Hi friends,

How are you feeling coming into the holidays?

I know how hard everyone in this space tends to work, so as we come into the holiday season I really hope you get a bit of time off to rest, recharge and do something you love.

Before we dive in to today’s post, the 2024 Mental Health Founder and Operator Survey is open for just a few more days. I’d really love to hear what the year has been like for you. So if you’ve got 3 mins, please fill it out. Insights will be shared in an upcoming report.

Now for the today’s topic….

Of all the mental health research and innovation in 2024, what do mental health founders and operators need to know about? That’s the question I try to answer in today’s post.

While I usually focus on the commercial side of this industry, I think it’s important for operators to be aware of the scientific, clinical and technological developments happening in this space.

Now, you know I’m not a clinician. And I’m not a researcher either. I’m much more comfortable reading annual reports than talking about clinical developments.

But I’ve spent a lot of the last year reading mental health research, following the latest innovations and listening to people much smarter than me tell me what excites them. And while it may not be my area of direct expertise, I’ve a good nose for figuring out the things MH businesses leaders should be paying attention to.

That’s what we cover in this post. It’s the list research areas and innovations that I think are most interesting and most relevant to mental health founders as we end 2024.

We’ll cover;

• The impact of MH treatment on outcomes of physical conditions

• The growing role of consumer hardware in mental health

• Breakthrough Schizophrenia drug developments

• The growing popularity of Internal Family System therapy

• Advancements on the long-held promise of Biomarkers

• The AI explosion (in brief)

• Next generation psychedelics

THR Pro

The next THR Pro meet-up is happening on December 17th. If you’d like an invite, consider becoming a THR Pro member.

As a member, you’ll also get access to additional insights and data each month, including my most recent deep-dive on The Eight Major Trends Shaping the Mental Health Tech Industry in 2024.

The impact of MH treatment on outcomes of physical conditions

Eriz Arzubi recently sent me one of the most interesting papers I’ve read this year.

It’s about The Impact of Mental Health Treatment on Outcomes in Patients With Heart Failure and Ischemic Heart Disease and if you’re in mental health, you should read it.

The study found that “Mental health treatment for anxiety or depression has a significant impact on outcomes in patients with cardiovascular disease consisting of reduced hospitalizations, emergency department visits, and in some conditions improved survival.”

More specifically, individuals who received both psychotherapy and anti-depressants for anxiety or depression were 75% less likely to be rehospitalised, 74% less likely to have an emergency department visit, and 66% less likely to die from any cause.

These are increidble results!

A previous study on a similar vein from 2020 (Psychosocial Interventions and Immune System Function) found significant impact from mental health treatment on physical health by improving immune system function.

Apart from this being absolutely fascinating from a medical perspective, it helps build the case for getting insurers on board in their reimbursement of mental health treatment. As this study shows, there are very clear and tangible improvements in patient outcomes AND in cost savings for payers from the delivery of mental health treatment.

I’m looking forward to seeing more research supporting this and explaining more about the underlying mechanisms going into 2025. Hopefully payers will be reading the same research and allocating their dollars accordingly.

The growing role of consumer hardware in mental health

I’m seeing a lot more consumer hardware being used in mental health and I’m pretty excited about that fact.

It’s allowing us to collect some really interesting data but perhaps more importantly, actually deliver therapeutic interventions in new and exciting ways.

On the data collection side, generic wearables like smart watches continue to increase in popularity - no surprise there - gathering an increasing amount of relevant data (at one point this year I was wearing a Whoop, a Garmin watch AND an Oura Ring…).

I must admit that for a long time, I’ve felt the promise of these wearables has exceeded the reality. But I’m starting to see signs that this might be shifting.

For my physical health, the AI Whoop Coach is actually really good. It’s probably the best real-world implementation of wearable data plus AI that I’ve seen and think we could take a lot from it into the mental health world.

We’ve now also got mental health specific wearables focused on collecting relevant data. Look at Feel Therapeutics and their wearable for example. Their vision of “bringing continuous and passive monitoring in the field of mental health to generate evidence, and enable precise support and interventions 24/7” is pretty compelling.

This is all allowing us to collect more data, the impact of which we’ll discuss more in the biomarkers section, but I think the coolest thing I’ve seen this year is the evolving role of consumer hardware in the actual delivery of mental health treatment.

For example:

• Flow Neuroscience are delivering impressive results for the treatment of depression using their at home tDCS headset that costs less than $500

• Neurode is using non-invasive electrical stimulation targeting the prefrontal cortex in order to monitor and treat symptoms of ADHD.

• Dharma DR have developed a set of “tabs” to facilitate bilateral stimulation for therapeutic purposes, particularly in the context of EMDR therapy.

• Freespira offer a device designed for at-home treatment of panic disorder and PTSD, focusing on retraining breathing patterns to alleviate symptoms.

• And of course we have lots of interesting companies using other people’s VR hardware to deliver specific interventions, like what oVRcome provide for exposure therapy.

• Several companies are also exploring the use of EEG sensors in consumer devices to create biofeedback loops and personalized interventions.

And there’s lots more that I haven’t mentioned.

Now, I’m no neurotech expert, but from the outside, I see a tonne of innovation happening in this space (specifically around Vagus Nerve Stimulation). I’m really excited by developments here as they have the promise of offering impactful, cost effective treatments for many disorders.

If you really wanna get hyped up about this area, go watch the promo video on this Neurable product page. No idea if this thing works, but damn it sounds cool doesn’t it?

I think all leaders should be watching what’s happening in consumer hardware and thinking about the opportunities it may present for their mental health business.

Breakthrough Schizophrenia drug developments

For the last few decades we’ve seen limited advancements in the medication used for mental disorders. Most current psychiatric drugs work via similar mechanisms as those introduced in the seventies.

However, we saw some genuinely interesting developments in this field in 2024, specifically around Cobenfy.

In September, the FDA approved Bristol Myers Squibb’s Cobenfy (xanomeline and trospium chloride). This is the first new pharmacological approach for treating schizophrenia in over 50 years!

So what is interesting about this drug and how does it work?

Cobenfy, however, targets receptors associated with the cholinergic neurotransmitter system – a system that plays a significant role in memory, learning, blood pressure, heartbeat control, movement and more.

Cobenfy was originally developed by Karuna Therapeutics Inc. (acquired by BMS in 2024) and funded by The Wellcome Trust. It’s a great success story and a cause for great hope in the treatment of serious mental illnesses like Schizophrenia.

Whilst not a new drug development, a significant regulatory change is going to make some promising medication more available to patients with Severe Mental Illness. In November, the FDA announced their decision to remove the current requirements of the Clozapine Risk Evaluation and Mitigation Strategy (REMS) program.

What does this mean? Well, REMS was a program to protect patients against severe neutropenia (low white blood cell count) which is a potentially life-threatening side-effect of Clozapine. The program had some strict requirements, like mandating that prescribers document absolute neutrophil count (ANC) results and that pharmacies verify these results before dispensing the medication. 

Clozapine has demonstrated unique efficacy in reducing suicidality and mortality in patients with serious mental illnesses, but the heavy administrative burdens associated with the REMS program prevented it from being utilised to its full potential. 

The FDA voted against the necessity of REMS requirements 14 to 1, recognising that the existing regulatory hurdles were overly burdensome compared to the risk of clozapine-related neutropenia. 

If we continue to see innovation in drug development and improved regulation like this, prescribing organisations will be able to utilise them to improve outcomes for their patients.

Internal Family System Therapy

This is a bit more niche, but I thought it would be interesting to look at some of the trends in psychotherapy this year.

One trend that was hard to ignore is the growing popularity of Internal Family Systems (IFS) therapy.

If you’re not familiar with IFS, it’s a psychotherapeutic approach that sees the mind as composed of multiple distinct “parts,” each with its own feelings, roles, and needs.

It helps individuals by encouraging a compassionate and curious relationship among these parts. The therapy aims to recognize these elements and bring them into harmony. The outcome? People tend to achieve greater self-awareness and emotional balance. It’s recognised as an evidence-based practice by the Substance Abuse and Mental Health Services Administration (SAMHSA), with several studies demonstrating significant symptom reduction and improvements in self-compassion.

Although IFS has been around for a long time, it has become much more popular in recent years.

Why?

It’s haard to say exactly but I’ve got a hunch. I think it’s because it’s a form of therapy that aligns well with the dominant cultural understandings and expectations of 2024 - especially among young people.

IFS is non-pathologizing and it’s trauma-informed - something that resonates with both therapists and clients in 2024, and fits well with the modern understanding of mental health as multifaceted and relational. It also emphasises self-compassion, internal harmony, and the integration of different "parts" of the psyche. All elements that align with the growing trends toward holistic, client-centered, and evidence-supported therapeutic approaches.

Media has latched onto this alignment of IFS therapy with the culture of 2024. Just go on to “Therapy Tok” today and you’ll find a bunch of videos espousing IFS therapy.

This cultural alignment and associated media attention has driven demand from clients, with increasing numbers of people coming to therapy looking specifically for IFS therapy.

Some providers have even struggled to keep up. Despite over 45,000 psychotherapists listing IFS as part of their practice on Psychology Today (as of April 2024), many training centres have had to implement lottery systems due to overwhelming interest.

If you’re a care provider you should be aware of this trend for increased demand for IFS.

However, the more interesting takeaway is actually on a more meta level.

Provider organisations need to understand that clients are increasingly coming to therapy with demands for a specific type of care, usually driven by cultural and media influences. While this is probably not helpful from a quality of care perspective, we shouldn’t ignore these shifts in expectations from clients and need to be able to deal with them accordingly.

The Long-Held Promise of Biomarkers

For decades, researchers have searched for relevant biomarkers for mental disorders. Finding accurate biomarkers can help us increase the accuracy and objectivity of diagnosis (a huge challenge), improve treatment and enhance our actual understanding of the biological underpinnings of psychiatric conditions.

Looking at just one 2024 study shines a light on how impactful such biomarkers could be. This study on Digital Biomarkers in Depression found that; “depressed participants' real-life behavior such as reduced communication with others can be tracked by passive data.”

While this finding is somewhat intuitive, the next finding was much more meaningful…

“Machine learning models for the classification of depression have shown accuracies up to 0.98, surpassing the quality of many standardized assessment methods.”

Imagine a world where we can passively monitor mental health, use that data to identify at-risk populations, accurately diagnose those patients and then deliver personalised, early intervention. Jeez that would be great!

Of course, we are not there yet.

But what is the current state of biomarkers in mental health?

From my assessment, I’d say;

• We don’t yet have robust biomarkers that can be used broadly in the diagnosis or treatment of mental health

• However, progress is accelerating, with an increase in both the total volume of research being conducted in this area and the number of promising studies being released

• As data availability and research intensity continues to increase, we can expect this acceleration of progress to continue, with the probability of finding robust biomarkers increasingly accordingly.

If you fancy some additional reading on this topic, here are a few of the more interesting developments I’ve seen in this area recently;

• This study in Nature demonstrated an ability to accurately predict mood episodes in mood disorder patients using wearable sleep and circadian rhythm features. Interestingly, daily circadian phase shifts were the most significant predictors

• Another study in Nature, looking at precision medicine for psychotic disorders found “biomarkers that were predictive of high hallucinations and of high delusions states, and of related future psychiatric hospitalizations”.

• Another 2024 study found that inflammatory biomarkers (including leukocytes, haptoglobin, CRP, and IgG) were associated with a subsequent risk of psychiatric disorders, and thus might be used for high-risk population identification. Interestingly, it also suggested a possible causal relationship between leukocytes and depression.

• An interesting company to follow in this space is Alcediag. They just released this paper on the establishment of an RNA editing signature for the diagnosis of certain psychiatric conditions and have a lot of other interesting research worth a read.

Due to the acceleration of progress in this area, and the size of the potential impact, this is an area founders should be paying close attention to.

Digital mental health companies are well positioned to take advantage of developments in biomarkers and will be able to use it to deliver higher quality care, reduce costs and stand out from traditional providers.

The AI explosion

I was halfway through writing this AI chapter when I realised that to do it justice, it requires an entire post to itself. So I’m going to keep this very brief with the promise that I’ll write much more in other posts about the role I see AI playing in mental health.

It’s almost hard to find an area of mental health that AI hasn’t touched, but here are a handful of the more interesting things I’ve been seeing this year;

• Combining the power of AI with the increased availability of data and emerging research on biomarkers and phenotypes is absolutely fascinating to me. Not only can AI be incredibly helpful in the search for new biomarkers, its power in predictive modelling can support early detection. Because early detection is so critical in mental health, I’m pretty bullish on this use case.

• Slingshot are building a foundational model for psychology.

• Limbic have built Clinical AI tools focused on patient referral and clinical assessment that are already being used in 40% of NHS mental health clinics.

• Kintsugi are using facial and voice analysis to provide real-time emotional feedback to therapists, aiding in the early detection of emotional distress.

• Everyone and their mother is building an AI driven, mental health chatbot. Consumer demand for this is enormous (unfortunately, Charachter AI “psychologist” bots have had hundreds of millions of conversations with users) but safety is an obvious and major concern. I’m closely following who is doing what in this space.

• I think using AI for treatment personalisation has a lot of potential. For example… a lot of the last generation of digital mental health companies were based on guiding users through static content journeys on apps. Using generative AI to personalise this content and make it much more engaging will improve outcomes and help with retention - both challenges for many mental health businesses.

AI is not a panacea. But we would be fools to ignore the presence of such a powerful technology in the face of such a serious challenge. As promised, I’ll be back with more in-depth content on this topic soon.

Next Generation Psychedelics

The advancement of Psychedelics is one of our greatest reasons for hope in mental health. Whilst controversial in many circles, there is clear evidence that they hold great promise for improving outcomes for patients. That said, 2024 has been a year of evolution for psychedelics.

Despite coming into 2024 with momentum, the industry took a big hit in August of this year, when the FDA decided against the approval of Lykos Therapeutic’s MDMA treatment for PTSD.

Given the promising Phase II and Phase III studies, this was both a surprise and setback for Lykos and the industry.

So what went wrong?

Many of the concerns were related to doubts about efficacy, and whether the studies conducted by Lykos Therapeutics were able to assess this properly. Notably, the psychotherapy experiences of the participants in the trials were highly varied, which made it tough to pin down the specific benefits of the psychedelic component of the trial.

Many psychedelic businesses are now looking to next generation psychedelics as the future.

Specifically, they are looking at new and improved drugs that extract the benefits of psychedelics whilst minimising its potential harms, thus making them more palatable to regulators and safer for patients.

One interesting development is the emergence of psychoplastogens that deliver the neuroplastic effects of previous generation psychedelics but without the hallucinogenic effects (the trip).

This year we’ve seen biotech giants like AbbVie team up with companies like Gilgamesh Pharmaceuticals to pursue these next-gen psychedelic therapies. It will be interesting to see how this progresses.

While there are clear benefits to removing the hallucinogenic elements of the treatment, some argue the therapeutic magic of psychedelics lies in the ‘transcendental’ psychedelic experience itself.

These believers are staying “true to the trip“ of psychedelics, with their version of next-gen treatments focused instead on reducing unwanted side-effects. Mindstate for example, has developed what they call a ‘psychedelic tofu’, a somewhat bland psychedelic that can be paired with other compounds to trigger desired effects in the brain. In September, Mindstate got approval from the FDA to start testing this drug.

This industry can’t seem to stay away from controversy, but my objective assessment is that the treatments look promising and I’m excited to see what further research is going to bring.

Considering the amount of interest in this space, the amount of capital that has been invested in it (especially from before 2021) and the potential upside if these treatments start to get approved, it’s something we should all be keeping an eye on.  

That’s all for this week.

As always, I’d love to hear your thoughts on this topic? What developments are you most excited about? What have I missed?

Send me an email and let me know.

Sincere thanks to Eriz Arzubi MD, Dilpreet Buxi PhD, Brad Mossel, Sebastian Rositano MD MPH, Royan Kamyar MD MBA, Clarissa Yates PhD and Elizabeth Hong for their help with this report.

But wait, before you go! Remember to contribute to our founder and operator survey.

Otherwise, see you back here next week!

Keep fighting the good fight!

Steve

Founder of The Hemingway Group

P.S. feel free to connect with me on LinkedIn

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