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PubMed2001

Antidepressant versus placebo for depressed elderly.

BACKGROUND: Depression warranting intervention is found in ten percent of people over the age of 60. Older depressed people are more likely to die than non-depressed. Relatively few receive therapeutic interventions, and those that do, tend to receive low dose antidepressant therapy. Depression in older people is thought to differ in terms of aetiology, presentation, treatment and outcome than in younger people. Concomitant physical illness and increasing social, physical and neurophysiological diversity are associated with the ageing process. Consequently drug treatment of older patients is often carried out in institutions and on patients suffering from multiple physical problems. OBJECTIVES: To determine the efficacy of antidepressant medication compared with placebo in the treatment of depression in older patients. SEARCH STRATEGY: The search strategy incorporated: electronic literature searches of databases held by the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group (CCDAN) (see Collaborative Review Group Search Strategy). Reference lists of related reviews and references of located studies. Contact was made with authors working in the field. SELECTION CRITERIA: All randomised, placebo controlled trials using antidepressants in the treatment of the presenting episode of depression in patients described as elderly, geriatric senile or older adult. DATA COLLECTION AND ANALYSIS: Two types of data were extracted (if available) from each study. The first type of data was dichotomous data, this consisted of recovered/not recovered. The second, continuous data,included: Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Rating Scale (MADRS) and other depression rating scale scores. An analysis using Peto Odds ratios for the dichotomous data and weighted mean difference for continuous data was performed using RevMan 3.1. The presence of heterogeneity of treatment effect was assessed. MAIN RESULTS: Seventeen trials contributed data to the analyses comparing the efficacy of antidepressant treatment and placebo. Analyses of efficacy was based on 245 patients treated with TCAs (223 with placebo), 365 patients treated with SSRIs (372 with placebo) and 58 patients treated with MAOIs (63 with placebo). The standardised effect size for the three groups respectively were: TCAs; OR: 0.32 (0.21,0.47), SSRIs; OR; 0.51 (0.36,0.72), MAOIs: 0.17 (0.07,0.39). REVIEWER'S CONCLUSIONS: TCAs, SSRIs and MAOIs are effective in the treatment of older community patients and inpatients likely to have severe physical illness. At least six weeks of antidepressant treatment is recommended to achieve optimal therapeutic effect. There is little evidence concerning the efficacy of low dose TCA treatment. Further trials are required before low dose TCA treatment is routinely recommended.

Aged↗
PubMed2001

Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug.

OBJECTIVE: To evaluate the short-term efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis (AS). METHODS: The study was a 6-week randomized, double-blind, placebo-controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain > or =40 mm on a 100-mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]). RESULTS: Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were -13 mm, -21 mm, and -27 mm (P = 0.006) for pain and 1, -6, and -12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively. CONCLUSION: The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage, with significant improvement of both pain and function in patients with AS.

Adult↗
PubMed1994

Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial.

OBJECTIVE: To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine. METHODS: Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo. RESULTS: After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2-9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response. CONCLUSION: Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.

Amitriptyline↗
PubMed2005

A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the safety and efficacy of etanercept in the treatment of uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Children who met the American College of Rheumatology diagnostic criteria for JIA with active uveitis, who had anterior chamber cells of >/=1+ or requiring topical corticosteroid >/=3 times daily, and who were on a stable regimen for arthritis treatment were eligible. Study participants received etanercept (0.4 mg/kg) or placebo administered subcutaneously twice weekly for 6 months. All participants received open-label etanercept for an additional 6 months. RESULTS: Five patients received placebo and 7 received etanercept. Three of the 7 patients treated with etanercept and 2 of the 5 placebo-treated patients were considered ophthalmic successes (P = 1.0). One patient in each treatment group was considered a treatment failure. Three of the 7 etanercept-treated and 2 of the 5 placebo-treated patients were neither successes nor failures by our definition. There were no serious adverse events for any patient during the entire study period. Reports of minor infections were comparable in each treatment group, 71% for etanercept and 60% for placebo (P = 0.58). CONCLUSION: In this small pilot study there was no apparent difference in the anterior segment inflammation between patients treated with etanercept and placebo. The stringent criteria used to measure ophthalmic success of treatment and the small patient population limit the implications of our findings.

Adolescent↗
PubMed2005

Continuous indices of core data set measures in rheumatoid arthritis clinical trials: lower responses to placebo than seen with categorical responses with the American College of Rheumatology 20% criteria.

OBJECTIVE: To describe indices that are continuous counterparts of categorical responses to the American College of Rheumatology 20% improvement criteria (ACR20), ACR50, and ACR70, which extend rheumatoid arthritis (RA) clinical trial results and recognize clinical worsening (as well as improvement) with active and placebo treatments. METHODS: Data from a clinical trial of leflunomide, methotrexate, and placebo treatment over 1 year were reanalyzed. Percent change was computed for each of the 7 components of the ACR core set of outcome measures. Four continuous indices were computed: 1) ACR-N (lowest of 3 values: number of swollen joints, number of tender joints, and median of the other 5 measures); 2) composite (median of all 7 measures [3 patient and 3 assessor measures plus erythrocyte sedimentation rate]); 3) patient-only (median of physical function, pain, and global status); and 4) assessor-only (median of number of swollen joints, number of tender joints, and global status). Means, medians, categorical 20%, 50%, and 70% responses, and continuous probability plots were computed according to each index for the 3 treatment groups and were compared with one another and with standard ACR20, ACR50, and ACR70 responses. RESULTS: Mean levels of improvement calculated using the different methods, in patients taking leflunomide, placebo, and methotrexate, respectively, were as follows: ACR-N 20%, -12%, and 13%; composite 43%, 9%, and 33%; patient-only 36%, 0%, and 26%; assessor-only 50%, 20%, and 44%; and ACR20 52%, 26%, and 46%. Differences between leflunomide and placebo were 30-36%, and differences between methotrexate and placebo were 24-26%. CONCLUSION: Continuous indices may be an informative addition to categorical ACR 20%, 50%, or 70% responses to compare efficacies of various treatments in RA, and to describe lower responses to placebo by recognizing worsening as well as improvement.

Antirheumatic Agents↗
PubMed2005

Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA). METHODS: Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area. RESULTS: At week 12, 58% of the adalimumab-treated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and well-tolerated. CONCLUSION: Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.

Adalimumab↗
PubMed2002

Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) versus placebo in active spondylarthropathy.

OBJECTIVE: To confirm in a placebo-controlled trial the safety and efficacy profile of infliximab in short-term treatment of patients with active spondylarthropathy (SpA). METHODS: Forty patients with active SpA were randomly assigned to receive an intravenous loading dose (weeks 0, 2, and 6) of 5 mg/kg infliximab or placebo. Evaluations for efficacy and safety were performed at weeks 1, 2, 6, 8, and 12. The primary end points of this study were the improvements in patient and physician global assessments of disease activity on a 100-mm visual analog scale. RESULTS: Both primary end points improved significantly in the infliximab group compared with the baseline value, with no improvement in the placebo group. As early as week 2 and sustained up to week 12, there was a highly statistically significant difference between the values for these 2 end points in the infliximab versus the placebo group. In most of the other assessments of disease activity (laboratory measures, assessments of specific peripheral and/or axial disease), significant improvements were observed in the infliximab group compared with the baseline value and compared with placebo. Minor adverse events not causing discontinuation were equally observed in both treatment groups. There was one severe drug-related adverse event, in which a patient developed disseminated tuberculosis. CONCLUSION: Tumor necrosis factor alpha blockade with infliximab in patients with active SpA was well tolerated and resulted in significant clinical and laboratory improvements in this short-term, placebo-controlled study. However, the occurrence of tuberculosis in one patient necessitates strict inclusion criteria and long-term followup.

Adult↗
PubMed2004

Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial.

BACKGROUND: The authors previously reported the efficacy of a dose of 4 mg of zoledronic acid in reducing skeletal complications in patients with bone metastases secondary to lung carcinoma and other solid tumors (except carcinomas of the breast and prostate). In the current study, they update these results and report the long-term efficacy and safety of 21 months of treatment with zoledronic acid in a randomized, placebo-controlled trial. METHODS: A total of 773 patients were randomized to receive zoledronic acid (4 mg or 8 mg) or placebo via a 15-minute infusion every 3 weeks for 21 months. The 8-mg dose later was reduced to 4 mg (8/4-mg group). The primary efficacy endpoint was the percentage of patients at 21 months with >/= 1 skeletal-related event (SRE) (pathologic fracture, spinal cord compression, radiation therapy to bone, or surgery to bone). Secondary analyses (time to first SRE, annual incidence of SREs, and multiple-event analysis) included hypercalcemia of malignancy. RESULTS: Fewer patients treated with zoledronic acid developed at least 1 SRE at 21 months compared with patients treated with placebo (39% of those treated at the 4-mg dose [P =0.127] and 36% of those treated at the 8/4-mg dose [P = 0.023], compared with 46% of those treated with placebo). Furthermore, 4 mg of zoledronic acid significantly delayed the median time to first SRE (236 days with 4 mg vs. 155 days with placebo; P = 0.009) and significantly reduced the annual incidence of SREs (1.74 per year with the 4-mg dose vs. 2.71 per year with placebo; P = 0.012). Moreover, the 4-mg dose of zoledronic acid was found to reduce the risk of developing a skeletal event by 31% (hazard ratio of 0.693; P = 0.003). Zoledronic acid was found to be well tolerated with long-term use; the most commonly reported adverse events in all treatment groups included bone pain and the transient, acute-phase reactions of nausea, anemia, and emesis. CONCLUSIONS: To the authors' knowledge, zoledronic acid is the first bisphosphonate to demonstrate long-term safety and efficacy in this patient population.

Antineoplastic Agents↗
PubMed2005

Moving from empirically supported treatment lists to practice guidelines in psychotherapy: the role of the placebo concept.

The use of placebos is the "gold standard" in studies of investigational drugs, and of other medical procedures as well. Several recent trends have suggested the use of placebos in studies of psychotherapy to isolate effective treatment components, and as a basis for establishing lists of empirically supported treatments. Unlike within the domain of medicine, in which the logic of placebos is relatively straightforward, the concept of placebo as applied to psychotherapy is fraught with both conceptual and practical problems. The evidence-based practice of psychotherapy can best be promoted through the development of practice guidelines, for which psychotherapy placebos are unnecessary. Moreover, even if problems associated with psychological placebos could be overcome, they are not necessary in psychotherapy research.

Empirical Research↗
PubMed2001

The placebo response to citric acid-induced cough: pharmacodynamics and gender differences.

Characteristics of the response to placebo in a citric acid-induced cough challenge were investigated as part of a randomized, double-blind crossover trial to assess the antitussive effect of dextromethorphan. Baseline cough responses were established on two occasions in 22 healthy subjects. They received 60 ml placebo antitussive syrup and cough frequency following five inhalations of 10% citric acid over 5 min was measured at regular intervals up to 12 h. Response-time models of varying complexity were used to describe the placebo cough suppression data. The cough response to placebo was also compared to that of the untreated state. The placebo cough response was best characterized by a non-linear increase in cough suppression up to a maximum reduction of 1.6 coughs from baseline at 4-4.5 h, followed by a non-linear return to baseline. The cough response in the untreated state was not different from that of placebo (P=0.99). Females coughed more frequently than males (median number of coughs=10.5 vs. 9.0, respectively P<0.001; Mann-Whitney U test), and adaptation to the cough stimulus was significantly more rapid in females (P<0.025). Accordingly, in trials that use citric acid-induced cough, gender should be considered in study design, particularly in relation to the timing of measurements.

Administration, Inhalation↗
PubMed1986

Comparison of the effects of pre-exercise feeding of glucose, glycerol and placebo on endurance and fuel homeostasis in man.

Six men were studied during exercise to exhaustion on a cycle ergometer at 73% of VO2max following ingestion of glycerol, glucose or placebo. Five of the subjects exercised for longer on the glucose trial compared to the placebo trial (p less than 0.1; 108.8 vs 95.9 min). Exercise time to exhaustion on the glucose trial was longer (p less than 0.01) than on the glycerol trial (86.0 min). No difference in performance was found between the glycerol and placebo trials. The ingestion of glucose (lg X kg-1 body weight) 45 min before exercise produced a 50% rise in blood glucose and a 3-fold rise in plasma insulin at zero min of exercise. Total carbohydrate oxidation was increased by 26% compared to placebo and none of the subjects exhibited a fall in blood glucose below 4 mmol X 1-1 during the exercise. The ingestion of glycerol (lg X kg-1 body weight) 45 min before exercise produced a 340-fold increase in blood glycerol concentration at zero min of exercise, but did not affect resting blood glucose or plasma insulin levels; blood glucose levels were up to 14% higher (p less than 0.05) in the later stages of exercise and at exhaustion compared to the placebo or glucose trials. Both glycerol and glucose feedings lowered the magnitude of the rise in plasma FFA during exercise compared to placebo. Levels of blood lactate and alanine during exercise were not different on the 3 dietary treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Comparative efficacy and safety of bupropion and placebo in the treatment of depression.

This was a 4-week, three-center, double-blind, randomized, parallel, placebo-controlled evaluation of the efficacy and safety of bupropion in hospitalized depressed patients. Results from 27 placebo and 48 bupropion-treated patients were analyzed for efficacy and safety. Assessments of efficacy and safety were made at baseline and weekly during the study. Preliminary and secondary measures of efficacy included the Clinical Global Impressions for severity (CGI-S) and improvement (CGI-I) of illness, Hamilton Depression and Hamilton Anxiety Scales, and the Zung Self-Rating Scales for depression and anxiety. Assessments of safety included vital signs, electrocardiogram, clinical laboratory tests, and adverse experiences. Dosages of bupropion were 300-600 mg/day. Results showed that bupropion was significantly (P less than 0.01) more effective than placebo at termination of study on the CGI-S, CGI-I, Hamilton Depression and Hamilton Anxiety Scales. On the Zung Self-Rating Depression and Anxiety Scales, statistical trends favored bupropion at termination of study over placebo (P less than 0.10). Adverse events in the bupropion and placebo groups were minimal with notable absence of sedation and anticholinergic- and cardiovascular-related side effects. We conclude that bupropion was significantly more effective than placebo in treating depression and accompanying anxiety in depressed inpatients.

Adult↗
PubMed1978

The placebo dilemma.

Placebos have been used since about 1950 in evaluation and interpretation of drug efficacy, especially of new drugs, and in comparison with existing compounds to establish their clinical therapeutic value. There are a number of problems connected with use of an "inert nothing" the informed consent, which is required in a human experiment, the doctor's consciousness of deceitful behaviour, the potential risk for the patient and the doctor, the high effect rate of placebos (+/- 35%), unexpected side-effects, dependency of patients on placebos, discovery by the patient of the placebo treatment, factors independent of the medication, such as the doctor's bias, the nurses influence, the significance of colour, the inconsistency of placebo-reactor or non-reactor types and the genetic state of the patient, as well as the problems associated with a double blind test, which can hardly be used when a patient has previously received a medicine, such as morphine, with its euphoric effect, and the colour change produced in urine by drugs like rifampicin or riboflavin. Only a well-trained and experienced clinical observer should employ a placebo in establishing the therapeutic value of drugs whilst avoiding undesirable pitfalls.

Double-Blind Method↗
PubMed1996

Velnacrine for the treatment of Alzheimer's disease: a double-blind, placebo-controlled trial. The Mentane Study Group.

The present study examines the safety and efficacy of the centrally acting cholinesterase inhibitor, velnacrine, in treating the cognitive symptoms of Alzheimer's disease. Seven hundred thirty-five patients with mild-to-severe Alzheimer's disease were treated in a double-blind, placebo-controlled study. Following the screen visit, patients were treated with velnacrine (10, 25, 50 and 75 mg t.i.d.) or placebo in a double-blind dose-ranging study to identify velnacrine-responsive patients and their best dose. Following placebo washout velnacrine responsive patients were randomly assigned to their best dose of velnacrine (N = 153) or placebo (N = 156) in a six week double-blind dose-replication study. Primary efficacy measures were the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS) and the Physician's Clinical Global Impression of Change. Statistically significant improvement was observed in both primary efficacy measures in velnacrine-treated patients during the dose-replication study. Velnacrine patients scored better on the cognitive subscale of the ADAS than placebo patients (P < 0.001), with patients receiving the highest velnacrine dose averaging a 4.1-point improvement with respect to screen values. Clinical Global Impression of Change scores of velnacrine-treated patients were significantly improved at the end of the 6 weeks of treatment when compared to those of placebo patients (P < 0.05). The most common side effect was asymptomatic elevation in liver transaminase levels, which occurred among 29% of patients. These data suggest that velnacrine produces modest clinical improvement in a subset of patients with mild-to-severe Alzheimer's disease.

Adult↗
PubMed2006

Slow-release lanreotide in Graves' ophthalmopathy: A double-blind randomized, placebo-controlled clinical trial.

SS analogs are an attractive alternative in treating Graves' ophthalmopathy (GO). Most of the previous studies were uncontrolled and enrolled few patients. The present study was conducted as a larger scale, prospective, randomized controlled study to determine the effectiveness of a slow-release formulation of lanreotide in GO. Sixty patients with active GO received an im injection every two weeks of either lanreotide 30 mg or placebo for 12 weeks. They were then followed and further treated in the traditional way if necessary. The Clinical Activity Score (CAS) was the primary efficacy criterion. Proptosis, diplopia, corneal erosion or ulcer, visual acuity, extraocular muscle movement and intraocular pressure were also evaluated. At the end of the 12 weeks, the mean CAS was not significantly decreased in the lanreotide group compared to the placebo group. The overall mean difference of proptosis between these two groups also did not reach significance at 12 weeks. Only diplopia at downward gaze had significant improvement for the lanreotide- treated group vs placebo group (p = 0.03). No differences were observed between the two groups compared to other outcome measures. During the 24-month follow-up after the clinical trial, 14 patients received eye surgery in the placebo group compared with 10 patients in the lanreotide group (p = 0.29). Six patients received methylprednisolone pulse therapy in the placebo group and two patients in the lanreotide group (p = 0.25). In conclusion, lanreotide treatment had no significant effects on GO compared with placebo.

Adolescent↗
PubMed2003

Expectations and placebo responses to caffeine-associated stimuli.

RATIONALE: To test the theory that expectations control placebo responses. OBJECTIVE: Subjects (n=20) were asked how much they expected their arousal to increase after one or two cups of coffee, and were subsequently exposed to one or two cups of decaffeinated coffee, or to caffeine equivalent to one or two cups of coffee (200 and 400 mg). The expectancy theory of placebo responses predicts a positive correlation between expectations and actual placebo responses. METHODS: Dependent variables were acoustic startle eyeblink and skin conductance responses, blood pressure and heart rate, and measures of subjective arousal. RESULTS: Caffeine increased startle eyeblink and skin conductance responses, as well as blood pressure and subjective arousal. Decaffeinated coffee increased startle eyeblink and skin conductance responses, but had no effect on subjective arousal, although the participants clearly expected increased subjective arousal after both one and two cups of coffee. However, there were significant correlations between the alertness expected after coffee, and the actual alertness recorded after decaffeinated coffee. CONCLUSIONS: The main finding in this study was that relatively strong expectations about the effects of coffee did not generate placebo responses after administration of decaffeinated coffee. Expectations were dose dependent, whereas the placebo response was not. However, expected alertness after coffee predicted recorded alertness after coffee. In sum, the expectancy theory of placebo effects received only limited support.

Adolescent↗
PubMed2001

Acetaminophen analgesia in children: placebo effect and pain resolution after tonsillectomy.

BACKGROUND: Pharmacodynamic models of acetaminophen analgesia in children have not explored the efficacy of single oral doses greater than 40 mg/kg. METHODS: Children aged 9.0 +/- 3.0 years (+/- SD) and weight 37.9+/- 16.6 kg undergoing outpatient tonsillectomy were randomised to receive acetaminophen elixir 40 mg/kg (n = 12). high dose acetaminophen elixir 100 mg/kg (n =20) or placebo (n=30) 0.5 -1 h preoperatively. No other analgesics were given. Individual acetaminophen serum concentrations and pain scores [visual analogue scale (VAS) 0-10] were measured over a 4-8 h postoperative period. These data were pooled with data from a previous study investigating acetaminophen pharmacodynamics (n = 120) and analysed using a non-linear mixed effect model. Placebo effects and drug effects were modelled using effect-site concentration models. RESULTS: A one-compartment model with first-order input, lag time and first-order elimination was used to describe the population pharmacokinetics of acetaminophen. Pharmacokinetic parameter estimates were similar to those previously described. Pharmacodynamic population parameter estimates [population variability coefficient of variation (CV)] for a maximum analgesic effect (Emax) model, in which the greatest possible pain relief (VAS 0-10) equates to an Emax of 10, were Emax 5.17 (64%) and 50% effective concentration 9.98 mg/l (107%). The equilibration half-life (t(eq)) of the analgesic effect compartment was 53 min (217%). A placebo drug model for the effects of placebo response had a t(eq) of 1.96 h (40%), an elimination half-life of 2.06 h (50%) and a potency of 1.54 pain relief units (24%). CONCLUSIONS: High dose acetaminophen (100 mg/kg) was no more effective than 40 mg/kg and was associated with increased nausea and vomiting. A target effect compartment concentration of 10 mg/l is expected to produce a pain reduction of 2.6 units. The placebo model accounted for a maximum pain reduction of 5.6 units at 3 h. The combination of placebo effect and preoperative acetaminophen 40 mg/kg results in pain scores below 4 units for 5 h postoperatively.

Acetaminophen↗
PubMed2003

Prior and concurrent administration of recombinant human megakaryocyte growth and development factor in patients receiving consolidation chemotherapy for de novo acute myeloid leukemia--a randomized, placebo-controlled, double-blind safety and efficacy study.

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) administered after acute myeloid leukemia (AML) chemotherapy (CT) failed to shorten the time of transfusion-dependent thrombocytopenia in a previous study. In this multicenter, randomized, placebo-controlled, double-blind study we determined the effect of administration of PEG-rHuMGDF prior to CT and of administration prior, concurrent, and 1 day post CT on platelet recovery and transfusion requirements in patients receiving consolidation CT for de novo AML. Patients were randomized to receive either 30 microk/kg PEG-rHuMGDF as a single dose on day -6 ( n=37), placebo as a single dose on day -6 ( n=9), 30 microk/kg PEG-rHuMGDF administered on day -6 followed by 10 microg/kg on days -5 to day 6 (through CT and including the day after CT, n=35), or placebo administered on day -6 to day 6 ( n=9). The median times to transfusion-independent platelet recovery to >20x10(9)/l were 24.5 and 24.0 days in the PEG-rHuMGDF day -6 group and PEG-rHuMGDF day -6 to 6, respectively, compared to 21.0 days in the placebo group. There were no significant differences in the number of days of platelet transfusions between either PEG-rHuMGDF schedule or placebo. The PEG-rHuMGDF day -6 to 6 group had a delayed absolute neutrophil count (ANC) recovery compared to either placebo or PEG-rHuMGDF day -6 treated patients. Thus, alteration of the scheduling of PEG-rHuMGDF in terms of earlier dosing before and during chemotherapy did not improve platelet recovery but rather delayed hematopoietic reconstitution. Although unexpected, these observations may be of major relevance for the design of future clinical trials with recombinant thrombopoietins.

Adult↗