Clinical Research: Phase 1 - Phase 4

Making the Case for Long-acting Antipsychotic Treatment

Medical science is making significant advances in treating schizophrenia, but for all the progress we’ve seen, patients don’t benefit much unless they regularly take their medications. Second-generation (or atypical) long-acting injectable antipsychotic treatments (LATs) that ensure consistent administration of medication have become widely available over the past 15 years, but they remain a tough sell for many patients and psychiatrists.

And then there’s the prevalence of associated symptoms with schizophrenia that antipsychotic drugs don’t treat. Managing these symptoms is essential to improving patient outcomes but remains an elusive goal, even after decades of progress.

Long-acting injectable antipsychotic treatment — pros and cons

Orally administered drugs remain the treatment mainstay for schizophrenia patients, but their efficacy is limited — often severely — by patients’ inability or refusal to follow doctors’ orders. Often they forget to take their pills, or decide they don’t need them because their symptoms seem sufficiently under control. Other patients may seek to avoid side effects. And those suffering from paranoia may see their antipsychotic meds as part of an insidious plot to harm them.

Second-generation LATs such as aripiprazole, olanzapine, paliperidone, or risperidone, administered bi-weekly, monthly or even quarterly, can efficiently address the adherence problem, but have yet to gain much traction despite their widespread availability. The United States, in particular, lags in its embrace of LATs, with fewer than 10 percent of patients with schizophrenia using them. Overall, the uptake has been higher in Europe, but not by that much: Even in Spain, where these drugs have seen the greatest acceptance, fewer than one in three patients receive an LAT.

The reasons LATs are used so infrequently are plentiful on the part of patients, their families, and their treating physicians. Some patients find the prospect of injections, even infrequent ones, too unpleasant. Others want to retain the option of adjusting their meds according to how they feel, and some fear side effects that cannot be mitigated once a long-term dose has been administered. Families often share these concerns, although family members who have had to live through repeated relapses and rehospitalizations of their loved ones are more supportive of LATs.

For their part, some psychiatrists avoid injectables based on their personal beliefs. Inoculations are, after all, invasive and could be viewed as coercive. Taking medication, they argue, should be voluntary on the patient’s part, even if failure to take the prescribed medication may lead to worsening of symptoms, often resulting in relapse and hospitalization. This position is at odds with the field’s widely held position that maintaining consistent dosing is essential to successfully managing what is generally a long-term (and perhaps lifetime) disease.

Dealing with associated symptoms of schizophrenia

While currently available drugs generally do a good job of addressing the core symptoms of schizophrenia like delusions and hallucinations, they are significantly less effective at treating common associated symptoms such as depression and impairment of cognitive and functional abilities. These represent significant predictors of overall patient outcomes; therefore, much more research into new treatments and modes of action is needed.

Depressive symptoms are very commonly associated with schizophrenia, but available antidepressants are generally not effective in these patients. Many big pharmaceutical companies have recently backed away from neuroscience, ceding this niche to biotech and small pharma companies that now provide substantial efforts in this area.

Effectively treating the core symptoms with long-acting drugs represents an effective strategy for addressing associated symptoms of schizophrenia. Once a patient is settled into a treatment routine with guaranteed adherence, we can pursue remedies for the associated symptoms unencumbered by the “noise” that results from inconsistently administered treatments. As industry and the provider community join forces to increase the acceptance and use of long-acting injectable antipsychotics, they will see greater progress in addressing both the core and associated symptoms of schizophrenia.

Further Reading:

Operational Challenges of Neuroscience Clinical Trials, Part 1: Overview

4 Obstacles to Collecting Quality Data in Psychiatric Drug Trials