Placebos Heal

Brinkhaus, D. Pach, R. Luedtke, S. N. Willich (2008) Who controls the placebo Introducing a Placebo Checklist for pharmacological trials. Contemporary Clinical Trials, 29, 149-156. 

Brunoni, M. Lopes, T. J. Kaptchuk, F. Fregni (2009) Placebo response of non-pharmaco-logical and pharmacological trials in major depression a systematic review and meta-analysis. FLOS One, 4, e4824. 

Benedetti, M. Schedlowski (2008) New insights into the placebo and nocebo responses. Neuron, 59, 195-206. 

Finniss, T. J. Kaptchuk, F. Miller, F. Benedetti (2010) Biological, clinical, and ethical advances of placebo elfects. Lancet, 375, 686-695. 

Kaptchuk, J. M. Kelley, A. Deykin, P. M. Wayne, L. C. Lasagna, I. O. Epstein, I. Kitsch, M. E. Wechsler (2008) Do placebo responders exist Contemporary Clinical Trials, 29, 587—595. 

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With that story as part of his family lore, Wager grew up sceptical of claims about the healing power of the mind, but he also developed a keen interest in the kinds of health-related outcomes that might be affected by belief. That interest eventually led him to conduct scientific investigations of the placebo effect, studies that have given him an international reputation. 

The authors concluded first that patients can be willing to take placebo and can improve despite disclosure, and that belief in the pill as drug was not a requirement for improvement.. . . Improvement was not related to belief in the nature of the pills but did appear related to certainty of belief (p. 344). Placebos apparently need not be lies that heal (Harrington, 1997). 

Kokol R, Berger C, Haas J, Kopera D (2005) Venous leg ulcers no improvement of wound healing with 685-nm low level laser therapy Randomized, placebo-controlled, double-blind study. Hautarzt 56(6) 570-575... 

The guanosine analog penciclovir, the active metabolite of famciclovir, is available for topical use. Penciclovir cream (1%) is effective for the treatment of recurrent herpes labialis (Table 49-1). When applied within 1 hour of the onset of prodromal symptoms and continued every 2 hours during waking hours for 4 days, median time until healing was shortened by 17 hours compared with placebo. Adverse effects are uncommon, although application site reactions occur in about 1%. 

Docosanol is a saturated 22-carbon aliphatic alcohol that inhibits fusion between the plasma membrane and the HSV envelope, thereby preventing viral entry into cells and subsequent viral replication. Topical docosanol 10% cream is available without a prescription application site reactions occur in approximately 2%. When applied within 12 hours of the onset of prodromal symptoms, five times daily, median healing time was shortened by 18 hours compared with placebo in recurrent orolabial herpes. 

To test for the hallucinogenic activity of S. divinorum in human beings, we drank the infusion of the leaves and waited for the effects to occur. Within 30 min we began to see visions, which lasted for several hours. This allowed rapid confirmation of the mint s psychotropic activity. But more interesting from a therapeutic standpoint are the other properties attributed to the plant properties that are much more difficult to assess. Are these concepts that are translatable into our western (orthodox) healing theory, or is ska Maria Pastora being used as a magical treatment (for a placebo effect) Extended observations in the field by an acute observer would undoubtedly be more fruitful than immediate attempts to isolate compounds responsible for these purported activities. 

Most clinical experience with iloprost has been gained in patients with critical leg ischemia. An intermittent intravenous infusion of up to 2 nanograms/kg/minute for 2-4 weeks reduced rest pain and improved ulcer healing in roughly half of the patients with critical leg ischemia, including diabetics. Compared with placebo, the improvement obtained with iloprost was significant in most but not all individual clinical trials. In addition, a meta-analy-sis showed a 15% reduction in major amputation rate compared with placebo (2). 

The long-term use of oxandrolone has been studied in children with very severe bums (covering 40% or more of the body surface). Under controlled conditions, 84 children (56 girls and 28 boys mean age 8 years) received treatment for 1 year with placebo or oral oxandrolone 0.1 mg/kg bd (92). At discharge (95% healed) and at 6, 9, and 12 months after the burn, oxandrolone improved lean body mass, bone mineral content, and bone mineral density compared with placebo and there was no adverse effect on hepatic transaminases. The latter finding, and the absence of other adverse effects, suggests that this treatment of very severely burnt children is defensible. 

Penciclovir [pen SIK lo veer] is an acyclic guanosine nucleoside derivative that is active against herpes simplex virus Types I and II, and against varicella-zoster virus. Penciclovir is only administered topically (Figure 37.8). Penciclovir is monophosphorylated by viral thymidine kinase, and cellular enzymes form the nucleoside triphosphate, which inhibits herpes DNA polymerase. Penciclovir triphosphate has an intracellular half-life 20 to 30 times longer than does acyclovir triphosphate (see p. 365). Penciclovir is negligibly absorbed from topical application, and is well tolerated. Both healing and pain are shortened approximately one-half day in duration, compared to placebo-treated subjects. 

A placebo-controUed study of patients with stromal keratitis receiving topical prednisolone and trifluridine showed no benefit to adding oral acyclovir in terms of time to healing or treatment failure, likelihood of resolution, or 6-month best corrected acuity (HEDS). 

A small, randomly assigned, double-blind, placebo-controUed study of patients with dendritic HSV keratitis treated with oral acyclovir or topical acyclovir ointment showed no significant difference between treatment groups in the number of patients healed or the median healing time (CoUum et al.). 

A double-blind placebo-controUed trial showed 800 mg more effective than 400 mg of oral acyclovir for significantly accelerated time to 50% scabbing, accelerated time to 50% healing, less frequent formation of new lesions, and reduced duration and severity of pain. AU participants had localized zoster rashes present for 72 hours or less (Huff et al.). 

A multicenter, randomized, double-blind, double-placebo, parallel-design study of immunocompetent patients with recurrent HSV genital infections showed no significant difference between oral famciclovir and oral acyclovir in time to complete healing, resolution of symptoms, or frequency, type, and severity of adverse events (Chosidow et al.). 

A large, multicenter, randomized, double-blind, placebo-controlled study evaluated the treatment effect of famciclovir on herpes zoster and post-herpetic neuralgia in immunocompetent participants and found faster resolution of post-herpetic neuralgia, faster lesion healing, and a safety profile similar to the placebo group (Tyring et al.). 

In a randomized, double-blind, placebo-controlled study in Saudi Arabia of oral fluconazole (200 mg/day for 6 weeks) in the treatment of cutaneous leishmaniasis, 106 patients were assigned to fluconazole and 103 to placebo (28). Follow-up data were available for 80 and 65 patients respectively. At the 3-month follow-up, healing of lesions was complete in 63 of the 80 patients who took fluconazole and 22 of the 65 patients who took placebo (relative risk of complete healing, 2.33 95% Cl = 1.63, 3.33). Adverse effects were mild and similar in the two groups. 

In a multicenter, randomized, placebo-controlled, doubleblind study of 0.2% glyceryl trinitrate ointment in 132 patients with anal fissures over at least 4 weeks, healing rates were similar with glyceryl trinitrate and placebo, but adverse events were more frequent in those who used glyceryl trinitrate 34% complained of headache and 5.9% had orthostatic hypotension (16). 

Altomare DF, Rinaldi M, Milito G, Arcana F, Spinelli F, Nardelli N, Scardigno D, Pulvirenti-D Urso A, Bottini C, Pescatori M, Lovreglio R. Glyceryl trinitrate for chronic anal fissure—healing or headache Results of a multicenter, randomized, placebo-controled, double-blind trial. Dis Colon Rectum 2000 43(2) 174-81. 

To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac, 12 healthy volunteers took consecutive 2-week courses of omeprazole 40 mg/day or placebo, with diclofenac given in the second week of each course, in a double-blind, crossover study (3). Omeprazole did not accelerate the healing of pre-existing mucosal lesions or prevent the development of small diclofenac-induced mucosal lesions. Omeprazole increased serum gastrin in all subjects. 

Placebo effect or placebo response has been referred to as the lie that heals.It is the change in patient condition due to a symbolic intervention and increased awareness (e.g., consultation, procedure) rather than pharmacologic or physiologic intervention. It is used to eliminate observational bias in many clinical trials. " Elements of placebo response exist in almost every patient encounter. Variables that have been shown to affect patient outcomes... 

Preliminary placebo-controlled studies with esomeprazole indicate that maintenance of erosive esophagitis healing occurs in 54% to 94% of patients after 6 months of 10-mg to 40-mg doses of esomperazole. Doses of 20 mg to 40 mg were superior to the 10-mg dose. Studies are needed comparing esomeprazole to the other proton pump inhibitors in maintenance therapy for GERD. 

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