A Phase 2 interventional study of methylphenidate (Ritalin®) and Reboxetine in PTSD and Posttraumatic Stress Disorder, sponsored by University of Haifa. Recruiting at 1 site in Israel. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-08-18.
Sponsored by University of Haifa · Phase 2, Interventional, and Treatment
Posttraumatic stress disorder (PTSD) is a chronic and often treatment-resistant psychiatric condition that emerges following exposure to trauma and is characterized by intrusive thoughts, emotional dysregulation, and cognitive impairments. In Israel, the prevalence of PTSD has increased significantly in the aftermath of the October 7, 2023 terror attacks, emphasizing the urgent need for more effective, accessible, and personalized interventions.
Existing treatments, such as trauma-focused CBT and SSRIs, remain only partially effective, with side effects that reduce adherence and limit long-term recovery. The proposed randomized controlled trial will assess and compare two promising treatment modalities: (i) a new pharmacological combination of reboxetine and methylphenidate, designed to enhance noradrenergic and dopaminergic pathways involved in attention and emotional regulation, and (ii) dog-assisted therapy (DAT), a non-pharmacological, group-based intervention shown to reduce PTSD symptoms and improve functioning. One hundred sixty adults with PTSD will be randomized into four groups: pharmacological treatment, placebo, DAT, or occupational therapy. The study will use validated clinical scales (CAPS-5, GAD-7, CAARS, DLQ, WHOQOLBREF) alongside neurophysiological tools (EEG, EDA, ASAT-based EMG). Data will feed into a machine-learning model to identify predictors of treatment response and support the development of personalized, neurobiologically informed approaches.
Posttraumatic Stress Disorder (PTSD) is a chronic and debilitating psychiatric condition characterized by intrusive memories, avoidance behaviors, hyperarousal, and emotional numbing. It is estimated that it affects 5.3% of the Israeli general population, though following the October 7, 2023 terror attacks, probable PTSD nearly doubled, from 16.2% to 29.8%, highlighting the urgent national need for effective and scalable PTSD interventions.
Given its high prevalence and physical and mental consequences, adequate treatment is needed. Current first-line therapies (TF-CBT and EMDR) are effective but are time-intensive, require specialized clinicians, and are not suitable for all patients. Pharmacological interventions, particularly SSRIs yield partial response rates (\~60%) and often cause adherence-limiting side effects (e.g., major changes in body weight or loss of sexual drive). These limitations underscore the need for novel, tolerable, and mechanistically targeted therapies.
Arising evidence suggests a correlation between sensory dysfunction, impaired attention, and PTSD symptoms. The importance of combined treatment specifically targeting these difficulties has been suggested by us. Recent evidence suggests that PTSD involves dysregulation in both noradrenergic and dopaminergic systems, which play critical roles in attention, arousal, and emotional processing. Reboxetine, a norepinephrine reuptake inhibitor (NRI), and methylphenidate, a dopamine-enhancing psychostimulant, are hypothesized to have synergistic effects on PTSD-related cognitive and emotional deficits. Our lab's prior results suggest that this combination is safe, well-tolerated, and effective in reducing both clinician-rated PTSD symptoms, and neurophysiological dysregulations related to sensory gating and attention regulation, sensory processing, participation and quality of life.
Animal-assisted therapies, and DAT in particular, are increasingly recognized for their potential to reduce PTSD symptoms and improve emotional regulation. DAT programs for US veterans diagnosed with PTSD were found to be a helpful complementary or alternative treatment option for the veterans, demonstrating signs of meaningful improvements in mental and social health, lower PTSD symptoms severity and higher psychosocial functioning in veterans owning a psychiatric service dog, and positive correlation between Animal-assisted interventions (AAI) and a reduction of posttraumatic symptomatology. DAT programs have also been shown to foster resilience among veterans and their families. A meta-review found that DAT was as effective as traditional psychotherapy in symptom reduction. Our lab conducted a controlled study involving adolescents exposed to interpersonal trauma, showing significant improvement in PTSD symptoms, depression, and attentional regulation after a year-long dog training program (also on the dogs' attention and anxiety-like behavior).
Despite growing support for DAT and emerging evidence comparing DAT to psychotherapeutic interventions for PTSD symptomatology, no studies to date have directly compared pharmacological vs. animal-assisted therapy in PTSD. Moreover, there is a lack of objective, physiology-based tools to monitor treatment efficacy and guide individualized care. This study aims to bridge both gaps, combining a novel pharmacological strategy with neurophysiological diagnostics in a rigorously controlled, head-to-head RCT. Therefore, a four-arm randomized controlled trial (RCT) involving 160 adults diagnosed with PTSD, allocated to one of the following groups: 1. Combined pharmacological treatment (reboxetine + methylphenidate) 2. Pharmacological placebo control 3. Dog-assisted therapy (DAT) 4. Active control: Occupational therapy (OT) The pharmacological arm is double-blinded and placebo-controlled, while the DAT/OT arms are open-label, with participant preference and suitability guiding allocation. The study includes repeated measurements at multiple time points, combining subjective and objective outcomes.
2,682 studies on the registry are indexed under Stress Disorders, Post-Traumatic; 601 are open to participants now.
This study's planned enrollment of 160 is above the median of 69 across 2,196 interventional studies indexed under Stress Disorders, Post-Traumatic.
Browse Stress Disorders, Post-Traumatic studies →University of Haifa is the lead sponsor of 105 studies on the registry; 27 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The trial starts with four days of treatment with 2mg of reboxetine every morning at 8 am. For the rest of the first three weeks, the participants will increase their dosage to 4mg every morning. During the fourth week, the participants will continue taking 4mg of reboxetine every morning at 8 am and additionally take 10mg of methylphenidate (or matching placebo) twice daily, i.e., in the morning at 8 am and at noon.
Drug: methylphenidate (Ritalin®) · Drug: Reboxetine
The patients will take placebos according to the medication schedule of the treatment group.
Drug: Placebo
. To encompass DAT protocol variability, it will be provided by certified rehabilitation farms in Israel and the US. The twenty-four DAT group therapy weekly sessions, over six months, will be conducted by licensed clinicians trained in occupational therapy, social work, psychology, and counseling, and are certified (diploma) to facilitate group therapy using therapy dogs. The clinicians have, on average, over four years of experience in providing services to people diagnosed with PTSD. Groups will typically have eight to fifteen human participants, depending on the rehabilitation farm. The DAT session's duration will last between fifty to sixty minutes. In generalization, session protocol will include: (i) defining a subject for each of the twenty-four AATx sessions, from which the clinicians will extract the therapeutic messages they would like to convey (e.g. regaining a sense of control, dealing with feelings of anger, guilt or shame, reducing feelings of alienation and distance);
Behavioral: Dog-Assisted Therapy
The occupational therapy schedule will roughly follow the same timeline as the dog-assisted therapy group. Therapy will be provided by licensed occupational therapists.
Behavioral: Occupational Therapy
Ritalin 10mg
Also known as: Ritalin
Reboxetine 4mg
Placebo matched to Reboxetine
Placebo matched to Ritalin
Dog-Assisted Therapy
Occupational Therapy
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
PTSD symptom severity score. Total of 56 questions. Minimum score 0, maximum score 80. A higher score reflects a worse outcome.
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
General Anxiety Disorder-7 (GAD-7)
Self-report scale to evaluate general anxiety symptoms.
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
Conners' Adult ADHD Rating Scales (CAARS)
Measures attentional and executive function impairments commonly comorbid with PTSD.
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
Daily Life Questionnaire (DLQ)
Assesses the impact of symptoms on functional capacity in everyday contexts.
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
World Health Organization Quality of Life - BREF (WHOQOL-BREF)
A comprehensive index of physical, psychological, and social quality of life domains.
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
Electroencephalography (EEG)
To assess resting-state brain activity (bandwidths delta, theta, alpha, beta, gamma) and ERPs associated with sensory gating, attention and emotional regulation (i.e., P50, N100, P200 and P300).
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
Electrodermal Activity (EDA)
To measure autonomic nervous system responses, including arousal and reactivity under baseline and taskrelated conditions.
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
Electromyography (EMG) - Auditory Sustained Attention Test (ASAT-based)
Developed in our lab (Maoz et al., 2021), this test quantifies startle reflex modulation in response to repeated auditory stimuli of varying intensities, reflecting disruptions in sustained attention and emotional reactivity
Time frame: Participants will be measured at three time points: (i) Baseline - on the 1st day of the trial before starting the DAT or another OT intervention; (ii) on the twenty-fourth week; and (iii) Follow-up - six weeks after completion of the trial.
Plan to share: No
Started Aug 2026 (actual). Primary completion is estimated for Aug 2028, 24 months after the start.
Of 87 non-industry phase 2 interventional studies under Stress Disorders, Post-Traumatic, half reached primary completion within 46 months of starting (the median), counting those still running; a quarter within 35 and three quarters within 59. This study's planned 24 months is below that.
Counting every sponsor, half of 118 studies reached it within 38 months; a quarter within 23 and three quarters within 53.
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Studies of the drugs tested here: Methylphenidate · Reboxetine
Stress Disorders, Post-Traumatic →