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P.4.a.005 An investigation of clinical factors influence the therapeutic response of paroxetine in patients with panic disorder
S480
P.4.a Anxiety disorders and anxiolytics – Anxiety disorders (clinical)
the Hamilton anxiety scale (HAM-A) and of 1 on the Clinical Global Impression – Severity (CGI-S). In addition, comorbidity with depression was assessed with the Hospital Anxiety and Depression Scale and the functional consequences of the disorder by the Sheehan Disability Scale (SDS). Results: The study population consisted of 618 patients diagnosed with generalized anxiety disorder, 365 (59.1%) seen in primary care and 253 (40.9%) in psychiatric care. The treatment consisted mainly of medication (96%) with combined psychotherapy (67.9%), or psychotherapy alone (3.4%). Antidepressants were taken by 87.1% of the patients and anxiolytics by 58.1%. Mean treatment duration was 5.4 months. Based on the CGI-S (CGI-S=1) and the HAM-A (HAM-A 7) scales, 23 patients were considered as in remission, yielding a prevalence of 3.7% (95% CI: 2.2 – 5.2%) in the entire population. The proportion of patients in remission on the HAM-A (HAM-A 7) only, was 13.3% (95% CI: 10.6 – 16.1%). No difference was found between the care settings. The prevalence of HAM-A remission was lower when comorbid symptoms were present (9.3% vs 43.1%, p < 0.0001), more specifically in association with depressive mood (9.3% vs 21.7%, p < 0.0001), other anxiety disorders (7.5% vs 19.9%, p < 0.0001) and substance abuse (4.7% vs 15.6%, p = 0.0013). Remission also depended on the initial severity of the episode (p < 0.0001) the number of previous anxiety episodes (p < 0.0001) and treatment duration (p = 0.0007). The remission rate was lower in patients taking tranquillizers (8.5% vs 20.1%, p < 0.0001) but higher in patients taking antidepressants (14.7% vs 4.0%, p = 0.011) Functional impairment was important in non-remitters, with a SDS total score of 17.2±7.0 (range: 0 – 30) and was highly correlated with the HAM-A scores (r = 0.59, p < 0.0001). Remitters showed lower SDS scores than non-remitters on the 3 functioning scales (p < 0.0001). Less patients in remission experienced loss in working days than non-remitters (31.8% vs 56.8%, p = 0.020) Conclusions: Remission rates in patients treated for generalized anxiety disorder is extremely low and highly influenced by the presence of co-morbid symptomatology of depressive or other anxiety disorders. Remitters showed better overall functioning than non-remitters. References [1] Doyle AC, Pollack MH, 2003. Establishment of remission criteria for anxiety disorder. J. Clin. Psychiatry, 64 (suppl 15), 40−45 [2] Kjernisted KD, Bleau P, 2004. Long-term goals in the management of acute and chronic anxiety disorders. Can. J. Psychiatry, 49 (suppl 1), 51S-63S.
P.4.a.005 An investigation of clinical factors influence the therapeutic response of paroxetine in patients with panic disorder T. Ayugase1 ° , S. Ishiguro1 , T. Watanabe1 , M. Ueda1 , Y. Saeki1 , G. Hirokane2 , S. Morita2 , N. Yamada2 , K. Akiyama3 , K. Shimoda1 . 1 Dokkyo Medical University School of Medicine, Psychiatry, Tochigi, Japan; 2 Shiga University of Medical Science, Psychiatry, Otsu, Japan; 3 Dokkyo Medical University School of Medicine, Department of Biological Psychiatry and Neuroscience, Tchigi, Japan Selective serotonin reuptake inhibitors (SSRIs) are thought to interact with serotonergic system and be effective for treatment
of panic disorder (PD). This suggests a potential role of serotonergic system in panic disorder. And hyperthyroidism and hypothyroidism are commonly associated with psychiatric symptoms including anxiety and panic attack. In the present study, we investigated into associations between therapeutic response to paroxetine (PAX) in 2 weeks after the initiation of the treatment and plasma concentrations of PAX, 5-HTTLPR genotype, pretreatment thyroid function (FT3, FT4, TSH), and other clinical factors in patients with PD in a Japanese population. Subjects were 28 Japanese patients who fulfilled DSM-IV-TR criteria for a diagnosis of RD (male = 10, female = 18, mean age±SD = 34.0±7.4). Subjects were received 10 mg/day of PAX for 2 weeks as initial treatment. Severity of PD was assessed with the Panic and Agoraphobia Scale (PAS). We analyzed PAX plasma concentrations of subjects with HPLC and 5-HTTLPR variants were determined with polymerase chain reaction (PCR) techniques. A multiple regression analysis showed that PAS score at the baseline, plasma concentration of PAX, 5-HTTLPR genotype, TSH were significant factors indicating that these factors accounted for 83.2% (R2 = 0.832) of the variability of the clinical response to PAX (reduction of PAS score; PAS score at the baseline – PAS score at 2 weeks). The final model was described by the following equation (p < 0.05): Reduction of PAS score = −2.763 + 0.893×(PAS score at the baseline) − 0.529×(plasma concentration of PAX) − 9.383×(L/S = 1, S/S = 0) + 1.936×(TSH). At initial stage of pharmacotherapy with SSRIs, the desensitization of 5-HT1A autoreceptors contributes the clinical effect. The increase of serotonin in the somatodendritic area of cell bodies of serotonin neurons, before the down-regulation of 5-HT1A autoreceptors, might lead to lower the function of serotonin neurons and deteriorate symptom of panic disorder or impede the clinical effect, which might be caused by high plasma concentrations of PAX at the beginning of the pharmacotherapy with PAX for PD. In addition, the result of this study suggested that 5-HTTLPR S/S genotypes might have lower sensitivity to pharmacological effects of SSRIs than L allele carriers, because of the more reductions in the density of 5-HTT and 5-HT1A receptors, via latent higher concentration of serotonin in the synaptic cleft. L allele carriers were thought to be apt to lower the function of serotonin neurons with SSRIs at initial stage of the treatment. And low TSH level within normal limits was supposed to be a factor of low-response to SSRIs in PD. Furthermore, one subjects who was diagnosed as subclinical hypothyroidism (TSH: 5.80mU/ml) and excluded from the analysis showed low-response (the change of PAS score was 11 to 12). From the results of the present study, it was concluded that high plasma concentration of PAX, 5-HTTLPR L allele carrier, low TSH level within normal limits, and comorbidity of subclinical hypothyroidism might be associated with low-response to initial treatment with PAX of PD.
P.4.a.006 Evaluation of the prevalence of anxiety disorders with comorbidity of depression among geriatric psychiatry outpatients F. Beskardes1 ° , T. Ertan1 . 1 Istanbul University Cerrahpasa Medical Faculty, Psychiatry, Istanbul, Turkey The prevalence of anxiety disorders in elderly adults is a topic that has received scant attention, especially given the impressive amount of research on anxiety disorders over the past several
P.4.a Anxiety disorders and anxiolytics – Anxiety disorders (clinical)
the Hamilton anxiety scale (HAM-A) and of 1 on the Clinical Global Impression – Severity (CGI-S). In addition, comorbidity with depression was assessed with the Hospital Anxiety and Depression Scale and the functional consequences of the disorder by the Sheehan Disability Scale (SDS). Results: The study population consisted of 618 patients diagnosed with generalized anxiety disorder, 365 (59.1%) seen in primary care and 253 (40.9%) in psychiatric care. The treatment consisted mainly of medication (96%) with combined psychotherapy (67.9%), or psychotherapy alone (3.4%). Antidepressants were taken by 87.1% of the patients and anxiolytics by 58.1%. Mean treatment duration was 5.4 months. Based on the CGI-S (CGI-S=1) and the HAM-A (HAM-A 7) scales, 23 patients were considered as in remission, yielding a prevalence of 3.7% (95% CI: 2.2 – 5.2%) in the entire population. The proportion of patients in remission on the HAM-A (HAM-A 7) only, was 13.3% (95% CI: 10.6 – 16.1%). No difference was found between the care settings. The prevalence of HAM-A remission was lower when comorbid symptoms were present (9.3% vs 43.1%, p < 0.0001), more specifically in association with depressive mood (9.3% vs 21.7%, p < 0.0001), other anxiety disorders (7.5% vs 19.9%, p < 0.0001) and substance abuse (4.7% vs 15.6%, p = 0.0013). Remission also depended on the initial severity of the episode (p < 0.0001) the number of previous anxiety episodes (p < 0.0001) and treatment duration (p = 0.0007). The remission rate was lower in patients taking tranquillizers (8.5% vs 20.1%, p < 0.0001) but higher in patients taking antidepressants (14.7% vs 4.0%, p = 0.011) Functional impairment was important in non-remitters, with a SDS total score of 17.2±7.0 (range: 0 – 30) and was highly correlated with the HAM-A scores (r = 0.59, p < 0.0001). Remitters showed lower SDS scores than non-remitters on the 3 functioning scales (p < 0.0001). Less patients in remission experienced loss in working days than non-remitters (31.8% vs 56.8%, p = 0.020) Conclusions: Remission rates in patients treated for generalized anxiety disorder is extremely low and highly influenced by the presence of co-morbid symptomatology of depressive or other anxiety disorders. Remitters showed better overall functioning than non-remitters. References [1] Doyle AC, Pollack MH, 2003. Establishment of remission criteria for anxiety disorder. J. Clin. Psychiatry, 64 (suppl 15), 40−45 [2] Kjernisted KD, Bleau P, 2004. Long-term goals in the management of acute and chronic anxiety disorders. Can. J. Psychiatry, 49 (suppl 1), 51S-63S.
P.4.a.005 An investigation of clinical factors influence the therapeutic response of paroxetine in patients with panic disorder T. Ayugase1 ° , S. Ishiguro1 , T. Watanabe1 , M. Ueda1 , Y. Saeki1 , G. Hirokane2 , S. Morita2 , N. Yamada2 , K. Akiyama3 , K. Shimoda1 . 1 Dokkyo Medical University School of Medicine, Psychiatry, Tochigi, Japan; 2 Shiga University of Medical Science, Psychiatry, Otsu, Japan; 3 Dokkyo Medical University School of Medicine, Department of Biological Psychiatry and Neuroscience, Tchigi, Japan Selective serotonin reuptake inhibitors (SSRIs) are thought to interact with serotonergic system and be effective for treatment
of panic disorder (PD). This suggests a potential role of serotonergic system in panic disorder. And hyperthyroidism and hypothyroidism are commonly associated with psychiatric symptoms including anxiety and panic attack. In the present study, we investigated into associations between therapeutic response to paroxetine (PAX) in 2 weeks after the initiation of the treatment and plasma concentrations of PAX, 5-HTTLPR genotype, pretreatment thyroid function (FT3, FT4, TSH), and other clinical factors in patients with PD in a Japanese population. Subjects were 28 Japanese patients who fulfilled DSM-IV-TR criteria for a diagnosis of RD (male = 10, female = 18, mean age±SD = 34.0±7.4). Subjects were received 10 mg/day of PAX for 2 weeks as initial treatment. Severity of PD was assessed with the Panic and Agoraphobia Scale (PAS). We analyzed PAX plasma concentrations of subjects with HPLC and 5-HTTLPR variants were determined with polymerase chain reaction (PCR) techniques. A multiple regression analysis showed that PAS score at the baseline, plasma concentration of PAX, 5-HTTLPR genotype, TSH were significant factors indicating that these factors accounted for 83.2% (R2 = 0.832) of the variability of the clinical response to PAX (reduction of PAS score; PAS score at the baseline – PAS score at 2 weeks). The final model was described by the following equation (p < 0.05): Reduction of PAS score = −2.763 + 0.893×(PAS score at the baseline) − 0.529×(plasma concentration of PAX) − 9.383×(L/S = 1, S/S = 0) + 1.936×(TSH). At initial stage of pharmacotherapy with SSRIs, the desensitization of 5-HT1A autoreceptors contributes the clinical effect. The increase of serotonin in the somatodendritic area of cell bodies of serotonin neurons, before the down-regulation of 5-HT1A autoreceptors, might lead to lower the function of serotonin neurons and deteriorate symptom of panic disorder or impede the clinical effect, which might be caused by high plasma concentrations of PAX at the beginning of the pharmacotherapy with PAX for PD. In addition, the result of this study suggested that 5-HTTLPR S/S genotypes might have lower sensitivity to pharmacological effects of SSRIs than L allele carriers, because of the more reductions in the density of 5-HTT and 5-HT1A receptors, via latent higher concentration of serotonin in the synaptic cleft. L allele carriers were thought to be apt to lower the function of serotonin neurons with SSRIs at initial stage of the treatment. And low TSH level within normal limits was supposed to be a factor of low-response to SSRIs in PD. Furthermore, one subjects who was diagnosed as subclinical hypothyroidism (TSH: 5.80mU/ml) and excluded from the analysis showed low-response (the change of PAS score was 11 to 12). From the results of the present study, it was concluded that high plasma concentration of PAX, 5-HTTLPR L allele carrier, low TSH level within normal limits, and comorbidity of subclinical hypothyroidism might be associated with low-response to initial treatment with PAX of PD.
P.4.a.006 Evaluation of the prevalence of anxiety disorders with comorbidity of depression among geriatric psychiatry outpatients F. Beskardes1 ° , T. Ertan1 . 1 Istanbul University Cerrahpasa Medical Faculty, Psychiatry, Istanbul, Turkey The prevalence of anxiety disorders in elderly adults is a topic that has received scant attention, especially given the impressive amount of research on anxiety disorders over the past several