Pain is a leading reason why patients with GI disorders seek alternative therapeutic agents. Clinicians need to take a proactive stance in controlling use of those agents, Lawrence R. Schiller, MD, told an audience at the American College of Gastroenterology (ACG) 77th Annual Scientific Meeting in Las Vegas. Dr Schiller is ACG President and Program Director of the gastroenterology fellowship at Baylor University Medical Center in Dallas.
Non-narcotic agents can approach the effectiveness of opiates with less sensitization and fewer other adverse effects, Dr Schiller said. However, he cautioned that most of these options are off-label, and noted that discussing this issue with patients and involving them in any decisions regarding their use is important.
Several classes of drugs seem to have positive effects for patients with GI disorders, Dr Schiller suggested. They include NSAIDs, anticonvulsants, alpha-adrenergic agents, neuromuscular agents, and antidepressants.
NSAIDs reduce prostaglandin synthesis and sensitivity of primary afferent neurons; they may be useful in patients with abdominal wall pain and cancer, Dr Schiller noted. Ketorolac, an injectable NSAID, has efficacy close to that of morphine. However, these medications also have known adverse effects, including dyspepsia, ulcer disease, GI bleeding, diarrhea, and renal dysfunction, Dr Schiller added. Drug interactions also are possible.
Anticonvulsants, originally developed to reduce repetitive nerve discharges in the brain associated with seizures, were found to be useful in neuropathic pain and have since been explored for other pain symptoms. They have been found to be useful for such painful conditions as phantom limb, central pain syndrome, migraine, multiple sclerosis, and diabetic and peripheral neuropathy.
For pain, carbamazepine, an FDA-approved anticonvulsant for managing some painful conditions, should be prescribed at doses between 800 and 1200 mg/d, Dr Schiller explained. Carbamazepine should be taken with food to avoid gastric distress. Adverse effects include sedation, nausea, and vertigo; a complete blood cell count and liver tests should be undertaken regularly for patients who take this medication.
The anticonvulsant gabapentin also has been FDA-approved to manage some pain conditions. Gabapentin may be titrated to a maximum of 1200 mg TID. However, Dr Schiller usually finds that about 300 mg works well for his patients. Adverse effects may include somnolence, dizziness, and ataxia.
Pregabalin, a GABA analog that interacts with GABA receptor, is a third FDA-approved anticonvulsant. Pregabalin binds to voltage-gated calcium channel, Dr Schiller explained. This agent is effective in doses between 50 mg to 200 mg TID. Headache, dizziness, and somnolence are associated adverse effects. Pregabalin is regulated as a controlled substance.
Neuromuscular agents, such as baclofen and cyclobenzaprine, may be good as adjunctive medications, Dr Schiller noted.
Similarly, alpha-adrenergic agonists like clonidine also may be a good choice for controlling pain. Clonidine is associated with such adverse effects as dry mouth, drowsiness, fatigue, and dizziness, and its antihypertensive effect may be limiting. For analgesic effects with clonidine, Dr Schiller suggested that the patch delivery system works best.
The antidepressants (with the exception of imipramine) show promise, Dr Schiller said, but the data on antidepressant use in irritable bowel syndrome are mixed. He commented that these agents are not terrible, but not everyone will do better with them.
Tricyclic antidepressants (TCAs) tend to work better than selective serotonin reuptake inhibitors (SSRIs), according to Dr Schiller, who suggested that TCAs should be thought of as “pain modifiers.” Use caution when prescribing TCAs because of some adverse effects, heed the contraindications, he added.
There is less evidence for the effectiveness of SSRIs, and the adverse effects require monitoring, Dr Schiller noted. Despite limited data, he suggested that physicians become familiar with these agents, and consider when other conditions (eg, depression accompanying GI disorder pain) may call for their use.