Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. Double-blind, placebo-controlled study of the application of capsaicin cream in chronic distal painful polyneuropathy. The postmastectomy pain syndrome and topical capsaicin: a randomized trial. Topical capsaicin in the management of HIV-associated peripheral neuropathy. Topical capsaicin for treatment of hemodialysis-related pruritus. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Capsaicin Study Group. Topical capsaicin treatment of chronic postherpetic neuralgia. A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy.
A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial.
                Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires.
                During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001).
                A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference. We have completed a 12-week double-blind, placebo-controlled randomized study on the efficacy of the application of capsaicin (CAPS) cream (0.075%) in the treatment of chronic distal painful polyneuropathy. Forty patients were enrolled and 39 completed the study. The 2 limbs were randomly assigned to CAPS or placebo (PLAC). The cream was applied 4 times a day. The first tube contained the active PLAC, methyl nicotinate. In the final 4 weeks (single-blind wash-out phase), PLAC was administered bilaterally. Efficacy was evaluated using the following scales: (1) investigator global, (2) patient global, (3) visual analog (VAS) of pain severity, (4) VAS of pain relief, (5) activities of daily living, and (6) allodynia. Patients were examined at onset and at monthly intervals using a neurologic disability scale, nerve conduction studies, computer-assisted sensory examination for vibration and thermal cooling and warming, QSART (quantitative sudomotor axon reflex test) and quantitative flare response. There was no statistical evidence of efficacy of CAPS cream over PLAC for any of the pain indices. At early time points (1-4 weeks), there were a small number of indices that favored the PLAC. The percent of limbs that improved on the investigator's global scale were 51.3 vs. 53.8 at 4 weeks, 56.4 vs. 64.1 at 8 weeks and 59 vs. 66.7 at 12 weeks for CAPS vs. PLAC; no statistically significant difference was found. All the safety indices showed no difference between sides. We interpret the early hyperalgesia on the CAPS side as being responsible for the better performance of PLAC at early time points. The large percentage of limbs that improved may be a pronounced PLAC response. This paper describes a randomized parallel trial of topical 0.075% capsaicin versus vehicle (placebo) in the postmastectomy pain syndrome (PMPS). The study was double-blind in design; however, this was compromised by the burning sensation induced by capsaicin. We could not demonstrate a significant difference in the visual analogue scale (VAS) for steady pain although a trend was present. A significant difference was found, however, in the VAS for jabbing pain, in category pain severity scales, and in overall pain relief scales in favour of capsaicin. Five of 13 patients on capsaicin were categorized as good-to-excellent responses with 8 (62%) having 50% or greater improvement. Only 1 of 10 cases had a good response to vehicle with 3 rated as 50% or better. Distal symmetrical peripheral neuropathy (DSPN) is a particularly distressing pain syndrome associated with human immunodeficiency virus (HIV) disease. Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes, and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN. This multicenter, controlled, randomized, double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity, pain relief, sensory perception, quality of life, mood, and function for patients who received topical capsaicin to the corresponding measures for patients who received the vehicle only. Twenty-six subjects were enrolled in the study. At the end of 1 week, subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle (Mann-Whitney test; P = 0.042). The dropout rate was higher for the capsaicin group (67%) than for the vehicle group (18%) (chi 2 test of association; P = 0.014). There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain, worst pain, pain relief, sensory perception, quality of life, mood, or function at study entry or at any time during the 4-week trial. These results suggest capsaicin is ineffective in relieving pain associated with HIV-associated DSPN. Pruritus is a significant problem for many patients undergoing long-term hemodialysis. Topical capsaicin depletes and prevents the reaccumulation of substance P in peripheral sensory neurons. Substance P functions in the transmission of pain and probably itch sensations. An open-label, uncontrolled trial and a double-blind, vehicle-controlled trial were conducted to evaluate the efficacy and safety of capsaicin 0.025% cream in the treatment of localized areas of pruritus in patients undergoing long-term hemodialysis. Eight of nine evaluable patients in the open-label trial reported marked relief or complete resolution of itching during the study period, and two of five evaluable patients in the double-blind trial reported complete resolution of itching in the capsaicin-treated arm with no or minimal improvement in the vehicle-treated arm. Twelve patients in the open-label trial and two in the double-blind trial were unevaluable. No serious treatment-related adverse reactions occurred. To establish the effects of topically applied capsaicin on daily activities in patients with painful diabetic neuropathy.
                Investigators at 12 sites enrolled 277 men and women with painful peripheral polyneuropathy and/or radiculopathy in an 8-wk double-blind vehicle-controlled study with parallel randomized treatment assignments. Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and/or sleep. Either 0.075% capsaicin cream or vehicle cream was applied to the painful areas 4 times/day. A visual analogue scale of pain intensity and baseline measurements of the pain's interference with the ability to walk, work, participate in recreational activities, use shoes and socks, sleep, and eat were recorded at onset and at 2-wk intervals. A physician's global evaluation scale assessed changes in pain status from baseline.
                Statistically significant differences are percentage of patients with improvement in favor of capsaicin versus vehicle: 69.5 vs 53.4% with clinical improvement in pain status (P = 0.012), 26.1 vs. 14.6% with improvement in walking (P = 0.029), 18.3 vs. 9.2% with improvement in working (P = 0.019), 29.5 vs. 20.3% with improvement in sleeping (P = 0.036), and 22.8 vs. 12.1% with improvement in participating in recreational activities (P = 0.037).
                The results from this study suggest that topical 0.075% capsaicin is effective for reducing pain in patients with painful diabetic neuropathy with subsequent improvement in daily activities, enhancing the quality of the patient's life. Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia. In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period. Response to treatment was evaluated by visual analogue scales of pain and of pain relief, together with changes in a categoric pain scale and in a physician's global evaluation. Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables. After 6 weeks almost 80% of capsaicin-treated patients experienced some relief from their pain. Because capsaicin avoids problems with drug interactions and systemic toxicity, we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia. A large double-blind, vehicle-controlled study of 143 patients with chronic postherpetic neuralgia (PHN) was performed to evaluate the degree of efficacy of topically applied capsaicin 0.075% cream. In addition, the safety and efficacy of long-term application of topical capsaicin in PHN was assessed by following patients in an open-label study for up to 2 years. In the double-blind phase, 143 patients with PHN of 6 months' duration or longer were enrolled. Since epidemiologic studies of patients who receive no treatment have shown that only 10% to 25% of those with PHN after 1 month will still have pain at 1 year, two separate efficacy analyses were performed: one with all evaluable patients (n = 131) and the other with 93 patients whose PHN lasted for longer than 12 months prior to study startup. All efficacy variables, including the physician's global evaluation of reduction in PHN pain, changes in pain severity on the categoric scale, visual analogue scale for pain severity, visual analogue scale for pain relief, and functional capacity scale, showed significant improvement at nearly all time points throughout the study for both patient groups, based on duration of PHN pain. In contrast, the group receiving vehicle cream remained essentially unchanged. Data from the long-term, open-label phase (up to 2 years, n = 77), which immediately followed the 6-week blinded phase, showed that the clinical benefit in patients treated for a short (6-week) period with topical capsaicin could be maintained or amplified in most patients (86%) during prolonged therapy. There were no serious adverse effects observed or reported throughout the trial; in fact, the only side effect associated with capsaicin treatment was the burning or stinging at local sites of application (in 9% of patients) during exposures of up to 2 years (long-term phase). On the basis of these data, we conclude that capsaicin 0.075% cream is a safe and effective treatment for the pain of postherpetic neuralgia and should be considered for initial management of patients with this condition. An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.
There is insufficient evidence to assess the use of capsaicin in clinical practice.