- Email: [email protected]
P.4.a.001 Efficacy and tolerability of escitalopram as monotherapy or in combination with mirtazapine in generalized anxiety disorder (GAD)
P.4.a. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (basic) burden as well as the challenges associated with translating scales, and training raters. The scientific questions related to simplifying the PANSS are complex. Empirical data regarding sensitivity of items to detecting drug placebo differences, clinical trial requirements, rater skill levels, and theoretical concerns should be considered in selecting a subset of items for optimizing trial performance. To begin the process of optimizing signal detection, we explored several metrics using blinded data from two randomized controlled trials studies that utilized the PANSS to evaluate putative treatments for schizophrenia. Methods: We reviewed the Bracket clinical trial database and selected the two most recent schizophrenia trials for which baseline data was available. Scores for each of the PANSS items was classified as ‘Below clinical significance’ or ‘Clinically significant’. ‘Below clinical significance’ was operationally defined as item severity ratings of ‘1’ (Absent) or ‘2’ (Minimal − Questionable pathology; may be at the upper extreme of normal limits). ‘Clinically significant’ was operationally defined as the item severity ratings of 3 (mild) or higher. The frequency of scores ‘Below clinical significance’ was computed for each study. For each study, a descriptive analysis was conducted to determine the frequency that PANSS items were rated ‘Below clinical significance’ at baseline. Results: Two multicentre acute schizophrenia trials were identified. Study 1 included 463 subjects and was conducted at 71 sites in 12 countries. Study 2 included 815 subjects and was conducted at 110 sites in 16 countries. Table 1. Overall PANSS scores
Study 1 Study 2
N
Total, Mean (SD)
P Scale, Mean (SD)
N Scale, Mean (SD)
G Scale, Mean (SD)
463 815
97.5 (10.2) 95.1 (12.8)
25.5 (3.8) 25.3 (4.4)
24.9 (4.6) 23.3 (5.1)
47.2 (6.1) 46.5 (7.2)
In both studies, the ten items most frequently rated ‘Below clinical significance’ were: G14 Poor Impulse control, P7 Hostility, G5 Mannerisms and Posturing, G8 Uncooperativeness, G10 Disorientation, G6 Depression, G7 Motor Retardation, P5 Grandiosity, G1 Somatic Concern, and G3 Guilt Feelings. Conclusions: Items frequently rated absent at baseline may be a source of noise in RCTs. We identified 10 PANSS items that were often absent at baseline in two studies. An abbreviated PANSS might eliminate such items without loss of sensitivity. Further studies are required to determine the impact of a shorter simpler PANSS. References [1] Kay, S.R., L.A. Opler, and J.P. Lindenmayer, The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiatry Suppl, 1989(7): p. 59−67. Disclosure statement: Dr Sachs and co-authors are fulltime Bracket employees.
S507
P.4.a. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (basic) P.4.a.001 Efficacy and tolerability of escitalopram as monotherapy or in combination with mirtazapine in generalized anxiety disorder (GAD) G. Sulejmanpasic-Arslanagic1 ° , S. Fisekovic1 , S. Ler1 , A. Frenjo1 of Sarajevo Clinical Center, Psychiatric clinic, Sarajevo, Bosnia and Herzegovina
1 University
Purpose of the study: Generalized anxiety disorder (GAD) is a common anxiety disorder that involves chronic worrying, nervousness, and tension [1]. The symptoms of GAD are excessive and endure for most of the day nearly every day for a minimum of 6 months. Antidepressants have secured a primary role in the pharmacopoeia of GAD.Escitalopram is the S-enantiomer of the selective serotonin reuptake inhibitor (SSRI) citalopram and it is the most selective SSRI, with almost no significant affinity to other tested receptors. It is an effective first-line option in the management of patients with major depression, including severe forms, and various anxiety disorders [2]. Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA)and it’s primary use is the treatment of major depressive disorder and other mood disorders [3]. Its unique mechanism of action may account for its success in augmentation. Combining mirtazapine with a SSRI has been shown to be superior to antidepressants alone in generalized anxiety disorder (GAD). Whenever antidepressants are combined, the clinician should titrate the second antidepressant carefully and monitor for drug interactions, especially if one of the drugs is an SSRI. The purpose of present study was to asses efficacy and tolerability of escitalopram as monotherapy or in combination with mirtazapine in GAD. Materials and Methods: Single centre, nonrandomized, openlabel, parallel groups, in 30 inpatients diagnosed as GAD according to DSM IV Classification, received escitalopram as monotherapy (10−20 mg each morning) or combination of escitalopram (10 mg each morning) and mirtazapine (15−30 mg at bed time). Subjects were divided into two groups − escitalopram group (13) and escitalopram/mirtazapine group (17). Subjects had a physical exam and laboratory blood check before medication was started. The primary outcome measure was the change from baseline in total score on the Hamilton Rating Scale for Anxiety (HAM-A). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. To quantify the severity of anxiety symptomatology and psychotropic drug evaluation it was used initially and in every two weeks, then after four weeks throughout the investigational period and at the end of hospitalization. Results: The subject distribution was in favor in escitalopram/ mirtazapine group who represented 57% of the sample while remaining 43% of the subjects were in escitalopram group. A significant improvement in GAD symptoms was found in all two groups after treatment period, but patients co-treated with mirtazapine showed higher response rates at earlier evaluations. The mean reduction of total HAM-A score was 39.5% in escitalopram group and 41.1% in escitalopram/mirtazapine group. The results obtained on the Clinical Global Impression Scale indicate that the mean decline in 6 subjects was 36.7% (escitalopram group) and in 9 subjects 39.4% (escitalopram/mirtazapine
S508
P.4.a. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (basic)
group). The results indicate a statistically significant reduction of acute symptoms, resolving persistent and chronic anxiety, and prevention of relapse following treatment period with escitalopram as monotherapy or in combination with mirtazapine. Conclusion: Escitalopram as monotherapy or combined with mirtazapine is effective and safe in treatment of GAD, however, mirtazapine co-therapy might produce a more rapid response, and potentates action of antidepressants. Results do not suggest that addition of mirtazapine affects overall efficacy and safety of escitalopram. References [1] Connor KM., Davidson JRT., 1998. Generalized anxiety disorder:neurobiological and pharmacotherapeutic perspectives. Biol. Psychiatry 44, 1286–1294. [2] Davidson J., Bose A., Su G., 2002. Escitalopram in the treatment of generalized anxiety disorder.Int J. Neuropsychopharmacol. 5 (Suppl 1). [3] Gambi F., De Berardis D., Campanella D., et al., 2005. Mirtazapine treatment of generalized anxiety disorder: a fixed dose, open label study. J Psychopharmacol. 19(5): 483−7.
P.4.a.002 Heart rate variability in drug naive panic disorder patients compared with healthy controls S. Pirildar1 ° , G. Sart1 , M. Kayikcioglu2 , T. Kose3 1 Ege University, Psychiatry, Izmir, Turkey; 2 Ege University, Cardiology, Izmir, Turkey; 3 Ege University, Biostatics and medical informatics, Izmir, Turkey Purpose: Patients with panic disorder experience recurrent panic attacks which are characterized by episodes of intense anxiety accompanied of by a range of alarming somatic symptoms. These symptoms are suggestive of autonomic nervous system dysfunction. Growing evidence suggests that alterations in autonomic function contribute to the pathophysiology of panic disorder(1). A number of recent research have sought to demonstrate the autonomic underpinnings of panic disorder using the analysis of heart rate variability (HRV), a noninvasive, sensitive and dynamic indicator of autonomic regulation of the heart. Recently, measurements of HRV have also been increasingly applied to investigate autonomic regulation in affective disorders, and aberrant HRV patterns have been observed in various conditions including anxiety and major depression(2). The aim of the study is to evaluate 24 hour heart rate variability (HRV) in drug free panic disorder patients and compare the results with healthy controls. Method: Thirty two patients (20 female and 12 male) aged between 18−65 years and having a diagnosis of panic disorder on the basis of DSM-IV criteria and 24 healthy controls (17 female 7 male) were included in the study. Patients were assessed using Hamilton depression scale, Hamilton anxiety scale, panic disorder severity scale and anxiety sensitivity index. Heart rate variability was assessed by analyzing of 24 hour Holter ECG outcome. Time-related and frequency dependent parameters and sleepawakeness analysis were also performed. Statistics: The data was analyzed using SPSS for Windows 16.0 software. The differences in numerical variables between groups were analyzed by the t-test and Mann–Whitney U test. Differences in categorical variables were analyzed by chi-square analysis. A p value less than 0.05 was considered as statistically significant. Results: Heart rate values determined by 24 hours Holter ECG were not different in terms of time and frequency dependent parameters between patients and healthy controls. Total
power analysis (msn2) 3714.83±1897.03 in panic patients and 3501.12±1675.35 in controls p = 0.663; SDNN (msn) 148.43±38 in patients and 150.00±28.29 in controls were determined. RMSSD, pNN50, LF and HF values which demonstrate parasympatic activity were decreased in panic patients but the difference did not reach a statistically significant level. Although LF value which indicates sympathic activity and LF/HF value indicating sempatovagal activity were increased in panic disorder patients but not significantly. It is determined by the sleep-awakeness analysis that night time values demonstrating parasymphatic activity and day time values demonstrating symphatic activity were increased in panic patients but not significantly. Conclusion: Although studies indicate alterations in heart rate variability in panic disorder patients we didn’t determine any difference in heart rate variability parameters in drug free panic disorder patients and healthy controls. This study is important to evaluate implications for the cardiovascular risk in panic disorder and further research is needed. References [1] Diveky T, Prasko J, Latalova K, etal. 2012. Heart rate variability spectral analysis in patients with panic disorder compared with healthy controls. Neuro Endocrinol Lett. 2012; 33(2): 156−66. [2] McCraty R, Atkinson M, Tomasino D (2001) Analysis of twenty-four hour heart rate variability in patients with panic disorder. Biological Psychology (56).131–150.
P.4.a.003 Negative and biased facial emotion recognition of social anxiety disorder patients K.S. Oh1 ° , S.J. Cho2 , J.K. SaKong3 , E.J. Kim1 , S.W. Lim1 Samsung Hospital, Sungkyunkwan University, Seoul, South-Korea; 2 Gachon University, Gil Medical Center, Incheon, South-Korea; 3 )Dongguk University, School of Medicine, Gyeong-ju, South-Korea
1 Kangbuk
Purposes: Social anxiety disorder patients used to show some deficits in the ability of social cognition. Recognizing facial affect is an important component of our nonverbal communication system and an essential skill for successful adaptation and manipulation of the environment. However, some psychiatric disorders patients, such as anxiety disorder, depressive disorder, schizophrenia, show impairments in their ability to recognize facial emotions. Until recently, the emotion recognition ability is thought to be strictly involved also in different psychopathological disorders. It has been proposed that social anxiety disorder (SAD), among in the case of anxiety disorders, is characterized by biased processing of negative facial expressions. Our hupothesis is that social anxiety disorder patients will show deficits in facial recognition ability. The present study examined facial emotional recognition abilities of SAD patients, compared to those without an anxiety disorders, using a computerized facial labeling test. Methods: The SAD patients (n = 65) and healthy controls (n = 45) was included in this study. The recognition of facial expression was evaluated through a computerized facial labeling test composed of 42 faces of six kind of human emotions (Sadness, Anger, Disgust, Happy, Surprise and Fear) and 13 neutral faces with Ekman’s Pictures of Facial Affect. Participants had to identify the emotions portrayed by each face. The type of emotions selected from each 55 face respectively were evaluated
Study 1 Study 2
N
Total, Mean (SD)
P Scale, Mean (SD)
N Scale, Mean (SD)
G Scale, Mean (SD)
463 815
97.5 (10.2) 95.1 (12.8)
25.5 (3.8) 25.3 (4.4)
24.9 (4.6) 23.3 (5.1)
47.2 (6.1) 46.5 (7.2)
In both studies, the ten items most frequently rated ‘Below clinical significance’ were: G14 Poor Impulse control, P7 Hostility, G5 Mannerisms and Posturing, G8 Uncooperativeness, G10 Disorientation, G6 Depression, G7 Motor Retardation, P5 Grandiosity, G1 Somatic Concern, and G3 Guilt Feelings. Conclusions: Items frequently rated absent at baseline may be a source of noise in RCTs. We identified 10 PANSS items that were often absent at baseline in two studies. An abbreviated PANSS might eliminate such items without loss of sensitivity. Further studies are required to determine the impact of a shorter simpler PANSS. References [1] Kay, S.R., L.A. Opler, and J.P. Lindenmayer, The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiatry Suppl, 1989(7): p. 59−67. Disclosure statement: Dr Sachs and co-authors are fulltime Bracket employees.
S507
P.4.a. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (basic) P.4.a.001 Efficacy and tolerability of escitalopram as monotherapy or in combination with mirtazapine in generalized anxiety disorder (GAD) G. Sulejmanpasic-Arslanagic1 ° , S. Fisekovic1 , S. Ler1 , A. Frenjo1 of Sarajevo Clinical Center, Psychiatric clinic, Sarajevo, Bosnia and Herzegovina
1 University
Purpose of the study: Generalized anxiety disorder (GAD) is a common anxiety disorder that involves chronic worrying, nervousness, and tension [1]. The symptoms of GAD are excessive and endure for most of the day nearly every day for a minimum of 6 months. Antidepressants have secured a primary role in the pharmacopoeia of GAD.Escitalopram is the S-enantiomer of the selective serotonin reuptake inhibitor (SSRI) citalopram and it is the most selective SSRI, with almost no significant affinity to other tested receptors. It is an effective first-line option in the management of patients with major depression, including severe forms, and various anxiety disorders [2]. Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA)and it’s primary use is the treatment of major depressive disorder and other mood disorders [3]. Its unique mechanism of action may account for its success in augmentation. Combining mirtazapine with a SSRI has been shown to be superior to antidepressants alone in generalized anxiety disorder (GAD). Whenever antidepressants are combined, the clinician should titrate the second antidepressant carefully and monitor for drug interactions, especially if one of the drugs is an SSRI. The purpose of present study was to asses efficacy and tolerability of escitalopram as monotherapy or in combination with mirtazapine in GAD. Materials and Methods: Single centre, nonrandomized, openlabel, parallel groups, in 30 inpatients diagnosed as GAD according to DSM IV Classification, received escitalopram as monotherapy (10−20 mg each morning) or combination of escitalopram (10 mg each morning) and mirtazapine (15−30 mg at bed time). Subjects were divided into two groups − escitalopram group (13) and escitalopram/mirtazapine group (17). Subjects had a physical exam and laboratory blood check before medication was started. The primary outcome measure was the change from baseline in total score on the Hamilton Rating Scale for Anxiety (HAM-A). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. To quantify the severity of anxiety symptomatology and psychotropic drug evaluation it was used initially and in every two weeks, then after four weeks throughout the investigational period and at the end of hospitalization. Results: The subject distribution was in favor in escitalopram/ mirtazapine group who represented 57% of the sample while remaining 43% of the subjects were in escitalopram group. A significant improvement in GAD symptoms was found in all two groups after treatment period, but patients co-treated with mirtazapine showed higher response rates at earlier evaluations. The mean reduction of total HAM-A score was 39.5% in escitalopram group and 41.1% in escitalopram/mirtazapine group. The results obtained on the Clinical Global Impression Scale indicate that the mean decline in 6 subjects was 36.7% (escitalopram group) and in 9 subjects 39.4% (escitalopram/mirtazapine
S508
P.4.a. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (basic)
group). The results indicate a statistically significant reduction of acute symptoms, resolving persistent and chronic anxiety, and prevention of relapse following treatment period with escitalopram as monotherapy or in combination with mirtazapine. Conclusion: Escitalopram as monotherapy or combined with mirtazapine is effective and safe in treatment of GAD, however, mirtazapine co-therapy might produce a more rapid response, and potentates action of antidepressants. Results do not suggest that addition of mirtazapine affects overall efficacy and safety of escitalopram. References [1] Connor KM., Davidson JRT., 1998. Generalized anxiety disorder:neurobiological and pharmacotherapeutic perspectives. Biol. Psychiatry 44, 1286–1294. [2] Davidson J., Bose A., Su G., 2002. Escitalopram in the treatment of generalized anxiety disorder.Int J. Neuropsychopharmacol. 5 (Suppl 1). [3] Gambi F., De Berardis D., Campanella D., et al., 2005. Mirtazapine treatment of generalized anxiety disorder: a fixed dose, open label study. J Psychopharmacol. 19(5): 483−7.
P.4.a.002 Heart rate variability in drug naive panic disorder patients compared with healthy controls S. Pirildar1 ° , G. Sart1 , M. Kayikcioglu2 , T. Kose3 1 Ege University, Psychiatry, Izmir, Turkey; 2 Ege University, Cardiology, Izmir, Turkey; 3 Ege University, Biostatics and medical informatics, Izmir, Turkey Purpose: Patients with panic disorder experience recurrent panic attacks which are characterized by episodes of intense anxiety accompanied of by a range of alarming somatic symptoms. These symptoms are suggestive of autonomic nervous system dysfunction. Growing evidence suggests that alterations in autonomic function contribute to the pathophysiology of panic disorder(1). A number of recent research have sought to demonstrate the autonomic underpinnings of panic disorder using the analysis of heart rate variability (HRV), a noninvasive, sensitive and dynamic indicator of autonomic regulation of the heart. Recently, measurements of HRV have also been increasingly applied to investigate autonomic regulation in affective disorders, and aberrant HRV patterns have been observed in various conditions including anxiety and major depression(2). The aim of the study is to evaluate 24 hour heart rate variability (HRV) in drug free panic disorder patients and compare the results with healthy controls. Method: Thirty two patients (20 female and 12 male) aged between 18−65 years and having a diagnosis of panic disorder on the basis of DSM-IV criteria and 24 healthy controls (17 female 7 male) were included in the study. Patients were assessed using Hamilton depression scale, Hamilton anxiety scale, panic disorder severity scale and anxiety sensitivity index. Heart rate variability was assessed by analyzing of 24 hour Holter ECG outcome. Time-related and frequency dependent parameters and sleepawakeness analysis were also performed. Statistics: The data was analyzed using SPSS for Windows 16.0 software. The differences in numerical variables between groups were analyzed by the t-test and Mann–Whitney U test. Differences in categorical variables were analyzed by chi-square analysis. A p value less than 0.05 was considered as statistically significant. Results: Heart rate values determined by 24 hours Holter ECG were not different in terms of time and frequency dependent parameters between patients and healthy controls. Total
power analysis (msn2) 3714.83±1897.03 in panic patients and 3501.12±1675.35 in controls p = 0.663; SDNN (msn) 148.43±38 in patients and 150.00±28.29 in controls were determined. RMSSD, pNN50, LF and HF values which demonstrate parasympatic activity were decreased in panic patients but the difference did not reach a statistically significant level. Although LF value which indicates sympathic activity and LF/HF value indicating sempatovagal activity were increased in panic disorder patients but not significantly. It is determined by the sleep-awakeness analysis that night time values demonstrating parasymphatic activity and day time values demonstrating symphatic activity were increased in panic patients but not significantly. Conclusion: Although studies indicate alterations in heart rate variability in panic disorder patients we didn’t determine any difference in heart rate variability parameters in drug free panic disorder patients and healthy controls. This study is important to evaluate implications for the cardiovascular risk in panic disorder and further research is needed. References [1] Diveky T, Prasko J, Latalova K, etal. 2012. Heart rate variability spectral analysis in patients with panic disorder compared with healthy controls. Neuro Endocrinol Lett. 2012; 33(2): 156−66. [2] McCraty R, Atkinson M, Tomasino D (2001) Analysis of twenty-four hour heart rate variability in patients with panic disorder. Biological Psychology (56).131–150.
P.4.a.003 Negative and biased facial emotion recognition of social anxiety disorder patients K.S. Oh1 ° , S.J. Cho2 , J.K. SaKong3 , E.J. Kim1 , S.W. Lim1 Samsung Hospital, Sungkyunkwan University, Seoul, South-Korea; 2 Gachon University, Gil Medical Center, Incheon, South-Korea; 3 )Dongguk University, School of Medicine, Gyeong-ju, South-Korea
1 Kangbuk
Purposes: Social anxiety disorder patients used to show some deficits in the ability of social cognition. Recognizing facial affect is an important component of our nonverbal communication system and an essential skill for successful adaptation and manipulation of the environment. However, some psychiatric disorders patients, such as anxiety disorder, depressive disorder, schizophrenia, show impairments in their ability to recognize facial emotions. Until recently, the emotion recognition ability is thought to be strictly involved also in different psychopathological disorders. It has been proposed that social anxiety disorder (SAD), among in the case of anxiety disorders, is characterized by biased processing of negative facial expressions. Our hupothesis is that social anxiety disorder patients will show deficits in facial recognition ability. The present study examined facial emotional recognition abilities of SAD patients, compared to those without an anxiety disorders, using a computerized facial labeling test. Methods: The SAD patients (n = 65) and healthy controls (n = 45) was included in this study. The recognition of facial expression was evaluated through a computerized facial labeling test composed of 42 faces of six kind of human emotions (Sadness, Anger, Disgust, Happy, Surprise and Fear) and 13 neutral faces with Ekman’s Pictures of Facial Affect. Participants had to identify the emotions portrayed by each face. The type of emotions selected from each 55 face respectively were evaluated