Methylphenidate ER for Schizophrenia

Overseen by Naista Zhand, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: The Royal Ottawa Mental Health Centre

Must be taking: Antipsychotics

Disqualifiers: Hypertension, Cardiovascular, Pregnancy, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants can be on any antipsychotic medication, so it seems likely you can continue those.

Is methylphenidate generally safe for humans?

Methylphenidate has been studied for safety in children with ADHD, showing that it is generally well-tolerated, though some adverse reactions (unwanted effects) have been recorded. Dexmethylphenidate, a form of methylphenidate, has also been found to be effective and well-tolerated in clinical trials with children and healthy adults. ^{1 2 3 4 5}

How does the drug Methylphenidate ER differ from other treatments for schizophrenia?

Methylphenidate ER is unique because it is primarily used for ADHD and works by increasing dopamine and norepinephrine levels, which can actually worsen psychotic symptoms in schizophrenia, unlike typical antipsychotics that aim to reduce these symptoms. ^{5 6 7 8 9}

Research Team

Naista Zhand, MD

Principal Investigator

Royal Ottawa Mental Health Centre

Eligibility Criteria

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.

Inclusion Criteria

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

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

I am between 18 and 55 years old.

Exclusion Criteria

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

Have a history of head injury resulting in loss of consciousness

I have undergone electroconvulsive therapy in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 weeks of methylphenidate ER 36 mg or treatment as usual, followed by a switch in group assignments for another 4 weeks

8 weeks

Weekly visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at week 12

Treatment Details

Interventions

• Apo-Methylphenidate ER (Psychostimulant)

Trial Overview 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.

Participant Groups

Group I: Apo-Methylphenidate ER arm Experimental Treatment 1 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 arm Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

The Royal Ottawa Mental Health Centre

Lead Sponsor

Trials

24

Recruited

2,300+

Findings from Research

In a study involving children aged 6-12 years with ADHD, once-daily modified-release methylphenidate (EqXL) was found to be non-inferior to twice-daily immediate-release methylphenidate (MPH-IR) in reducing ADHD symptoms over three weeks.

Both formulations of methylphenidate were significantly more effective than placebo, and all treatments were well tolerated, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder. Findling, RL., Quinn, D., Hatch, SJ., et al.[2018]

In a study involving 76 children with ADHD, the intensive pharmacosurveillance program revealed that atomoxetine (ATX) and methylphenidate (MPH) are generally safe, with most adverse drug reactions (ADRs) being common, non-serious, and fully resolved, although weight loss was the most frequently reported ADR.

The program also identified some unexpected ADRs, such as hepatomegaly and suicidal ideation, highlighting the importance of ongoing monitoring to ensure drug safety in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of attention-deficit/hyperactivity disorder medications in children: an intensive pharmacosurveillance monitoring study. Ruggiero, S., Rafaniello, C., Bravaccio, C., et al.[2015]

In a study involving 184 participants, two long-acting formulations of Methylphenidate (MPH) were compared, revealing that while emotionality improved with treatment, sleep and appetite issues worsened, indicating a specific pattern of adverse effects.

The adverse events related to MPH, particularly sleep and appetite changes, were not predictable based on patient characteristics and did not correlate with the therapeutic benefits, suggesting that the mechanisms behind these side effects may differ from those that provide therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to methylphenidate treatment for attention-deficit/hyperactivity disorder: structure and associations with clinical characteristics and symptom control. Sonuga-Barke, EJ., Coghill, D., Wigal, T., et al.[2013]

In a 10-week interim analysis of the QU.E.S.T. trial involving 725 adults with ADHD, mixed amphetamine salts extended release (MAS XR) showed significant improvements in ADHD symptoms, with most participants (74.4%) reporting they were very much or much improved.

MAS XR treatment was generally safe, with only 6.9% of participants withdrawing due to adverse events, and common side effects included decreased appetite and dry mouth, indicating that the benefits of symptom relief were achieved with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An interim analysis of the Quality of Life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) evaluation of mixed amphetamine salts extended release in adults with ADHD. Goodman, DW., Ginsberg, L., Weisler, RH., et al.[2019]

Dexmethylphenidate, a chirally pure form of methylphenidate, has been shown to effectively manage ADHD in children at half the dose of traditional Ritalin, based on clinical trials involving 684 children.

The drug works by inhibiting the reuptake of norepinephrine and dopamine, and has been found to be well tolerated, with ongoing research to further understand its therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate--Novartis/Celgene. Focalin, D-MPH, D-methylphenidate hydrochloride, D-methylphenidate, dexmethylphenidate, dexmethylphenidate hydrochloride. [2018]

Methylphenidate can induce or worsen psychotic symptoms in patients with schizophrenia, as demonstrated in a case report of a young man who experienced acute cellulitis and psychosis after injecting the drug.

Even with ongoing antipsychotic treatment, the patient continued to experience psychotic symptoms linked to methylphenidate use, highlighting the challenge of managing both functional and organic psychoses in the same individual.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting a Case of Injecting Methylphenidate (Ritalin) Tablets, Intensified Symptoms of Schizoph-renia or Induce Separate Mental Disorder? Ghaffarinejad, A., Kheradmand, A.[2021]

Emerging treatments for schizophrenia, such as cannabidiol and lumateperone, aim to address a broader range of symptoms beyond just the positive symptoms typically targeted by existing antipsychotics, with some showing promise in treating negative and cognitive symptoms.

New long-acting injectable formulations like Aripiprazole Lauroxil and Perseris have been approved, providing rapid therapeutic levels without the need for initial oral treatment, which may improve adherence and reduce adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. Krogmann, A., Peters, L., von Hardenberg, L., et al.[2020]

In patients with schizophrenia, lower dopamine activity was associated with better word production, indicating that decreased dopamine may enhance certain neurocognitive functions.

Methylphenidate infusion led to increased disorganization symptoms and redundant errors in word production, suggesting that higher dopamine activity can exacerbate cognitive control issues and disorganized thinking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of methylphenidate effects on oral word production and symptoms in first-episode schizophrenia at acute and stabilized phases. Szeszko, PR., Bilder, RM., Dunlop, JA., et al.[2019]

In a study involving actively ill schizophrenic patients, intravenous methylphenidate was found to significantly worsen preexisting psychotic symptoms, such as hallucinations and delusions, more effectively than dextroamphetamine and levamfetamine.

These findings suggest that neurotransmitters like dopamine and norepinephrine may play a role in exacerbating symptoms of schizophrenia, although the complexities of these interactions indicate that further research is needed to fully understand their implications for diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylphenidate, dextroamphetamine, and levamfetamine. Effects on schizophrenic symptoms. Janowsky, DS., Davis, JM.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Safety of attention-deficit/hyperactivity disorder medications in children: an intensive pharmacosurveillance monitoring study. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Adverse reactions to methylphenidate treatment for attention-deficit/hyperactivity disorder: structure and associations with clinical characteristics and symptom control. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

An interim analysis of the Quality of Life, Effectiveness, Safety, and Tolerability (QU.E.S.T.) evaluation of mixed amphetamine salts extended release in adults with ADHD. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Dexmethylphenidate--Novartis/Celgene. Focalin, D-MPH, D-methylphenidate hydrochloride, D-methylphenidate, dexmethylphenidate, dexmethylphenidate hydrochloride. [2018]

6. Iran pubmed.ncbi.nlm.nih.gov

Reporting a Case of Injecting Methylphenidate (Ritalin) Tablets, Intensified Symptoms of Schizoph-renia or Induce Separate Mental Disorder? [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of methylphenidate effects on oral word production and symptoms in first-episode schizophrenia at acute and stabilized phases. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Methylphenidate, dextroamphetamine, and levamfetamine. Effects on schizophrenic symptoms. [2019]