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303. Response to flumazenil in women with premenstrual dysphoric disorder
Saturday Abstracts
dictionruy)regardless of perceived causality. The frequenciesof 18 new/worsenedAEs reported in the first four weeks (early-reporting interval)or the 22nd-26thweeks of treatment(late-reportinginterval) were comparedusingMcNemar’stest. Results:Patients(N=299) whosedepressionremittedwith 12weeksof fluoxetinetreatmententeredcontinuationtherapyand 174completed26 weeks of therapy.All early AEs which occurredin >5970of patients declinedsignificantly(p<.05) over time and no AEs occurredsignificantlymore frequentlyduringcontinuationtherapy. Discussion:CommonAEsassociatedwithinitiatingfluoxetinetreatment in depressed patients, including nausea, insomnia, nervousnessand somnolence,resolvein the majorityof patientsand arEsignificantlyless frequentwith ongoingtreatmentover a 6 monthperiod.In addition,no AEspresentinitiallybecomemorefrequent.Therapywithfluoxetine20 mg dailyis welltoleratedovera 6 monthperiodandmostAEsobserved early in treatmentresolve.
302. VALPROIC ACID AND HYPERAMMONEMIA IN A PATIENT WITH BIPOLAR DISORDER J.M. Sta. Romanal & R. Villalbal’2 IBrownUniversityDepartmentof Psychiatryand HumanBehavior, Providence,RI *VAMedicalCenter,Providence,RI Since the early 1980s,the neurologicalliterature has documentedthe occurrenceof hyperammonemia withvalproicacid(vPA) treatment.The clinical significanceof this fhfing remains controversial.Hyperammonemiamayoccurwithoutderangementof liverenzymetestsor mental status abnormality.Despite this controversy,hyperammonemiahas traditionallybeerrviewedas a markerof severeliver impairmentand a potentialcause of encephalopathy.With the increasinguse of VPA in bipolardisorder,psychiahistsmay overlookthis uncommonbut important sideeffect.We presenta case of a patientwithbipolardisorderwho was treatedwithVPAand becamelethargicand confusedin the context of hyperammonemiabut normal liver functiontests. Serial VPA and ammonialevels displayeda roughpositivecorrelation.
303. RESPONSE TO FLUMAZENIL IN WOMEN WITH PREMENSTRUAL DYSPHORIC DISORDER J.-M. Le Mel16do,M. Van Driel, N. Coupland, P. Lott & G.S. Jhangri Departmentof Psychiatryand ClinicalInvestigationUnit, University of Alberta,Alberta,Canada,T6G 2B7 There is evidenceto implicate GABAAreceptor abnormalitiesin the pathophysiologyof PremenstrualDysphoricDisorder (PMDD). The current methodsavailablefor tbe study of GABA~receptor function includechallengeswith the benzodiazepineantagonist,flumazerril.Induction of short lived panic symptomsfollowing administrationof flumazenilto panicdisorderpatientshas beeninterpretedas evidencefor altered GABA~receptorsensitivityin panic disorder.Our objectivein this pilot studywas to demonstratethat iv. administrationof flumazenil will inducemarkedpanic symptomsin PMDDwomencomparedwith none or few in healthy volunteers. The subjects were 11 healthy volunteersand 10 womenwith DSM-IVconfirmedPMDD.We used a doubleblindcross-overplacebo-cent.deddesign,withrandomizationof
BIOLPSYCHIATRY 1998:43 :1s-133s
91s
the order of the pkcebo and flumazenilinjection.All subjectsreceived both an injection of flumazeniland placebo during a single session, whichtookplaceduringthe late luterdphaseof the menstrualcycle (2 to 5 days heforethe menses).Flumazenil(2mg)or placebowere administered as a 20 ml iv. infusionover 60 sees. Behavioral responsesto ffumazenilwereevaluatedwitha PanicSymptomScale(PSS)and a 100 mmvisualanalogscafefor anxiety.Thepanic sumintensityresponseto flumazenilin PMDD women (27 * 16) was greater than in healthy volunteers(8 * 4) (p
304. COMPLIANCE WITH SSRI TREATMENT IN ADOLESCENT PSYCHIATRIC PATIENTS D.L. Pogge, J. Kraus, S. Borgaro, J. Stokes, A. Lloyd & P.D. Harvey FourWindsHospital,800 CrossRiverRd, Katonah,NY 10536 Little research has been performed on the prediction of medication compliancein adolescentpsychiatricpatients. With FDA approvalof SSRI use in adolescentand child patienta, such informationmay he criticalfor the developmentof optimaltreatmentstrategies.In this study 50 adolescentpsychiatricinpatientswithdepressiondiagnoseswhowere treated with SSRIantidepressantmedicationswere followedup 30 and 120 days post discharge and examined for medication compliance. Baselineseverityof depressionand globalpsychopathologywas examined, as was clinical changeduringhospitalizationand durationof the inpatientmedicationtrial. For the fmt 22 patienfi, medicationcompliancewas 64Z0at bothfollowups.Regressionanalysisfoundthat the best predictor of 30-day compliance was global clinical change during hospitaltreatment,accountingfor 40% of the variancein compliance. Specific changes in depressiondid not account for any variance in compliancewhen globalchangewas considered.The best predictorof 120compliancewas 30 day compliance,also accountingfor 40%of the variance.Althoughthis is nota formalefficacystudy,the resultsindicate that adolescentswith depressionwhoexperienceclinicrdchangeduring the initial stages of medicationtreatment are likely to comply with treatment for extendedperiods after discharge.Later research should addressthe specificityof medicationeffects,as comparedto psychotherapeuticor milieueffects, in order to identifythe specificpredictorsof medicationcompliance.
305. FLUOXETINE TREATMENT OF PANIC DISORDER:A RANDOMIZED, PLACEBOCONTROLLED, MULTI-CENTER TRIAL D. Michelson, R.B. Lydiard2, M.H. Pollack3, R. Tamural & R. Tepner 1 IEli Lilly and Company,Indianapolis,Indiana46285‘Medical Universityof SouthCarolina,Charleston,SouthCarolina29425 3MassachusettsGeneralHospital,Boston,Massachusetts02114 Objective:To assess outcomemeasuresin panic disorder.
dictionruy)regardless of perceived causality. The frequenciesof 18 new/worsenedAEs reported in the first four weeks (early-reporting interval)or the 22nd-26thweeks of treatment(late-reportinginterval) were comparedusingMcNemar’stest. Results:Patients(N=299) whosedepressionremittedwith 12weeksof fluoxetinetreatmententeredcontinuationtherapyand 174completed26 weeks of therapy.All early AEs which occurredin >5970of patients declinedsignificantly(p<.05) over time and no AEs occurredsignificantlymore frequentlyduringcontinuationtherapy. Discussion:CommonAEsassociatedwithinitiatingfluoxetinetreatment in depressed patients, including nausea, insomnia, nervousnessand somnolence,resolvein the majorityof patientsand arEsignificantlyless frequentwith ongoingtreatmentover a 6 monthperiod.In addition,no AEspresentinitiallybecomemorefrequent.Therapywithfluoxetine20 mg dailyis welltoleratedovera 6 monthperiodandmostAEsobserved early in treatmentresolve.
302. VALPROIC ACID AND HYPERAMMONEMIA IN A PATIENT WITH BIPOLAR DISORDER J.M. Sta. Romanal & R. Villalbal’2 IBrownUniversityDepartmentof Psychiatryand HumanBehavior, Providence,RI *VAMedicalCenter,Providence,RI Since the early 1980s,the neurologicalliterature has documentedthe occurrenceof hyperammonemia withvalproicacid(vPA) treatment.The clinical significanceof this fhfing remains controversial.Hyperammonemiamayoccurwithoutderangementof liverenzymetestsor mental status abnormality.Despite this controversy,hyperammonemiahas traditionallybeerrviewedas a markerof severeliver impairmentand a potentialcause of encephalopathy.With the increasinguse of VPA in bipolardisorder,psychiahistsmay overlookthis uncommonbut important sideeffect.We presenta case of a patientwithbipolardisorderwho was treatedwithVPAand becamelethargicand confusedin the context of hyperammonemiabut normal liver functiontests. Serial VPA and ammonialevels displayeda roughpositivecorrelation.
303. RESPONSE TO FLUMAZENIL IN WOMEN WITH PREMENSTRUAL DYSPHORIC DISORDER J.-M. Le Mel16do,M. Van Driel, N. Coupland, P. Lott & G.S. Jhangri Departmentof Psychiatryand ClinicalInvestigationUnit, University of Alberta,Alberta,Canada,T6G 2B7 There is evidenceto implicate GABAAreceptor abnormalitiesin the pathophysiologyof PremenstrualDysphoricDisorder (PMDD). The current methodsavailablefor tbe study of GABA~receptor function includechallengeswith the benzodiazepineantagonist,flumazerril.Induction of short lived panic symptomsfollowing administrationof flumazenilto panicdisorderpatientshas beeninterpretedas evidencefor altered GABA~receptorsensitivityin panic disorder.Our objectivein this pilot studywas to demonstratethat iv. administrationof flumazenil will inducemarkedpanic symptomsin PMDDwomencomparedwith none or few in healthy volunteers. The subjects were 11 healthy volunteersand 10 womenwith DSM-IVconfirmedPMDD.We used a doubleblindcross-overplacebo-cent.deddesign,withrandomizationof
BIOLPSYCHIATRY 1998:43 :1s-133s
91s
the order of the pkcebo and flumazenilinjection.All subjectsreceived both an injection of flumazeniland placebo during a single session, whichtookplaceduringthe late luterdphaseof the menstrualcycle (2 to 5 days heforethe menses).Flumazenil(2mg)or placebowere administered as a 20 ml iv. infusionover 60 sees. Behavioral responsesto ffumazenilwereevaluatedwitha PanicSymptomScale(PSS)and a 100 mmvisualanalogscafefor anxiety.Thepanic sumintensityresponseto flumazenilin PMDD women (27 * 16) was greater than in healthy volunteers(8 * 4) (p
304. COMPLIANCE WITH SSRI TREATMENT IN ADOLESCENT PSYCHIATRIC PATIENTS D.L. Pogge, J. Kraus, S. Borgaro, J. Stokes, A. Lloyd & P.D. Harvey FourWindsHospital,800 CrossRiverRd, Katonah,NY 10536 Little research has been performed on the prediction of medication compliancein adolescentpsychiatricpatients. With FDA approvalof SSRI use in adolescentand child patienta, such informationmay he criticalfor the developmentof optimaltreatmentstrategies.In this study 50 adolescentpsychiatricinpatientswithdepressiondiagnoseswhowere treated with SSRIantidepressantmedicationswere followedup 30 and 120 days post discharge and examined for medication compliance. Baselineseverityof depressionand globalpsychopathologywas examined, as was clinical changeduringhospitalizationand durationof the inpatientmedicationtrial. For the fmt 22 patienfi, medicationcompliancewas 64Z0at bothfollowups.Regressionanalysisfoundthat the best predictor of 30-day compliance was global clinical change during hospitaltreatment,accountingfor 40% of the variancein compliance. Specific changes in depressiondid not account for any variance in compliancewhen globalchangewas considered.The best predictorof 120compliancewas 30 day compliance,also accountingfor 40%of the variance.Althoughthis is nota formalefficacystudy,the resultsindicate that adolescentswith depressionwhoexperienceclinicrdchangeduring the initial stages of medicationtreatment are likely to comply with treatment for extendedperiods after discharge.Later research should addressthe specificityof medicationeffects,as comparedto psychotherapeuticor milieueffects, in order to identifythe specificpredictorsof medicationcompliance.
305. FLUOXETINE TREATMENT OF PANIC DISORDER:A RANDOMIZED, PLACEBOCONTROLLED, MULTI-CENTER TRIAL D. Michelson, R.B. Lydiard2, M.H. Pollack3, R. Tamural & R. Tepner 1 IEli Lilly and Company,Indianapolis,Indiana46285‘Medical Universityof SouthCarolina,Charleston,SouthCarolina29425 3MassachusettsGeneralHospital,Boston,Massachusetts02114 Objective:To assess outcomemeasuresin panic disorder.