Thursday, September 10, 2009

Lurasidone = Asenapine = Iloperidone

Last week I asked, rhetorically, whether I should waste my time reviewing the published researched on the potential new antipsychotic drug Dainippon (lurasidone). Luckily for me, there isn't much (1a, 1b).

Well that's not entirely true. I did come across this study titled, "公司已在美国启动供给N0的前列腺素" (2), and this one, "使用静脉注射免疫球蛋白" (3). At least, I think those are research articles..., I'm not quite sure.

Anyway, the great news is that there are plenty of press releases (4, 5) to extol the virtues of this drug prior to it being reviewed by the FDA and the psychiatric community (I just made myself laugh, that never happens 6).

Here are some quotes from this press releases:

"lurasidone was well-tolerated and had a relatively low discontinuation rate."

"Lurasidone's effect on weight was similar to placebo (median change 0.3 kg for overall lurasidone group vs. 0 kg for placebo) as was its effect on lipid and glucose measures. Lurasidone was also well tolerated with a lower overall discontinuation rate (31%) compared to placebo (43%) and few adverse event-related discontinuations (6% and 2% for the overall lurasidone group and placebo, respectively)."

"Adverse events seen in the trial were generally mild. The most commonly reported adverse events for lurasidone (greater than 5% and at least twice the rate of placebo) were akathisia (17.6% vs. 3.1% placebo), somnolence (11.7% vs. 5.5%), parkinsonism (6.8% vs. 0), and increased weight (5.1% vs. 2.4%)."


"The development program for lurasidone is intended to establish efficacy for the core symptoms of schizophrenia, characterize its safety profile and explore its effects in the treatment of cognitive impairment and other areas not adequately addressed by current therapies"


"If you look at the weight gain, the lipid changes, it's among the most benign of any antipsychotic drugs, clearly better than olanzapine, clozapine and Seroquel"


"From the point of view of efficacy and side effect profile, once a day administration, the fact that the lower dose works as well as the higher dose, I think this is going to have a very good chance of major acceptance among my colleagues"
Douche bag.

That last quote is from this press release (5), and that lower dose he is referring to is 40mg. I guess he didn't read this press release (4), which reported this, "also evaluated two other fixed doses of lurasidone, 40 mg/day and 120 mg/day, which did not demonstrate separation from placebo on the PANSS or CGI-S at study endpoint."

Here are the reported adverse events from this article (1):
From the press releases, "The most commonly reported adverse events for lurasidone (greater than 5% and at least twice the rate of placebo) were akathisia (17.6% vs. 3.1% placebo), somnolence (11.7% vs. 5.5%), parkinsonism (6.8% vs. 0), and increased weight (5.1% vs. 2.4%)."

"The most common adverse events reported at a frequency of at least 5% and at least twice the rate of placebo among the combined lurasidone doses in these trials were akathisia (11.6% vs. 4.7% placebo), somnolence (14.3% vs. 7.1%) and nausea (14.8% vs. 6.1%)."

Then there is this beauty, "the adverse events were generally mild, such as restlessness and sleepiness." That last statement just made my third testicle descend.

All side effects are from the 80mg dose.The above-referenced study had a relatively small sample size (n=90), which I think downplays the akathisia (8.9%), while the summarized studies in the press releases are larger (n=500 & n=392) and have the high rates of akathisia.

Important Point: Akathisia is not a MILD side effect. Just asked anyone who has ever experienced it.

"These data showed that lurasidone was well tolerated with a low propensity for EPS."

More Important Point: Akathisia and parkinsonism ARE extrapyramidal symptoms.

Here are the side effect profiles from two other antipsychotic drugs:
asenapine & risperidone

iloperidone & haloperidol
Wow, lurasidone has a higher report rate of akathisia than haloperidol! (17.6% versus 13.6%). Correction, that's high (really high) dose haloperidol (15mg) . Taken together, lurasidone does not look any different, just more of the same.

"Zyprexa and similar drugs can cause significant weight gain and have been linked to increased risk of diabetes...Lurasidone was well tolerated with a discontinuation rate nearly identical to placebo -- 40 percent versus 39 percent." Have they forgotten that there already is a class of drugs that do not cause those severe metabolic changes? They're the first generation antipsychotics.

"...but this class of drugs as a whole is so superior to the first generation drugs said Meltzer." In what way is that Dr. Meltzer? Efficacy? No. Side effects? Nope. Patient tolerance? No again.

I'm feeling the need to be sued for defamation: Dr. Meltzer is a flabby bag of douche!

There's no point in reviewing the efficacy results here. Just read any random antipsychotic clinical trial. The numbers are all the same. No new psychiatric drug, antidepresant, antipsychotic, mood stabilizer, whatever, has been shown to be more effective than its predecessors in a clinically meaningful way.

Key points to remember:
1. This drug is being pushed as safer. So is asenapine and iloperidone. So will any new drug on the horizon. It's marketing. You don't manipulate the identical set of brain receptors and get less side effects. You only get different side effects.
2. The majority of the authors on these study are employees of the pharma company sponsoring the trial. The same is true for the asenapine and iloperidone studies. That's called bias. Double blind does not mean a damn thing.
3. The remainder of the second generation antipsychotics are becoming generic. That means they will be prescribed less. That means there will be a void, which can be filled by newer more expensive drugs. Since these drugs are more of the same, patients don't necessarily receive a lower quality of care, while at the same time drug pimps can continue to rake in the cash (7).

I was right. This was a waste of time (8, 9). I'm through reviewing drug research.

* Special thanks to Neuroskeptic and Cypher for teaching me how to lift images from secured files =)

ResearchBlogging.org

Nakamura M, Ogasa M, Guarino J, Phillips D, Severs J, Cucchiaro J, & Loebel A (2009). Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. The Journal of clinical psychiatry, 70 (6), 829-36 PMID: 19497249

3 comments:

Neuroskeptic said...

"Just read any random antipsychotic clinical trial. The numbers are all the same. No new psychiatric drug, antidepresant, antipsychotic, mood stabilizer, whatever, has been shown to be more effective than its predecessors in a clinically meaningful way."

Not even... clozapine?

NeuroPsych15 said...

I knew I put my foot in my mouth with that statement. I agree that clozapine has been shown to be more effective than its predecessors and contemporaries in improving the core symptoms in those who do not respond to standard treatment. So my statement is not accurate in that sense(http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61764-X/fulltext#article_upsell)

But the health risks (e.g., myocarditis) prevent it from being widely used.

Also there is the issue of quality of life improvement (http://ebmh.bmj.com/cgi/content/extract/10/2/57)

S. Durrenberger. M.D. said...

Double blind does mean something, it actually validates the results, which you have nicely highlighted. It means that neither the patient nor the prescribing doctor knew whether the pills given were placebo or active medication. This assures there is no bias in the reporting of results and therefore assures that reported results are not exaggerated by the clinician. So, side effect reports are also more accurate... proving your point entirely!!!!