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A clinical pharmacist’s guide to long-acting injectable antipsychotics

Michael W. Jann

Long-acting injectable antipsychotics have been shown to prevent symptom relapse while addressing patient adherence. However, questions remain regarding their advantages and disadvantages, as well as which patients are appropriate candidates.

Healio Psychiatry spoke with Michael W. Jann, PharmD, FCCP, FCP, a clinical pharmacist specializing in mental health, about what clinicians should know when prescribing this important class of drug products. – by Stacey L. Adams

Question: What are the advantages of long-acting injectable (LAI) antipsychotics?

Answer: There are several advantages of LAIs. First, they provide reliable and quality information on how much medication the patient takes. They also provide a sustained and steady amount of drug, or drug concentration, in the body at any given time compared with oral doses that cause a peak and trough in drug concentrations over time.

Second, study after study has shown that they have a clinical efficacy in the prevention of symptom relapse, leading to reduced hospitalizations.

Third, they positively affect patient adherence. One could say there’s no medication that guarantees 100% patient adherence. And even though with LAIs there’s medication in the patient at the time of the injection and for the time that the injection is given — every month or every 2 or 3 months — the patient can change their mind and not come in for their injection. At that point, it gives the treatment team time to talk to the patient about adherence.

And lastly, they take away any potential treatment gaps. If you look at patients with chronic mental conditions, we know that taking daily medications for a long time period is a challenge, so LAI antipsychotics prevent any of those potential treatment gaps.

Advantages to the patient include confidence that treatment is taking place. Depending upon the formulation, they typically need to see a provider monthly. This gives the treatment team time to work on other aspects of their care, whether it’s occupational therapy or training. In my long experience, I’ve had very few patients agree to take a LAI at the first conversation, it’s usually about the third or fourth conversation.

   

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Q: What are the disadvantages?

Just like advantages, there are disadvantages. First, adherence is not guaranteed; patients can stop and decide they no longer want to take their injection. When you discuss taking antipsychotic medications with patients, if they’re going to refuse an oral medication, they’re likely going to refuse a LAI. You must work with the patient to first establish the rapport on adhere to therapy.

Second, there are a limited number of LAIs available, compared to the oral formulations. If a patient is on one of the medications that isn’t available in long-acting form, then the treatment team has to think about how to switch that patient. With antipsychotics, when a patient responds well to a specific medication, there can be a reluctance to make a change.

Third, there are side effects. When a LAI is brought to market, they’re usually brought first in oral formulation, so we know which side effects to expect. In a LAI, however, the obvious segue is that side effects can last longer; as long as a patient is on the medication. The way to address that is to increase patient awareness and have a plan to resolve potential side effects.

Fourth, LAI antipsychotics may stigmatize a patient as “non-adherent” with medication and health care professionals need to overcome and reduce that perception.

And lastly, LAIs can be expensive.

Q: What LAIs are available for use?

A: There are not many LAIs available.

First-generation LAI antipsychotics include:

• haloperidol decanoate,
• fluphenazine decanoate; and
• fluphenazine enanthate.

Second-generation atypical antipsychotics available for long-acting injection include:

• risperidone (Perseris Kit, Indivior Inc.; Risperdal Consta, Janssen),
• olanzapine pamoate (Zyprexa Relprevv, Eli Lilly),
• paliperidone palmitate in two formulations (Invega Sustenna, Janssen; Invega Trinza, Janssen); and
• aripiprazole in two formulations (monohydrate [Abilify Maintena Kit, Otsuka] and lauroxil [Aristada, Alkermes]).

There are scientific reasons that many LAI antipsychotics are unavailable. One is that the structure of the molecule may simply not allow for a long-acting formulation despite efforts in attempting the technology. The technology for LAIs is a very complicated process and some LAIs have several hundred or more patents. Therefore, going into the LAI technology is not for the “faint of heart” for the pharmaceutical industry.

When starting a patient on a LAI, typically, you have to keep the patient on an oral medication for 2 or 3 weeks as the medication is slowly released from the injection site. Two LAI products address the issue of the need for oral antipsychotics upon dosing initiation. Paliperidone palmitate was originally designed to be started without oral supplementation with the first dose of 234 mg given and then followed by a second 156 mg dose 1 week later (± 4 days). Aripiprazole lauroxil (AL) has a 1-day treatment initiation option where a patient receives one aripiprazole 30 mg oral dose plus injection AL 662 mg followed by the AL 441 mg or 882 mg administration The future of LAI antipsychotic development has emerged into a two-fold approach: developing a formulation or dosing process to minimize the initial oral dosing requirements and trying to lengthen the intervals between injections. For example, paliperidone palmitate is available with an every-3-month administration formulation and AL has both every-6- and 8-week injection products.

Q: In which patients should LAI antipsychotics be considered?

A: In theory, any patient who needs long-term therapy can be a candidate. However, we know that LAIs are underutilized for a variety of reasons. One reason could be perception of LAIs by patients and providers. It’s interesting, you would think a patient would prefer oral medications but until you ask, you don’t know. Asking the patient is a simple task. The real question — the art vs. science — is when to start a patient on a LAI. Do you wait until you start them on an oral and they relapse, or until adherence is an issue? But what if they relapsed and it wasn’t an adherence issue? Do you wait until they relapse two, three or four times? In my opinion, LAIs should not be reserved only for a patient who has multiple relapses, but that you should think about them as an option earlier in the patient’s treatment.

The recommendation for any LAI is to establish tolerability by trying the patient on a few days of an oral formulation, and if it’s tolerated, the patient is unlikely to have an allergic-type reaction to a LAI. Patients are typically started on oral formulations first, but it doesn’t mean they couldn’t try a LAI; there have been some studies of LAIs in patients with first-episode schizophrenia, but we don’t typically think about it.

Q: Do you have any tips for clinicians?

A: LAI antipsychotics provide consistent information — and quality information — for clinicians so that medication gaps are minimized. Be careful with oral medications; medication gaps are common and often underrecognized.

Second, clinicians should proactively address any potential side effects of LAIs, as well as have a plan in place for potential dose effects. Be objective in assessing the patient’s severity of side effects, but also recognize the patient’s subjective distress about side effects. Both aspects impact patient adherence to treatment.

Q: Anything else clinicians should know?

In general, one of the first things any health care professional should know regarding antipsychotic medications, is they need to get to know the patient’s beliefs and attitudes towards medications. Don’t oversell the medications. They will help to decrease symptoms, help the patient with their thinking, and lead to a decreased in relapse rate, but there’s no medication that will guarantee relapse prevention. Also, respect the patient’s reasons for nonadherence, don’t be punitive in that aspect. Work with them on ways to improve adherence and offer a LAI as a reasonable alternative. We know that patients’ — as well as clinicians’ — attitudes and behaviors change over time, that’s why it’s important to ask the question at every visit so that mutual respect develops.

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Michael W. Jann, PharmD, FCCP, FCP, is professor of pharmacotherapy, department of pharmacotherapy at University of North Texas System College of Pharmacy, UNT Health Sciences Center, Fort Worth, TX.

Disclosure: Jann reports no relevant financial disclosures.