Psychiatric aspects of therapy with corticosteroids in asthma

t?.6 Other topics $365 to mirtazapine does not result in a clinically relevant pharmacokinetic drug-drug interaction. The combination was well tolerated and no major clinically relevant adverse events were observed Conclusion: Despite a limited number of patients the present data suggest that a combination of risperidone and mirtazapine does not necessitate a change of dose of either drug and is well tolerated • • P300 amplitude has a heritability of 50-60%. First molecular genetic studies show linkage to chromosomes 2 and 6 and association to the cannabinoid receptor gene. Interestingly, P300 latency seems to be associated with variations in the DRD2 gene. We tested the hypothesis that interindividual differences in P300 parameters are associated with a polymorphism in the DRD3 gene. 30 fight handed, healthy, drug free randomly selected control subjects without somatic or psychiatric disorders as diagnosed by SKID were included. P300 parameters were registered using a classic oddball paradigm. P3a and p3b were separated by dipole source analysis. The distribution of a genetic polymorphisms in the DRD3 receptor gene (Bal I) was examined. The three possible groups for the polymorphism did not differ significantly in age and sex. There was no association with P300 latencies. We observed a significant association of the DRD3 genotype with the amplitude of the right p3a (p < 0.01) with marked differences between the homotygotes. This finding is one of the first steps towards the identification of genes which influence P300 electrogenesis. A replication study in a larger sample is under way. Mirtazapine in the treatment of irritable bowel syndrome: a pilot study L. Tanum 1, N. Moe 2. 1Dept. of Psychosomatic Medicine, National Uniuersity Hospital, 0027 Oslo; 2SmertemedisinskInstitutt, Rode Kors Klinikk, E Stangsgate 11-13, Oslo, Norway Aim: To assess efficacy and tolerability of mirtazapine (15~50 mg) in non-psychiatric patients with Irritable Bowel Syndrome (IBS) in an openlabel, non-comparative study. Methods: Twelve patients aged 18-60 years with a diagnosis of IBS according to Rome criteria, and with no additional somatic or psychiatric diagnosis, were included in a eight weeks study with mirtazapine. Efficacy was assessed as reduction in pain and primary target symptom using patient-rated Visual Analogue Scale (daily basis) and physicianrated Clinical Global Improvement Scale at every visit. McGill Pain questionnaire was also completed at every visit, together with recording of adverse events. Response was defined as at least 50% reduction in pain on both VAS and CGI. Results: Twelve patients were eligible for this study and 10 patients were designated as evaluable. Seven patients (70%) were classified as responders on Intention to Treat basis. Two patients dropped out due to adverse events. Clinical response were recorded within 6 days after start in all responders. After tapering of mirtazapine (weeks 9 and 12) a major relapse of symptoms were seen in 50% of the responders. Except for the two drop-outs, mirtazapine was generally well tolerated in these patients. Conclusion: These results suggest that mirtazapine is an efficacious and well tolerated drug with a fast onset of action in patients with IBS, but this needs further confirmation. • Impulsive aggression is associated with lifetime history of suicide attempt. Towards a description of patients with serotonergic dysfunction M. Sch~ifer, D. Rujescu, I. Giegling, G. Scheerer, A. Gietl, A. Ebner, R. Engel, H.-J. Mrller. Department of Psychiatry, Ludwig-Maximilians- Unioersity of Munich, Germany Introduction: Both, impulsive aggression and suicide attempts have been related to altered serotonergic neurotransmission. Brown Goodwin Assessment for Lifetime Aggression is negatively correlated to cerebrospinal fluid 5-HIAA. The aim of this study was to find possible psychological characteristics which could be useful for the definition of a phenotype characterized by altered serotonergic function and high risk for suicide attempts. Method: We compared 46 subjects with a life time history of at least one suicide attempt with 55 control subjects without psychiatric disorders as diagnosed by SKID-I and SKID-II. Both groups were characterized with the Brown Goodwin Assessment for Lifetime Aggression (BAA); Buss Durkee Hostility Inventory (BHI; Subscale Assault and Subscale Irritability) and the Barrat Impulsivity Scale (BIS). Results: The group of patients with a history of suicide attempts scored higher in BAA (p < 0.001) and BHI, Subscales Assault (p < 0.05) and Irritability (p < 0.0001). No difference was found for the BIS. Conclusions: The construct of impulsive aggression consisting of lifetime aggression, assault and irritability, but not impulsivity seems to characterize collectives with a lifetime history of suicide attempts compared to controls. This may help to further define a possible phenotype with serotonergic dysfunction for genetic studies in suicide. amplitude associated with genetic Pvariations 3 in the0isDRD3 0 dopamine receptor gene D. Rujescu, I. Giegling, A. Riehle, G. Juckel, P. Mavrogiorgou, G. Scheerer, D. MiJller, R. Engel, H.-J. Mfller, U. Hegerl. Department of Psychiatry, Ludwig-Maximilians-Uniuersity of Munich, Germany • Psychiatric aspects of therapy with corticosteroids in asthma E (~am t~elikel, 0. Saatqio(glu*, S. (~elikel, S. Tiirkcan, M. Yaman. Bakirkb'y State Hospital for Psychiatric and Neurological Diseases, istanbul, Turkey Asthma, a chronic disease characterized by life-threatening episodes, may cause psychiatric as well as physical symptoms. The treatment includes both acute and maintenance therapy, mainly corticosteroids, systemic or inhaled. There are several studies suggesting that corticosteroid therapy in asthmatic patients results in psychiatric disorder. In this study, the psychiatric aspects of corticosteroid use and its contribution to psychiatric symptomatology in asthmatics are investigated thoroughly. 90 asthmatic patients are compared in respect to corticosteroid use, using SCL-90 symptom inventory, Hamilton depression and anxiety rating scales (HAM-D, HAM-A), Spielberger state and trait anxiety inventories. 27% of asthmatic cases have systemic corticosteroid (oral + parenteral) use, with a mean dose of 48.67 + 44.21, whereas 77% have inhaled corticosteroid use, of which 98% with a duration shorter than 2 years and only 42% longer than 2 years. Among the sub-groups of SCL-90 symptom inventory, anxiety is found higher in asthmatics using corticosteroids than those who do not. However, no statistically significant difference is found in any sub-group of SCL-90 smyptom inventory corticosteroid user and non-user asthmatic patients. The average HAMD score is found 9.63 4- 7.35 in corticosteroid users whereas 9.55 -t- 4.97 in non-users. The average HAM-A score is 14.8 ± 8.80 in corticosteroid users whereas 16.82 ± 7.03 in non-users. No statistically difference is found in anxiety and depression levels of the two groups. The average state anxiety score is 40.32 + 10.06 in corticosteroid users whereas 38.55 + 10.05 in corticosteroid non-users. The average anxiety score is 43.63 =k 9.85 in corticosteroid users whereas 46.55 ± 11.38 in corticosteroid non-users. No statistically difference is found in state-trait anxiety levels between corticosteroid user and non-user asthmatic. 27% of our samples had current systemic corticosteroid use (all did use at least once in their lives), and only 13% complained of psychological symptoms, resolving spontaneously without any psychiatric treatment. These subjective psychiatic complaints include insomnia, anxiety, restlessness, nervousness ans psychomotor agitation. Our findings support opinions of certain authors, stating that corticosteroid therapy results in various psychiatric symptoms which resolve spontaneously in a few weeks upon discontinuing corticosteroid treatment. It is also known that psychiatric symptoms may appear during corticosteroid treatment $366 P.6 Other topics dose-dependently. Dosing and the duration in corticosteroid treatment is known to be important factor in the appearance of psychiatric symptoms. The relatively low levels o f anxiety in our sample of asthmatics seem to result from the relatively low corticosteroid doses as well as short duration. Reducing the dependence on systemic corticosteroid therapy, relying more on inhaled treatment might have diminished the anxiety levels of asthmatic patients in our sample. References [1] Ling MHM, Perry PJ, Tsuang MT. Side effects of corticosteroid therapy. Psychiaa'ic aspects. Arch Gen Psychiatry. 1991; 38: 471-477. [2] Milgrom H, Bender BG. Psychologic side effects of therapy with corticosteroids. Am Rev Respir Dis 1993; 147: 471-473. [3] Garden GMF,AyresJG. Psychiatricand social aspects of brittle asthma. Thorax 1993; 48: 501-505. Effect of acute tryptophan depletion on negative priming J. Wingrove, A.J. Bond, D.G. Critchlow. Section of Clinical Psychopharmacology, Institute of Psychiatry, King's College London, UK It has been suggested that serotonergic pathways may play an important role in inhibitory processes. Negative priming tasks, which require responses to target stimuli sharing characteristics with previously presented distractors, have been used as a measure of inhibitory processes operating in selective attention. Separate systems have been proposed for inhibition of spatial and identity information. Acute tryptophan depletion using an amino acid drink is a technique that has been widely used to study serotonergic function. Therefore this study was designed to investigate the effect of tryptophan depletion on location and identity negative priming. In an independent groups design experiment twelve women with Premenstrual Dysphoric Disorder (PMDD) and six women healthy volunteer controls, all aged between 23 and 45 years, were randomly assigned to receive either an amino acid drink containing tryptophan (balanced condition) or an amino acid drink without tryptophan (depleted condition). All women were tested during the pre-menstrual phase of their cycle. The negative priming task, which was based on Connelly and Hasher (1993), used a paired prime-trial/probe-trial procedure. Each trial consisted of two letters, one target and one distractor, one green and one red. The subject was required to name aloud the target letter. The task contained the following conditions, presented in random order: 1. I) identity suppression: the probe target has the same identity (i.e. is the same letter) as the prime distractor but has a different location. 2. 2) location suppression: the probe target has the same location as the prime distractor, but a different identity. 3. 3) combined identity and location suppression: the probe target shares both identity and location with the prime distractor. 4. 4) control: probe target and prime distractor share neither identity nor location. For each subject the identity, location and combined negative priming effects were obtained by subtracting the median reaction time for probe targets on control trials from the median reaction time for probe targets in the relevant condition. An independent t-test showed that location negative priming was significantly lower after tryptophan depletion than after the balanced drink (tl6 = 2.76, p < 0.02). This supports the role of serotonin in inhibitory mechanisms in the processing of visuospatial information. References [1] Connelly,S.L., Hasher, L., 1993. Ageing and the inhibition of spatial location. Journal of Experimental Psychology:Human Perception and Performance 19, 1238-1250 ~ A randomized double-blind placebo-controlled study of bupropion sustained release in obesity K. Gadde, K.R.R. Krishnan. Duke University Medical Center, Durham, North Carolina, USA Purpose: To evaluate whether bupropion sustained release (bupropion SR) is more effective than placebo as obesity treatment in moderate to severely obese subjects. Methods: Subjects with a body mass index (BMI) of 27 or greater were randomized to receive bupropion SR or placebo for eight weeks in a donhle-blind fashion. Bupropion SR was administered at a starting dose of 100 rag/day and was gradually increased as tolerated to a maximum of 200 mg twice a day. The subjects were instructed to follow a 1,600 kcal per day diet. Diet compliance was monitored with self-rated diaries. Subjects were excluded if they have concomitant psychiatric and/or eating disorders. Nonresponders (lost less than 4 kg or 5% initial body weight) in the initial eight week study were given the option to participate in an eight week crossover study where they received the alternative medication in the study. The initial medication was tapered-off over 3 days and after a 3-day washout, the alternative study medication was started. Subjects responding (lost more than 4 kg or 5% initial body weight) after the initial 8-week study were followed for 6 months. Results: FiRy obese (BMI 37.5 -4- 6.3) women, aged 24-51 were enrolled. Weight loss was greater in subjects who received bupropion SR compared with placebo as demonstrated by intent-to-treat analysis (% weight loss: bupropion SR 4.86 + 3.45 vs placebo 1.26 -4- 2.36; p = 0.0001) and completer analysis (% weight loss: bupropion SR 6.21 4- 3.09 vs placebo 1.56 -4- 2.95; p = 0.002). Among completers, more subjects receiving bupropion SR (67%) lost over 5% of their initial body weight compared with placebo (15%; p = 0.0009). The mean dose of bupropion SR was 352 nag per day. More subjects receiving placebo (32%) withdrew from the study due to dissatisfaction compared with those receiving bupropion SR (4%; p = 0.02). Bupropion SR was well tolerated with minimal side effects. Conclusion: Bupropion SR is significantly more effective than placebo in achieving weight loss in obese women. • Reboxetlne for treatment of bulimla nervosa (BN): first results U. Bailer, M. de Zwaan, N. El-Giamal, C. Lennkh, A. Strnad, S. Kasper. Department of General Psychiatry, University of Vienna, Austria Controlled studies suggest that most antidepressants are effective in the treatment of BN. We will report our clinical experience with 8 mg of reboxetine, a selective noradrenaline reuptake inhibitor (NARI) in outpatients with BN. The patients are assessed with the SCID, CGI, BDI, HAMD, EDI, SASS, daily self-ratings, and the UKU side effect scale. Until now, 7 patients, 6 females and 1 male, have been started on reboxetine. A treatment period of 12 weeks was planned. Three patients have already dropped out, 1 after 6 weeks and 2 after 4 weeks of reboxetine treatment. The reasons for premature attrition were rapid remission in 1 patient and adverse events in 2 patients. The most frequent adverse events were constipation (which led to an increase in laxative intake in 2 patients), dry mouth, insomnia, and vertigo. Those, who have already completed 12 weeks of treatment with reboxetine exhibited only moderate improvement of depression ratings as well as of eating pathology. References [I] Lennkh C, de Zwaan M, Kaspcr S: N e w aspects of diagnosis and pharmacotherapy of eating disorders.Int J Psychiatry Clin Practice 1:21-35, 1997 [2] Walsh BT, Wilson GT, Loeb KL, Dcvlin MJ, Pike KM, Roose SR Fleiss J, Waternaux C: Medication and psychotherapy in the treatment of bulimia ncrvosa. A m J Psychiatry 154: 523-531, 1997