What side effects are associated with this type of intervention?

Common treatments for schizophrenia, such as antipsychotics and psychostimulants, have several known side effects. Antipsychotics, including both first-generation and second-generation agents, can cause extrapyramidal symptoms (e.g., involuntary movements, parkinsonism, akathisia), sedation, weight gain, and metabolic syndrome. Psychostimulants, which are being studied for their potential to improve negative and cognitive symptoms through dopaminergic agonism, carry risks of relapse or worsening of psychosis, as well as potential side effects like headache and memory impairment. These treatments require careful monitoring to balance efficacy and safety.

What prior FDA approvals exist?

The FDA has approved several antipsychotic medications for the treatment of schizophrenia, primarily focusing on dopamine antagonism rather than agonism. These include first-generation antipsychotics like haloperidol and chlorpromazine, and second-generation antipsychotics such as risperidone, olanzapine, and aripiprazole. While psychostimulants with dopaminergic agonism, such as methylphenidate, are being studied for their potential to improve cognitive and negative symptoms in schizophrenia, they are not yet widely approved for this indication due to the risk of exacerbating psychosis.

What other types of research exist?

Promising alternatives to psychostimulants for treating schizophrenia in 2024 include memantine add-on therapy, noninvasive brain stimulation techniques, and second-generation antipsychotics with a lower risk of side effects. These options aim to improve negative and cognitive symptoms without increasing the risk of psychosis.

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Methylphenidate ER for Schizophrenia

Q: What is the mechanism of action of this treatment?

The most common treatments for schizophrenia include typical and atypical antipsychotics, which primarily work by antagonizing dopamine receptors, particularly the D2 receptor, to reduce psychotic symptoms. This is crucial for schizophrenia patients as it helps manage positive symptoms like hallucinations and delusions. However, dopaminergic hypoactivity is associated with negative and cognitive symptoms, which are less responsive to these treatments. Psychostimulants, which act as dopaminergic agonists, are being studied for their potential to improve these symptoms by enhancing dopamine activity. This approach is promising but requires caution due to the risk of exacerbating psychosis.

Phase 2

Recruiting

Led By Naista Zhand, M.D.

Research Sponsored by The Royal Ottawa Mental Health Centre

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Clinically stable for the past 8 weeks

Patients with schizophrenia spectrum illness, on any antipsychotic medication

Must not have

Have a contraindication to psychostimulants including: uncontrolled hypertension, significant cardiovascular abnormality including history of cardiac interventions, history of myocardial infarction, unstable arrhythmia, congenital heart disease, known family history of premature cardiac death (for males <45, females <55), known history of glaucoma, currently pregnant or planning to become pregnant, have a diagnosis of substance induced psychosis, have any of the following diagnoses: neurodevelopmental delay, intellectual disability, learning disorder or neurocognitive disorder (dementia), have a diagnosis of another currently significant and unstable psychiatric condition (i.e. depressive episode, active substance use disorder, etc.), have a history of previous safety concerns directly driven by positive symptoms (e.g history of suicide attempt as directed by auditory hallucinations), have current active suicidality

Have had treatment with ECT in the past 6 months

Timeline

Screening 3 weeks

Treatment Varies

Follow Up the panss-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12.

Awards & highlights

Summary

This trial is testing whether adding a medication can help improve symptoms in people with schizophrenia. The study involves 24 patients who are already stable on their current medications. The goal is to see if this additional treatment can make a difference in their symptoms.

Who is the study for?

This trial is for adults aged 18-55 with schizophrenia who have been stable for the past 8 weeks and are on antipsychotic medication. They must be able to communicate in English and not have age-related cognitive impairments, sensitivity to methylphenidate ER, significant heart issues, or a history of substance-induced psychosis.

What is being tested?

The study tests if adding Apo-Methylphenidate ER (a psychostimulant) can help improve negative symptoms and cognitive functions in patients with schizophrenia without causing a relapse or worsening of their condition.

What are the potential side effects?

Potential side effects may include worsening of psychotic symptoms due to increased dopamine activity from the stimulant. There's also concern about cardiovascular risks like increased heart rate and blood pressure.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My health condition has been stable for the last 8 weeks.

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I have a schizophrenia spectrum illness and am taking antipsychotic medication.

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I am between 18 and 55 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I cannot take psychostimulants due to my health conditions or current pregnancy.

Select...

I have undergone electroconvulsive therapy in the last 6 months.

Select...

I am allergic to methylphenidate ER, as confirmed by my doctor or pharmacy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ the panss-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~the panss-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12.

This trial's timeline: 3 weeks for screening, Varies for treatment, and the panss-6 will be completed at all time points (baseline, weeks 1-8, and at follow-up at week 12. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Defined as change in functioning

Secondary study objectives

Defined as change in cognitive functioning (domains include verbal memory, working memory, motor speed, attention and processing speed, verbal fluency and executive functioning)

Other study objectives

Defined as symptom severity (items include delusions, conceptual disorganization, hallucinations, blunted affect, social withdrawal, lack of spontaneity/flow of conversation)

Side effects data

From 2020 Phase 4 trial • 267 Patients • NCT02039908

51%

Appetite Loss

40%

Insomnia

33%

Irritability

29%

Picking at skin, nailbiting

21%

Dull, tired, listless

21%

Worried/Anxious

19%

Tearful, depressed

18%

Stomachache

13%

Headache

13%

Motor Tics

12%

Buccal-lingual movements

10%

Social Withdrawal

Hospitalized

100%

80%

60%

40%

20%

Study treatment Arm

Phase 1-Medication First

Phase 1 - Placebo First

Phase 2 - 7-Day Dosing

Phase 2 - 5-Day Dosing

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Apo-Methylphenidate ER armExperimental Treatment1 Intervention

Apo-Methylphenidate ER, 36 mg, oral, once a day, every morning, 4 weeks duration. Methylphenidate ER will be started at 18 mg to test tolerability and will be titrated at day 7 to a dose of 36 mg.

Group II: Treatment as usual armActive Control1 Intervention

Participants in the treatment as usual arm will continue with their current treatment as decided by their treatment team.

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for schizophrenia include typical and atypical antipsychotics, which primarily work by antagonizing dopamine receptors, particularly the D2 receptor, to reduce psychotic symptoms. This is crucial for schizophrenia patients as it helps manage positive symptoms like hallucinations and delusions. However, dopaminergic hypoactivity is associated with negative and cognitive symptoms, which are less responsive to these treatments. Psychostimulants, which act as dopaminergic agonists, are being studied for their potential to improve these symptoms by enhancing dopamine activity. This approach is promising but requires caution due to the risk of exacerbating psychosis.

Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future.[Diagnosis and treatment of motor phenomena in schizophrenia spectrum disorders].Treatment of early onset schizophrenia: recent trends, challenges and future considerations.