Antipsychotics for Agitation: Differences Between Tablets, Orally Disintegrating Tablets and Sublingual Formulations

Michael D. Jibson, MD, PhD

Professor of Psychiatry
Director of Residency Education
University of Michigan

Last updated: March 24, 2018
This presentation discusses how to prescribe oral antipsychotics for acute agitation (standard tablets, orally disintegrating tablets, and a sublingual formulation).

Orally disintegrating antipsychotics (Abilify Discmelt, Zyprexa Zydis, Risperdal M-Tab) are not absorbed transmucosally, they have to be swallowed. Orally disintegrating tablets are not more rapid than standard oral tablets. The advantage of ODTs is that they require a lower level of patient cooperation.

Asenapine (Saphris, Sycrest) is the only sublingual formulation, it requires higher patient cooperation than any of the other oral medications.

Oral or sublingual medications are convenient. They’re easy to administer. The patients find them much more acceptable than injections in most cases.

And there are a lot of options available. There are quite a number of medications that are out there. Ultimately, they will all work. If the patient is already familiar with one of them or taking one of them, then it’s a good strategy to just start with the medication that we know works for the patient. And to go with that, those medications are generally going to be available orally.

The disadvantages of the oral or sublingual medications are that none of the oral versions of these have been specifically approved by the FDA for acute agitation which means they haven’t all been systematically studied. Now, it doesn’t mean they don’t work. There are some other studies on some of them. But there’s just not as much information that’s available out there.

They also require patient cooperation. The patient has to be willing to say they’re going to accept the medication and actually do it.

And it’s difficult to verify whether the patient has complied with the medication.

Even equally important is that with the oral and sublingual medications the time to onset is slower and the time to peak concentration is slower.

There are several of the antipsychotic medications that are available in orally disintegrating tablets. This requires a lower level of cooperation and it’s difficult to cheek or discard the medication. The amount of time that it takes for these medications to dissolve is somewhat different among them. The fastest dissolving of them dissolves almost completely within about 3 to 5 seconds. And if you simply flick the medication, the patients are willing to open their mouth, have to be cooperative to that degree but you flick the medication into their mouth and it hits the oral mucosa. There’s usually enough saliva there that by the time they get their tongue around to locate the medicine it’s already well on its way to dissolving. Some of them take a little bit longer, 10 to 15 seconds. And so there is time for the patient to fiddle with the medication. But in general, you can be fairly assured that the medication is going to go where it’s supposed to go.

The thing to be aware of with orally disintegrating medication is that they are not absorbed transmucosally.

They have to be swallowed just like any other medication and they are not more rapid than standard oral formulations. There is no difference in those that dissolve in the mouth versus those that have to be swallowed as a pill in how long it takes them to get into the bloodstream. And it’s important to keep those things in mind.

Now, just one of the medications, asenapine, is available as a sublingual form and some of the benzodiazepines also. Among the antipsychotics, only that one.

It has a more rapid onset and time to peak concentration than the oral medications. But ironically, it actually requires a higher level of patient cooperation than the standard pills do because the pill has to be held under the tongue for quite some time before it fully is absorbed.

And it’s actually simpler for the patient to subvert this process by swallowing the medication because it’s not absorbed in the GI tract. And so the sublingual medication may be appropriate in some situations but probably not quite as good as the disintegrating tablets for ensuring that the medication actually gets where it’s supposed to go.

As we think about oral medications, the first-line oral medications starting with standard tablets, the first that I list here is haloperidol. I list it as first-line not because I think it’s more desirable than others but it is simply the most common. It’s readily available. We have lots of experience with it. And so it can be used.

This version of it is not FDA approved for agitation as I mentioned. The dose range is 2 to 5 mg per dose. For an acutely agitated patient, 5 mg is generally going to be the dose. The recommended frequency is every six hours.

The average 15 mg a day is pretty standard dose out in the community. Currently, the maximum recommended dose is about 30 mg a day based on the probability of side effects and what we know about saturation of dopamine receptors. Not much is going to happen other than side effects above 30 mg a day.

Time to peak concentration is about two hours. That’s relatively quick by oral standards. And so this medication is still a viable option. We’ll talk about specific advantages and disadvantages of this medication a little bit more subsequently.

The orally disintegrating and sublingual tablets listed alphabetically here, not as an endorsement of one over another, begins with aripiprazole. If we use an orally disintegrating tablet, the tablet is not FDA approved for agitation. The medication is but the studies that looked at that were for the injectable version of the medicine.

Usual dose range is 10 to 15 mg. Those are the only two sizes that these tablets come in. It can be given every two hours.

And the average dose on this is about 20 mg a day. The maximum recommended dose, and this is very rarely violated, is 30 mg a day.

Time of peak concentration is a bit slower. It’s about three to five hours. So that may be okay in an agitated patient who is not terribly acute but it might be a little bit long in some other patients.

Asenapine, the sublingual tablet I mentioned earlier, is also not approved for agitation specifically.

Dose range is either 5 or 10 mg twice a day and the average dose is 10 mg a day. Maximum recommended 20 mg a day.

This medicine is absorbed much more quickly from half an hour to one hour to peak concentration. And that in this setting would be its primary advantage.

The rapid disintegrating olanzapine. Olanzapine is a medication that is approved for acute agitation. Again, the studies that resulted in its approval involved an injectable form of olanzapine rather than the tablets. But the medication itself has been studied.

Dose range either 5 or 10 mg per dose. And in terms of dose equivalents, 5 mg of this medicine is probably equivalent to about 3 mg of haloperidol. So 5 to 10 mg is roughly the same dose range as the haloperidol dosing. And it can be repeated at intervals from 30 minutes to two hours.

The average dose is about 10 mg a day and the maximum recommended dose is somewhere around 30 to 40 mg. This is higher than FDA approved. FDA approval is limited to 20 mg a day. But these doses are known to be safe and you don’t hit saturation of the dopamine receptors until you get somewhere into that 30 to 40 mg a day range.

The biggest issue with this medication is time to peak concentration which is five to six hours. And so although the frequency with which doses can be given is fairly high, the time that it takes to get to a peak concentration is long. And so one has to take care not to give too many repeated doses while the medicine is still being absorbed. And just waiting on this after each dose is given is often an effective strategy.

Finally, risperidone has a rapid disintegrating tablet, not FDA approved for agitation.

Generally, 1 to 2 mg of this medication will be given. Again, this dose range of 1 to 2 mg is about the same as 5 mg of haloperidol. It may be given as often as every 30 minutes.

The average dose both in an acute state and for maintenance is 4 mg a day and we generally recommend not going higher than 6 to 8 mg a day even though much higher doses are FDA approved. At 6 to 8 mg a day, the frequency of side effects rises pretty dramatically and most of the benefits is going to be derived at the lower doses.

This medicine takes about three hours to get to peak concentration. A large part of the activity of risperidone is through an active metabolite and so the three hours to peak concentration includes that active metabolite.

So the major points to keep in mind here, the orally disintegrating tablets are handy because they require a lower level of cooperation and they are fairly acceptable to the patients but it is important to remember that they are not more rapid than the standard oral formulations.

That aripiprazole, olanzapine and risperidone are available in these disintegrating formulations.

The sublingual formulation which is absorbed most rapidly still requires a higher level of cooperation really than any of the other medications in a dose range that can be given a couple of times a day and would be likely to act more rapidly.


  1. Wilson MP, et al. The Psychopharmacology of Agitation: Consensus Statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup, West J Emerg Med (2012) 13: 26;
  2. Haloperidol Drug Information. In: UpToDate, Sokol N (Ed), UpToDate, Waltham, MA; 2017. Available at
  3. Abilify (aripiprazole) [package insert]. Otsuka America Pharmaceutical, Inc. Available online at,021713s030,021729s022,021866s023lbl.pdf
  4. Saphris (asenapine) [package insert]. Actavis, Inc. 2017. Available online at
  5. Zyprexa (olanzapine) [prescribing information]. Indianapolis, IN: Lilly USA LLC; 2017. Available at
  6. Risperdal (risperidone) [package insert]. Janssen Pharmaceuticals, Inc. 2017. Available online at

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