Possible Dangers Associated with Saphris (Asenapine)

[Cuttlefish]

A psychopharmalogically inclined friend of mine and I were discussing new antipsychotics that were in various stages of development. One of these drugs that we talked about was Asenapine. "There's one issue about that drug though", he commented. "It activates the same 5HT2B receptors that Fenfluramine does". "You mean Phen-Fen?", I asked. "Yes", he responded. "A few people have died from cardiac arrest during clinical testing, actually".

I told him that Asenapine is now in the US market as Saphris, is actively being prescribed by psychiatrists, and is possibly being given to people who are inpatient at the moment, as it is the new drug on the block. I remember when I was in the hospital, and the medication that was given to patients possibly needing an antipsychotic was Invega because it was the new drug at the time. He was really surprised that it was now in the market since he was under the impression that it was going to be tested more before being released.

Here's a link to the article which discusses some of the relevant information as it pertains to this warning from a report by the FDA discussing the controversy within the administration itself about the approval and release of Asenapine by Schering-Plough. Yes, this information is, in fact, from an anti-pharmaceutical blog.

FDA Reviewer on Asenapine

However, this blog entry is referring to an actual and extensive report by the FDA. Here is a link to the full, 1067 page FDA report (it's a rather large PDF document, so hopefully you have a recent version of Adobe Acrobat installed on your computer).

UCM173877

Amendment 027 submitted June 13, 2008 fails to address the concerns raised regarding metabolism and mass balance as outlined in the original NDA review and clearly cannot address concerns regarding metabolism raised in this amendment. A critique of this amendment may be found in § 4.6 Appendix 6-Review of Amendment 027 Submitted June 13, 2008.

Asenapine causes serious cardiovascular toxicities including death due to pulmonary arterial hypertension and both direct and indirect effects on the myocardium, and also likely via indirect effects on platelet aggregation. These toxicities may either manifest acutely or chronically. Pharmacology / Toxicology data indicates that asenapine affects bone remodeling and ossification and this may be of concern during pregnancy, in growing children, and in other populations where bone remodeling is an issue, e.g. elderly women and renal failure patients.

Asenapine appears likely to cause pulmonary arterial hypertension in neonates, resulting in death and maiming of children, and may even cause death simply by breast feeding infants by exposed mothers to drug postnatally. There is also a probability that asenapine causes other connective tissue disorders, such as hernias and

rupture of tendons in addition to other problems.

Animal studies indicate that there may be an increase in motor activity. For a drug that may be used to treat bipolar disorder or ‘off-label’ for bipolar II, bipolar depression, or bipolar spectrum disorder in children increased motor activity could be mistaken for a symptom of the illness and not drug toxicity and could induce prescribers to inappropriately increase the dose, which would increase the risk of chronic cardiopulmonary toxicity.

Asenapine also appears to cause agranulocytosis and there is a possible risk of aplastic anemia. Mechanistically effects on platelet aggregation and strokes are also expected.

Death from asenapine can come suddenly and without warning in otherwise young healthy individuals due to arrhythmias or strokes with symptoms easily misattributed to something else such as orthostatic hypotension. More likely most serious cardiovascular toxicities are cumulative resulting in a Phen-Fen type toxicity especially when dosed for over a year, although symptoms which are likely to be misattributed to something else, (e.g. fatigue), may occur as soon as the first dose.

The entire development program appears designed to minimize detection and quantification of risks and thereby precludes the ability to write appropriate labeling. In fact it is this reviewer’s opinion that in several instances the sponsors’ actions clearly rise to the level of unlawful conduct and must be reported to the criminal investigators.

Preliminary review indicates that it is also less safe than competing agents and offers few if any advantages. With respect to benefit there is insufficient data to presently support use in schizophrenia and as for bipolar disorder the data indicted that only the most severely ill (YMRS > 27) may benefit with a few weeks of treatment but possibly not beyond that. Thus even efficacy in bipolar disorder I needs to be confirmed.

After further review this reviewer believes that Asenapine is unacceptably dangerous at this time, there was inadequate information submitted to assess safety and such information was expected. There is insufficient information to determine if it will have the effects it purports to as suggested in the labeling.

At the bottom of the blog entry quoting this report, there is an index of sorts in green print. You can use that index to navigate to the negative arguments against the approval of Asenapine in the PDF document (instead of having to look through all 1067 pages of the entire report). If Clozapine and Serzone are to be seen as lessons from the past, then we know that deaths directly attributed to the use of a medication do not have to be high in number at all for the drug to be pulled from the market (I believe that the incidence of fatal agranulosis and liver failure attributed to Clozapine and Serzone respectively is less than 1%). However, since this drug is now active in the market, the deaths that would convince the FDA to remove Asenapine from the market will now have to occur in the general population, as opposed to those that occur in clinical trials.

Edited November 1, 2009 by Cuttlefish

[SashaSue]

I'm not about to read 1000+ pages of criticisms of a med I'll probably never take. But just from your excerpts, it seems that the dangers cited are for breast feeding babies, or very young children. There are plenty of meds on which women are strongly discouraged from breast feeding, and the best ways of treating young children with bipolar diagnoses are very controversial.

From what I'd previously read about it, I saw nothing about anyone dying during the trials. And contrary to your info., I remember the trials looking pretty good, both efficacy and side effect wise.

I'm not clear as to what point you're trying to make by bringing in Serzone and Clozapine, as clozapine, at least, is still on the market, and widely regarded as a very effective medication.

Since your concern began with your friend's comparing Saphris to Fen-Phen, it seems worth mentioning that Fen-Phen was a combination of two meds, neither particularly dangerous on its own. Since no one's likely to be trying Saphris as a weight loss med, I dont think there's too much danger of a Fen-Phen type phenomenon.

[nalgas]

I'm not clear as to what point you're trying to make by bringing in Serzone and Clozapine, as clozapine, at least, is still on the market, and widely regarded as a very effective medication.

So's Serzone, actually, but only as a generic. They stopped making/marketing the brand name version after all the fuss, but the med itself wasn't banned/un-approved or anything. Other places still make it, and it's still used occasionally.

[AirMarshall]

I'll be really blunt since I ran out of lithium 3 days ago. This is BULLSHIT, however well intentioned.

Let's start off by blowing up the two blogs. One written by an unemployed newspaper writer who's qualifications include being bipolar and winning regional industry award for FOOD REVIEWS. Yeah right. credible. not. He claims not education or training in pharmacology, science, chemistry, biology, that would qualify him to open his damn mouth on these topics.

-The other blog is purely anti pharmaceutical/anti psychiatry. We have no fricken clue who is writing their crap.

-The thousand page briefing document (if it is genuine) is nothing more than a compilation of memos over about a 1.5 year period. It appears to be created as a reference to those memos and NOT as a comprehensive discussion of the safety of the product. Many of the memos are "pre meeting" documents outlining the agenda and decisions to be discussed during that meeting, however we do not see the meeting notes on the outcomes.

-The memos are not posted chronologically in the document, hence it is possible to read a memo near the end which was actually written and distributed 18 months earlier. This may give the mistaken impression that topics of concern were not addressed, when they may have been resolved.

-The bloggers selectively ignore statements in their same quoted documents that say "maybe, possible, could", which strongly undercut their single sentence assertions of danger and disaster. Further they make no responsible attempt to track a particular issue thru to resolution. When a document mentions that an issue is referred to another researcher who determines that it is not a problem, they ignore it and assume that it is automatically a systematic action to cover up, bungle, or irresponsibly favor the manufacturer.

- The scientific method and medicine too, has a natural sort of give and taken. Seldom are there absolutes values of safe/unsafe, effective/ineffective, good/bad. Opinions may be opposing, interpretations of the same day likewise. A balance must be struck based up a reasonable amount of research, for a reasonable cost, in a reasonable time, by reasonable people who are technically competent. The internet has made possible the spread of a hysterical paranoia among people who don't know shit. Let the experts do their jobs!

a.m.

[Cuttlefish]

There is a give and take to every antipsychotic that I can think of. I also highly doubt that the recommendations made during the approval process of any psychiatric medication agreed with each other. Unfortunately, we will not know if these negative views on Asenapine hold water until it has been in the market for some time, and the side effects are noted among the general population.

The idea of bringing up Serzone and Clozapine into this was that they were both removed from the market after they were found to have fatal side effects.

However, both medications are, in fact, still used because they are extremely effective. The Serzone generic is still available, and Clozapine was reinstated after it was found to be one of the most effective, if not the most effective antipsychotic. The difference between their past and current use, however, is that the people who take them are now aware of those risks, and have the appropriate testing done to avoid death. Serzone users have their liver functioning tested regularly, and Clozapine users have their blood cell counts tested regularly.

Saphris is a new medication. It may very well be extremely effective, and, should it cause deadly side effects as the critics of its approval say, similar precautions could be taken for its users in the future. But we will not know about all of the risks of this drug until it has been prescribed to the public for a time.

My reasons for posting this were noble, if not misguided. The critics are probably wrong, but there is the chance that their concerns are valid, and if they are, we are looking at yet another medication oriented series of lawsuits in the near future.

[Velvet Elvis]

At the bottom of the blog entry quoting this report, there is an index of sorts in green print. You can use that index to navigate to the negative arguments against the approval of Asenapine in the PDF document (instead of having to look through all 1067 pages of the entire report). If Clozapine and Serzone are to be seen as lessons from the past, then we know that deaths directly attributed to the use of a medication do not have to be high in number at all for the drug to be pulled from the market (I believe that the incidence of fatal agranulosis and liver failure attributed to Clozapine and Serzone respectively is less than 1%). However, since this drug is now active in the market, the deaths that would convince the FDA to remove Asenapine from the market will now have to occur in the general population, as opposed to those that occur in clinical trials.

Cloozapine is still one of (if not the) most effective APs on the market. Yeah the side effects are drastic but so are the conditions it's intended to treat.

As long as Saphris is being used to treat acute psychosis from bipolar or schizophrenia I don't see the problem with it. If they try and extend it to treat depression and anxiety, yeah, that's a problem.

With all meds you've got to weigh the risks of the side effects against the risks of the conditions they are designed to treat.

[Cuttlefish]

So reading through the FDA document (not just the parts with arguments against Saphris), it appears that Saphris is an antagonist of the 5HT2B receptor. The risk of Phen-Fen-like heart damage comes when a substance is an agonist of the 5HT2B receptor. The proposed danger comes from the possibility of an as of yet unknown, hypothetical metabolite of Saphris that could be an agonist of the 5HT2B receptor.

This led me back to my friend's comparison of Asenapine to Fenfluramine (Phen-Fen is a combination of drugs, but Fenfluramine is a part of Phen-Fen, Pondimin, that is infamous for causing damage to the heart). Was Fenfluramine itself an agonist of the 5HT2B receptor? Or was it one or more of its metabolites? I found this study about Fenfluramine's effects on the various receptors, including the 5HT2B receptor, versus its metabolites and other drugs.

Possible Involvement of 5-HT2B Receptors in Cardiac Vulvopathy

The norfenfluramines had high affinity (10 to 50 nmol/L) for the5-HT_2B receptor, in confirmation of recent studies. Functionalstudies demonstrated that the norfenfluramines were full agonistsat the 5-HT_2B site. The fenfluramines, in contrast,bound to the 5-HT_2B receptor with K_i values of 5 µmol/L.

So Fenfluramine itself is an agonist as well! It's its metabolites that cause the damage to the heart that Phen-Fen is famous for. Now I was curious why these concerns with Asenapine were not bought up with related atypical antipsychotics like Olanzapine or Quetiapine, or were at least not mentioned by critics in the report.

Asenapine: A Novel Pharmacologic Agent

It would appear that Asenapine has a unique receptor profile that is different from the atypical antipsychotics that have come before it. From research, it appears to be the only atypical antipsychotic that affects the 5HT2B receptor in such a manner, thus the argument of the few critics (who didn't seem to be liked very well by their peers, admittedly) against the approval of Asenapine based on the idea that it can cause Phen-Fen-like heart damage.

Were there accounts in the report of otherwise physically healthy people having to discontinue Saphris because of serious cardiac events, sometimes requiring medical intervention? Yes. They were not usually fatal though, and the users usually recovered after discontinuing the drug. However, the idea of Saphris causing Phen-Fen-like heart damage is based on the presumption that, like Fenfluramine, one or more of its metabolites will be a potent agonist of the 5HT2B receptor.

Possible? Yes. Imminent? Not necessarily.

(As a side note my psychopharmalogically inclined friend also told me that Asenapine is considered a dirty drug in pharmacology because it affects so many different receptors in the body. So in medication land, some drugs are considered "cleaner" than others!).

Edited November 1, 2009 by Cuttlefish

[AirMarshall]

It's really late and I'm getting punchy. I did read the summary of the article about Fenfluramine and heart valve damage. I can't follow up on it tonite(morning). However, the argument I would use against all this worry is this article is 10 years old and if it represents the strongest evidence against this drug then the whole house of cards falls.

A 10 year old hypothesis about AAP's that has generated no dangerous results, and a hypothetical metabolite perhaps causing unproven heart problems.

Areas for followup: Later articles citing the 2000 Fenfluramine hypothesis, and examine the exact type of heart problems of those in the phase III trials suffered. Are they the same as with Fen?

nite. a.m.

[Cuttlefish]

It's really late and I'm getting punchy. I did read the summary of the article about Fenfluramine and heart valve damage. I can't follow up on it tonite(morning). However, the argument I would use against all this worry is this article is 10 years old and if it represents the strongest evidence against this drug then the whole house of cards falls.

A 10 year old hypothesis about AAP's that has generated no dangerous results, and a hypothetical metabolite perhaps causing unproven heart problems.

Areas for followup: Later articles citing the 2000 Fenfluramine hypothesis, and examine the exact type of heart problems of those in the phase III trials suffered. Are they the same as with Fen?

nite. a.m.

Here's a more recent study detailing the effects of drugs that agonize the various 5HT receptors of the heart, including Norfenluramine, on the hearts of animal subjects:

5-Hydroxytryptamine (5HT) Receptors in the Heart Valves

The next is a quote from the (less accusatory half of the) FDA report of all of the reported deaths of the patients who were given Asenapine during the duration of the clinical trials:

There were 27 deaths in the asenapine program overall (including the death in a patient in the clinical pharmacology program), including 22 in patients taking asenapine.

-8 of the asenapine deaths were suicides (see discussion under 5.2.4)

-9 of the asenapine deaths were from serious medical events that are relatively common as background events [pulmonary embolism (2), pneumonia, CVA, complications of

seizure, metastatic lung cancer, fetal death in premature delivery, heart failure, MI]. All of these deaths were plausible, in my view, as background events for the patients who

experienced them, and there is no obvious pattern to any of these deaths. The seizure death occurred on day 204 of treatment, and it is unknown whether or not it was related

to taking asenapine, but could have been. Seizure is a recognized risk of most antipsychotic drugs. (Dr. Levin fully discusses these cases and I will not further discuss

them.)

-1 of the asenapine deaths was from multiple drug overdose; this was a patient who was abusing cocaine, methadone, diazepam, and diphenhydramine, and this death should not

be attributed to asenapine.

-2 of the deaths occurred in patients who were no longer taking asenapine, and should not have been linked to asenapine (041013-28 and A7501018-10021006).

-Insufficient information was provided for 2 of the deaths (unfortunately, in both instances, it appears that follow-up information would not be obtainable):

Pages 267-270 of the report describe the known cardiovascular adverse events. None of them seemed to be due to valvular heart disease, as would be expected by a Phen-Fen-like agonist of the 5HT2B receptor. It is alarming that many of the adverse events were in more or less physically healthy patients, but most of the adverse events were not attributed only to Asenapine, but a combination of preexisting conditions and Asenapine. Many of these adverse events necessitated medical intervention, but overall, there were only 22 deaths that could be partially or directly attributed to Asenapine in the first half of the report. Unfortunately, the other half of the report is against Asenapine's approval, and so half of the report either shows additional deaths that were not reported, or half of the report exaggerates the amount of deaths that were due to cardiac arrest and/or heart failure.

However, you guys should probably know that it would appear that the main opponent to Asenapine's approval tried to pin a subject's death from a stab wound inflicted by his partner on Asenapine! In my opinion, it wouldn't be a bad idea to include a black box warning of an increased risk of suicide like Quetiapine does, and perhaps even a warning of an increased risk of cardiac and circulatory arrest like Clozapine does. This in addition, of course, to the warning of increased risk of death in elderly patients that all antipsychotics seem to have.

[nalgas]

However, you guys should probably know that it would appear that the main opponent to Asenapine's approval tried to pin a subject's death from a stab wound inflicted by his partner on Asenapine! In my opinion, it wouldn't be a bad idea to include a black box warning of an increased risk of suicide like Quetiapine does, and perhaps even a warning of an increased risk of cardiac and circulatory arrest like Clozapine does. This in addition, of course, to the warning of increased risk of death in elderly patients that all antipsychotics seem to have.

And apparently an increased risk of getting stabbed. Heh.

[AirMarshall]

The bigger take away lesson: Don't bring a pill bottle to a knife fight in bed.

a.m.

[SashaSue]

It's really late and I'm getting punchy. I did read the summary of the article about Fenfluramine and heart valve damage. I can't follow up on it tonite(morning). However, the argument I would use against all this worry is this article is 10 years old and if it represents the strongest evidence against this drug then the whole house of cards falls.

A 10 year old hypothesis about AAP's that has generated no dangerous results, and a hypothetical metabolite perhaps causing unproven heart problems.

Areas for followup: Later articles citing the 2000 Fenfluramine hypothesis, and examine the exact type of heart problems of those in the phase III trials suffered. Are they the same as with Fen?

nite. a.m.

Here's a more recent study detailing the effects of drugs that agonize the various 5HT receptors of the heart, including Norfenluramine, on the hearts of animal subjects:

5-Hydroxytryptamine (5HT) Receptors in the Heart Valves

The next is a quote from the (less accusatory half of the) FDA report of all of the reported deaths of the patients who were given Asenapine during the duration of the clinical trials:

There were 27 deaths in the asenapine program overall (including the death in a patient in the clinical pharmacology program), including 22 in patients taking asenapine.

-8 of the asenapine deaths were suicides (see discussion under 5.2.4)

-9 of the asenapine deaths were from serious medical events that are relatively common as background events [pulmonary embolism (2), pneumonia, CVA, complications of

seizure, metastatic lung cancer, fetal death in premature delivery, heart failure, MI]. All of these deaths were plausible, in my view, as background events for the patients who

experienced them, and there is no obvious pattern to any of these deaths. The seizure death occurred on day 204 of treatment, and it is unknown whether or not it was related

to taking asenapine, but could have been. Seizure is a recognized risk of most antipsychotic drugs. (Dr. Levin fully discusses these cases and I will not further discuss

them.)

-1 of the asenapine deaths was from multiple drug overdose; this was a patient who was abusing cocaine, methadone, diazepam, and diphenhydramine, and this death should not

be attributed to asenapine.

-2 of the deaths occurred in patients who were no longer taking asenapine, and should not have been linked to asenapine (041013-28 and A7501018-10021006).

-Insufficient information was provided for 2 of the deaths (unfortunately, in both instances, it appears that follow-up information would not be obtainable):

Pages 267-270 of the report describe the known cardiovascular adverse events. None of them seemed to be due to valvular heart disease, as would be expected by a Phen-Fen-like agonist of the 5HT2B receptor. It is alarming that many of the adverse events were in more or less physically healthy patients, but most of the adverse events were not attributed only to Asenapine, but a combination of preexisting conditions and Asenapine. Many of these adverse events necessitated medical intervention, but overall, there were only 22 deaths that could be partially or directly attributed to Asenapine in the first half of the report. Unfortunately, the other half of the report is against Asenapine's approval, and so half of the report either shows additional deaths that were not reported, or half of the report exaggerates the amount of deaths that were due to cardiac arrest and/or heart failure.

However, you guys should probably know that it would appear that the main opponent to Asenapine's approval tried to pin a subject's death from a stab wound inflicted by his partner on Asenapine! In my opinion, it wouldn't be a bad idea to include a black box warning of an increased risk of suicide like Quetiapine does, and perhaps even a warning of an increased risk of cardiac and circulatory arrest like Clozapine does. This in addition, of course, to the warning of increased risk of death in elderly patients that all antipsychotics seem to have.

Just to be clear here, Asenapine is an antaganist at a receptor of which Fenlurazine, is an agaonist, and for some reason we're still discussing the likelihood of similar events from the two? Does this make sense in some way I'm not smart enough to grasp today?

[SashaSue]

an admittedly quick search of fda.gov brought me nothing having anything to do with thie discussion. Same with the PI sheet. No big concerns about heart issues, none of it. I think it's black boxed for use in senior's with dementia, but that's it. It's never a bad idea to check sources before posting controversial info. Just saying.

[nalgas]

Can "just sayin'" just die already? Thanks.

[buddha443556]

Got my hot little hands on a couple sample boxes of Saphris. It looks like one really dirty antipsychotic. Considering my reactions to other psych meds, SCA sounds good. Wish me luck, I start it tomorrow night. Maybe I'll get my birthday wish.

[buddha443556]

First pill, knocked me out for 15 hours. Recommended dose is 5mg twice a day. I'm only doing 5mg once a day because I'm medication intolerant. Heck of a nap.

[Cuttlefish]

First pill, knocked me out for 15 hours. Recommended dose is 5mg twice a day. I'm only doing 5mg once a day because I'm medication intolerant. Heck of a nap.

I guess it's sedating then? I was thinking it would be activating, like Abilify maybe. I hope it kicks your psychosis in the junk!

[buddha443556]

First pill, knocked me out for 15 hours. Recommended dose is 5mg twice a day. I'm only doing 5mg once a day because I'm medication intolerant. Heck of a nap.

I guess it's sedating then? I was thinking it would be activating, like Abilify maybe. I hope it kicks your psychosis in the junk!

Sedating, fatiguing but give it time to build up in my system ... then I'll have the interesting side-effects.

So far diarrhea and fatigue. It's a nasty tasting pill, sublingual - you stick it under your tongue, makes my tongue numb. You would think for 10 bucks a pill they could afford a little mint flavoring!

That 15 hour nap did wonders for the psychosis.

[buddha443556]

Sedation is over, insomnia is back. Titrating up to 5mg BID. If I don't move around, it's not so bad, when I do it feels like I'm dragging an anchor. Joints hurt. Stool was rather black yesterday, check it again next time maybe it was just something I ate. Have had some gut pain just after taking the med, doesn't last long and seems to be getting less intense with every dose.

I have serious doubts about anything that doesn't help me sleep. I only get worse without sleep. One of the nice thing about Invega is I slept normal till I had problems with it.

[Guest Misty]

DH had his first dose tonight. out cold. please oh please Miss Saphris take the voices away. we have tried everything else.

[Guest KitKat]

I am being treated with Saphris as an "off label" treatment. So far, I feel normal. I am not so worried about side affects. I am pleased that I am feeling better.

[DarkTriad69]

took my first Saphris tablet 2 nights ago.... knocked out for like 20 hours with crazy dreams. i have real bad allergies so when i first took it i couldn't breathe but was too tired to do anything about it.....scary stuff. took an allgery pill and went back to sleep fine. now its my second "morning" on it, and i am awake. its 5:26 a.m. and can't get back to sleep. hopefully this med is a lifesaver and changer. although i'm worried about the "dangers" on it. so far it's okay, although the real problem was the allergies.

[Guest sean37]

You dipshit! asenapine acts as an antagonist at the 5ht2b receptor. It does not stimulate it. Same as zyprexa.

[Velvet Elvis]

You dipshit! asenapine acts as an antagonist at the 5ht2b receptor. It does not stimulate it. Same as zyprexa.

Let's see. According to RxList:

Asenapine exhibits high affinity for serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, and 5-HT7 receptors (Ki values of 2.5, 4.0, 0.06, 0.16, 0.03, 1.6, 0.25, and 0.13 nM), dopamine D2, D3, D4, and D1 receptors (Ki values of 1.3, 0.42, 1.1, and 1.4 nM), α1 and α2-adrenergic receptors (Ki values of 1.2 and 1.2 nM), and histamine H1 receptors (Ki value 1.0 nM), and moderate affinity for H2 receptors (Ki value of 6.2 nM). In in vitro assays asenapine acts as an antagonist at these receptors. Asenapine has no appreciable affinity for muscarinic cholinergic receptors (e.g., Ki value of 8128 nM for M1).

http://www.rxlist.com/saphris-drug.htm

It looks like you're right, but that's no reason to call him a dipshit.

[Guest BGHaze]

I'll be really blunt since I ran out of lithium 3 days ago. This is BULLSHIT, however well intentioned.

Let's start off by blowing up the two blogs. One written by an unemployed newspaper writer who's qualifications include being bipolar and winning regional industry award for FOOD REVIEWS. Yeah right. credible. not. He claims not education or training in pharmacology, science, chemistry, biology, that would qualify him to open his damn mouth on these topics.

-The other blog is purely anti pharmaceutical/anti psychiatry. We have no fricken clue who is writing their crap.

-The thousand page briefing document (if it is genuine) is nothing more than a compilation of memos over about a 1.5 year period. It appears to be created as a reference to those memos and NOT as a comprehensive discussion of the safety of the product. Many of the memos are "pre meeting" documents outlining the agenda and decisions to be discussed during that meeting, however we do not see the meeting notes on the outcomes.

-The memos are not posted chronologically in the document, hence it is possible to read a memo near the end which was actually written and distributed 18 months earlier. This may give the mistaken impression that topics of concern were not addressed, when they may have been resolved.

-The bloggers selectively ignore statements in their same quoted documents that say "maybe, possible, could", which strongly undercut their single sentence assertions of danger and disaster. Further they make no responsible attempt to track a particular issue thru to resolution. When a document mentions that an issue is referred to another researcher who determines that it is not a problem, they ignore it and assume that it is automatically a systematic action to cover up, bungle, or irresponsibly favor the manufacturer.

- The scientific method and medicine too, has a natural sort of give and taken. Seldom are there absolutes values of safe/unsafe, effective/ineffective, good/bad. Opinions may be opposing, interpretations of the same day likewise. A balance must be struck based up a reasonable amount of research, for a reasonable cost, in a reasonable time, by reasonable people who are technically competent. The internet has made possible the spread of a hysterical paranoia among people who don't know shit. Let the experts do their jobs!

a.m.

I have been diagnosed with Manic Bipolar Skitzo problems. I have tried many meds to try to conrol my anger issues, but they have all failed, even caused me to be more paranoyed than usual. One med even caused an allergic reaction to it. I have recently been put on Saphris, but am having difficulty wanting to take the medication. I think doctors should evaluate the prescriptions they are given out more closely and understand that not everyone will react to the same meds. It has gotten to where they just prescribe what the hell they want to and don't give one concern about the patients they are given it to. So how do we actually know if any of the medications they are given us is safe? We don't and should be skeptical about what we endure in our bodies, because not knowing could give people a bad reaction or they could loss their lives over what they think that the dr. is given them is safe and effective. So I will warn people, observe and investigate any prescription given to you, because this is your life and you only get one life to live.

Edited September 6, 2010 by null0trooper

[Guest Bunny]

I will begin by saying all of this is foreign to me. My husband is now taking saphris 3 times a day at 10 mg each. He has taken this for the pass 9 1\2 months. My husband was diagnosed with having schizophrenia since he was 24 years old. He is now 57 he has taken different medication over the years and in his mind nothing has worked.

This pass New Year's Eve he begin taken Saphris I have notice some positive things working. One, he is more calm, he doesn't have the feeling or thoughts as often as he did. He also seems happy and more confident. he would have bad feeling and hear voices while driving but those feelings has even slow down. Now for down falls, My husband went from being very sexually active to not having sex at all. he does not want to do his favorite thing that much like fishing, sailing, and movies; in fact nothing we use to do while dating and even since we have married. He sleeps all day from the time he comes home from work he takes his meds and he sleeps 12 hours wakes up and sleeps on the chair until it's time for work again. We've have not have sex for almost 10 months I had suggested him having is levels checked after seeing the commercial isitlow.

He bought his concerns to his Therapist that prescribe this new medication he was told that he is getting older and that's all it is; that if you weigh the odds not having sex come last with the progress that we have seen. I agree to a point but this medication as it states in the inserts provided is given to elderly who is either under nurses care even in nursing homes who is not active in the community. My husband is to young in my opinion to go through this.

I think that is stupid to tell any person especially someone who is a newlywed that your old and sex should be on hold to see if there's progress. His Therapist told him that he does not have sex and that is not an issue in his home; This is about my husband not him. I wanted to join my husband on his visit to share my concerns, my husband felt this would not be a good idea.

My husband bought this also to his family doctor attention who check his hormone level and found it is really low and he is taking shots for it; His family doctor also share that maybe he should take a lesser dose of saphris maybe 2 time daily to see if it might help, he was told by his Therapist not to sway away from his present dose. The shots my husband is taken is slowly working he is getting pimples and aggressiveness like you see in teenage boys But No sex.

He has not had an orgasms in 10 months even with taking Calais nothing is working. I am in search of some kind of help. My husband and I have only been married for three years and you can imagine how difficult this has been. I thought maybe the doctor is right maybe it is age. We are thirteen years different in age but I know lots of men in their 50's who have normal sex lives. It make me angry when his doctors tells him this, I think it is the medicine that is affecting him! We went from having no sex problems to no sex in ten months. Any information anyone can give me regarding this issue or even something we can try will be so appreciated thanks worried in Texas

Bunny

At the bottom of the blog entry quoting this report, there is an index of sorts in green print. You can use that index to navigate to the negative arguments against the approval of Asenapine in the PDF document (instead of having to look through all 1067 pages of the entire report). If Clozapine and Serzone are to be seen as lessons from the past, then we know that deaths directly attributed to the use of a medication do not have to be high in number at all for the drug to be pulled from the market (I believe that the incidence of fatal agranulosis and liver failure attributed to Clozapine and Serzone respectively is less than 1%). However, since this drug is now active in the market, the deaths that would convince the FDA to remove Asenapine from the market will now have to occur in the general population, as opposed to those that occur in clinical trials.

Cloozapine is still one of (if not the) most effective APs on the market. Yeah the side effects are drastic but so are the conditions it's intended to treat.

As long as Saphris is being used to treat acute psychosis from bipolar or schizophrenia I don't see the problem with it. If they try and extend it to treat depression and anxiety, yeah, that's a problem.

With all meds you've got to weigh the risks of the side effects against the risks of the conditions they are designed to treat.

[null0trooper]

I will begin by saying all of this is foreign to me. My husband is now taking saphris 3 times a day at 10 mg each. He has taken this for the pass 9 1\2 months. My husband was diagnosed with having schizophrenia since he was 24 years old. He is now 57 he has taken different medication over the years and in his mind nothing has worked.

Bunny,

Welcome to the bottom line with regard to mental health treatment: the person being treated has to decide what being able to function in society is worth to himself. For the majority of people, the only cost is one or two cheap pills a day. For the rest of us the question, the cost in medication and/or side effects - even for partial relief - is higher. It is probably the medication that is leaving him sedated and uninterested in sex. It is certainly the medication that is allowing him to work and spend more or his remaining time with you than with the voices.

If the reduced action in the bedroom has you bothered to the point of counting *his* orgasms and looking for ways to change his treatment so you can get more sex, it's time for you to seek some counseling for ways to deal with the changes.

[gizmo]

There has got to be a hierarchy for getting on mental meds.

1. reduction of symptoms

2. little to no side effects such as sleeping all day, dulled cognition,etc

3. Return to normal productive life.

...

Curing of sexual side effects. Your husband is doing well now. Why go and tinker with his med, against doctor advice.

I have a sexual side effect problem because of one of my meds. I am trying to get stable before I deal with it, Needless to say there are a lot of things that you can sexually satisfying that have nothing to do with penis involvement? Or without orgasm?

[Guest susie1sexylady@aol.com]

My Dr. started me on this a month ago.I brought it home&was afraid to start.I have never done anti-P's before. It's for Manic-depression. I did take one a few weeks ago slept like a baby,but felt hung-over all day.

I took one again last night after a manic episode of being up for a day&half. I feel like crap. Slept well,but feellike I have a cold?Also my back is killing me today? I don't like what I have been reading about it.especially the paper in the trail samples.

Iam not taking it anymore. I have meds for pain due to arthrisis in my spine,so I gotta watch what I take.Also Iam on Klonapine. I can't find anythin that works for me.

Iam 54 tomorrow. Iam not going to take this even though I slept good. Thanks for the info.SUSIE

[Stars]

I have tried several of the new Atypical AP's. I was on 1 mg of stelazine for 18 yrs and developed TD. I pucker like a guppy and blow . My doc took me off of stelazine and has tired all of the known AP"s. Geodon causes me to have what feels like a really bad instant painic attack. Abilify looked like it was going to be the ticket, but at about 2 weeks I got manic on it, so we stopped it. Latuda causes manic feeling right away. Zyperxa helps but I have diabetes and the weight gain is not acceptable. Plus it causes TD after 1 or 2 days, but I save it for emergencies. Seroquel at 25 mg for a while was great, helped me sleep but still left me not wanting to do anything but stay in bed. Risperdal left me swollen and punch drunk. I tied lamictal and it made me manic right away too. Right now I am on Seroquel XR 50 and Strattera 40 mg am but am staying up nights and sleeping days. I have no motivation to anything.

Last time I saw Pdoc he gave me samples of several AP's and said try them . I just tried the Saphris , but just took 1/2 of the 5 mg b/c if It is stimulating maybe I wont' be awake all night. All I feel from this is slightly more focused and a bit of buzzing in my ears and my sinuses and nose feel less congested( sort of like a decongestant effect). I feel a bit of chest discomfort , sort of like a do when I have anxiety attacks, ( dull ache in the sternum) but nothing else yet. I get this same effect with most antidepressants. Usually whatever dose is the typical dose I end up being able to take 1/3 or 1/4 that dose. I feel like I might be able to sleep but who knows.

Related to the post regarding this issue:

Sex is very important in a marriage and since there are numerous things to choose from I would not choose a drug that affected sex unless it was the last drug on earth. Sex and marriage are very important to your stability too.

I'd give anything to be able to just take that 1mg of stleazine again but the TD I have is really embarrassing and gests activated easily.I have been dx with Psychotic depression . It has been resistant to treatment since I had to stop the stleazine. I am even considering ECT.

I hope the saphris helps b/c so far Seroquel is been the only one I can tolerate that does not activate my TD but only at low dose, do I will probably know by am. So far I am feeling a slight movement in my upper lip so that is Not good.

Edited May 13, 2013 by Stars

[Stars]

This drug is stimulating for me. I slept for about 2 hours and woke up and have not been able to rest all day. so for sure if I take this again it will be an AM drug.

[tashakitty]

I have tried several of the new Atypical AP's. I was on 1 mg of stelazine for 18 yrs and developed TD. I pucker like a guppy and blow . My doc took me off of stelazine and has tired all of the known AP"s. Geodon causes me to have what feels like a really bad instant painic attack. Abilify looked like it was going to be the ticket, but at about 2 weeks I got manic on it, so we stopped it. Latuda causes manic feeling right away. Zyperxa helps but I have diabetes and the weight gain is not acceptable. Plus it causes TD after 1 or 2 days, but I save it for emergencies. Seroquel at 25 mg for a while was great, helped me sleep but still left me not wanting to do anything but stay in bed. Risperdal left me swollen and punch drunk. I tied lamictal and it made me manic right away too. Right now I am on Seroquel XR 50 and Strattera 40 mg am but am staying up nights and sleeping days. I have no motivation to anything.

Last time I saw Pdoc he gave me samples of several AP's and said try them . I just tried the Saphris , but just took 1/2 of the 5 mg b/c if It is stimulating maybe I wont' be awake all night. All I feel from this is slightly more focused and a bit of buzzing in my ears and my sinuses and nose feel less congested( sort of like a decongestant effect). I feel a bit of chest discomfort , sort of like a do when I have anxiety attacks, ( dull ache in the sternum) but nothing else yet. I get this same effect with most antidepressants. Usually whatever dose is the typical dose I end up being able to take 1/3 or 1/4 that dose. I feel like I might be able to sleep but who knows.

Related to the post regarding this issue:

Sex is very important in a marriage and since there are numerous things to choose from I would not choose a drug that affected sex unless it was the last drug on earth. Sex and marriage are very important to your stability too.

I'd give anything to be able to just take that 1mg of stleazine again but the TD I have is really embarrassing and gests activated easily.I have been dx with Psychotic depression . It has been resistant to treatment since I had to stop the stleazine. I am even considering ECT.

I hope the saphris helps b/c so far Seroquel is been the only one I can tolerate that does not activate my TD but only at low dose, do I will probably know by am. So far I am feeling a slight movement in my upper lip so that is Not good.

I also have TD and have gotten very fat (again!) after another run of Neurontin. I got kidney disease from decades on lithium, stopped it went away. Have taken almost everything. Got TD from decades on Stelazine, but was able to work for decades, but BP II turned into BP I Ultra Ultra Rapid Cycling  NON-STOP for 12 years, had to quit work. Got into suicidal depression now and more deperate than ever. abilify was a miracle drug for me, but triggered TD. Want to try Saphris or Latuda now and don't hear anyone talking about having TD, etc-also afraid of Getting diabetes and/or worsening TD. What do you or anyone out there think about this-have similar problems/experience?