Repetitive Transcranial Magnetic Stimulation for Opiate Use Disorder

Prescription opiate use disorder (OUD) is common in the United States, with high morbidity
and mortality. Despite the availability of opiate replacement therapies, many individuals
continue to abuse opiates and relapse rates remain high. Uncontrolled pain and opiate craving
are both commonly reported by OUD individuals attempting abstinence, and likely contribute to
relapse. As such, development of novel treatment strategies targeting pain and craving would
have important clinical implications.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation
technique which is currently FDA-approved as a treatment for major depressive disorder. TMS
is actively being pursued as a treatment for chronic pain disorders as well as for substance
use disorders. In chronic pain patients, there is promising data suggesting that treatment
with excitatory rTMS to the dorsolateral pre-frontal cortex (DLPFC) can have an anti-pain
effect. A single session of excitatory DLPFC rTMS can decrease the perception of laboratory
induced pain, decrease the amount of self administered morphine following open gastric bypass
surgery and decrease the affective and sensory components of pain following laparoscopic
gastric-bypass surgery. While the effects of a single session last for only approximately 1
hour, repeated sessions appear to have an additive and more durable effect, and following 15
sessions, the subjective experience of provoked pain has been shown to decrease by as much as
37%. In addition to the literature in laboratory induced pain, there is also preliminary data
suggesting that rTMS may be an effective treatment for chronic pain disorders. In substance
use disordered populations, the use of rTMS has garnered significant attention as an
innovative tool to decrease craving [see reviews:. Several single session rTMS studies have
demonstrated that applying excitatory rTMS to the DLPFC can decrease cue-induced craving in
nicotine, cocaine, and alcohol use disordered populations. As expected, single session
studies have only found small temporary reductions in craving; however, these promising data
have led to preliminary clinical trials using multiple sessions of rTMS in alcohol, nicotine
and cocaine use disorders. The largest such clinical trial (n=130 smokers) demonstrated that
13 sessions of DLPFC rTMS resulted in six month tobacco abstinence rates of 33% .

To date there has been limited work examining the effect of rTMS on craving or pain in
individuals with OUD. Drawing from the published literature suggesting that excitatory rTMS
applied to the DLPFC can reduce both pain and craving, our group completed a preliminary
sham-controlled crossover study in prescription OUD patients with chronic pain. Our data
suggest that a single session of excitatory DLPFC rTMS acutely decreased opiate cue induced
craving and thermal pain sensitivity in this group. The promising results from our single
session trial parallel the single session results found in nicotine and cocaine use
disordered populations which subsequently translated into positive multiple session clinical
trials. As such, it follows that a trial utilizing multiple sessions of rTMS in OUD patients
may yield positive results.

40 participants (20/group) admitted to an inpatient community treatment facility for opiate
detoxification will be given 18 sessions of either active or sham rTMS applied to the DLPFC,
in an accelerated fashion over three days (6-sessions each day).

Inclusion Criteria:

1. Participants must be able to provide informed consent and function at an intellectual
level sufficient to allow accurate completion of all assessment instruments.

2. Participants must meet DSM-5 criteria for moderate or severe OUD. While individuals
may also meet criteria for use disorders of other substances (with the exception of
alcohol or benzodiazepines), they must identify prescription opiates as their primary
substance of abuse.

3. Participants must be admitted to the inpatient unit for opiate detoxification.

4. Participants must consent to random assignment.

Exclusion Criteria:

1. Participants who are pregnant will be excluded.

2. Participants with a history of/or current psychotic disorder will be excluded.

3. Participants with a history of dementia or other cognitive impairment will be
excluded.

4. Participants with active suicidal ideation, or a suicide attempt within the past 90
days will be excluded.

5. Participants with contraindications to receiving rTMS (including a history of
seizures, or any implanted metal above the neck) will be excluded.

6. Those with unstable general medical conditions will be excluded.

7. Those who are currently using naltrexone, or tramadol, will be excluded.

8. Those with alcohol or benzodiazepine use disorders will be excluded due to increased
risk of seizure.