There are new meds that don't target dopamine and still work

Medications
1

So much for the dopamine hypothesis of schizophrenia. :thinking:

https://news.sunovion.com/press-release/sunovion-and-psychogenics-announce-sep-363856-has-received-fda-breakthrough-therapy

It just goes to show that nobody has a clue what causes it. But we knew that already.

Is the dopamine hypothesis finished ?

6 Likes
2

Maybe schizophrenia causes high dopamine not high dopamine causes schizophrenia.

3 Likes
3

Unfortunately my doc is super into the d2 receptor occupancy theory. He wonā€™t increase my meds because ā€˜I think all your dopamine receptors are filledā€™

1 Like
4

what does breakthrough designation therapy mean in terms of years realistically?

5
LIMITATIONS OF THE DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA

Current research shows that one-third of individuals with schizophrenia do not respond to non-clozapine antipsychotics despite high levels of D2-receptor occupancy.

Furthermore, a study using tetrabenazine (used as augmentation) which depletes presynaptic dopamine was not found to be effective in augmenting a clinical response in schizophrenia. [8]

Therefore, for a significant number of patients with schizophrenia, the basis of their symptoms is either unrelated to dopaminergic dysfunction or is associated with something more than just dopamine excess.

Alternatively, this could also mean that for some patients with schizophrenia there might be a non-dopaminergic sub-type of schizophrenia.

The current dopamine hypothesis of schizophrenia does not adequately explain the cognitive and negative symptoms. Current treatments which modulate dopamine transmission have only modest effects in improving these symptoms.

It has taken two decades for the dopamine hypothesis to evolve and reach its current state. More recent evidence shows another neurotransmitter, glutamate playing an essential role in schizophrenia.

The future likely holds a lot more secrets about schizophrenia which should unravel with the advances in understanding the brain.

5 Likes
6

My guess would be this isnā€™t it for the dopamine hypothesis, because apparently one of the mechanisms is to modulate presynaptic dopamine function - even though it doesnā€™t block dopamine, or target dopamine directly. It seems like it acts upstream of whatever causes excess dopamine production.

Sunovion presented two posters highlighting new data at ACNP 2019. The first poster titled, ā€œThe Novel, Non-D2 Psychotropic Agent SEP-363856 Modulates Presynaptic Dopamine Function in Mice,ā€ (Poster #M178) presented data in support of the novel mechanism of action of SEP-363856.

One of the more replicated findings in schizophrenia models is increased presynaptic dopamine synthesis capacity.

But this seems like it would be better with fewer side effects if they could start at the source and not have excess dopamine in the first place, rather than just block it in multiple regions of the brain, some where it is needed and some where it isnā€™t.

Also I donā€™t think even in the dopamine hypothesis that scientists think that is the ONLY neurotransmitter that is changed, or even that itā€™s always changed, in everybody.

2 Likes
7

Great insight @twinklestars ! Thanks !

2 Likes
8

Thereā€™s still other ones that, so far as we know today donā€™t act on dopamine, like Naben.

Maybe we will find out they do, or maybe we will find out that they still work anyway because itā€™s complicated and thereā€™s a lot of stuff going on in there.

2 Likes
9

I just read the title of this and thought wowwwwwwwwwwwwwwwwww okā€¦

this is news

1 Like
10

too bad I am too scared to try new meds lol

1 Like
11

Iā€™m the same. I think Iā€™ll be on my current meds for life. Better the devil you knowā€¦

1 Like
12

For negative symptoms like low motivation, energy etc DMG is best, for flat affect phophatidylserine soy version is best.

1 Like