Depression in the Patient with Chronic Pain Gary E

Depression in the Patient with Chronic Pain Gary E. Ruoff, MD Kalamazoo, Michigan

The management of patients with chronic pain is a chal patients who are depressed require aggressive, full- lenging clinical problem that frequently requires a multi dose treatment with antidepressants. Treatment should disciplinary approach. Depression is a common comor be selected based on a prior clinical response, the side- bidity associated with chronic pain, occurring in as effect profile, the dosing schedule, and the potential for many as 50% of chronic pain patients. Depression may drug interactions. The newer antidepressants, including develop secondarily or independently of the chronic the selective serotonin reuptake inhibitors venlafaxine pain syndrome, or it may occur as the primary cause of and nefazodone, are therapeutic options for the treat chronic pain. Regardless of their etiology, evidence ment of depression in the patient with chronic pain. exists to suggest that depression and chronic pain share

common biologic pathways, namely, the serotonergic KEY WORDS. Pain; chronic disease; depression; drug (5-HT) and noradrenergic systems. Chronic pain therapy. J Fam Pract 1996; 43(suppl):S25-S34

espite advances in pain management of chronic pain. Alternatively, depression may be the techniques, the patient with chronic pain primary disorder, with chronic pain occurring as a continues to represent a clinical chal manifestation of an affective disorder. Depression lenge. Chronic pain encompasses a and chronic pain may also occur independently, as in broad spectrum of pathophysiologic eti the patient with a family history of depression who ologyD and psychological underpinnings. Chronic suffers a traumatic injury with subsequent long-term pain may originate from four potential sources: (1) pain. It has also been suggested that clinical depres an undiagnosed medical or surgical disease; (2) a sion does not alter the experience of pain but lowers psychiatric disorder; (3) a neurologic lesion; or (4) a the pain threshold.3 somatic lesion (eg, metastatic tumor, chronic back pain, headaches, HIV-associated neurological prob DIFFERENTIATING ACUTE AND lems). In some patients, chronic pain serves as a pro CHRONIC PAIN tective function associated with the disease state (eg, patients with arthritis or other joint disease). Acute pain and chronic pain are distinguished by the However, one frustrating element of managing the temporal course, response to treatment, and associ patient with chronic pain is that, in some cases, no ated psychological sequelae (Table 1). The purpose identifiable underlying source of medical, psychi of acute pain is as a protective response or warning atric, or neurological disease can be determined.1 signal of injury or noxious stimulus. In general, acute Chronic pain is a public health problem of some pain is localized, is short-lived, and responds to anal significance. In 1979, chronic pain was responsible gesics. Acute pain frequently suggests a medical for an estimated 7 million days lost from work and problem and is often one of the first clues to disease. for associated costs of $40 billion in the United Autonomic physiologic symptoms are present in States.2 When translated into current dollars, the patients with acute pain, hi addition, patients experi economic burden of chronic pain has a huge impact. ence fearfulness or anxiety in anticipation of the The relationship between chronic pain and pain, and they are able to accurately describe the depression is complex and not entirely understood. pain sensation as crushing, burning, stabbing, or Depression may occur secondarily as a complication throbbing.' Acute pain is associated with trauma, surgical procedures, or disease and generally sub Revised, submitted, September 30, 1996. sides with healing. Address correspondence to Gary E. Ruoff, MD, 6565 West The physical and psychological spectrum of Main, Kalamazoo, MI 49009.

chronic pain is markedly different (Table 1) and cal study. These findings are consistent with those of much more difficult to manage. In contrast to acute the NHANES-1 (National Health and Nutrition pain, chronic pain tends to persist beyond the course Examination Studies) Epidemiologic Follow-Up of initial injury, or is out of proportion to the injury, Study (NHEFS) of 2341 adults in which 16.4% of sub and has minimal protective function. Chronic pain jects with chronic musculoskeletal pain were clini may be associated with specific disease states, such cally depressed. In contrast, only 5.7% of persons in as diabetic neuropathy, migraine headaches, and the NHEFS sample without evidence of chronic pain arachnoiditis. Chronic pain is persistent and is of were depressed."’ greater than 6 months’ duration rather than being Does depression increase the risk of developing a transient and self-limited. The severity of chronic chronic pain syndrome? Longitudinal assessment of pain ranges from mild to excruciating. Regardless of patients from a large health maintenance organiza severity, the presence of chronic pain may have a tion revealed that depressed patients were more profound impact on quality of life. Chronic pain likely to develop chest pain, headache, or temporo often requires a multidisciplinary approach to treat mandibular disorder (TMD) pain over a 3-year peri ment that can include pharmacotherapy, behavior od than were nondepressed controls.6 Depression modification, psychotherapy, and neurosurgery.1 often manifests not as the typical symptoms of depressed mood or loss of interest in usual activities, EPIDEMIOLOGY OF DEPRESSION but as somatic complaints, including pain.T IN CHRONIC PAIN STATES The relationship between medically unexplained pain and depression has been studied in one family Depression is a common finding in patients with medicine practice.8 In this study of 101 depressed chronic pain. Dworkin and Gitlin reviewed a number patients and 101 age- and gender-matched non of studies that evaluated the incidence of depression depressed controls, the incidence of pain was signif (using DSM-III criteria for diagnosing depression) in icantly greater in depressed patients before they patients with chronic pain (Table 2).J Although these were diagnosed with depression (Figure 1).' studies do not give the actual prevalence of depres Medically unexplained pain was defined as pain that sion in chronic pain patients, they do provide an esti was not associated with a definite diagnosis or infec mate. Between 1.5% and 57% of patients with chron tion, such as headache, backache, or pelvic pain. ic pain were found to have major depression. In addi Still, once the diagnosis of depression was made and tion, the lifetime prevalence of depression in these antidepressant treatment or psychotherapy presum patients ranged from 20% to 70%. The proportion of ably started, the incidence of pain in the depressed patients who had suffered major depression at other group did not differ from that in the controls.8 times in their lives was at least 2-fold higher than the prevalence of depression observed during the clini EXPERIENCE OF PAIN IN COMORBID DEPRESSION TABLE 1 ______Clinical depression has a profound influence on a Differentiation Between Acute and Chronic Pain patient’s perception of chronic pain. The relationship Acute Chronic between pain behavior and depression was assessed Feature of Pain Pain Pain in a study of 37 adults participating in an inpatient Associated with trauma or disease +++ ++ chronic pain management program.' Pain behavior Pain related to intensity of disease ++ + was defined as verbal complaints, nonverbal com Pain related to stage of healing + - plaints (eg, groaning), facial grimaces, standing pos Pain subsides with healing - ture, mobility, body language, reliance on supportive Psyche involved + +++ equipment, and medication use. Patients were cate Lifestyle involved + +++ gorized in terms of low depression (Beck Depression Family involved + +++ Inventory [BDI] score 0 to 5) or high depression (BDI Social environment affects pain + +++ 6 to 21). When trained nurse observers rated patients for Minus - sign = not related; + = slightly related; ++ = moderately pain behavior, there was no significant difference related; and +++ = strongly related. between depressed and nondepressed patients

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TABLE 2 ------

Major Depression in Patients with Chronic Pain

Major Depression (%)

Current N Investigators Setting Population Episode Lifetime 106 Benjamin et al, 1988 Outpatient pain clinic Chronic pain 33.0 —

Bouckoms et ai, 1985 62 Inpatient neurosurgery Pain >6 months 24.2 —

Chaturvedi, 1987 203 Outpatient psychiatry Pain >3 months 6.9 —

Fishbain et al, 1986, 1988 283 Pain clinic Pain >2 years 4.6 — France et al, 1984, 1985, 1987, 1988 15-80 Inpatient pain program Low back pain >6 months 30.8-54.5 —

Goldenberg, 1986 82 Arthritis clinic Fibrositis/fibromyalgia 13.4 59.8 Haley et al, 1985 63 Pain clinic Chronic pain 49.2 — Hudson etal, 1984, 1985 23-31 .Arthritis clinic Fibrositis/fibromyalgia 25.8-26.1 71.0 Katon et al, 1985 37 Inpatient pain program Pain >1 year 32.4 56.8 Katon et al, 1985 49 Psychiatric consultation Chronic pain 57.1 —

Kirmayer et al, 1988 20 Rheumatology practice Fibromyalgia — 20.0 Large, 1986 50 Psychiatric consultation Pain >6 months 6.0 — Love, 1987 68 Private practice clinics Low back pain >6 months 25.0 — Magni et al, 1984 29 — Pelvic pain >6 months 17.2 — Merskey et al, 1987 32 Psychiatric consultation Chronic pain 28.1

Muse, 1985 64 Pain clinic Pain >6 months 1.5 — Reich et al, 1983 43 Pain board Chronic pain 23.2 — 13.2 — Remick et al, 1983 68 Psychiatric consultation Atypical facial pain 30.0 — Turner et al, 1984 40 Pain clinic Pain >6 months 28.0 64.0 Harrop-Griffiths et al, 1988; 25 Laparoscopy patients Pelvic pain >3 months Walker et al, 1988

Adapted from Dworkin and Gitlin, 1991, with permission.*

tion of pain and the pathogenesis of depression. (Figure 2).3 However, patient self-rating scores of Support for the theory that depression and chronic- pain behavior in both categories were always higher pain share a common pathway comes from the than observer scores. Moreover, depressed patients observations that the neurotransmission of pain rated themselves with significantly higher pain may be mediated, in part, through serotonergic- behavior scores (P< .05).3 These findings suggest mechanisms." In addition, the tricyclic antidepres that depressed patients perceive their pain as more sants (TCAs) and other antidepressants have been severe than do nondepressed patients. shown to be effective in the treatment of a variety of chronic pain syndromes, including peripheral COMMON BIOLOGIC PATHWAYS FOR neuropathic pain, headache, migraine, facial pain, PAIN AND DEPRESSION fibrositis, and rheumatic pain." The TCAs amitriptyline (with both serotonergic The neurotransmitters serotonin (5-HT) and norepi and noradrenergic effects) and desipramine (with nephrine have been implicated in both the percep

The Journal of Family Practice, Vol. 43, No. 6 (Suppl), 1996 S 2 7 DEPRESSION AND THE PATIENT WITH CHRONIC PAIN

FIGURE 1 addition, patients may be more Complaints of pain before and after the time that depression was diagnosed in responsive when asked about other depressed patients and nondepressed controls in a primary care practice. Modified from Wilson et al, 1983, with permission.8 symptoms of depression, such as loss of interest or pleasure in former ly pleasurable activities, sleep distur bances, fatigue, changes in weight, and poor concentration. Patients should also be questioned about sui cidal tendencies.4 Major depression is diagnosed when a patient fulfills the criteria published in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), published by the American Psychiatric Association (Table 3).18

TREATMENT APPROACHES

Regardless of whether depression is secondary to the pain syndrome or is the primary condition, the mood dis order should be thoroughly assessed and treated pharmacologically. predominantly noradrenergic effects) have shown Psychotherapy may also be a useful treatment efficacy in the treatment of diabetic neuropathy.11 approach in the depressed patient with chronic pain. Clomipramine, a TCA with potent serotonergic prop The large number of clinically effective antidepres erties, has shown clinical response in the treatment sants available enables therapy to be tailored to indi of diabetic neuropathy.12 The selective serotonin vidual patients based on a previous antidepressant reuptake inhibitors (SSRIs) have also been shown to response, the side-effect profile, the dosing sched elicit pain relief in patients with diabetic neuropathy ule, and the potential for drug interactions. Because in some,1314 but not all11 studies. The SSRIs have also of the dysfunctional lives often led by patients with been used, with some success, in the treatment of chronic pain, the impact of antidepressants on qual- chronic headache.15-17 These observations suggest a ity-of-life factors is an important consideration in the common biologic pathway for both depression and selection of antidepressant therapy. chronic pain. S e l e c t iv e S e r o t o n in R e u p t a k e DIAGNOSIS OF DEPRESSION IN THE I n h ib it o r s PATIENT WITH CHRONIC PAIN The SSRIs, fluoxetine, sertraline, and paroxetine, are now considered the first-line treatment for depres Many patients with chronic pain will resist the pos sion because of their demonstrated efficacy and sibility of a psychiatric diagnosis, such as depres well-tolerated side-effect profile, particularly when sion, even if the depression is caused secondarily by compared with the TCAs or the monoamine oxidase the syndrome of chronic pain. These patients tend to inhibitors (MAOIs).19 The side-effect profile of the mask their psychological distress and deny that they SSRIs is directly related to their antidepressant are depressed. In such cases, questions that sympa mechanism of action, which is to selectively inhibit thize with the patient (eg, “Your pain must be hard to 5-HT uptake by the presynaptic neurotransmitter. handle. Do you ever feel low because of it?”) or nor The spectrum of side effects associated with SSRIs malize their experience of pain (eg, “Many of my consists of nausea, headache, sleep disturbance, and other patients with pain feel down. Has this ever sexual dysfunction.19'20 The SSRI-related side effect of happened to you?”) may facilitate assessment. In nausea typically occurs early in the course of treat-

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ment and often resolves within 1 to 2 weeks of begin Patients baseline bowel function may also be a ning therapy.21 lactor in the selection of an SSR1, particularly in Suicide and suicidal tendencies are among the patients with opioid-related constipation or diarrhea most serious consequences of untreated or inade due to chemotherapy or radiation therapy. For quately treated depression and can be a major risk example, sertraline is associated with diarrhea or factor in the patient with chronic pain. The SSRIs loose stools in some patients, whereas paroxetine is possess a significantly higher therapeutic index and associated with mild constipation.2127 An awareness are safer than the TCAs or MAOIs when taken in an of these opposing gastrointestinal effects will allow overdose19 situation and therefore represent a safer antidepressant therapy to be tailored to individual option for treating the depressed patient with suici patients. dal tendencies. Dosing guidelines for the SSRIs and other newer Recognition of the individual differences between antidepressants are listed in Table 4. The most com SSRIs can be exploited to clinical benefit in selected mon initial and clinically effective dose of both flu patients. For example, some patients have difficulty oxetine and paroxetine is 20 mg per day. However, accepting their disease and exhibit extreme anxiety many patients require the initial 50-mg dose of ser about the course and prognosis of their pain. traline to be titrated up to 100 to 150 mg per day.2,42,2 Patients whose depression in the setting of chronic As clinical experience with the SSRIs has grown, pain includes significant symptoms of anxiety may so have reports of drug interactions with these respond favorably to treatment with a nonactivating agents. Patients with chronic pain are likely to be agent. In clinical studies, paroxetine is associated taking a large number of different drugs, and the with a low incidence of exacerbating existing anxi addition of an SSRI or any other antidepressant for ety symptoms or of inducing the emergence of anxi the treatment of depression should be undertaken ety during treatment.22'23 Of the SSRIs, fluoxetine is with careful consideration of the potential for drug more likely to produce symptoms of anxiety, feelings interactions. of inner restlessness, and nervousness.24'25 To mini Combined therapy with an SSRI and an MAOI has mize these symptoms, a short 2-week course of resulted in the serotonergic syndrome, a potentially alprazolam (0.5 to 4.0 mg per day) therapy that is fatal overstimulation of central 5-I1T receptors." gradually tapered and discontinued may be pre Patients are also vulnerable to the serotonergic syn scribed during initiation of fluoxetine therapy.26 drome when discontinuing an SSRI and switching to an MAOI. Therefore, at least 2

__ Figure 2 ------weeks should lapse between stop ping therapy with paroxetine or Mean pain behavior ratings from patients (self-rating) and nurses (observer rating). sertraline (ie, SSRIs wit h half-lives Reproduced from Krause et al, 1994, with permission.3 of approximately 24 hours) and beginning therapy with an MAOI. Longer washout periods of at least 5 weeks and as long as 8 to 10 weeks in the elderly should be followed when discontinuing the longer-acting fluoxetine.27 Drug interactions mediated through the inhibition of cyto chrome P450 drug-metabolizing enzymes in the liver are now rec ognized as a potential conse quence of therapy with the SSRIs or other newer antidepressants. In vitro studies have shown that each of the SSRIs inhibits cytochrome P450 3A4, an enzyme that is believed to be the predom-

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TABLE 3 day) may reduce the clinical conse Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) quences of this drug interaction. Criteria for Major Depressive Episode Nonetheless, the initial dose of the TCA may need to be reduced, blood levels of At least 5 of the following symptoms are present during the same period. the TCA should be followed, and clinical Either depressed mood or loss of interest or pleasure must be present. response should be monitored. Symptoms are present most of the day, nearly daily, for at least 2 weeks: Clinical observation of interactions • Depressed mood (sometimes irritability in children and adolescents) between fluoxetine, sertraline, and flu- most of the day, nearly every day voxamine and drugs metabolized by • Markedly diminished interest or pleasure in all or almost all activities cytochrome P450 2C (eg, phenytoin, most of the day, nearly every day diazepam, warfarin, and tolbutamide) • Significant weight loss/gain or decrease or increase in appetite also suggests the potential for interac • Insomnia/hypersomnia tions mediated by inhibition of • Psychomotor agitation/retardation cytochrome P450 2C.35 Fluvoxamine is • Fatigue or loss of energy unique among the SSRIs because it is a • Feelings of .worthlessness or excessive inappropriate guilt potent inhibitor of cytochrome P4501A2, • Impaired concentration or indecisiveness and concomitant therapy has resulted in • Recurrent thoughts of death, suicidal ideation with or without a specific clinically important increases in plasma plan, or suicide attempt concentrations of theophylline, caffeine, Modified from DSM-IV, 1994, with permission.'8 and clozapine.35

V e n l a f a x in e inant drug-metabolizing enzyme in the liver.34 Of the The antidepressant properties of venlafaxine are due SSRIs, fluvoxamine (an SSRI that is indicated for to the selective inhibition of norepinephrine and obsessive-compulsive disorder in the United States serotonin uptake.39 Venlafaxine therapy is associated but that is widely used as an antidepressant in with side effects that include nausea, vomiting, Europe) and, to a lesser extent, fluoxetine are the blood pressure increases, sexual dysfunction, sweat most potent inhibitors of cytochrome P450 3A4 and ing, and somnolence. The side-effect profile of ven are the most likely SSRIs to be involved in drug inter lafaxine is clearly dose-related. For example, treat actions mediated by this enzyme. Drugs that are ment-emergent nausea, which can be severe with metabolized by cytochrome P450 3A4 include carba- higher doses, is minimized by beginning treatment mazepine, alprazolam, triazolam, midazolam, terfe- with low doses (eg, 25 mg per day) that are gradual nadine, and astemizole.35 Interactions between terfe- ly increased. When venlafaxine has been adminis nadine and drugs that inhibit cytochrome P450 3A4 tered in doses of 375 mg or more, systolic blood pres (eg, erythromycin and ketoconazole) have resulted sure has been observed to increase by 7.5 mm Hg. in fatal ventricular' arrhythmias.36'37 As a result, the Such small increases in blood pressure may be of concomitant use of fluvoxamine and terfenadine or concern for patients with borderline or existing astemizole is contraindicated.38 hypertension. Fluoxetine, sertraline, and paroxetine inhibit TCA Venlafaxine is an effective antidepressant, but its metabolism by cytochrome P450 2D6, and instances side-effect profile suggests that it be reserved for use of markedly elevated TCA concentrations have in treatment-refractory depression.4043 The total daily occurred. Interactions between these SSRIs and dose of venlafaxine (150 to 225 mg) is divided into 2 TCAs are uncommon in the family practice setting or 3 doses per day (Table 4). because such combination therapy is generally reserved for treatment-refractory patients seen by T r a z o d o n e psychiatrists. If a TCA is administered for purposes Trazodone, an effective antidepressant, is believed of pain management to a patient also receiving an to exert its antidepressant effects through inhibition SSRI for treatment of depression, the potential exists of serotonin reuptake and 5-HT2 receptor antago for elevated TCA concentrations and clinical seque nism.44'45 Sedation, orthostasis, priapism, dizziness, lae. However, the lower doses of TCAs used for headache, and nausea are associated with tra adjunctive pain management (eg, 10 to 100 mg per zodone4647 and may limit its use as monotherapy for

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depression. However, the sedating properties of tra T r ic y c l ic A ntidepressants zodone are often used to clinical advantage by Despite their proven efficacy in the treatment of administering this drug as a nighttime adjunct to depression, the TCAs are now considered seeond- patients with sleep disturbances in doses of 50 to 100 or third-line therapy when compared with the mg. Antidepressant doses of trazodone range from newer antidepressants that are significantly bet 200 to 600 mg per day in divided doses. ter tolerated. Low doses of TCAs have been shown to have an analgesic effect in chronic pain Ne f a z o d o n e (eg, 25 to 150 mg of amitriptyline)."’ The analgesic Nefazodone, which is a better-tolerated analogue of efficacy of the TCAs in the absence of depression trazodone, is a 5-HT2-receptor antagonist with mod suggests that these drugs have intrinsic analgesic est inhibition of 5-HT uptake. Unlike trazodone, nefa activity independent of their antidepressive zodone does not negatively impact sleep architec effects. The broad-spectrum pharmacology of ture or cause orthostasis or priapism.27 42 Nefazodone these agents includes interactions with choliner is a potent inhibitor of cytochrome P450 3A4 and is gic, histaminergic, serotonergic, and dopaminer contraindicated for combined use with terfenadine gic receptors. This nonspecific mechanism of or astemizole. Concurrent use of nefazodone with action is also responsible for the variety of side alprazolam, triazolam, or midazolam requires that effects associated with TCA therapy, including the dose of the benzodiazepine be reduced48 in order dry mouth, constipation, blurred vision (anti to prevent enhanced sedation, impaired cognition, cholinergic effects), sedation, weight gain (anti- and hangover effects. The relatively short elimina histaminergic effects), and sexual dysfunction tion half-lives of nefazodone and its pharmacologi (serotonergic effects).4560 The TCAs are also cally active metabolites require that the total daily extremely lethal in an overdose situation and are dose of 300 to 600 mg per day be administered in associated with orthostatic hypotension (with divided doses (Table 4). subsequent falls and fractures), cognitive dys function, and cardiac effects causing bundle

Bu p r o p io n branch or complete heart block and sudden The mechanism of action of bupropion is not death.27 TCA therapy should be initiated with con known but may possibly be related to relatively servative low doses and plasma-concentration weak effects on noradrenergic, dopaminergic, monitoring. It is particularly important that TCA and serotonergic systems.45 Bupropion is not levels remain within the therapeutic range (eg, 50 associated with the anticholinergic, antihistamin- to 150 ng/mL for nortriptyline; 125 to 300 ng/mL ergic, or cardiac effects of the TCAs or venlafax- for desipramine) in elderly or cardiac patients. ine. In addition, sexual dysfunction and lethality Plasma-concentration monitoring is not neces in an overdose situation are not problems gener sary for imipramine and doxepin. If a TCA is to be ally associated with bupropion treatment. used, nortriptyline and desipramine are the best- However, the dopaminergic properties of bupro tolerated agents in the class. Once tolerance to pion are responsible for activation, appetite sup side effects has been established, doses should be pression, insomnia, psychotic symptoms and, titrated periodically to achieve the maximal ther rarely, seizures.49 Depressed chronic pain patients apeutic effect. who exhibit symptoms of psychomotor retarda M o n o a m in e O x id a s e I n h ib it o r s tion (eg, slowed down) or who have gained con siderable weight may do well with bupropion (MAOIs) The potential for fatal food (eg, cheeses, wine, and therapy. Still, if the depression is characterized by other tyramine-containing foods) and drug interai - loss of interest in food and subsequent weight tions (eg, SSRIs, TCAs, and sympathomimetics) and loss, the appetite-suppressing properties of intolerable side effects limit the use of the MAOIs bupropion may be a disadvantage. Activation and phenelzine and tranylcypromine. Chronic pain the extremely low risk of seizures associated with patients also being treated with meperidine or high bupropion therapy may be minimized by adminis doses (or overdoses) of a TCA may develop severe tering no more than 450 mg per day in doses that hyperpyrexia during concomitant administration ol do not exceed 150 mg and in dosing intervals of at an MAOI.5152 least 6 hours (Table 4).

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TABLE 4

Dosing Guidelines for the Newer Antidepressants: SSRIs, Venlafaxine, Nefazodone, and Bupropion

P °se______Fluoxetine Sertraline Paroxetine Venlafaxine Nefazodone Bupropion Adult patients Usual starting dose (mg/day) 20 50 20 75 200 200 (100 mg BID) Usual clinically effective antidepressant dose (mg/day) 20 100-150 20 150-225 300-600 300-450 (<150 mg TID)

Elderly patients Usual starting dose (mg/day) 5-10 25 10 37.5 100 75

Usual clinically effective antidepressant dose (mg/day) 10-20 25-200 10-40 75-225 100-600 75-300

BID denotes twice a day; SSRIs, selective serotonin reuptake inhibitors; TID, three times a day.

The spectrum of side effects associated with of depression, and a family history should be taken. MAOI therapy includes nonaccommodating ortho Family members or other caregivers may provide static hypotension, dizziness, headache, dry mouth, invaluable information about changes in the patient’s insomnia, sedation, memory impairment, fainting, mood and functioning. Clinical depression that is constipation, blurred vision, nausea, peripheral treated appropriately and early in its course is more edema, urinary hesitation, weakness, myoclonal likely to respond to antidepressant therapy. Effective jerks, weight gain, and sexual dysfunction.53 These treatment of depression is a critical element to significant limitations to therapy underlie the use of breaking the pain cycle and to improving quality of MAOIs as third-line treatment options for depres life in patients with chronic pain. sion. REFERENCES 1. Fields HL, Martin JB. Pain: pathophysiology and manage CONCLUSIONS ment. In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL, eds. Harrison’s principles of interna) medicine, 13th ed. New York: McGraw-Hill, 1994:53-5. Chronic pain patients may be particularly resistant 2. NINCDS Report of the Panel on Pain to the National Advisory to a diagnosis of depression because, in their minds, Council of the National Institute of Neurological it implies that their pain is all in their heads. Also, Communication Disorders and Stroke. Washington, DC departm ent of Health, Education, and Welfare, 1979. despite inroads in the awareness and understanding 3. Krause SJ, Wiener RL, Tait RC. Depression and pain behavior of psychiatric disorders, a diagnosis of depression in patients with chronic pain. Clin J Pain 1994; 10:122-7. still carries with it an element of social stigma for 4. Dworldn RH, Gitlin MJ. Clinical aspects of depression in many patients. Educational efforts directed at both chronic pain patients. Clin J Pain 1991; 7:79-94. 5. Magni G, Marchetti M, Moreschi CL, Merekey H, Luchini SR. the patient and family members will assist in con Chronic musculoskeletal pain and depressive symptoms in vincing them of the biological nature of depres the National Health and Nutrition Examination. I. Epidemiologic follow-up study. Pain 1993; 53:163-8. sion—it is not just a weakness of character—and its 6. Von Korff M, Le Resche L, Dworkin SF. First onset of common response to antidepressant treatment. Patients pain symptoms: a prospective study of depression as a risk should be counseled about side effects and the factor. Pain 1993; 55:251-8. expected time to onset of antidepressant response. 7. Katon W, Von Korff M, Lin E, et al. Distressed high utilizers of medical care. DSM-III-R diagnoses and treatment needs. Gen Clinicians must carefully assess patients prior to Hosp Psychiatry 1990; 12:355-62. initiating antidepressant therapy. However, once 8. Wilson DR, Widmer RB, Cadoret RJ, Judiesch K. Somatic symptoms: a mEyor feature of depression in a family practice. depression is diagnosed, treatment in the patient J Affect Disord 1983; 5:199-207. with chronic pain is no different than in patients 9. Hunskaar S, Rosland JH, Hole K. Mechanisms of without pain. Antidepressant therapy should be orphenadrine induced antinociception in mice: a role for sero tonergic pathways. Eur J Pharmacol 1989; 160:83-91. started early and in full doses.47 Patients with chron 10. Magni G. The use of antidepressants in the treatment of ic pain should be screened proactively for symptoms chronic pain. A review of the current evidence. Drugs 1991;

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The Journal of Family Practice, Vol. 43, No. 6 (Suppl), 1996 S 3 3 DEPRESSION AND THE PATIENT WITH CHRONIC PAIN

DISCUSSION depression or it may result from the severe pain Dr De Wester: Is there a particular population the patient is experiencing. Similarly, fatigue, with chronic pain that is more likely to develop which is another common manifestation of depression? depression, may actually be due to the debilitat ing nature of the patient’s disease. Patients with Dr Ruoff: In general, the longer patients have chronic pain treated in specialized settings, such pain, the greater the risk of depression. In my as pain clinics and hospitals, are more likely to be experience, chronic pain involving the neck and diagnosed with depression because practitioners lower back appears to be a trigger point for in these areas are aware of the high incidence of depression. It seems that the functional limita comorbidity. I think there is a need for more edu tions associated with pain in these areas are more cational efforts in the primary care setting con pronounced, including decreased range of cerning the prevalence and treatment of depres motion, tenderness, and inability to perform, sion in the chronic pain patient. which perpetuates feelings of dependency and inadequacy and therefore increases the incidence Dr Susman: What about the concept of receptor of depression observed in this population. fatigue? Many patients with chronic pain are being treated with centrally acting analgesics that Dr Richardson: You mentioned that there is a have activity at the serotonin receptor. Is there a high incidence of depression in chronic pain decreased antidepressant response when you try patients, but is there a problem with underdiag to treat these patients with antidepressants? nosis of the depressive component? It seems that many of the symptoms associated with depres Dr Ruoff: Especially for patients who are depen sion can also be attributed to chronic pain. dent on narcotics or who are receiving multiple pain medications, antidepressants will not have a Dr Ruoff: It is true that symptoms of chronic stimulatory response on the serotonin receptor pain can “mask” depression, which contributes to until we withdraw the narcotic or decrease the the underdiagnosis of depression in the general dose. Once the patient has a narcotic-free period, population. For example, difficulty sleeping or we will see an improved response to antidepres early-morning awakening may be a sign of sant therapy.

S 3 4 The Journal of Family Practice, Vol. 43, No. 6 (Suppl), 1996