Change of Circulating Vascular Endothelial Growth Factor Level and Reduction of Anhedonia Are Associated in Patients With Major Depressive Disorder Treated With Repetitive Transcranial Magnetic Stimulation.

Aim: Vascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressant therapies as it plays a significant role in the neurogenesis. Anhedonia, an endophenotype of major depressive disorder (MDD), is related to the dorsolateral prefrontal cortex, the major focus of brain stimulation in MDD. The aim of our study was to analyze the change of serum VEGF level after rTMS treatment in association with anhedonia. Materials and Methods: A dataset of 17 patients with TRD who were treated with antidepressants and bilateral rTMS for 2 × 5 days was analyzed. Depression was measured by the Montgomery-Asberg Depression Scale (MADRS) and anhedonia by the Snaith-Hamilton Pleasure Scale (SHAPS) for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2), and on the 28th day (V3). The level of VEGF was measured by ELISA assay. Results: There was no significant association between MADRS scores and serum VEGF levels at any timepoint. The decrease in the SHAPS score was significantly associated with the increase in VEGF level between V1 and V2 (p = 0.001). The VEGF levels were significantly higher in non-responders than in responders (p = 0.04). The baseline VEGF level has been proven as a significant predictor of treatment response (p = 0.045). Conclusion: Our results suggest that serum VEGF can be sensitive to the changes of anhedonia during rTMS treatment. Considering that the most widely used depression scales are not applicable for the assessment of anhedonia, measurement of anhedonia in rTMS treatment studies of patients with TRD can be suggested as more appropriate data on distinct pathogenic pathways and specific biomarkers of the disorder.

[Can we influence the negative drug attitude? Interpretation of the rejection of COVID-19 vaccine in the light of results of a pilot study].

Background and purpose: Vaccination refusal is a serious obstacle to minimizing the spread of COVID-19. Nevertheless, the rejection of vaccine can be considered the result of a negative attitude towards medical treatment, and according to our previously published data, it can be influenced by the underlying affective state. Increased incidence of affective disorders and anxiety could be observed globally during the pandemic, which may have a significant impact on vaccination acceptance. The aim of our pilot study was to determine the association between clinical improvement of affective and neurocognitive symptoms and change of drug attitude and health control beliefs in a sample of psychiatric patients. Methods: A data set of 85 patients with psychiatric disorder has been analysed with the use of Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) with 5 subscales (Negative Aspect of Medication - NA; Positive Aspect of Medication - PA; Doctor health locus of control- Doctor HLOC; Internal HLOC; Psychological Reactance - PR); Hospital Anxiety Depression Scale (HADS-Anx; HADS-Dep) and neurocognitive tests, such as the Stroop test and the Trail Making Tests. All the tests were performed before and after a 14 days treatment. Paired t-tests and generalized linear models were performed to assess the associations between the variables. Results: The baseline scores of NA and HADS-Anx correlated significantly (p=0.001) and after two weeks of treatment NA decreased (p=0.001), while Doctor HLOC and Internal HLOC increased (p=0.001 and p=0.006). The patients performance of the neurocognitive tests improved (all p<0.05). The reduction of HADS-Anx (p=0.002) and HADS-Dep (p=0.006) scores showed significant associations with the decrease of NA. Increase of the PA score was associated with reduction of HADS-Dep (p=0.028). Improvement of neurocognitive functions had no effect on PHBQPT scores. Conclusion: Important conclusions can be drawn regarding the rejection of the COVID-19 vaccine based on the associations found between the intensity of affective and anxiety symptoms and the attitude towards treatment. Our findings suggest that affective symptoms have a negative influence on the attitude towards treatment and that the improvement of these symptoms can facilitate the acceptance of the therapy, regardless of diagnosis. The modest effect of the improvement of neurocognitive functioning on the attitude towards drugs and the significant role of affective-emotional factors suggest that the accep-tance of vaccination probably cannot be facilitated solely with the aid of educational programs. Considering the increasing incidence of affective disorders during the COVID-19 pandemic, the screening of affective and anxiety symptoms and treatment of these disorders could be an important step towards the acceptance of the vaccine. Although psychiatry is not considered as a frontline care unit of the COVID cases, more attention is needed to pay on the availability of mental health services because refuse of vaccine can develop due to affective disorders too.

Poor Adherence to Oral Psychiatric Medication in Adults with Bipolar Disorder: The Psychiatrist May have More Influence than in Other Severe Mental Illnesses.

Objective: Medication adherence in bipolar disorder (BD) may be influenced by 6 selfreported dimensions: 1) high/low psychological reactance, 2) high/low internal healthlocus of control (HLOC), 3) high/low doctor HLOC, 4) pharmacophobia, 5) pharmacophilia, and 6) skepticism about a specific medication. This study in Spain, Argentina, and Venezuela included 142 outpatients with BD prescribed 320 psychiatric medications and 1230 other psychiatric outpatients prescribed 2134 medications. Methods: Logistic regression models included adherence for each psychiatric medication, measured by the Sidorkiewicz Adherence Tool as the dependent variable. The models provided adjusted odds ratios (ORs) of dichotomous independent variables: clinical variables and 6 self-reported dimensions. Results: ORs significant in both groups were: 1) high doctor HLOC (OR=1.87 in BD, OR=1.25 in other patients), 2) high psychological reactance (respectively OR=0.572, OR=0.798), 3) pharmacophobia (respectively OR=0.361, OR=0.614), and 4) skepticism about a specific medication (respectively OR=0.300, OR=0.556). Two ORs were only significant in BD patients: medication duration > 1 year (OR=0.449), and extreme polypharmacy (OR=2.49). The study included 104 BD patients prescribed 122 mood stabilizers and 136 other patients prescribed 140 mood stabilizers. Two ORs were significant for mood stabilizer adherence only in BD patients: high doctor HLOC and skepticism (respective ORs=2.38, OR=0.390). The study included 87 BD patients prescribed 97 antipsychotics and 417 other patients prescribed 458 antipsychotics. Four ORs were significant for antipsychotic adherence only in the BD group. Conclusions: Future studies of adherence to all/specific medications should explore the specific city/commonality of these dimensions, particularly doctor HLOC, in BD versus other psychiatric patients. (Neuropsychopharmacol Hung 2021; 23(4): 347-362).

Adherence to psychiatric medications: Comparing patients with schizophrenia, bipolar disorder and major depression.

Findings of three articles reporting results in 1372 stabilized outpatients taking 2454 medications in Spain, Argentina, and Venezuela were combined. Prevalence of good adherence was not obviously different across diagnoses: 69.5% (N=212) for schizophrenia, 66.3% (N=142) for bipolar disorder, and 69.8% (N=521) for depression. Besides the focus on stabilized outpatients, other study biases included use of a research sample; limited to oral medications, ignoring long-acting injectable antipsychotics; and lack of data on active substance abuse, clinical severity, and insight. Logistic regression models explored predictors of good vs. poor adherence. The six self-reported variables studied were pharmacophobia, pharmacophilia, high psychological reactance, high internal health locus of control (LOC), high doctor LOC, and skepticism concerning specific medications. ORs were significant in 56% (47/84) of the statistical tests vs. 24% (23/98) of ORs significant in case of 7 demographic/clinical variables (p=0.001). At least 2/3 of the ORs for pharmacophobia, pharmacophilia and skepticism were significantly associated with adherence in cases and controls, indicating their independence from diagnoses. In need of replication, three other self-reported measures had differential effects on adherence across diagnoses. High psychological reactance was associated with decreased adherence to antidepressant medications in general, or for patients with mood disorders. High internal LOC as associated with poor adherence may reflect the distrust patients with schizophrenia or severe bipolar disorder have of other people. High doctor LOC was significantly associated with increased adherence only in patients with bipolar disorder, but was significant for all medications, mood stabilizers and antipsychotics, indicating the relevance of the patient-psychiatrist relationship in these patients. (Neuropsychopharmacol Hung 2021; 23(4): 363-373).

Poor Adherence to Oral Psychiatric Medication in Adults with Depression: Psychological Reactance May Have Specific Effects in Depression.

Objective: Medication adherence in psychiatric disorders, including depression, may be influenced by 6 self-reported dimensions: 1) high/low doctor health locus of control (HLOC), 2) high/low internal HLOC, 3) high/low psychological reactance, 4) pharmacophilia, 5) pharmacophobia, and 6) skepticism about a specific medication. This study in Spain, Argentina, and Venezuela included 521 outpatients with depression prescribed 920 psychiatric medications and 851 other psychiatric outpatients prescribed 1534 medications. Methods: Logistic regression models were completed in patients with depression and psychiatric controls. The dependent variable was adherence for each psychiatric medication (Sidorkiewicz Adherence Tool). The models provided adjusted odds ratios (ORs) of dichotomous independent variables: clinical variables, and 6 self-reported dimensions. Results: ORs significant in both diagnostic groups were: 1) pharmacophobia (OR=0.500 in depression, OR=0.599 in other patients), 2) pharmacophilia (respectively OR=1.51, OR=1.65), 3) treatment for 1 year (respectively OR=0.731, OR=0.608), 4) geriatric age (respectively OR=2.28, OR=3.02), and 5) skepticism about a specific medication (respectively OR=0.443, OR=0.569). Two ORs were significant in the depression group, but not in the controls: the country of Spain (OR=0.744), and high psychological reactance (OR=0.685). The study included 470 depression patients prescribed 510 antidepressants and 348 other patients prescribed 370 antidepressants. One OR was significant for antidepressant adherence in both groups: high psychological reactance (respectively OR=0.597, OR=0.561). Conclusions: All clinical studies using self-report include biases but the most important is lack of access to patients not coming for treatment. Future studies should further explore the specificity/commonality of these dimensions, particularly psychological reactance, in depression versus other psychiatric disorders. (Neuropsychopharmacol Hung 2021; 23(4): 374-387).

Poor Adherence to Oral Psychiatric Medication in Adults with Schizophrenia May Be Influenced by Pharmacophobia, High Internal Health Locus of Control and Treatment Duration.

Objective: This study in Spain, Argentina, and Venezuela included 212 schizophrenia outpatients prescribed 387 psychiatric medications and 1,160 other psychiatric outpatients prescribed 2,067 medications. Methods: Logistic regression models included adherence for each psychiatric medication, measured by the Sidorkiewicz Adherence Tool, as the dependent variable. The models provided adjusted odds ratios (ORs) of dichotomous independent variables: 1) clinical variables, 2) subscales from the Patient Health Beliefs Questionnaire on Psychiatric Treatment (presence/absence of pharmacophobia and pharmacophilia and high/low psychological reactance, internal health locus of control [HLOC] and doctor's HLOC) and 3) presence/absence of skepticism toward each medication measured by the Beliefs about Medicines Questionnaire (BMQ). Results: ORs significant in both groups were: 1) pharmacophobia (OR=0.389 in schizophrenia, OR=0.591 in other patients and not significantly different) and 2) pharmacophilia (respectively OR=2.18, OR=1.59 and significantly higher in schizophrenia: p=0.012). Prescribing the medication for >1 year increased adherence in schizophrenia (OR=1.92) while decreasing it in others (OR=0.687). Four ORs were significant in the schizophrenia group but not in the controls: treatment for >1 year (OR=0.161), high internal LOC (OR=0.389), extreme polypharmacy (OR=1.92) and the country of Spain (OR=0.575). Regarding antipsychotics, the study included 204 schizophrenia patients prescribed 240 antipsychotic medications and 301 other patients prescribed 315 antipsychotic drugs. Three ORs were significant for antipsychotic adherence in the schizophrenia group: pharmacophobia (OR=0.324), treatment for >1 year (OR=0.362), and skepticism about specific antipsychotics (OR=0.535). Conclusions: Future adherence studies for antipsychotic/all medications should further explore the specificity/commonality of these dimensions in schizophrenia versus other psychiatric patients. (Neuropsychopharmacol Hung 2021; 23(4): 388-404).

What is the dominant treatment attitude of psychiatric patients?

Background: Patients' attitude towards drug treatment is of prognostic value regarding adherence. However, few detailed analyses have been performed regarding the influencing factors of the treatment attitude of psychiatric patients. Methods: We enrolled in the study 295 psychiatric inpatients and analyzed the data obtained using the recently developed Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT), the Behavioural Inhibition/ Activation System (BIS/BAS) Scale, and the Hospital Anxiety and Depression Scale. We created a 'dominant treatment attitude' (DTA) variable from the 5 subscales of the PHBQPT. Results: The most common DTA was the Doctor HLOC and the rarest proved to be the Psychological Reactance. The double DTA carriers were the most frequently occurring multiple DTAs. We found that the Doctor-HLOC coupled most frequently with the Positive Aspect and the DoctorHLOC with the Internal-HLOC. The Doctor-HLOC score was higher while the BAS Fun seeking score lower in the case of patients treated for affective disorders compared to patients who belonged to the psychosis and personality disorder subgroups. Conclusions: Screening of DTAs in psychiatric patients can provide useful information for the planning of a more effective therapeutic strategy. (Neuropsychopharmacol Hung 2021; 23(2): 308-318).

Health Control Beliefs and Attitude Toward Treatment in Psychiatric and Non-Psychiatric Clinical Samples.

Although there is accumulating evidence on the potential influencing factors of medication adherence, the knowledge about patients' attitudes and beliefs toward treatment is only partly utilized in adherence-improving strategies. Several internal and external factors determining adherence have been described regarding many chronic somatic diseases but in recent research, insight on psychiatric patients has been exclusively lacking. As a result, there is a scarcity of effective adherence-improving interventions. Identification of any specific differences or similarities between the attitudes toward treatment of psychiatric and non-psychiatric patients would help to support adherent behavior. We recruited 189 participants from four departments of general psychiatry (GEN PSYCH, n = 106), addictology (ADDICT, n = 42) and somatic diseases (NON PSYCH, n = 41). The Patient's Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) was performed to assess the patients' attitude toward drug treatment, perceived health locus of control, and psychological reactance. The most robust difference of the PHBQT scores occurred between the GEN PSYCH and ADDICT subgroups. ADDICT patients scored significantly higher on the internal and external health locus of control and on the Psychological Reactance subscale as well. While GEN PSYCH subjects provided higher scores on the Positive Aspect of Medication compared to ADDICT persons. Interestingly, the only difference between the GEN PSYCH and NON-PSYCH groups was the more pronounced mistrust in physicians in the case of psychiatric patients. Our data suggest that mistrust toward medication does not differ in psychiatric and non-psychiatric samples, while the acceptance of the doctor's competency may be stronger in the non-psychiatric sample. The analysis of these factors provides information which could help us better understand this important issue and to develop more efficient interventions for improving adherence.

Peripheral endocannabinoid serum level in association with repetitive transcranial magnetic stimulation (rTMS) treatment in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and well tolerable biological intervention in major depressive disorder (MDD) contributing to rapid symptom improvement. Molecular mechanisms underpinning the therapeutic effects of rTMS have still not been clarified. Recently published animal data implicated relevant associations with changes in endocannabinoid (eCB) brain levels during rTMS treatment, human studies, however, have not been published. In our study we assessed the detailed phenotypic spectrum of MDD and serum 2-arachidnoylglycerol (2-AG) and anandamide (AEA) levels in 18 patients with treatment-resistant depression before, immediately following, and two weeks after completion of a 10-day rTMS treatment. We found significant associations between serum 2-AG level changes from pretreatment to 2 weeks after treatment and symptom reduction. The greater the increase of 2-AG levels, the greater the improvement of depressive (p = 0.031), anxious (p = 0.007) and anhedonia symptoms (p = 0.047). Here we report for the first time a significant association of human circulating eCB and antidepressant effect of rTMS. Our data may indicate that direct stimulation of targeted brain areas can rapidly alleviate depressive complaints via activation of the eCB system.

[Validation and analysis of the Patient's Health Belief Questionnaire on Psychiatric Treatment in a sample of Hungarian psychiatric patients].

OBJECTIVES: Patients' attitude towards treatment is one of the most signifi cant factors which has determining eff ect on suffi cient adherence. Data are lacking on Hungarian patients' attitude towards psychiatric treatment, however, high prevalence of suicide suggests that eff ectiveness of psychiatric treatments need to be improved. To pave the way for such studies, we performed the validation of the recently developed Patients' Health Belief Questionnaire on Psychiatric Treatment (PHBQPT) in a sample of Hungarian psychiatric patients. METHODS: We enrolled 188 Hungarian patients diagnosed with psychiatric disorders. The PHBQPT was translated into Hungarian by our group. Comparison of item and subscale mean scores with the original data are presented. Internal consistency, item-total and item-item correlations were calculated and factorial structure was analysed. RESULTS: Single item means, the highest item score and subscale mean scores were similar to data published in the original article. The factorial analysis confi rmed the validity of a fi ve-subscale structure in our sample. The eff ects of gender and age were not signifi cant on any of the subscales. CONCLUSIONS: The PHBQPT is a valid, reliable instrument with replicable psychometric properties. The Hungarian version is suitable for clinical practice and for further investigations on attitudes towards psychiatric treatment.

[The first lockdown due to COVID-19 pandemic from the psychiatric patients' perspective: an ambulatory care client experience survey]. / A COVID-19 járvány miatt elrendelt elso veszélyhelyzet a pszichiátriai betegek szemszögébol: gondozói felmérés.

INTRODUCTION: The coronavirus pandemic (COVID-19) required the declaration of a state of emergency in Hungary from 11 March 2020 to 18 June 2020. These governmental actions led to changes in everyday life, implementation of new rules, and reduced access to healthcare. Hospital beds were reserved for emergency use, face-to-face ambulatory care was mainly replaced by telemedicine. In our study we assessed opinion of the patients in two outpatient psychiatric care units in Budapest regarding the state of emergency. METHODS: We enrolled 438 patients in the survey (305 women and 133 men, mean age: 51.9±16.2 years). The patients completed a short questionnaire on a voluntary and anonymous basis following verbal informed consent. The questionnaire was comprised of 10 items and a 12-item "Problem Evaluation Scale" (fear, isolation and healthcare subscales). The comparison of groups was done using general linear models (GLM), pairwise comparison was performed using Tukey's test for post hoc analysis. The data set was analyzed with SPSS software, version 24.0. RESULTS: Up to 34% of enrolled patients believed that their condition worsened during the state of emergency, but 12% of these patients thought that this worsening was not related to the state of emergency. Twice as many patients (12.8%) were concerned about their financial situation than about their health status (6.1%). Loneliness and the implementation of specific regulations didn't cause relevant distress in almost half of the patients, isolation was the most frequently (55.2%) reported difficulty. The worsening of health status was reported more frequently (p=0.001) by the patients younger than 50 years, the sensation of fear was stronger (p=0.045), and they reported more serious adaptation difficulties (p=0.003) than subjects older than 50 years. Isolation caused significantly (p=0.003) more serious distress among women. The abundance of pandemic-related information caused more distress in the case of patients treated for anxiety than participants treated for psychotic disorders (p=0.024). Patients suffering from affective disorders perceived more pronounced feelings of vulnerability compared to patients treated for psychotic disorders (p=0.004). CONCLUSION: Approximately half of the enrolled psychiatric patients was able to adapt to this situation without major difficulties, the other half of this sample was more or less distressed by these circumstances. Unfortunately, depletion of emotional, psychological, social and material resources can be expected during the next stage of the pandemic. As a result, we can expect further worsening of the above presented aspects.

[Health control beliefs and chronic illness:how do they relate?] / Egészségkontrollhit és krónikus betegség:hogyan hatnak egymásra?

The health locus of control has been extensively analyzed in diff erent patient populations suff ering from chronic somatic illnesses due to its infl uence on adherence to long-term therapies. Despite of the fact that adherence is one of the most important factors which needs to be taken into consideration in the oupatient care of psychiatric patients, there is a scarcity of studies regarding HLOC in this population. In this review we provide an overview of study results regarding HLOC in somatic and psychiatric patients. Based on these results we conclude that in the case of patients suff ering from chronic illnesses, a higher internal HLOC is associated with less severe depressive symptoms and better adherence and quality of life. Nevertheless, the results of the follow-up studies indicate that change of HLOC (from internal to external) can be adaptive when the outcome is not favourable or the treatment is not eff ective. The continuous evaluation of HLOC of psychiatric patients in treatment may provide necessary information for the planning of interventions to help this process. Taking into consideration that the patients' perception of control is often impaired due to the nature of psychiatric illnesses we propose evaluation of psychobiological factors infl uencing health locus of control in order to facilitate the planning of these interventions.

[Pharmacological treatment and health control beliefs from the perspective of psychiatric patients: differences in attitudes]. / Gyógyszeres kezelés és egészségkontrollhit a pszichiátriai betegek szemszögébol: attitudbeli különbségek.

INTRODUCTION: Patients' attitudes towards psychiatric treatment have an important influence on therapeutic outcome. Health beliefs and the patient's attitude towards the psychiatrist and medical treatment are determined by several factors about which there is only a scarce knowledge. In our study we used the Patient's Health Belief Questionnaire on Psychiatric Treatment, PHBQPT) to assess the beliefs and attitudes of patients suffering from psychiatric disorders. METHODS: We recruited 115 inpatients from the Nyíro Gyula National Institute of Psychiatry and Addictions. Patients were categorized into 5 classes based on ICD-10 (addictions-F1x; psychotic disorders-F2x; affective disorders-F3x; anxiety disorders-F4x; and personality disorders-F6x). Subjects voluntarily and anonymously completed the PHBQPT questionnaire and answered 4 additional items regarding their opinion about the efficacy of drugs and the placebo effect. We compared the scores of the items and the total scores of subscales of the PHBQPT scale between disorder categories using ANOVA tests. RESULTS: Total scores did not diff er significantly in our sample compared to those in the publication of the original version of the PHBQPT scale. The most robust diff erences were found between patients with addictions and psychotic patients on the external and internal control subscales. F1x subgroup could also be distinguished from other psychiatric disorders on certain health belief related items. However, patients with personality disorder and affective disorder felt that the efficacy of medications in general was the weakest. The impression that in the drug effect is individually modified in case of a given patient was more frequent in the F1x and F2x groups and rare in the group of subjects with anxiety disorders and personality disorders. CONCLUSION: The Hungarian version of the PHBQPT can be used in case of Hungarian psychiatric patients; the similarity shown by the results points at the fact that attitude towards treatment is independent of cultural and healthcare system diff erences. Our results highlight that there are variances between different psychiatric disorders in health belief and attitude towards drug treatment. Our study emphasizes the importance of thorough assessment of patients' attitude that is necessary to conceive an effective adherence improving intervention.

[Effect of placebo response on results of antidepressant clinical trials]. / A placeboválasz hatása az antidepresszívumokkal végzett klinikai vizsgálatok eredményére.

Provocative data have been published regarding the results of clinical trials executed in order to assess the efficacy of antidepressants (AD) during the past years. Beside the continuously increasing placebo response the efficacy of ADs could not be differentiated from the effect of placebo in more than half of the studies. Several factors have been identified in the background of this phenomenon, researchers have proposed numerous possible solutions for this issue, including systematic re-evaluation of data, reconsideration of tools used for assessment of efficacy, of study design and of statistical methods. Multiple different possible interpretations, problem definitions and explication models can be found in the literature providing an overview which can be useful for clinicians and researchers as well. The following review summarizes the data and results which help in drawing a more detailed picture about the relationship between AD and placebo effect. The way this specific problem is addressed points beyond the actual topic, as it challenges the dilemmas of evidence-based medicine. As a conclusion it can be stated that despite the fact that the degree and relevance of placebo effect is the subject of continuous debate, the use of placebo is still unavoidable in clinical trials and deepening the knowledge on this topic is required.

[Psychobiological background and clinical aspects of the placebo effect in psychiatry]. / A placebo-hatás pszichobiológiai háttere és klinikai vonatkozásai a pszichiátriában.

The placebo-effect is present in almost every field of medicine, however, in the assessment of the effect of psychotropic drugs it is a major problem. The rise of the placebo-effect in clinical trials is observed during the last decades, in spite of all efforts to introduce new methods in clinical trials to overcome this problem and the number of studies aiming to unveil the mechanisms that lie in the background that this phenomenon have risen. A considerable amount of data has accumulated regarding the psychobiological background of placeboeffect, however, the details of underlying mechanisms are still not clear. Furthermore, the lack of objective tools for the assessment of the phenotypic changes during the treatment of psychiatric disorders makes it even more difficult to differentiate the symptom intensity changes related to drug response from the placebo effect. The consequences of this scarcity of information concerning the background of placebo-effect may hinder the development of new compounds, having enormous medical, scientific and economical disadvantages. In this review we summarise the psychobiological mechanisms in the background of placebo effect and its impact on clinical trials.