The Effect of Transcranial Magnetic Stimulation and Oral Ketamine Combination Treatment on severity of symptoms in Post-Traumatic Stress Disorder (TMS-OK PTSD)
This double-blinded, randomised controlled trial (n=100) aims to assess the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS) and oral ketamine (OK) as a combination treatment for Post-Traumatic Stress Disorder (PTSD).
Detailed Description
Randomised, parallel-group, double-blinded Phase II trial comparing active iTBS plus weekly oral ketamine (1 mg/kg, 6 doses) with sham iTBS plus the same ketamine regimen over a 6-week treatment period and 2 follow-ups.
TMS is delivered five days per week (30 sessions total); ketamine is administered on-site once weekly with 2-hour observation. Primary outcome includes PTSD symptom change (PCL-5) between baseline and follow-ups.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
TMS-OK
experimentalActive iTBS plus oral ketamine (OK) over 6 weeks.
Interventions
- Ketamine1 mg/kgvia Oral• weekly• 6 doses total
Oral ketamine 1 mg/kg once weekly for 6 weeks; observed up to 2 hours post-dose.
- Compoundvia Other• five days/week for 6 weeks• 30 doses total
iTBS to left DLPFC at 80% RMT; 20 2-second trains per session; session 20–30 minutes including setup.
TMS-sham + OK
active comparatorSham TMS plus oral ketamine (OK) over 6 weeks.
Interventions
- Ketamine1 mg/kgvia Oral• weekly• 6 doses total
Oral ketamine 1 mg/kg once weekly for 6 weeks; observed up to 2 hours post-dose.
- Compoundvia Other• five days/week for 6 weeks• 30 doses total
Sham produces <10% electrical output with auditory/tactile mimicry; session ~20–30 minutes.
Participants
Inclusion Criteria
- Current PTSD diagnosis
- Persons (male/female/other) aged over 18 years
- Participants must be able to understand and provide consent on the Participant Information and Consent Form (PICF).
- Participants must be able to tolerate the ketamine treatment, TMS treatment/sham TMS treatment, rating scales, blood testing and urinalysis in order to remain in the study and this will be monitored on an ongoing basis, as per the methodology.
Exclusion Criteria
- Psychiatric conditions:
- Psychosis
- Mania/hypomania
- Acute suicidality requiring urgent psychiatric intervention
- History of ketamine use disorder
- History of epilepsy/seizures
- Physical conditions:
- Active or inactive implants (including device leads), including deep brain stimulators, cochlear implants, and vagus nerve stimulators
- Ferrous metal pins or plates in or near the head (within 30 cm of the coil), including implanted electrodes/stimulators, aneurysm clips or coils, stents, or bullet fragments
- History of epilepsy or unexplained seizure history
- Previously undergone TMS treatment
- Uncontrolled/severe symptomatic cardiovascular disease (recent MI within 6 months; history of stroke; hypertension resting BP >150/100)
- Body weight >130 kg
- History of intracranial mass, intracranial haemorrhage/stroke, cerebral trauma/traumatic brain injury or increased intracranial pressure
- LFTs out of normal range as specified (ALT >135 U/L; AST >123 U/L; GGT male >210 U/L; GGT female >135 U/L; Total bilirubin >60 µmol/L; Albumin <25 g/L or >150 g/L; ALP >345 U/L)
- Previous reaction to ketamine
- Pregnant, breastfeeding, or planning pregnancy during the trial
- Simultaneous participation in another clinical intervention trial
- Participants with a history of substance use disorder (excluding ketamine use disorder) must abstain for 2 weeks prior and for remainder of trial