Topical amitriptyline combined with ketamine for the treatment of erythromelalgia: a retrospective study of 36 patients at Mayo Clinic.

BACKGROUND: Erythromelalgia is an uncommon neurovascular disorder characterized by redness, increased skin temperature, and pain that usually occurs in the extremities. Treatment remains challenging because of its varying response to medical therapy. The objective of this study was to assess the response of erythromelalgia to compounded topical amitriptyline-ketamine. METHODS: We retrospectively evaluated 36 patients with erythromelalgia who were treated with compounded topical amitriptyline-ketamine from January 1, 2004, through January 31, 2011. RESULTS: Thirty-two patients (89%) were female. Mean (standard deviation) age was 44.7 (15.8) years (range, 5-74 years). Patients applied the medication 1 to 6 times per day (median, 5 times). One patient (3%) had complete relief from symptoms, 14 (39%) had substantial relief, 12 (33%) had some relief, 7 (19%) had no relief, and 2 (6%) had local worsening of symptoms. No patients had systemic adverse effects. CONCLUSIONS: A majority of patients with erythromelalgia (75%) reported improvement in pain with topical application of a compounded amitriptyline-ketamine formulation. The medication was well tolerated.

Bioidentical compounded hormones: a pharmacokinetic evaluation in a randomized clinical trial.

OBJECTIVE: Bioidentical compounded hormone therapy is popular among patients, but providers do not have pharmacokinetic information or dosing guidelines for these preparations. Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice. METHODS: We conducted a randomized, blinded, four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream (Bi-est (80:20); 2.0, 2.5, or 3.0 mg)+compounded oral progesterone 100 mg, or to a conventional estradiol patch (Vivelle-Dot™ 0.05 mg)+Prometrium™ 100mg. Serum levels of estrone, estradiol, estriol, and progesterone were obtained at multiple time intervals during the first 24-h, and at steady-state. RESULTS: Results were analyzable for 37/40 women. Study medications were well tolerated. The AUC at 24h and at steady-state for estrogens remained consistently lower for all doses of Bi-est tested relative to the patch. The difference was statistically significant for Bi-est 2.0mg (AUC-estradiol=181 vs. 956; p<0.001) and 2.5mg (AUC-estradiol=286 vs. 917; p<0.001). Estriol levels remained low in all study arms. Serum progesterone levels were comparable in conventional vs. compounded groups. CONCLUSIONS: This pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the standard-dose estradiol patch. To find comparable doses, further studies are needed. This successfully conducted randomized controlled study attests to the feasibility of using a similar design in the setting of a larger clinical trial.

Topical amitriptyline-ketamine for treatment of rectal, genital, and perineal pain and discomfort.

BACKGROUND: Pain in the rectal, genital, and perineal area is a common condition treated by pain physicians. These chronic pain syndromes are therapeutically challenging because both interventional and drug therapies often are ineffective. OBJECTIVES: To determine if pelvic pain can be treated effectively with compounded topical amitriptyline-ketamine. STUDY DESIGN: A retrospective review of medical records. SETTING: A single academic medical center in the United States. METHODS: We identified all patients treated with topical amitriptyline-ketamine from January 1, 2004, through November 28, 2011. Medical records were evaluated to determine the diagnosis for which the medication was prescribed. Treatment efficacy and any adverse effects were recorded. RESULTS: Of the 1,068 patients who received amitriptyline-ketamine, 13 had the medication prescribed for genital, rectal, or perineal pain and had medication efficacy recorded. Of these 13 patients, one (8%) had complete relief, 6 (46%) had substantial relief, 4 (31%) had some relief, and 2 (15%) had no response. One patient reported occasional irritation while using topical amitriptyline-ketamine with lidocaine; no other patients reported local or systemic adverse effects. LIMITATIONS: Retrospective review; lack of uniform system for pain grading; concurrent use of other medications. CONCLUSIONS: Topical amitriptyline-ketamine provided a high rate of pain relief with a low adverse-effect burden in patients with pelvic pain. This topical medication could offer an effective, noninvasive, nonopioid therapy for pain in the rectum, perineum, and genitals.