for Tourette Syndrome and we find that about a quarter of the patients who happen to be in residential senior care facilities are getting this kind of medicine it's often associated with fatal pneumonia associated with stroke and hip fracture and cognitive dysfunction inappropriate use of the medicine this medicine is often used misused abused it's given to inpatients and people on chronic care facilities and prisoners to keep them in order the misuse can sometimes be oral sometimes people sniff the drug to use it intravenously sometimes they mix it with other illicit drugs actually has street names it's called quail or susie-q or maybe heroin when it's mixed with cocaine it's called a cue ball mixed with THC tetrahydrocannabinol it's called a mac ball this is a drug remember for schizophrenia and for bipolar disorder and for major depressive disorder yet two-thirds of the initial prescriptions are written by general practitioners who have minimal training in psychiatry and little understanding of the potential downside of these kind of medicines now interestingly it's not used for treatment of schizophrenia or bipolar disorder in the majority of people who are taking the drug even though those are the only indications it's used at low dose typically between 25 to 200 milligrams actually 25 percent of the patients are getting just 25 milligrams and that dose is only meant as a titration it's not met for people to be on at a routine drug level drug amount and the doctors who are giving the drug out think that modi's at low doses is gonna cause the side-effects but it does cause the same side effects often times in the same amount now between the years 2000 and 2011 there was a two-fold increase in the number of people receiving the atypical antipsychotics and the one that rose the most was seroquel and it's not because people were switching from other drugs to seroquel and it's not because we've changed the way we diagnose psychiatric disease but here in the United States by 2010 this drug was the fifth leading prescription in the United States bringing in almost 7 billion dollars a year and of course the drug manufacturers Troezen akka well they had charges false and misleading information being provided to the medical profession about the risks they had problems with their marketing material there was an onslaught of litigation federally and from a state level and counties individual patients but the company claimed today we have First Amendment rights to go and promote the drug the way we want the way we think it's appropriate to promote it well by the year 2011 they had over a billion dollars in settlements with the government actually one lady who is taking the low-dose hundred milligrams a day said she was walking around smacking her lips puckering her lips like a fish and repetitively licking her lower lip she had marked deterioration in the quality of life taking this drug well the company pays doctors to put the names on articles at Damon the company has ghostwritten they pay doctors the lecture others they pay what they call thought leaders there's direct consumer advertising false claims made to doctors drugs used for insomnia a dose of 25 to 100 milligrams there's no evidence that it works it does indeed have sedative and hypnotic properties just like an antihistamine anti serotonin drug but on systemic reviews there is absolutely no evidence that this drug should be used for insomnia unless a person has bipolar disorder and/or schizophrenia and then used to treat those diseases and just as a side benefit have some improvement in the sleep but at a recent study Madigan air force base their army base I'm sorry they found that the most common indication for seroquel the most common prescription for seroquel was for insomnia 57% of the people infer anxiety about 20% of the people and in fewer than 10 percent of the people the drug was used for appropriate indications now as an example there was a study on the drug for borderline personality disorder the company AstraZeneca sponsored it it was headquartered at the University of Minnesota where dr. Charles Schultz was the head of Psychiatry supposed to be an eight week trial supposed to involve a hundred patients supposed to take two years to finish but they had a terrible problem with recruitment they had a lack of oversight they had among the participants two patients who were in a residential treatment facility for sex offenders who didn't have bipolar disorder I'm sorry didn't have borderline personality disorder but they got into the study and actually one of them was acting as a cook for the facility and stirred his seroquel into oatmeal that was served to a bunch of other individuals both patients and staff they thought there was something funny about the way they felt something peculiar about the color of their oatmeal well the outside experts excoriated the University this is a major university at the University of Minnesota excoriated for lack of oversight inadequate care of the patients lack of control of the medicine it was so bad that the state commissioned the review and as a result dr. Schultz stepped down and the psychiatric Department was banned from conducting further drug studies well the studies for schizophrenia doesn't work it's modest improvement yes indeed it does work in some patients they don't return to normal it's helpful for the positive symptoms the people who have the delusions and hallucinations and the excitement and grandiosity and hostility and the aggressive behavior that's due to its action in blocking dopamine in Lisl limbic pathways of the brain and it's helpful for the negative symptoms the symptoms but the blunted effect and being socially withdrawn and emotionally withdrawn difficulty in abstract thinking that's due to the blocking of serotonin in the frontal cortex well so the drug seems to be good on the other hand on careful evaluation definitive conclusions aren't necessary because of the number of people who withdrew from the studies and the lack of data regarding the economic outcomes and social functioning of the patients and the quality of life of the patients well how about does it do better for bipolar disorder well actually seroquel is the first drug that was approved for both the depression and the mania associated with bipolar disorder so for the cute mania can be used as a sole therapy or can be used adjunctive lee with lithium or valproate studies are relatively short-term studies are relatively small there is benefit yes indeed but it's certainly not a homerun in the same thing for the depressive disorder associated with bipolar disorder now we have major depressive disorder by itself not associated with bipolar disorder and it can be used as adjunctive therapy not as sole therapy the company keeps trying to get the drug approved as sole therapy but as of April of 2019 the Advisory Committee to the Food and Drug Administration again said no this is not appropriate we are concerned about the safety of the drug and we are concerned about the sudden cardiac death associated with the drug so no you do not have permission to market the drug as sole therapy for major depressive disorder major depressive disorder is being diagnosed phenomenally commonly among people between the ages of 25 and 44 it's estimated that somewhere around 10% of men and up to 25% of women suffer from major depressive disorder and that includes a quarter of the people who have cancer and diabetes or heart disease or that a stroke so we have a problem with diagnoses and we have a problem with therapy this is an awful area of medicine there's a problem with overdose of the drugs so if you overdose on the drug it could increase your heart rate decrease your blood pressure could cause some problems with sedation and drowsiness that can go on to delirium and sometimes coma sometimes people develop a rythme and some people die actually in Australia it's one of the most common causes for overdose and as a matter of fact very substantial percentage of the people who overdose on the medicine overdose on this Eric well don't even have any approved indication for taking the drug in the first place now we're not certain how the drug works but it seems to be an antagonist of the receptors for dopamine and for most of the types of serotonin and for histamine and for noradrenaline but it doesn't have any activity at the benzodiazepine receptor has anti histamine effects sedative effects that seem to be about the same as simply taking a benadryl or a doxepin naima Tripp Tulane all of which would probably be a heck of a lot safer if you have a sleeping disorder than taking seroquel at very low doses it's an antihistamine at moderate doses Bennett's serotonin receptor blocker and it higher doses that's when the dopamine blocking comes into effect you have to block at least 65% of the dopamine receptors but not more than 80% it doesn't work well for schizophrenia if you're below 65 percent blockage of the receptors but you develop too many side effects if you get over 80 percent of the receptors that are blocked so very critical to get the correct dose and if you happen to decide to stop the medicine you have to be careful of withdrawal reactions if you stop to suddenly nausea vomiting loss of appetite restlessness sweating and trouble sleeping and numbness and muscle pain it usually goes away in a relatively short period of time about a week rarely some people when they stop the medicine even if they never had a problem with psychoses they could have hallucinations and delusions peak blood level if you take the immediate release form is about an hour and a half the delayed release is about six hours best taken with a high fat meal that increases the concentration by about 25 to 50 percent inside the bloodstream it's metabolized in the liver the half-life is about 7 hours it has a major metabolite it has a half-life of about 12 hours clearance is about 40% reduced and people over age 65 that's why we started relatively low dose if a person has renal insufficiency there's about a 25% reduction in the clearance but the dose doesn't really have to be reduced because there doesn't seem to be any change in the plasma concentration that 70% is eliminated in the urine about 20% is eliminated in the feces animals that are studied they develop thyroid gland adenoma xand mammary gland adenocarcinoma is associated with the increased burrell actin we mentioned and an increase in the incidence of cataracts well does it work different than any of the other atypical antipsychotics no they're all actually about the same little difference but not all that much as far as the positive symptoms the delusions and hallucinations it doesn't work quite as well as some of the other drugs works a little bit better than some of the other drugs to the negative symptoms that withdrawal the emotional problems for a cognitive benefit seem to work a little bit better actually in 2013 the Cochrane collaborative study looked at 15 of the atypical antipsychotics and they found that seroquel might work about 10-15 percent better than the Jia done works about as well as Haldol and abilify looks maybe slightly less than respite all and zyprexa a VA study looked at people who were taking low-dose medicine the average dose was about 116 milligrams these people were taking 116 milligrams for an average of 44 months and remember there is no 116 milligram dose there people are supposed to be on typically average adult between 400 800 milligrams these people are taking a low dose for as long as a hundred 80 months they had negative metabolic consequences even at the low dose and surprisingly even twenty of the 400 or so people who were on the study they were taking another atypical antipsychotic in addition now interestingly a company Loui pharmaceuticals they purchased the right to sell seroquel in 51 countries including China the United Kingdom Brazil Mexico Saudi Arabia they purchased the drug for 260 million dollars cash and then benefits depending on how well they were able to sell the drug another 270 million dollars or so so in other words they bought the rights in 51 countries for around 500 2530 million dollars now in 2017 those 51 countries accounted for only a hundred forty-eight million dollars in sales and in Asia including China only 74 million dollars in sales but if we look at 2010 the drug company sold over five billion dollars worth of Seroquel in 2012 globally over six billion dollars that was the fifth largest prescription drug used in the United States even it went all after went off patent still selling billions of dollars and settling for billions on the with the Food and Drug Administration and the government for false and misleading advertisement for defrauding Medicaid still their lawsuits being filed even though the drug has been off patent for a while and it has to do with what's known as pay for delay the last suit filed in September of 2019 and the FDA has a revolving door where people work for the FDA then they go to work for the drug companies and unfortunately sometimes when we work for the FDA they're not very harsh at least as far as the drug and drug oversight is concerned so how much does it cost well you could take a month of the immediate release generic form if you got thirty of the 300 milligram form you could go over to Costco or Walmart and buy that for $9 or $15 but if you went to CVS it will cost you $109 with the coupon from good rx if you went to Walgreens it will cost you 121 dollars if you've got the brand-name drug it would cost $500 and if you went to seroquel the delayed response generic form 30 milligram I'm sorry 30 pills that 300 milligrams gonna cost you and between 25 and 30 dollars unless you go to CVS it's 82 dollars and good Walgreens it's gonna be $160 or you could buy the name brand drug for between 650 and 700 dollars so that's the story of Seroquel seroquel and its generic equivalent quetiapine they're very potent drugs they have very real side effects they do serve a purpose and when they're used correctly they do improve the lives of people who have schizophrenia and bipolar disorder but unfortunately the drugs are far too frequently used off-label & inappropriately and they result in significant harm and worse yet the drugs are prescribed so frequently to the elderly in nursing homes and chronic care facilities to ease the job of the care taker not the patient and these drugs should not be used butene lee as a sleeping pill if you're receiving a drug like seroquel generic for name-brand or any of the other atypical antipsychotics do make certain that you have an appropriate indication to take the drug anyway thanks for watching i'm dr. ken landau if you enjoyed the show please tell a friend maybe consider subscribing appreciate your interest see you soon [Music] [Music] [Music]

Channel: wellnowdoctor

Views: 29,168

Rating: 4.7845602 out of 5

Keywords: Seroquel, antipsychotic, quetiapine, zyprexa, risperdal, schizophrenia, bipolar disorder, mania, depression, sleeping pill, tardive dyskinesia, suicide, tremor, ptsd, dementia, antihistamine

Id: Vb9b5roLqBs

Length: 36min 42sec (2202 seconds)

Published: Wed Oct 23 2019