The Frontier Psychiatrists is a newsletter, and podcast, with occasional videos. It’s written by the Owen Scott Muir, M.D., DFAACAP. As part of my ongoing “farewell to meds” by a physician who has moved his focus to interventional brain stimulation approaches to healing, I have written a series of articles revisiting the data on the medications I was trained to prescribe, with a more skeptical eye. This is a part one article on Abilify, where I take a look at the data for the On-label FDA-approved indications. It’s not that funny, in all fairness.
Today, I’m reviewing the data on the role of Abilify (aripiprazole) in the treatment of individuals with bipolar disorder. I think well of Otsuka, the company that brought Abilify to market. This doesn’t mean they are saints, but they have comported themselves well as far as an outsider, like myself, can know.
Bipolar disorder—the renamed illness that used to be called Manic-Depressive Illness—has episodes of both mania and depression, as well as mixed episodes of “both at once.”
Otsuka performed 6 studies on the use of Abilify as an acute treatment for bipolar mania, as submitted to the FDA (trials of monotherapy and augmentation with lithium or valproate, both of which I’ve previously reviewed and have available for readers behind those links):
One sort of obvious note, but I’ll make it anyway. Abilify comes in dosages down to 2mg. The pill sizes are, in fact, 2mg, 5mg, 10mg, 15mg, 20mg, and 30mg. The studies are all done at a minimum of 15mg in adults and 10mg in 10-17-year-olds.
The doses in Medicaid populations1 reflect the doses in those acute mania trials, as well.
It is worth noting in clinical practice, many patients are started on tiny doses of Abilify and kept on tiny doses of Abilify with bipolar disorder. Abilify also has data as a mono-therapy in “maintenance” of bipolar disorder, aka to reduce the risk of relapse to mania or depression, which they accomplished by randomizing patients who remitted with Abilify treatment to Abilify or placebo and seeing how long it took for them to relapse:
During the randomization phase, ABILIFY was superior to placebo on time to the number of combined affective relapses (manic plus depressive), the primary outcome measure for this study. A total of 55 mood events were observed during the double-blind treatment phase.
Again, this data was from individuals treated with 15-30mg dosages. I wasn’t able to find reliable data on how the drug works in patients treated with tiny doses as I often seen used by other prescribers in clinical practice.
A subsequent meta-analysis published in Molecular Psychiatry in 2017 by Kishi, Et. al.2 demonstrated the FDA had been on the money in approving the drug in this indication, with superiority to placebo demonstrated both in terms of response to treatment (blue = better than placebo).
The data on all-cause discontinuation of treatments in bipolar disorder is below…(our favorite outcome measure for effectiveness since my two-part articles on how to read the CATIE study, linked, ever-so-helpfully, there):
So, does Abilify “work” for bipolar mania? Yes. Does it prevent relapse to depression or mania alone OR with lithium / Depakote? Also Yes. With the crucial asterisk, the dosages used to demonstrate efficacy are all higher doses than are often used in clinical practices. It is very hard to determine from the data I was able to evaluate what a tiny dose of Abilify does, or doesn’t do.
What I have not addressed is the lack of efficacy in bipolar depression. We will save that for tomorrow. It is worth noting that the vast majority of the time spent sick with bipolar disorder is spent depressed.3 These symptoms are not addressed much in the above data, which is a serious issue.
That will be tomorrow…probably!
Citrome, L., Reist, C., Palmer, L., Montejano, L., Lenhart, G., Cuffel, B., ... & Sanders, K. N. (2009). Dose trends for second-generation antipsychotic treatment of schizophrenia and bipolar disorder. Schizophrenia Research, 108(1-3), 238-244.
Kishi, T., Ikuta, T., Matsuda, Y., Sakuma, K., Okuya, M., Nomura, I., ... & Iwata, N. (2022). Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials. Molecular psychiatry, 27(2), 1136-1144.
Tondo, L., H Vazquez, G., & J Baldessarini, R. (2017). Depression and mania in bipolar disorder. Current neuropharmacology, 15(3), 353-358.