The Centers for Disease Control and Prevention (CDC) does not consider opioids a first-line therapy. CDC opioid prescribing guidelines favor nonopioid therapies for chronic pain outside of active cancer, palliative care and end-of-life care. These include acetaminophen or ibuprofen, physical therapy, exercise and cognitive behavioral therapy.

Clinicians should consider opioids only when the benefits for pain and function outweigh the risks and only after discussing the risks and benefits with the patient. If opioids are used, the CDC advises prescribing immediate-release opioids, rather than long-acting or extended-release opioids, at the lowest effective dose, combined with other therapies.

Providers need to educate every patient taking opioids, or the patient’s guardian, covering the risks, benefits and alternatives to opioids, particularly the risks of tolerance and dependence. Patients between 14 and 55 need to be educated about the risk of controlled substance use during pregnancy, including fetal opioid dependency and neonatal abstinence syndrome.

For acute pain, according to the CDC, clinicians should prescribe no more than is needed for the duration of pain severe enough to require opioids. Three days or fewer is often sufficient; more than seven days is rarely needed, according to the CDC.

The CDC guidelines recommend clinicians reevaluate the benefits and harms with a patient within one to four weeks of starting opioid therapy.

Norton Medical Group opioid guidelines (based on Kentucky and Indiana state medical board guidelines) distinguish between initial and short-term (less than 90 days) and long-term prescribing of controlled substances for pain.

For short-term opioid use, Norton Medical Group guidelines prohibit the use of controlled-release opioids such as OxyContin, fentanyl patches or methadone for acute pain that is not directly related to, or in close time to, a specific surgery or major trauma.

If a patient is experiencing breakthrough pain, the provider should identify the trigger or triggers for each episode and determine whether the pain can be controlled with nonopioid medications. If not, the provider can add an “as-needed” controlled substance to the regimen.

For long-term use (prescribing medication more than 90 days), providers need a detailed medical history, physical exam, working diagnosis, treatment plan, urine drug screen and written consent to treat. They also need to review Kentucky All Schedule Prescription Electronic Reporting (KASPER)/Indiana Scheduled Prescription Electronic Collection & Tracking Program (INSPECT) reports and provide patient education. Initially, a patient needs to be seen every month until medication doses are stabilized and thereafter once in four months or on a schedule determined by the provider’s professional judgment.

State standards for opioid prescribing

Kentucky requires electronic prescribing for all controlled substances. Under Kentucky standards, providers should not prescribe more than a three-day supply for acute conditions unless the provider determines it is medically necessary. Exceptions to this standard are allowed for chronic pain, hospice or end-of-life care, pain following a major surgery or significant trauma, or as part of a narcotics treatment program.

Indiana standards call for an initial prescription of no more than seven days, with the same exceptions as Kentucky. If prescribing for a longer time, the rationale must be documented in the patient’s chart.

Dangers of high doses

Clinicians should carefully reassess evidence of risks and benefits when considering increasing dosage to a 50 morphine equivalent daily dose (MEDD) per day or higher. For patients with a MEDD greater than 50, Norton Medical Group guidelines say practitioners should follow up more frequently, consider referring to a specialist and consider prescribing naloxone. Prescribers should avoid prescribing a dosage of 90 morphine milligram equivalents (MME) or higher.

Epidemiology studies show opioid-related overdose risk is dose dependent. One study published in JAMA found higher opioid doses were associated with an increased risk of opioid overdose death, with a mean dosage of 98 MEDD among overdose deaths.

The Department of Veterans Affairs Opioid Taper Decision Tool says clinicians should consider tapering if the dosage is 90 MEDD or higher, if there is no pain reduction or improvement in function, if the side effects are severe and unmanageable or if the patient asks to discontinue therapy. Tapering typically involves dose reduction of 5% to 20% every four weeks.

Other reasons to consider tapering are overdose, unsafe behaviors such as early refills, concerns related to substance use disorder, and medical or mental health comorbidities, according to the VA. A final reason to consider tapering opioid is concomitant use of benzodiazepines or other medications that increase risk.

Opioids and benzodiazepines

Norton Medical Group advises against prescribing opioid pain and opioid cough medicines with benzodiazepines and other central nervous system (CNS) depressants whenever possible. If the benefits are deemed to outweigh the risks, the clinician should check KASPER and INSPECT for the previous 12 months for patient use of opioids, benzodiazepines or other central nervous system depressants and current prescribing by another provider.

VA patients with an opiate and benzodiazepine prescription have been found to have increased risk of drug overdose death in a dose-response fashion. Another cohort study showed that patients taking both medications concurrently are at 10 times higher risk for overdose-related deaths than the patients who are taking only opiates.

The respiratory centers are inhibited by opiates through the mu and delta opioid receptors. Benzodiazepines act on respiratory centers via GABA receptors. So, both benzodiazepines and opioids concurrently are able to alter respiratory patterns.

Studies have shown benzodiazepines noncompetitively inhibit opiate metabolism, leading to enhanced effects of opiates. These effects compounded with health conditions such as chronic obstructive pulmonary disease (COPD) and sleep apnea certainly can cause respiratory depression.

If the patient is taking benzodiazepines for anxiety or insomnia, the provider should consider prescribing a non-benzodiazepine alternative first and consider referral to a mental health professional.

If a provider is prescribing both opioids and a benzodiazepine or CNS depressant concurrently, the lowest possible effective dose should be used. Tapering these patients should begin with the opioid. Tapering benzodiazepines needs to be done slowly. Abrupt withdrawal has been associated with rebound anxiety, seizures, delirium tremens and, in rare occasions, death.

Long-term opioid prescribing guidelines

For long-term prescribing, in addition to a physical and gathering relevant histories, according to Norton Medical Group guidelines providers should screen patients for opioid use disorder, overdose and diversion using validation tools. The patient should complete an objective pain assessment tool and undergo a baseline drug screen, repeated annually. Patients at moderate or high risk for opioid use disorder require more frequent oversight.

If there is a reasonable likelihood the patient has substance use disorder or dependence, the practitioner should facilitate referral to an appropriate treatment program or incorporate this information into the evaluation and treatment.

If a patient is noncompliant, a practitioner should consider a controlled taper, no longer prescribing or dispensing the controlled substance, or referral to an addiction specialist.

Opioid tapering should be the result of a collaboration between the provider and the patient. Tapering plans should be individualized and should minimize symptoms of opioid withdrawal and minimize pain with nonopioid medications and nonpharmacological treatments.

Taper initiation requires significant motivation on the part of the patient. The clinician should make it clear that the tapering is done in the best interest of the patient. It is very important to establish clear goals for tapering. Goals should be mutually agreeable and reasonable. Anxiety and fear are common, and they should be addressed with compassion and reassurance.

If the patient has a serious mental illness, or is at high risk of suicide, the provider should offer a consultation with a behavioral health provider prior to starting the taper.

Abrupt tapering or sudden discontinuation should be avoided. A decrease of 10% per month is a reasonable starting point for tapering. Tapering can be faster in patients who have taken opioids for shorter periods. During the taper, patients should receive appropriate care from mental health providers.

Adjust the taper according to the patient’s response — slowing or pausing if necessary — but do not reverse the taper. Providers should advise patients that it takes as little as a week to lose tolerance and that returning to previously prescribed higher dose carries a significant risk of overdose.

Opioid withdrawal symptoms during taper

Acute opioid withdrawal symptoms

• Rapid, short respirations
• Anxiety/restlessness
• Runny nose
• Tearing eyes
• Sweating
• Insomnia
• Dilated reactive pupils

Late opioid withdrawal symptoms (usually lasting from days to weeks)

• Tremor
• Diffuse muscle spasms/aches
• Piloerection
• Nausea
• Vomiting
• Abdominal pain
• Fever
• Chills
• Occasionally increased white blood cell count

Prolonged opioid withdrawal symptoms

These may last for weeks or months, aren’t life-threatening and can be minimized with slow tapering. They include:

• Irritability
• Fatigue
• Bradycardia
• Decreased body temperature
• Craving
• Insomnia

Opioid withdrawal treatments

• Autonomic symptoms such as sweating, tachycardia, myoclonus can be treated with clonidine, baclofen, gabapentin and tizanidine
• Anxiety, dysphoria, lacrimation and rhinorrhea: hydroxyzine or diphenhydramine
• Myalgias: tizanidine, nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen
• Sleep disturbance: trazodone
• Nausea: prochlorperazine or ondansetron
• Abdominal cramping: dicyclomine
• Diarrhea: loperamide or bismuth sulfate

Patients should be monitored for withdrawal symptoms during opiate taper, which differs for immediate release versus sustained release opioids. The onset of acute withdrawal phase will be anywhere from five to 15 hours.

Refer to interventional pain management when patient is experiencing worsening of pain due to opiate taper. There are several interventional pain management options for common pain conditions to aid in a smooth weaning process. Sometimes it’s even better to involve a specialist before starting taper to obtain a second opinion regarding process of tapering or to initiate interventional pain management options prior to tapering.

Reviewed by Raghunath S. Gudibanda, M.D., pain medicine specialist with Norton Pain Management Associates.