Pharmacologic Therapy of Chronic Pain

Narcotics

Although narcotics are arguably the most effective of available analgesic agents, their use is commonly perceived to lead to addiction, leading to a reluctance on the part of most gastroenterologists to use these agents. We agree that such agents should be avoided as far as possible in patients with the functional bowel syndromes. However, many, if not most, other patients with chronic abdominal pain will at some point in time require their use and the compassionate physician is often faced with no other alternative to relieve suffering. The key elements that make for comfortable and judicious use of these drugs is a solid patient-physician relationship, careful patient selection, and the adherence to a fairly rigid protocol for prescription that also includes certain expectations from the patient (eg, restriction of analgesic prescribing to a single physician, return to work, etc). When mild chronic pain necessitates analgesic use, weak opi-oids such as propoxyphene or codeine, are often used, even though they are probably no more potent than simple analgesics, such as acetaminophen alone. More severe pain requires stronger analgesics; for short term use meperidine or morphine can be used. For patients requiring long term analgesics, sustained release preparations, such as transdermal fentanyl (Durgesic), are probably more useful. Agents with mixed agonist-antagonist profiles, such as methadone and buprenorphine, have been advocated by some to avoid addiction, although their use in chronic abdominal pain is not well substantiated.

Opioid analgesics have an adverse effect on GI motility and in addition can induce or exaggerate nausea. Tramadol (Ultram) is a good agent to use in patients with underlying dysmotility, such as gastroparesis, because it is reported to cause less GI disturbance. Meperidine (Demerol) is generally felt to be the drug of choice for patients with pancreatitis because of its lesser tendency to cause sphincter of Oddi spasm; however, this has only been shown to be true at subanalgesic doses. Because it is more likely to produce other side effects, however, it is seldom used for chronic pain management.

Antidepressant Agents as Analgesics

The class of agents that we prescribe most often for chronic abdominal pain is tricyclic antidepressants (TCAs). The efficacy of these drugs has been best validated in patients with somatic neuropathic pain syndromes. Effective analgesic doses are significantly lower than those required to treat depression, and there is reasonable evidence to conclude that the beneficial effects of antidepressants on pain occurs independently of changes in mood. However, in this regard, diminution of anxiety and restoration of mood and sleep patterns should be considered desirable even if they represent primary neuropsychiatric effects of the drug. There are details on psychotropic medications in a separate chapter on functional GI disorders (see Chapter 43, "Psychotropic Drugs and Management of Patients with Functional Gastrointestinal Disorders").

Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine (Paxil), sertraline (Zoloff), and fluoxetine (Prozac), which are currently the mainstay in the treatment of depression, have fewer side effects and have also been advocated for patients with chronic abdominal pain, particularly for patients with functional constipation as they can increase bowel movements and even cause diarrhea. However, they have been less well evaluated in the management of pain per se than TCAs; at the present time, the literature suggests the efficacy of these agents for chronic pain is equivocal at best. Newer antidepressants the serotonin/norepinephrine reuptake inhibitors such as venlafaxine (Effexor) hold more promise in this regard but have not been subjected to extensive testing in this setting. An older agent in the same class, trazadone (Desyrel), has been used with good effect in patients with noncardiac chest pain; although it does not have the usual side effects of the TCAs, it is more sedating and can cause priapism in males.

Before beginning antidepressants it is important to assess the psychological profile of the patient, as this may be important in determining the choice of therapy. If the patient is not depressed, it is critical to spend some time explaining the scientific rationale for the use of antidepressants, with an attempt to clearly separate the analgesic effects from the antidepressant ones. We usually begin with nortryptiline (Pamelor) at a dose of 10 to 25 mg/d and progress as required (and tolerated) to no more than 75 to 100 mg/d. This is given at night and will almost immediately begin helping with disturbed sleep pattern that often accompanies chronic pain. Daytime sedation may occur but tolerance develops rapidly. Tolerance to the antimuscarinic effects may take longer and it is important to advise the patients about this. In the absence of significant side effects, the dose of the antidepressant is gradually increased until adequate benefit is achieved or the upper limit of the recommended dose is reached. It is also important to tell the patient that the analgesic effect may take several days to weeks to develop and that unlike conventional analgesics, the drug is not to be taken on a as needed basis but on a fixed schedule. A trial of at least 4 to 6 weeks at a stable maximum dose is recommended before discontinuation. At that time one may consider switching to another class of antidepressants such as nefazadone (Serzone), mirtazepine (Remcron), or venlafaxine (Effexor). Venflaxinemay also be substituted for a TCA if excessive sedation is observed with the latter.

If the patient is depressed, then it may be more appropriate to use full antidepressant doses of a drug that also has analgesic properties. This could be either a TCA with a low side-effect profile or perhaps one of the newer agents discussed above (not an SSRI). If the patient is already on an antidepressant, but this does not have proven analgesic activity (such as an SSRI), consideration should be given to switch to one that does or to use small doses of a TCA, if tolerated. Such decisions should be made in conjunction with the psychiatrist taking care of the patient.

Other Drugs

A variety of drugs including neuroleptics (fluphenazine [Prolixin], haloperidol [Haldol]), and antiepileptics (pheny-

toin [Dilantin], carmazepine) have been used in chronic somatic pain with equivocal evidence of efficacy and a significant risk of adverse effects. However, we frequently use gabapentin ( Neurontin), a drug with considerable more promise and safety that is widely used for neuropathic pain syndromes. Although admittedly anecdotal, our experience suggests that it may be useful in patients with functional bowel pain syndromes, especially in patients with diabetic gastro-paresis. It can also be used in patients with chronic pancreatitis, in an attempt to "spare" narcotic use. Finally, mention must be made of the use of benzodiazepines, which are frequently used by patients with chronic pain including insomnia, anxiety, and muscle spasm. Although useful in these settings for short term use, there is a significant risk for dependence on these drugs and there is little, if any, evidence that they have any real analgesic effect.

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