I feel like this post just keeps getting longer and more boring. I hope to make a clean short post about Vraylar, and a separate post on Rexulti and Abilify. Such interesting medications!
Brexpiprazole (Rexulti) is a new antipsychotic that came about at about the same time as cariprazine. Cariprazine and brexpiprazole (I just love saying these names, don’t you?) both function as partial agonists of the dopamine-2 receptor (D2) which is a trait that they inherited from their mother molecule Aripiprazole (Frankel & Schwartz, 2017). So, aripiprazole, cariprazine, and brexpiprazole are all similar in a lot of ways but slightly different in some ways. Today, I want to mainly focus on cariprazine because I have so much information on this new medication, but there is not a lot of info out here on the interwebs.
Disclaimer: Sadly, I don’t get paid by any pharmaceutical companies. That is one reason why I will mostly use the generic name of the medication for this blog. I am not endorsing any particular company, however, I am kind of excited about these medications. I think that cariprazine will help a lot of people who have not tolerated other mental health medications in the past.
Another disclaimer: I might talk about using these medications for things that are not officially FDA approved. Getting FDA approval for a medication takes a long time and a ton of money. We use medications for non-FDA approved things all the stinking time! For example, when you took ibuprofen for your headache, did you stop to look whether that was FDA approved usage? Probably not, but common sense and science and past experience tell you that ibuprofen will probably work for your headache. Therefore, I will be applying common sense, science, and past experience to the new medication cariprazine, and think through some ways that it might be used that are not officially FDA approved.
Disclaimer number three: These medications are freaking expensive. You can’t afford them out of pocket. However, there are usually great coupons and patient assistance programs available. I filled a script for free with one coupon, and then got another coupon to pay $15 per month. Not too bad for what I consider a life-saving medication. The cash price for thirty pills of cariprazine was $1153.97 at Walmart (February 2017).
Aripiprazole, brexpiprazole, and cariprazine are slightly different in a how they work on the various brain chemicals. So, if you tried one of these medications and did not like one of the side effects, you might do okay on one of the other medications.
When talking about these anti-psychotics, everyone spends a lot of time discussing the neurotransmitters, like serotonin and dopamine. This is like discussing calculus in your advanced physics music theory class. It is so complicated! If you don’t understand it, that’s okay, because no one does. The only people who pretend to understand this are the drug reps who give you the same speech over and over about which neurotransmitters this medication is working on, and why that is so great. However, it depends on where in the brain the neurotransmitter is working, also. So for example, antagonizing serotonin-2a leads indirectly to downstream effects that raise dopamine in brain areas (nigrostriatal system) that are sensitive to bad movement side effects (extrapyramidal symptoms). The theory is that these newer antipsychotics have fewer side effects because the old-school antipsychotics fried the dopamine in the movement areas of the brain and the new ones leave dopamine alone in that area of the brain.
Aripiprazole (Abilify) and cariprazine (Vraylar) both work on upregulating dopamine-2 (D2) receptor levels in various brain regions. Aripiprazole has less effect on dopamine-3 (D3) than cariprazine. High cariprazine doses increase serotonin 1a (5-HT1A) receptors.
Antagonism of serotonin-2A-receptors allows greater dopamine activity in the nigrostriatal pathway while lowering psychotic symptoms by preferentially dampening the mesolimbic pathway.
I need a good brain photo to go here. Thanks wikiphotos:
Long-term administration of aripiprazole and cariprazine had similar effects on serotonin-1a (5-HT1A), NMDA, and AMPA receptors. However, cariprazine more profoundly increased D3 receptors while aripiprazole selectively reduced 5-HT2A receptors. These results suggest that the cariprazine uniquely affects dopamine D3 receptors. And with its effects on serotonin and glutamate receptor subtypes, improves the clinical benefits, safety, and the tolerability of this med (Choi, Adham, Kiss, Gyertyan, & Tarazi, 2017).
Cariprazine is called a “dopamine D3/D2 receptor partial agonist antipsychotic”
In a 6-week, randomized, placebo-controlled schizophrenia trial the most common adverse events were akathisia (14 %), insomnia (14 %), and weight increased (12 %). Serious AEs occurred in 13 % of patients; 11 % discontinued the medication because of adverse events. “Mean changes in metabolic parameters were generally small and not clinically relevant”. The small body weight increase matched the average body weight increase of Americans in general who eat too many carbohydrates and soda. Nobody dropped out of the study, or quit the med, because of metabolic changes (think diabetes, metabolic syndrome) or body weight increase. Most importantly (ahem, risperidone), ”long-term cariprazine treatment was not associated with prolactin elevation or clinically significant changes in cardiovascular parameters”. “CONCLUSIONS: In this 48-week, single-arm trial, open-label cariprazine (1.5-4.5 mg/day) treatment was generally safe and well tolerated with no new safety concerns associated with long-term treatment” (Durgam et al., 2017).
Another study had similar results. The risk of discontinuation due to adverse events for cariprazine was similar to that for placebo. However, “Cariprazine was associated with higher risks of EPS-related events than was placebo, including risk of akathisia, tremor, and restlessness.” Akathisia is that feeling of being keyed-up like you have to keep moving constantly. Technically, it is a movement disorder, with a feeling of inner restlessness. EPS means “extrapyramidal symptoms”. These are the big scary, permanent movement disorders that other antipsychotic medications cause. Risperdal causes prolactin to go up, so you get man-boobs if you are a dude, and you can lactate. This is really bad on your body and kills your testosterone level. “CONCLUSION: There was a statistically significant higher risk of EPS-related AEs and a slight increase in mean body weight with cariprazine. There were no statistically significant effects on prolactin level or cardiovascular parameters.” (Lao, He, Wong, Besag, & Chan, 2016).
Hey, if you have questions, post them in the comments! I printed off about 30 studies on cariprazine, so I can look up more information if you have questions. Thanks!
Choi, Y. K., Adham, N., Kiss, B., Gyertyan, I., & Tarazi, F. I. (2017). Long-term effects of aripiprazole exposure on monoaminergic and glutamatergic receptor subtypes: comparison with cariprazine. CNS Spectr, 1-11. doi:10.1017/S1092852916000894
Durgam, S., Greenberg, W. M., Li, D., Lu, K., Laszlovszky, I., Nemeth, G., . . . Volk, S. (2017). Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study. Psychopharmacology (Berl), 234(2), 199-209. doi:10.1007/s00213-016-4450-3
Frankel, J. S., & Schwartz, T. L. (2017). Brexpiprazole and cariprazine: distinguishing two new atypical antipsychotics from the original dopamine stabilizer aripiprazole. Ther Adv Psychopharmacol, 7(1), 29-41. doi:10.1177/2045125316672136
Lao, K. S., He, Y., Wong, I. C., Besag, F. M., & Chan, E. W. (2016). Tolerability and Safety Profile of Cariprazine in Treating Psychotic Disorders, Bipolar Disorder and Major Depressive Disorder: A Systematic Review with Meta-Analysis of Randomized Controlled Trials. CNS Drugs, 30(11), 1043-1054. doi:10.1007/s40263-016-0382-z