Dr. Craig Chepke, member, Board of Directors, The CURESZ Foundation, Private Practice Psychiatrist, and Adjunct Assistant Professor of Psychiatry, University of North Carolina School of Medicine

Long-Acting Injectable Antipsychotics: Hope in a Needle

When the FDA authorized the first vaccines for COVID-19, they were called miracles of modern medicine and  saviors of society. Pictures of people weeping tears of joy while receiving the vaccine flooded the internet. What stood out to me was that these were not people who were already sick with COVID— they were completely healthy. But they saw the vaccine as a symbol of hope and the first step in overcoming the oppression of living in fear of an uncertain future. It made me wonder, why do we have such a hard time believing that people living with schizophrenia could find hope in a needle too?

Long-Acting Injectable antipsychotics (LAIs) offer numerous well-documented potential advantages for the treatment of adults with schizophrenia, but less than 15% receive them1. Perhaps one reason they are so underutilized is that clinicians have assumed that patients would not be interested in receiving an injection every 2 to 4 weeks, as LAIs historically required. However, I can attest that even if the COVID vaccine needed to be taken every month to stay safe, I would still want to be the first in line!

Furthermore, recent advances have allowed the interval between injections of certain LAIs to increase dramatically over the past decade. For instance, paliperidone palmitate was introduced as a once-a-month LAI in 2009, but a newer preparation given just every 3 months became available in 2015. Even more exciting, a version administered every 6 months is likely to be approved by the FDA later in 2021. If this pace continues, perhaps there could be a once-a-year version in 2027!

There is considerable evidence that schizophrenia is a neurodegenerative brain disorder, similar to Parkinson’s or Alzheimer’s Disease, but that psychotic relapses drive the progressive loss of brain tissue2. As such, clinicians must think about relapse prevention in schizophrenia with the same urgency that we currently attempt to prevent someone from having a second or third strokes3. Broader use of LAIs could go a long way towards minimizing the brain loss and the resulting decline in functionality and quality of life that each relapse brings. Research has shown LAIs may reduce relapse rates in schizophrenia by 20% and mortality risk by 33% compared to taking the same antipsychotic in oral form4,5.

Despite these substantial benefits, most clinicians seem to reserve LAIs solely for patients who are more severely or chronically ill6. In contrast, clinicians typically prescribe medications that slow the decline of Alzheimer’s Disease early in the illness to protect the person’s mental functioning at a higher level rather than waiting until there’s less quality of life left to preserve. Given the evidence that each relapse accelerates the cognitive and functional decline for people with schizophrenia, LAIs should be considered as an early option, not a last resort intervention. There is no grace period for the destructive effects that schizophrenia has on the brain.

Some clinical practice guidelines have begun to recommend using LAIs in first-episode psychosis, and I have adopted this approach in my practice7. I explain it to patients with the analogy that if I jumped out of an airplane, I’d prefer to open my parachute at 50,000 feet above the ground, not 50 feet. In the fight to achieve a richer, fuller, and longer life, LAIs are too powerful of a tool to be as underutilized as they are. Earlier aggressive treatment of first-episode psychosis and subsequent relapses with LAIs can dramatically improve long-term outcomes.

I have found that LAIs can be a remarkable source of positivity in the lives of people with schizophrenia. With the confidence that the medication’s consistency is optimal and the improved stability that LAIs often bring, both the clinician and the patient can focus on other issues such as deepening their therapeutic alliance or working on coping skills. The next step could be to foster the engagement needed to successfully pursue even higher goals, like going back to school, getting a job, or finding a relationship. LAIs can be life-saving interventions, but only if clinicians do their part by offering and educating about them. We need to do everything we can to make a person’s first episode of schizophrenia their last episode— and for some we can start by helping them find hope in a needle.

  1. Offord, S, et al. “Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral.” Journal of Medical Economics2 (2013): 231-239.
  2. Andreasen, N., et al. “Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study.” American Journal of Psychiatry6 (2013): 609-615.
  3. Nasrallah HA. FAST and RAPID: acronyms to prevent brain damage in stroke and psychosis. Current Psychiatry. 2018;17(8):6-8.
  4. Kishimoto, T, et al. “Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies.” The Lancet Psychiatry(2021).
  5. Taipale, H, et al. “Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia.” Schizophrenia Research 197 (2018): 274-280.
  6. Kishimoto, T, et al. “Effectiveness of long-acting injectable vs. oral antipsychotics in patients with schizophrenia: a meta-analysis of prospective and retrospective cohort studies.” Schizophrenia Bulletin 44.3 (2018): 603-619.
  7. Florida Medicaid Drug Therapy Management Program. 2019–2020 Florida Best Practice Psychotherapeutic Medication Guidelines for Adults.