Opioid use disorder (OUD), formerly known as opioid addiction, affects millions of people each year, with many cases reaching the offices of mental health professionals. In 12- to 17-year-olds, the overall 12-month prevalence is 1.0% and, in those 18 years and older, the prevalence is at least 0.37%, not counting those who are incarcerated with OUD.1 The disorder affects more than 2.1 million people and results in 47,000 deaths per year in the United States.2

Those who seek treatment for OUD have various options to choose from, including pharmacological and behavioral approaches. This review will focus on buprenorphine/naloxone (Suboxone) as one medication intervention. (Other common medication-assisted drugs for OUD include methadone and naltrexone.)

About Medication-Assisted Treatment for Opioid Addiction

The buprenorphine/naloxone 4:1 combination tablet is taken sublingually. Buprenorphine is a partial agonist with high affinity, low activity, and slow dissociation at the mu-opioid receptor, allowing it to displace full agonists. Buprenorphine also has less abuse potential and fewer negative side effects due to its ceiling effect. (More on the buprenorphine’s bioavailability and clinical considerations on our sister site PPM). On the other hand, naloxone is an antagonist at the mu-opioid receptor which has poor bioavailability when taken sublingually but good bioavailability when taken parenterally. The latter point is the primary reason why the injectable formulation is not commonly used –  it would precipitate withdrawal.

Before initiating therapy, the candidacy of a potential patient must be considered. The candidate’s history, ability to adhere to a treatment plan, psychiatric stability, and other biopsychosocial factors should be assessed. Of note, concurrent use of alcohol or other sedative-hypnotics should be avoided when starting medication-assisted treatment (MAT) for OUD due to risk of overdose from the combined effects with buprenorphine. The candidate should also have sufficient time from their last opioid use such that they may be experiencing some withdrawal signs at the time of induction.

MAT with buprenorphine/naloxone is often conducted in three stages: induction, stabilization and maintenance, and cessation, as described below. Of note, there are several recommendations relating to this substance’s use, of which we report some of the most common algorithms used in clinical practice (see also, the latest HHS guidelines on buprenorphine prescribing waiver guidelines).

Induction of Buprenorphine/Naloxone

During the induction phase of treatment, the goal is to determine the dose of drug needed to stop withdrawal symptoms, which will depend on the severity of the precipitated symptoms using the Clinical Opiate Withdrawal Scales (COWS). Examples of common precipitated withdrawal symptoms seen include tachycardia, diarrhea, sweating, vomiting, and runny nose. Symptoms can range from mild to severe.  Criteria that make induction with buprenorphine/naloxone appropriate, are a COWS score greater than 12, no contraindications and no use of long-acting opioids for at least the past 30 hours. Some contraindications include abnormal liver function, respiratory distress, and acute alcohol intoxication. Prior to starting, basic labs including CBC, BMP, UDS, HIV, as well as a hepatitis screen, should be taken.3

After assessing the above parameters, induction may begin. On Day 1, buprenorphine/naloxone is started at a dose 4 mg/1 mg, followed by close monitoring of the precipitated withdrawal symptoms for the next 2 to 4 hours. If withdrawal symptoms resolve, then no further doses will be needed on the first day. However, if the withdrawal symptoms persist after a few hours, then another dose of 4 mg/1 mg may be given with reassessment following another few hours. If there is resolution, no further doses are needed on Day 1. This cycle should be repeated until a stable dose has been found that resolves withdrawal symptoms. Of note, the maximum dose given on Day 1 should be 12mg/3mg.4

The patient should return for treatment the following day. On Day 2, first assess to see if the patient is showing withdrawal symptoms. If no such symptoms are seen, administer the final dose determined on Day 1. If withdrawal symptoms have persisted since the last dose of Day 1, then give the total dose of Day 1 (which would be 4mg, 8mg or 12mg depending on resolution of withdrawal) and reassess in a few hours. If the symptoms are not resolved, then administer another dose of 4 mg/1 mg. Again, repeat this cycle until withdrawal symptoms resolve. The maximum dose of MAT on Day 2 should be 16 mg/4 mg. After finalizing the dose, consider titrating up to its optimal dose, which is greater than 12 mg/3 mg (if the final dose was below this dosage), for better management and retention rate.

Doses may be reviewed and adjusted every 1 – 3 days as needed. Following induction, the most common 24-hour doses are 8 mg/2 mg, 12 mg/3 mg and 16 mg/4 mg.4

Stabilization and Maintenance with Buprenorphine and Naloxone

The stabilization phase starts when the patient is no longer experiencing withdrawal symptoms, side effects, or cravings for opioids. During this phase, frequent assessments for dosage adjustments should be made, with changes in 2/.5-4/1 mg increments until the patient is on a stable dose. One common sign that may warrant a higher dose is when the patient feels better during the day but starts to develop withdrawal symptoms at night when the medication wears off.3

If a patient has continued illicit opioid use and/or cravings at 32/8 mg, the dose should be maintained as there is no evidence for increased efficacy at higher doses. In fact, it is thought that 95% of the receptors are saturated at a dose of 16/4 mg, which is why this is a common maintenance dose for patients (nearly all patients will stabilize on doses of 16mg/4mg-24mg/6mg). 3

When checking for stability, the timeline for follow-up during this period may be as follows: patients should be monitored each week for the first month, then once every other week for the following month. If there is continued success, then a provider can see the patient at 1-month intervals for maintenance follow-ups for the indefinite future. At each appointment, a urine drug screen should be obtained. Basic routine laboratory testing should not be necessary (unless indicated) as this would have already been taken during initial evaluations.4

Cessation of MAT for OUD

To taper a patient off buprenorphine/naloxone MAT, a gradual detoxification over a long period is recommended. Here are some general guidelines:

  1. If the dose was 8 mg or greater, then decrease the dose by 4 mg every 4 weeks. If the dose was less than 8 mg, then decrease the dose by 2 mg every 4 weeks.
  2. When the dose reaches 2 mg, stay at 2 mg for 4 weeks.
  3. Afterward, decrease the dose by 1 mg for 1 week.
  4. Following this, decrease the dose to 0.5 mg daily for 1 week.
  5. Finally, decrease the dose and frequency to 0.5 mg every other day for 1 week.

Other protocols for dosing recommendations exist if a decision is made to taper off of buprenorphine/naloxone MAT in a shorter period of time. Example scenarios where this may be indicated include the need for surgery or pain management intervention. Buprenorphine/naloxone cannot be given with pain medications (opioid agonists) as the naloxone (an opioid antagonist) would block the analgesic effects.

Editor’s Note: FDA approved a higher dosage of naloxone on April 30, 2021 – naloxone hydrochloride nasal spray 8 mg (previously 2 mg and 4 mg had been approved) for the treatment of opioid overdose.

Residents’ Corner: Tips from the Authoring Residents

“One main challenge is that Suboxone will not help a patient if they do not change their fundamental thinking in terms of addiction. This involves separating healthy thinking from addicted thinking which will take time. Until this happens, it helps to have an understanding that setbacks and relapses will happen. To overcome this, during appointment times, I have found it helpful to incorporate motivational interviewing into the treatment plans.”

–Danielle Weitzer, DO

“In addiction patients, there is usually an underlying trauma. Until that trauma is assessed and treated, there will be a lot of uncertainty in this patient population. As such, many patients can and will be lost to follow-up even with appropriate treatment with Suboxone. Therefore, at the start of treatment, it will be helpful to do an in-depth assessment of the patient’s needs. Once this is completed, it would be best to try to coordinate all treatment services within the same program if possible to try to increase overall compliance.”

–Sung Kang, DO

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Last Updated: Jun 15, 2021