- Email: [email protected]
Moclobemide and sleep
S226
PI Afective
disorders and antidepressants
with the overall melatonin levels during the night and with the magnitude of the 02:0@-04:00 secretory peak of its production. Results: Mean height and weight did not differ between the two groups. Depressives had a higher mean age than controls (44.37 f 12.6 vs 38.87 f 7.8 years, t-test 2-tail sig. p = 0.03). The mean value f SD of baseline melatonin for depressives and controls was 0.234 f 0.107 and 0.297 f 0.105 mnoVlt respectively (t-test 2-tail sig. p = 0.01). The mean melatonin value after clonidine administration for depressives and controls was 0.209 & 0.111 and 0.282 f 0.117 nmol/lt respectively. This value was significantly different from the baseline melatonin value only in the depressed group (t-test for paired samples 2-tail sig. p = 0.04). Conclusions: 1) Depressed patients have significantly lower overnight urinary melatonin concentrations than normal controls, a finding corroborating for the existence of the proposed “low melatonin syndrome” in depression. 2) Clonidine administration significantly reduces melatonin levels in depressed but not in control subjects, a fact indicating to the presence of presynaptic az-adrenoreceptor supersensitivity or azadrenoceptor up-regulation in depression.
-1
The role of olanrapine
in dysphoric
mania
A. GonzPlez-Pinto, B. Lalaguna, E Mosquera, J.L. POrez de Heredia, B. Femandez de Corres. Psychiatric Department, Santiago Apostol Hospital, Osakidetza Mental Health System, Vitoria, Spain
Objective: Dysphoric mania has a high prevalence among manic patients who need hospitalization and could predict poorer outcomes. The aim of this study was to evaluate the depressive symptoms during acute mania among manic patients who were hospitalized in our Unit, and to compare the outcomes among dysphoric patients treated with olanzapine and dysphoric patients treated with other antipsychotics. Method: 81 patients who met DSM IV criteria for Bipolar disorder (manic or mixed episode), and who have been hospitalized in our Unit for a period of 2 years were included in the study. A clinical protocol was specially made for this study. The protocol includes Susan McElroy criteria for dysphoric mania, HDRS, Young mania rating Scale (Y-MRS), PANS& CGI scale, administered treatment at admission, and follow-up during the hospitalization and discharge also with these scales. Results: 39 patients (48%) had 2 o more symptoms of McElroy criteria for disphoric mania. There were no differences between disphoric and non-disphoric patients in manic symptoms at admission measured by Young scale, but disphoric patients had significantly more puntuation in HDRS (p < 0.05). Women with disphoric mania had longer stays than men with disphoric mania (p < 0.05). All patients were treated with mood stabilizers and antipsychotics. People treated with olanzapine in combination with mood stabilizers (mostly lithium and valproate), tended to improve more in manic symptoms (p < 0.07) and improved more in depressive symptoms (p < 0.05) than people treated with other antipsychotics. Conclusions: Olazapine combined with mood stabilizers could be specially useful in the treatment of Dysphoric mania. Controlled studies in dysphoric mania with olanzapine are needed to replicate these results.
[p.1.0541
Moclobemide
and sleep
N. Stanley, I. Hindmarch. HPRU Medical Research Unit, Unioersity of Surrey, Egerton Road, Guildford Sum, GU2 LYE UK
The vast majority of studies investigating the effects of antidepressants on sleep have been performed in depressed patients, in such studies it is difficult to separate the potential of a drag to effect sleep, from the underlying sleep disturbance found in such patients. Studies investigating the effects of moclobemide on sleep in depressed patients have reported that moclobemide exerts it’s antidepressant effect whilst lacking the striking REM suppressant effects observed with most other antidepressants. It has been postulated that one possible explanation for this is due to the mild REM suppressant effects being counteracted by the expected increase in REM sleep that normally occurs during recovery from depression. The
results from patient studies can only indicate the interaction between the effects of a drag on sleep and the disturbed sleep found in that population, rather than the true effects of the drug alone. In order to measure the inherent potential of antidepressant medications to affect sleep it is important to measure their effects in healthy volunteers using a fixed time in bed. The present double blind placebo controlled study using normals and a fixed time in bed was designed to clarify the true potential of moclobemide to affect sleep. Sixteen male subjects were aged between 18 and 35 years, (median 25 years), participated in the study. The medications under investigation were moclobemide 450 mg mane & 600 mg mane, dothiepin 75 mg nocte & 150 mg nocte and placebo. They took each treatment for a period of 2 days with one dose at 0930 hours and one at 2130 hours. Each treatment period was separated by a 7 day washout period. Time in bed (TIB) in this study was kept constant, set at 480 mins with lights out at 2330 and awake time at 0730. Whilst dothiepin had significantly longer sleep period (p = 0.003), a shorter sleep latency @ < 0.001) and a higher sleep efficiency (p < 0.001) than moclobemide the was no significant difference between the drugs in terms of total sleep time. Dothiepin 150 mg had a significantly (p < 0.001) longer REM latency than the other four drugs, and placebo a significantly shorter REM latency (p < 0.003) however there was no difference between dothiepin 75 mg and moclobemide 450 mg or 600 mg. Dothiepin 150 mg had significantly shorter REM than the other treatments but again there were no differences between dothiepin 75 mg and moclobemide 450 mg or 600 mg. Dothiepin 150 mg also had significantly (p = 0.001) more the stage 4 sleep than the other treatments. The results for as compared to placebo. In this study dothiepin 150 mg exhibited the classical action of a TCA i.e. increased REM latency, decreased REM, increased sleep efficiency, decreased sleep latency and increased stage 4, the action of dotbiepin 75 mg was less pronounced. However doses of moclobemide were found to suppress REM sleep in a similar way to dothiepin 75 mg. The effects on sleep observed in a study of this nature are a reflection of the pharmacological profile of moclobemide rather than it’s antidepressant action.
Ip.1.0551
Efficacy and tolerability of the hyperlcum special extract LI 160 in young and elderly outpatients with depressive disorders: a drug monitoring study
E. Holsboer-Trachsler, S. Henauer’, Ch. Vanoni*. (Study funded by Medichemie AG, Switzerland): Psychiatric Uniuersiv Hospital, Department of Depression Research, Sleep Medicine and Neumphysiology, CH4025 Base6 ‘PharmaPart AG, CH-8036 Ziirich: 2Geneml Pmctice. CH4013 Basel, Switzerland There is evidence that extracts of hypericum are more effective as placebo in the treatment of mild to moderate depression, are as effective as standard antidepressive treatment and have fewer side effects (1). Although many preparations of St. Johnswort have been investigated a recent overview concludes that there is only for LI 160 extract a sufficient number of trials to be defined as herbal antidepressant (2). One of the strengths of hypericum is the good tolerance which is especially important for elderly outpatients. Therefore our ambulatory drug monitoring study was analyzed focussing on the influence of age on efficacy and tolerability. Patients and Methods: 647 patients suffering from mild to moderat depression (ICD-10) treated for 6 weeks with hypericum extract LI 160 (Jarsin 300), 1 tablet t.i.d. The age of the patients ranged from 15 to 94 years (mean 49 years). Psychopathology was measured after 3 and 6 weeks. Results: The condition of the patients improved in 75% (primary endpoint). The von Zerssen depression score decreased from 19.8-21.2 (95%~Cl) at baseline to 8.1-9.3 at week 6 (p < 0.001). All symptoms were improved at week 3 (~45 y: 72%; 45-65 y: 74%; >65 y: 51%) and further at week 6 (88%/82%/77%). The condition improved somewhat slower in patients older than 65 years. The severity of the depression did not appear to have an effect on the outcome. Adverse events were reported by 17% of the patients (gastrointestinal lo%, phototoxic 3%).
PI Afective
disorders and antidepressants
with the overall melatonin levels during the night and with the magnitude of the 02:0@-04:00 secretory peak of its production. Results: Mean height and weight did not differ between the two groups. Depressives had a higher mean age than controls (44.37 f 12.6 vs 38.87 f 7.8 years, t-test 2-tail sig. p = 0.03). The mean value f SD of baseline melatonin for depressives and controls was 0.234 f 0.107 and 0.297 f 0.105 mnoVlt respectively (t-test 2-tail sig. p = 0.01). The mean melatonin value after clonidine administration for depressives and controls was 0.209 & 0.111 and 0.282 f 0.117 nmol/lt respectively. This value was significantly different from the baseline melatonin value only in the depressed group (t-test for paired samples 2-tail sig. p = 0.04). Conclusions: 1) Depressed patients have significantly lower overnight urinary melatonin concentrations than normal controls, a finding corroborating for the existence of the proposed “low melatonin syndrome” in depression. 2) Clonidine administration significantly reduces melatonin levels in depressed but not in control subjects, a fact indicating to the presence of presynaptic az-adrenoreceptor supersensitivity or azadrenoceptor up-regulation in depression.
-1
The role of olanrapine
in dysphoric
mania
A. GonzPlez-Pinto, B. Lalaguna, E Mosquera, J.L. POrez de Heredia, B. Femandez de Corres. Psychiatric Department, Santiago Apostol Hospital, Osakidetza Mental Health System, Vitoria, Spain
Objective: Dysphoric mania has a high prevalence among manic patients who need hospitalization and could predict poorer outcomes. The aim of this study was to evaluate the depressive symptoms during acute mania among manic patients who were hospitalized in our Unit, and to compare the outcomes among dysphoric patients treated with olanzapine and dysphoric patients treated with other antipsychotics. Method: 81 patients who met DSM IV criteria for Bipolar disorder (manic or mixed episode), and who have been hospitalized in our Unit for a period of 2 years were included in the study. A clinical protocol was specially made for this study. The protocol includes Susan McElroy criteria for dysphoric mania, HDRS, Young mania rating Scale (Y-MRS), PANS& CGI scale, administered treatment at admission, and follow-up during the hospitalization and discharge also with these scales. Results: 39 patients (48%) had 2 o more symptoms of McElroy criteria for disphoric mania. There were no differences between disphoric and non-disphoric patients in manic symptoms at admission measured by Young scale, but disphoric patients had significantly more puntuation in HDRS (p < 0.05). Women with disphoric mania had longer stays than men with disphoric mania (p < 0.05). All patients were treated with mood stabilizers and antipsychotics. People treated with olanzapine in combination with mood stabilizers (mostly lithium and valproate), tended to improve more in manic symptoms (p < 0.07) and improved more in depressive symptoms (p < 0.05) than people treated with other antipsychotics. Conclusions: Olazapine combined with mood stabilizers could be specially useful in the treatment of Dysphoric mania. Controlled studies in dysphoric mania with olanzapine are needed to replicate these results.
[p.1.0541
Moclobemide
and sleep
N. Stanley, I. Hindmarch. HPRU Medical Research Unit, Unioersity of Surrey, Egerton Road, Guildford Sum, GU2 LYE UK
The vast majority of studies investigating the effects of antidepressants on sleep have been performed in depressed patients, in such studies it is difficult to separate the potential of a drag to effect sleep, from the underlying sleep disturbance found in such patients. Studies investigating the effects of moclobemide on sleep in depressed patients have reported that moclobemide exerts it’s antidepressant effect whilst lacking the striking REM suppressant effects observed with most other antidepressants. It has been postulated that one possible explanation for this is due to the mild REM suppressant effects being counteracted by the expected increase in REM sleep that normally occurs during recovery from depression. The
results from patient studies can only indicate the interaction between the effects of a drag on sleep and the disturbed sleep found in that population, rather than the true effects of the drug alone. In order to measure the inherent potential of antidepressant medications to affect sleep it is important to measure their effects in healthy volunteers using a fixed time in bed. The present double blind placebo controlled study using normals and a fixed time in bed was designed to clarify the true potential of moclobemide to affect sleep. Sixteen male subjects were aged between 18 and 35 years, (median 25 years), participated in the study. The medications under investigation were moclobemide 450 mg mane & 600 mg mane, dothiepin 75 mg nocte & 150 mg nocte and placebo. They took each treatment for a period of 2 days with one dose at 0930 hours and one at 2130 hours. Each treatment period was separated by a 7 day washout period. Time in bed (TIB) in this study was kept constant, set at 480 mins with lights out at 2330 and awake time at 0730. Whilst dothiepin had significantly longer sleep period (p = 0.003), a shorter sleep latency @ < 0.001) and a higher sleep efficiency (p < 0.001) than moclobemide the was no significant difference between the drugs in terms of total sleep time. Dothiepin 150 mg had a significantly (p < 0.001) longer REM latency than the other four drugs, and placebo a significantly shorter REM latency (p < 0.003) however there was no difference between dothiepin 75 mg and moclobemide 450 mg or 600 mg. Dothiepin 150 mg had significantly shorter REM than the other treatments but again there were no differences between dothiepin 75 mg and moclobemide 450 mg or 600 mg. Dothiepin 150 mg also had significantly (p = 0.001) more the stage 4 sleep than the other treatments. The results for as compared to placebo. In this study dothiepin 150 mg exhibited the classical action of a TCA i.e. increased REM latency, decreased REM, increased sleep efficiency, decreased sleep latency and increased stage 4, the action of dotbiepin 75 mg was less pronounced. However doses of moclobemide were found to suppress REM sleep in a similar way to dothiepin 75 mg. The effects on sleep observed in a study of this nature are a reflection of the pharmacological profile of moclobemide rather than it’s antidepressant action.
Ip.1.0551
Efficacy and tolerability of the hyperlcum special extract LI 160 in young and elderly outpatients with depressive disorders: a drug monitoring study
E. Holsboer-Trachsler, S. Henauer’, Ch. Vanoni*. (Study funded by Medichemie AG, Switzerland): Psychiatric Uniuersiv Hospital, Department of Depression Research, Sleep Medicine and Neumphysiology, CH4025 Base6 ‘PharmaPart AG, CH-8036 Ziirich: 2Geneml Pmctice. CH4013 Basel, Switzerland There is evidence that extracts of hypericum are more effective as placebo in the treatment of mild to moderate depression, are as effective as standard antidepressive treatment and have fewer side effects (1). Although many preparations of St. Johnswort have been investigated a recent overview concludes that there is only for LI 160 extract a sufficient number of trials to be defined as herbal antidepressant (2). One of the strengths of hypericum is the good tolerance which is especially important for elderly outpatients. Therefore our ambulatory drug monitoring study was analyzed focussing on the influence of age on efficacy and tolerability. Patients and Methods: 647 patients suffering from mild to moderat depression (ICD-10) treated for 6 weeks with hypericum extract LI 160 (Jarsin 300), 1 tablet t.i.d. The age of the patients ranged from 15 to 94 years (mean 49 years). Psychopathology was measured after 3 and 6 weeks. Results: The condition of the patients improved in 75% (primary endpoint). The von Zerssen depression score decreased from 19.8-21.2 (95%~Cl) at baseline to 8.1-9.3 at week 6 (p < 0.001). All symptoms were improved at week 3 (~45 y: 72%; 45-65 y: 74%; >65 y: 51%) and further at week 6 (88%/82%/77%). The condition improved somewhat slower in patients older than 65 years. The severity of the depression did not appear to have an effect on the outcome. Adverse events were reported by 17% of the patients (gastrointestinal lo%, phototoxic 3%).