As with Mr. B, a patient who abstains from 1 substance might start abusing another. This “replacement” is part of an “addiction interaction” theory that recognizes multiple substance and/or behavioral addictions in a patient.4 “Replacement” addiction indicates that substance abuse therapy is not adequately addressing some issues.
Coordinating concurrent depression and substance abuse treatment is critical. Although Mr. B’s ongoing psychosocial stress was addressed to varying degrees, endogenous opioid system derangements and/or prolonged opioid withdrawal may have been missed.
TREATMENT: Medication change
We discontinue methylphenidate because it is causing anxiety while leaving Mr. B’s depression unabated. Also, methylphenidate can be addictive.
Over several weeks, we titrate venlafaxine to 300 mg/d and continue mirtazapine, 30 mg at bedtime. We start weekly individual psychotherapy and encourage Mr. B to regularly attend Alcoholics Anonymous (AA) meetings, which he had been attending intermittently for years.
After 1 month, Mr. B’s depression improves marginally, but his depressed mood, anergia, and flat affect persist. He has not relapsed into alcohol or benzodiazepine dependence but reports occasional cravings for opioids and longs for the profound antidepressant effect they once gave him.
The authors’ observations
Sublingual buprenorphine is not FDA-approved to treat depression, although several small studies have described its antidepressant efficacy.5-7 How exogenous opioids reduce depressive symptoms is unknown, although some researchers believe that endogenous opioids:
- work with the mesolimbic dopaminergic system to mediate pleasure and reward
- modulate the mesolimbic system
- or have the same attenuating effect on both psychic and physical pain.
Poll
The endogenous opioid system includes several classes of opioid peptides and receptors, including mu and kappa receptors.8 Mu receptors mediate opioid effects such as euphoria, respiratory depression, miosis, constipation, and physical withdrawal. Because buprenorphine is a partial mu agonist, it has no additional opioid effect beyond the patient’s maximum tolerable dosage.9 Buprenorphine thus has a lower abuse potential, causes less severe physical withdrawal, and is much safer in overdose than the full mu receptor agonists heroin or methadone.9,10Buprenorphine also is a kappa receptor antagonist, which might explain its antidepressant efficacy.11 Whereas full mu agonism mediates euphoria, kappa receptor agonism results in dysphoria. By contrast, kappa receptor antagonism might cause a more stable, noneuphoric antidepressant effect.
Based on Mr. B’s clinical status, we ask him to consider sublingual buprenorphine/naloxone to treat depression and prevent relapse to opioid addiction.
The authors’ observations
Mr. B’s opioid addiction history and type of depression support buprenorphine augmentation. Whereas switching antidepressants or starting ECT would address only his persistent depression, buprenorphine also would target his opioid craving.
Numerous conventional psychotropics have not alleviated Mr. B’s depression, and changing antidepressants might nullify his small gains over the past month. We might consider ECT if buprenorphine does not reduce his depression.
Doctors need to obtain a waiver from the Drug Enforcement Administration (DEA) before using buprenorphine to treat opioid dependence—its approved indication (Box 1). This waiver is not necessary for off-label buprenorphine use. We needed the DEA waiver for Mr. B because we were using buprenorphine to treat opioid relapse prevention as well as depression. To prescribe buprenorphine without a DEA waiver, document that you are using the drug only for the off-label purpose.
How to obtain a DEA waiver for outpatient buprenorphine use
The Drug Enforcement Administration (DEA) requires physicians to obtain a waiver to use buprenorphine to treat opioid dependence in outpatients. This waiver exempts outpatient practitioners from the DEA requirement that only specially licensed opioid treatment programs—such as methadone clinics—can dispense opioid medications.
To obtain the waiver, a physician must:
- show competency to use buprenorphine—usually by completing an 8-hour training course
- certify that he/she can conveniently refer patients for psychosocial treatment.
To receive DEA-approved buprenorphine training, in person or online, contact:
- American Society of Addiction Medicine. (888) 362-6784, www.asam.org/BuprenorphineCME.html
- American Academy of Addiction Psychiatry. (401) 524-3076, www.aaap.org/buprenorphine/buprenorphine.htm
- American Psychiatric Association. (703) 907-7300, www.psych.org/edu/bup_training.cfm
- American Osteopathic Academy of Addiction Medicine. (800) 621-1773, ext. 8163, www.aoaam.org.
For information on obtaining the waiver, visit www.buprenorphine.samhsa.gov.
Buprenorphine risks
Overdose. Buprenorphine can be abused by grinding and dissolving tablets, then injecting them intravenously. Doing this while under the influence of benzodiazepines or other sedatives can cause respiratory depression, leading to coma or death.
Combination buprenorphine/naloxone carries a much lower risk of IV overdose than buprenorphine alone because naloxone blocks mu opioid receptors. This formulation was created specifically to prevent buprenorphine misuse. Because naloxone is metabolized hepatically, it is not pharmacologically active when taken orally and will not block buprenorphine’s effect when buprenorphine/naloxone is taken as prescribed.
Physical dependence and withdrawal. Long-term buprenorphine use can cause physical dependence. Abrupt discontinuation or excessively high doses can precipitate withdrawal. How withdrawal is precipitated is unclear, although some believe the drug displaces itself from mu receptors when doses are too high. Myalgia, headache, abdominal discomfort, rhinorrhea, anxiety, and irritability are common buprenorphine withdrawal symptoms. The dosage at which the drug precipitates withdrawal varies with each patient’s tolerance for opioids.