FDA Approves First Oral Treatment for Postpartum Depression
fda.gov
fda.gov
This is great news. We need better treatments for PPD, which is real and very serious that can cause long term lasting effects in serious cases without treatment, and can sadly even be fatal.
Quality of life has risen steeply over the past several decades but mothers still walk an unpaved road. It's deeply worrying the lack of support and proactive care new mothers receive from medical professionals, though it is getting better, just very slowly.
I hope this helps many new families survive and thrive.
> It's deeply worrying the lack of support and proactive care new mothers receive from medical professionals, though it is getting better, just very slowly.
Agree, I don't treat or interact with PPD patients in my professional practice but my closest friend is an OBGYN and we've had many discussions about this over the years.
At least in most academic practices all patients are provided with education during the later stages of pregnancy and prior to discharge postpartum with typically one routine follow-up visit planned.
It's better than when I was a medical student but it seems a significant gap still exists between that and transitioning back to the patient's primary care provider who also tend to be more heterogenous in availability and knowledgeability about PPD.
Psychiatry no doubt has a lot of problems with it. But it's also the only game in town for a huge amount of people. What's the alternative? Prayer circles? Ayahuasca tourist traps? Cannabis? Homeopathy? Give me a break. Conventional medicine has always been imperfect, and has always improved over time. That's no less true of psychiatry than any other subfield. Whatever "alternative" therapies are truly effective tend to be incorporated into it eventually. In psychiatry we've seen this with meditation, and we're seeing it now with psychedelics.
I imagine there are many professional forums filled with people who know topic X inside out therefore assume they must also be an authority on unrelated topics Y and Z. But I also suspect there’s something about software engineering, perhaps the ability to succeed despite being deeply antisocial, or being very male dominated that means women’s mental health in particular is always going to be a dumpster fire discussion topic.
This is reminiscent of the Texas district judge who decided to controversially overrule the FDA on a medication safety decision that recently made the news, not good company one wants to have and I'm hoping is coincidental than suggestive of similar biases.
I keep thinking about Michael Crichton. He transmorphed from reality-based to nutter. What happened? Religion wasn't a factor. So what radicalized him?
Historian Joanna Radin's theory, paraphrasing, is that Crichton's full faith and trust in The System was so completely shattered, by the Vietnam War and other outrages, that he completely flipped.
The Speculative Present - How Michael Crichton Colonized the Future of Science and Technology https://www.journals.uchicago.edu/doi/epdf/10.1086/704047
The theme of the second season of Jill Lepore's The Last Archive podcast is about skepticism ("What fed Doubt?") S01E06 "It Came From Outer Space" includes the example of Crichton's radicalization.
https://www.thelastarchive.com/season-2-episodes
Lepore has completely opened up my mind about anti-science, conspiracy, and other social pathogens. Made me a bit more empathetic.
Highest recommendation.
I'm currently on a psychiatrist prescribed drug which is illegal in Japan, which means I have to discontinue it before an upcoming trip. This is not a new drug, it's a generic.
So is it "insane that a group of educated and seemingly intelligent doctors" in the U.S. are prescribing this drug or "insane that a group of educated and seemingly intelligent doctors" at the Japanese equivilent to the FDA are not authorizing this drug?
I mean, it can't possibly be the case that neither group knows what it's doing, and that our scientific understanding of the brain is primitive, correct? One group has to be the insane one, right?
Well... if we're talking psychiatrists, they choose the thing they wanted to be highly qualified in. So, any potential "expert" that would disagree with their research methods was selected out so as to not become an expert in the first place.
I guess if I have a point it's that I don't think shouting "trust the science" or "trust the experts" and beating one's chest is contributing much to the conversation.
> So, any potential "expert" that would disagree with them was selected out so as to not become an expert in the first place.
Anyone with some form of training or practical experience in an academic biomedical field (clinical or research) and has knowledge of how to synthesize and analyze evidence in order to make logical arguments may be considered a relevant expert, this is a much larger group than psychiatrists and is how FDA committees are constructed.
Most notably this includes (and is not limited to) other physicians and providers, pharmacologists, pathologists, physiologists and epidemiologists.
> I guess if I have a point it's that I don't think shouting "trust the science" or "trust the experts" and beating one's chest is contributing much to the conversation.
One should absolutely "trust the experts" when it comes to determining safety of a therapeutic or definition of a disease. These are determined by scientific processes and debate based on evidence and not philosophical thoughts and feelings.
Given how complex modern life is one has to defer to experts and regulators on many things beyond medicine. Some other examples: motor vehicles, aviation, building codes, financial institutions and encryption.
> I'd also say that the more I've learned about psychiatry (including as a customer) the lower the opinion I have of it.
The limitations in psychiatric medicine and research are widely acknowledged and not a novel insight that the FDA and medical community are ignorant of as many commenters here seem to believe.
One might expect someone who acknowledges the limits of psychiatry wouldn't be chest beating so aggressively about the greatness of the scientific process.
One might also expect a person concerned with mental health issues wouldn't throw around the term "insane" so casually.
>These are determined by scientific processes and debate based on evidence and not philosophical thoughts and feelings.
Who needs philosophy? Just have faith, am I right? That's what science is all about. What do we mean by science? Don't ask that kind of philosophical question. Just have faith.
SSRIs don’t work for many people and we only found out 2-3 years ago.
Opioids were prescribed to half of America for back pain.
That gives scope for healthy scepticisms at least. Just because you might have some anecdotal evidence of some chemicals working, doesn’t mean it works for others or that it leads to a good place.
Lastly - there are clearly lifestyle and even moral choices that people make or don’t make that can lead to mental health issues. Just from a common sense perspective it seems much healthier to try and deal with these first, with therapy, than just medicating. And not just therapy. Exercise, diet. We know these affect mental health, yet pills are easy, and they make doctors money.
medicating is much easier than searching, finding and healing the cause. Therapy takes years, if not decades. I can understand why people pick the easier route, but easier is not always better. Also, are you just permanently going to be on pills then? I mean it’s a great subscription business, I can see that.
Initial treatment recommendations:
For mild to moderate postpartum unipolar major depression, we suggest psychotherapy as initial treatment. This approach is consistent with multiple practice guidelines, and is especially useful for lactating patients who do not want to expose their infants to antidepressants.
However, antidepressants (eg, selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors, bupropion, and mirtazapine) are a reasonable alternative if psychotherapy is not available, not successful, or is declined, or if the patient has previously responded to antidepressants.
In addition, combination treatment with pharmacotherapy plus psychotherapy is useful for some patients.
Source: UpToDate.
> And you don’t even know if it works.
While evidence for SSRIs is weak in meta-analyses this is not one of them. I will also agree that a single trial (i.e. the original post and what led to approval) is not definitive but does in fact suggest it works and will continue to be assessed in post-market studies.
It's not some earth shattering revelation that "SSRIs don't work for many people". This has been known since SSRIs first appeared on the scene. This is also true of any other treatment you can think of. The reason they became the first choice as far as antidepressants go is they were a lot safer and better tolerated than the older alternatives. Besides, there's a lot more to psychiatry than just SSRIs. But with people like you it's always about SSRIs. Can't shut up about the SSRIs. If you hadn't noticed, this new drug is not an SSRI!
Psychiatrists recommend therapy, they recommend changes in diet and they recommend exercise. Clinical psychology, though technically a separate discipline from psychiatry, not being under the umbrella of medicine, is very much developed, researched and practiced in tandem and cooperation withpsychiatry, and vice versa.
You're constructing an elaborate strawman here, where the only reason for using drugs is some evil financial motive. It's just not that simple. There bad apples, and perverse incentives, but not only bad apples. Most doctors do in fact care about helping their patients.
Therapy can't fix everything. Therapy alone is not always sufficient and can be just as hit and miss as medication. Not everything is some deep personal issue that needs to be analysed and resolved. Mental disorder is often genetic, even neurological in nature. All the therapy in the world won't stop a bipolar person from cycling between mood disturbances, or someone with ADHD from being unable to concentrate.
We can't throw the baby out with the bathwater. Medication, therapy, meditation, diet, exercise, sleep hygiene are all part of the psychiatric toolbox.
Looking at how many people are medicating for mental health issues in the west (or world), I find it extremely unlikely this is because all these people have gone through therapy, exercise and diet and they have to take medication.
No. It’s the easy route to some sort of medicated happiness, and it’s profitable, so everyone does it.
But this many people shouldn’t be doing it. They shouldn’t be taking the easy route, because it’s not dealing with many issues we should be dealing with, as society and as individuals.
Saying it's "medicated happiness" is ridiculous fearmongering. Antidepressants do not make you happy. They do not change how you think or how you act. They can't. If you think they do, you do not know what you're talking about.
You know why my wife had PPD? Because being a mother is hard, and she also had a lot of unresolved anger and issues towards her own mother, and she was reminding herself of her own mother and causing quite a bit of anxiety. We were also at an extremely difficult part of our relationship, we basically hated each other for a year.
What did we do? We both went to therapy, and asked the hard questions about why this was happening, and how to resolve them. My wife spent 6 months in therapy and resolved the issues with her mother, and now she is happy with her own performance as a mother. We went to couples therapy, which was extremely hard, but after over a year, we are basically in love again, and we are STARTING to understand what patterns are causing our issues, and how to deal with them.
We took no medication. But we were on the road to depression, but decided to actually look behind WHY this was happening.
Popping pills of course is much easier. You don't need to face your demons, or your parent's demons.
The trouble is it is at crucial times in life like childbirth when these demons emerge. Yet hardly anyone wants to face them anymore. This is not mentally healthy. And what's even worse, you are very likely to pass on many of these issues to your children if they remain unresolved.
I know this is counter to 70% of what americans believe in, but it's the hard truth, and I think many people deep down know this is the truth, but it's just much easier to take pills and bury the fact that EVERYONE has mental issues that need resolving, without taking medication.
I'm not talking about the extreme cases btw. I know in some instances medication is necessary. But it is WAY overused, to get out of making hard choices.
To further illustrate the accessibility point when I lived in Canada therapy was not covered by the public health system and is entirely out of pocket.
In the US it obviously depends on the highly variable coinsurance/copay and assumes you can either take time off work or find a provider that works outside of business hours.
A 30-day supply of Lexapro is $4.50 and also has evidence that it works.
You and your spouse have had your experiences which are completely valid and true. Your truth does not invalidate others' truth. This medicine is for them, not you.
However your experience seems to prevent you from seeing the bigger picture.
"Popping pills" is probably chosen not because people don't want to solve problems and change their lives. It is probably because it is only available solution at that time to actually function as a person and member of the society.
It is great that you had money and event time to go to therapy for 6 months as new parents. A lot of parents of newborns will simply not be able to afford it both financially and because of time constrains. Did you bring your new born to the therapy? How much did it cost? Would every single mother be able to afford 6 months of therapy? Some middle-lower class family? Some family in very rural area? Please try to see a bigger picture here and befriend more people from different paths of life.
People take pain medication for back pain not because they don't want to fix their backs. If anybody could fix their back today instead of taking pills they would do it.
If you only found out 2-3 years ago that SSRIs don't work for many people that's decidedly a you-problem. Psychiatry has known this for ages, which is one of the reasons that depression treatment is still tricky. You have to try what works for each person individually. And usually it's a combination of things.
PPD aside, if we're talking about the issues that psychiatry seeks to alleviate, every one of those 'solutions' has had thousands of advocates/adherents/patients that claim to have gained positive effect.
and before I get considered a proponent of any of those; i'm not -- but I recognize the cohort of people who claim to have gained benefit just as I recognize the group who claim to have benefited from psychiatry.
mental health needs not be a monopoly; many people go through issues that they fix through specific personal events or patterns that are specific only to them.
You can complain about the style of thinking that you encounter on HN without disparaging the things that have helped people outside of clinical settings.
Mental health and well-being is one of the most mysterious things that we study, if a suicide or otherwise bad decision is staved off by chanting in makeup and visiting exotic locations then so be it, that's what worked for them.
And another aside : psychiatry will never incorporate extreme things that may help certain individuals, nor should they -- but that means that the breadth of things that are helpful is greater than the breadth of things that will ever fall within the umbrella of clinical mental health; so you should probably hold off on judging things based on whether or not the industry has adopted them.
I can imagine something like this doing something similar.
> This relatively modern phenomenon is practiced predominantly by white, middle class, married women in the global North, and has grown rapidly since the 1970s
> Whilst prevalence is difficult to estimate, placentophagy is known to be practiced in North America, Oceania and Europe, plus parts of Latin America, the Middle East and Asia and is apparently growing in popularity. In a 2018 study of a medical records dataset for births outside of hospitals containing 23,242 birth events in the United States, 30.8% of mothers consumed their placenta. From 2009 to 2015 Google searches for “placenta encapsulation” increased 100-fold.
https://bmcpregnancychildbirth.biomedcentral.com/articles/10...
This review article provides an overview for the curious.
https://www.sciencedirect.com/science/article/pii/S000293781...
It was compared to placebo.
People are rightly highly suspicious of Big Pharma.
I like the idea of a novel class but I won't pay attention to this new, expensive drug until it proves significant efficacy over older cheaper drugs (like Alprazolam and Zolpidem/Zopiclone).
Technically it's a Z-drug (like Zolpidem/Ambien) which are non-benzodiazapine positive allosteric modulators of GABA_A However, since it's a neurosteroid most will probably not think of it as such. (It's name does begin with Z though... And end in -one like a steroid).[Note below]
Anyways, it's licensed for 2 weeks only, side effects are drowsiness, sleepiness and cognitive impairment. You mustn't drive within 12 hours of a dose.
It's best effects are where the depression is associated with insomnia and anxiety.
It was compared to placebo not Alprazolam (Xanax) which has some antidepressant activity. That's just how you seek market Auth when nothing else is licensed. That's just smart.
But you have a GABA agonist you must only use for the short term with primary anxiolytic and hypnotic effects. That will be widely used because otherwise you need off license script and will likely put even more people on the path to SSRI.
[0] this is a reckless insightless cognitive impairment think Roseanne Bar racist tweet.
Absolutely, but that should only trigger scrutiny which in this case would provide several answers for why this is a good thing and not a BigPharma scam.
> efficacy over older cheaper drugs (like Alprazolam and Zolpidem/Zopiclone).
This drug, and the IV formulation it is based on (Zulresso), are not the same as and have different mechanisms from sedative-hypnotics which as an aside are not indicated as monotherapy for PPD (or any depression, don't give a downer to someone down). The mainstay of treatment is SSRIs.
This class (which is the only FDA approved drug class for PPD) is an analogue of the endogenously produced metabolite of progesterone and the mechanism is not fully understood.
To your point of head to head trials, you are correct they do not exist at this time and will eventually be done however all of these are still new.
What we have right now are indirect comparative analyses which while limited show stronger magnitude effects than SSRIs.
https://www.frontiersin.org/articles/10.3389/fphar.2022.9500...
But the network meta analysis did not show zuranolone beating placebo due to wide effect size.
I'm old enough to remember the studies in the 90s where we so the saw the same thing with benzos and TCAs and SSRIs.
Alprazolam beats SSRI for depression with significant anxiety and insomnia with faster onset but treatment must be time limited.
That's uncanny to me esp as both are PAM for GabaA
It did not, using 1 of the studies, but my optimism is that the drug it was based on (brexanolone) was significant and is unfortunately only available IV (so difficult to access and expensive), so the hope is that this will play out similarly and why I feel is sufficient reason to give Big Pharma the benefit of the doubt that this isn't purely a money making play.
> Alprazolam beats SSRI for depression with significant anxiety and insomnia with faster onset but treatment must be time limited.
Sure, for anxiety-predominant scenarios but as you're alluding to there are significant dependence and abuse risks and hence why they're used as adjuncts.
If this turns out to work in the same pathway but safer that would be a huge win. If it turns out to work in the same pathway but not safer than non-benzo sedatives then you're right it's a scam. With that said:
> That's uncanny to me esp as both are PAM for GabaA
My clinical pharmaceutical resource lists mechanism not fully known. This is getting outside of my comfort zone to comment on validity or fully understand but this editorial (citing for my own accessibility) suggests a different mechanism from benzodiazepines:
Antonoudiou et al. (6) offer key insights into the potential mechanisms of rapid affective switching following brexanolone treatment of postpartum depression, despite the use of male subjects for all the studies. The remarkable discoveries include the parallels in human and rodent brain network dynamics associated with depression that are responsive to GABAergic analogs of allopregnanolone, the role of δ-subunit–containing receptors in some of these effects in mice, and the lack of effect of benzodiazepines on the electroencephalographic network dynamics, consistent with the lack of antidepressant efficacy of these compounds.
https://www.sciencedirect.com/science/article/pii/S000632232...
Antonoudiou et al: https://www.sciencedirect.com/science/article/pii/S000632232...
My son was born a little over 9 months ago. He's healthy, delightful, and utterly normal—and yet I, his father, still ended up with postpartum depression. I think it's underreported and under-appreciated that fathers can also have serious postpartum mental health issues.
I've been taking Lexapro since January to manage the symptoms, predominantly anxiety, and feel great from it. I haven't experienced any noticeable side-effects that you might normally associate with SSRIs, and I'm incredibly grateful that I was in a position to start taking it.
New dads: if you feel unusually down, anxious, frustrated, angry, or depressed, consider talking to your PCP about treatment. Taking medication is not an admission of failure. Being a father is tough, but it shouldn't feel impossible.
edit: see my replies for exactly why I don't like discussing this.
Edit 2: since I’m concerned that some asshole in my replies might dissuade some folks who might seek care from seeking it, please check this article out: https://health.clevelandclinic.org/yes-postpartum-depression...
8-10% of new fathers experience postpartum depression.
On a personal and professional level I'm greatly appreciative of your decision to share your experience and contribute to the destigmatization and increased awareness of male mental health despite anticipating attacks.
> New dads: if you feel unusually down, anxious, frustrated, angry, or depressed, consider talking to your PCP about treatment. Taking medication is not an admission of failure. Being a father is tough, but it shouldn't feel impossible.
Amen. Being the internet, people are going to be jerks but I for one appreciate you sharing your experience.
After the birth of a son life changed 180 - no free time, no personal time etc etc. All you can expect. Less sleep, a lot of unknowns and anxieties. Again - expected. Less time with wife. Feelings of down, depression. Some anger problems. But it all looks like everyday life and everybody experiences stuff like that.
Then my father died. So I became "the man of the family".
Then corona hit. Then unknowns at work.
Then one day I was playing with my son and he hit his back and I felt so sick. However x-rays just nothing and he was just fine the next day. Life continues.
And one day I was just chilling and having some alone time and it all hit me like a train. Suddenly I thought I am gonna die. Somehow my heart will fail (my father had heart problems) and basically I could not function as a person. I just wanted that somebody would take me to the hospital or something and just care for me so if my hearts starts failing medics would be near. I couldn't work. One of the worst weeks or so of my life.
Of course my heart was just fine.
All these things were accumulating for some time already. The very same Lexapro helped me a lot. No side effects whatsoever. After a few months I felt like I was actually young again. Things started to improve both at home and at work. Anxiety is 99% gone. I am just so glad I got help. Actually I was forced to as I couldn't function.
I guess body should have be adjusted to increased levels of serotonin and lowering the dose very slowly should help the body to adjust the levels by itself. Nothing that was not done by millions of people already.
You have to titrate off a lot of them, but that's true of a lot of drugs and that's also not addiction.
Benzos _are_ potentially addictive, but if used correctly can help a lot. They also aren't generally prescribed as first-line treatments.
"An orally active inhibitory pregnane neurosteroid, zuranolone acts as a positive allosteric modulator of the GABAA receptor."
Interesting. I was expecting another SSRI or something similar.
edit: nevermind i guess drugs are classified by their chemistry rather than their effects
However, since it's a neurosteroid most will probably not think of it as such. (It's name does begin with Z though... And end in -one like a steroid).
Anyways, it's licensed for 2 weeks only, side effects are drowsiness, sleepiness and cognitive impairment. You mustn't drive within 12 hours of a dose.
It's best effects are where the depression is associated with insomnia and anxiety.
It was compared to placebo not Alprazolam (Xanax) which has some antidepressant activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139029/#:~:tex....
https://en.wikipedia.org/wiki/Pregnanolone#Biological_functi...
This cited paper[3] also tested similar neurosteroids in progesterone receptor knockout mice and still found anxiolytic effects.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139029
[2] See Figure 3A in [1]
What? This claim is easily falsifiable. Section 8.2, Lactation:
> Available data from a clinical lactation study in 14 women indicate that zuranolone is present in low levels in human milk.
> A steady-state milk study was conducted in 14 healthy lactating women treated with daily oral administration of 30 mg of ZURZUVAE for 5 days. At steady state (Day 5), the calculated maximum relative infant dose for ZURZUVAE was < 1%. The daily infant dose was low (approximately 0.0013 mg/kg/day), reflecting a mean relative infant dose of 0.357% compared to the maternal dose. Concentrations of ZURZUVAE in breastmilk were below the level of quantification limit (BQL) by 4-6 days after the last dose.
In the past, new mothers were surrounded by a whole village of women who would help care for the woman and the baby.
Many times now, women are isolated with maybe the father present. And even then there are pressures to get back to work.
This isn’t to discount or minimize postpartum depression, but if we as a society set up people for failure which require them to take a pill to get better, maybe something needs to be rethought.
https://www.sciencedirect.com/science/article/abs/pii/S01650...
> Additionally, prevalence was significantly higher in women from low and middle income countries compared to women from high income countries (OR 1.8, 95% CI 1.4–2.2). The overall pooled prevalence was 11.9% of women during the perinatal period (95% CI 11.4–12.5).
https://en.wikipedia.org/wiki/Postpartum_depression#Epidemio...
For example, in Malaysia, most people no longer live in villages but it's counted as a middle income country.
I don't know how we would have managed the little one in the first years just the two of us. It really does that a village to raise a child, literally and figuratively.
My daughter went to daycare at exactly 18 months, but it was quite a ride before that. I work for home so I was there for my family, but let's just say that my productivity was sacrificed to do that.
I have no idea how single parents manage it.
Social support is less important risk factor, while factors like marital satisfaction and partner's depression are more important. For women, adverse events such as loss of a loved one, husband's loss of job or serious economical issues seem to be important too (Escriba-Aguir et al. 2010).
This is also quite concordant with the fact that PPD is more common in less developed countries, as mentioned in another comment.
I love GABA agonists from benzos, benzo likes to phenibut and really wonder how it feels. If it feels the same way, then it feels like being wrapped in comfortable cotton, with all worries gone -heaven on earth. Hence the extreme addiction risk.
So one would assume so. The risks are reduced due to it being event related treatment (delivery) and time limited license (14days).
Alprazolam similarly has antidepressants effects and similar might work for PPD given its insomnia/anxiety predominant features.
FDA approved it based on placebo studies as there are no licensed pills for PPD. This is bag Sage/Biogen buckets of money.
I tried to read up on it but I am left utterly confused. Are benzos and z-drugs GABA agonists, GABA positive allosteric modulators or both?
Benzos and Z-drugs are considered PAMs, it's possible some have some intrinsic activity but otherwise they simply potentiate other agonists.
The big benefit here is that they are far less likely to cause death when taken alone.
The confusion is that any positive effect is typically called agonist and any negative effect called an antagonist when discussed informally.
However, since it's a neurosteroid most will probably not think of it as such. (It's name does begin with Z though... And end in -one like a steroid).
Anyways, it's licensed for 2 weeks only, side effects are drowsiness, sleepiness and cognitive impairment. You mustn't drive within 12 hours of a dose.
It's best effects are where the depression is associated with insomnia and anxiety.
It was compared to placebo not Alprazolam (Xanax) which has some antidepressant activity.
https://www.fiercepharma.com/pharma/sage-biogens-postpartum-...
> Alongside Friday’s approval, the partners also received a rejection for Zurzuvae in adults with major depressive disorder (MDD). The FDA told the partners their application didn’t provide “substantial evidence of effectiveness” and that additional studies would be needed. Sage and Biogen said they are reviewing possible next steps.
https://www.fiercebiotech.com/biotech/sage-braces-layoffs-pi...
The biggest factor is that this stuff is basically a Z-drug like Zolpidem/Ambien and so treatment is time limited.
That makes it harder to use with MDD.
At the same time it did not conduct comparative studies to TCA, SSRI or other modern antidepressants.
"Treatment as usual" would likely be a short course of Z-drug.
If a man went to the doctor and said I've lost my dad and I'm low, anxious and can't sleep one would imagine this would work. We don't know if it would work better than an antidepressant, or sedative because no comparison was done.
https://slate.com/technology/2022/11/brain-development-25-ye...
> When we spoke, I told Steinberg his work had been referenced in this way. “Oh no,” he said, laughing. I then asked whether he had insights about where the figure 25 came from, and he said roughly the same thing as Cohen: There’s consensus among neuroscientists that brain development continues into the 20s, but there’s far from any consensus about any specific age that defines the boundary between adolescence and adulthood. “I honestly don’t know why people picked 25,” he said. “It’s a nice-sounding number? It’s divisible by five?”
> Kate Mills, a developmental neuroscientist at the University of Oregon, was equally puzzled. “This is funny to me—I don’t know why 25,” Mills said. “We’re still not there with research to really say the brain is mature at 25, because we still don’t have a good indication of what maturity even looks like.”
For the lack of pediatric indication, it's almost certainly because the clinical trials used 18-45 as the inclusion criteria. This is typically done as it is (expectedly) easier to get Institutional Review Board ethics approvals for adults and considerably easier to recruit patients both simply because it's easier to recruit adults as well as the relative prevalence of adult PPD patients.
I'm not a psychiatrist but the similar intravenous drug this is based on (brexanolone) is approved at ages 15 and over so I don't expect there is any reason this would be ineffective.
So, the opposite of "effective".
So if you're already suicidal, you can regain the ability to act on it before you get relief
QED.
Furthermore, subjects with suicidal ideations or attempts are disqualified from clinical trials. In practice, this also means that any subject with depression is disqualified and shall not participate in any clinical trial for "antidepressants".
How does it feel to know that a drug that's supposed to treat depression, and may cause suicidal ideations and attempts, was never tested on anyone who was depressed?
SSRIs and suicide risk remains controversial, habinero is describing one possible explanation and what I was taught in medical school over a decade ago. The label language is clear but you are failing to understand the complexity and rationale behind the warning and actual clinical implications. This is not unexpected as monographs are intended for a medical expert audience who are trained in their interpretation.
To keep it simple for everyone I suggest we defer to the Chair of the FDA proceedings that led to the boxed warning for his explanation as he is undoubtedly more of an expert than any of us on this matter (shortened for brevity):
It seems inconceivable that antidepressants would induce suicidality in the absence of other associated or antecedent behavioral changes. The essential message of the Black Box is to remind prescribers and consumers about the importance of monitoring closely for adverse behavioral changes during ... antidepressant therapy in order to reduce the risk of suicidality in patients through age 24 years. The intention was not to discourage appropriate prescribing of antidepressants for youth with depression, OCD or anxiety disorders.
In fact, some evidence .... suggested substantial reductions in antidepressant medication prescriptions in children and adolescents following the Black Box Warning ... For the majority of these patients, the benefits of antidepressants greatly outweigh the risks. Nevertheless, we agree ... that prescribers have a “duty to warn” and highlight the need for adequate training for all potential prescribers during medical school and residency programs.
https://www.frontiersin.org/articles/10.3389/fpsyt.2020.0036...
I will again note that for Zurzuvae the boxed warning was downgraded.
> Furthermore, subjects with suicidal ideations or attempts are disqualified from clinical trials.
https://www.nature.com/articles/npp2011247
https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2...
I found these 2 pharmacotherapy RCTs on patients with suicidal ideation within 30 seconds of Googling.
> In practice, this also means that any subject with depression is disqualified and shall not participate in any clinical trial for "antidepressants".
> was never tested on anyone who was depressed?
How are you making this leap that none of the RCTs enrolled patients with depression? You do realize it's a minority that have suicidal ideation right?
Also, this rant is hilariously incorrect. You...do know that manufacturers continue to collect reports on side effects outside of clinical trials, right?
Eating fish a few times a week won't lower your IQ, but if you're pregnant, the mercury content could leave your child permanently mentally disabled. Still-developing bodies and minds can be much more sensitive and delicate than an adult. Just because a drug has been shown to be safe and effective for adults doesn't mean it will be equally safe and effective for children.
The standard or care is education and it’s… well… well intentioned but deeply insufficient sometimes.
I’m so happy to see some additional treatments.
Might be better off just smoking a joint.
There's also no credible evidence that cannabis is an efficacious treatment for postpartum depression.
But sure, why even bother with science? Just smoke a joint...
Also - you can acquire postpartum depression while pregnant. You can get pregnant soon after having a baby. But hey, science.
As far as I can tell that warning might be just boilerplate for antidepressants these days.
Similarly for foetal harm it's on animal studies and they advice effective contraception for 1 week after last dose while they collect data.
So if you're already suicidal, you can get the ability to act on it before you start getting relief from ideation.
It's also worth remembering that many people do benefit very fast from SSRIs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211759/
The idea that improvement was endogenous or exogenous is itself important for that person's resilience and esteem. So I wonder if there is a bit of a white lie there?
End of day I think scrambling the brain is almost always the wrong choice. That these things are so heavily prescribed and marketed - what does that say?
This is like pretending that anyone who gets antibiotics is weak and if you just exercise, you can beat infected wounds.
Before antibiotics, people just died from wounds. Before AD, people spent their whole lives trapped by things we can do something about now.
Psychotropic pharmaceutical drugs are mind-altering substances. They place people in an "altered state of consciousness". Does this sound familiar.
When my cousin was allegedly afflicted by "chronic major depression", and he was prescribed Prozac, his mother commented "it's like I have my Joey back!" because his mood had lifted and he was acting very differently, different from his behavior in the past year or so, perhaps more like he was as a small child. His Mom always referred to them as Happy Pills. This was the regime when she would remind him to take his dose in the morning. "Take your Happy Pills."
Of course this behavior was mostly because he had been seeing a therapist and was getting some positive attention and reassurance. The SSRI drug soon triggered progressively more intense outbursts of rage and irrational behavior, and it would not be discovered for 5 years that he actually had a more serious mental illness, and the diagnosis and administration of SSRIs had been hasty and improper, exacerbating his condition.
I have been on several and I'm speaking from experience. They do not make you happy. They do not induce euphoria. What they do is relieve depression. Instead of being nonfunctional and crippled, you get some energy and mood back. Ideally, enough to let you work on other things and help you get back to stable.
Plenty of people only need them for a limited time, and that's just fine.
It’s also created a culture of using a pill to solve a problem and yes in some extreme cases it’s probably necessary but I think there’s bigger issues and lots of people with very poor values that create lasting unhappiness.
There was no magic beforetime when we were all happy peasants or hunter-gatherers, singing in the countryside. Humans have always lived with pain and depression and suffering, and to pretend there's any moral good to that is ridiculous, no more than there's any moral good to dying from an infection. Dying from infected wounds is "normal". Being permanently crippled from breaking a bone is 'normal".
People are so weird about things that actually help others.
Why would you mention the number of items on the scale, but not mention the number of points the drug gained? Is it that professionals normally refer to it as the "17-item Hamilton depression rating scale"?
That they're mentioning the number of points in the scale, but not the number of points gained, makes me wonder if this barely limped into significance under the most favorable conditions.
Correct. "17-item Hamilton depression rating scale" (or HAMD-17) is the precise name of the scale; "17-item" is required to distinguish it from other variations with different numbers of questions.
The precise improvement in scoring is undoubtedly present in the clinical trial paper, but isn't relevant to a FDA press release about their approval of the drug.
https://dcf.psychiatry.ufl.edu/files/2011/05/HAMILTON-DEPRES...
Exactly. If it isn’t harmful, it doesn’t have to be very helpful — the effect can be small and significant.
That’s a big “if” though.
Both Zurzuvae and Placebo showed improvement in HAM-D over the 15 day period, but Zurzuvae showed a greater improvement. (From 28.6 to 13, vs 28.8 to 17.2, for a difference of -4.0 points, where lower is better.)
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/21...
Which is why everyone wanted to see it compared to Alprazolam/Xanax or Zopiclone
[1] https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/21...
Not depressed: 0–7 Mild (subthreshold): 8–13 Moderate (mild): 14–18 Severe (moderate): 19–22 Very severe (severe): >23
So, a 4 point difference vs placebo is what I would consider a "clinically significant" improvment, e.g. about the difference between mild vs. moderate, or moderate to severe.
https://en.wikipedia.org/wiki/Hamilton_Rating_Scale_for_Depr...
a four point improvement could be a person stops fidgeting during the interview
daily reminder that psychology is the worst science in terms of the replication crisis
No, it is trivially easy to find out that PPD is neither uniquely American, nor does the US appear to be the country with the highest rates of occurrence.