Prescription opioids can be prescribed by doctors to treat moderate to severe pain following surgery or injury, or for malignant conditions such as cancer.

In recent years, there has a been a tremendous increase in the reception and use of prescription opioids for the treatment of chronic, non-cancer pain (CNCP), such as pain seen in rheumatological diseases and back pain, despite the serious risks and unproven long-term effectiveness. For most patients, opioids are relatively safe and effective when used as prescribed by a medical professional for a short period. However, chronic opioid use can lead to opioid dependence and/or addiction and overdose. To reduce this risk, it is important for healthcare providers to avoid transitioning patients from using opioids for acute pain management to a more long-term use for chronic pain.

Controlled substance agreements (CSAs) are designed to encourage strict adherence and alleviate risk associated with opioid prescribing.

It is a well-established fact in the medical community that patients on chronic opioid use often have significantly more health care visits. But new research published in Mayo Clinic Proceedings shows that adhering to a standardized care process model for opioid prescriptions appears to reduce the overall number of health care visits for these patients while maintaining safety.

Researchers believe the controlled substance agreement (CSA) offers patients on opioid therapy a structure and reduces the likelihood that these patients seek medical attention to further manage or diagnose their pain.

Such agreements include patient psychological screening, pain monitoring, refill documentation, evaluation of opioid use through prescription monitoring programs and urine drug testing. The agreement also includes;

  • Guidance on having one care team handle opioid prescriptions
  • Guidelines for safe medication storage
  • Dose adjustment without contacting the prescribing provider.
  • The requirement for urine drug testing
  • Expectations for follow up appointments

Researchers found that patients who signed up for an opioid controlled substance agreement appeared to have a significant drop in primary care visits while the use of emergency department services remains unchanged. But the researched observed that radiology visits increased during the observation period. The agreement was associated with decreased hospital admissions, and primary care and specialty visits among patients diagnosed with chronic health conditions. The agreement also played a significant role in the number of healthcare visits based on age, among other patient factors.

Dr Jon Ebbert, M.D., a Mayo Clinic primary care physician believes patients on long-term opioid therapy often needs more medical attention. These standardized opioid plans are contained in a detailed approach for managing health care utilization, at the same time providing patients with consistent and reliable access to pain management strategies. Dr. Ebbert is a researcher in the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.

“Once patients are on a controlled substance agreement, substituting phone calls or secure messaging for office visits could improve efficiency and quality of care for some of our patients,” Dr Ebbert adds

For the study, 772 patients from Mayo Clinic enrolled in a controlled substance agreement from 1st July to 31st December 2015. The researchers then used billing data to compare patients’ visits for one year before and after the agreement to evaluate how many patients had increased or decreased health care visits.

As part of the ongoing research, the team hopes to learn if guidelines for the treatment of chronic pain are associated with the reduced opioid use

The study’s lead author is Lindsey Philpot, Ph.D., an epidemiologist in the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.

This research was made possible by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery and the Mayo Clinic College of Medicine and Science.

Mayo Clinic is a non-profit organization committed to clinical practice, education, and research, providing expert, comprehensive care to everyone who needs healing.




Guideline for Prescribing Opioids for Chronic Pain

The centre for disease control (CDC) developed and published guidelines for prescribing opioids for patients with chronic pain. The guidelines were developed with the aim of ensuring patients have access to safer, more effective chronic pain treatment while reducing the risks associated with chronic opioid use, including opioid use disorder and overdose and death. The Guideline is not applicable to patients going through any active cancer treatment, palliative care, or end-of-life care. The guidelines were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation.

In summary, the guidelines are as follow

  • Opioids should never be the first-line or routine therapy for chronic pain. It should only be considered if expected benefits outweigh possible risks to the patient
  • Clinicians should establish realistic treatment goals with all patients.
  • Before initiating and during therapy, clinicians should discuss benefits and risks and availability of nonopioid therapies with the patient.
  • Clinicians should prescribe immediate-release opioids instead of extended-release/long-acting.
  • Clinicians should start with the lowest effective dosage.
  • When opioids are used for acute pain, clinicians should prescribe less dosage needed for the expected duration of pain.
  • Clinicians should follow-up patients within 1 to 4 weeks of initiating opioid therapy to evaluate the benefits and risk.
  • Clinicians should review the patient’s history of controlled substance prescriptions using a state prescription drug monitoring program.
  • Clinicians should use urine drug testing to detect any undisclosed substances or prescribed opioids.
  • Clinicians should avoid prescribing opioid and benzodiazepines together.
  • Clinicians should offer or arrange for patients with opioid use disorder.





Hasegawa, K., Brown, D., Tsugawa, Y., & Camargo, C. (2014). Epidemiology of Emergency Department Visits for Opioid Overdose: A Population-Based Study. Mayo Clinic Proceedings89(4), 462-471. doi: 10.1016/j.mayocp.2013.12.008

Philpot, L., Ramar, P., Elrashidi, M., Mwangi, R., North, F., & Ebbert, J. (2017). Controlled Substance Agreements for Opioids in a Primary Care Practice. Journal Of Pharmaceutical Policy And Practice10(1). doi: 10.1186/s40545-017-0119-5

Philpot, L., Ramar, P., Elrashidi, M., Sinclair, T., & Ebbert, J. (2018). A Before and After Analysis of Health Care Utilization by Patients Enrolled in Opioid Controlled Substance Agreements for Chronic Noncancer Pain. Mayo Clinic Proceedings. doi: 10.1016/j.mayocp.2018.05.008