Stabilization Phase

Nothing  in  the world can  take the place of  persistence.   Talent  will not;
nothing  is  more  common  than  unsuccessful  men with talent.   Genius
will not; unrewarded genius is almost a proverb.  Education alone will not; the world is full of educated derelicts. Persistence and determination
alone are omnipotent.       ---Calvin Coolidge

The initial daily buprenorphine dose currently recommended is 4 to 8mg, although higher doses have been given. Clinicians generally start with 4mg Suboxone, and if withdrawal signs do not worsen, give a second 4-mg dose in 2-4 hours.  Some clinicians provide an additional dose (2 to 4mg) for the patient to take at home if withdrawal symptoms re-emerge during the first 24 hours.   

Practitioners  should  monitor  for indications of buprenorphine
-precipitated  withdrawal, including sweating, anxiety, cravings
and gastrointestinal symptoms such as abdominal cramps,
diarrhea, and/ or nausea.  Such symptoms may appear within 1(1/2) hour after buprenorphine dosing, peak within 1(1/2) to 3 hours and diminish thereafter(Lintzeris et al., 2001).  This differs from withdrawal caused by underdosing of buprenorphine, which can occur during the latter part of a 24-hour dosing interval.

Clinicians  can  achieve the maintenance dose of buprenorphine
by doubling the dose each day up to a maximum of 24 to 32mg (Ling et al.,1998; Ling and Smith 2002).   If induction occurs too slowly, patients might terminate their treatment (Matticke et al., 2003; Petitjean et al.,2001) A number of studies have shown that a target dose of 16mg can be reached in two to three days (Johnson, Syrain, Amass 2003) with minimal withdrawal effects (Johnson et al., 1989; Kuhlman et al., 1998).  To manage the patient's transition from Subutex to Suboxone therapy, the clinician needs simply to replace the dose of Subutex with Suboxone containing the same amount of buprenorphine. 

Buprenorphine blood concentrations stabilize after approximately 7 days of consistent dosing (Chiang and Hawks, 2003).    If withdrawal symptoms subsequently emerge during
any 24-hour dosing interval, the dose is too low and should be increased.  

Stabilzation Phase

The induction phase is completed and the stabilization phase (usual duration approximately 1 to 2 months) is begun when the patient is experiencing no withdrawal symptoms, is experiencing minimal or no side effects, and no longer has uncontrollable cravings for opioid agonists.  As with any pharmacotherapy, the goal of buprenorphine treatment is to treat with the minimum dose of medication needed to address target signs, symptoms, desired benefits, and laboratory indices while minimizing side effects. Elimination of objective evidence of opioid use (negative toxicology) represents the key target sign for which to strive. The goal is to reduce self -reported cravings and self-reported use of illicit opioids. One benefit worth achieving is a self-reported increase in opioid blockade such that self-administered illicit opioids induce little or no euphoria. A reduction in opioid-positive toxicology specimens confirms a successful direction in treatment.

Dosage adjustments may be necessary during early stabilization, and frequent contact with patients increases the likelihood of compliance. Until full stabilization is achieved, weekly assessments of patients may be indicated to make necessary dosage adjustments. With stabilization goals in mind, doses of buprenorphine/naloxone may be increased in 2/0.5-4/1 mg increments per week until stabilization is achieved. Nearly all patients will stabilize on daily doses of 16/4-24/6 mg; some, however, may require up to 32/8 mg daily.

Some patients may prefer or may respond better to less than -daily dosing regimens of buprenorphine. It is possible that less -than-daily dosing will most likely be advantageous in an OTP or other directly observed dose setting, where daily visits might otherwise be required. A variety of studies have shown the efficacy of alternate-day or thrice-weekly buprenorphine administration (Amass et al. 2000; Bickel et al. 1999; Perez de los Cobos et al. 2000; Petry et al. 1999). The typical method of determining the dose for less-than-daily dosing regimens was to double (for alternate-day dosing) or triple (for every -third -day dosing) the stable daily dose for the patient. Although all regimens were determined to be safe and, in most cases, effective, several authors noted that some subjects were more likely to have urine samples positive for opioids on the less -than-daily dosing regimens. During induction and early stabilization daily dosing is recommended.

If a patient continues to use illicit opioids despite the maximal treatment available in the physician's clinical setting, the physician should consider referral to a more intensive therapeutic environment.

Maintenance Phase

The longest period that a patient is on buprenorphine is the period of maintenance. This period may be indefinite. It is easy for physicians to lessen their vigilance during this period, but significant considerations still must be addressed. Attention must be maintained to the psychosocial and family issues that have been identified during the course of treatment. Other issues that will need continual monitoring are related to cravings for opioids and to preventing relapse. Some other issues related to opioid abuse that need to be addressed during maintenance treatment include, but are not limited to, the following:

*Psychiatric comorbidity

*Somatic consequences of drug use

*Family and support issues

*Structuring of time in prosocial activities

*Employment and financial issues

*Legal consequences of drug use

*Other drug and alcohol abuse

The   frequent   presence   of  some  or  all  of  these  problems underscores the importance of providing nonpharmacological services  to address  comprehensively the needs of patients and to maximize the chances of the best possible outcomes.

Long-Term Management 

The design of long-term treatment depends in part on the patient's personal treatment goals and in part on objective signs of treatment success. Maintenance can be relatively short -term (e.g., <12 months) or a lifetime process. Treatment success depends on the achievement of specific goals that are agreed on by both the patient and the physician. Following successful stabilization, decisions to decrease or discontinue buprenorphine should be based on a patient's desires and commitment to becoming medication-free, and on the physician's confidence that tapering would be successful.

 Factors to be considered when determining suitability for long -term medication-free status include stable housing and income, adequate psychosocial support, and the absence of legal problems. For patients who have not achieved these indices of stabilization, a longer period of maintenance, during which they work through any barriers that exist, may be appropriate. Data suggest that longer duration of medication treatment is associated with less illicit drug use and fewer complications.

 References:  (1) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction (TIP 40) Chapter 4
                       (2)  Practical Considerations For The Clinical Use of Buprenorphine  Hendree' E. Jones -Science Practice Perspectives August 2004

Compiled And Edited By: Deborah Shrira  
Updated: 5 April 2007