Long-Acting Injectable (LAI) Antipsychotics
Antipsychotic agents are often discontinued without provider consultation, leading to poorer outcomes and quality of life. Luckily, newer formulations are continually being developed to help address barriers to care and promote tolerance. Long-acting injectable (LAI) antipsychotics are becoming more widely used in psychiatric care today. Currently, there are 6 antipsychotics that are available in LAI formulations: fluphenazine, haloperidol, aripiprazole, olanzapine, paliperidone, and risperidone. In this post, we discuss long-acting injectables and their advantages and disadvantages.
When To Consider LAIs
LAIs are most commonly used in managing schizophrenia, but may also have a place in schizoaffective, bipolar, and major depressive disorders. LAIs are effective in providing symptomatic relief through slow drug release over an extended period of time. Studies also suggest that LAIs may provide additional benefits over oral agents by reducing rates of rehospitalization, reducing the risk of relapse, improving quality of life, and improving adherence, though the data is mixed. Generally, most patients who have already had a good response to an oral antipsychotic are good candidates for LAIs. A patient-centered approach should be taken for each patient when considering LAIs, but those who may benefit from LAIs include:
- Those who are high-risk (e.g. multiple relapses, frequent hospitalizations)
- Those who are non-adherent to oral antipsychotics (e.g. lack insight, side effects, hallucinations, delusions, cognitive impairment)
- Those experiencing dose-dependent adverse effects (e.g. EPS, sexual dysfunction).
- Those who have poor or unpredictable oral absorption (following bypass or other GI issues).
- Those who prefer less frequent dosing. Depending on the product, LAIs can be dosed anywhere from every 2 weeks to every 6 months.
|-Less frequent dosing may improve adherence|
-Reduced rate and frequency of hospitalization
-LAIs with longer half-lives delay the time to relapse
-LAIs bypass oral absorption
-SGAs provide higher trough and lower peak levels, reducing the risk of side effects and breakthrough symptoms
-Reduce the risk of overdose
|-Less frequent dosing doesn’t necessarily ensure compliance|
-Must have a good response to an oral antipsychotic prior to switching to an LAI
-Needle phobia/hesitancy is a barrier
-LAIs differ in administration
-Oral overlap may be required
-Adverse effects may persist longer if they emerge during treatment
-Less flexibility in dosingRefrigeration may be required
-Injection site reactions can be painful or irritating
Newer Versus Older LAIs
All LAIs have similar efficacy, meaning no agent has been proven superior to another. The main difference that primarily exists relates to adverse effects, which can be anticipated based on its generation. Second-generation antipsychotics (SGAs) have a much more favorable side effect profile than first-generation antipsychotics (FGAs).
How To Transition To An LAI
Tolerability of an oral antipsychotic should be ensured first prior to starting an LAI. Then, patients are usually transitioned to the LAI formulation of the same antipsychotic. Each LAI varies by its formulation and administration. Depending on the technology and half-life of the drug, oral overlap or loading doses may be needed to maintain or achieve adequate drug levels. Treatment can be delayed and put a patient at risk for relapse if an oral agent has not been trialed prior to initiating or if overlap is not provided when indicated.
Long-acting Injectables Advantages and Disadvantages – Adverse Effects
The side effects of an LAI are comparable to that of its oral formulation. Since they provide lower, more consistent blood concentration levels, LAIs avoid high peak and low trough levels, avoiding dose-related side effects and reducing the risk for subtherapeutic levels. However, LAIs have longer half-lives than their oral counterpart and could potentially prolong adverse effects if they do emerge during treatment. Local injection site reactions are a concern with any injectable medication and occur in up to 10% of patients. Higher doses of LAIs require larger volumes and are therefore limited to gluteal administration. Improper intramuscular administration can result in sciatic nerve injection injury (SNII).
Olanzapine is unique in that it is the only LAI that has a REMS program. Post-injection delirium sedation syndrome (PDSS) is a rare side effect believed to occur from inadvertent administration of olanzapine intravascularly. Symptoms of PDSS closely resemble the symptoms of an overdose of olanzapine (e.g. confusion, disorientation, anxiety, dizziness, sedation, EPS). Most patients will experience symptoms within the first-hour post-injection (if at all) but are required to be monitored for 3 hours following administration.
LAIs are a great option for patients who tolerate oral antipsychotics but experience dose-related side effects, prefer less frequent dosing, have difficulties with maintaining adequate adherence, or have issues with oral administration. Each LAI utilizes different technology to achieve longer-lasting effects and prolonged time to relapse, and therefore have varying administration instructions.
This article was written by Alyssa Butterfield, PharmD Candidate, in collaboration with Eric Christianson, PharmD, BCPS, BCGP