Olanzapine with Samidorphan was approved—will you all use it?

[birchswing]

Only available as a fixed dose combo—Samidorphan not available on its own. Supposed to mitigate weight gain, but I wonder if it has any effect on the underlying metabolic changes olanzapine causes.

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[splik]

samidorphan is a drug in search of a disease. alkermes wanted to sell bupe with it for depression but the FDA did not want to approve bupe for depression with or without samidorphan. Then they were looking at using it for alcohol and cocaine use disorder. Then, because there was some data for naltrexone for weight loss, they came out with adding samidorphan to zyprexa for weight loss. Well, if you're that worried about weight gain, olanzapine is not a good bet. Even w/ samidorphan almost 20% of pts have a >10% gain in weight (compared with about 30% with zyprexa alone). Next, it's going to be tough to get prior-authorization for this. You might as well try adding naltrexone first. Or else use some more established approaches like metformin or even topiramate. And no, it does not impact the metabolic risk from olanzapine which is probably driven by its effects on M3 muscarinic receptors

 

[comp1]

I mean...I guess if olanzapine is all that works for them AND they have problematic weight gain... The antipsychotic market is so huge, even tiny players will be a big deal.

 

[nexus73]

samidorphan is a drug in search of a disease. alkermes wanted to sell bupe with it for depression but the FDA did not want to approve bupe for depression with or without samidorphan. Then they were looking at using it for alcohol and cocaine use disorder. Then, because there was some data for naltrexone for weight loss, they came out with adding samidorphan to zyprexa for weight loss. Well, if you're that worried about weight gain, olanzapine is not a good bet. Even w/ samidorphan almost 20% of pts have a >10% gain in weight (compared with about 30% with zyprexa alone). Next, it's going to be tough to get prior-authorization for this. You might as well try adding naltrexone first. Or else use some more established approaches like metformin or even topiramate. And no, it does not impact the metabolic risk from olanzapine which is probably driven by its effects on M3 muscarinic receptors

If naltrexone is so great why can't i get a free steak dinner while I zone out on a power point presentation about it?

 

[birchswing]

samidorphan is a drug in search of a disease. alkermes wanted to sell bupe with it for depression but the FDA did not want to approve bupe for depression with or without samidorphan. Then they were looking at using it for alcohol and cocaine use disorder. Then, because there was some data for naltrexone for weight loss, they came out with adding samidorphan to zyprexa for weight loss. Well, if you're that worried about weight gain, olanzapine is not a good bet. Even w/ samidorphan almost 20% of pts have a >10% gain in weight (compared with about 30% with zyprexa alone). Next, it's going to be tough to get prior-authorization for this. You might as well try adding naltrexone first. Or else use some more established approaches like metformin or even topiramate. And no, it does not impact the metabolic risk from olanzapine which is probably driven by its effects on M3 muscarinic receptors

Interesting palace intrigue. I had never heard of the drug before. I had heard of doctors prescribing metformin with AAPs as you mentioned, which seems more sensible in that metformin actually addresses metabolic changes.

Edit: Have you all ever seen some of those overweight people TV shows? I swear I have seen some where the person is 400 plus pounds, they do the lab work, and the doctor comes back saying, "You don't have it now, but if you keep this up, you could get diabetes one day." And I'm sort of dumbfounded. If you've made it to 400 lbs without getting T2D, well you're not healthy, but you kind of beat the system and won the lottery in one very specific way. All that is to say, I don't understand the focus exclusively on weight with this new drug combo over overall cardiovascular disease risk, which weight is certainly part of, but not the only factor.

 

[Stagg737]

samidorphan is a drug in search of a disease. alkermes wanted to sell bupe with it for depression but the FDA did not want to approve bupe for depression with or without samidorphan. Then they were looking at using it for alcohol and cocaine use disorder. Then, because there was some data for naltrexone for weight loss, they came out with adding samidorphan to zyprexa for weight loss. Well, if you're that worried about weight gain, olanzapine is not a good bet. Even w/ samidorphan almost 20% of pts have a >10% gain in weight (compared with about 30% with zyprexa alone). Next, it's going to be tough to get prior-authorization for this. You might as well try adding naltrexone first. Or else use some more established approaches like metformin or even topiramate. And no, it does not impact the metabolic risk from olanzapine which is probably driven by its effects on M3 muscarinic receptors

Nice summary, also the major study backing it's efficacy had a crap-ton of confounding factors making the results highly suspect. I won't be prescribing it any time soon, if ever.

If naltrexone is so great why can't i get a free steak dinner while I zone out on a power point presentation about it?

Because it's generic. Gotta go to those Contrave seminars if you want the filet.

 

[aim-agm]

samidorphan is a drug in search of a disease. alkermes wanted to sell bupe with it for depression but the FDA did not want to approve bupe for depression with or without samidorphan.

More complicated than that. The studies for buprenorphine/samidorphan were generally failures, and IIRC in one the drug actually did worse than placebo. The company was hoping that buprenorphine's antidepressant activity was related to kappa-antagonism rather than mu-agonism...turns out that mu-agnonism is a really good way of treating depression and kappa-antagonism isn't.

 

[clausewitz2]

samidorphan is a drug in search of a disease. alkermes wanted to sell bupe with it for depression but the FDA did not want to approve bupe for depression with or without samidorphan.

The efficacy data were also incredibly underwhelming. They barely achieved significance on their outcome measures and that significance seemed to be driven mostly by an enormously response in a very small number of subjects. This understandably raises concerns for a compound that has such huge potential for abuse.

Mind, I would have rather had ALKS 5461 in a heartbeat instead of brexanolone, but c'est le vie.

 

[Stagg737]

The efficacy data were also incredibly underwhelming. They barely achieved significance on their outcome measures and that significance seemed to be driven mostly by an enormously response in a very small number of subjects. This understandably raises concerns for a compound that has such huge potential for abuse.

Mind, I would have rather had ALKS 5461 in a heartbeat instead of brexanolone, but c'est le vie.

Iirc the main study they cite screened patients for substance abuse disorders but didn't include cannabis use in that screening. Kind of a hugely relevant factor to leave out...