Feeling Depressed? ALKS 5461: The Fix of the Future?

Are there new antidepressants coming

“Okay, I’m depressed. And I can’t find an antidepressant that works. I don’t expect something new and exciting to hit pharmacy shelves tomorrow, but is anything at least in the pipeline?”

Do you see how ALKS 5461 is put together? Part of it’s about the ‘antidepressant effects’ generated by buprenorphine. And the checks-and-balances are provided by ALKS 33.

I ran a poll on Chipur not long ago posing this question: If you had to choose just one method of treatment for your mood or anxiety disorder, what would it be? The choices were meds, psychotherapy, and spirituality.

The race was close, but meds led the pack.

Being an emotional/mental health professional – more importantly an anxiety/mood disorder vet – I’ve never had an issue with psychotropic medications, as long as there’s a good match between condition and med. Still, psychotherapy and spirituality are important recovery tools that need to be utilized even if one elects to go the meds route.

I’m frequently asked if I know of any meds in development addressing the mood and anxiety disorders. So I try to stay up-to-date.

Recently I found something I believe you’ll find interesting and encouraging.

Alkermes (Dublin, Ireland) has come up with an investigational drug they’re calling ALKS 5461. Sounds so “hush-hush,” don’t you think?

If all goes according to plan, ALKS 5461 will be available as an adjunct med, providing relief for treatment resistant depression. By the way, that’s accomplished with abuse and dependence-checked opioid power.

Incidentally, Alkermes is the same corporation that developed and markets Vivitrol. It’s the injectable form of naltrexone, primarily used to manage alcohol and opioid dependence.

Do I have your attention?

So What is ALKS 5461?

ALKS 5461 is actually a two molecule combo. Molecule number one is buprenorphine. Heard of it? It’s a semi-synthetic opioid that’s used to treat opioid addiction, as well as moderate acute and chronic pain in non-opioid-tolerant individuals.

Actually, buprenorphine is a partial opioid agonist, so it’s maximal effects are less than full agonists such as heroin.

Maybe you know this, but it’s an active ingredient in the medications Suboxone (with naloxone) and the transdermal patch Butrans.

“Okay, so wait a minute, I’m going to be taking something that may be addictive for my depression?” Yep! But let’s not forget about ALKS 5461’s second molecule – ALKS 33.

ALKS 33, an opioid antagonist, acts as a barrier to the binding of buprenorphine to the receptors that make us feel euphoric. It’s those very receptors that are responsible for the craving of opiates.

Do you see how ALKS 5461 is put together? Part of it’s about the “antidepressant effects” generated by buprenorphine. And the checks-and-balances are provided by ALKS 33.

What’s All the Hubbub?

So why is everyone getting so excited about ALKS 5461 – an investigational drug? Well, it brought quick relief to all 32 major depressive disordered participants in a blind, placebo controlled study (participants didn’t know if they were taking ALKS 5461 or the infamous sugar-pill).

What’s more, all 32 participants had zippo luck with fluoxetine (Prozac) or venlafaxine (Effexor).

“When Can I Get Some?”

It seems we’ve established the fact that ALKS 5461 is a potentially game-changing drug for the treatment of depression. Okay, great – how long before we see it on pharmacy shelves?

Fact is, we may not. I mean, Alkermes could pull the plug on it anytime if it’s not living up to expectations during the FDA approval process. For now, however, ALKS 5461 is in Phase 2 clinical trials. Um, but it could take seven years before it’s approved.

But take heart – the FDA has Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review approaches that are intended to make therapeutically important drugs available earlier. So if ALKS 5461 is really “all that,” perhaps we won’t have to wait seven years to give it a go.

Now, you may be thinking, “Geez, thanks Bill. You get me all worked-up over a potentially game-changing med and it could be seven years away – if it hits the market at all.”

Well, you may have me there. However, you need to not only know the mood and anxiety disorder relief meds in the pipeline – you need to know creative efforts are being made to lend a hand to those enduring depression, anxiety, or bipolar disorder.

Feeling depressed? ALKS 5461 may in fact be the fix of the future.

And now you know…

UPDATES October 2017…

  • Alkermes has initiated its rolling submission of a New Drug Application (NDA) to the FDA, seeking marketing approval of ALKS 5461. Submission completion is expected by year-end 2017
  • ALKS 5461 was designated Fast Track by the FDA in October of 2013
  • ALKS 33 now has a name: samidorphan
  • I believe it’s reasonable to add good old fashion major depressive disorder to treatment resistant depression as ALKS 5461 treatment targets

Would you like to read more Chipur mood and anxiety disorder articles? Have at hundreds of titles.

  • Sarah June 21, 2013, 7:16 am

    I suffer with Major Depression, when is this medication going to be available? Can I be a subject to try this medication?

    • chipur June 21, 2013, 9:46 am

      Hi Sarah!
      Thank you for visiting Chipur and participating in the discussion. Unfortunately, I’m thinking GLYX-13, if it makes it through clincial trials, may not be on pharmacy shelves for a couple of years yet. It’s always difficult to write these pieces because, though it’s hopeful and important information, there is a significant time-lag to reality. Renee provided a link to clinicaltrials.gov. If you hit the home page, type in GLYX-13 in Search for Studies. You’ll see there are several, and they’re recruiting.

      Again, thanks for checking-in.

  • Stevo1035 May 3, 2014, 2:29 pm

    I see this is now in phase 3 trials. Given that it was granted fast track status, and that they anticipate completion of phase 3 by the end of this year, is there an estimated time we can expect for it to be approved? Assuming it passes phase 3 of course. I don’t know anything about fast track status as far as how much more quickly the FDA moves to stamp approval or disapproval. Thank you in advance.

    • chipur May 3, 2014, 3:53 pm

      Hey Stevo!

      My understanding is after Phase 3 – and drug proves to be safe and effective – the drug company files New Drug Application (NDA)/ Biologics License Application (BLA). If approval comes, it’s typically 1-2 years after these applications have been filed. The fast track designation? Drug can receive Priority Review. How much time does that knock-off the drug hitting shelves? I just don’t know. Further, my searching didn’t reveal any info as to on-the-shelves date for ALKS 5461..

      Sure appreciate your visit and comment. Wish I could have come up with something more definitive…


      • Stevo1035 May 7, 2014, 12:33 pm

        Thank you so much for your reply Bill. I have bad depression and OCD/anxiety and I have become treatment resistant to the SSRI’s and SNRI’s, so I’m really hoping something novel comes available sooner than later.

      • Chipur May 7, 2014, 3:47 pm

        Well, you’re welcome, Stevo. Wish I had more to offer. This one is still a ways off, but it’s hopeful stuff chipur.com/i-feel-depressed-so-whats-in-the-relief-pipeline-lets-chat-glyx-13/


  • Chipur October 9, 2014, 9:59 am

    Got the drop on me there, Tex. But it is an interesting angle…

  • Big Ben October 30, 2014, 9:43 pm

    While the clinical trials take years people who suffer from “treatment resistant” depression commit suicide on a daily basis. The ones who survive do what it takes regardless if the government approves.

    • Chipur October 31, 2014, 9:57 am

      Appreciate your visit and comment, Big Ben. Yeah, no doubt, an incredibly frustrating set of circumstances. I don’t understand why the majority don’t (want to) attach the concept of mortality rate to depression – just like cancer, etc. Why are those enduring emotional/mental situations left to their own devices? Hmmm.
      Again, thanks for stopping-by. Hope you continue to…

  • Michelle Hoyland May 8, 2015, 11:19 am

    2016 expected availability according to Mental Health Daily. This is going to revolutionise treatment of MDD, mood disorders, anxiety disorders… Why hasn’t anyone thought of this before now. Seems so simple really. So many big Pharma kicking themselves right now.

    • Chipur May 8, 2015, 4:15 pm

      Thanks for the update, Michelle. Dang, I wrote this piece about 2.5 years ago. Sad it’s taken this long to come as far as it has (with more time to go). And it’s had fast track status. We’ll all keep our fingers crossed.

      Appreciate the visit and participation…

  • BCat May 10, 2015, 9:35 pm

    Yes, yes. This sounds very promising. I have been lately involved in trying out pharmaceuticals that are quite cutting edge, many have been developed in Russia and Japan and are not yet in any schedule in this country. They’re available through nootropic vendors throughout the internet but not in the public eye. I wonder if some ferreting research will uncover a source for ALKS 6581? You can bet I’m on it like a fly on honey!

    • Chipur May 11, 2015, 10:02 am

      By George, BCat – let us know what you come up with with that “fly on honey” due diligence. Your participation here is important, as you’re always “cutting edge.”

      Thank You…

      • BCat May 12, 2015, 4:16 pm

        Aww, thanks Bill. You always make me feel good. I’m not sure if you think publishing this is ethical for your readers. Everything these sites sell is legal in this country, at least so far. Feel free to edit. The best site I’ve found for cutting edge substances not yet out on the market it tocris.com Pretty expensive for very small amounts but since they usually have to be reconstituted and injected (took HGH shots for years for fibro so I’m not shy about subcutaneous routes), they might end up not so teeny. Haven’t yet ordered from them so I don’t know if you have to be associated with a research org. Anyhoo, they don’t yet have ALKS 5461, but they would be the ones when and if the chemical structure is released from the manufacturer. At any rate, it’s a good source for many of the clinical trial meds whose chem structure has been released.

        A russian site for nootropics is awakebrain.com. I found an interesting product there called etifoxine which is a GABA a agonist that acts like a benzo but doesn’t have tolerance or addictive potential. Have been using it @ 2 caps twice a day when I need it for anxiety and it seems to help but is not as strong as lorazepam, which Wiki says it compares to, but lasts longer anyway although it takes what seems like 2-3 hours to come on. You may want to edit the following because this Japanese pharmacy sells some pretty potent real-life benzo’s, but they’re not illegal here, although they are in Japan w/o a prescription and they could lead to abuse and tolerance. Some forums I’m on say they are completely reputable as far as sending their products and if my order comes in as promised, I would say this site is a gem: http://www.mimaki-family-japan.com.

        Another real interesting route are the ethnobotanicals which are not illegal and have some fascinating and ancient uses. A good site is shamansgarden.com with great customer support. You’ll get lost exploring all the products and their histories. I recently ordered blue lotus and blue lily resin and have it steeping is some gently heated Stoli vodka to mix with wine which is said to potentiate the chemistry. An ancient Egypt recreational substance (and supposedly an aphrodisiac – wink wink). Happy exploring!

      • Chipur May 12, 2015, 7:27 pm

        Holy mackerel, BCat – you never cease to amaze me (us?). I appreciate you sharing your research with us. And, you know, I understand your concern re potential info edits, but readers are big girls and boys – they’re gonna’ pursue what they’re gonna’ pursue. Hey, as long as I’m not endorsing anything illegal, let there be a free internet! Right?

        I’m glad you frequent Chipur, BCat. And grateful that you share…

      • BCat May 13, 2015, 8:31 pm

        Free internet would be rad! While we’re at it, let’s get rid of GMOs. Great, great book on the subject is ‘Altered Genes, Twisted Truth’ by Steven Druker. Read it and weep. My husband passed this book on to a manager at Safeway who is verrrrry interested in the subject but doesn’t know the gnarly details. Who knows, maybe he started a revolution/evolution.

      • Chipur May 14, 2015, 5:24 pm
      • BCat May 15, 2015, 2:48 pm

        Yeah, Wiki’s pretty good but this article does not highlight all that’s wrong with GM foods or how the FDA has purposely deceived us in not reporting the many research pubs that should raise huge concerns (think baksheesh). Oh well, this is not really the venue to step up on my soapbox.

      • Chipur May 15, 2015, 8:02 pm

        You can soapbox it anytime, BC. Just wanted to provide a starting link. If one is motivated to up the research ante – onward and upward…


  • BCat May 10, 2015, 9:58 pm

    Oh, bummer. This article http://pro.psychcentral.com/drugs-in-the-pipeline-alks-5461/005986.html states that Phase II trials have found buprenorphine combined with samidorphan still has abuse potential. Again, buprenorphine is definitely not a warm fuzzy opioid feeling, it’s weak but stodgy, and I can’t understand what all the hoopla is about re it’s antidepressant activity.

    • Chipur May 11, 2015, 10:07 am

      Good read for everyone, BCat.

      From the article – “It will be crucial to thoroughly evaluate the safety data of ALKS-5461 to determine whether the addition of a mu antagonist prevents withdrawal complications or abuse. And we should use extra caution before using existing compounds such as Suboxone or buprenorphine off label in our depressed patients without a full understanding of the risks involved.”

      Hopefully, we’ll come by that “full understanding.”


  • Patience Spina October 14, 2015, 1:10 am

    I wonder if it could be used to treat heroin addiction since it has the affect of heroin without the addictive factor.

    • Chipur October 14, 2015, 7:15 pm

      Yeah, who knows, Patience. I’m not smart enough to give you the best answer, but let’s wait and see. Incidentally, the trials continue. Here’s some good current info https://en.wikipedia.org/wiki/ALKS-5461

      Appreciate your visit and contribution. Please come back…

      • Sarah October 15, 2015, 2:00 pm

        That sounds like a good idea, I know a lot of people using heroin because they are depressed or they are depressed because they are heroin addicts, either way anything has to be better than methadone and the antidepressants the doctors are giving out like smarties.

      • Chipur October 15, 2015, 6:36 pm

        Hi, Sarah – thanks for your visit and participation. “…antidepressants the doctors are giving out like smarties.” I love it. And it’s true, isn’t it? You know, I have never (nor will I ever) passed judgment on someone for the psychotropics they choose to use. However, I get so ticked-off when I think about the meds being prescribed without full disclosure re efficacy, side effects, etc. That just ain’t right.

        Stop-by again, okay?

  • BCat October 20, 2015, 1:26 pm

    Might be interested in this forum article that describes many new pipeline drugs:


    • Chipur October 20, 2015, 6:56 pm

      Hey! There’s BCat. Welcome back. Appreciate the link. Readers, BCat always has great stuff to offer. If I were you, I’d check it out…