Lurasidone (Latuda): A complete review of an atypical antipsychotic
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- Опубликовано: 30 май 2024
- In this video, we discuss the atypical antipsychotic medication, lurasidone (Latuda). We discuss what lurasidone is, its mechanism of action, what it is used for, its side effects, and potential drug interactions.
Intro 0:00
What is lurasidone (Latuda)? 00:51
What is lurasidone (Latuda) used for? 02:20
How long does lurasidone (Latuda) take to work? 03:09
Is lurasidone (Latuda) addicting? 04:11
Lurasidone (Latuda) side effects 04:48
Lurasidone (Latuda) drug interactions 07:33
Final thoughts on lurasidone (Latuda) 08:58
Resources:
Deprescribing Guide: amzn.to/4dZEUMk
Stahl's Prescribing Guide: amzn.to/3UXj8QL
🎥 This video was edited by:
Rahul Kanchi / rahulkanchi24
🚑 If you are in a mental health crisis, please dial 9-8-8 from the U.S. Or text HOME to 741741 and connect to a crisis counselor.
You can find a list of international crisis lines here: blog.opencounseling.com/suici...
Patient Resource:
Latuda Savings www.latuda.com/bpd/latuda-sav...
Patient Guide: medlineplus.gov/druginfo/meds...
References:
Latuda (2013). FDA Label, retrieved from www.accessdata.fda.gov/drugsa...
Stahl, S. M., Grady, M. M., & Muntner, N. (2021). Stahl's essential psychopharmacology: Neuroscientific basis and practical applications. Cambridge University Press.
Stahl,S. (2017). Stahl’s Essential Psychopharmacology: Prescriber’s Guide, 6th Ed. Cambridge University Press.
Disclaimer: All of the information on this channel is for educational purposes only and not intended to be specific/personal medical advice or substitute for diagnosis and treatment of any conditions discussed herein. Furthermore, watching these videos or getting answers to comments/questions, does not establish a provider-patient relationship. Please consult with your own health care provider for proper diagnosis and treatment.
I take Latuda for bipolar 1 maintenance. I’ve been taking it just over 2 years and it has changed my life. Before Latuda my medications like abilify etc didn’t help much. I struggle with BOTH depression AND mania and I feel it helps with both. I’ve had much less symptoms of either. Before Latuda I had a serious depression for about 4 months which turned into a mixed state and put me in the hospital.
I got a new psychiatrist and she saved my life giving me Latuda. I have been extremely stable now. I’m doing well at work and I’ve been able to hold a good job down for a long time, I’m getting married and I bought a house with my fiancé. My house looks pretty okay, I have hobbies and side projects, my kids are doing well. It literally turned my life around. I hope this medication always works for me. I’m 36 and I wonder if I took it until old age, what will happen to me as I won’t be able to take it anymore. Hopefully by then medical science has come up with a cure for things like bipolar 1 lol. Anyway… life changing and life saving medication.
Thanks for sharing your story! I'm glad to hear you found a treatment that works good for you.
Thank so such, I would like to know if you was taking it when you was a pregnant, your answer really could help me.
Thank you for sharing, post like this give me hope for the future.
Thats good to hear. Right now my life is a mess. I just started Lithium a month ago but because of my kidneys, my doctor stopped it and I just put me on Latuda.
Thank you for sharing! Exactly what? I’m looking for for bipolar, one maintenance, but I was just concerned because it’s only off label that helps with Mania.
I took latuda in 2014 for bipolar psychosis was a miracle medicine anxiety and paranoia wiped out then I stopped all medication at the time bad idea now 3 years being removed from latuda I will be restarting it to bring balance back into my life and shed the weight that olanzapine has caused great medicine
Thanks for sharing your story! I hope you find your balance again soon 🙏🏽
I was on Olanzapine like seven years ago. It was the first psy medication I was put on. I was 109 pounds and after taking Olanzapine I was 190. Quite depressing. I starting taking Risperdone which also caused weight gain. I've been off Risperdone for four months now. And I'm thinking of taking Latuda but I have PTSD because I don't want to gain more weight.
Hello! What dosage worked for you? I’m on 80mg
Latuda was a very intense medication for me. I had to stop taking the medication because I would have fainting spells, and I would constantly shake/ have tremors. Mentally I didn’t experience emotions. I was called the “non-chalant” friend because I literally did not care about anything. I was also taking fluvoxamine, so I believe I should’ve been on a smaller dose than I was.
I just started latuda this week and so far I like it. My co-pay was going to be $200 a month, but it finally went generic and my co-pay is now just $15 a month.
I just took my 1st pill of latuda, Iam so scared right now not knowing what to expect, what can I expect please let me know thank u
@@jerryzigler1313It’s probably the best thing I’ve tried. And I’ve tried 21 meds.
@@jerryzigler1313What happened in the end
Thank YOU!Very helpful!!!💓
It is really usefull, thanks alot
There is a generic now. It's still very expensive. It runs around $1100 without insurance and only $60 with my insurance. The price is still a huge issue for a lot of people. I've been taking it for about two months now for bipolar. It seems to be working the best compared to the others. The only side effect I've experienced is constipation.
My case is different, my sugar levels are high and I am pre diabetic and weight gain from 145 to 172 pounds, but really helps me feel better.
Thank you! I feel so much more confident in my knowledge of this medication.
I started Latuda last year then stopped after a few months. I then fell into a major depression. Like I couldn't shake it! So my better half told me to take my Latuda. I did and I've felt absolutely fantastic for months. So my lesson is listen to my doc. As well as my wife. Hahaha
I’d be interested to see comparisons and videos on adhd and the medications used if that’s something you could cover!!
Thank you ❤
Youre an angel thanks for explaining how it actually works!
You're welcome 😊
I have just started on this
Another medication that causes almost no weight gain is Geodon. It is also chemically the closest antipsychotic to latuda. Could you make a video on Geodon?
This is the 5th medication I've tried for bipolar disorder. And so far I've been able to tolerate the side effects the best. I get a fair bit of nausea. But I have promethazine that helps quell it.
I just started this med and I hope that it helps because I don't like being in bad moods for no reason at all. No reason I should feel that way and it's not fair to my family. I started a 20mg dose so here we go. Thanks for the video. Buttered toast is 110 cal per slice so I eat 3 and a cup of coffee in the morning.
Best of luck!
How did you manage? Still on it?
@@LostMyMeds yes. And I like it makes me feel level headed no impulse and I can think clearly when I need to. I have no loss of energy or willingness to do things I love. Hope this helps.Thank you for asking ^_^
😊 I wish you the best I think that's a good idea to toast in the coffee I might try that cuz sometimes I just don't know about those Cal also I have to say I'm taking the same dosage you are and I'm so far I'm happy with it although I have noticed that I tend to be more thirsty so I have to drink extra water but I think overall generally good health you know you eat right do all the things that you know to do then any medication that's prescribed and like this one should have a good effect I like what you said about being in bad mood for no reason at all I can definitely relate ❤high five
Im gonna start latuda this week, in past i use paxil, how do you feel?
About to start Latuda, been on risperidone for about 6 years and gained 60lbs in the first 2 months and had to be strict on dieting to prevent it from getting worse. Excited to see how it goes now that i wont be fighting my meds to just maintain weight but actually lose it
This RX is expensive, it's a co-pay of $95 USD for me but I was paying for Viibryd the same I'm hoping this helps my drug-resistant depression. I've been on so many but I have to switch around every 6 months because the efficacy of the drugs stop working.
You are super smart.
Hi. Can you please do a video on how to handle the side effects of Latuda and atypical antipsychotics in general especially akathisia? Your channel has been so helpful in my research while working with my psychiatrist.
Thanks for the video idea. I'll consider it.
In rough order of consideration: propranolol, cogentin, benzodiazepine, mirtazipine, gabapentin…. There is a lot for the doctor to consider with each one and dosing is often wrong. Your question is great. Akathisia is a scourge that providers do not take seriously enough. It is hard to diagnose and empathy is for it is scant. Even more complicated by the fact that patients often can’t put it into words.
Just wondering if you can cover Seroquel XR for bipolar thanks. Great video 😊
Thanks for the video idea, I will consider it.
Please make a video on Geodon and Seroquel. Thank you :)
ruclips.net/video/FmXKjVNFb-I/видео.html here's the link to the Seroquel video. A video on geodon will be coming later, thanks for the video idea.
Latuda made it able for me to quit lamictal which I thought I was going to be on for life. It works better and controls my mania and depressive symptoms. Just went from 20 to 40 mg after 1 year. No side effects but am going to do a lipid panel
I think my son found this video and was very pleased ..so I watched it…
I am confused about the interactions… Should my sons am Fluoxetine dose be lowered to 20mg sine starting Latuda.. not sure why he needs both .
He takes 40 mg of fluoxetine in the morning and (he has been on that for almost 6 years now) and
started Latuda six months ago as a replacement for the Risperdal, (which was so weight inducing).He takes the Latuda at night after having consumed up to 350 cal or with the light snack.
* just prior to starting the latuda my son was at a weight of 321 pounds, had high blood pressure,undiagnosed sleep apnea with centrals, was exhibiting hypoxia, (dosing off, falling down and out of bed) He tripped and fell -landed on his foot, broke it in 4 places..
Again this was six months ago…
He is presently on home BiPap therapy and with the change to Latuda and addition of Metformin,he has managed to lose about 50 pounds. He’s doing much better.
Thank you for this video, I just started Latuda after gaining weight and elevated cholesterol levels with Seroquel. I've tried many different medications and Seroquel worked the best but the weight gain and high cholesterol was just not working for me, so hopefully this is the one.
How did you get on with it? I have the same situation except im on olanzapine weight gain is terrible. I believe latuda doesn't cause that.
I had no idea Seroquel also caused elevated cholesterol! I had a blood test recently and thought maybe my diet was out of whack cause it was rather high for someone my age. Thank you for sharing your experience! I just stopped Seroquel and was switched to Latuda. Really hoping it works out!
@levelheaded-mind can you make a video about bipolar2 & antidepressants please
Thanks for the video idea. I will consider it.
@@LevelheadedMind thank you , can you do caplyta as well it’s a new drug ..
Is taking Lurasidone with Aripiprazole safe? Can it help avoid depressive and psychotic relapses??
I found this medication very effective. Serendipitously my dr and I discovered during a cross-taper with Aripiprazole that my mood improved dramatically. In the case of this combination I believe the Abilify occupied most of the D2 receptors but that Latuda had a significant effect on 5HT2a and 5HT7 receptors. What are your thoughts on the matter? Unfortunately for me about 5 years ago I developed benign essential tremor and had to be placed on Primidone (I work in a psych facility where I sometimes have to give injections so no choice there). The Primidone is such a strong metabolic inducer when my dr checked my Latuda level it was undetectable (it was checked because I began to decompensate after the Primidone was brought on board). By the way I just love the videos. Keep them coming!
That is unfortunate for the primidone, latuda interaction. Did your provider discuss other treatment options for the tremor that may benefit and not have this interaction? As for the use of 2 antipsychotics, I do not advocate for this, increased risks of side effects. May even be the cause of the tremors.
The neurologist tried propranolol to no avail. I don't want to do the ultrasound procedure since it's not reversible or the deep brain stimulation for other reasons.. Before that my psychiatrist tried cogentin for the tremor and it did nothing. We up to 3mg bid which is of course way too much although my cognition was very effected so I doubt I was metabolizing it too quickly. Regarding the two antipsychotics my psychiatrist discontinued the aripiprazole without a taper but it takes about one week to wash out. He added the full dose of Latuda at once. Within days the effect was remarkable regarding the depression and emotional reactivity and I felt better than I had felt in the 20 plus years I've had my Bipolar Disorder. Then in another few days I started to decompensate. The Abilify was added back in and the effect came back. There were no obvious adverse effects with the combination. I've only read (as I'm not a practitioner by any means) that Aripiprazole's D2 affinity is so strong that it essentially displaces any attachment of any other antipsychotic medication. I do get your objection to the concomitant use of multiple antipsychotics and I know it's generally frowned on. The forensic facility I work at does not infrequently use Haldol and Zyprexa together but you rarely see two atypicals or two typicals use together. The essential tremor according to what I've read is caused by the loss of GABA neurons in cerebellum not in the nigrostriatal region (thank goodness) and I'm sure that's why the cogentin was a dud. Actually the tremor came on a couple years after I was started on the combination. The Primidone does work it's just not a pleasant addition (sedation). Anyway, thanks for reading my book. Lol. I would love to be a psych nurse practitioner but alas the tremor throws a fly in the ointment because I would have get my RN first.
@@bpggg thanks for sharing your story, I hope you are able to find a suitable treatment, perhaps switching to Vraylar may be helpful?
@@LevelheadedMind Vraylar is a no go unfortunately. It has the same metabolism issues with the Primidone. I l already take Abilify at 60mg (not a typo) due to Primidone and I'd have to take a double dose of the Vraylar and the insurance would have a cow about that. A good suggestion otherwise I say. Barbiturates are a bummer. I manage to do well enough. Meds are necessary but not sufficient. I enjoyed your very thorough and thoughtful video on neuroplasticity. It incorporates a lot of those other elements that extend beyond the meds. Thank you for sharing your knowledge with your ever-growing RUclips following 😊
Would love a video on Vraylar
I just hopped off vraylar after 4 weeks! Went manic lol everyone’s different though 🤷🏿♀️
Can Latuda be used off label for autism? Would it possibly be a better choice than abilify since it doesn't cause weight gain?
Before latuda I couldn't talk at all or bein in social settings now I'm a party animal and I can shit talk with the best of em.
Would this work with risperdal risperdal helps ocd but I need a higher dose can’t increase as it causes grinding so was thinking to combine the two
Using 2 antipsychotics is not advised due to increasing side effects, particularly the extra pyramidal symptoms. However, it is done in extreme cases, but patient must be monitored closely.
Thanks for your video about medication. Very informative. As I live in Australia not all the meds that are in the USA are available in Australia. I was diagnosed with Bipolar 2 and have gone through the medication Merry go round as most patients do. I'm currently taking Lamotrigine as a mood stabiliser and prior to that was on Sodium Valporate. I was recently given Allegron to supposedly help with sleep but it doesn't really work except for first couple of days. It also made me eat more so I stopped. I'm trying to get a medication that helps with Bipolar depression and that lifts my mood and also that doesn't cause weight gain or sexual dysfunction but still haven't found one yet. Do you know of any or could recommend any?
Latuda and Vraylar are good options if they are available to you. You'd only need low doses for a Bipolar 2 diagnosis. Ask your provider about these meds.
@@LevelheadedMind Thanks very much for your suggestions. I really appreciate it ❤️
Natural herbal sleep aids are Passionflower capsules 1,000 mg and Valerian root capsules. Helps my daughter... ♥️ Hope you can get a good night's rest. Sleep is so very important 😴... Blessings!
Hey hello I like to see if you’ve tried seroquel which is for bipolar depression and other mental disorders,& also try trazadone it is for insomnia it really works and it’s really good..thanks anyway take care..
Can you do a video on rexulti please and thank you!
Thank you for the video idea, I will consider it.
Is it okay to take this while eating toast with peanut butter on the toast or other high calorie toppings on the toast with it.I read when I eat things with food items to make sure I am at 350mgs or higher by reading the nutritional facts on food items and adding up the calories for each food item to make sure I hit that number.
Yes, eat 350 calories or more for best absorption.
is it ok to take it with fluoxetine?
Excellent video. I was diagnosed in 2018 with Bipolar 1. I am currently taking as I am in a biplar depressive episode - Latuda at 40 mg. Can you please tell me if Latuda and be taken as a maintenance treatment to lower the risks of further bipolar 1 depressive episodes?
Hey David I"m bipolar depressive too with anxiety It works wonder.
@@JDOGFTW Thanks
Yes, that is its primary use.
Speaking from my personal experience, yes. I have not had a serious depressive or manic episode in over 2 years since starting Latuda. Maybe the worst I’ll get is “a little depressed” for a week or 2, or light hypomania for a few days. Nothing serious or destructive though. To me, it’s the perfect medication. I hope it goes well for you too.
I'm a little confused about the interactions, i take Luvox in the morning and my psychiatrist just prescribed latuda at nights is it bad?
There is a risk for serotonin syndrome so you need to watch put for those symptoms.
Is Lurasidone safe to take with sodium valporate (mood stabilizers)
Yes it is.
Rexulti please
I got told to split the pills (cause of free samples) and been having side effects has this been heard of is their any info on why it's not good to split the pill?
You can split Latuda, this is common practice. If you're having side effects its not due to splitting the pill. Talk with your provider about it. The side effects may be transient and go away in a week. If not, perhaps you need a different treatment.
Can you do Rexulti vs Latuda? Making the switch after taking Rexulti for 2 1/2 years
That's a great video idea! I'll consider it. Thanks.
Can Latuda help insomnia due to MDD with mixed features, cptsd and anxiety? My Dr wants to try it to augment my 20mg of Cymbalta. (We already tried raising Cymbalta and it made everything worse)
I haven't used it for insomnia, but it is possible it could help since it has sedating effect and also good for those with comorbid anxiety. But always make sure there aren't any underlying issues, like nutrient deficiencies, first. Get your labs checked as I mention in this video ruclips.net/video/BJW06Ap-TmM/видео.htmlsi=3n9Agf0oiauvGk5t
Been trying to get a straight answer 20mg latuda with 300mg hcl buporion
Yes, ok combo- I answered your question in a previous post. Thanks for watching.
Serious question… Does this mean that Lurasidone/Latuda decreases serotonin???
No, it increases serotonin 5Ht1 and decreases others to increase dopamine and norepinephrine. All of it's differeny effects on serotonin whether antagonizing or agonism improve mood.
How does Latuda effect libido?
What’s the beat in the background 😅
That's my jam.
So it’s off label to help mania? Meaning it never was tested or it s not got good evidence?
Off label means not FDA approved. So it didn't go through clinical trials for that indication. It costs money to go through each trial for FDA indication.
@@LevelheadedMind great thank you!
Is bipolar 2 depression treated with different agents than bipolar 1 depression? Thanks
No, they are both treated with mood stabilizers, however, with Bipolar II efficacy is seen at lower doses.
Thank you
Hi Dr. ❤I been prescribed this for anxiety, some depression and insomnia depression. I’ve tried everything from Ssri’s to Snri and can’t stand the side effects. My Dr. don’t think I’m bipolar but I wonder what your opinion is in this. Hope you can help and thank you for your time.
Always search for root causes of your symptoms first before medicating. I made a video on it here ruclips.net/video/XRBr9pEKnx0/видео.html
We've had to keep bumping up my dose of Latuda. I have Manic Bipolar. I just took my first dose of 120mg. I can''t seem to get enough of this stuff to treat my manicness. It does help me sleep well and I'm pretty much living a normal lifestyle. This hasn't helped the non stop talking a mile a minute, and certain days I still have mood swings. But these have gotten better as we've gone. I was getting intense sweating on lower doses but its gotten better as we've gone up. I took Abilify for the past 20 years and gained an insane amount of weight. Switched to Latuda and the weight gain stopped. I would say overall this has been the best one so far. I've almost tried probably the rest of them. All of them resulted in extreme fatigue, made me gain weight quicker, and just didn't make me feel well. The only other one I was on that helped me lose a bunch of weight on was Geodon but the side effects sucked and snowballed month after month. I had a reaction on Fanapt that nearly killed me. Woke up every night sweating and felt like my heart was beating too fast made me feel wiped out and like I had just run a marathon in my sleep. Best to take Latuda with food because it really helps absorb the medicine. But its best to take it an hour before bedtime with a snack because it kicks like a mule and puts me to sleep quick.
I'm glad to hear you found something that works for you.
Im trying to go from 80 to 60. It was too much of a decrease so i think i was able to cut some old pills into a 10mg increment n take 70mg tonight. I been crying all day. N irritable. 😢 at 80 w the new med im on, vraylar , i cant even join a conversation at times. I want 9ff vraylar too its not for me
Is it ok to take Latuda 80mg with Valproate acid and Lamictol ?
I diagnosed with OCD and sever mood swings after the birth of my baby. I was diagnosed with Bipolar disorder and depression. Doctor prescribed me 500 mg of Valproate one in morning and one at night and Lamictol 25 mg one in morning and 2 at night including one benzodiazepine (diazepam)
Now he’s asking me to add Latuda in my recent treatment of 80mg.
Is it Ok ? My Baby is 6 months old now and i have still anxiety, sometimes bad mood swings and manic and also OCD.
Ask your doctor. You can also check web MDs free drug interactions checker online.
So does latuda stop the release of dopamine?
It blocks the release of D2 at receptor sites, so doesn't completely block dopamine, but turns down the specific D2 receptor, which is overactive in Bipolar and schizophrenia.
@@LevelheadedMind thank you very much I mean I actually know quite a bit but no one could give me the exact answer because most of them are generic even like when you read the medication and the chemical structure but anyways I didn't want to be putting both in my body and one's defeating the other. But I have always had a problem sleeping and I can tell you this I really feel like Latuda helps. I really don't know what's in that little pill but I got one more question for you. So I'm on 20 mg at night right now. I'm 185 lbs 5 11. I am not seeing any side effects right now which is great but let's say if she does bump me up to 40
How does it block dopamine but also enhance it?!?
Via partial agonism.
I have taken Latuda 20mg for 5 days. Loss of appetite and also extreme drowsiness at Night. I feel so much Anxiety taking this medicine. Intense Anxiety that I can’t even tolerate. Drowsiness and Loss of appetite is the side effect of this medication 💊? And also Anxiety is the beginning symptoms of taking this medication and later anxiety will be ok.
I feel so much anxiety that I can’t even bear. It’s just for the beginning or what ?
Ask to cut in half? I’m starting on 10mg. Take with food.
Not eating can cause people anxiety. So maybe try to eat some proteins and healthy fats.
My son had the most horrible rash on Lurasidone once he went from 20 to 40 mg.
Have you heard of of folks with BPD having success with this or other cluster Bs?
Haven't seen any specific data pertaining to Latuda and borderline PD, but generally speaking, atypical antipsychotics have been shown to be helpful in that population in low doses.
I love you ❤
Does latuda work for social anxiety
No indications for use in social anxiety.
I took this drug, and my empathy is just gone, and I feel some emotions again, but I had to fake emotions for 3 years off all medication. This medication changed me in a way there I don't feel like myself. I don't know who I am. It's an awful experence. I want to be human again.
This is how i feel on vraylar. Any imprivenent for you yet?
@@nativechique7589 I am a lot better. I was alcoholic all long.
Can you take Latuda as a pen?
Made me shake and scared lol
So Is It Very Likely To Have Heart Problem Over The Years?
Don't say that
@@JDOGFTW Just Being Honest
If it’s problematic for patients 65yrs or older, why begin a regime that isn’t sustainable over time?
All of the antipsychotics have that warning. That is why you need to weigh risk vs benefit in the case of long term treatment.
@@LevelheadedMind thank you for replying. I’m an Army vet with PTSD & bipolar. Currently taking Depakote and my doctor offered Latuda for bipolar depression. I’m afraid to take it because I’m not a suicide risk so the worst is daily interruptive depression. I am afraid to start such a regimen that has a point where it becomes a lethal threat. Lithium seems the only other alternative and that has similar severe side effects that I feel cursed to be sad until I meet God. Sounds gloomy but I’m actually trying to be logical. Any thoughts? Thank you
@@DoodlesRdope I'm 42 only 23 years away from that dark box baby if i make that old.
I couldn't work in day time
I’m on lithium and Latuda..
How is that working? My doctor is talking about starting me in lithium as well with latuda
@@heychunkybutt2010how is that working
Hi I am also on lithium and lurasidone
Trust the medicine bro I"m telling you.
Akathisia this shit made me psychotic and want to die. Took over 5 years for most akathisia from it to lessen.
Boy I gained 100 pounds on rispderal BOIIIIII
Why do Americans call doctors providers?
I'm not a doctor, I'm a nurse practitioner. Since many patients see both doctors and nurse practitioners who prescribe them medication, it's easier to just say your provider since it covers both.
Ngl being prescribed Latuda felt like I was being diagnosed with Schizophrenia I was like “AYYEEE WYM 🧍🏽♀️” It’s the second time my doctor tries an antipsychotic on me so I’m getting a bit suspicious 😅 I hope it works cause I’ve tried everything under the sun at this point… My problem is that I can’t stick to any treatment… I never take it for more than a year… I’m getting too old to do that though, I want to get my life going… I’m bipolar 2 btw
I’ve been taking Latuda for 3 weeks now!!! What a miracle drug!! My depression has significantly improved and my sleep schedule is almost entirely fixed. My ability to think clearly has also improved a lot along with my memory. I’m really grateful to have access to this medicine. I hope I can finally live a normal life, of course with patience and regular visits to my psychiatrist.
I’m hoping this works for you. It’s worked for me like day 1… and I’m only on 10mg to start - had to cut 20mg in half.
Doing in with ketogenic diet which may explain why lower dose is so effective.