Therapeutic drug monitoring in psychiatry.

In medicine, there are two main methods of improving the healthcare provided: perfecting (optimizing) the existing ones and seeking new treatment procedures. Despite of tremendous development in the central nervous system research, current treatment of severe mental illnesses, such as schizophrenia and depressive disorder, is suboptimal. Nowadays, optimization of treatment in psychiatry includes therapeutic drug monitoring (TDM) and pharmacogenomic testing, which examines genetic variation involved in medication metabolism and drug action. The TDM enables to determine drug concentrations in blood and adjust the dose accordingly if clinical effects correlate better with drug blood levels than drug doses. The first international guidelines for TDM in neuropsychopharmacology were published in 2004 and regularly updated. The recent update provides therapeutic reference ranges for a majority of commonly prescribed psychiatric medications and gives example of patients regularly treated in clinical practice profiting from TDM (using antipsychotics and changing their smoking habits). TDM in psychiatry is an underused tool, given its ability to optimize treatment, as well as to improve treatment effectiveness.

Stereotactic radiotherapy for spinal hemangioblastoma - disease control and volume analysis in long-term follow up.

Background: This retrospective analysis evaluated the long-term outcome of spinal stereotactic body radiotherapy (SBRT) treatment for hemangioblastomas. Materials and methods: Between 2010 and 2018, 5 patients with 18 Von-Hippel Lindau-related pial-based spinal hemangioblastomas were treated with fractionated SBRT. After precisely registering images of all relevant datasets, we delineated the gross tumor volume, spinal cord (including intramedullary cysts and/or syrinxes), and past radiotherapy regions. A sequential optimization algorithm was used for dose determinations, and patients received 25-26 Gy in five fractions or 24 Gy in three fractions. On-line image guidance, based on spinal bone structures, and two orthogonal radiographs were provided. The actuarial nidus control, surgery-free survival, cyst/syrinx changes, and progression-free survival were calculated with the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: The median follow-up was 5 years after SBRT. Patients displayed one nidus progression, one need of neurosurgery, and two cyst/syrinx progressions directly connected to symptom worsening. No SBRT-related complications or acute adverse radiation-related events occurred. However, one asymptomatic radiological sign of myelopathy occurred two years after SBRT. All tumors regressed; the one-year equivalent tumor volume reduction was 0.2 mL and the median volume significantly decreased by 28% (p = 0.012). Tumor volume reductions were not correlated with the mean (p = 0.19) or maximum (p = 0.16) dose. Conclusions: SBRT for pial-based spinal hemangioblastomas was an effective, safe, viable alternative to neurosurgery in asymptomatic patients. Escalating doses above the conventional dose-volume limits of spinal cord tolerance showed no additional benefit.

From Personalized Medicine to Precision Psychiatry?

Personalised medicine aims to find an individualized approach for each particular patient. Most factors used in current psychiatry, however, depend on the assessment made by the individual clinician and lack a higher degree of reliability. Precision medicine bases decisions on quantifiable indicators available thanks to the tremendous progress in science and technology facilitating the acquisition, processing and analysis of huge amounts of data. So far, psychiatry has not been benefiting enough from the advanced diagnostic technologies; nevertheless, we are witnessing the dawn of the era of precision psychiatry, starting with the gathering of sufficient amounts of data and its analysis by the means of artificial intelligence and machine learning. First results of this approach in psychiatry are available, which facilitate diagnosis assessment, course prediction, and appropriate treatment choice. These processes are often so complex and difficult to understand that they may resemble a "black box", which can slow down the acceptance of the results of this approach in clinical practice. Still, bringing precision medicine including psychiatry to standard clinical practice is a big challenge that can result in a completely new and transformative concept of health care. Such extensive changes naturally have both their supporters and opponents. This paper aims to familiarize clinically oriented physicians with precision psychiatry and to attract their attention to its recent developments. We cover the theoretical basis of precision medicine, its specifics in psychiatry, and provide examples of its use in the field of diagnostic assessment, course prediction, and appropriate treatment planning.

Plasma Levels of Long-Acting Injectable Antipsychotics in Outpatient Care: A Retrospective Analysis.

PURPOSE: Antipsychotic efficacy in schizophrenia depends on its availability in the body. Although therapeutic outcomes remain still far from satisfactory, therapeutic drug monitoring is not a common part of clinical practice during treatment with long-acting injectable antipsychotics (LAI AP). The real effectiveness of LAI AP is thus uncertain. PATIENTS AND METHODS: We made a retrospective evaluation of plasma levels of LAI AP. Collection of blood samples was performed just before the drug application and one week later. Forty patients with a stabilized clinical condition and steady-state plasma levels were included. RESULTS: In the observed cohort of patients, flupentixol decanoate (n = 23) was the most often used drug, followed by fluphenazine decanoate (n = 7), haloperidol decanoate (n = 5), paliperidone palmitate (n = 3), and risperidone microspheres (n = 2). Just 5 of 40 patients were treated with a monotherapy. In the period before the application, 60% of the patients did not reach the therapeutic reference range (TRR) and 20% of the patients had an undetectable plasma level. At the time of collection of the second blood samples performed after 7 days, 24% of the patients were under the TRR. CONCLUSION: We have found a surprisingly high incidence of plasma levels under the TRR in patients treated with LAI AP. Notwithstanding individual variability in pharmacokinetics, it seems that LAI AP may be underdosed in usual clinical practice.

Medical Students' Career Choice and Attitudes Toward Psychiatry: Case of the Czech Republic.

OBJECTIVE: A survey among medical students of all medical schools in the Czech Republic was conducted to investigate attitudes and views of psychiatry and career choice of psychiatry. METHODS: A Czech version of the Attitudes to Psychiatry Scale (APS) and a questionnaire surveying demographic characteristics and choices of future specialty were distributed to all medical students of eight medical schools in the Czech Republic via the schools' internal communication systems in the form of an anonymous online questionnaire. RESULTS: Out of a total of 10,147 medical students in the Czech Republic (academic year 2019/2020), 2418 students participated in the survey (response rate 23.8%). Psychiatry as a non-exclusive career choice was considered by 31.3% respondents; child and adolescent psychiatry was considered by 15.4% respondents. Psychiatry as the only choice was considered by 1.6%, and child and adolescent psychiatry was not considered at all. The interest in both specialties was declining since the first year of study. The status of psychiatry among other medical specialties was perceived as low; students were rather discouraged from entering psychiatry by their families. They did not feel encouraged by their teachers to pursue career in psychiatry despite the fact that they were interested in psychiatry. They also felt uncomfortable with patients with mental illness. CONCLUSIONS: Despite high enthusiasm for psychiatry in the first year of medical school, only a small proportion of medical students consider to choose psychiatry, and especially child and adolescent psychiatry, as a career at the end of medical school.

What Does Antidepressant Drug level Monitoring Reveal About Outpatient Treatment and Patient Adherence?

INTRODUCTION: The evaluation of plasma levels of antidepressants may improve the treatment outcome. The aim was to verify adherence and adequacy of administered doses of antidepressants among patients hospitalized for inadequate outpatient therapeutic response. METHODS: Selective serotonin reuptake inhibitors or venlafaxine plasma levels were assessed on the first day of hospitalization and after 3 days of controlled administration. The patients were considered adherent if the plasma level on admission was within the interval of the minimum and maximum plasma level on the fourth day, expanded by 30%. The adequacy of antidepressant doses used during the outpatient treatment was assessed by comparing the plasma level on the fourth day with the therapeutic reference range. RESULTS: Out of 83 patients, 52 (62.7%) were adherent. The plasma levels of antidepressants on the fourth day were found to be within the therapeutic reference range in 35 (43.2%) patients. The same number manifested levels below the therapeutic reference range. In 11 (13.6%) patients, the levels were higher than recommended. No significant difference in rate of adherence was found among individual antidepressants. CONCLUSION: The results show that antidepressant nonresponders are frequently under-dosed or nonadherent.

Novel treatment options in depression and psychosis.

In spite of tremendous development in central nervous system research, current treatment is suboptimal, especially in severe mental disorders. In medicine, there are two main methods of improving the health care provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring but also implementation of general trends in the clinical practice. New pharmacological options include new more sophisticated forms of monoaminergic drugs, old drugs rediscovered on the base of a better understanding of pathophysiology of mental illnesses, and drugs aimed at new treatment targets. In depression, treatment resistance to antidepressive pharmacotherapy represents one of the most important clinical challenges. Switching to monotherapy with new multimodal/multifunctional antidepressants and augmentation with new atypical antipsychotics (aripiprazole and brexpiprazole) may be promising options. Further, current evidence supports utility and safety of adjunctive treatment of nutraceuticals. Novel approaches being studied include ketamine and opioids. Recent advances in technology and emerging knowledge about dysfunctional brain circuits and neuroplasticity have led to the development of different new neuromodulation techniques usually used as add-on therapy. Antipsychotics are still the cornerstone of the current treatment of schizophrenia. Two new partial dopamine agonists, brexpiprazole and cariprazine, are now available in addition to aripiprazole. Although the mechanisms of action are similar, the two agents differ in terms of their pharmacodynamic profiles. Further, two new formulations of long-acting injections of second-generation antipsychotics (aripiprazole lauroxil and 3-month paliperidone palmitate) were introduced into clinical practice. New treatment options not yet available include cannabidiol, glutamate modulators, and nicotine receptors agonists.

Relationship between rapheal echogenicity and personality as possible markers of a disposition to develop depressive and anxiety disorders.

Early diagnosis of anxiety and depression may be facilitated by the use of neurobiological markers. In depression and panic disorder, transcranial sonography (TCS) has revealed decreased echogenicity of the brainstem raphe (BR). The aim of the present study was to detect whether decreased echogenicity of the BR correlates with personality features described in the five-dimension model, especially neuroticism. We examined 100 healthy volunteers using quantitative and qualitative TCS, the five-dimension revised NEO Personality Inventory, Beck´s scales of anxiety and depression, and the Social Re-adjustment Rating Scale (SRRS). Visual BR anechogenicity was found in 11 subjects, BR hypoechogenicity in 29 subjects, and normal BR echogenicity in 60 subjects. The visual assessment correlated with the digital assessment. Comparing the groups with visual BR anechogenicity and BR normoechogenicity, only increased SRRS score and increased agreeableness z-score were significant. Our hypothesis that BR hypoechogenicity reflects an inclination for depression and anxiety characterized by the personality dimension neuroticism was not supported. However, this disposition may be present in a different state, such as stress.

A Comparative Study of Tower of London Scoring Systems and Normative Data.

OBJECTIVE: Tower of London (ToL) is a planning ability task that includes multiple versions. The original ToL was developed by Shallice together with two scoring systems (ToL-SS). Another two ToL-SS were proposed by Anderson et al. and Krikorian et al. The purpose of this study is to provide normative data for four ToL-SS and explore the effects of demographic variables on ToL performance. Furthermore, we aimed to determine the discriminative validity of these ToL-SS in clinical samples. METHOD: Four groups were included in the study: a normative sample of healthy adults (HC; n = 298); patients with Parkinson's disease with mild cognitive impairment (PD-MCI; n = 52) and without cognitive impairment (PD-ND; n = 57); and patients with schizophrenia (SCH; n = 28). The effects of demographic variables on ToL-SS were examined in the HC group. Between-groups comparisons of ToL-SS were conducted using regression analysis with dummy codes. RESULTS: All four ToL-SS were not significantly affected by age, whereas the effect of gender and education is not consistent. ToL-SS significantly (p < .05) differentiate HC from PD-MCI and SCH. Cohen's effect size coefficients d range from 0.68 to 1.29. Internal consistency coefficients (Cronbach's α) of ToL-SS range from 0.33 to 0.60. CONCLUSIONS: Despite poor to questionable internal consistency of ToL-SS, the discriminative validity and clinical utility for assessing planning deficits in PD-MCI and SCH are high. This study provides normative standards for all four ToL-SS on an adult population for use in clinical practice.

A Case Report of Clonazepam Dependence: Utilization of Therapeutic Drug Monitoring During Withdrawal Period.

Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence.

Fast simultaneous LC/MS/MS determination of 10 active compounds in human serum for therapeutic drug monitoring in psychiatric medication.

A UPLC/MS/MS method with simple protein precipitation has been validated for the fast simultaneous analysis of agomelatine, asenapine, amisulpride, iloperidone, zotepine, melperone, ziprasidone, vilazodone, aripiprazole and its metabolite dehydro-aripiprazole in human serum. Alprenolol was applied as an internal standard. A BEH C18 (2.1 × 50 mm, 1.7 µm) column provided chromatographic separation of analytes using a binary mobile phase gradient (A, 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B, 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Mass spectrometric detection was performed in the positive electrospray ionization mode and ion suppression owing to matrix effects was evaluated. The validation criteria were determined: linearity, precision, accuracy, recovery, limit of detection, limit of quantification, reproducibility and matrix effect. The concentration range was as follows: 0.25-1000 ng/mL for agomelatine; 0.25-100 ng/mL for asenapine and iloperidone; 2.5-1000 ng/mL for amisulpride, aripiprazole, vilazodone and zotepine; 2.3-924.6 ng/mL for dehydroaripiprazole; 2.2-878.4 ng/mL for melperone; and 2.2-883.5 ng/mL for ziprasidone. Limits of quantitation below a therapeutic reference range were achieved for all analytes. Intra-run precision of 0.4-5.5 %, inter-run precision of 0.6-8.2% and overall recovery of 87.9-114.1% were obtained. The validated method was successfully implemented into routine practice for therapeutic drug monitoring in our hospital.

Transcranial sonography of brainstem structures in panic disorder.

Panic disorder has been associated with altered serotonin metabolism in the brainstem raphe. The aim of study was to evaluate the BR echogenicity on transcranial sonography (TCS) in panic disorder. A total of 96 healthy volunteers were enrolled in the "derivation" cohort, and 26 healthy volunteers and 26 panic disorder patients were enrolled in the "validation" cohort. TCS echogenicity of brainstem raphe and substantia nigra was assessed on anonymized images visually and by means of digitized image analysis. Significantly reduced brainstem raphe echogenicity was detected more frequently in panic disorder patients than in controls using both visual (68% vs. 31%) and digitized image analysis (52% vs. 12%). The optimal cut-off value of digitized brainstem raphe echogenicity indicated the diagnosis of panic disorder with a sensitivity of 64% and a specificity of 73%, and corresponded to the 30th percentile in the derivation cohort. Reduced brainstem raphe echogenicity was associated with shorter treatment duration, and, by trend, lower severity of anxiety. No relationship was found between echogenicity of brainstem raphe or substantia nigra and age, gender, severity of panic disorder, or severity of depression. Patients with panic disorder exhibit changes of brainstem raphe on TCS suggesting an alteration of the central serotonergic system.

Comparison of heart rate variability in patients with panic disorder during cognitive behavioral therapy program.

BACKGROUND: Many authors suggest that there is low reactivity of autonomic nervous system and reduced heart rate variability in patients with panic disorder. The patients are therefore exposed to increased cardiac mortality. Power spectral analysis is a successful tool in detecting autonomic instabilities in many disorders. SUBJECTS AND METHODS: The aim of our study is to monitor the activity of the autonomic nervous system through heart rate variability measured in the beginning and end of a therapeutic cognitive behavioral therapy (CBT) program in patients with panic disorder. We measured 31 patients with panic disorder in the beginning (1st measurement) and end of a therapeutic CBT program (2nd measurement). The autonomic nervous system (ANS) has been evaluated in three positions (supine - standing - supine). The evaluated parameters of the HRV linear analysis were: RR interval, HF, LF, VLF band and VLF + LF / HF ratio. RESULTS: Spectral activity in the very low frequency band was significantly higher in the 2nd measurement compared to the 1st measurement in the standing position. The ratio of the spectral activity at lower frequencies (VLF+LF) to high frequency (HF) was significantly lower in the supine position. CONCLUSION: This study demonstrated an improvement of neurocardiac control regulation after a therapeutic CBT program in patients suffering from panic disorder.

Liquid chromatography-tandem mass spectrometry method for determination of five antidepressants and four atypical antipsychotics and their main metabolites in human serum.

The rapid and simple ultra performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination parent drugs: sertraline, fluoxetine, citalopram, paroxetine, venlafaxine, clozapine, olanzapine, quetiapine, risperidone, and their active and nonactive metabolites N-desmethylsertraline, norfluoxetine, desmethylcitalopram, didemethylcitalopram, N-desmethylvenlafaxine, O-desmethylvenlafaxine, N-desmethylclozapine, N-desmethylolanzapine, 2-hydroxyolanzapine and 9-hydroxyrisperidone in human serum. Precipitation of serum proteins was performed with a precipitation reagent consisting of 0.05% solution of ZnSO(4)·7H(2)O in acetonitrile/methanol (40:60, v/v). Alprenolol was used as an internal standard. Chromatographic separation was carried out on a BEH C18 column using gradient elution mobile phase A (2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v) and B (2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v). Electrospray in positive mode was used for ionization. Detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring. Analysis time was 5 min. Drugs were separated into three groups with low, medium and high levels. Correlation coefficients of calibration curves were in the range 0.995-1.000. Coefficients of variation were 4.2-9.5% for intra-assay and 3.0-11.9% for inter-assay. Recoveries were 87.1-110% for intra-assay and 88.1-108.2% for inter-assay. The method was fully validated and can be successfully applied for routine analyses.

Genome-wide association studies in schizophrenia, and potential etiological and functional implications of their results.

BACKGROUND: Despite the fact that the genetic basis of schizophrenia has been intensively studied for more than two decades, our contemporary knowledge in this field is rather fractional, and a substantial part of it is still missing. The aim of this review article is to sum up the data coming from genome-wide association genetic studies in schizophrenia, and indicate prospective directions of further scientific endeavour. METHODS: We searched the National Human Genome Research Institute's Catalog of genome-wide association studies for schizophrenia to identify all papers related to this topic. In consequence, we looked up the possible relevancy of these findings for etiology and pathogenesis of schizophrenia using the computer gene and PubMed databases. RESULTS: Eighteen genome-wide association studies in schizophrenia have been published till now, referring to fifty-seven genes supposedly involved into schizophrenia's etiopathogenesis. Most of these genes are related to neurodevelopment, neuroendocrinology, and immunology. CONCLUSIONS: It is reasonable to predict that complex studies of sufficiently large samples, involving detection of copy number variants and assessment of endophenotypes, will produce definitive discoveries of genetic risk factors for schizophrenia in the future.

Heart rate variability spectral analysis in patients with panic disorder compared with healthy controls.

OBJECTIVES: The aim of our study is to measure very low frequency band (VLF), low frequency band (LF) and high frequency band (HF) components of R-R interval during orthostatic test in patients with panic disorder and a comparison with healthy controls. METHODS: We measured HRV in 31 patients with panic disorder and 20 healthy controls. Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI (MINI international neuropsychiatric interview). Autonomic nervous system (ANS) has been evaluated during orthostatic change in three positions. Intensity of symptoms was assessed using psychiatric scales. RESULTS: There were highly statistically significant differences between panic patients and control group in all components of power spectral analysis in 2nd and 3rd VLF components and in HF components of 2nd. We have found highly statistically significant negative correlations between level of dissociation measured by DES and some parameters of ANS. We found negative correlations between the age of the patient and activity of ANS, and negative correlations between activity of ANS and duration and onset of disorder and dosage of antidepressants. CONCLUSION: These findings demonstrate a lower parasympathetic activity and higher sympathetic/parasympathetic ratio in panic disorder patients measured during the changes of postural position in comparison with healthy controls. Autonomic dysregulation is associated with panic disorder and has the relation with the level of dissociation, the age of patiens and age of onset of disorder.

Genomic copy number variations: A breakthrough in our knowledge on schizophrenia etiology?

OBJECTIVES: The term "copy number variation/variant" (CNV) denotes a DNA sequence with a magnitude of 1 kb at least which is differently represented among individuals based on its deletion or duplication. Since 2008, multiple studies have reported copy number variations in schizophrenia, and they seem to fill in a gap in our knowledge on the genetic background of schizophrenia. The aim of this review is to sum up the current findings related to CNVs in schizophrenia in order to facilitate further research. METHODS: We searched the PubMed computer database using the key words "schizophrenia AND CNVs" on 26th October 2011. Out of 91 obtained results, we selected the references based on their relevance. RESULTS: The CNVs at genome loci 1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, 16p13.1 and 22q11.2 were associated with schizophrenia most frequently. The data provide evidence for low prevalent, but highly penetrant CNVs associated with schizophrenia. CNV deletions show higher penetrance than duplications. Larger CNVs often have higher penetrance than smaller CNVs. Although the vast majority of CNVs are inherited, CNVs that have newly occurred as de novo mutations have more readily been implicated in schizophrenia. De novo CNVs may be responsible for the presence of schizophrenia in only one of the two monozygotic twins, who otherwise have identical genomes. CONCLUSION: Identifying CNVs in schizophrenia can lead to changes in the treatment and genetic counselling. Our knowledge on the genetic background of neurodevelopmental disorders may also reduce stigma in schizophrenia.

Panic disorder, autonomic nervous system and dissociation - changes during therapy.

OBJECTIVES: Alarming somatic symptoms and in particular the cardiovascular symptoms, are the characteristic features of panic attacks. Increased cardiac mortality and morbidity have been proposed in these patients. Power spectral analysis of electrocardiogram R-R intervals is known to be a particularly successful tool in the detection of autonomic instabilities in various clinical disorders. Heart rate variability (HRV) has been found to be the outcome of rapidly reacting cardiovascular control systems. The aim of our study is to measure very low frequency band (VLF), low frequency band (LF) and high frequency band (HF) components of R-R interval during orthostatic experiment in patients with panic disorder before and after treatment and compares it with healthy controls. METHODS: We assessed heart rate variability in 19 patients with panic disorder before and after 6-weeks treatment with antidepressants combined with cognitive behavioral therapy (CBT) and in 18 healthy controls. Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI (MINI international neuropsychiatric interview). Patients were treated with CBT and psychotropics. They were regularly every week assessed using CGI (Clinical Global Impression), BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory). Heart rate variability was assessed during 3 positions (1st - 5 min supine; 2nd - 5 min standing; 3rd - 5 min supine) before and after the treatment. Power spectra were computed for very low frequency - VLF (0.0033-0.04 Hz), low-frequency - LF (0.04-0.15 Hz) and high frequency - HF (0.15-0.40 Hz) bands using fast Fourier transformation. RESULTS: Nineteen panic disorder patients resistant to pharmacological treatment entered a 6-week open-label treatment study with combination of SSRI and CBT. The combination of CBT and pharmacotherapy proved to be an effective treatment in these patients. The patients significantly improved during the study period in all rating scales. There were highly statistical significant differences between panic patients and control group in all components of power spectral analysis in 2nd (VLF, LF and H in standing) and in two component of 3rd (LF and HF in supine) positions. There was also a statistically significant difference between these two groups in LF/HF ratio in standing position (2nd). During therapy there was a tendency increasing values in all three positions in components of HRV power spectra, but HF in 1st supine position was the only component where the increase reached the level os statistical significance. CONCLUSIONS: These findings demonstrate a lower autonomic activity in panic disorder patients measured during the changes of postural position in comparison with healthy controls and tendency to increase this autonomic power during the treatment.