What a Prescriber Should Know Before Writing the First Prescription

What a Prescriber Should Know Before Writing the First Prescription

by Howard A. Heit, MD, FACP, FASAM

& Douglas L. Gourlay, MD, MSc, FRCPC, FASAM

Expert authors received compensation from Janssen Pharmaceuticals, Inc. for their contributions to PrescribeResponsibly.com
The Importance of Definitions

Knowing the precise definitions that are listed in Table 1 will allow healthcare professionals to improve their understanding of the interface of pain and addiction and their clinical practice.19 Confusion between physical dependence and addiction may contribute to the undertreatment of chronic pain.19

Physical dependence and addiction can coincide, but physical dependence is neither necessary nor sufficient to make a diagnosis of addiction.20 Physical dependence is an expected, neuropharmacological adaptation that occurs as a result of chronic exposure to an agonist class of drug.21 Addiction is a much more complex biobehavioral phenomenon.19

Physical dependence is a natural, expected neuroadaptive response that can occur with opioids, alcohol, benzodiazepines, corticosteroids, antidepressants, diabetic agents, cardiac medications, and many other medications used in clinical medicine. Abrupt cessation of these medications can produce a withdrawal syndrome that can include, but is not limited to, nausea, vomiting, diaphoresis, diarrhea, abdominal cramps, seizures, anhedonia, dysphoria, and in some cases, death.20

Tolerance is also a natural, expected physiologic response that can occur with exposure to certain classes of drugs, especially alcohol and opioids. The key to this definition is that all other factors remain stable so that only the physiologic response to the drug can be evaluated.19 In fact, tolerance is neither good nor bad. It occurs at different rates, to different effects in different patients, over time. So while there is relatively rapid tolerance to the cognitive blunting effects of the opioid class of drug, tolerance to the constipating effects of opioids rarely occurs.21

Concurrent diagnoses such as addiction or pseudoaddiction can be confirmed only by careful evaluation and rational pharmacotherapeutic management of the pain. While a diagnosis of addiction is made prospectively over time, a diagnosis of pseudoaddiction is usually made retrospectively. When reasonable limits and boundaries are placed on a patient, and yet he or she continues to step out of bounds, addiction or pseudoaddiction should be considered.20

Healthcare professionals with improved understanding of the definitions on the basic scientific and clinical levels will be better able to evaluate and treat patients with chronic pain, with or without the disease of addiction.

Disease of Addiction

The healthcare professional must recognize addiction as a treatable, albeit irreversible, brain disease — that is, a distinct medical condition that may or may not be associated with the patient’s pain syndrome.20 One can treat acute pain in the face of an active addiction; however, the treatment of chronic pain in a patient with an active addiction seldom is successful. The patient must be willing to work a program for both diagnoses. The pain specialist must have a rudimentary knowledge of addiction medicine, and the addiction specialist must understand the basics of pain management.

Drugs of misuse act at local cellular and membrane sites that are within a neurochemical system called the reward and withdrawal pathway.22 This pathway is in the mesolimbic dopamine system of the primitive brain, and addiction causes a disruption of this pathway. This disruption is mediated via receptor sites and neurotransmitters. Central to this reward and withdrawal pathway is the neurotransmitter dopamine, which has been shown to be relevant not only to drug reward, but to food, drink, sex, and social reward.23

One of the most common reasons for relapse of patients with addiction is stress.22 It stands to reason that if a patient with chronic pain is in recovery from drug or alcohol use, and his or her pain is inadequately treated, the patient may turn to licit or illicit drugs and/or alcohol to anesthetize the pain.

Opioid Agreements

Informed consent is part of an initial evaluation. Healthcare professionals must discuss with, and answer any questions about, the proposed treatment plan, including anticipated benefits and foreseeable risks. Written opioid agreements (OA) facilitate the documentation of informed consent, patient education, and compliance in the management of chronic pain.24

A well-written agreement establishes the responsibilities of a healthcare professional to the patient and vice versa. It outlines the treatment plan and documents informed consent. The OA establishes boundaries and consequences for drug misuse or diversion. Noncompliance with the agreement can aid in the diagnosis of the disease of addiction or substance misuse, which would often require a change in the treatment plan. Table 2 delineates the salient points of an OA.25

The agreement, whether written and signed or informal, must be part of an environment of care that emphasizes honest and open communication. A practice policy for all patients prescribed opioids to sign a medication management agreement is often a simple and effective way to approach this often uncomfortable issue. The agreement should be reasonable, readable, and flexible.25


Before writing the first prescription, the healthcare professional should know the basic definitions and principles common to pain and addiction medicine and establish the boundaries through an opioid agreement.20,26 Risk can never be eliminated, but it can usually be managed. By approaching these patients within a biopsychosocial framework, the healthcare professional can give the patient the best quality of life possible, given the reality of his or her clinical situation.

TABLE 1: Definitions

1. Aberrant behavior is when the patient steps outside the boundaries of the agreed upon treatment plan, which is established as early as possible in the healthcare professional-patient relationship.20
2. Abuse is any use of an illicit drug with the intentional self-administration of a medication for nonmedical purpose such as altering one's state of consciousness (eg, getting high). A licit substance such as alcohol also can be abused.27
3. Addiction is a primary, chronic, neurobiologic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. Addiction is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm and craving.21
4. Diversion is the intentional removal of a medication from legitimate distribution and dispensing channels for illicit sale or distribution.27
5. Iatrogenic addiction occurs when a patient with a personal or family history of alcohol, drug addiction, or abuse is appropriately prescribed a controlled substance and subsequently in the therapeutic course, meets the diagnostic criteria for addiction to that substance.25
6. Misuse is use of a medication (for a medical purpose) other than as directed or as indicated, whether willful or unintentional, and whether harm results or not.27
7. Physical dependence is a state of adaptation that is manifested by a drug-class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.21
8. Pseudoaddiction is a syndrome that causes patients to seek additional medications due to inadequate pharmacotherapy being prescribed. Typically when the pain is treated appropriately, the inappropriate behavior ceases.25
9. Pseudotolerance is the need to increase medication such as opioids for pain when other factor(s) are present such as disease progression, new disease, increased physical activity, lack of compliance, change in medication, drug interaction, addiction, and/or deviant behavior.25
10. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time.21

TABLE 2: Treatment Agreement for Opioid Analgesic Maintenance Therapy for Noncancer/Cancer Pain25

  • Goals of therapy
  • Single prescriber, if possible
  • Informed consent on all opioid analgesic risks
  • Definition of addiction, tolerance, and physical dependence
  • Need for patient disclosure of substance abuse history; psychiatric history including history of sexual, physical, or verbal abuse; and medications currently prescribed
  • Need for complete, honest self-report of pain relief, side effects, and function at each medical visit
  • Establishment of regular medical visits
  • Requirement for prescription renewal only during regular office hours
  • Conditions of noncompliance (eg, evidence of drug hoarding or use of any illegal drug may cause termination of the healthcare professional–patient relationship)
  • Use of the word may instead of will in the agreement, so clinical judgment can be used in each situation
  • Patient consent to random urine drug tests and pill counts
  • Permission for the practice to contact appropriate sources to obtain or provide information about the patient's care or actions
  • Recovery program for substance misuse or addiction (patients must agree to concurrent assessment and treatment of their substance use disorder)

References Used in the Section:

  • 19 Heit, HA. Addiction, Physical Dependence, and Tolerance. Journal of Pain & Palliative Care Pharmacotherapy. 2003; 17(1):15-29.
  • 20 Gourlay, D. and H. Heit, Pain and Addiction: managing risk through comprehensive care. Journal of Addictive Diseases. 2008; 27(3):8.
  • 21 Definitions Related to the Use of Opioids for the Treatment of Pain. American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine. 2001.
  • 22 Koob GF, Moal ML. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001; 24(2):97-129.
  • 23 Nestler EJ. Molecular basis of long-term plasticity underlying addiction. Nature Reviews Neuroscience. 2001; 2(2):119-28.
  • 24 Fishman SM, Bandman TB, Edwards A, et al. The Opioid Contract in the Management of Chronic Pain. The Journal of Pain and Symptom Management. 1999; 18(1):27-37.
  • 25 Heit HA, Lipman AG. Pain: Substance Abuse Issues in the Treatment of Pain. In RJ Moore (ed). Pain: A Biobehavioral Approach to Pain. New York: Springer, 2007; 363-380.
  • 26 Gourlay D, Heit H, Almarhezi A. Universal Precautions in Pain Medicine: A rational approach to the management of chronic pain. Pain Medicine. 2005; 6(2):107–112.
  • 27 Katz NP, Adams EH, Chilcoat H, et al. Challenges in the Development of Prescription Opioid Abuse-deterrent Formulations. Clin J Pain. 2007; 23(8):648-660.