Managing Breakthrough Pain

Orlando—Approximately 12.5 million people in the United States have cancer, according to the National Cancer Institute, and the numbers are increasing. Each year, there are 1.5 million new cases of cancer, while 500,000 die from the disease.

As more therapies are approved and doctors and researchers better understand the disease, two-thirds of cancer patients survive for more than 5 years, although many suffer from lingering pain following treatment.

At the AAPM meeting, healthcare professionals discussed issues related to cancer-related pain during a satellite symposium titled Managing Breakthrough Pain Across the Provider Continuum. Teva Pharmaceuticals supported the session with an educational grant.

Paul Arnstein, RN, PhD, clinical nurse specialist for pain relief at Massachusetts General Hospital, said more than 100 million Americans have chronic pain. The condition accounts for $600 billion per year in health and disability costs, affects people’s health, longevity, and quality of life, and contributes to learning, memory, and emotional difficulties.

For cancer patients, the prevalence of pain varies depending on the stage and type of disease: 25% to 60% of patients who are receiving treatment and 62% to 86% of patients with advanced disease have pain.

There are 2 main categories of pain, according to Dr. Arnstein. Nociceptive pain is caused by activity in neural pathways in response to potentially tissue-damaging stimuli, while neuropathic pain is initiated or caused by primary lesion or dysfunction in the nervous system.

Meanwhile, Dr. Arnstein defined breakthrough pain as a transitory increase in pain that has a negative effect on function or quality of life in patients who have adequately controlled pain at baseline and receive analgesic drug therapy on most days. He noted that among cancer patients, 33% in community settings, 40% in outpatient settings, 50% to 90% in inpatient settings, and 80% in home care or inpatient hospice have breakthrough pain. In addition, among noncancer patients, 48% treated in primary care and 74% treated in pain clinics have breakthrough pain.

The characteristics of breakthrough pain differ. Some people have an episode per day, while others have several per hour. For the most part, the episodes are brief, although some can last for several hours. In addition, the episodes can be predictable or can appear without any advanced warning.

When assessing pain, Dr. Arnstein said he asks patients about the pain’s intensity on a 0 to 10 scale, the location/body parts affected, the duration of the pain, and any aggravating or alleviating factors associated with the pain. After prescribing treatment, he follows up and asks if they have had reduction in pain intensity, if they are active, if they are having any adverse effects, and if they are displaying any aberrant behaviors.

Dr. Arnstein noted it is important to evaluate any signs of addiction. He mentioned the American Society of Addiction Medicine’s characteristics of addiction, which include an inability to consistently abstain from drugs, an impairment in behavioral control, a craving or increased hunger for drugs or rewarding experiences, a diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response.

Risk Assessment and Evaluation

Although primary care physicians often evaluate patients who complain about pain, they have a difficult time treating and assessing pain, according to Paul P. Doghramji, MD, medical director of health services at Ursinus College in Collegeville, Pennsylvania. They have an inadequate knowledge of pain, have trouble evaluating pain and substance abuse, and have concerns about side effects, tolerance, and addiction to medications.

Before prescribing medications, Dr. Doghramji said physicians should give patients a physical examination and inquire about their current and past illnesses, substance abuse, mental health, and medications. Patients are at an increased risk for aberrant behaviors if they are 45 years of age or younger, smoke cigarettes, have a substance use disorder or major psychiatric disorder, have a family history of prescription drug or alcohol abuse, or have a history of legal problems.

If physicians choose to prescribe opioids or other pain medications, Dr. Doghramji said they should teach patients about the risks and benefits of the drugs, provide them with rules about how often they can refill the medications, and alert them of responsibilities such as not sharing, selling, or trading the medications or trying to obtain medications from another provider without approval. Patients and providers should work together to assess pain and evaluate the safety and efficacy of the medications.

“It’s a shared responsibility,” Dr. Doghramji said. “Communication must happen.”

Although there are several tools are available to estimate the risk of noncompliant opioid use, Dr. Doghramji said none are perfect. However, he added that the following tools all are effective: the Opioid Risk Tool (ORT), the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), the Current Opioid Misuse Measure (COMM), and the Diagnosis, Intractability, Risk and Efficacy (DIRE) instrument.

Lynn Webster, MD, created the ORT in 2005 for use in primary care settings. It asks about the patient’s and family’s history with substance abuse (alcohol, prescription drugs, and illegal drugs), the patient’s age, the patient’s history of preadolescence sexual disease, and the patient’s psychological diseases (attention-deficit/hyperactivity disorder, obsessive compulsive disorder, bipolar disorder, schizophrenia, and depression).  Dr. Doghramji said patients who are categorized as high risk on the ORT have an increased likelihood of displaying abusive drug-related behavior.

The SOAPP-R is a 24-item questionnaire and takes less than 10 minutes to complete, according to Dr. Doghramji. It was developed based on expert consensus regarding which patients will require more or less monitoring when they are on long-term opioid therapy. Meanwhile, the 7-item DIRE takes less than 2 minutes to administer and score and is intended for use in primary care settings. Dr. Doghramji said research has found that scores on the DIRE correlate well with compliance and efficacy to long-term opioid therapy. In addition, the COMM is intended only for clinicians, contains 17 questions, and takes fewer than 10 minutes to finish. The COMM helps clinicians decide how closely to monitor patients and to justify referrals to specialty pain clinics, according to Dr. Doghramji.

Dr. Doghramji also recommended that providers schedule follow-up visits every month and give patients urine or serum drug screenings, which can uncover illicit drug use or confirm compliance with treatments. He said that if patients have an abnormal test, providers should address the issue. They can then choose to refer the patient to substance abuse counseling or treatment, dismiss the patient, or refuse to prescribe further controlled substances.

Breakthrough Pain Treatments

Michael J. Brennan, MD, senior attending physician at Bridgeport Hospital in Bridgeport, Connecticut, said treating breakthrough pain in cancer patients should be incorporated into their regimen and can involve pharmacologic and nonpharmacologic elements.

Pharmacologic options include monotherapies such as morphine, oxycodone, hydromorphone, or oxymorphone, or a combination of opioids and non-opioids. Dr. Brennan added that the following may offer relief, too: ice, heat, corsets, counter irritant creams, ace wraps, massage, physical therapy, pacing, deep breathing, relaxation techniques, and patient education about the need to reduce activities and use specific aids for activities of daily living. However, he said that the nonpharmacologic treatments do not have much of an effect on breakthrough pain episodes.

Dr. Brennan mentioned the World Health Organization (WHO) pain ladder that defines pain on a 10-point scale. Mild pain is a score from 1 to 4, moderate pain is a score of 5 or 6, and severe pain is a score from 7 to 10. The WHO recommends providers begin treatment with non-opioid agents such as aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs).

If the pain is not controlled, the WHO suggests patients can progress to take weaker opioids such as codeine or tramadol. If the pain continues or increases, patients may receive stronger opioids such as fentanyl or morphine.

For breakthrough pain, Dr. Brennan said adjuvant analgesics such as antidepressants and anticonvulsants may be effective but non-opioid analgesics are not usually effective because of dose-limiting toxicities, a slow onset of action, and a relatively long duration of action. He added that patients with mild cancer pain typically take acetaminophen, while NSAIDs are used for background pain. However, research has indicated those drugs should not be used for breakthrough pain in cancer, according to Dr. Brennan.

Patients with cancer-related breakthrough pain usually take short-acting opioids. They can also have an around-the-clock opioid dose increase if there are no treatment-limiting adverse effects, although Dr. Brennan warned that providers and patients should closely monitor adverse effects.

Dr. Brennan said opioid medications come in several formulations, including through oral, intravenous, inhaled, intranasal, and sublingual administration. He discussed transmucosal immediate-release fentanyl, which has a rapid onset of action and a short duration. He noted that a study of cancer patients found that oral transmucosal fentanyl citrate was successful at treating breakthrough pain and that patients rated the pain relief as very good to excellent. Adverse events included somnolence (9% of patients), constipation (8%), nausea (8%), dizziness (8%), and vomiting (5%).

The fentanyl buccal tablet is also safe and effective, according to Dr. Brennan. A study of 646 non-cancer patients found that 11% discontinued use because of an adverse event, while most of the adverse events were mold-to-moderate and typical of those associated with opioids.

Another trial of 232 patients who had cancer-related breakthrough pain found that 88% favored the fentanyl buccal tablet over their previous medications because of its time to onset, convenience, and ease of administration. Common adverse events included nausea (37% of patients), vomiting (22%), dizziness (20%), fatigue (16%), constipation (14%), anemia (14%), headache (14%), somnolence (13%), and peripheral edema (13%). Fentanyl also comes as a soluble film, a sublingual tablet, a sublingual spray, and a nasal spray, according to Dr. Brennan.

Dr. Brennan said providers and patients need to be aware of adverse events associated with opioids, including sedation and drowsiness, sleep disturbances, constipation, opioid-induced immunologic affects, opioid-induced hormonal changes, opioid-induced hyperalgesia, and opioid-induced bladder dysfunction.