Methylphenidate ER for Schizophrenia

Overseen By Naista Zhand, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: The Royal Ottawa Mental Health Centre

Must be taking: Antipsychotics

Disqualifiers: Hypertension, Cardiovascular, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Apo-Methylphenidate ER (a form of methylphenidate) can improve negative and cognitive symptoms in people with schizophrenia. These symptoms often complicate daily life, affecting motivation and thinking skills. The trial compares the effects of Apo-Methylphenidate ER to usual treatment methods. Individuals with schizophrenia who are on stable antipsychotic medication and have been stable for the past four weeks might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that methylphenidate ER, a medication often used for ADHD, might pose risks for people with schizophrenia. Some reports have mentioned mental health issues such as confusion and hallucinations. Additionally, it could worsen existing mental health symptoms. However, some studies suggest that careful use of methylphenidate ER can improve symptoms in schizophrenia without causing serious side effects. Weighing both the potential benefits and risks is important when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Most treatments for schizophrenia focus on balancing neurotransmitters like dopamine and serotonin using antipsychotic medications. However, Apo-Methylphenidate ER is unique because it targets the dopamine system differently, typically used for ADHD, by enhancing dopamine release and reuptake inhibition. This approach could potentially manage symptoms like cognitive impairment and negative symptoms in schizophrenia, areas where current antipsychotic treatments often fall short. Researchers are excited about this treatment because it offers a novel mechanism of action that could complement existing therapies and improve overall patient outcomes.

What evidence suggests that Apo-Methylphenidate ER might be an effective treatment for schizophrenia?

Research has shown that methylphenidate ER can help people with schizophrenia. In this trial, participants in the Apo-Methylphenidate ER arm will receive this treatment to assess its effects on symptoms like lack of motivation and difficulties with memory or thinking. These improvements suggest that methylphenidate ER might help people with schizophrenia function better in daily life. Although methylphenidate is usually used for ADHD, early findings are promising for its use in schizophrenia. However, caution is necessary because it might worsen symptoms of psychosis. ^{4 5 6 7 8}

Who Is on the Research Team?

Naista Zhand, MD

Principal Investigator

Royal Ottawa Mental Health Centre

Are You a Good Fit for This Trial?

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.

Able to communicate in English

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Apo-Methylphenidate ER

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC524494/

Efficacy of two once-daily methylphenidate formulations ... Results. Symptom control from 1.5 through 6.0 hours post-dose was as good with lower doses of Metadate CD (20 and 40 mg) as with higher ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4564067/

ADHD & Pharmacotherapy: Past, Present and Future Efficacy of pharmacotherapy in treating ADHD symptoms has generally been considerable with at least ¾ of individuals benefitting from pharmacotherapy, typically ...

3. en.wikipedia.org en.wikipedia.org/wiki/Methylphenidate

Methylphenidate For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamines, alleviating the executive functioning deficits ...

4. researchgate.net researchgate.net/publication/393907212_Current_insights_into_the_safety_and_adverse_effects_of_methylphenidate_in_children_adolescents_and_adults_-_narrative_review

(PDF) Current insights into the safety and adverse effects of ... Methylphenidate (MPH) is a central nervous system stimulant that is approved and widely used for the treatment of attention-deficit ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11350445/

Adjunctive methylphenidate extended release in patients ... Adjunctive methylphenidate ER 36 mg improves functional outcome in patients with schizophrenia, who are admitted to the inpatient Recovery ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC181133/

Methylphenidate Abuse and Psychiatric Side Effects - PMC Reports of psychiatric symptoms that have occurred include euphoria, delirium, confusion, toxic psychosis, and hallucinations.

7. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-medications-used-treat-attention

Safety Review Update of Medications used to treat ADHD Study findings reported no evidence of increased risk of serious cardiovascular effects among children and young people who use ADHD medications.

8. mayoclinic.org mayoclinic.org/drugs-supplements/methylphenidate-oral-route/description/drg-20068297

Methylphenidate (oral route) - Side effects & dosage Methylphenidate is used to treat attention deficit hyperactivity disorder (ADHD). It belongs to the group of medicines called central nervous system (CNS) ...