Inert Pill Research Articles

Placebo and Nocebo Responses in Pharmacological Trials of Tic Disorders: A Meta-Analysis.

Clinical trials of new drugs for tic disorders (TD) often fail to yield positive results. Placebo and nocebo responses play a vital role in interpreting the outcomes of randomized controlled trials (RCTs), yet these responses in RCTs of TD remain unexplored. The aim was to assess the magnitude of placebo and nocebo responses in RCTs of pharmacological interventions for TD and identify influencing factors. A systematic search of the Embase, Medline, Cochrane Central Register of Controlled Trials, and PsycINFO databases was conducted. Eligible studies were RCTs that compared active pharmacological agents with placebos. Placebo response was defined as the change from baseline in TD symptom severity in the placebo group, and nocebo response as the proportion experiencing adverse events (AEs) in this group. Subgroup analysis and meta-regression were performed to explore modifying factors. Twenty-four trials involving 2222 participants were included in this study. A substantial placebo response in TD symptom severity was identified, with a pooled effect size of -0.79 (95% confidence interval [CI] -0.99 to -0.59; I2 = 67%). Forty-four percent (95% CI 27% to 63%; I2 = 92%) of patients experienced AEs while taking inert pills. Sample size, study design, and randomization ratio were correlated with changes in placebo and nocebo responses. There were considerable placebo and nocebo responses in TD clinical trials. These results are of great relevance for the design of future trials and for clinical practice in TD. PROSPERO registration ID CRD42023388397. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cure Rates of Control Interventions in Randomized Trials for Onychomycosis Treatments: A Systematic Review and Meta-Analysis.

<p>Background: The efficacy of antifungals for onychomycosis has been determined in randomized controlled trials (RCTs); interestingly their control arms have demonstrated some therapeutic effects. These controls constitute either placebos (inert pills) or vehicles (all but the antifungal component of the creams). The objective of this research was to determine (i) whether RCT controls exhibited statistically-relevant efficacy rates (i.e. beyond the "placebo effect"), (ii) whether oral and topical controls differed in their efficacies, and (iii) if the efficacy rates of the controls correlated with those of the active comparator associated with that control.</p> <p>Methods: RCTs of oral and topical monotherapies for dermatophyte toenail onychomycosis were identified through a systematic literature search. For our meta-analyses of cure rates the double arcsine transformation was used. The N-1 chi squared test was used to determine whether the cure rates significantly differed between topical and oral controls. Correlation was investigated using Kendall rank correlation tests.</p> <p>Results: The pooled mycological, complete, and clinical cure rates of all control interventions (n = 19 trials) were 9%, 1%, and 6%, respectively. The pooled efficacy rates for oral and topical controls were: mycological cure rate, 7% and 12% (p=0.0016); complete cure rate, 1% for both; and clinical cure rate, 4% and 8%, respectively (p=0.0033). For oral RCTs, the respective cure rates of the active therapies were not correlated with controls. However, for topical RCTs, as the mycological and clinical cure rates of the active therapy increased, so did those of the topical vehicle associated with the active therapy in question, and vice versa.</p> <p>Conclusions: The topical vehicle cure rates were often higher than the oral placebo cure rates, likely due to the presence of non-antifungal chemicals (e.g. moisturizers, urea) with antifungal and debriding properties, which are not present in oral controls.</p>.

Understanding the Neurocomputational Mechanisms of Antidepressant Placebo Effects.

Over the last two decades, neuroscientists have used antidepressant placebo probes to examine the biological mechanisms implicated in antidepressant placebo effects. However, findings from these studies have not yet elucidated a model-based theory that would explain the mechanism through which antidepressant expectancies evolve to induce persistent mood changes. Emerging evidence suggests that antidepressant placebo effects may be informed by models of reinforcement learning (RL). Such that an individual’s expectation of improvement is updated with the arrival of new sensory evidence, by incorporating a reward prediction error (RPE), which signals the mismatch between the expected (expected value) and perceived improvement. Consistent with this framework, neuroimaging studies of antidepressant placebo effects have demonstrated placebo-induced μ-opioid activation and increased blood-oxygen-level dependent (BOLD) responses in regions tracking expected values (e.g., ventromedial prefrontal cortex (vmPFC)) and RPEs (e.g., ventral striatum (VS)). In this study, we will demonstrate the causal contribution of reward learning signals (expected values and RPEs) to antidepressant placebo effects by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC and μ-opioid striatal RPE signal using pharmacological approaches. We hypothesized that antidepressant placebo expectancies are represented in the vmPFC (expected value) and updated by means of μ-opioid-modulated striatal learning signal. In a 3 × 3 factorial double-blind design, we will randomize 120 antidepressant-free individuals with depressive symptoms to one of three between-subject opioid conditions: the μ-opioid agonist buprenorphine, the μ-opioid antagonist naltrexone, or an inert pill. Within each arm, individuals will be assigned to receive three within-subject counterbalanced forms of TMS targeting the vmPFC—intermittent Theta Burst Stimulation (TBS) expected to potentiate the vmPFC, continuous TBS expected to de-potentiate the vmPFC, or sham TBS. These experimental manipulations will be used to modulate trial-by-trial reward learning signals and related brain activity during the Antidepressant Placebo functional MRI (fMRI) Task to address the following aims: (1) investigate the relationship between reward learning signals within the vmPFC-VS circuit and antidepressant placebo effects; (2) examine the causal contribution of vmPFC expected value computations to antidepressant placebo effects; and (3) investigate the causal contribution of μ-opioid-modulated striatal RPEs to antidepressant placebo effects. The proposed study will be the first to investigate the causal contribution of μ-opioid-modulated vmPFC-VS learning signals to antidepressant placebo responses, paving the way for developing novel treatments modulating learning processes and objective means of quantifying and potentially reducing placebo effects during drug development.Trial Registration:ClinicalTrials.gov Identifier: NCT04276259.

Naltrexone during pain conditioning: A double-blind placebo-controlled experimental trial.

Naltrexone reversibly blocks the effects of opioids and has been shown to decrease placebo analgesia. However, it is not clear (1) to what extent naltrexone affects pain modulation in a nontreatment context, for example, in response to pain cues or (2) how naltrexone given prior to pain-cue learning shapes pain responses. In a double-blind procedure prior to pain-cue conditioning, 30 healthy participants were randomized to receive an oral dose of naltrexone (50 mg) or inert pill. During functional magnetic resonance imaging, high and low pain pressures were paired with two different visual cues: a high pain cue and a low pain cue (learning sequence). During a test sequence, medium levels of pressure were used for both cues and the difference in subjective pain ratings following high and low pain cues was calculated. Results showed significant conditioned pain responses across groups (P < .001); however, no significant difference between participants receiving naltrexone or inert pill (P = .193). There was a significant correlation between the difference in high and low pain ratings during the learning sequence and the effect of high and low pain cues during the test sequence (r = .575, P = .002). Functional magnetic resonance imaging analyses revealed no significant difference in brain activation between groups. Here, we demonstrate comparable learning of pain responses in participants treated with naltrexone or inert pill. The results point to the possibility that associative learning, and conditional responding to pain cues, is not dependent on endogenous opioids. Our results, using pain-cue conditioning to create reduced pain responses, contrast previous studies where opioid antagonists significantly reduced the placebo effect in treatment of pain.

The Myth of the Placebo Response.

The placebo response is a myth. It does not exist in reality, and continuing to name it is hindering the optimal application of science to healing in medicine. On the surface, it is obvious that, when defined as a biological response to an inert pill (like a sugar pill), the idea of a “response” to a placebo is impossible. Inert treatments by definition do not produce responses. So why do we continue to ponder why people get better from taking inert substances and base our acceptance of legitimate treatments on demonstrating that they go beyond that response? The problem arises because we have flawed assumptions of the value that reductionistic science and the demonstration of specific effects has for healing. To support those flawed assumptions, we support the idea of “the placebo response.” This causes confusion among patients, clinicians, regulators, and even scientists. Legitimate medical treatments have become defined as those that do more than produce a placebo response. An entire pharmaceutical industry and its regulators attempt to control and profit by proving that small molecules produce a clinical effect greater than the placebo response. Billions of dollars are made when that is proven, often even when the size of the response in the active over the placebo group is miniscule. The fact is people heal and that inherent healing capacity is both powerful and influenced by mental, social, and contextual factors that are embedded in every medical encounter since the idea of treatment began. In this chapter, I argue that our understanding of healing and ability to enhance it will be accelerated if we stop using the term “placebo response” and call it what it is—the meaning response, and its special application in medicine called the healing response.

Interaction between disgust proneness and perception of treatment efficacy predicts response to a disgust placebo.

Placebo responsiveness is highly variable across individuals and has been shown to be difficult to predict solely based on personality traits. The present study examined the interaction between a specific trait and state variable (disgust proneness and perceived effectiveness of a disgust placebo) on placebo responsiveness. We presented 145 participants with an inert pill, which was introduced as an effective anti-nausea drug. Disgust responses were elicited by a validated picture set, which was viewed once with and once without the disgust placebo. The results showed that the placebo was effective in reducing experienced disgust. When predicting placebo responsiveness, the results showed a significant interaction between perceived treatment effectiveness and disgust proneness. Specifically, effectiveness ratings were a significant predictor of placebo response only for individuals high in disgust proneness. The results suggest that the joint consideration of specific state and trait factors can be used to optimize placebo responsiveness.

Challenges of differential placebo effects in contemporary medicine: The example of brain stimulation.

‘Differential placebo effects’ is the concept that different types of placebos (e.g. inert pill versus sham device) may yield different magnitudes of placebo effects. This issue has been pushed into the spotlight by recent clinical trials of new technologies reporting unexpectedly large placebo effects from sham devices/procedures needed to maintain blinding integrity. In this Neurology Grand Rounds, we use transcranial magnetic stimulation as a model to explore the principles and implications of differential placebo effects. We highlight emerging research on the neurobiology of placebo effects and analyze fundamental questions of measuring efficacy in contemporary medicine.

Effect of Vitamin D on Muscle Function and Injury in Elite Adolescent Dancers: A Randomized Double-Blind Study.

A number of studies have noted low levels of vitamin D in dancers, and this has been associated with increased risk of injuries and decreased muscle-strength indices. The aim of the present study was to examine whether vitamin D supplementation over a 4-mo period can improve muscle function and injury incidence. A total of 84 participants volunteered; exclusion criteria and dropout (19%) reduced the cohort to 67 participants (females = 29 and males = 38; 17-19y). Participants were randomly assigned to either an intervention or placebo group (2∶1 ratio). All provided a venous blood sample before and after the 4-mo study period. The intervention group received 120,000 IU vitamin D to be taken over a 1-wk period, and the placebo group received the same number of inert pills. Participants completed a series of muscle function tests before and after the monitoring period. Injury incidence was recorded by the independent health team at the school. Preintervention, 6% of the cohort were vitamin D deficient, 81% were insufficient, and 13% had sufficient levels; postintervention, 53% were insufficient and 47% were sufficient. The intervention group reported a significant increase in serum 25(OH)D3 (57%; P < .00) and isometric strength (7.8%; P = .022) but not muscle power. There was a significant association between traumatic injury occurrence for the intervention and control groups (10.9% vs 31.8%; P < .02). Vitamin D supplementation decreased the numbers of deficient and insufficient participants in this cohort. The intervention group reported a small significant increase in muscle strength that was negatively associated with traumatic injury occurrence.

Super Pill is Less Effective than an Ordinary Mint in Altering Subjective Psychological Feeling States within a Few Minutes

ABSTRACTExpectations shape human behavior. Initial drug use might be associated with information-based expectations. In this study, we presumed that changes in affect and perceived physical wellbeing will be stronger after receiving an active placebo (Tic Tac mint; n = 40), than a pure placebo (inert pill; n = 40) given as a mood-enhancing “super pill.” After baseline measures, participants completed a treatment-expectancy scale, ingested the mint/super pill, and attended to the effects over 3-minutes. Subsequently, they completed again the psychological tests. Expectancy scores were positive and did not differ between the groups. The pure placebo group increased in physical wellbeing but less than the active placebo group, which also showed an increase in positive affect. Negative affect decreased in both groups. The Tic Tac produced greater affective changes than the pure placebo. Since these are new findings on the ultra-short placebo effects on affect, the results might have relevance for drug-use studies.

Investigating visual effects of a disgust nocebo with fMRI.

There is growing evidence that placebos are able to influence visual perception. A previous functional magnetic resonance imaging study on the processing of disgust images demonstrated that a ''disgust placebo'' (inert pill administered with the verbal suggestion of an anti-nausea medication) reduced visual cortex activity and connectivity. In the present functional magnetic resonance imaging investigation, visual effects corresponding to a ''disgust nocebo'' (an odorless substance introduced as an aversive smell that enhances disgust feelings) were examined. Data from 29 females were reanalyzed. They viewed disgusting, fear-eliciting, and neutral images once with and once without the nocebo. In the nocebo condition with disgusting images disgust experienced that significantly increased fusiform gyrus activation, which also showed enhanced coupling with the amygdala and several (extra)striate cortex regions. The nocebo changed the affective value and motivational relevance of the stimuli as well the perception of basic visual features. These findings demonstrate that nocebo-related expectations can have a strong influence on the experience of sensory input.

Network analysis of the genomic basis of the placebo effect.

The placebo effect is a phenomenon in which patients who are given an inactive treatment (e.g., inert pill) show a perceived or actual improvement in a medical condition. Placebo effects in clinical trials have been investigated for many years especially because placebo treatments often serve as the control arm of randomized clinical trial designs. Recent observations suggest that placebo effects may be modified by genetics. This observation has given rise to the term "placebome," which refers to a group of genome-related mediators that affect an individual's response to placebo treatments. In this study, we conduct a network analysis of the placebome and identify a placebome module in the comprehensive human interactome using a seed-connector algorithm. The placebome module is significantly enriched with neurotransmitter signaling pathways and brain-specific proteins. We validate the placebome module using a large cohort of the Women's Genome Health Study (WGHS) trial and demonstrate that the placebome module is significantly enriched with genes whose SNPs modify the outcome in the placebo arm of the trial. To gain insights into placebo effects in different diseases and drug treatments, we use a network proximity measure to examine the closeness of the placebome module to different disease modules and drug target modules. The results demonstrate that the network proximity of the placebome module to disease modules in the interactome significantly correlates with the strength of the placebo effect in the corresponding diseases. The proximity of the placebome module to molecular pathways affected by certain drug classes indicates the existence of placebo-drug interactions. This study is helpful for understanding the molecular mechanisms mediating the placebo response, and sets the stage for minimizing its effects in clinical trials and for developing therapeutic strategies that intentionally engage it.

Testing the effects of a disgust placebo with eye tracking

Previous neuroimaging research showed that a disgust placebo (inert pill presented with the verbal suggestion of disgust relief) reduced visual cortex activation during the viewing of disgust-inducing images. In order to investigate whether this effect of automatic emotion regulation was associated with changed visual scanning patterns of the pictures, we conducted two eye tracking experiments. In the first study, 23 women underwent a retest design during which they passively viewed images depicting disgusting, fear-eliciting, neutral items and fractals both with, and without a placebo. The placebo provoked a substantial decrease in experienced disgust. Although none of the recorded eye movement parameters (number of fixations, fixation duration, saccade amplitude, blinking rate) showed placebo-related changes, placebo effects were suggested by an analysis of spatial fixation patterns. In the second study, which focused on attentional (dis)engagement, 46 women looked at two pictures which were presented side-by-side on the screen. These picture pairs (disgust-neutral, neutral-neutral) were once viewed with and once without a placebo. The placebo again provoked a marked decrease of experienced disgust and enhanced the number of fixations for disgusting images. This change might reflect a greater willingness of the participants to view these stimuli while on the placebo.

Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia.

The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

Is acupuncture no more than a placebo? Extensive discussion required about possible bias.

Numerous randomized controlled trials (RCTs) of acupuncture have been conducted in recent years. The results of several studies implied that acupuncture was only a powerful placebo; however, certain studies demonstrated that verum acupuncture had a greater effect than placebo and the mechanisms between a verum acupuncture group and a placebo/sham group were different. Researchers attempted to investigate the inherent factors that may potentially influence the results of trials. Certain problems observed in acupuncture RCTs also occurred in RCTs in other fields, including insufficient sample size, high dropout rates, inadequate follow-up and randomization. The study of acupuncture is so complex that specific methodological challenges are raised, which are frequently overlooked, including sham interventions, blinding, powerful placebo effects (even stronger than an inert pill) and variations in acupuncture administration. The aforementioned problems may contribute to bias, and researchers systematically attempt to solve these problems. The present review aimed to suggest techniques to design high-quality studies, minimize the placebo effect and optimize acupuncture administration in acupuncture studies. If these problems are addressed, then the results of acupuncture studies may be different.

Placebo treatment can alter primary visual cortex activity and connectivity

Placebo treatment can alter brain activation in regions implicated in affective processing and cognitive control of emotions. This functional magnetic resonance imaging (fMRI) study investigated whether a placebo can additionally modulate visual cortex activity and connectivity during affective picture perception. The participants underwent a retest design where they were presented with disgusting, fear-eliciting and neutral pictures both with, and without a placebo (inert pill presented with the suggestion that it can reduce disgust symptoms). The placebo provoked a strong decrease in experienced disgust. This was accompanied by a reduced activation of the primary visual cortex, which showed reduced interaction with the amygdala and the insula. Accordingly, placebos are able to affect basic perceptive processes.

Disgust regulation via placebo: an fMRI study

The present fMRI study investigated whether placebo treatment can change disgust feelings. Disgust-prone women underwent a retest design where they were presented with disgusting, fear-eliciting and neutral pictures once with and once without a placebo (inert pill presented with the suggestion that it can reduce disgust symptoms). The placebo provoked a strong decrease of experienced disgust, which was accompanied by reduced insula activation. Exploratory psychophysiological interaction analyses revealed decreased connectivity in a network consisting of the insula, the amygdala, the anterior cingulate cortex and the orbitofrontal cortex. Moreover, the placebo increased amygdala-DMPFC coactivation. Our findings suggest that placebo use can modulate a specific affective state and might be an option as a first therapy step for clinical samples characterized by excessive and difficult-to-control disgust feelings.

Reactor runaway due to statistically driven axial activity variations in graded catalyst beds: Loading from pre-measured single tube aliquots

Highly exothermic catalytic reactions are often carried out in fixed bed, multi-tubular reactors that use a graduated catalyst activity profile. By increasing the effective catalytic activity in zones along the axial coordinate, the decreasing driving force that occurs as reactants are consumed can be compensated by increasing catalytic activity. This not only helps balance the heat generation rate along the reactor with the heat removal capabilities but it allows the attainment of very high conversion of one or more reagents while maintaining high reactor productivity. Partial oxidation reactions often use such strategies to manage the heat of reaction while minimizing the amount of recycle required. Industrial examples of such processes include ethylene oxychlorination to 1, 2-dichloroethane, propylene oxidation to acrylic acid and ortho-xylene oxidation to phthalic anhydride.Lower activity zones of catalyst are often created by diluting active catalyst pills with similar-sized pills of inert materials. This avoids the need to develop several catalyst formulations for a single process and allows fine-tuning of catalyst zoning profiles. However, loading a mixture of active and inert pills into a reactor tube is an inherently statistical process, which produces non-uniform activity profiles. The effect of this statistical non-uniformity has been studied for the case where tubes are loaded from catalyst drums - an essentially infinite reservoir, but not for the case where the correct amounts of catalyst and diluent are pre-weighed for each tube before loading. This method ensures the total number of active pills in the diluted zone is always correct but it does not eliminate the random axial activity variability that is inherent in sampling from mixtures of active and inert pills. When loading a reactor tube from a pre-weighed single tube aliquot, the reservoir is finite; the loading process is a series of Bernoulli trials without replacement and the statistics of loading are described by the hypergeometric distribution.We have modeled the behavior of reactor tubes loaded in this way for tube to pill diameter ratios (N) between 3 and 10, which covers the typical range of commercial practice for such reactor systems. While the total number of active pills is always correct for this type of reactor tube, the statistical variability in the axial activity profile can cause significant numbers of tubes to run away, despite the fact that the tube would be stable with a flat activity profile. This effect is exacerbated by smaller tube to particle ratios (N values) and greater extents of catalyst dilution.While this loading scheme is still subject to statistical variability, our results show that tubes loaded from pre-weighed, single tube aliquots perform significantly better than those loaded from an infinite reservoir (55 gallon drum for example ) where the correct total activity is not guaranteed and the catalyst loading statistics are described by the binomial distribution.

Placebo mechanisms for drug dose reduction: what is the evidence?

The mechanisms that generate and steer the placebo response in clinical trials and clinical practice are increasingly better understood. Pavlovian conditioning of physiological responses to medication that are associated with the intake of a drug, and expectation-driven evaluation of symptoms and symptom changes by the patient after the intake of a presumed medication, contribute to symptomatic improvement as well after intake of an inert pill (placebo), as long as he/she is unaware of its nature [1]. It has also been shown that the likelihood of receiving active treatment in clinical trials modulates the placebo response [2]. Recent research has, however, shown that even the knowledge to receive a placebo will generate clinical improvements as long as the patients have had a positive experience (history) with medication and positive expectations are maintained [3]. Separating expectancy-mediated and conditioned placebo responses may be feasible in experimental research, but in clinical trials as well as in daily routine, “much like the laws of gravity, the laws of learning are always in effect” [4] and do not allow such isolation. If expectation and conditioning are ingredients of the placebo response, the quest of how to make use of them in medical practice and research arises. One precondition is to rigorously follow principles of ‘associative learning’ that were set by Ivan P Pavlov. This was realized by – among others – Robert Ader (1932–2011), a psychologist at the Rockefeller University (NY, USA) who pioneered psychoimmunology, the investigation of CNS influence and control of immunological functions using Pavlovian conditioning principles since 1975 [5]. In the 1980s, Ader had hypothesized that the placebo effects as seen in clinical studies, specifically with randomized, placebo-controlled crossover trials (a frequently used design until today), may be due to conditioning [6]. He was among the first to propose using a conditioning procedure to partially replace drugs with placebos in tandomized-controlled trials [7], and he even patented a “Method and device for administering medication and/or placebo” to test his hypotheses [101]. In an initial study, the effects of atenolol, a beta-blocker, were investigated in 24 patients with mild or moderate hypertension [6]. Patients received either placebo, followed by the drug, followed by no treatment (Group 1); or the drug, followed by placebo (Group 2); or the drug, followed by no treatment (Group 3); with each period lasting for 1 week. Prior to drug intake, Group 1 did not differ from Group 2 and 3 in the average blood pressure taken daily at home. After 1 week of drug treatment for all, blood pressure and heart rate were significantly lower in the placebo treated group (Group 2) than in the nontreatment controls (Groups 1 and 3), indicating that the placebo response was more than a residual drug effect. This is consistent with a conditioning model of the placebo effect. Such a conditioned response to placebo pills can be achieved if it is preceded by an acquisition period that is sufficiently long and effective.

A novel placebo-controlled clinical study design without ethical concerns – The free choice paradigm

All doubled-blinded and placebo-controlled randomized drug trials carry the ethical limitation that up to 50% of patients are treated by an inert placebo pill for a prolonged period of time, and that treatment effects of the drug have to be separated from unspecific (placebo) effects that also occur in the drug arm of the treatment. We propose the “free choice paradigm” (FCP) as an alternative. It allows patients to choose between two pills identical in shape and colour of which one is the drug and the other is the placebo (in a double-blinded fashion), and drug efficacy is assessed as the difference in the number of events (days) one pill is chosen over the other. Advantages as well as disadvantages and limitations of the FCP still need to be assessed, as need the computational statistics to demonstrate superiority of drug over placebo. Ethical limitations are, however, minimized.

P-649 - Placebo effect in clinic of forensic psychiatric examination

In forensic psychiatry placebo is used rather rarely. It is because forensic psychiatrists don't have enought qualification in this area and they have to work with the special type of patients, who are difficult to communicate and create a rapport with. The patients of forensic psychiatrists always have a conscious intention to simulate or to develope a mental derangement to avoid crimanal liability. Using of placebo in forensic psychiatry gives an opportunity to differ simulation from true mental disorder in a 90% of cases. In subjectively difficult situation (being in prison, incarceration) different mental disorders usually progress. We examined about 100 patients who showed symptoms of different mental aberrations which made it hard to diagnose actual condition of the patient.Placebo procedure is when a patient is given an inert pill, told that it may improve his or her condition, but not told that it is in fact inert. It may make the patient to believe the treatment will change his or her condition and this belief may produce a subjective perception of a therapeutic effect, causing the patient to feel their condition has improved or an actual improvement in their condition. As the result of using the placebo we overcame such symptoms like:· insomnia· headaches · psychic tension· collapse· tremor· hysterical paroxysmal· mutismAfter using of the placebo these symptoms quickly disappeared and we were able to diagnose actual condition of the patient and bring him to justico.