ACTIE: Proef naar het toevoegen van buprenorfine, cognitieve gedragstherapie en TMS om de resultaten van langdurige opioïdetherapie voor chronische pijn te verbeteren (ACTION)

Inclusion criteria:

Age >/= 18 years

English-speaking

On LTOT, defined as taking prescription opioid therapy for 90 days or more

Past week average morphine equivalent dose (MED) >/= 20mg

Willing and able to complete written informed consent

Willing and able to use a mobile/cell phone

Have at least one additional risk for opioid toxicity or overdose from the following list:

Opioid Toxicity or Overdose Risks:

1. Taking benzodiazepines with opioids
2. Substance Use Disorder diagnosis [non-tobacco; Opioid Risk Tool]

2) Having ever experienced an overdose 4) Current major medical problem [e.g. mod-severe liver disease, pancreatitis, chronic pulmonary disease, untreated sleep apnea, hospitalized for an acute medical issue in the past 6 months]a,b 5) Response to BPI Item 8 <30%, suggesting less than moderately clinically meaningful response to pain treatmentc 6) Co-morbid psychiatric diagnosis [Opioid Risk Tool] 7) Signs of opioid misuse [any score >0 on the following COMM Items: 3,4,5,9,10,11,14,15,16] 8)Opioid Risk Tool >3 or Current Opioid Misuse Measure ≥ 9 9) Struggling with any of the following side effects from opioids [self-report]

1. Dizziness and/or falls
2. Difficult-to-manage stomach pain, nausea, constipation or GI issues
3. Fatigue or low energy
4. Sleepiness or sedation
5. Trouble with memory or thinking clearly [COMM Item 1>0]
6. Other troublesome side effect [open answer]

Exclusion criteria:

Known allergy to buprenorphine

Active moderate or severe substance use disorder with the exception of those listed below:

1. . Those with nicotine use disorder.
2. . Those meeting criteria for prescription opioid use disorder using only prescribed opioids will be considered on a case-by-case basis.

Cognitive disorder limiting ability to consent or fully participate in the brief cognitive intervention

Receiving methadone or buprenorphine treatment for OUD or pain

Taking naltrexone

Pregnancy

Currently incarcerated

Taking medications that prolong QTc interval, as determined by study investigators

Personal/immediate family history of Long QT Syndrome.

Significant or unstable condition/s or treatments that may impact safe participation in the study (as determined by the study investigators) such as significant cardiac condition (e.g. poorly-controlled heart failure, current or past cardiac arrhythmia, sustained systolic blood pressure >180), significant metabolic disorder (e.g. labile diabetes, significant electrolyte abnormality), cancer (e.g. brain cancer, chemotherapy-induced cognitive impairment), major psychiatric disorder (e.g. active bipolar disorder, schizophrenia spectrum or other psychotic disorder, suicidal/homicidal intent within the past month, or any suicide attempts within the past year or current active suicidal ideation, as determined by medical clinician), developmental disorder (e.g. autism spectrum disorder, intellectual disability), or other neurologic disease (e.g. movement disorder, multiple sclerosis, moderate to severe brain injury).

Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days.

TMS contraindications (e.g., ferromagnetic implants, conditions or treatments that lower seizure threshold, taking contraindicated medications, no identifiable motor threshold, as determined by study investigators).