Methylphenidate for Post-Traumatic Stress Disorder

Overseen By Chen Lin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must not be taking: Antipsychotics, Mood stabilizers, Stimulants, others

Disqualifiers: Cognitive impairment, Bipolar, Schizophrenia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if methylphenidate, a medication commonly used for ADHD, can benefit veterans with both post-traumatic stress disorder (PTSD) and a recent stroke. Researchers are examining whether this treatment can improve PTSD symptoms such as social withdrawal and mood, as well as aid in stroke recovery. Participants will receive either methylphenidate or a placebo (a pill with no active medication) to compare outcomes. Veterans with military-related PTSD who have experienced a stroke within the past year may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

You will need to stop taking antipsychotics, mood stabilizers, stimulants, and any form of methylphenidate (MPH) at least two weeks before starting the trial. If you are on any of these medications, you should discuss with your doctor how to safely stop them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that methylphenidate, a medication often used for ADHD, is usually well-tolerated by people with PTSD and those who have had a stroke. In earlier studies, patients taking methylphenidate reported very few negative side effects. For instance, a small study found that methylphenidate helped reduce PTSD symptoms like social withdrawal and hypervigilance. Another study discovered that it also improved mood and daily activities in stroke patients. These results suggest that methylphenidate is relatively safe and could be helpful for people with PTSD and those recovering from a stroke. ^{1 2 3 4 5}

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

Researchers are excited about using methylphenidate for PTSD because it offers a fresh approach by targeting the brain's dopamine and norepinephrine systems, which are often involved in attention and alertness. Unlike traditional PTSD treatments that typically focus on serotonin, such as SSRIs, methylphenidate's unique action could address symptoms like concentration issues and fatigue more directly. Additionally, its potential for rapid effect, possibly within days, sets it apart from other options that can take weeks to show results. This could provide a quicker relief option for those struggling with PTSD symptoms.

What evidence suggests that methylphenidate might be an effective treatment for PTSD?

Research has shown that methylphenidate, a medication often used for ADHD, may help reduce PTSD symptoms such as avoidance and being easily startled. In this trial, some participants will receive methylphenidate, which studies have shown can significantly decrease PTSD symptoms, suggesting its effectiveness. Additionally, this medication might improve mood and daily activities after a stroke. Clinical trials have demonstrated that it is well-tolerated, with few side effects, making it a promising option for veterans dealing with both PTSD and stroke recovery. Other participants in this trial will receive a placebo for comparison. ^{4 6 7 8 9}

Who Is on the Research Team?

Chen Lin, MD

Principal Investigator

Birmingham VA Medical Center, Birmingham, AL

Are You a Good Fit for This Trial?

This trial is for US military veterans who have both PTSD and a recent ischemic stroke. They must not be on certain psychiatric medications, have had their first-ever stroke within the last year, and women must use birth control if of child-bearing potential. Exclusions include severe cognitive impairment, major psychiatric disorders other than PTSD, or being in another intervention trial.

Inclusion Criteria

Your total score on the CAPS-5 test from the past week is 27 or higher during the initial visit.

The traumatic event that caused PTSD happened during adulthood before having a stroke.

You are diagnosed with post-traumatic stress disorder (PTSD) using the MINI International Neuropsychiatric Inventory (MINI) for DSM-5.

Exclusion Criteria

You have a high risk of suicidal thoughts or behavior that requires hospitalization or extra treatment.

You are currently taking part in another study for PTSD or stroke.

I am currently in psychotherapy and can continue it during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Methylphenidate or placebo to evaluate therapeutic effects on PTSD symptoms and post-stroke recovery

6 months

Up to twice daily dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylphenidate
• Placebo

Trial Overview

The study tests whether Methylphenidate (MPH), a stimulant that can improve PTSD symptoms and post-stroke recovery, is effective for veterans with both conditions. Participants will either receive MPH or a placebo to compare outcomes.

How Is the Trial Designed?

Group I: Methylphenidate Experimental Treatment 1 Intervention

Patient with both PTSD and recent history of stroke. Methylphenidate active arm. The oral dosing maximum will be up to 20mg twice daily.

Group II: Placebo Placebo Group 1 Intervention

Patient with both PTSD and recent history of stroke. Placebo control arm. The frequency will be up to twice a day, with oral dosing.

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

Approved in United States as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in Canada as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in European Union as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Methylphenidate and dexmethylphenidate are effective and safe treatments for adults with ADHD, supported by a review of clinical trials, although the evidence is less extensive compared to children and adolescents.

Higher doses of these medications are linked to improved treatment responses, but there are moderate safety concerns, highlighting the importance of individualized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of methylphenidate and dexmethylphenidate in adults with attention deficit/hyperactivity disorder. Sopko, MA., Caberwal, H., Chavez, B.[2021]

The study involved 119 preschool children aged 4 to <6 years with ADHD, showing that the methylphenidate hydrochloride extended-release capsule (MPH-MLR) significantly reduced ADHD symptoms, with mean ADHD-RS-IV scores dropping from 40.8 to 19.5 during the open-label phase.

In a double-blind phase, children receiving MPH-MLR had a significantly greater improvement in ADHD symptoms compared to those on placebo, with common side effects including decreased appetite and insomnia, consistent with known effects of methylphenidate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder. Childress, AC., Kollins, SH., Foehl, HC., et al.[2021]

A review of 18 clinical trials found that atypical antipsychotics, particularly risperidone and quetiapine, provide a modest benefit in treating PTSD symptoms, especially intrusive thoughts and hypervigilance.

The effect sizes from double-blind placebo-controlled trials were small, indicating that while there is some positive response, larger studies are necessary to better understand the effectiveness and potential side effects of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of atypical antipsychotic medications for posttraumatic stress disorder. Ahearn, EP., Juergens, T., Cordes, T., et al.[2015]

In a study involving 132 participants, dexmethylphenidate hydrochloride (d-MPH) significantly improved ADHD symptoms compared to placebo, showing effectiveness in both teacher and parent assessments, as well as in math performance.

Both d-MPH and d,l-threo-methylphenidate (d,l-MPH) were well tolerated, with d-MPH potentially offering a longer duration of action, although both treatments demonstrated similar efficacy overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder. Wigal, S., Swanson, JM., Feifel, D., et al.[2022]

In a 12-week trial involving 32 participants with PTSD and/or TBI, methylphenidate significantly improved cognitive complaints compared to placebo, indicating its potential efficacy for these conditions.

The treatment was well tolerated, suggesting a favorable safety profile, but further research with a larger sample size is needed to confirm these promising results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury. McAllister, TW., Zafonte, R., Jain, S., et al.[2018]

In a review of Vietnam veterans with combat-related PTSD who had not responded to previous treatments, adding quetiapine led to significant improvements in PTSD symptoms: 35% in re-experiencing, 28% in avoidance/numbing, and 65% in arousal.

Quetiapine was administered at low doses (average 155 mg) and was associated with minimal side effects, suggesting it may be a safe adjunctive treatment for refractory PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quetiapine for treatment of refractory symptoms of combat-related post-traumatic stress disorder. Sokolski, KN., Denson, TF., Lee, RT., et al.[2017]

In a 1-year study involving 282 children aged 6-12 with ADHD, SDX/d-MPH was found to be safe and well tolerated, with 60.1% of participants experiencing treatment-emergent adverse events, mostly mild to moderate.

The treatment led to significant reductions in ADHD symptoms, demonstrating sustained efficacy over the year, comparable to other methylphenidate products, with no unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study. Childress, AC., Marraffino, A., Cutler, AJ., et al.[2023]

A review of 13 case reports and analysis of 25,556 adverse drug event reports revealed that combining methylphenidate and risperidone in children with ADHD and conduct disorder is associated with a significant risk of movement disorders, particularly when risperidone is tapered or switched.

The data suggests that the risk of movement disorders increases when both medications are used together, highlighting the need for careful monitoring of patients during treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Movement disorders and use of risperidone and methylphenidate: a review of case reports and an analysis of the WHO database in pharmacovigilance. Stämpfli, D., Weiler, S., Burden, AM.[2021]

SSRIs are the first-line treatment for PTSD, but they only help about 60% of patients, with less than 30% achieving full remission, highlighting the need for alternative treatments.

Risperidone has the strongest evidence as an effective add-on therapy for patients who do not respond well to SSRIs, while prazosin shows promise for treating PTSD symptoms like nightmares and insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review. Berger, W., Mendlowicz, MV., Marques-Portella, C., et al.[2022]

Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, and sertraline show a statistically significant but small effect in reducing PTSD symptoms compared to placebo, based on a systematic review of 115 randomized controlled trials.

Prazosin and risperidone also demonstrate small positive effects when used to augment other treatments, but no single pharmacological intervention was found to be superior to others in head-to-head comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Hoskins, MD., Bridges, J., Sinnerton, R., et al.[2023]

Selective serotonin reuptake inhibitors (SSRIs) like sertraline and paroxetine are the most effective first-line treatments for PTSD, showing significant efficacy in short-term trials (6-12 weeks) and reducing relapse rates with continued treatment for 6-12 months.

If SSRIs are not effective, alternative treatments such as serotonin-potentiating non-SSRIs and atypical antipsychotics can be considered, with the latter showing promise in managing symptoms like paranoia and flashbacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SSRIs versus non-SSRIs in post-traumatic stress disorder: an update with recommendations. Asnis, GM., Kohn, SR., Henderson, M., et al.[2022]

Pharmaceutical treatments, particularly amitriptyline, imipramine, and quetiapine, significantly improve symptoms of combat-related PTSD compared to placebo, with a moderate effect size across various PTSD symptoms.

While there was no significant increase in overall adverse events from these medications, higher discontinuation rates due to adverse effects were noted, indicating the need for careful monitoring in patients, especially those with severe PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness, Acceptability and Safety of Pharmaceutical Management for Combat-Related PTSD in Adults Based on Systematic Review of Twenty-Two Randomized Controlled Trials. Yan, JZ., Liu, JL., Li, XZ., et al.[2022]

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