P.1 Affective disorders andantidepressants S4-65

signed-rank test). Mean YMRS and HDRS scores were significantlylower after follow-up than at baseline (p < 0.01 t Student paired test).Mean risperidonedose was 3.2 mg/day.

Discussion: Although Dwight et al (1994) reported an increase ofmanic symptoms in 6 bipolar patients treated with risperidone, pre­liminary data suggest that some atypical antipsychotic drugs, such asclozapine, may have not only antipsychotic effects, but also thymolepticeffectson schizoaffective and rapidly cycling bipolar patients (Suppes etal, 1994).The results of the presentstudyseemto confirmthat risperidonecould be a good choice in the treatmentof refractory rapidcyclingbipolardisorder.

References

Dwight, M.M., Keck, P.E., Stanton, S.P., Strakowski, S.M., and McElroy, S.L.(1994) Antidepressant activity andmaniaassociated with risperidone treatmentof schizoaffective disorder. Lancet 344, 554--555.

Suppes, T.,Phillips, K.A., and Judd, C.R. (1994) Clozapine trea~ent of.nonpsy­chotic rapid cycling bipolar disorder: a report of three cases. BiOI Psychiatry 36,338--340.

Vieta, E.,Gast6, C; andEscobar, R.Treatment ofdysphoric mania with risperidone.Human Psychopharmacology, in press.

IP.1.01SI Thesafety profile of fluvoxamine inelderlypatients

W. Wagner1, V. Hauser 2, L.F.Wong2. I Solvay Human Health Division,Hans Beckler Allee20, Hannover 30173, Germany; 2 SolvayPharmaceuticals, 901SawyerRoad, Marietta, GA30062, USA

The safety profile of the selective serotonin reuptake inhibitor (SSRI)fluvoxamine has been extensively assessed world-wide and informationfrom 66 post-marketing studiesconductedin 34,587patientshas recentlybeen published (Wagner et al., 1994). This constitutes the largest col­lection of safety data ever presented for an antidepressant and clearlydemonstratesthat fluvoxarnine is safe and well tolerated. The efficacy offluvoxamine in the managementof depressionin elderlypatientshasbeenconfirmedin a number of studies and evidence suggests that it is at leastas effective as the tricyclic antidepressants whilst having a better safetyprofile (Tebbs and Martin, 1987; Wakelin, 1986),The safety profil~ of adrug is especially important in elderly patients who tend to be frail andsuffering from coexistent conditions and are therefore more susceptibleto age-related symptomsand side effects.

The safetyprofileof fluvoxarnine has also beenspecifically assessedinthe 4,843 elderly,mainly depressed patients (65 years or older; range 65to 97 years) who were enrolled in the world-wide post-marketing studies.The daily dose of fluvoxamine ranged from less than 50 to 300 mg (themost common dose range was 100 to 149 mg which was given to 47.2%of patients) and the studies were conducted over periods of up to oneyear.The most conservative, or cautious,categorywaschosenthroughoutthe analysis in situationswhere more than one categorywas applicable.

Overall, 3,250 patients (67.1%) completed the study period; adverseeventsaccountedfor the discontinuation of 894 patients(18.5%). At leastone adverse event was reported by 2,228 patients (46.0%), the most fre­quently affected body systems being the 'gastrointestinal' and 'nervous'systems. Nausea was the most common adverse event, occurringin 747patients (15.4%), followed by somnolenceand asthenia, each reportedin314 patients (6.5%). At least one serious adverse event was experiencedby 135 patients (2.8%),hospitalisation being the most widespread classi­fication (113 patients;2.3%).Twenty-six patientsdied;none of the deathswere consideredto be related to fluvoxamine treatment. The incidence ofoverall suicidalitywith fluvoxamine was low (0.48%).

In conclusion, the results from this extensive world-wide assessmentof the safety profile of fluvoxarnine indicate that it is well toleratedin elderly patients and thus may be a good alternative to the tricyclicantidepressants, especially in this more vulnerable population.

References

Tebbs VM, Martin AI. Affective disorders intheelderly: J,OOO patient GPtrial onnew drug. Geriatric Medicine 1987; 17: 17-21.

Wagner W, Zaborny BA, Gray TE. Fluvoxamine, A review of its safety pro­file in worldwide studies. International Clinical Psychopharmacology J994; 9:222-226.

Wakelin J. Fluvoxamine in the treatment of the older depressed patient; double­blind, placebo-controlled data. International Clinical Psychopharmacology 1986;I: 221-230.

IP.1.016! Flu~oxamlne e~ective inpreventing recurrence ofmajor depresslon

J.L. TerraI, F. Noel2. I CHSLe Vinatier, Service d'lnjormation etd'Evaluation Medicale, 95 BlvdPinel, 69677 Bran Cedex, France;2 Solvay Human Health, CJ vanHoutenlaan 36, 1381 CPWeesp, TheNetherlands

Although patients frequently experience recurrence of major depres­sion, few studies have been conducted to investigate potential long-termpreventative treatments. The selective serotonin reuptake inhibitor flu­voxamine has proven efficacy and safety in the long-term treatment ofdepression (Martin & Wakelin, 1986; Ottevanger, 1994) and evidencesuggests that it may be effective in preventing recurrence (Franchini etaI., 1994).The aim of this double-blind, placebo-controlled, randomised,multicentre, parallel-group studywasto assess theefficacy of fluvoxaminein preventing recurrence of DSM-ill-R majordepression.

The study was divided into three phases. The first two phases wereopen and lastedfor 6 and 18 weeks, respectively. Only the responders(asassessedby the Montgomery-Asberg DepressionRating Scale [MADRS]and Clinical Global Impression [COlD were allowed to continue tothe further phases (phase Il and Ill). Patients received fluvoxamine upto 300 mg/day during phase I, whilst the dosage was reduced to 100mg/day during phase II. During phase ill, the patients were randomisedto receive double-blind treatment with fluvoxamine 100 mg/day (n =110) or placebo(n = 94) for a further 12 months. Patients were assessedmonthly on the MADRSand at three-monthly intervals on the CGI andCovi anxietyscales.

The incidence of recurrenee was significantly higher with placebothanwith fluvoxamine (35.1 % vs 12.7%; P < 0.(01). Moreover, the timeto recurrence was significantly longer in the fluvoxamine group than inthe placebo group (181 vs 96 days; p = 0.005). Fluvoxamine was alsosignificantly superiorto placeboin termsof the meanMADRStotal score(7.8 vs 12.5; p < 0.001), COl severity of illness score (1.8 vs 2.4; p =0.01) and Covi anxietyscale total score (4.7 vs 5.8; P = 0.002) at the endof the study.

Therewasno difference betweenthe groups in the incidenceof adverseevents(35%with fluvoxamine and 37% with placebo). The mostcommonevents with fluvoxamine were headache (5%), abdominal pain (5%) andweightincrease(5%),whilstplacebo wasmost frequentlyassociatedwithheadache (13%), abdominal pain (4%) and nausea (4%). There were nochanges in vital signs in either group.

The results show that fluvoxamine has marked beneficial effects inpreventing the recurrence of DSM-ill-R major depression and is safeduringlong-termadministration.

References

Franchini, L., Gasperini, M.and Smeraldi, E. (1994) A 24-month follow-up studyofunipolar subjects: a comparison between lithium and ftuvoxamine. Journal ofAffective Disorders 32,225-231.

Martin, AJ. and Wakelin, J. (1986) Fluvoxamine - a baseline study of clinicalresponse, long term tolerance andsafety inageneral practice population. BritishJournal ofClinical Practice 40,95-99.

Ottevanger, E.A. (l994) Long term treatment with ftuvoxamine in depression.Neuropsychopharmacology to (Suppl 3), 100S.

IP.1,017 1 Thecomparative effects of single andmultipledoses of R5-8359, moclobemlde andplacebo onpsychomotor function inhealthy subjects

K. Puechler, K. Scheffler, C.-H. Wauschkuhn, A. Plenker. SankyoEurope GmbH, Immermannstrasse 45, Dusseldorf40210, Germany

The psychophysiological/-motor effects of RS-8359 were evaluated intwo, double-blind, double-dummy, cross-over studies. In the first, 10healthy males (mean age 31 years, mean body weight 79 kg) receivedthree differentsingledosesof RS-8359(50, 100or 300mg),moclobemide(150 mg)- as a reference- and placebo. In the second, 16similarsubjects