Risk of Breakthrough Symptoms With Long-Acting Injectable Medications

NCT05473741 | Completed

• 1 other identifier: 176/2020
• Study Type: observational
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective longitudinal cohort study will follow patients with schizophrenia who are treated with second generation long-acting injectable antipsychotic medications (LAIs) for 48 weeks to determine the risk of psychotic symptom relapse when treatment adherence is established. The study is designed to minimize the other factors that have contributed to breakthrough psychotic symptoms in patients treated with LAIs including poor adherence, substance use, concurrent mood disorders, poor treatment response, failed cross-titration, and insufficient dosing. Eligible subjects will undergo a screening visit to document that inclusion criteria are met and those meeting exclusion criteria are excluded. Participants will be assessed every 12 weeks to determine whether they remain in remission or meet criteria for a relapse. More comprehensive assessment will be completed at the beginning of the study (baseline visit), at the 24-week study midpoint and the 48-week study endpoint. Plasma antipsychotic levels will be measured at these three study time points to investigate associations between plasma levels and remission/relapse status as well as side effects. Plasma prolactin will also be measured to assess the association with sexual side effects. Hemoglobin A1c and measures of total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol will be obtained to assess the effects of SGA LAIs on these measures.

Conditions

Schizophrenia; Schizophrenia Relapse

Keywords

Schizophrenia; Relapse; Long-acting injectable antipsychotics; Remission

Outcome Measures

Primary Outcomes (1)

• Clinical Global Impressions Schizophrenia Scale (CGI-SCH) - Positive Symptoms Change subscale

  Subjects will be considered to have relapsed during the study if they are assessed as having a change score of 6 ("much worse") or 7 ("very much worse") on the Clinical Global Impressions Schizophrenia Scale (CGI-SCH) - Positive Symptoms Change subscale (Haro et al., 2003). The minimum score on this scale is "1" - "Very much improved" and the maximum score is "7" - "Very much worse". A higher score means a worse outcome.

  Assessed at 12 weeks, 24 weeks, 36 weeks and 48 weeks

Secondary Outcomes (12)

• Clinical Global Impression Schizophrenia scale

  Assessed at 24 weeks and 48 weeks

• Brief Psychiatric Rating Scale

  Assessed at 24 weeks and 48 weeks

• Calgary Depression Scale

  Assessed at 24 weeks and 48 weeks

• VAGUS Insight Into Psychosis Scale

  Assessed at 24 weeks and 48 weeks

• Personal and Social Performance Scale

  Assessed at 24 weeks and 48 weeks

Study Arms (1)

SGA-LAI

Outpatients with schizophrenia treated with second generation long-acting injectable antipsychotics whose psychotic symptoms have remitted.

Drug: Second Generation Long-Acting Injectable Antipsychotic Medications

Interventions

Second Generation Long-Acting Injectable Antipsychotic Medications DRUG

Patients who have been stabilized on long-acting injectable formulations of paliperidone palmitate, risperidone and aripiprazole will be followed for 48 weeks to determine the rate of relapse when adherence is established. Blood samples to measure plasma antipsychotic levels and prolactin levels, and urine samples for drug screen will be collected at baseline and at the 24-week and 48-week time points.

Also known as: paliperidone palmitate, risperidone, aripiprazole

SGA-LAI

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The target population is individuals diagnosed with schizophrenia whose psychotic symptoms have remitted and are receiving outpatient care at the Centre for Addiction and Mental Health (CAMH) in Toronto, Ontario, Canada. Patients who have been stabilized on long-acting injectable forms of either paliperidone palmitate, risperidone or aripiprazole with be invited to participate in this study. Participants will be recruited from seven CAMH outpatient treatment clinics that provide follow-up to individuals diagnosed with schizophrenia.

You may qualify if:

• DSM-5 Schizophrenia
• Age 18-65 years
• On SGA LAI: paliperidone palmitate (4-week or 12-week formulations), risperidone or aripiprazole
• Receiving LAI injections through clinical services based at CAMH
• History of improvement in psychotic symptoms with antipsychotic medication as evidenced by a rating of mild or less on the Clinical Global Impression - Severity (CGI-S) for Positive symptoms
• Demonstrated adherence to LAIs defined as not having received any injections more that 7 days past its due date in the past 3 months
• On stable dose of LAI for 3 months or longer
• Capable of providing informed consent for participation in this study

You may not qualify if:

• Current DSM-5 major depressive episode or manic episode
• Receiving any oral antipsychotic medication in the past 3 months
• History of organic brain disease (e.g. cerebrovascular accident, Huntington's Disease, Parkinson's Disease, epilepsy, etc.)
• History of untreated or unstable medical illness (e.g. thyroid disease, cancer)
• History of electroconvulsive therapy (ECT) in the past year
• History of suicide attempt in the past 3 months
• History of psychiatric hospitalization in the past 3 months
• Inability to read and communicate in English

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Janssen Inc.: collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H3, Canada

Location

Related Publications (14)

• Alphs L, Nasrallah HA, Bossie CA, Fu DJ, Gopal S, Hough D, Turkoz I. Factors associated with relapse in schizophrenia despite adherence to long-acting injectable antipsychotic therapy. Int Clin Psychopharmacol. 2016 Jul;31(4):202-9. doi: 10.1097/YIC.0000000000000125.

  PMID: 26974214 BACKGROUND

• Gaebel W, Schreiner A, Bergmans P, de Arce R, Rouillon F, Cordes J, Eriksson L, Smeraldi E. Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable vs quetiapine: results of a long-term, open-label, randomized clinical trial. Neuropsychopharmacology. 2010 Nov;35(12):2367-77. doi: 10.1038/npp.2010.111. Epub 2010 Aug 4.

  PMID: 20686456 BACKGROUND

• Gaebel W, Riesbeck M, Wolwer W, Klimke A, Eickhoff M, von Wilmsdorff M, Lemke M, Heuser I, Maier W, Huff W, Schmitt A, Sauer H, Riedel M, Klingberg S, Kopcke W, Ohmann C, Moller HJ; German Study Group on First-Episode Schizophrenia. Relapse prevention in first-episode schizophrenia--maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia. J Clin Psychiatry. 2011 Feb;72(2):205-18. doi: 10.4088/JCP.09m05459yel. Epub 2010 Jun 29.

  PMID: 20673559 BACKGROUND

• Haro JM, Kamath SA, Ochoa S, Novick D, Rele K, Fargas A, Rodriguez MJ, Rele R, Orta J, Kharbeng A, Araya S, Gervin M, Alonso J, Mavreas V, Lavrentzou E, Liontos N, Gregor K, Jones PB; SOHO Study Group. The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia. Acta Psychiatr Scand Suppl. 2003;(416):16-23. doi: 10.1034/j.1600-0447.107.s416.5.x.

  PMID: 12755850 BACKGROUND

• Ikai S, Remington G, Suzuki T, Takeuchi H, Tsuboi T, Den R, Hirano J, Tsunoda K, Nishimoto M, Watanabe K, Mimura M, Mamo D, Uchida H. A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: implications for dopamine D2 receptor occupancy during maintenance treatment in schizophrenia. J Clin Psychiatry. 2012 Aug;73(8):1147-52. doi: 10.4088/JCP.12m07638.

  PMID: 22967779 BACKGROUND

• Kapur S, Zipursky R, Jones C, Remington G, Houle S. Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry. 2000 Apr;157(4):514-20. doi: 10.1176/appi.ajp.157.4.514.

  PMID: 10739409 BACKGROUND

• Kapur S, Zipursky RB, Remington G. Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry. 1999 Feb;156(2):286-93. doi: 10.1176/ajp.156.2.286.

  PMID: 9989565 BACKGROUND

• Kirson NY, Weiden PJ, Yermakov S, Huang W, Samuelson T, Offord SJ, Greenberg PE, Wong BJ. Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry. 2013 Jun;74(6):568-75. doi: 10.4088/JCP.12r08167. Epub 2013 Apr 19.

  PMID: 23842008 BACKGROUND

• Kishimoto T, Hagi K, Nitta M, Leucht S, Olfson M, Kane JM, Correll CU. Effectiveness of Long-Acting Injectable vs Oral Antipsychotics in Patients With Schizophrenia: A Meta-analysis of Prospective and Retrospective Cohort Studies. Schizophr Bull. 2018 Apr 6;44(3):603-619. doi: 10.1093/schbul/sbx090.

  PMID: 29868849 BACKGROUND

• Kishimoto T, Nitta M, Borenstein M, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013 Oct;74(10):957-65. doi: 10.4088/JCP.13r08440.

  PMID: 24229745 BACKGROUND

• Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, Borenstein M, Kane JM, Correll CU. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014 Jan;40(1):192-213. doi: 10.1093/schbul/sbs150. Epub 2012 Dec 17.

  PMID: 23256986 BACKGROUND

• Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012 Jun 2;379(9831):2063-71. doi: 10.1016/S0140-6736(12)60239-6. Epub 2012 May 3.

  PMID: 22560607 BACKGROUND

• Olivares JM, Sermon J, Hemels M, Schreiner A. Definitions and drivers of relapse in patients with schizophrenia: a systematic literature review. Ann Gen Psychiatry. 2013 Oct 23;12(1):32. doi: 10.1186/1744-859X-12-32.

  PMID: 24148707 BACKGROUND

• Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS, Gretchen-Doorly D, Marder S, Nuechterlein KH. 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. 2015 Aug;72(8):822-9. doi: 10.1001/jamapsychiatry.2015.0270.

  PMID: 26107752 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

1. Urine drug screens 2. Plasma antipsychotic levels 3. Plasma prolactin levels 4. Hemoglobin A1c 5. Lipid panel including total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol

MeSH Terms

Conditions

Schizophrenia; Recurrence

Interventions

Paliperidone Palmitate; Risperidone; Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrimidinones; Piperazines; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Robert B Zipursky, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2022
• First Posted: July 26, 2022
• Study Start: January 11, 2023
• Primary Completion: October 27, 2025
• Study Completion: October 27, 2025
• Last Updated: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)