Placebo Effect In Patients Research Articles

Placebo Effects On 6-minute Walk Test And Peak Oxygen Consumption In Patients With Heart Failure: A Systematic Review Of Contemporary Randomized Controlled Trials

Placebo Effects On 6-minute Walk Test And Peak Oxygen Consumption In Patients With Heart Failure: A Systematic Review Of Contemporary Randomized Controlled Trials

Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

The placebo effect in depression clinical trials is a substantial factor associated with failure to establish efficacy of novel and repurposed treatments. However, the magnitude of the placebo effect and whether it differs across treatment modalities in treatment-resistant depression (TRD) is unclear. To examine the magnitude of the placebo effect in patients with TRD across different treatment modalities and its possible moderators. Searches were conducted on MEDLINE, Web of Science, and PsychInfo from inception to June 21, 2021. Randomized clinical trials (RCTs) were included if they recruited patients with TRD and randomized them to a placebo or sham arm and a pharmacotherapy, brain stimulation, or psychotherapy arm. Independent reviewers used standard forms for data extraction and quality assessment. Random-effects analyses and standard pairwise meta-analyses were performed. The primary outcome was the Hedges g value for the reported depression scales. Secondary outcomes included moderators assessed via meta-regression and response and remission rates. Heterogeneity was assessed with the I2 test, and publication bias was evaluated using the Egger test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks. Fifty RCTs were included involving various types of placebo or sham interventions with a total of 3228 participants (mean [SD] age, 45.8 [6.0] years; 1769 [54.8%] female). The pooled placebo effect size for all modalities was large (g = 1.05; 95% CI, 0.91-1.1); the placebo effect size in RCTs of specific treatment modalities did not significantly differ. Similarly, response and remission rates associated with placebo were comparable across modalities. Heterogeneity was large. Three variables were associated with a larger placebo effect size: open-label prospective treatment before double-blind placebo randomization (β = 0.35; 95% CI, 0.11 to 0.59; P = .004), later year of publication (β = 0.03; 95% CI, 0.003 to 0.05; P = .03), and industry-sponsored trials (β = 0.34; 95% CI, 0.09 to 0.58; P = .007). The number of failed interventions was associated with the probability a smaller placebo effect size (β = -0.12; 95% CI, -0.23 to -0.01, P = .03). The Egger test result was not significant for small studies' effects. This analysis may provide a benchmark for past and future clinical RCTs that recruit patients with TRD standardizing an expected placebo effect size.

Response efficacy and heterogeneity of antipsychotic drugs in schizophrenia: Systemic review and meta-analysis.

This meta-analysis aimed to assess antipsychotic and placebo effects in patients with schizophrenia at the level of symptom factors. A systematic literature search up to June 2020 was undertaken and 62 studies were included, with 23,478 patients with schizophrenia at the study baseline point. We calculated mean differences with 95% confidence intervals. The comparison was made according to the study content using a continuous method with a random-effects model. Patients with schizophrenia treated by antipsychotic drugs had a significantly lower psychiatric rating scale total score; lower clinical global impression of severity; lower positive and negative syndrome scale; and lower assessment of negative symptoms total score, when compared to placebo treated patients. Patients with schizophrenia treated with an antipsychotic drug show a much greater improvement and lower inconsistency in the level of symptom factors when compared to the effects of placebo. Our findings evidence for a comparatively homogeneous outcome of the antipsychotic-treatment in improving schizophrenia symptoms. This opposes the notion of the presence of patient sub-groups with treatment non-responsive schizophrenia.

Neurotransmitter systems involved in placebo and nocebo effects in healthy participants and patients with chronic pain: a systematic review.

The investigation of neurotransmitter systems in placebo and nocebo effects has improved our understanding of these phenomena. Yet, most studies involve healthy participants. Because the pain modulatory system may differ in healthy participants and patients with chronic pain, it is important to investigate the evidence for neurotransmitter involvement in placebo and nocebo effects in each of these populations. PubMed, Embase, and Scopus databases, and the Cochrane Library were searched for articles investigating the endogenous opioid, endocannabinoid, dopaminergic, oxytocinergic, vasopressinergic, and cholecystokininergic (CCKergic) systems in placebo and nocebo effects in pain. Twenty-eight placebo and 2 nocebo studies were included. Vote counting was used to balance the number of positive vs negative findings. In healthy participants, the endogenous opioid, endocannabinoid, and vasopressinergic systems were involved in placebo effects, whereas findings on the dopaminergic and oxytocinergic systems were mixed. In patients with chronic pain, only 4 studies investigated neurotransmitters showing no involvement of the endogenous opioid system and mixed findings regarding the dopaminergic system. As to nocebo effects, 2 studies suggest that the CCKergic system is involved in nocebo effects in healthy participants. Overall, research has come a long way in specifying the neurotransmitter systems involved in placebo effects in healthy participants. Yet, evidence for the involvement of neurotransmitter systems in placebo effects in patients with chronic pain and in nocebo effects in healthy participants and patients is scarce. Based on the existing evidence, this systematic review suggests that knowledge obtained in healthy participants may not necessarily be transferred to chronic pain.

The effect of cranial electrotherapy stimulation on sleep in healthy women

Objective: Cranial electrotherapy stimulation (CES) is considered to be a potential treatment for insomnia. Women are more likely to suffer from insomnia than men. Therefore we studied the effect of CES on sleep efficiency in young healthy women. Methods: A randomized, controlled clinical study was conducted on 40 women (age 18–35 years) without sleep disorders. Each subject underwent two nights of polysomnography in a sleep center. During the second night, we applied CES with a commercial device (Alpha-Stim 100) using either active or sham stimulation (double-blinded). Sleep was evaluated with respect to differences between the active and sham modes. Sleep electroencephalogram (EEG) analysis was applied to determine frequency changes. Results: In our study we found no evidence of any direct influence of the Alpha-Stim 100 on sleep. After application of CES, we determined no significant differences between the active group and the control group (sham). Using EEG spectral analysis there was evidence of a frequency-lowering influence on the low-α frequency band (8–10 Hz). Conclusions: At most we may assume a reproducible effect on the α frequency measured in the EEG for application of CES with current levels >100 µA and presumably also with frequencies >0.5 Hz, with application directly at the cranium. We found no influence on sleep parameters. The effect on the low-α band evidenced in quantitative EEG analysis would require further investigation in a study with sufficient effect size. Significance: This is the first study to investigate the effects of CES with polysomnography during and after therapy. Our study contributes to the few controlled trials that have been conducted to study CES and its effects on the EEG α band.Highlights• This is the first study to investigate the effects of the Alpha-Stim in polysomnography during and subsequent to therapy.• In a quantitative electroencephalogram analysis we studied the data obtained for systematic changes.• To minimize placebo effects in patients with sleep disorders, we conducted the tests on subjects without such disorders.

What Is Minimally Required to Elicit Placebo Effects?

Placebo effects have often been attributed to cognitive processes described as "learning" and/or "expectancy," yet the role of conscious awareness is unclear. Furthermore, little is known about the placebo effects in patients with limited cognitive abilities, such as intellectual disability. Here, recent data on placebo mechanisms in patients with impaired cognitive function will be discussed, as well as experimental studies investigating how implicit cognitive processes may shape placebo effects. Together these studies comment on the minimum requirements in order to elicit placebo effects, both from the view of conscious awareness and from the perspective of Intelligence Quotient and basic brain function. Together with recent conceptualizations of placebo effects in terms of predictive coding, there is evidence to suggest that placebo effects are fundamental responses of the brain that have developed to promote survival.

Clinical Use of Placebo Effects in Patients With Pain Disorders.

The analgesic placebo effect is well documented by numerous studies. Many important influencing factors, however, are yet to be discovered. In the arena of placebo effects and clinical implications, expectancies play a central role. Expectancies are shaped by processes of classical and social learning as well as verbal instructions and are strongly related to emotional factors. Expectancies trigger a cascade of endogenous opioids and non-opioids, which alter the experience of pain. For clinical application it is important to know, that placebo research yields ethical possibilities to use placebo effects without deception and without using placebos. Since placebo effects contribute to responses to active analgesics, it is feasible to enhance patients' benefits from pain treatments by increasing the additional placebo effect. There are several possibilities to use the placebo effects via shaping and adapting information about analgesic medication and via associating medication intake with a positive context. A positive patient-clinician communication atmosphere is very important to generate clinically meaningful placebo effects in pain medicine.

Does conditioned pain modulation predict the magnitude of placebo effects in patients with neuropathic pain?

Conditioned pain modulation (CPM) is a validated measure of the function of endogenous pain inhibitory pathways. Placebo effects reflect top-down inhibitory modulation of pain. CPM and placebo effects are both influenced by expectations, albeit to varying degrees, and are related to neurotransmitter systems such as the endogenous opioid system, and it can be speculated that CPM responses are positively associated with the magnitude of placebo effects. Yet, no studies have tested this. The study included 19 patients with neuropathic pain. CPM was quantified as the difference in pressure pain threshold (PPT) as measured at the middle deltoid muscle before and after 5-min exposure to the cold pressor test (CPT) (conditioning pain stimulus). Placebo effects were tested via open and hidden applications of the pain-relieving agent lidocaine (2mL) using a disinfection napkin controlled for no treatment. The mean (SD) PPT was 668.7 (295.7)kPa before and 742.3 (370.8)kPa after the CPT. The mean (SD) CPM response was -73.6 (214.0)kPa corresponding to an 11% increase in PPT, reflecting a normally functioning endogenous pain modulatory system. Large and significant placebo effects were observed in ongoing neuropathic pain intensity (p=0.002). The CPM response did not predict the magnitude of the placebo effect (p=0.765). Moreover, there were no interaction effects for the moderator variables: clinical pain level (p=0.136), age (p=0.347) and gender (p=0.691). Conditioned pain modulation and placebo effects do not seem to be associated in patients with neuropathic pain. Conditioned pain modulation and placebo effects are endogenous pain-modulating phenomena that are influenced by some of the same mechanisms. This study suggests that CPM and placebo effects in neuropathic pain are independent phenomena that may be mediated by different mechanisms.

Efficacité et tolérance des IPDE-5 dans le traitement de la dysfonction érectile chez le patient schizophrène : une revue de la littérature

IntroductionSexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients. This literature review aimed to summarize the current data on the efficacy and tolerability of PDE-5 inhibitors in the erectile dysfunction in schizophrenic patients. Material and methodsPubMed, PsycInfo and Cochrane databases were searched for studies published until August 2014. ResultsOnly 6 studies met the inclusion criteria. Three were randomized, double-blind, cross-over, placebo-controlled trials and three were open studies. Various scales were used to measure erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, quality of life and intensity of schizophrenic symptoms. In the 3 randomized studies (one with sildenafil 25–50 mg, one with lodenafil carbonate 80 mg/j and the last one with tadalafil 10 mg), the rate of participants who completed the trial was high (around 95 %). All three included patients with schizophrenia or schizophrenia spectrum disorders. Patients reported significant improvement on sexual dysfunction. However, no statistical difference was reported between lodenafil and placebo, on different scales, suggesting a very important placebo effect in patients with schizophrenia. All three found a good tolerance of PDE-5 inhibitors. Side effects were rare and were mainly nasal congestion, headaches, nausea and dizziness. There were no major side effects or drug interactions. Considering the 3 open studies, 2 involved sildenafil and one tadalafil. All concluded in improved erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included. DiscussionLittle data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients. ConclusionIn total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia.

Factors Influencing the Placebo Effect in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: An Analysis of Two Randomized Clinical Trials.

ObjectiveTo explore factors related to the placebo effect in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).MethodsThis was a retrospective cohort study of patients with POAG and patients with OH who were treated with placebo. The patients’ data were extracted from two randomized, double-masked, parallel, multicenter clinical trials (trial 1 and trial 2) in Japan. We explored the baseline factors that were associated with the intraocular pressure (IOP)-lowering effect of placebo ophthalmic solution after 4 weeks of instillation treatment at two time points by using multivariable models. The time points were Hour 0 (between 08:30 and 10:30 before instillation) and Hour 2 (within 1.5 to 2.5 h after instillation and by 12:30) at the baseline date and after 4 weeks. The changes in IOP from baseline to 4 weeks at the two time points were evaluated for the IOP-lowering effect induced by placebo instillation.ResultsOf the 330 patients included in the two trials, 89 patients were eligible for the analysis. The results of the multivariable analysis for Hour 0 indicated a high IOP at the baseline date (coefficient: 0.24, 95% confidence interval (CI): 0.02 to 0.46, P = 0.03), and the magnitude of the IOP fluctuation at the baseline date (coefficient: 0.57, 95% CI: 0.24 to 0.90, P = 0.001) was associated with the IOP-lowering effect after 4 weeks. With respect to Hour 2, the trial type was associated with the IOP-lowering effect (coefficient: -1.15, 95% CI: -2.14 to -0.16, P = 0.02).ConclusionsA large fluctuation in IOP during the day is associated with the IOP-lowering effect induced by placebo in patients with POAG or OH. This finding would be helpful to researchers when designing studies related to glaucoma in the early stages of clinical development of drugs.

Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression.

High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD). In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) were studied with positron emission tomography and the µ-opioid receptor-selective radiotracer [11C]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of µ-opioid receptor binding. Higher baseline µ-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r = 0.48; P = .02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, were associated with increased placebo-induced µ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala (nucleus accumbens: r = 0.6; P < .001). Placebo-induced endogenous opioid release in these regions was associated with better antidepressant treatment response, predicting 43% of the variance in symptom improvement at the end of the antidepressant trial. These data demonstrate that placebo-induced activation of the µ-opioid system is implicated in the formation of placebo antidepressant effects in patients with MDD and also participate in antidepressant responses, conferring illness resiliency, during open administration. clinicaltrials.gov Identifier:NCT02178696.

Factors Influencing the Placebo Effect in Patients Suffering From Mental Disorders in Romania

Introduction Nowadays, numerous definitions of placebo and the placebo effect have been proposed. Mechanisms of action have been intensely studied and interesting theories have emerged. It is well-known that the effects of the drugs are influenced by the clinical setting. The complexity of human mind and the social context make the patient highly suggestible to (auto)suggestion. Objectives To assess factors influencing placebo effect in Romanian patients with mental disorders. Material and Methods We present 5 clinical cases from our medical practice and compare them to cases from medical literature: 68 years old woman, psychiatric inpatient complaining of insomnia, with medically treated hypertension; 65 years old woman, neurological inpatient complaining of severe back pains that were neurologically uncommon, but impaired her walking and caused sleep disturbances and were not alleviated by a complex and combined analgesic pharmacotherapy; 70 years old woman, known for doctor shopping, came at the Neurology Emergency Department at 1:30 am for headache, foot burns, and abnormal gait; 48 years old man, psychiatric inpatient complaining of ‘paralyzed bowels”, ‘pain in the legs”, and ‘paralyzed muscles” after undergoing a surgical intervention for an abdominal hernia; 50 years old woman, inpatient suffering from schizophrenia at a Chronic Psychiatric Disorders Department, often complaining of headaches. Patients received different forms of placebo therapy. Results All patients were placebo-responders. We noticed decrease of placebo effect in some patients in chronic use, and spectacular amelioration of symptoms when there was a high rate of allegiance. Conclusion Allegiance is an important factor for placebo effect.

The Effect of Inactivated Lactobacillus LB Fermented Culture Medium on Symptom Severity: Observational Investigation in 297 Patients with Diarrhea-Predominant Irritable Bowel Syndrome

Introduction: Little is known about the intensity of symptoms of diarrhea-predominant IBS (IBS-D) or the consequences of the disease on patients’ health-related quality of life (HRQOL). This observational investigation assessed the symptoms (abdominal pain, bloating, number of stools per day, and stool consistency), impact on HRQOL, and consequence on anal continence in 297 patients with IBS-D before and after 1 month of probiotic treatment with Lacteol (inactivated Lactobacillus LB plus fermented culture medium). Methods: Functional assessment using a standardized visual analogue scale in order to quantify abdominal pain, bloating, and quality of life before and after 1 month of treatment with 2 capsules/day of Lacteol. The number of symptomatic days per week, number of stools, consistency of stools, secondary fecal incontinence rate, and potential trigger effect of food were quantified. A χ² test was used to compare qualitative data and the variance of quantitative criteria was analyzed. Results: The pain score decreased from 4.46 ± 0.15 on a scale of 0–10 before treatment to 2.8 ± 0.14 after treatment (p < 0.0001). Bloating decreased from 4.49 ± 0.18 to 2.5 ± 0.15 on a scale of 0–10 (p < 0.0001). The HRQOL score, which is inversely correlated with quality of life, decreased from 5.99 ± 0.14 to 3.92 ± 0.16 (p < 0.0001). In this cohort study, the fecal incontinence rate secondary to diarrhea was clearly higher than that of the general population: 18% versus a prevalence of 9–10%, according to different studies. The mean number of stools per week decreased from 17.59 to 12.83 after treatment (p < 0.0001). Before treatment, 54% of patients had watery stools and 46% had smooth stools; at the end of treatment, only 18.5% of patients still had watery stools, and 34% had normal stools. 52% of patients attributed their symptoms to their diet: 34% to vegetables, 29% to fruit, 15% to milk, 15% to fat, 6% to peppers and spices, and 4% to sugar. Conclusion: This observational investigation shed new light on patients with IBS-D, the HRQOL of which is altered by a fecal incontinence rate twice as high as that of the general population. Correlation with diet is confirmed by 1 out of 2 patients reporting poor tolerance of fiber and dairy products. Nutritional management should thus be part of these patients’ treatment. Inactivated Lactobacillus LB plus fermented culture medium is a probiotic drug that has been used by physicians for a long time to treat patients with diarrhea. Strongly concentrated, it has no side effects and seems to help these patients. Due to a strong placebo effect in patients with this pathology, however, a controlled study is necessary to confirm this result.

L’effet placebo : généralités et spécificités en psychiatrie (dépression et schizophrénie)

Placebos, consequences of their use, the placebo effect and the associated negative effects, the nocebo effect, have been widely studied. However, the lack of any consensus definition makes the interpretation and analysis of such findings difficult. In this article, we will review existing definitions and factors affecting the placebo effect in medicine. We will then consider the possible mechanisms of action of the placebo effect, with a view to improving understanding of this issue. Finally, we will analyse data relating to placebos used in psychiatry and, more specifically, for schizophrenic patients. In an extensive review of the literature, we identified the various factors playing a role in the appearance of placebo effects in general medicine. As well as purely factual elements, such as the disorder, the sex of the subject and the treatment given, the placebo effect is strongly correlated with the quality of the relationship between the doctor and patient and with the capacity of the patient to communicate and establish a link. The attitude of the doctor, the temperament of the subject and the expectations and beliefs of each also contribute to the appearance and extent of a placebo effect. We then investigated placebo effects in psychiatry, particularly in depressed patients (the most widely studied condition) where studies have shown particular efficacy. We also addressed the use of placebos in schizophrenia: the placebo effect in patients with this disorder is essentially used as a tool for assessing new molecules to be released onto the market but the phenomenon itself has been little studied, if at all. Thus, it is of particular interest to consider in detail the use of placebos in schizophrenia, to try to gain a deeper understanding of the factors involved. This will allow potential specific effects associated with placebo use in this disorder to be established, improving the integration of placebos into therapy and to optimize the efficacy of treatment prescribed, taking into account mental state; indeed, the placebo effect is present in all treatments, whether involving a placebo or an active compound.

Placebo effect in patients with irritable bowel syndrome

The placebo effect has evolved from being considered a nuisance factor in clinical research to a hot topic of scientific investigation. New research findings show that a placebo has real psychobiological and biological effects that are attributable to the overall therapeutic context. Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract that shows a significant placebo response of around 40–50% among different clinical trials.A positive patient-practitioner relationship can enhance the placebo effect in IBS patients.Emerging literature using functional brain imaging has started to document the neuronal changes associated with the placebo phenomenon in IBS patients, showing aberrant neural network during visceral placebo analgesia when compared to controls. Further promotion and integration of laboratory and clinical research are encouraged to advance the understanding of placebo mechanisms in IBS patients.

Randomised controlled trial: placebo effect

Kirsten Patrick explains a study that tries to pick apart the placebo effect in patients with irritable bowel syndrome

Immediate Early Genes after Pulsed Radiofrequency Treatment: Neurobiology in Need of Clinical Trials

Immediate Early Genes after Pulsed Radiofrequency Treatment: Neurobiology in Need of Clinical Trials

Longevity of the placebo effect in patients enrolled in angiogenesis and laser myocardial revascularization trials

Longevity of the placebo effect in patients enrolled in angiogenesis and laser myocardial revascularization trials

A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms

The objective was to test effects of ethyl eicosapentaenoate (E-E) on persistent ongoing symptoms in patients receiving different types of anti-schizophrenic drugs, typical antipsychotics, new atypical antipsychotics, and clozapine. 115 patients with DSM-IV-defined schizophrenia were studied, 31 on clozapine, 48 on new atypical drugs and 36 on typical antipsychotics. Placebo or 1, 2 or 4 g/day of E-E was given for 12 weeks in addition to the background medication. The main assessment was change from baseline to 12 weeks on the PANSS and its sub-scales. There were no treatment-related side effects or adverse biochemical or haematological effects. Patients on 2 and 4 g/day E-E showed significant reductions in triglyceride levels which had been elevated by clozapine. In patients given 2 g/day E-E there were improvements on the PANSS and its sub-scales, but there was also a large placebo effect in patients on typical and new atypical antipsychotics and no difference between active treatment and placebo. In patients on clozapine, in contrast, there was little placebo response, but a clinically important and statistically significant effect of E-E on all rating scales. This effect was greatest at 2 g/day. There was a positive relationship between improvement on rating scales and rise in red blood cell arachidonic acid concentration.

The long-term effects of placebo in patients with chronic schizophrenia

Background: It has been hypothesized that placebo periods may increase long-term morbidity for patients with schizophrenia. In this study, the long-term effect of a placebo period was evaluated in a group of relatively treatment-refractory patients with chronic schizophrenia. Methods: This retrospective study examined behavioral rating scores for 127 patients with chronic schizophrenia who were placed in a double-blind placebo study on the inpatient units of the National Institute of Mental Health Neuropsychiatric Research Hospital. Patients were rated daily with the Psychiatric Symptom Assessment Scale (PSAS), an extended and anchored version of the Brief Psychiatric Rating Scale (BPRS). At the end of the placebo phase, most patients were placed on haloperidol. Pre-placebo baseline PSAS ratings were compared with, first, discharge ratings and second, post-placebo ratings. To determine expected variability in the course of illness, patients in the placebo group were compared with patients hospitalized during the same time period, but who did not enter the placebo study. Results: By discharge, ratings for placebo patients had returned to baseline. Post-placebo ratings were quite variable. Although many of the placebo patients had returned to baseline by day 3 of the post-placebo phase, others had not returned to baseline by post-placebo day 42. PSAS Total Scores for patients who left the study early were no different at baseline, placebo, or through post-placebo day 35 compared with patients who completed the study. Conclusions: The results indicate that given a sufficiently lengthy recovery period, patients with chronic schizophrenia who go through a placebo phase return to baseline, but that the speed with which they attain that recovery is highly variable. Biol Psychiatry 1999;46:1092–1105