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Long-Acting Injectables For Schizophrenia

Schizophrenia

 


Transcript:

Schizophrenia is a complex condition characterized by positive symptoms such as hallucinations, delusions, disorganized thinking, and abnormal motor behaviors. Negative symptoms such as lack of motivation, reduced feeling of pleasure, affective blunting, alogia, avolition, and anhedonia are additional hallmarks of this disorder. Patients suffering from schizophrenia also commonly deal with comorbidities like tobacco and drug use.

Together, these symptoms lead to the profound inability to structure and organize one’s life. This interferes with all manner of activities of daily living, including the ability to participate in medical care.

The onset of schizophrenia typically occurs in late adolescence into early adulthood.

Unfortunately, patients commonly experience relapses and remissions throughout the course of their lives, with each subsequent relapse potentially leading to further deterioration. This is devastating not only to the patient, but also to family and friends. Schizophrenia is also associated with a high suicide rate.

For this reason, the goals when treating schizophrenia include both symptom management to improve functioning and quality of life and relapse prevention. Nonadherence to an effective medication is directly associated with increased rates of relapse.

Antipsychotics have traditionally been used as the primary mode of treatment for schizophrenia. They are most effective in treatment of positive symptoms and prevention of relapse. Because each successive relapse is thought to be more injurious and because medications are less effective in managing negative symptoms and cognitive dysfunction, the goal is to keep patients out of relapse or active psychosis.

Oral antipsychotics (OAPs) have demonstrated efficacy for schizophrenic patients. However, a significant number of patients continue to experience symptoms and relapse when taking OAPs.

Furthermore, adherence continues to be an obstacle for patients prescribed OAPs, as these drugs have to be taken every day and these powerful medications can have unintended side effects as well.

Up to 50% of patients are estimated to be at least partially nonadherent with oral medications.

Long-acting injectables (LAIs), also called depot antipsychotics, were initially developed to enable maintenance of stable plasma drug concentrations and therefore reduce the risk of relapse and adverse events.

First-generation antipsychotic (FGA) LAIs were initially developed more than 50 years ago to improve adherence and reduce symptom exacerbation, relapse, and rehospitalization. 
However, these did carry some concerns regarding side effects, especially those with movement disorders.

Second-generation antipsychotic (SGA) LAIs were later developed and demonstrated improved tolerability in patients. However, these can also lead to side effects, particularly metabolic changes, causing unwanted outcomes like weight gain.

LAIs offer additional attributes such as more reliable drug delivery, a reduction in peak-trough level differences, greater dosing precision, and reduced pill burden.  

These are especially helpful for people with erratic schedules or co-morbid conditions that can interfere with taking medication daily. Additionally, these are a valuable route for patients in unstable housing situations where theft may occur or medications may be lost.

LAIs are injected intramuscularly or subcutaneously. The unique formulation of LAIs ensures that the drug is slowly absorbed from the injection site into the body’s circulation.
Importantly, absorption is slower than elimination, driving the extended duration of LAIs’ effects.

Studies have reported various findings on medication adherence rates and relapse rates or rehospitalizations with LAIs compared to oral antipsychotics. For example, one meta-analysis reported improvement with LAIs in these areas in 60 studies, no significant difference in 252 studies, and reduction in these areas in 16 studies as compared to oral antipsychotics.

Furthermore, LAIs provide clinician awareness of adherence because of patient tardiness or absence at injection appointments. This provides additional opportunities to check in with patients and develop a good rapport to build a therapeutic alliance.

Implementing LAIs does not come without obstacles.

First, patients receive little information about them.

Additionally, some patients have misconceptions that LAIs are only for chronically ill patients, or they have a fear of injections and/or injection site pain.

Access to LAIs can also be limited by insurance policies.

Transportation to appointments can be a significant concern for patients. Maintaining the appointment schedule can lead to changes in daily routines, vacations, changes in employment, or changes in the lives of caregivers. 

The failure of these medications to address negative symptoms and cognitive impairment is an obstacle, as patients with several negative symptoms may not benefit much.

Interestingly, when patients start to feel better, it can lead them to believe that they can go without medication. 
Lastly, some patients share concerns that using LAIs means losing control over taking medications.

Overall, antipsychotic medications are effective treatment options to reduce symptoms of schizophrenia.  

Healthcare providers should always try a patient on oral medications first, before trying an LAI.

Each type of medication does carry a risk for certain side effects. Likewise, each type provides specific attributes that may benefit patients with different circumstances.

With such a strong link between adherence and relapse rates, long-acting injectable antipsychotic drugs provide an exciting treatment option to improve long-term outcomes for patients.