Patients who are prescribed stable doses of analgesics (usually around-the-clock chronic opioid therapy) for moderate to severe chronic pain are often generally well-controlled with regard to their pain management. However, even though their pain may usually be well-controlled, these patients may experience episodic “flares” of increased pain, called breakthrough pain. This can present a significant treatment challenge.

Terminology

Significant attention has been given to the fact that there has been an inconsistent use of the term “breakthrough pain”, and experts in the field of pain management have called for a universally accepted definition. Recent chronic pain guidelines¹ define breakthrough pain as transient or episodic exacerbation of pain that occurs in patients with pain that is otherwise considered stable but persistent. It may be practical to think of breakthrough pain as a situation or phenomenon that occurs in an otherwise stable patient, rather than a distinct type of pain. It is also important to consider that experts usually agree that there is likely little difference between the experience of breakthrough pain in patients with cancer, and in those with noncancer pain. The diagnosis of breakthrough pain is contingent on the fact that it occurs in the patient who normally has adequately controlled baseline pain, regardless of the diagnosis, and that for a variety of reasons, pain sometimes “breaks through”.

Clinical Context

Breakthrough pain should be assessed separately from the baseline pain being treated, to determine if it is related to one of a number of possible etiologies, including:

• Direct effect of the underlying condition (e.g., progression)
• An indirect effect of the underlying condition (e.g., decreased level of activity due to disability)
• Direct or indirect effect of the treatment
• Concomitant medical conditions

Once identified, breakthrough pain can often be classified into one of these three categories:

• Spontaneous
  • Idiopathic in nature, and not related to any provoking cause

• Incident
  • Precipitated by an event
    • Volitional
      • Precipitated by increased activity (e.g., walking or exercise)
      • Related to ADL
    • Non-volitional
      • Precipitated by an involuntary activity (e.g., breathing, coughing)
    • Procedural
      • Related to a therapeutic intervention (e.g., interventional procedure or a dressing change)

• Analgesic dose-related (also referred to as end-of-dose failure)
  • Decreased analgesic blood levels
  • Drug-drug interactions

Appropriate evaluation of breakthrough pain may require additional diagnostic testing, follow-up visits, or consultation in order to identify the etiology of the pain or the factors precipitating it. Similar to the baseline, or background pain, breakthrough pain can be nociceptive, neuropathic, or mixed in origin. It is important to evaluate and adequately treat breakthrough pain, as left untreated it can be associated with a number of disruptive consequences, including:

• Physical
  • Decreased function
    • Muscle wasting
    • Stiffness
    • Constipation
    • DVTs
    • Pneumonia
• Psychological
  • Mood disorder
    • Anxiety
    • Depression
    • Social interaction
  • Disturbed sleep patterns

Assessment

Assessment of breakthrough pain parallels the standard approach to assessment and re-assessment of any kind of chronic pain. Important areas for probing include all details about the breakthrough pain including location, onset, temporal nature, quality, and exacerbating or alleviating factors. It is also vital to inquire about medication adherence to the regimen for the baseline background pain, as lack of adherence could undermine efficacy, and be responsible for poor pain control.

Criteria for diagnosis include:

• Presence of controlled, but persistent background pain, treated with chronic analgesic therapy (usually opioid)
• Experience of one or more severe episodes of pain in the face of a usually stable and effectively employed treatment regimen

Management

The core principle of management of breakthrough pain “should include consideration of specific therapies directed at the cause of the pain or the precipitating factors, or nonspecific symptomatic therapies intended to lessen the impact of breakthrough pain when it occurs.”¹ Additionally, efforts should be directed towards optimal treatment of the underlying condition, whenever possible. Specific treatment strategies include:

• Modification of current analgesic regimen
  • Dosage adjustment
  • Opioid rotation
  • Addition of a shorter-acting agent specifically for breakthrough episodes
  • Non-opioids (e.g., NSAIDS, other co-analgesics)
• Non-pharmacologic therapy
• Acupuncture
• Massage
• Cognitive behavioral approaches

Although it is often considered to be a sign of poorly controlled background pain in cancer patients, breakthrough pain is prevalent, and it varies in how it presents in patients with chronic noncancer pain.² A hallmark of the primary treatment for breakthrough pain in malignant pain, is with immediate-release, short-acting opioids on a pre-emptive or as-needed basis, in addition to the usual analgesic regimen. Although this strategy is often employed in patients with noncancer pain, more evidence is needed for the long-term use of short-acting opioids for breakthrough pain in these patients to be considered routine.

Clinicians should weigh the risk/benefit ratio when considering the addition of an as-needed opioid for rescue treatment of breakthrough pain. It is imperative to consider other treatment options, such as non-opioid drug therapies and non-pharmacologic treatments. It is also important to consider the possibility of aberrant drug-related behavior relative to the availability of medication prescribed for breakthrough pain. Access to a short-acting drug in opioid-experienced patients may increase the risk of aberrant behaviors in those already engaging in them, or at high risk to do so. In patients at low risk for aberrant drug-related behaviors, a trial of an as-needed opioid with routine follow-up and monitoring may be a reasonable strategy. “In patients at higher risk for aberrant drug-related behaviors, a trial of an as-needed opioid should only occur in conjunction with more frequent monitoring and follow-up. In all cases, clinicians should carefully assess for aberrant drug-related behaviors and progress toward meeting therapeutic goals, and periodically reassess relative benefits to risks of the as needed opioid to make appropriate decisions regarding continuation of this therapy.”¹

References

1. Chou R, Fanciullo GJ, Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal Of Pain: Official Journal Of The American Pain Society 2009;10(2):113-130.

2. Portenoy RK, Bennett DS, Rauck R, Simon S, Taylor D, Brennan M, Shoemaker S: Prevalence and characteristics of breakthrough pain in opioid-treated patients with chronic noncancer pain. J Pain 7:583-591, 2006.

A corresponding version of this article that is appropriate for your patients, titled Breakthrough pain: Finding the right balance and a lesson How opioids can help with breakthrough pain are now available at www.painACTION.com.