Psilocybin Compassionate Use in Germany: Lea Mertens and Andrea Jungaberle on the First Patients, Payers and Practicalities

Last summer, Germany’s medicines regulator quietly green-lit a psilocybin
compassionate use program, the first such pathway in the European Union
(see Germany Establishes EU’s First Psilocybin Compassionate Access
Program). Two centres are permitted to offer psilocybin dosing at present:
OVID Clinic Berlin, a private clinic in the nation’s capital, and the Central
Institute of Mental Health (CIMH) in Mannheim, a public hospital.

On the final day of the Interdisciplinary Conference on Psychedelic Research
(ICPR) in Haarlem, the Netherlands, our Editor Josh Hardman sat down with
two of the people at the centre of the project: Lea Mertens, a researcher and
psychotherapist who is first-author on the two primary publications associated
with the EPIsoDE study (one in JAMA Psychiatry, and another in Psychotherapy
and Psychosomatics), which formed the basis for the compassionate use
program; and Dr. Andrea Jungaberle, a medical doctor and psychotherapist
who co-leads OVID Clinic Berlin with Dr. Gerhard Gründer, with whom Mertens
also works closely.

Here, they discuss the experiences of the first few patients to receive
psilocybin under the program at OVID, progress in securing coverage from
public and private German insurers, Mannheim’s list of 700 patients who have
expressed interest, and the flexibilities the compassionate use model affords
compared with clinical trials.

Josh Hardman, Psychedelic Alpha: So, you have two quite different
sites, right?

Lea Mertens: Yes, we have two centres. Andrea is at OVID in Berlin,
and we’re a big public hospital, so it’s quite different; it’s a big
machine. We are at the point where we are just implementing the
program in our hospital, which we are hoping to do in an outpatient
setting. We have started screening people.

Hardman: Has it been tough getting buy-in from colleagues at
Mannheim, or have most people been open to it?

Mertens: They’re open to it, it’s just a large hospital and more of a
rigid system, so it’s just trying to find the proper and optimal way to
actually do it, and to document it. It’s got to be covered by the public
insurance.

Hardman: So, the goal is for all of the compassionate use treatment
to be covered by public insurance at your centre?

Mertens: Yes. And it would be covered already if you do it on an
inpatient basis, because then it would just fall under the normal daily
copay that you get anyway, no matter what treatment the person
receives. But doing it inpatient has other challenges: you need to have
a bed available, and so on. That’s quite difficult, because we’re a
general public psychiatric hospital covering the whole area of
Mannheim.
We’re currently awaiting approval from BfArM [(Germany’s drug
approval body)] for also doing it outpatient. We believe the basis for
that is there, based on the existing studies. If that approval comes, we
would most likely do it on an outpatient basis, because it’s easier to
do and there’s less risk for public insurance to question it.

Hardman: That’s very interesting. One of the criticisms of similar
programs in the U.S. is that it’s not always accessible for patients who
do not have private health insurance.

Andrea Jungaberle: Around 10% of the general population in
Germany have private insurance, because all public servants are on
private insurance, for example. The goal we’ve reached now at OVID
is that, because we do it as a stay at the day clinic, we also go via
copay, so nobody pays for the compassionate use element if they are
on private insurance. They pay for the day clinic stay, and the insurance covers
it.
We actually got the largest German private insurer to kind of fast
track us, so we have an agreement with them that we will get the
approval within a week if it’s granted, instead of seven or eight weeks.

Editor’s Note: In Germany, psychotherapeutic day clinics
serve as a middle ground between outpatient and inpatient
services. Patients visit a clinic each day and participate in a
structured program of activities that often includes
individual and group psychotherapy, psychoeducation, art
or occupational therapy, and physical activity.

Hardman: So, private (but not public) insurers require a patient-by
patient prior authorisation to cover; but you don’t have to get patient
by-patient authorisation from BfArM or some other authority to
treat?

Jungaberle: Right. We don’t have to talk to the authorities, so it’s
different to Switzerland.
There are a certain number of patients we are allowed to treat, and
it’s basically up to Gerhard Gründer as the head of the program to
sign off on the patient, and then we can apply for the coverage, and if
the private insurance agrees on it, they cover the full eight weeks of
day clinic stay that we have embedded it into. Since the largest
German insurer has now given us this priority status, it’s getting
easier to also talk to the others.
We have not had any approval process finally rejected by private
insurers if the conditions were met correctly. But it has been a longer
process, so sometimes people had to appeal two or three times to get
it covered.
We also have a few international patients coming in, because we’re
not restricted to German residents. We actually got an Austrian
private insurer to cover their patient’s stay at ours, which might be a
precedent for other countries in Europe as well.
Hardman: Interesting. And the drug product itself is at no cost to
patients, right?

Jungaberle: Yes, the German compassionate use states that the drug
has to be offered to the patient free of charge; we can only charge for
treatment around it. The situation we’re in now is that we get 50 cases
per site per year of free drug product from Filament Health. If we
want to do more, we’d have to pay for it. The price isn’t clear yet.
Mertens: Right. We get the product for free, but we have to pay out of
pocket for the handling and logistics of getting the import permits
and stuff, which is not much, but as a public research group, it’s still
something.

Hardman: I understand the group in Czechia have had a philanthropic
donation to buy 250 doses,

Jungaberle: A donation would be great! As I say, there was no direct
cost for us with the doses, but for the bureaucracy.
We’re also trying to raise patient grants so we can take people in who
couldn’t pay out of pocket and aren’t privately insured. As far as I
know, Lea, you’ve got 700 people in the queue who would be
interested.

Mertens: I’m not managing the queue, but it’s a lot, and it’s already
difficult to handle the wait list.
Hardman: So, you’re screening patients at Mannheim but have not
dosed any yet. At OVID, you have seen a few, right?

Jungaberle: We have treated three, and we are dosing number four
next week.

Hardman: And how have those three sessions gone?

Jungaberle: The first was a patient who was already part of the
EPIsoDE trial and had benefited for a very long time, so she was much
better after years of chronic depression and only relapsed into
treatment-resistant depression that lasted about six months after she
had long COVID. She was at the day clinic for a total of 12 weeks,
partly because she just needed time, and partly because she was still
waiting for the substance to arrive.
She was dosed in week 8 of her stay, had a good experience, and was
able to, in her words, bring home a lot of the learnings she had
already made the decade before.

Patient number two was a veteran. We don’t have that many in
Germany, somebody who had been fighting in several peace missions,
but also, of course, carrying a gun and using it in the late ‘90s and
coming back with a mixture of long-lasting depression, but also PTSD
symptoms. He went into the treatment with a lot of aggression,
permanently on high alert, everything triggering him. So, we actually
were a bit concerned how we were going to manage the session.
That also went extremely well. He really understood what was going
on in his life and how he never quite switched out of war mode. He
went from a Beck Depression Inventory score in its 40s, which is very
high, to below 5, which is not qualified as depressed anymore.
The third patient was a chronically depressed patient who had been
in and out of therapy, hospitals and different treatments for more
than 15 years, and that has also been beneficial. She is not as acutely
better as the other two, but she is definitely doing well.

What they all shared was that the experience wasn’t all easy, that they
found it challenging, but the challenges really helped to understand
what the issues were and work on them. They are in integration
processes, they are also still in therapy, and have all understood that
it’s very necessary to keep on working on their topics in the future as
well.

Hardman: Very interesting. How many more patients do you plan on
seeing in the coming months?

Jungaberle: We’ve got the next 10 or so lined up, already screened,
already partially reimbursed, so we’re waiting for some decisions.
Since we’re such a small facility, we can’t admit more than one
compassionate use patient per week, because we have to integrate
that into the day clinic.

Mertens: It’s going to be the same for us, but we might offer a group
setting at some point.

Hardman: Would that require you going back to the regulator and
asking if you can do it in group settings?
Mertens: No, it explicitly allows group administration. Then again, it
would be new processes. But it would be good, because our team is
equally small. So, it could help in terms of man- and woman-power
wise, and also financially, of course.

Hardman: Is there a lot more flexibility in the compassionate use
program vs. a clinical trial like EPIsoDE?

Mertens: There’s much more flexibility. We’ve pretty much defined a
minimum that is based on the EPIsoDE trial. So, two sessions before
and after dosing. But we have the option of actually extending it as
much as needed, because they would just be regular psychotherapy
sessions, in a sense.
Also, the manual currently provides the option of re-dosing under
certain conditions, and we didn’t have that in the study. If someone is
going to be dosed two times, three times, four times, that’s a longer
therapy process.

Jungaberle: All three people we have dosed so far had this very
intense preparation time, because it was three or four weeks in the
day clinic, seeing therapists every day, working every day, and then
also the integration took about the same amount of time.
They really benefited, but even these people said they’re so happy
that theoretically, if they deteriorated, they knew they would be able
to come back. We heard that so many times in the EPIsoDE trial that
somebody actually got better and said, “Yeah, but what do I do if it
gets worse? I’ve been worse so many times in my life.”

Mertens: Yeah, it’s a very different setting in a trial, because there’s
pressure around it. Your day clinic setting probably gives it some
more calm, so that it’s easier to really dive into the experience.

Jungaberle: There’s so much more happening around it. Now, we have
patients who have done the treatment and are in the phases of
integration. The next people come in, and they talk to each other, and
suddenly there are expectations going in directions I never expected,
because somebody is sharing his or her experience with patients who
are coming into the treatment program.
There are so many variables you can’t control in this situation, and we
will have to get used to how to manage these interactions among
people.

Hardman: So, you are embedding the psilocybin within a very
‘involved’ model of care at OVID, by the sounds of it.

Jungaberle: It is only financially viable if people are in the day clinic
for a minimum of six or eight weeks. The main treatment phase of the
Compassionate Use lasts a minimum of three weeks, but most people
need more time to settle into the treatment process properly, and
definitely benefit from far more chances to learn and integrate
afterwards.
We are actually kind of practicing the opposite model to what is being
done on the clinical trials. Where trials may try to go for limited care,
limited psychological support, our patients have had between 50 and
100 hours of psychotherapy in individual and group sessions, body,
art, music therapy, and so on, during the time they are with us.
This is kind of the maximum care model, and it’s going to be
interesting to us to see what that does. It doesn’t mean that this will
all be necessary for every patient, but it surely stabilises treatment
effects for patients that have been severely affected long-term.

Hardman: Thinking about different types of patients, the program is
currently approved for treatment-resistant depression, given the
EPIsoDE population. What level of evidence do you think regulators
would need to expand it to broader indications?

Mertens: Yes, there are a whole lot of prerequisites that have to be
fulfilled for a compassionate use program to be feasible in Germany,
and they are indication-specific. That indication must be a “serious
debilitating or life-threatening disease”, and there must be ongoing
clinical trials with the drug product. We are more flexible with regard
to comorbidities, but treatment-resistant depression remains the
primary indication.

Jungaberle: It’s also interesting because you sometimes have people
coming in who have two equally burning problems. For example, we’re
now seeing a patient who has severe complex PTSD, and of course,
treatment-resistant depression, and her ticket into the
compassionate use program is the depression, but she’s somebody
with extremely strong startle reflexes, for example, and is very much
affected by PTSD, and that’s a different case to handle altogether, in
my opinion.

Mertens: But that’s just regular psychiatry, right? We have those
categories, but whether they are distinct entities is another question.

Hardman: Presumably many patients that will be going through this
process will have engaged in psychotherapy beforehand. Do you think
that supports their capacity to benefit from psilocybin?

Mertens: Yes, I’ve had wonderful processes with people who’ve done
extensive work beforehand, where they had understood a lot,
cognitively, but hadn’t managed to really connect with those cognitive
insights. For example, the ability to really feel self-compassion might
be lacking. In EPIsoDE, I saw some patients finally able to translate or
feel that, for the first time, and I think those were some of the most
beautiful processes.

Jungaberle: I call these patients ‘goldfish patients’, because they’re
like a goldfish sitting in a glass by a lake, and they can see the water,
they know exactly where they would have to swim to get out into
freedom, and there’s just this glass wall. Sometimes the psilocybin
therapy is just getting out of your little fishbowl and into the lake.

Hardman: That is very interesting. Terence Ching, who’s working on
psilocybin for OCD research, shared something similar in an
interview.

Mertens: The constructs are already there, and then you can work
with them in integration, and it can just ‘click’.

Hardman: Has there been much media interest in the compassionate
use program?

Mertens: There was when it was approved, and following the EPIsoDE
publication. We get regular requests from journalists, and we have
also connected journalists to EPIsoDE trial participants, but we try to
be careful there.

Jungaberle: There might be another documentary coming up, but it’s
not about squeezing out all the media attention. I’m just glad also to
be able to do my job on the ground.

Mertens: At the moment I’m really reluctant to speak a lot about the
program, because we already have these lengthy wait lists. If we put it
out there more and more and more, there will be more patient requests, and if we don’t have the teams to manage all these requests, what are we gaining from it?

Jungaberle: It’s a bit of a different situation for us, because we have to
build the waitlist still.

Hardman: What are you most excited about with this program, Lea? Is
it a source of intellectual inquiry for you?

Mertens: I’m also a psychotherapist, so from the clinical perspective I
am very excited that we can also, for example, help former EPIsoDE
patients who may benefit further. We have some requests from
previous participants.
I’m also excited about the flexibility the program offers, because one
of the things I disliked about the trial is that we had to be strict. So, I
am excited to be flexible and offer another 4, 5, or 6 integration
sessions, if I think it’s worthwhile, before going into a potential next
dosing session. So generally, being able to let the patient’s process
guide the dosing sessions rather than having a strict manual we have
to follow.

Hardman: On the topic of flexibility, are you using 25 mg or can you
be flexible there, too?

Jungaberle: We can be flexible. We had a patient who was 120 kg,
mostly muscle mass, and we gave him 30 mg. It was exactly the right
decision. Anything else would have been underdosing him.
We also don’t have to taper all of the serotonergic antidepressants
anymore. I actually found Sandeep Nayak’s presentation super
interesting, the option of escalating the dose in-session. I really would
love to have this option.

Editor’s Note: Earlier in the day, Johns Hopkins researcher
Sandeep Nayak presented findings from a study of
psilocybin-assisted therapy for chronic PTSD in adults on
SSRIs. In the open-label trial, participants initially received
25 mg but could be given a booster dose to reach 35 mg.

Mertens: We also have the option of going lower. In the trial I have
seen a potential need for this, mostly in women who are already quite
in contact with their emotions and maybe also a bit dysregulated. But
the standard dose will remain 25 mg, because that is what the
empirical evidence supports as an antidepressant dose.

Jungaberle: At OVID, we would have to readmit them for a second or
third dose, and this is quite a strain. So, we will try to stick with one
dose for now. But being able to tell a patient that we have the option
to do so, I think it takes the pressure off people. In the EPIsoDE trial,
there was a lot of pressure on people, especially if they had placebo in
the first session, that they really had to get it right in the second
session.

Read on our website: https://psychedelicalpha.com/news/psilocybin
compassionate-use-in-germany-lea-mertens-and-andrea-jungaberle
on-the-first-patients-payers-and-practicalities/