Trivedi 2021 (ADAPT-2): naltrexone and bupropion for methamphetamine use

What they tested

Adults with moderate or severe methamphetamine use disorder got extended-release injectable naltrexone (380 mg every 3 weeks) plus extended-release bupropion pills (450 mg a day), or matching placebo shots and pills. Neither participants nor staff knew who got which.

The trial ran in two 6-week stages. In stage 1, people were randomly assigned in a 0.26:0.74 ratio to the medicines or placebo. People on placebo who didn't respond were randomly assigned again, 1:1, for stage 2. A response meant at least three methamphetamine-negative urine samples out of four at the end of a stage, with urine tested twice a week.

What they found

In stage 1, 18 of 109 people (16.5%) on the medicines responded, against 10 of 294 (3.4%) on placebo. In stage 2, 13 of 114 (11.4%) on the medicines responded, against 2 of 111 (1.8%) on placebo.

Weighted across both stages, the response was 13.6% with naltrexone-bupropion and 2.5% with placebo, an overall treatment effect of 11.1 percentage points (P<0.001).

Side effects of the medicines included stomach and gut problems, tremor, malaise, heavy sweating and loss of appetite. Serious adverse events happened in 8 of 223 people (3.6%) who got naltrexone-bupropion.

Limits

• Even on the medicines, most people did not respond, and the authors describe the response as low.
• It lasted 12 weeks, so it can't say what happened after treatment.
• It tested one combination, the naltrexone injection every 3 weeks plus bupropion 450 mg a day, so it says nothing about naltrexone pills or about either drug alone.

What it means if you're considering naltrexone

This trial is about methamphetamine, not alcohol or opioids. Injectable naltrexone plus bupropion led to more responses than placebo, but only a small minority of people responded, so the benefit was real but limited.