Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia: A Randomized Clinical Trial

Shayne Kreutzer, PharmD candidate of 2016, Mercer University College of Pharmacy

Risperdal® (risperidone) is an atypical antipsychotic that is indicated for the treatment of schizophrenia, as stated in the package insert. The package insert also says that it can be used for the treatment of irritability associated with autistic disorder, in combination or monotherapy for the treatment of acute manic or mixed episodes associated with bipolar I disorder. In adults, the package insert stated the initial dose is 2 mg, with a target dose of 4 to 8 mg and an effective dose range of 4 to 16 mg.1


According to Pharmacothearpy: A Pathophysiologic Approach, schizophrenia is one of the most complex and challenging psychiatric disorders. It is a heterogeneous syndrome of disorganized and bizarre thought, delusions, hallucinations, inappropriate affect, and impaired psychosocial functioning. The textbook also states that there is evidence of dopaminergic-receptor defects in schizophrenia.2

Title: Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia: A Randomized Clinical Trial
Design Randomized controlled trial
Objective Compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia
Study Groups Randomized to long-acting injectable risperidone [40] Randomized to oral risperidone [43]
§  Randomized to cognitive remediation (CR) [19] §  Randomized to CR [22]
§  Randomized to healthy-behaviors training (HBT) [21] §  Randomized to HBT [21]
Methods Patients were provided treatment with antipsychotic medication, regular psychiatrist visits and weekly individual case management by masters and doctoral degree-level therapist. After a 3-week lead in period of oral risperidone, patients were assessed then randomly assigned to either treatments described. Patients were then randomized within their groups to receive CR or HBT.
Duration March 16, 2005 to September 27, 2012
Primary Outcome Measure Psychotic relapse and control of breakthrough psychotic symptoms
Oral risperidone Long-acting injectable risperidone
Baseline Characteristics Mean age 21.1 21.9
Male sex 79% 78%
Race (White) 54% 45%
Time since psychosis onset 7.9 (+/-6.6) months 6.9 (+/-6.8) months
Results Of the 83 patients, 16% had a return of psychotic symptoms that met the exacerbation and/or relapse criteria during the 12-month follow-up period. Between the study groups, 5% of the long-acting injectable risperidone group experienced a psychotic exacerbation and/or relapse compared to 33% in the oral risperidone group.
Adverse Events Common Adverse Events:

Oral risperidone: Akasthisia: baseline 2.9% vs end point 3.3%; Involuntary movements: baseline 5.9% vs end point 10%

Long-acting injectable risperidone: Involuntary movements: baseline 0% vs end point 0.2%

Serious Adverse Events: 0%
Percentage that Discontinued due to Adverse Events: long-acting injectable risperidone 10% vs oral risperidone 21%
Study Author Conclusions Long-acting injectable antipsychotic medication was well accepted by patients with a recent first episode of schizophrenia. Long-acting injectable medication led to better medication adherence, greater relapse preventions and better psychotic symptom control than oral antipsychotic medication.

There is a clear advantage of long-acting injectable risperidone over oral risperidone. Long-acting injectable risperidone, based on this study, seems to be an excellent choice in patients who recently had their first psychotic episode. There seemed to be a number of advantages in the long-acting injectable risperidone in comparison to oral. Although this study’s results conflict with recent studies, the difference was the focus on these patients who had their first psychotic episode.



  1. Drugs@FDA: FDA Approved Drug Products. Drugs@FDA: FDA Approved Drug Products. FDA/Center for Drug Evaluation and Research, 1993. Web. 29 June 2015. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=RISPERDAAL.
  2. Crismon M, Argo TR, Buckley PF. Chapter 50. Schizophrenia. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=45310501. Accessed June 29, 2015.
  3. Subotnik KL, Casaus LR, Ventura J, et al. Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia : A Randomized Clinical Trial. JAMA Psychiatry. Published online June 24, 2015. doi:10.1001/jamapsychiatry.2015.0270.

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