Extended Antipsychotic Dosing for Schizophrenia

Overseen By Gary Remington, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antipsychotics

Must not be taking: Depot antipsychotics

Disqualifiers: Substance use disorder, Neurological condition, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 22

Duration: 52 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taking antipsychotic medications like olanzapine (Zyprexa) or risperidone (Risperdal) every other day is as effective as daily dosing for individuals with schizophrenia. Researchers are examining if less frequent dosing reduces side effects, potentially enhancing overall wellbeing and daily functioning. Participants will be divided into two groups: one will continue their daily medication routine, while the other will switch to an every-other-day schedule. This trial may suit those who have been stable on their current antipsychotic medication for at least three months and are not experiencing substance use issues. As a Phase 4 trial, it involves FDA-approved treatments and aims to understand how they can benefit more patients, offering participants a chance to contribute to valuable research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it seems you will continue with your current antipsychotic medication, either daily or every other day. You should discuss your specific situation with the trial team.

What is the safety track record for these treatments?

Previous studies have shown that olanzapine is safe for treating schizophrenia, with most patients tolerating it well over time. Some side effects, such as weight gain and drowsiness, are usually manageable.

Research on risperidone also indicates it is generally safe, with many patients tolerating it well. Mild side effects, like headache or dizziness, may occur.

Both drugs have approval for treating schizophrenia, confirming their general safety. This trial tests whether taking these medications every other day is as effective as daily dosing. The goal is to determine if this approach might reduce side effects while still effectively controlling symptoms. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the extended antipsychotic dosing trial for schizophrenia because it explores a novel dosing schedule that could improve patient outcomes. Unlike traditional treatments that require daily medication, this trial investigates the potential benefits of taking olanzapine or risperidone on an alternate-day basis. This could lead to fewer side effects and improve medication adherence, making life easier for patients. If successful, this dosing method might provide a more flexible and manageable approach to schizophrenia treatment.

What evidence suggests that extended dosing of antipsychotics is effective for schizophrenia?

Research has shown that both olanzapine and risperidone effectively treat symptoms of schizophrenia. Olanzapine often proves more effective than other antipsychotic drugs in improving these symptoms. In real-world use, risperidone has demonstrated safety and effectiveness when taken once a day. Long-term studies indicate that risperidone can help prevent symptoms from returning and maintain stability. In this trial, participants in the Extended Dosing Group will switch to an alternate-day dosing schedule with either olanzapine or risperidone. Although specific data on alternate-day dosing is limited, the success of daily use suggests that exploring different dosing schedules could be worthwhile. ^{1 6 7 8 9}

Who Is on the Research Team?

Gary Remington, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with schizophrenia or related disorders, stabilized on oral risperidone (1-6mg) or olanzapine (5-20mg). Participants must be able to communicate in English and provide consent. Women of childbearing age need a negative pregnancy test and reliable contraception; men cannot father a child during the study.

Inclusion Criteria

I have been diagnosed with a schizophrenia spectrum or other psychotic disorder.

(iv) ability to communicate in English

(vii) evidence of adherence with current AP treatment

Exclusion Criteria

Current diagnosis of substance use disorder according to DSM-5 criteria (verified through the MINI for Psychotic Disorders (Version 7.0.2) and a positive drug screen for street and /or prescription drugs not prescribed to the participant by treating physicians

I haven't had a depot antipsychotic injection in the last year.

I have not taken Olanzapine or Risperidone recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to either daily or alternate day antipsychotic dosing for 1 year

52 weeks

22 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olanzapine
• Risperidone

Trial Overview The study tests if taking antipsychotics every other day ('extended' dosing) is as effective as daily dosing for schizophrenia treatment. It compares side effects, wellbeing, and functioning between usual daily medication intake and alternate-day dosing over one year.

How Is the Trial Designed?

Group I: Extended Dosing Group Experimental Treatment 3 Interventions

Participants taking olanzapine or risperidone or paliperidone will be switched to an alternate day dosing schedule.

Group II: Treatment as Usual group Active Control 1 Intervention

Participants will continue to take their olanzapine or risperidone or paliperidone following the same prescribed daily schedule.

Olanzapine is already approved in United States, European Union for the following indications:

Approved in United States as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy
• Off-label use for cancer cachexia and anorexia

Approved in European Union as Zyprexa for:

• Schizophrenia
• Bipolar disorder
• Depression
• Nausea and vomiting associated with chemotherapy

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Published Research Related to This Trial

Antipsychotic medications are essential for treating schizophrenia, but high doses often do not provide additional benefits for most patients, with effective doses typically being lower than 15-20 mg of haloperidol or 500-800 mg of chlorpromazine.

Clozapine remains the preferred treatment for patients who do not respond well to other medications, while risperidone is noted for its effectiveness and safety, although further research is needed to fully understand its advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipsychotic medication in the treatment of schizophrenia. Kane, JM.[2013]

In a 6-month study involving 5134 patients with paranoid schizophrenia, risperidone long-acting injectable (RLAI) demonstrated significant improvements in both clinical severity and patient functioning, indicating its efficacy in routine clinical practice.

The treatment was generally well-tolerated, with 20% of patients experiencing treatment-emergent adverse events, the most common being akathisia and weight gain, but overall, the study confirmed RLAI's good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders. Parellada, E., Kouniakis, F., Siurkute, A., et al.[2019]

Olanzapine demonstrated statistically significant improvements in both efficacy and safety compared to risperidone in treating schizophrenia, based on a meta-analysis of randomized, double-blind studies.

The analysis showed that olanzapine was associated with fewer anticholinergic side effects and lower dropout rates, indicating it may enhance patient quality of life and treatment adherence over both short (≤12 weeks) and longer-term (>12 weeks) periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of olanzapine versus risperidone for the treatment of schizophrenia: a meta-analysis of randomised clinical trials. Mudge, MA., Davey, PJ., Coleman, DK., et al.[2014]

In a study of 151 hospitalized elderly patients with psychosis, both risperidone and olanzapine demonstrated similar efficacy, with around 78% of risperidone patients and 75% of olanzapine patients responding positively to treatment.

Both medications were found to be relatively safe, with adverse events reported in 16-17% of patients in each group, suggesting they can be effective options for treating psychosis in elderly patients with other medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with the atypical antipsychotics--risperidone and olanzapine in the elderly. Madhusoodanan, S., Suresh, P., Brenner, R., et al.[2019]

In a study of 34 patients with schizophrenia who were nonresponsive or intolerant to risperidone, olanzapine treatment led to a significant reduction in symptoms, with an average 25% decrease in PANSS scores after 14 weeks.

Olanzapine was well tolerated, with no patients discontinuing due to intolerable side effects, suggesting it is a safe alternative for those who did not respond to risperidone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for the effectiveness of olanzapine among patients nonresponsive and/or intolerant to risperidone. Dossenbach, MR., Kratky, P., Schneidman, M., et al.[2018]

Atypical antipsychotics, like clozapine, show dose-related efficacy in treating schizophrenia, with clozapine being effective up to 600 mg/day, but higher doses may increase the risk of seizures.

Olanzapine's efficacy is dose-related within the 10-20 mg/day range, and higher doses may improve efficacy without significantly increasing adverse events, indicating a need for further research on optimal dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose response and atypical antipsychotics in schizophrenia. Kinon, BJ., Ahl, J., Stauffer, VL., et al.[2018]

In a clinical safety review involving 2500 patients treated with olanzapine for acute schizophrenia, the overall discontinuation rate was low, indicating good tolerability of the medication.

While olanzapine was associated with some significant adverse effects such as somnolence, weight gain, and elevated liver enzymes, it showed minimal risk for parkinsonism, akathisia, and no cases of hematotoxicity, making it a relatively safe option compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of olanzapine. Beasley, CM., Tollefson, GD., Tran, PV.[2018]

In a report involving three treatment-resistant schizophrenic patients, high dosages of olanzapine (35, 40, and 60 mg/day) were successfully administered without any side effects, suggesting that higher doses may be effective and well-tolerated.

The findings indicate that some patients who do not respond to standard doses of olanzapine (up to 20 mg/day) may benefit from increased dosages, highlighting the need for further clinical studies to explore this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose olanzapine for treatment-refractory schizophrenia. Lerner, V.[2019]

The optimal daily doses for treating schizophrenia are established at 4-6 mg for risperidone and around 15 mg for olanzapine, which can guide more effective clinical practice.

Economic and efficacy analyses suggest that risperidone should be the first choice for treating schizophrenia, while olanzapine and clozapine are recommended as second-line therapies, highlighting the need to reassess current treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The economic value of atypical antipsychotics: A comparison of risperidone and olanzapine revisited. Lecompte, D., Cookson, RF.[2014]

In a 14-week trial involving 43 patients with treatment-resistant schizophrenia, olanzapine showed modest effectiveness, with 16.7% of participants meeting response criteria, particularly at doses higher than 20 mg.

While olanzapine treatment led to improvements in cognitive and depression/anxiety symptoms, it also resulted in a significant decrease in extrapyramidal side effects, suggesting it may be a viable option before considering more complex treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine for schizophrenia refractory to typical and atypical antipsychotics: an open-label, prospective trial. Lindenmayer, JP., Volavka, J., Lieberman, J., et al.[2019]

In a study of 78 acute schizophrenia patients, augmenting risperidone with olanzapine did not show a significant advantage over simply increasing the risperidone dose for improving symptoms after 2 weeks.

Patients who had their risperidone dose increased had a shorter time to treatment discontinuation compared to early responders, suggesting that while both strategies were similar in efficacy, the increased dose may lead to quicker treatment changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison between augmentation with olanzapine and increased risperidone dose in acute schizophrenia patients showing early non-response to risperidone. Hatta, K., Otachi, T., Sudo, Y., et al.[2018]

In a 1-year study involving 431 patients with schizophrenia, higher doses of olanzapine (up to 15 mg/day) significantly improved overall psychopathology and positive psychotic symptoms compared to a low dose of 1 mg/day and haloperidol.

Olanzapine was associated with fewer extrapyramidal symptoms than haloperidol, although it did lead to some weight gain and transient increases in prolactin levels, which were less severe than those caused by haloperidol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. Beasley, CM., Hamilton, SH., Crawford, AM., et al.[2022]

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