Methylphenidate for Post-Traumatic Stress Disorder

Overseen by Chen Lin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: VA Office of Research and Development

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

Disqualifiers: Cognitive impairment, Bipolar, Schizophrenia, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial aims to see if the medication Methylphenidate (MPH) can help Veterans who have both PTSD and have had a stroke. MPH is thought to improve brain function, which may reduce PTSD symptoms and help with stroke recovery. Methylphenidate (MPH) is a stimulant drug commonly used to treat attention-deficit hyperactivity disorder (ADHD) and has shown potential in treating cognitive and emotional symptoms in various neuropsychiatric conditions.

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 methylphenidate effective for treating post-traumatic stress disorder (PTSD)?

A small study found that methylphenidate helped improve cognitive and emotional symptoms in people with PTSD or traumatic brain injury, suggesting it might be beneficial for PTSD. However, more research is needed to confirm these findings. ^{1 2 3 4 5}

Is methylphenidate generally safe for use in humans?

Methylphenidate, used for conditions like ADHD, is generally considered safe in humans, with common side effects including decreased appetite, weight loss, and insomnia. Serious side effects are rare, and the safety profile is consistent across different formulations and age groups. ^{6 7 8 9 10}

How does the drug methylphenidate differ from other drugs for PTSD?

Methylphenidate, commonly used for ADHD, is unique in treating PTSD as it targets cognitive complaints and emotional symptoms, showing significant improvement in a small study, unlike the more commonly used SSRIs which have limited efficacy. This suggests methylphenidate could be a novel option for those not responding to traditional antidepressants. ^{1 2 3 11 12}

Research Team

Chen Lin, MD

Principal Investigator

Birmingham VA Medical Center, Birmingham, AL

Eligibility Criteria

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

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

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Methylphenidate (Central Nervous System Stimulant)
• Placebo (Behavioural Intervention)

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.

Participant Groups

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 Canada for the following indications:

Approved in Canada 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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. England 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

A review of atypical antipsychotic medications for posttraumatic stress disorder. [2015]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Quetiapine for treatment of refractory symptoms of combat-related post-traumatic stress disorder. [2017]

5. Switzerland 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. [2022]

6. United States 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. [2023]

7. United States 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. [2021]

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

The safety and efficacy of methylphenidate and dexmethylphenidate in adults with attention deficit/hyperactivity disorder. [2021]

9. United States 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. [2022]

10. Germany 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. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review. [2022]

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

SSRIs versus non-SSRIs in post-traumatic stress disorder: an update with recommendations. [2022]