A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection

Inclusion Criteria Concurrent Medication: Allowed: * Aspirin and acetaminophen. * Nonsteroidal anti-inflammatory agents. * Opiates. * Pyridoxine (only if accompanied by isoniazid). * ddI, ddC, d4T, and 3TC if on a stable dose. * AZT. * Cimetidine if on a stable dose. NOTE: * Per 3/16/95 amendment, Lactaid may be taken by lactose-intolerant patients for effects of lactose in placebo capsules. Concurrent Treatment: Allowed: * Acupuncture. Patients must have: * Documented HIV infection. * Painful peripheral neuropathy. NOTE: * Patients in ACTG blinded studies of dideoxynucleosides such as ddI, ddC, and d4T are encouraged to enroll in this study. Prior Medication: Allowed: * Prior ddI, ddC, d4T, or 3TC, if on a stable dose for at least 8 weeks prior to study entry. * Prior cimetidine if on a stable dose for at least 2 weeks prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: * Diabetes mellitus. * Neurological disease of sufficient severity to confound the evaluation of peripheral neuropathy, such as myelopathy without neuropathy. (NOTE: Patients with both myelopathy AND painful peripheral neuropathy are eligible.) * Electrocardiogram (EKG) indicating malignant arrhythmia or cardiac conduction disturbances (such as second or third degree AV block, anterior hemi-block, or prolonged QT interval). * Suicidal thoughts of sufficient severity to require treatment with antidepressant medication. Concurrent Medication: Excluded: * Phenytoin or carbamazepine (unless on stable dose for 8 weeks prior to study entry). * Capsaicin. * Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine (except as dispensed for this study). * Disopyramide. * Procainamide. * Quinidine. * Tocainide. * Flecainide acetate. * Encainide. * Lidocaine. * Cisplatin. * Vincristine. * Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to previously taking these drugs). * Any investigational drugs other than 3TC (except with permission of the protocol team). * Terfenadine (if concurrent with ketoconazole). Patients with the following prior conditions are excluded: * Documented history of cardiac disease. * History of allergy to, or intolerance of, tricyclic antidepressants, mexiletine, or benztropine. Prior Medication: Excluded: * Prior disopyramide. * Prior procainamide. * Prior quinidine. * Prior tocainide. * Prior flecainide acetate. * Prior encainide. * Prior lidocaine. * Cisplatin or vincristine within 8 weeks prior to study entry. * Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin within 8 weeks prior to study entry (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to taking these drugs). * Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine, within 4 weeks prior to study entry. * More than 50 percent change in the weekly dosage of any pain control medications within 2 weeks prior to study entry. Per 3/16/95 amendment: * ddI, ddC, d4T, or 3TC within 8 weeks prior to study entry ONLY IF dideoxynucleoside dosing was suspended or permanently discontinued. Risk Behavior: Excluded: * Active drug or alcohol abuse.