Abilify (aripiprazole)

Abilify is the drug I add to an antidepressant when the antidepressant is doing maybe sixty percent of the job and we need to find the other forty. It’s an atypical antipsychotic (a newer-generation antipsychotic, the kind that came after Haldol and Thorazine and is mostly used these days for schizophrenia, bipolar mania, and stubborn depression). At the doses we use for augmentation it isn’t really being used as an antipsychotic at all. We’re using it for partial-responder depression, which is the most common reason it ends up on a prescription pad in outpatient psychiatry.

The doses for augmentation are tiny compared to what gets used in schizophrenia. We’re talking 2mg, sometimes 5mg, occasionally 10mg if somebody needs more. Schizophrenia doses start at 10mg and run up from there. It’s basically a different drug at different doses, which is the part that surprises people who’ve heard of Abilify and assume any dose of it is going to turn them into a zombie. Two milligrams does not turn anybody into a zombie.

Why we add instead of switching

Most people on an SSRI (the standard serotonin-based antidepressants like Lexapro or Zoloft) who aren’t fully responding are getting some benefit from the medication… they’re sleeping again, they’re not crying at car commercials, the bottom-of-the-well feeling has lifted. But they’re still flat, still not enjoying the things they used to enjoy, still struggling to get through a workday without staring at a wall for forty minutes. Switching SSRIs is a six-week experiment with the possibility you end up worse than where you started, having lost the partial response you already had. Adding Abilify is a one-to-two week experiment with a much higher hit rate.

The data on augmentation is actually good, which is unusual in a field where the data is often equivocal. STAR*D (the big real-world depression study from the early 2000s, still the largest of its kind) and a pile of follow-up trials show augmentation beats switching for partial responders. That lines up with what most prescribers see in practice. The patients who go from 60% better to 90% better usually do it on a combination of medications, not on a different solo drug.

The metabolic stuff

Abilify is one of the cleaner atypicals on weight and metabolic stuff, which is most of why it gets used over olanzapine or quetiapine for augmentation. Olanzapine (Zyprexa) works great and will also put 25 pounds on you in six months and crank your A1C (the blood test for blood sugar control over time) into prediabetic territory. Abilify mostly doesn’t do that. Some people gain five or ten pounds the first few months and then it levels off. Some gain nothing. A few gain more, and if you’re one of those, we have a conversation about whether the benefit is worth the trade.

The metabolic monitoring is still real. Baseline weight, baseline lipids, baseline A1C. Recheck at three months and then yearly. Not because Abilify is dangerous, but because middle-aged guys in Oregon and Washington tend to already be one cheese plate away from prediabetes, and now they’re on a drug that nudges in that direction. The honest thing to do is keep an eye on the numbers so we catch the shift early if it shows up.

Akathisia is the side effect nobody warns you about

Akathisia is the inability to sit still, and if I had to pick one side effect to explain in detail to every patient starting Abilify, this would be it, because it gets missed constantly. It’s not anxiety, though it feels like anxiety. It’s a motor restlessness that lives in your legs and your chest and makes you want to crawl out of your skin. Patients describe it as feeling like they need to be doing something but can’t figure out what… like an internal vibration that won’t quit, like the urge to pace without any direction to pace in. It’s miserable and it’s the single most common reason people quit Abilify, often without telling their prescriber what the problem was.

Two things about akathisia worth knowing up front. One, it usually shows up in the first two weeks, which means if you make it past four weeks without it, you’re probably fine for the long haul. Two, lowering the dose almost always fixes it. The patients who get akathisia on 5mg are often perfectly fine on 2mg, and 2mg still does the augmentation job. So if you start feeling like there are ants under your skin a week or two in, call, don’t just quit silently. The fix is usually a dose adjustment away.

The other side effect worth naming, even though it’s rare, is the impulse-control thing. Abilify is a partial dopamine agonist (meaning it activates dopamine receptors but only partially, which is how the drug threads the needle between underactivating and overactivating that system). In a small percentage of people that partial activation can crack open impulse control in ways that show up at the casino, on porn sites, or with the credit card. If your wife says you’re acting weird with money, that’s a thing to mention at the next visit. It’s not common, but when it happens, it’s significant and it usually resolves with dose adjustment or stopping the drug.

What’s nice to hear when it works

Buried under the side-effect warnings is the part nobody leads with. When Abilify augmentation works, it works fast (often within a couple of weeks instead of the four-to-six the original SSRI took) and it works specifically on the symptoms that the SSRI couldn’t get to. The flat affect, the anhedonia (not enjoying anything anymore, even things you used to love), the inability to feel pleasure or interest or motivation. That’s the layer SSRIs are notoriously bad at. Abilify often pulls that part up.

The kind of guy who’s been on Lexapro for a year and a half and tells his wife “I’m not depressed exactly, I’m just not here” is the patient where 2mg of Abilify can be the difference between staying flat for another year and actually feeling like himself again. The drug doesn’t make anybody high, doesn’t change their personality, doesn’t dull anything. It just fills in the part the SSRI didn’t reach.

The kind of patient this works for

The pattern is the partial-responder. SSRI for a year or two, the worst of the depression lifted but the recovery stalled out at somewhere between 50 and 70 percent. The person is functioning. He’s making it to work, making it through dinner, then going to bed at eight because nothing feels worth doing. The wife is saying he’s “around” but not really there. The kids notice but don’t say anything.

Add 2mg of Abilify and the most common pattern is that around week three, the patient starts doing things again that he stopped doing two years ago. The hobby he used to be obsessed with. The house project. The weekend plans with friends. Nobody describes it as feeling high or feeling different. They describe it as feeling like themselves, which is the part SSRIs alone often can’t get to and which is most of the point of augmenting in the first place.

The patients who go from 60% better to 90% better usually do it on a combination, not a different monotherapy.

Where I land on medication, and where you land is up to you

Augmentation is one of those decisions where the patient-autonomy piece matters more than usual, because the patient is being asked to add a second drug on top of a first drug that’s already partly working, and the trade-off is real. If you’re sitting at 60% recovered, and the SSRI alone has been tolerable for two years, the question isn’t whether the medication is broken. It’s whether 60% is good enough for you and whether the upside of finding another 30% is worth the downside of a second medication and its side effects.

That’s a personal call, not a clinical one. I’m a provider, not a parent. My job is to lay out the honest take… how often augmentation works, what the side effects look like, what the trade-offs are. Your job is to decide what you want to do with that information. If you want to try Abilify, the prescription gets written. If you want to stay where you are and see if the next six months drift further toward better on the medication you’re already on, that’s also a defensible answer. The appointment isn’t mine, it’s yours.

What not to do

Don’t stop it cold turkey if you’ve been on it for a while. It’s not Effexor-level discontinuation (that one will rough you up for weeks if you skip a dose), but you can get a rebound of whatever the Abilify was suppressing, and if it was suppressing depression, that’s not a great time to find out. We taper down over a few weeks.

Don’t drink heavily on it… not because there’s some catastrophic interaction, just because alcohol is a depressant and you’re on a med for depression, and the math on that doesn’t really pencil out. A beer with dinner, sure. Five beers on a Saturday is going to feel worse than it used to and you’re going to wake up Sunday convinced the medication isn’t working when really the alcohol just sabotaged it.

And tell whoever’s prescribing it if you start feeling restless, even a little. Akathisia gets worse the longer it gets ignored, the fix is usually a dose change, and the worst version of this story is the patient who quietly tolerates it for three months, decides the drug is awful, stops it on his own, and never tries augmentation again.

Bottom line

If you’re on an antidepressant and you’re 60% of the way to where you want to be, augmentation with low-dose Abilify is one of the higher-yield moves on the table. The watch-outs are akathisia in the first month and the metabolic stuff over the long haul. Both are manageable if the patient and the prescriber actually talk about what’s going on instead of one of them quietly quitting the drug. The combo is supposed to do what the solo drug couldn’t, and when it works, it works on the part that was still missing.

Sources

1. Berman RM, Marcus RN, Swanink R, et al. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007;68(6):843-853. PMID 17592907.
2. Nelson JC, Papakostas GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry. 2009;166(9):980-991. PMID 19687129.
3. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. PMID 17074942.