The Buzz on Long-Acting Injectable Antipsychotics

Read the accompanying CME to this podcast: Understanding Long-Acting Injectable Antipsychotics for Better Treatment Adherence.

In this podcast, Michael Jann, PharmD, discusses clinically relevant issues around long-acting injectable antipsychotics, or LAIs. Dr Jann contributed a peer-reviewed CME article for the March 2020 issue of Psychiatric Times titled Understanding Long-Acting Injectable Antipsychotics for Better Treatment Adherence. Michael Jann is a Professor of Pharmacotherapy at the University of North Texas System College of Pharmacy and founder of Jann Medical Writing. He has authored over 250 peer-reviewed publications, abstracts, books chapters, and other publications. He is the senior editor for the book Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents, and an editorial board member for six medical and scientific journals.

Psychiatric Times (PT): What are the top benefits of using LAI antipsychotics?

Michael W. Jann, PharmD (MWJ): There several “top” benefits of using LAI antipsychotic agents. The LAI agents address both adherence and non-adherence issues and both issues becomes a non-issue. The provider doesn’t need to worry about how or when a person takes their medication. For example, for any antipsychotic medication taken orally, how times during the week did my patient really actually take it? Patient adherence with oral antipsychotics can be overestimated while non-adherence underestimated by providers and caregivers.

The LAI agents benefit patients with consistent dosing-studies have clearly demonstrated their efficacy in both the acute treatment and long-term maintenance paradigms. The prevention of relapse is a major benefit for LAI agents. No medication can totally prevent a relapse. However, if a patient does relapse while on an LAI agent, a question regarding a patient’s adherence can be “ruled” out and we know that patient relapse can be due to other factors beyond medications.

The safety profile of LAI agents are well known, as these medications are typically FDA approved as an oral product prior to development into an LAI formulation. Providers, patients, and caregivers can be informed of these potential safety issues with appropriate steps to mitigate or minimize their occurrences.

From a patient’s perspective, the daily routine of taking an oral medication can become a “chore” and after a while, it can become a “burden.” While a patient may typically initially refuse to accept an LAI agent, persistence by providers and working with the patient and their caregivers as an optional alternative therapy often leads to acceptance.

PT: For those clinicians still wary or concerned about using LAI antipsychotics, what advice can you offer?

MWJ: I wish in a “perfect” world that every patient who needs an antipsychotic medication would be 100% adherent to their oral medications and take them as prescribed.  But, this is the “nature” of mental health and our patient population. Bear in mind that it’s about the patient. Patient adherence is such an important issue knowing that medications play a vital role in the acute and long-term management of our patients. The LAI preparations offer a viable option for our patients, caregivers, and providers.

As providers, we shouldn’t hesitate to utilize what options that we do have available. When a prescription is made to the patient, essentially, it is a medication “order” just like writing into the patient’s chart (or EHR). If the patient is unable to fully comply with your medication order due to their mental condition, what is the best option for the patient? We need to have the best interests of the patient and always be prepared to offer an LAI agent.

As a provider, you always concerned about safety and side effects. If a patient is given an LAI, what happens if a side effect occurs? The best approach to that is to start with the oral agent prior to the LAI. We know the safety profile of these agents. One of the most serious adverse effect from an antipsychotic is neuroleptic malignant syndrome (NMS). However, it is very rare, and when you use the oral agent prior to the LAI, you have the best information about the medication and carefully monitor your patients.

Another concern is that when the patient accepts an LAI agent, the main concern is that-not all antipsychotic agents are available as an LAI agent. You may need to switch the patient from their existing agent to an oral agent that is available as an LAI.

Here, in the US, there are only two monthly depot first generation LAI agents-fluphenazine and haloperidol-while only five second generation agents (SGA) LAI products (risperidone microsphreres, olanzapine pamoate, paliperidone, palmitate, and aripiprazole monohydrate and lauroxil). Risperidone also has a monthly formulation that can be given subcutaneously.

Beyond the monthly dosing interval, paliperidone palmitate has a product given once every three months and pripiprazole lauroxil has an every 6 and 8-week preparations.

LAI dosing has been simplified for providers. Most LAI products requires some overlap with their corresponding oral product. However, paliperidone palmitate does not require any oral overlap and the initial 234 mg injection followed by the 156 mg injection a week later. Aripiprazole lauroxil has an option with a one-day dose initiation product where the patient can be given one oral aripiprazole 30 mg dose and a single injection of aripiprazole lauroxil 662 mg that is then followed by the monthly injection. Maintenance dosing for monthly and products with longer intervals are known and individualized.

Information for providers on any missed injection doses and what the steps are needed is available.

Every situation regarding LAI use has been taken into account for the patient and the providers to remove barriers for their usage.

PT: What do you think will be the next game changer in antipsychotic treatment?

MWJ: That’s a very interesting question! Technology has made tremendous progress in medication delivery. For LAI’s, we do have some views into that arena:

1. We’ve seen LAI agents start out as risperidone microspheres but that needed to be given every 2 weeks. Typically, the injection intervals were monthly for most of the agents. Now, we’ve seen agents developed for beyond the monthly intervals and presently as long as every three months. There’s formulations under development for longer than three months, why not every six months or longer?

2. A monthly subcutaneous (SQ) risperidone preparation is available but has a dose limitation. More dosing options should be developed but also more agents developed for SQ administration.

3. Another route would implantable antipsychotics that last at least six months or eventually longer time-periods. Other medications are already available as implants.

Transcript modified for clarity. -Ed