How come meds like Vraylar and Abilify reduce positive symptoms?

Meds like Vraylar and Abilify are partial dopamine agonists at D2 receptors while other AP’s are antagonists. I get how the antagonists reduce positive symptoms by reducing dopamine but the partial agonists perplex me. If they are activating your receptors how do they reduce hallucinations? And does that mean they won’t make negative symptoms as bad?

I dont know but for some abilify really does nothing. I would read into the pharmacology of these drugs for the answer. Not a very helpful answer from me. Just wanted to point out that those two drugs have been thought of as 1)energizing and 2) not helpful for positive symptoms for some
So it must depend on how schizophrenia effects your brain specifically if wether these drugs would be helpful or not.

Because they’re weak antipsychotics designed for mood symptoms as opposed to psychotic symptoms, but they can also help mood disorders with psychotic features.

edit: That said, we really don’t know what causes psychosis because it’s different in everyone. The dopamine theory makes no sense, because if it were solely true, then a) psychotic depression would be impossible, and b) we’d only need one universal medication because everyone’s reason for being psychotic would be exactly the same.

4 Likes

I guess because we still know basically nothing about psychosis and other conditions. So the meds are just about throwing everything at the wall and hoping something will stick. It’s why some meds work for some people and do nothing for others.
What is vraylar? Is it new?

It’s still a mystery!..

1 Like

I think they are antagonists at the main d2 dopamine sites but agonists at some of the other ones

Vraylar is a partial agonist at D2 and D3 receptors with higher affinity for D3 receptors. I think it’s new.

Ok so think of dopamine channels as being doors. A full antagonist means the door is completely closed. These are what older antipsychotics are. The issue with the door being fully closed is that we NEED dopamine for things like motor skills, so people end up getting issues like tardive dyskinesia and even parkinsonism. So, they invented the partial agonists. For these meds, the door is open, but only a little bit, so some dopamine can still get in but not the huge flood that’s normally present in psychosis. That way we get the dopamine we need to prevent motor disorders, while preventing things like worsening of negative symptoms and the motor disorders I mentioned.

Theoretically anyways. Sometimes these even still block too much dopamine depending on the individual and what amount they need.

5 Likes

You seem pretty knowledgeable and well read on the subject. I don’t like the idea of my dopamine being completely blocked so the partial agonists are probably better for me. I’m on invega and have had pretty severe negative symptoms and I’m switching to Vraylar and I read that it can improve negatives.

I’m on just aripiprazole for more than 2 years and I’m pretty stable. I don’t have positive symptoms since 2015, the first time I was hospitalized. Actually, I’m on a low dose of aripiprazole for more than a year and I’m still stable. I hope things keep going well.

I started with 20 mg of aripiprazole and lowered it to 5 mg. But I did it with medical supervision and a lot of therapy work.

It really depends. Most antipsychotics reduce positive symptoms. I’ve never been on Vraylar. Abilify didn’t do anything for me except make me extremely angry. Abilify actually has a warning that says it can increase aggression. The best combination I’ve been on is 12 mg of paliperodone and 1 mg of haloperidol. (And 200 mg of Lamictal for mania). The main reducer of positive symptoms is dopamine D2 antagonism. Almost all antipsychotic medication does this. Well, except Vraylar and Abilify. These two are actually D2 agonists. Which is opposite of almost every other antipsychotic. So it’s counterintuitive, I don’t know why these reduce positive symptoms in some. (Abilify didn’t for me). I heard Vraylar is for everything–psychosis, anxiety and depression. (But not mood).

I am a neuroscience major psych minor currently going for my second degree in nursing with the goal of becoming a psychiatric nurse practitioner, I’ve also taken both pharmacology and neuro psychopharmacology, so yes I like to think I know a bit on the topic :wink: I like sharing what I’ve learned wherever I can! I think knowledge can be important for recovery.

1 Like

When I switched from olanzapine to aripiprazole, I became a bit emotionally unstable. My switch was too fast and I noticed I was getting more confused. Hopefully I voluntarily admited myself into the hospital (in order to prevent psychosis) and my doctor managed the medication again with olanzapine. Then we tapered off olanzapine slowly after hospitalization and I got better.

I read an article that switching antipsychotics with different action mechanisms may cause many adverse effects. I think some pdocs are not always aware of it.

I am on Vraylar now and it’s helping with positive symptoms fairly well at the moment, but we all know that can change. I’ve tried just about everything out there and some of my symptoms can’t seem to be controlled…