SchizophreniaNCT05473741

Risk of Breakthrough Symptoms With Long-Acting Injectable Medications

An observational study of Schizophrenia and Schizophrenia Relapse, run by Centre for Addiction and Mental Health at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Schizophrenia, Schizophrenia Relapse
What is being tested?: Second Generation Long-Acting Injectable Antipsychotic Medications
Type of treatment: Injection or infusion
How many people: 51 participants
Where: 1 siteCanada
Study dates: 11 Jan 2023to 27 Oct 2025
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Adult, Older adult

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.

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Canada1 site

Centre for Addiction and Mental Health
Toronto, Ontario, M6J 1H3

Other trials in Canada

About this study

Official title: Risk of Breakthrough Symptoms On Antipsychotic Maintenance Medication When Remitted Patients Are Treated With Long-Acting Injectable Medications

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.

Read the detailed description

Rationale and Study Objectives In this study, we aim to determine the likelihood that relapse of psychosis will occur when patients with schizophrenia who have experienced a remission of their psychotic symptoms are adherent to treatment with a second generation antipsychotic (SGA) LAI on which they have been stable at a therapeutic dose for at least three months.

Primary objective:

To estimate the rate of psychotic relapse in patients with schizophrenia whose psychotic symptoms have remitted and who are adherent with second generation LAIs for maintenance treatment.

Secondary objectives:

To determine whether the risk of psychotic relapse is associated with antipsychotic plasma levels in patients treated with second generation LAIs.

Study design:

This prospective longitudinal cohort study will follow patients with schizophrenia who are treated with the second generation LAIs (paliperidone palmitate, risperidone or aripiprazole) 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, concurrent mood disorders, poor treatment response, failed cross-titration, and insufficient dosing.

Laboratory tests:

The following laboratory tests will be carried out at the baseline visit, 24-week visit and 48-week visit:

Urine drug screen - to document use of cannabis and other common recreational drugs. This will allow us to determine whether substance use is associated with the risk of relapse in remitted patients with established adherence to LAIs.
Plasma antipsychotic levels - to determine whether trough (pre-injection) plasma levels are associated with risk of relapse and medication side effects
Plasma prolactin - to determine whether the incidence and severity of sexual dysfunction is associated with antipsychotic plasma levels The following laboratory tests will be carried out at the baseline visit and 48-week visit:
Hemoglobin A1c - to determine the effects of LAIs on blood sugar levels
Lipid panel - to determine the effects of LAIs on total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol

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 CAMH outpatient treatment teams in Toronto, Ontario, Canada, that provide follow-up to individuals diagnosed with schizophrenia including:

Downtown Central Flexible Assertive Community Treatment (DC-FACT)
Downtown West Flexible Assertive Community Treatment (DW-FACT)
Downtown East Flexible Assertive Community Treatment (DE-FACT)
Slaight Centre Early Intervention Service (SCEIS)
Forensic Outpatient Program for Schizophrenia (FOPS)
Psychosis Coordinated Care Service (PCCS)
General Psychosis Service (GPS)

All outpatients of the above clinics who are receiving treatment with LAI paliperidone, risperidone, or aripiprazole will be invited to participate in this study if they are considered to meet inclusion criteria and do not meet any of the exclusion criteria listed below. A screening visit will be scheduled for potential participants who express interest in the study. The study and procedures involved with be explained to eligible participants and informed consent will be obtained for study participation by the study research coordinator or research assistant. A baseline visit will then be scheduled.

Study Duration:

The study duration will be 48 weeks rather than 52 weeks as participants treated with LAIs are most commonly administered medication at intervals of two, three, four or twelve weeks. Each of these intervals would fit with major assessments as 24 weeks (study mid-point) and 48 weeks (study end-point).

Study Visit:

At the screening visit, the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) will be administered to determine if the subject meets criteria for schizophrenia and that they do not meet diagnoses that would exclude them from study participation. Screening for other exclusion criteria including medical disorders, concomitant medications, and suicide attempts or hospitalizations in the past 3 months, will be completed at this visit. Subjects who do not meet inclusion criteria or who meet exclusion criteria will be informed and will not participate in further assessments.

Following the Screening visit, all subjects will be assessed at the following time points: Baseline, 12-week, 24-week, 36-week and 48-week visits, with more comprehensive assessments carried out at baseline, 24 weeks and 48 weeks. The following laboratory tests will be carried out at the baseline visit, 24-week visit and 48-week visit: urine drug screen, plasma antipsychotic levels, plasma prolactin. Height will be collected at baseline and weight and waist circumference will be collected at these time points. Hemoglobin A1c and a lipid panel will be obtained at baseline and 48 weeks.

Conditions: Schizophrenia, Schizophrenia Relapse
Being tested: Second Generation Long-Acting Injectable Antipsychotic Medications
Keywords: Schizophrenia, Relapse, Long-acting injectable antipsychotics, Remission
Medical subject headings: Schizophrenia, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Second Generation Long-Acting Injectable Antipsychotic MedicationsDrug
Also called paliperidone palmitate, risperidone, aripiprazole
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.

Study groups in NCT05473741
Study group	Role	What they receive
SGA-LAI		Outpatients with schizophrenia treated with second generation long-acting injectable antipsychotics whose psychotic symptoms have remitted. Receives: Drug: Second Generation Long-Acting Injectable Antipsychotic Medications

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Assessed at 12 weeks, 24 weeks, 36 weeks and 48 weeks

Secondary outcomes (12)

Clinical Global Impression Schizophrenia scale
Clinical Global Impression Schizophrenia scale (CGI-SCH) (Haro et al., 2003) The minimum score is "1" - "Normal, not ill" and the maximum score is "7" - "Among the most severely ill". A higher score means a worse outcome.
Measured: Assessed at 24 weeks and 48 weeks
Brief Psychiatric Rating Scale
Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962) This scale measures psychiatric symptoms on a scale from 1-7, where 1 is the least severe and 7 is the most severe. The 24 signifies that it is the longer version of the assessment which includes 24 questions. The minimum score is 24 and the maximum score is 168. A higher score means more severe symptoms/ worse outcome.
Measured: Assessed at 24 weeks and 48 weeks
Calgary Depression Scale
Calgary Depression Scale (CDS) (Addington et al., 1993) This scale is a nine-item structured interview that assesses the level of depression in people with schizophrenia. Items are measured on a 4-point Likert-scale from "0" to "3" where higher ratings indicate more depressive symptoms and a worse outcome. The minimum total score for the scale is "0" and the maximum score is "27" with higher scores indicating more severe depressive symptoms.
Measured: Assessed at 24 weeks and 48 weeks
VAGUS Insight Into Psychosis Scale
VAGUS Insight Into Psychosis Scale (Gerretsen et al., 2014) The VAGUS is a 10-item self-report scale that uses 10-point Likert scales to capture subtle changes in degree of insight into illness. The minimum score is 0 and the maximum score is 10. Higher scores reflect better insight and lower scores indicate poorer insight.
Measured: Assessed at 24 weeks and 48 weeks
Personal and Social Performance Scale
Personal and Social Performance Scale (PSP) (Morosini et al., 2000) This scale assesses a patient's degree of impairment in four domains. Each domain is rated on a six-point scale from absent to very severe. Using the ratings on the four sub-dimensions, one total score on a 100-point scale is created, where 100 is no impairment and 0 is the most severely impaired.
Measured: Assessed at 24 weeks and 48 weeks
Satisfaction with Life Scale
Satisfaction with Life Scale (SWLS) (Diener et al., 1985) This is a 5-item instrument designed to measure global cognitive judgments of satisfaction with one's life. Each item is rated from "0" to "7" with total scores ranging from "0" to "35". Higher scores indicate better outcomes.
Measured: Assessed at 24 weeks and 48 weeks
Single-Item Happiness Questionnaire
Single-Item Happiness Questionnaire (SIQ) (Abdel-Khalek, 2006) This scale involves answering a single question with ratings ranging from "0" to "10" with higher scores indicating better outcomes/greater happiness.
Measured: Assessed at 24 weeks and 48 weeks
Quality of Life Scale
Quality of Life Scale (QLS) (Heintichs et al., 1984) This is a 21-item assessment that evaluates the adequacy of an individual's psychosocial functioning over the past month on 7-point Likert scales (items rate from "0" to "6") with a higher score meaning better functioning. The minimum total score is "0" and the maximum score is "126" with higher scores indicating better outcomes.
Measured: Assessed at 24 weeks and 48 weeks
UKU Side Effect Rating Scale
Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale (Lingjaerde et al., 1987) The scale involves rating 48 side effects on a 4-point scale from "0" to "3" with higher scores indicating more severe side effects.
Measured: Assessed at 24 weeks and 48 weeks
Subjective Well-Being Under Neuroleptics Scale
Subjective Well-Being Under Neuroleptics Scale (SWN) (Naber et al., 2001) This is a self-rated scale consisting of 20 items that are assessed on a 6-point Likert scale. Each item is rated from "1" to "6". The minimum score is 20 and the maximum score is 120. Higher scores indicate better subjective well-being.
Measured: Assessed at 24 weeks and 48 weeks
Barnes Akathisia Scale
Barnes Akathisia Scale (BAS) (Barnes, 1989) This scale is scored on Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness. Each are rated on a 4-point scale from "0" to "3" and are summed to yield a total score ranging from 0 to 9, with 9 being the most severely affected. There is also a Global Clinical Assessment of Akathisia item that is rated from "0" - "Absent" to "5" - "Severe Akathisia".
Measured: Assessed at 24 weeks and 48 weeks
Arizona Sexual Experiences Scale
Arizona Sexual Experiences Scale (ASEX) (McGahuey et al., 2000) This is a five-item rating scale assessing sexual dysfunction with each item rated from "1" to "6". Possible scores range from 5 to 30, with the lower scores indicating better sexual functioning and higher scores indicating worse sexual functioning (i.e. more sexual dysfunction).
Measured: Assessed at 24 weeks and 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Jan 202327 Oct 2025

First posted26 Jul 2022
Study start11 Jan 2023
Primary completion27 Oct 2025
Study completion27 Oct 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (14)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05473741
Sponsor's protocol ID: 176/2020
Status last verified: Mar 2026
First submitted: 22 Jul 2022
Last updated: 14 Apr 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 26974214
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.
PubMed 20686456
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.
PubMed 20673559
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.
PubMed 12755850
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.
PubMed 22967779
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.
PubMed 10739409
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.
PubMed 9989565
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.
PubMed 23842008
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.
PubMed 29868849
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.
PubMed 24229745
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.
PubMed 23256986
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.
PubMed 22560607
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.
PubMed 24148707
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.
PubMed 26107752

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Risk of Breakthrough Symptoms On Antipsychotic Maintenance Medication When Remitted Patients Are Treated With Long-Acting Injectable Medications
ClinicalTrials.gov ID: NCT05473741
Acronym / sponsor ID: 176/2020
Conditions: Schizophrenia, Schizophrenia Relapse
Keywords: Schizophrenia, Relapse, Long-acting injectable antipsychotics, Remission
Study type: Observational
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: Centre for Addiction and Mental HealthUniversity, hospital or other
Collaborators: Janssen Inc.
Study start: 11 Jan 2023 (actual)
Primary completion: 27 Oct 2025 (actual)
Study completion: 27 Oct 2025 (actual)
First posted: 26 Jul 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Primary objective:

To estimate the rate of psychotic relapse in patients with schizophrenia whose psychotic symptoms have remitted and who are adherent with second generation LAIs for maintenance treatment.

Secondary objectives:

To determine whether the risk of psychotic relapse is associated with antipsychotic plasma levels in patients treated with second generation LAIs.

Study design:

Laboratory tests:

The following laboratory tests will be carried out at the baseline visit, 24-week visit and 48-week visit:

Urine drug screen - to document use of cannabis and other common recreational drugs. This will allow us to determine whether substance use is associated with the risk of relapse in remitted patients with established adherence to LAIs.
Plasma antipsychotic levels - to determine whether trough (pre-injection) plasma levels are associated with risk of relapse and medication side effects
Plasma prolactin - to determine whether the incidence and severity of sexual dysfunction is associated with antipsychotic plasma levels The following laboratory tests will be carried out at the baseline visit and 48-week visit:
Hemoglobin A1c - to determine the effects of LAIs on blood sugar levels
Lipid panel - to determine the effects of LAIs on total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol

Participants will be recruited from CAMH outpatient treatment teams in Toronto, Ontario, Canada, that provide follow-up to individuals diagnosed with schizophrenia including:

Downtown Central Flexible Assertive Community Treatment (DC-FACT)
Downtown West Flexible Assertive Community Treatment (DW-FACT)
Downtown East Flexible Assertive Community Treatment (DE-FACT)
Slaight Centre Early Intervention Service (SCEIS)
Forensic Outpatient Program for Schizophrenia (FOPS)
Psychosis Coordinated Care Service (PCCS)
General Psychosis Service (GPS)

Study Duration:

Study Visit:

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
SGA-LAI	–	Drug: Second Generation Long-Acting Injectable Antipsychotic MedicationsOutpatients with schizophrenia treated with second generation long-acting injectable antipsychotics whose psychotic symptoms have remitted.

Who may qualify

Ages: 18 to 65 years
Sex: All
Age groups: Adult, Older adult
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.

Key inclusion criteria (8 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Second Generation Long-Acting Injectable Antipsychotic MedicationsAlso: paliperidone palmitate, risperidone, aripiprazolePatients 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.	Drug	SGA-LAI

Primary outcome

Clinical Global Impressions Schizophrenia Scale (CGI-SCH) - Positive Symptoms Change subscale
Time frame: Assessed at 12 weeks, 24 weeks, 36 weeks and 48 weeks
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.

12 secondary outcomes

Clinical Global Impression Schizophrenia scale
Time frame: Assessed at 24 weeks and 48 weeks
Brief Psychiatric Rating Scale
Time frame: Assessed at 24 weeks and 48 weeks
Calgary Depression Scale
Time frame: Assessed at 24 weeks and 48 weeks
VAGUS Insight Into Psychosis Scale
Time frame: Assessed at 24 weeks and 48 weeks
Personal and Social Performance Scale
Time frame: Assessed at 24 weeks and 48 weeks
Satisfaction with Life Scale
Time frame: Assessed at 24 weeks and 48 weeks
Single-Item Happiness Questionnaire
Time frame: Assessed at 24 weeks and 48 weeks
Quality of Life Scale
Time frame: Assessed at 24 weeks and 48 weeks
UKU Side Effect Rating Scale
Time frame: Assessed at 24 weeks and 48 weeks
Subjective Well-Being Under Neuroleptics Scale
Time frame: Assessed at 24 weeks and 48 weeks
Barnes Akathisia Scale
Time frame: Assessed at 24 weeks and 48 weeks
Arizona Sexual Experiences Scale
Time frame: Assessed at 24 weeks and 48 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2026.
Background: PubMed 26974214Alphs 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.
Background: PubMed 20686456Gaebel 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.
Background: PubMed 20673559Gaebel 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.
Background: PubMed 12755850Haro 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.
Background: PubMed 22967779Ikai 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.
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Background: PubMed 9989565Kapur 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.
Background: PubMed 23842008Kirson 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.
Background: PubMed 29868849Kishimoto 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.
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Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert B Zipursky, MD principal investigator

Centre for Addiction and Mental Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Schizophrenia and Schizophrenia Relapse, run by Centre for Addiction and Mental Health at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Global Impressions Schizophrenia Scale (CGI-SCH) - Positive Symptoms Change subscale (time frame: Assessed at 12 weeks, 24 weeks, 36 weeks and 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05473741, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2026.