As aripiprazole, brexpiprazole, and cariprazine are partial-dopamine agonists with potent binding affinities to the D2 receptor, do they prevent augmentation effects (or worsen psychosis) when two or more antipsychotics are combined?
Certainly, there is data suggesting worsening psychosis when aripiprazole has been added to other agents (Takeuchi and Remington, Psychopharmacology 2013). Additionally, the idea of competitive inhibition is supported by the reversal of hyperprolactinemia when aripiprazole is added to another antipsychotic.
I can find no data of this phenomenon occurring yet with brexpiprazole or cariprazine.
Not impressed with any additional efficacy over 2nd gen AAPs. Also not impressed that AP polypharmacy adds much to monotherapy. Over the years I have seen many side effects including severe Parkinsonism and tardive dyskinesia from 3rd gen augmentation of antidepressants - even in low doses (so far both aripiprazole and brexpiprazole).
Drugs work best when they are new. Hence the adage, "Be quick to use this new medication before it stops working!"
Problems of low efficacy and adverse effects take time to emerge.
To be sincere I read somewhere of an addictive strategy for poor responder to a AP based on adding aripiprazole. In some case I have seen aripiprazolo work well with aloperidol or bromperidol. In Italy we dont have yet the two other AP.
Edward Shorter holds that the present anti-psychotics do not have the efficacy of the original drugs, and that generally Clorpromazine, the first, is more effective than recent ones.
I'm perfectly agree with Giovanni Portuensi as we sometimes use the strategy to add aripiprazole to poor responders to 1st and 2nd gen AAPs. Althoug there is data suggesting worsening psychosis when aripiprazole has been added to other agents, personally I have never seen it in clinical practice so far. I often found instead the reversal of hyperprolactinemia when aripiprazole is added to another antipsychotic
I really like his work but Edward Shorter is clearly wrong on the efficacy of chlorpromazine (CPZ). It was common to see people on very high doses of CPZ because it was the only thing available and although they were sedated they were clearly still symptomatic and had neurological side effects. The patients knew it as the "Thorazine shuffle" and wanted to avoid the medication for that reason.
All of the first generation drugs were a nightmare in terms of neurological and in some cases cardiac side effects. That is never absolute but if I look out on an inpatient unit today - there is nobody out there with tardive dyskinesia. With first generation APs at least 1/4 of the patients were affected and most were bipolar patients.
I used 1st generation AP for many, many years and I still prefer them. If patients had a "shuffle", it is because they were overdosed. Chlorpromazine was in fact a miracle and most of the drugs were cardiovascularly safe. Now patients, even on low doses become obese, develop diabetes, cardiovascular sequelae, and die before their time. Tardive dyskinesia was a problem for sure, but obesity kills.
Aripiprazole, being a partial dopamine agonist, does make some people more psychotic, but others appear to do well. It would be important to find out why.
I can not quite agree with that. I have several patients with schizophrenia who are stabilized with aripiprazole in the long acting injection form.