• Physiological adaptation to the effects of the opioid
• Progressive desensitization to the opioid
• Changes in the central nervous system
• Development of specific symptoms upon discontinuation of the opioid

According to the DSM-IV, the hallmark of drug dependence is continued use "despite [the patient's] knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance."¹

The standard of "continued use despite harm" is important because patients may become tolerant or even physically dependent on opioids without its being cause for concern.^1-3 In fact, most patients who are appropriately using opioids to treat a chronic condition report improvements to their overall quality of life, regardless of how their bodies may have adapted to the continued opioid use over time.⁴

For information on the DSM-IV criteria for dependence, see How do physicians diagnose opioid dependence?

The fact that some individuals may initially choose to misuse opioids does not negate dependence being classified as a disease—voluntary choices contribute to the onset or severity of a number of chronic diseases, including hypertension, coronary heart disease, and diabetes.⁷ Furthermore, while the initial choice to use opioids may have been voluntary, once opioid dependence develops, use is compulsive—not voluntary.⁷

Chronic opioid use is a precursor to the brain changes characteristic of opioid dependence, but it is only one of the etiologic factors in the development of the disease.^3,6 Chronic opioid use alone does not cause opioid dependence.

Mu receptors in the brain adapt to chronic opioid use by becoming opioid tolerant. Tolerance (and withdrawal symptoms upon opioid discontinuation) signifies that a patient is physically dependent on opioids.⁶

The neurological changes that produce opioid tolerance/physical dependence are well understood. Furthermore, these changes appear to correct themselves within a period of weeks after opioid use has ceased.⁶

By contrast, the neurological changes that produce opioid dependence are wider-ranging, more complex, and less well understood.⁶ These changes cause heightened opioid cravings, independent of any withdrawal symptoms, and lead to compulsive drug-seeking and drug-taking behavior.⁸

Instead of reversing themselves, the alterations that cause opioid dependence can persist for months and even years after drug use has ceased.⁹

For these reasons, opioid dependence is viewed as a chronic brain disease, similar to Alzheimer's disease or schizophrenia. However, the behavioral component of this condition is not memory loss or unusual mood changes, but a compulsion to use opioids.⁵

Now, for the first time in almost 30 years, qualified physicians have the legal right to use opioids to treat opioid dependence in an office setting.

Presently, fewer than 25% of opioid-dependent individuals in the United States receive any type of care for their condition.² This situation is attributed in part to the stigma and inconvenience that have come to be associated with methadone and methadone clinics (regardless of their numerous successes).²

The significance of office-based treatment lies in its potential to enhance both treatment privacy and overall access to care in this undertreated population.

The prospect of a more confidential treatment option is expected to encourage many opioid-dependent patients to finally seek medical attention.

According to DATA 2000, SUBOXONE and SUBUTEX are handled just like other Schedule III medications dispensed by your pharmacy.

• Because a special waiver is required to prescribe buprenorphine for office-based treatment of opioid dependence, your pharmacy will need to verify that the prescribing physician is DATA 2000 certified (verifying DATA 2000 waivers)
• Physicians must write their "X" DEA number on all SUBOXONE and SUBUTEX prescriptions to treat opioid dependence.

As a pharmacist, the scope of your contribution—covering everything from the general (eg, stocking buprenorphine) to the individual (eg, counseling patients about possible side effects)—allows you the opportunity to reinforce both patients' and physicians' efforts.

Areas where your involvement helps support the success of office-based treatment in your community may include:

• Learning about opioid dependence and its treatment
• Helping opioid-dependent patients to feel at ease
• Counseling patients about potential side effects and drug-drug interactions
• Advising patients on the safe and appropriate use of their medications
• Ordering buprenorphine and keeping it in stock
• Protecting patient confidentiality
• Verifying that physicians are certified to prescribe buprenorphine
• Referring patients with opioid dependence to physicians certified to prescribe buprenorphine
• Maintaining appropriate records

You may be interested to read some of the more recent demographic and trend data for this patient population.

More on the pharmacist's role is available under How can I contribute to patients' success with buprenorphine?

The stigma that surrounds treatment for substance abuse in general—and opioid dependence in particular—has a significant effect on patient behavior. Fear of being exposed as opioid dependent compels many patients to conceal their treatment; others are too ashamed even to seek treatment.

With office-based treatment, there is nothing to distinguish opioid-dependent patients from those being seen for more everyday afflictions. The prospect of a more confidential treatment option is expected to encourage many untreated patients to finally pursue medical attention for their opioid dependence.

Office-based treatment is also designed to make treatment more easily available, and so widen patients' access to opioid-dependence care.

By giving physicians the legal right to treat opioid dependence in an office setting, DATA 2000 not only decentralized pharmacologic care of this condition, it also created an opportunity to enhance treatment confidentiality, thereby potentially attracting new patients to be treated for the first time.

• Complete an approved 8-hour CME course
• Notify the government of their intent to use buprenorphine for treatment of opioid-dependent patients.

In addition, physicians must meet BOTH of the following criteria:

• Have the capacity to provide or to refer patients for necessary ancillary services, such as psychosocial therapy
• Agree to treat no more than 30 patients at any one time in their individual or group practice

Under DATA 2000, some physicians are exempt from the 8-hour CME requirement on the basis of their specialty or other professional experience, but the other conditions listed above still apply.

Physicians interested in becoming certified to prescribe buprenorphine are encouraged to visit buprenorphine.samhsa.gov, OpioidDependence.com, or DocOptIn.com.

See the full text of DATA 2000 for more information about certification requirements.

There are a number of ways to verify that a physician has a valid waiver for prescribing buprenorphine:

• Check that the physicians' DEA number begins with an "X"
• Check the Substance Abuse and Mental Health Services (SAMHSA) Physician Locator. This website lists the physicians in each state that have DATA 2000 waivers
• Physicians can elect not to be included in this list
• Call SAMHSA at (866) 287-2728 ((866) BUP-CSAT) to verify that a physician has a valid DATA 2000 waiver
• Call the physician directly and ask to have his/her DEA registration certificate faxed to you

When verifying a physician's waiver, it is a violation of federal regulations to disclose the name of the patient for whom the buprenorphine prescription was written—even if you are speaking with people who already know the patient is being treated for opioid dependence (eg, the prescribing physician). This subject is addressed in more detail below.

For this reason, federal regulations protect the privacy of patients' medical information, namely Title 42 Part 2 of the Code of Federal Regulations (42 CFR Part 2) and the Health Insurance Portability and Accountability Act (HIPAA).

As a pharmacist, you are most likely already well acquainted with HIPAA as well as HIPAA compliant.

You may not be as familiar with 42 CFR Part 2. In short, this regulation states that patient-identifying information pertaining to treatment for substance abuse be handled with a greater degree of confidentiality than patients' general medical information.

Under 42 CFR Part 2, before a physician can disclose any information to a third party about a patient's treatment for substance abuse, that physician must first obtain the patient's signed consent.

Consequently, if a physician were to call in a patient's SUBOXONE prescription without first receiving the patient's signed consent to do so, that physician would be in violation of 42 CFR Part 2.

When a physician directly transmits a SUBOXONE prescription to your pharmacy, any redisclosure of that patient-identifying information by the pharmacy is prohibited without the patient's signed consent.²

According to 42 CFR Part 2, the following elements are required for a consent for to be considered valid:

• Patient's name, physician's name, pharmacist's name
• Purpose of the disclosure; recipient of the disclosure
• What information will be released
• An indication that the patient understands s/he can revoke this consent at any time and that this revocation can be verbal
• The date and terms under which the consent expires
• Patient's dated signature

For more information, visit hipaa.samhsa.gov.

• Tolerance (defined as a need for substantially greater amounts of an opioid to achieve the desired effect or a substantially reduced effect with continued use of the same amount of the opioid)
• Withdrawal (which, for opioid dependence, is characterized by certain symptoms that appear when heavy or prolonged use of the opioid ceases or when an opioid antagonist is taken after a period of opioid use)
• Frequent use of larger amounts of the opioid than planned or use of it over a longer period than planned
• Persistent desire to cut down or control use of the opioid or trying unsuccessfully to do so
• Devotion of a great deal of time toward obtaining the opioid, using it, or recovering from its effects
• Surrendering of or reduction of important social, occupational, or recreational activities because of opioid use
• Continued use of the opioid despite knowing that one has a persistent or recurrent physical or psychological problem probably caused or made worse by the opioid

Naloxone is an opioid antagonist that is included to help deter diversion and misuse. When the buprenorphine/naloxone tablet is taken sublingually as prescribed, the naloxone is not absorbed into the bloodstream sufficiently to have any effect. However, if the tablet is crushed and injected by someone who either has recently used or is dependent on a full opioid agonist (eg, morphine, methadone, or heroin), the naloxone will cause that person to experience opioid withdrawal symptoms.

One of the most valuable functions that you provide is counseling patients.

• Understand the importance of maintaining patient confidentiality
• Special federal regulations apply to the confidentiality of personally identifying information pertaining to substance abuse treatment (42 CFR Part 2) and the privacy of health records (HIPAA)
• Enhance patient confidentiality by providing a private area for patient counseling
• Counsel patients on the appropriate sublingual dosing instructions for buprenorphine (see Dosing Instructions Tear Pad)
• Take into consideration that:
• Patients may be experiencing uncomfortable symptoms
• An accepting, positive attitude on your part is critically important to patients

• Order buprenorphine through a pharmaceutical wholesaler.
• Follow the federal and state requirements that you use for stocking and dispensing other Schedule III medications. Pharmacists and pharmacies are not required to have any special credentials for dispensing buprenorphine above or beyond those required for other Schedule III medications.
• Provide the names of physicians qualified to prescribe buprenorphine to customers who inquire about buprenorphine treatment and to physicians whose practices serve people who may have developed opioid dependence. Qualified physicians can be found through:
• Suboxone.com
• buprenorphine.samhsa.gov
• As with many prescription opioid medications that you dispense, take steps to avoid diversion by:
• Maintaining open communication with physicians who prescribe buprenorphine
• Being alert to patients presenting simultaneous prescriptions for buprenorphine or other opioids from more than one physician
• Bearing in mind that the DATA 2000 allows each physician or group practice to treat no more than 30 patients with buprenorphine at one time, and contacting the physician or group for verification should you receive a large number of prescriptions from any of these sources

The FDA buprenorphine pages feature information for pharmacists, physicians, and patients, questions and answers about SUBOXONE and SUBUTEX, and a range of other information.

Detailed information about DATA 2000 and the physician waiver process can be found at buprenorphine.samhsa.gov or by contacting SAMHSA directly:

SAMHSA Buprenorphine Information Center
Phone: (866) 287-2728 ((866) BUP-CSAT)
E-mail: info@buprenorphine.samhsa.gov