First-Time Opioid Therapy: An Interactive Case History 2023

In this series of analyses, we have broken down the various aspects of the newly released revisions to the CDC Clinical Practice Guideline for Prescribing Opioids for Pain to help clinicians, patients, and caretakers alike understand their nuances and to provide expert review of their applicability, potential benefits, and potential concerns. Herein, we apply the guidelines to a patient case around initiating an opioid in a patient with chronic pain.

Joanna is a 78-year-old female patient who presents to the interdisciplinary pain clinic for an initial visit. Her primary complaint is chronic neck pain since around 2006 without initial injury or precipitating event, and s/p two reported neck surgeries in 2008 and 2010 (no notes confirming these surgeries). The patient denied pain ever improving after either surgery, just noticing that it felt different afterward. She reported that over the past few years her pain has been worsening.

She describes the pain as revolving around her neck with specific pain in the cervical spine, as well as radiating features from the central spine. She noted that it constantly feels aching, tight, and cramping, though when it flares up can feel like a “knot.” She noted that during these maximum pain days, the pain travels up her head causing severe headaches. The patient denied any radiating features to her pain traveling down either arm.

Joanna reports that she is able to maintain a good level of functionality though sometimes her motivation seems to be lacking, which is almost always directly correlated with mood, and as of late this has been seemingly worse. She reported trying to do stretches, but has trouble remembering to do them every day, and noted that stretching/PT helps significantly, though insurance only covers three months at a time. She has noticed that times and periods when she reduces activity/stops exercising pain significantly increases, which triggers her flare ups. One area of concern is that she occasionally skips social activities due to her pain.

Imaging

X-ray of cervical spine from November 2022 showed multilevel severe spondylosis and degenerative disease.

MRI of cervical spine from March 9, 2015, showed endplate osteophytosis at C5-6 and slight mass effect on cord with mild bilateral neuroforaminal narrowing, and mild neuroforaminal stenosis at C6-7 mostly from facet outgrowth.

HTN, sleep apnea, major depressive disorder, chronic kidney disease stage IV, valvular heart disease on chronic warfarin, asthma (mild), vertigo.

Current Medications

1. bupropion 300 mg PO once daily (depression)
2. desvenlafaxine 200 mg PO once daily (pain and depression)
3. warfarin 3mg PO once daily (dose controlled by warfarin clinic; for chronic anticoagulation for valvular heart disease)
4. lisinopril 20 mg PO once daily (hypertension)
5. furosemide 20 mg PO once daily (hypertension and to control peripheral edema)
6. omeprazole 10 mg PO once daily (GERD)

Prior utilized medications included baclofen, methocarbamol, tizanidine, duloxetine, and gabapentin.

Non-Pharmacologic Modalities Trialed

Joanna reports trying these alternative therapies as well:

• Heat: continues to give good relief, can help when having cramping/spasm attack, using once daily
• Ice: no significant benefit noticed
• TENS: uses occasionally, allows for some benefit; sometimes forgets to use it
• Physical therapy: tries to go when her insurance allows her, though they only cover up to 3 months at a time; seems to get good benefit when she does engage
• Massage therapy: used to go once a month, cannot go anymore because too expensive, was helpful
• Acupuncture: interested but understands can be expensive
• Chiropractic: never found benefit in past
• Pain interventions: reported having multiple injections and ablations in the past; never noticed huge benefit; last seen and followed by an interventionist 6 months ago; deemed not a candidate for spinal cord stimulator trial
• Spinal surgery: most recent evaluation in January 2016, denied anything could be done, per patient

• Depression: Patient reported extensive history of major depressive disorder, and reported that she had been relatively stable as of late on current regimen and continued close monitoring with psychiatry and psychotherapy. While she acknowledges pain has certainly made her mood worse overall, she feels control over the depression with her current medications and working with therapy.
• Sleep: denied any sleeping problems
• Tobacco use: denied
• Alcohol use: denied
• Substance use: denied

Joanna’s situation is a relatively common case seen not only in pain management clinics but also across the spectrum of primary care, as individuals with complex medical histories and limited potential options may find themselves in difficult situations trying to transition when their prior provider leaves the clinic (retirement or otherwise).

The 2022 CDC opioid prescribing guidelines help explain how to identify if patients who have not yet been exposed to chronic opioid therapy could be candidates for therapy, how to specifically initiate therapy, and how to manage patients on opioid therapy.¹

Q: Is the patient a candidate for opioids?

Assessment

The first recommendation for establishing whether someone is a candidate for opioids is to conduct a thorough assessment including history, functionality, past medical history (PMH), imaging/testing, prior modalities (non-pharmacologic and pharmacologic) trialed, current modalities being used, mood/behavioral health. These, among others, are not only recommended by the CDC when assessing any person presenting with chronic pain (especially patients on chronic opioids)¹ but also by several pain-related guidelines.²⁻⁴ Thorough evaluations help to identify what pain pathology is underlying as well as how the patient is doing on a subjective basis and in terms of daily functionality.

Patient Input

The next part of the assessment is to clarify the patient’s goals of care, including desired functionality, and quality of life. All of this should be discussed regardless of the use of opioids.

The description of her pain is also vastly important, as that may help dictate our approach to treatment, as she is having significant spinal pain itself and spasticity.

Q: What modalities outside of opioids could be considered?

While the 2022 CDC chronic opioid prescribing guideline clarifies that not every single non-opioid modality is required to be trialed before opioids can be used, the agency does make clear that the overwhelming evidence suggests a multimodal approach to achieve better pain and functionality outcomes.¹ Further, it is noted that opioids should not be used as a first-line treatment approach in the majority of patients living with chronic pain (which is agreed with and supported by past guidelines/evidence).¹

Physical Therapy

Regarding non-pharmacologic modalities for patient Joanna, perhaps the most important to consider optimizing would be physical therapy/physical activity. Joanna acknowledged significant benefit with regard to PT in the past, however because it is very common for insurance providers to cover 3-month stints (even for chronic pain), it seems PT could not be a sustaining option. It may be important to strategize with Joanna on ways to stretch and strengthen at home or in local gyms and pools (at least until another stint of PT is covered by insurance).

While working with spinal specialists/interventionists to assess for different types of interventional procedures could be beneficial, it did sound like the patient has exhausted several of those options already and affordability specialists could become a concern. Our medical group has a sports medicine team that works on physical medicine and rehabilitation (PM&R), which could be a great option for Joanna, especially given the musculoskeletal features of pain. Other pain-related specialists, such as rheumatologists and neurologists, would likely offer little benefit in this case because of the pathology and symptomology of her pain.

Regarding non-opioid pharmacologic modalities for Joanna, unfortunately, we appear to be much more limited. Due to her significant PMH (older age, CAD, chronic anticoagulant use, and CKD status), oral NSAIDs should be avoided, as they directly increase gastrointestinal bleeding risk when combined with anticoagulants,⁵⁻¹¹ risk of cardiovascular events (class effect),¹² and progression of chronic kidney disease.¹²⁻¹⁴ Acetaminophen at low doses (daily dose below 3000 mg) would be relatively safe for the patient to trial.

Further, it is agreed that utilization of an antidepressant with serotonergic and noradrenergic activity may not only can help improve depression but may help reduce neuropathic and nociceptive components of pain (via inhibition of descending pain pathways).

However, this patient is already maintained on the SNRI desvenlafaxine with good efficacy from a depression perspective. Other SNRIs such as duloxetine and venlafaxine are cleared by the kidneys, and would be significantly limited regarding dosing,¹⁵⁻¹⁷ while milnacipran is not covered by the patient’s insurance. Tricyclic antidepressants (TCAs) should be avoided in this case considering their risk of use in older patients.¹⁸

While muscle relaxants could be beneficial, Joanna has already trialed and failed baclofen, tizanidine, and methocarbamol. Cyclobenzaprine, a commonly prescribed muscle relaxant, has almost the same exact chemical structure as amitriptyline (a TCA), thus increases risk of falls. Carisoprodol, orphenadrine, and dantrolene also have substantial risks, therefore would be recommended to be avoided for now; though may be beneficial to consider going forward.

One class of medication that could potentially offer some benefit to Joanna could be topical analgesics (especially OTC products). Any products containing low percentages of NSAIDs, including diclofenac or methyl salicylate, could be used in the upper back/neck area to help drive down local inflammation. In general, those products have very low systemic absorption, thus intermittent use would not be expected to increase risk of systemic side effects. Further, products with counterirritants (menthol, capsaicin, etc) and local anesthetics (lidocaine) could be beneficial in this case to modulate peripheral neuronal signaling, which could allow for reduction in certain pain symptoms. Menthol and capsaicin could be particularly of interest, given their ability to modulate the TRP family of receptors on peripheral neurons.¹⁹

The team agrees that a low-dose opioid would be an appropriate therapeutic choice – in addition to low-dose acetaminophen, OTC menthol and methyl salicylate cream, and referral to PM&R.

Q: Prior to initiating opioids, what needs to be discussed with the patient?

Side Effect Risks

There are several opioid-related side effects that should be considered for every patient before starting an opioid (as should be the standard for any medication). These include:

• risk of overdose via respiratory depression
• addiction potential (opioid use disorder, OUD)
• opioid-induced constipation
• nausea/vomiting
• hypogonadal axis suppression
• among others

Importantly, there are some clinically validated scoring tools to evaluate risk level (not always correlated with appropriateness to prescribe). One of the more important risk tools is the Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (RIOSORD) scoring tool, which has been clinically validated and helps calculate an estimated percent probability of an opioid-induced respiratory depression event within the following six months.²⁰˒²¹

The tool accounts for several aspects of a patient’s PMH and concurrent medications. Critically, the tool is not designed to determine whether someone should not receive an opioid in an absolute sense, but to help increase awareness of who may be at greater risk of a respiratory depression event, and thus may require greater respiratory monitoring, more gradual dose implementations, and may benefit from receiving naloxone (now available OTC) to be used in an emergency opioid overdose situation.²⁰⁻²¹

Our patient has a RIOSORD score of 13 points, putting her at a risk class of 4 (out of 7), with an estimated probability of OIRD event at 15%. Therefore, it would be appropriate and safer to offer naloxone to her to be used in case of an emergency overdose event.

Given Joanna’s age, opioid-induced constipation and hypogonadal axis suppression also need to be addressed. For these risks, counseling is the most important step (especially for constipation) to ensure the patient is able to monitor for side effects. In general, to counteract the constipation effects of opioids, use of stool softener with a laxative is enough to keep bowel movements regular. Occasionally, peripherally acting mu-opioid receptor agonists (PAMORAs) are required for more resistant cases of opioid-induced constipation.

There have also been several scoring tools developed to evaluate risk of potential OUD or misuse of opioid analgesics, including:

• Screener and Opioid Assessment for Patients with Pain (SOAPP-r)²²
• Diagnosis, Intractability, Risk, Efficacy tool (DIRE)²³
• Opioid Risk Tool (ORT-r)²⁴

While these tools have been clinically validated and can be advantageous when used to help identify who may benefit from greater monitoring, they should not be used overtly to necessarily justify avoiding opioids in patients.

Drug Monitoring

The final assessments for all patients starting on and continuing opioids include review of prescription drug monitoring programs (PDMPs) and obtaining urine or serum drug screens. PDMPs are state-run electronic databases that help track prescribing and dispensing of all controlled substances. Although their utilization depends on the specific state, they can be helpful in identifying specific controlled substances patients have been prescribed prior to their appointment.

Further, once testing is performed, while this may help clinical decision-making, it is equally important to understand how to communicate results to patients in a non-judgmental and non-biased way. This is especially important if the patient does test positive for an illicit substance or if there are licit substances in the urine (alcohol, etc). Communicating appropriately with patients to assess for potential underlying use disorders is paramount to ensure not only safe medications are used for pain, but also in allowing patients a chance to access help/further treatment if use disorders are identified.

Q: When should we see Joanna next?

Considering Joanna’s age and level of pain, it was recommended to follow up in about 2 to 3 weeks initially for close monitoring, to ensure she is tolerating the hydrocodone well and is responding to it. Certainly, if she is doing well and stable from a pain/functionality perspective, continuation of hydrocodone could be appropriate. We would then refer to guidance around maintenance and continuing opioids (see sample case).