Understanding Long-Acting Injectable Antipsychotics for Optimal Management of Mental Disorders

Treatment goals for patients with psychiatric conditions

In people with mental disorders, treatment goals have shifted from tranquilizing to addressing symptoms, preventing relapse and reducing adverse events (AEs) and, further, to improving functionality and quality of life.¹

In schizophrenia, Professor Correll discussed the importance of early treatment initiation as remmision and long term recovery rates are higher in treated first episode patients (FEP). Inadequate therapy can lead to cycling through relapse and remission without full recovery.²

Maintenance therapy is key for reducing relapse rates

Maintenance treatment is also key as multiple relapses in schizophrenia are associated with increased symptoms and disability, greater healthcare resource use and neuropathological decline.³ Patients most at risk of relapse include males, younger patients, those with a substance use disorder and where duration of first hospital stay is longer.⁴

Professor Carroll evidenced how relapse can be reduced by maintenance treatment with an antipsychotic.⁵ However, once an efficacious and tolerable treatment dose is found, it should be continued as relapse risk increases if doses are reduced.⁶

The use of long-acting injectable antipsychotics in schizophrenia

Compared to placebo, both oral antipsychotics (OAP) and LAIs are advantageous in terms of preventing relapse in schizophrenia.⁵ However, LAIs are associated with a lower risk of relapse or hospitalization compared to OAPs,⁷ with one study in early phase schizophrenia finding LAI use led to a 29.4% overall risk reduction.⁸

It has also been shown that risk of treatment discontinuation is lowest with an LAI. This is true when compared to all OAP and in head-to-head comparisons between an LAI and its own oral formulation.⁴ Frequencies of AEs with LAIs have not been shown to be different to those with OAPs,⁹ including for neuroleptic malignant syndrome.¹⁰

Long-acting injectable antipsychotics can enhance treatment adherence

A network meta-analysis found that in terms of relapse and acceptability, most of the LAIs are similar to each other;¹¹ however, LAI formulations can differ according to route of administration (intramuscular or subcutaneous), dose interval (from 2 weeks to 6 months) and whether initiation requires dose titration.¹² This, highlighted Professor Correll, means that the right formulation and dose can be more individualized to patient needs.

In one study conducted in the US, clinics that used a once-monthly LAI for FEP, compared to treatment as usual, found significant improvements in time to first hospitalization (hazard ratio 0.56; 95% confidence interval 0.34−0.92; p=0.02).¹³ Another study found that when followed for up to 2 years, FEP administered an LAI showed improvements in core psychopathology, functionality and quality of life.¹⁴

The biggest risk for mortality in schizophrenia is through suicide followed by causes such as infections, endocrine disorders and respiratory conditions. The risk ratio for all-cause mortality, mortality from suicide and from natural causes is reduced with the use of antipsychotics, with a larger risk reduction with second generation LAIs compared to antipsychotics as a class.¹⁵

Discussing LAI use with patients

Professor Correll highlighted how, when discussing LAIs with patients, psychiatrists tend to focus more on the modality of the formulation rather than the benefits.¹⁶ As such, he reported how having a discussion with a patient regarding their feelings about an LAI can greatly increase acceptance.^16,17 Training for staff on how best to approach such discussions was part of a successful US study, where staff were informed and trained on LAI effectiveness and rationale for use, ways to transition to an LAI and how best to communicate with patients and their families.¹⁷

Understanding how to communicate the advantages of long-acting injectable antipsychotics to patients is vital

Long-acting injectable use in bipolar disorder

Some LAI are also indicated for bipolar disorder and can be significantly more efficacious for relapse prevention and all-cause discontinuation rates compared to placebo.¹⁸ However, a 2020 poll of psychiatrists found that for 80%, the percentage of their patients with bipolar disorder receiving a LAI was less than 5%.¹⁹