Psychiatric–Medical ComorbidityPharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews
Introduction
Pain is the most common symptom reported in both the general population and the general medical setting [1], [2], [3]. Pain complaints account for more than 40% of all symptom-related outpatient visits or over 100 million ambulatory encounters in the US alone each year [4]. Pain costs the US over US$100 billion each year in health care and lost productivity [5]. Pain medications are the second most prescribed class of drugs (after cardiac–renal drugs), accounting for 12% of all medication prescribed during ambulatory office visits in the United States [6]. Clinicians are being pressured to respond to pain as the “fifth vital sign” [7]. Indeed, persistent pain is a major international health problem [8], prompting the World Health Organization to endorse a global campaign against pain [9]. Persistent pain may lead to excessive surgery or other expensive or invasive procedures and is also the leading reason for use of complementary and alternative medicine [10]. Pain is also among the most common reasons for temporary as well as permanent work disability [11].
Pain is even more prevalent in patients with psychiatric comorbidity, particularly mood disorders. The overlap between pain and depression ranges from 30% to 60% [12], [13], [14]. Pain is a strong predictor of both the onset and persistence of depression [15], and depression is likewise a powerful predictor of pain, particularly persistent pain [8], [12]. Concurrent pain and depression have a much greater impact than either disorder alone on multiple domains of functional status as well as health care utilization [12]. Comorbid depression worsens disability and decreases active coping in patients suffering from pain [16], [17]. Comorbidity decreases the likelihood of a favorable response of either condition to treatment and also diminishes patient satisfaction with treatment [18], [19], [20], [21], [22]. Thus, assessing the presence and severity of pain in patients with depression, particularly those not responding to initial treatment, as well as strategies for effectively and efficiently integrating evidence-based depression care into the management of patients with chronic pain, is sorely needed [23].
Although not as extensively studied, the comorbidity of pain with anxiety appears to be nearly as strong as its comorbidity with depression [1], [24], [25], [26], [27]. Indeed, a global study conducted by the WHO in 17 countries involving more than 85,000 community-dwelling adults showed that pain was associated with mood and anxiety disorders, but not with alcohol abuse or dependence [28]. The prevalence of specific mood and anxiety disorders was lowest among persons with no pain, intermediate among those with one pain site and highest among those with multisite pain problems. Relative to persons not reporting pain, the age- and sex-adjusted odds ratios were 1.8 (1.7–2.0) for mood disorders and 1.9 (1.8–2.1) for anxiety disorders for persons with single-site pain; and 3.7 (3.3–4.1) for mood disorders and 3.6 (3.3–4.0) for anxiety disorders among those with multisite pain.
The focus of this review will be twofold. First, we will discuss major classes of medications as they relate to pain management. Second, we will briefly address several specific categories of disorders chosen because they (1) account for the most common types of chronic pain; (2) are conditions for which pain management is the principal focus; and (3) have been studied in numerous clinical trials. The prototypical diseases that will be discussed will be musculoskeletal disorders [principally fibromyalgia (FM), low back pain and osteoarthritis (OA)] and neuropathic pain (NP). Musculoskeletal disorders account for more than two-thirds of pain-related outpatient visits, and NP is not only common but is also a popular target for clinical trials in pain and therefore a common reason for seeking a Food Drug Administration (FDA) indication for treatment of pain. We will not address acute pain (e.g., injury-related or postoperative pain), cancer pain, headache and visceral pain.
Section snippets
Strength of evidence
The major sources of information for this narrative review are meta-analyses and systematic reviews published since 2005. Individual randomized clinical trials (RCTs) were not included unless we found multiple recent trials on new treatments that had not yet been synthesized into a systematic review. In some reviews, the magnitude of treatment effect as a continuous outcome was reported as an effect size (ES), calculated as the mean change in treatment group minus mean change in control group
Nonopioid analgesics
Aspirin and other related compounds constitute a class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs have three desirable pharmacological effects — anti-inflammatory, analgesic and antipyretic. All NSAIDs and COX-2 agents appear equally effective in the treatment of pain disorders [30]. While gastrointestinal (GI) adverse effects have traditionally been considered the most common and worrisome complication, cardiovascular risk has gained increasing attention, prompting
Neuropathic pain
Neuropathic pain is characterized by continuous or intermittent spontaneous pain, typically characterized by patients as burning, aching or shooting. Up to 3% of the general population reports NP at some time [86]. NP is most commonly associated with painful diabetic neuropathy, PHN or lumbar nerve root compression. Other causes of NP include cancer-related pain, spinal cord injury, post-stroke pain, HIV-associated neuropathy, phantom limb pain and trigeminal neuralgia.
Four drugs are FDA
Stepwise selection of pharmacotherapy
This review has synthesized conclusions from evidence-based reviews of pharmacotherapy for chronic pain. In addition to summarizing the various classes of medications, we have discussed four of the most common disorders in which pain is a predominant treatment target: NP, FM, low back pain and OA. Table 3 provides a stepped approach to the selection of pharmacotherapy based upon the evidence from clinical trials. Table 4 highlights the classes of medications that should be considered in the
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The Psychiatric–Medical Comorbidity section will focus on the prevalence and impact of psychiatric disorders in patients with chronic medical illness as well as the prevalence and impact of medical disorders in patients with chronic psychiatric illness.