{mosimage}R Gregory Lande, DO, FACN
Walter Reed Army Medical Center
INTRODUCTION
Chronic pain is common; an estimated 20% of primary care visits focus on this problem. Nearly 25% of patients with diabetes develop neuropathic pain. Traumas, strokes, HIV/AIDS, and alcohol abuse are other common medical problems that can produce a chronic pain disorder. The aging American population guarantees the continued prominence of chronic pain disorders.
Managing chronic pain is one of the most challenging problems that both physicians and patients face. Extensive diagnostic assessment may shed little light on the etiology of the disorder, leaving both the physician and the patient in an uncomfortable position. The physician’s goal is pain control, which may not produce total relief from symptoms. Multiple interventions may be required to manage the patient’s expectations when intractable pain relentlessly intrudes on his or her daily life. An empathetic health care provider can offer education, emotional support, medical referrals as needed, and, perhaps most importantly, a wide range of pharmacologic interventions to palliate the discomfort.
An effective approach for the management of chronic pain begins with a thorough assessment and concludes with a targeted biopsychosocial treatment plan. The assessment identifies the functional disability associated with the pain and provides sufficient justification for educational interventions. In addition, the social impact of the debilitating pain disorder might lead the physician to suggest counseling opportunities for the immediate family. Naturally, the patient’s principal objective is maximum pain relief. Among the pharmacologic options available and in addition to standard analgesic remedies, antidepressants can be an important ally in the physician’s quest for safe pain management.
USE OF ANTIDEPRESSANTS IN THE MANAGEMENT OF CHRONIC PAIN
Pain and depression are closely intertwined, strongly hinting at a shared neurophysiology. As a consequence, one prevailing pharmacologic strategy identifies a central role for serotonin and norepinephrine reuptake inhibitors (SNRIs).1 Other justifications, even without a common biologic rationale, strongly support the use of antidepressants in the management of chronic pain. For example, chronic pain characteristically causes sleep problems, anxiety, and depression, all of which may improve with antidepressant treatment.2 Providing an effective, nonhabituating sleep medication that also improves mood may significantly enhance the patient’s quality of life.
Clinical evidence suggests that antidepressants exert their beneficial analgesic effect directly, apart from the physiologic mood improvement. When examining the use of antidepressants among persons who have fibromyalgia or diabetic peripheral neuropathic pain, a recent study concluded that more than 75% of the improvement in painful symptoms was due to the direct analgesic role of the medication.3 Patients may initially not appreciate the recommendation of taking an antidepressant for a pain disorder, but a moment’s education stressing the unique analgesic action of antidepressants should satisfy that concern.
Clinical investigators report effective pain relief across the spectrum of presently available antidepressants. Not surprisingly, the bulk of published studies focus on the tricyclic antidepressants (TCAs). Their efficacy in chronic pain management is well established.4,5 The efficacy of antidepressants, specifically TCAs, in the management of chronic pain is recognized in clinical practice guidelines;6,7 typical guidelines recommend the initial use of TCAs for neuropathic pain. Studies have revealed that patients with specific pain disorders, such as diabetic neuropathy and postherpetic neuralgia, seem more likely to benefit from TCAs than patients who experience the chronic discomfort associated with neck or back pain.8
Although TCAs have a long-established record of safety, efficacy, and tolerability in the role of augmenting chronic pain management, prudent prescribing requires awareness of the major adverse effects of TCAs, which predominantly cluster around cholinergic, histamine, and adrenergic receptor activity. As a consequence, dry mouth, sedation, constipation, urinary hesitancy, and orthostatic hypotension are among the potential adverse effects. Additionally, TCAs should be used with considerable caution in the presence of certain medical conditions, such as glaucoma and benign prostatic hypertrophy. They should also be avoided in the presence of second- or third-degree heart block or a prolonged QT interval.9
Chronic pain management with TCAs can usually be achieved at much lower doses than those typically required for an antidepressant effect. Clinicians can expect results at one half of the antidepressant doses. For example, a starting dose of desipramine would be 10 mg, with 10-15 mg adjustments made weekly until improvement is noted or a dose of 50 mg is reached. Limited improvement at 50 mg might justify a tricyclic blood level test, dose increase, or referral to a specialty pain management clinic.
Other classes of antidepressants have also been studied in the management of chronic pain conditions. The secondary amines, such as desipramine or nortriptyline, also provide effective relief from chronic pain. A particular advantage of the secondary amines is better tolerability and safety, which is the result of less intense anticholinergic adverse effects and less sedation. As a consequence, these medications may be the better and safer choice for chronic pain management in elderly patients.10 Clinical evidence also supports the efficacy of the newer selective serotonin reuptake inhibitors (SSRIs) in relieving chronic pain, although the data may be, comparatively, less convincing.11,12 This may, in part, be because of the broader array of neurotransmitters that are involved in the maintenance of chronic pain, instead of simply serotonin. TCAs and secondary amines inhibit the reuptake of both serotonin and norepinephrine.
The notion that other neurotransmitters are involved in mediating pain is further supported by the emerging efficacy of SNRIs in relieving chronic pain. Venlafaxine is an SNRI used in the treatment of chronic disorders such as fibromyalgia and postmastectomy pain syndrome.13 Duloxetine is an SNRI with clinical treatment indications for both major depression and diabetic peripheral neuropathic pain. This newer antidepressant is a more potent inhibitor of serotonin and norepinephrine reuptake than are other similar medications. As with TCAs, duloxetine’s analgesic effects appear independent from its antidepressant actions. Duloxetine is the first antidepressant approved by the US Food and Drug Administration (FDA) for the management of the pain associated with diabetic peripheral neuropathy. Numerous studies positively cite duloxetine’s effectiveness in managing pain among elderly patients, its role in managing fibromyalgia, and its relief of the pain associated with diabetic peripheral neuropathy.14-16
CONCLUSION
The basis for all treatment of chronic pain conditions begins with a thorough pain assessment. The assessment should include the use of structured instruments to determine both the severity of pain and the associated functional impairments. A psychological assessment is an important routine step in the development of a chronic pain care plan. The assessment must also include a determination of the patient’s safety in terms of potential suicide risk. In conjunction with or in lieu of analgesic options, antidepressant therapy or augmentation may be suggested for patients with lingering stress, depression, insomnia, and lack of remission with standard analgesic remedies. Given the breadth of available clinical research and comparatively lower cost for TCAs, this class of antidepressants remains the preferred initial option, but the newer antidepressants (eg, venlafaxine, duloxetine) should be considered an alternative if TCAs prove ineffective.
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