Towards a precision psychiatry: the new drugs that are transforming depression and schizophrenia

• Mental Health Another look at schizophrenia: "The diagnosis is the beginning of a story of overcoming"

• Interview "We have good professionals who have evolved, but the infrastructure and attention are deplorable"

"We are entering the era of precision psychiatry; there is good hope that we are witnessing a paradigm shift in the development of new drugs in mental health

.

This is stated by

, head of the Psychiatry and Psychology Service of the Hospital Clínic, in Barcelona, ​​and scientific director of Cibersam.

In his opinion, the

in this area -compared to 138 in October

e of 2019- are few if compared to the R&D of the sector in other areas, but they do represent a qualitative advance since

If we look back seven years -he points out- we would see that many of the drugs in development or that reached the market provided very little advantages compared to what was previously available".

Moreover, Vieta considers that as precision psychiatry advances and the use of more specific biomarkers -those currently being used, such as those for inflammation or neuroplasticity, are generic or very transversal in all psychiatric pathologies-, there will be even more relevant qualitative leaps, because

, or because there will be biomarkers or other tests that will not be based only on the clinic."

The psychiatrist explains that the indications that the

FDA

and the

EMA

currently approved "are based on clinical constructs that are descriptions of groupings of symptoms, but not on biological substrates or biological targets that are what a drug actually acts on," adding that "the correlation between the biological and the clinical is imperfect, that's why

". However, he points out that "it is still a bit premature and we have not yet reached the point of having reliable and specific biomarkers

although, he insists, "

", partly also because the pharmaceutical companies themselves are looking for developments that bring more benefits than the so-called

-medicines very similar to those that already exist- that compete in a market, moreover, largely made up of generics today".

However, the

according to data from the US pharmaceutical employers

PhRMA

, are also a small quantum leap.

The US organization includes in the report all the compounds being developed by pharmaceutical companies with a presence in the United States -of North American origin or subsidiaries of foreign companies-, that is, practically the entire sector, and includes products between phases I and III of clinical research, and those pending a regulatory decision.

In line with the prevalence of diseases in this area, the

takes the cake and

, followed by the

and disorders of

, both with 35 compounds in development.

Indeed, in the last two or three years they have discovered

innovators that are transforming the therapeutic areas of the

in which changes are actually taking place that can also generate more benefits for developer companies due to their degree of innovation.

In depression, for example, it has been decisive to discover "the relevance of the mechanisms of glutamate agonists and serotonergic or psychedelic agonists.

Among the first, the

-already on the market- has opened the new frontier of treatments that are not only based on the inhibition of monoamine reuptake (as in traditional antidepressants).

Among psychedelics, which are in phase II-III, the innovation is that they are

, instead of being drugs that antagonize its transport, the indirect pathway present in traditional antidepressants, still useful, but whose effect takes longer and is less potent.

Preliminary data reveals that the two new mechanisms are more powerful, much faster acting and

, an indication of the ones that will develop the most in the short term," says Vieta.

There are several companies that are working on these and other innovative lines of research and development, but

, according to the PhRMA report.

Two of them, the American Janssen and the Danish Lundbeck, have accumulated a long history of specialization in the field of mental health and have made significant contributions in the field of mental health.

current.

The first, specifically, made available to Spanish patients in 2022 both the aforementioned

in a nasal spray, "the first and only drug approved in Spain

, an area where no new mechanism of action has been launched in the last 50 years, and with significant unmet needs", and biannual paliperidone palmitate for

, which is the longest dosing interval available for an antipsychotic in Europe, with the advantage that this implies in quality of life and the risk of relapse," says Henar Hevia, medical director of

Janssen Spain

.

SHUTTERSTOCK

Since Dr. Paul Janssen developed the pioneering antipsychotic haloperidol in the 1950s - which revolutionized the standard of care for schizophrenia and is on the list of essential medicines of the

WHO

- Until today, the North American company has abounded in R&D in schizophrenia, major depressive disorder or bipolar disorder, as well as in other areas of neuroscience such as

Hevia agrees with Vieta that research in the area of ​​neurosciences is especially challenging, "taking into account the difficulty that this area entails, given the

, the research still in progress on clear biomarkers and the need to have systematized records that make it possible to carry out studies with Big Data.

In this sense, it is necessary to continue advancing in the personalization of treatments and in the knowledge of the clinical subtypes", comments Janssen's spokeswoman.

One of these Janssen development innovations, and among which PhRMA stands out for its high innovation, is

,

which is currently under investigation as an adjunctive treatment for major depressive disorder with symptoms of anhedonia.

"Today, phase 2 studies are being developed that also include the participation of Spanish centers," explains Hevia.

lundbeck

, for its part, is working on improved formulations of some of its most emblematic products and on new therapeutic lines, after more than 70 years of R+D+i focused on the central nervous system, "which allows us to be a benchmark in treatments for

, as well as a

of scientific, medical and social institutions in the field of brain health", says Susana Gómez-Lus, the company's medical and Market Access director in Spain.

the danish company

, and bases its current scientific activity on a research strategy directed especially at four areas defined by Gómez-Lus:

focusing on neurotransmission or synaptic dysfunction to recover those brain circuits;

to address protein-related neurodegenerative disorders;

the

-targeting selected pathways of pain signals and stress response-, and the

, focusing on brain function through the immune system.

The R&D of these and other companies in psychiatry sometimes has additional obstacles, such as the not infrequent coexistence of more than one psychiatric pathology in the same patient.

"When examining a drug, it is a matter of excluding everything that could interfere with that evaluation. For example - indicates Eduard Vieta -

, such as alcohol, to combat anxiety or depression.

Challenges in essays

The psychiatrist explains that this type of patient cannot be included in the trials because the consumption of other substances is a confounding variable when evaluating the strict role of the tested compound for depression or anxiety.

"Ultimately," he says,

;

most of those a psychiatrist sees are

.

In psychiatric pathology we sometimes talk about comorbidity when two pathologies coexist, although in reality what there is is a pathology with symptoms of another or symptoms of both;

The delimitation is not as categorical as having or not having multiple sclerosis".

Lastly, the Clinic specialist highlights the

in psychiatry, that "

in recent years in two ways: every time there is

-before we were a recruiting country but without so much direct scientific contribution-, and every time there are

, to the point that today it is one of the great countries in Europe in this field.

There is a long way to go and improve, for example, in the agility for the approval of trials by ethics committees, which are a bit slow, although it has been improved".

The most innovative, according to PhRMA

-A

Orally administered as adjunctive treatment for

.

Kappa opioid receptors are involved in anxiety-like, dysphoric, aversive, and drug-seeking behavioral responses.

KOR antagonists, which play an important role in stress and mood regulation, block kappa opioid receptors and reduce these responses, producing antidepressant and antiaddictive effects.

-A

of a single daily administration for the

.

The GABA system is a critical neurotransmitter signaling pathway that is responsible for the flow of information within the intricate circuitry of the brain and central nervous system.

The GABA system contributes significantly to regulating function and dysfunction of the central nervous system which are known to be at the center of numerous psychiatric disorders.

-A

in development for the

(PTSD).

TRP channels are expressed in the brain and are involved in innate fear function and anxiety-like behavior.

For example, TRPC5 increases cholecystokinin activity, which increases neural anxiety.

By inhibiting TRPC4/5 activity and thus reducing CCK activity, depressive and anxious behaviors are suppressed.

The medicine

.

-A

(TAAR1);

receptor that plays a significant role in the regulation of dopamine, norepinephrine, and serotonin neurotransmission in the central nervous system.

Studies show that TAAR1 activation could

currently marketed as movement disorders and weight gain.

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