304 ['-2 Antidepressants: basic and clinical studies

References Katz, I. R 11993) Drug treatment of depression m the frad elderly: discussion of the NIH

consensus development conference on the diagnosis and treatment of depression in late life Psychopharmacology Bulletin 29, 101-108

Wagner, W, Zaborny, B A and Gray. T E (1994) Fluvoxamme A review of its safety profile in world-wide studies International Clinical Psychopharmacology 9,222 226

I P-2-87 i Comparison of the safety and tolerance of fluvoxamine and sertraline in depressed outpatients

CB. Nemeroff 1, PT. Ninan 1, J.C. Ballenger 2, j . Feighner 3, JH. Greist 4, W M Patterson 5 1 Empty University School of Medicine, Atlanta, GA, 2 Medical University of South Carolina, Charleston, SC, 3 Feighner Research Institute, San Diego, CA; 4 Dean Foundation for Health Research Education, Madison, WI, 5 Birmingham Research Group, Birmingham, AL

Because of the improved safety profile relative to older antidepressants (eg tricyclics), selective serotonin reuptake inhibitors (SSRIs) have become the drugs of choice in the treatment of major depressive disorder However, few trials have been conducted which compare SSRIs directly

The comparative safety, tolerance and efficacy of LUVOX'" (fluvoxamine maleate} Tablets, 50-150 mg daily versus Zoloft ® (sertraline HC]), 50-200 mg daily, were stud~ed m outpatients with DSM-IIFR-defined Major De- pressive Disorder in a randomizea, double bhnd, parallel-group, multicenter study After s one- to two week placebo runin, patients were random- ized to double-blind treatment for seven weeks. Efficacy was evaluated primarily by the Hamilton Psychiatric Rating Scale for Depression (HAM-D) Secondary and supportive measures of efficacy included HAM-D factors scores, the Clinical Global Impression Scale (CGI), the Hamilton Psychiatnc Rating Scale for Anxiety (HAM-A), the Raskin-Cow Scale and the SCL-55 Safety evaluations included vital s~gns, clinical laboratory tests (hematol ogy and biochemistry}, the Sexual Symptoms Distress Index, monitoring of adverse events and concomitant medicat ions

Of 114 patients screened for the study, 97 patients were randomized: 49 to f luvoxamine and 48 to sertrahne. The majority of patients had no other Axis I disorder nor had they been on treatment with psychotropic medicine m the past three months The mean total daily dose after titration was 123.75 mg for f luvoxamine and 137.10 mg for sertraline. Mean HAM D 21-item total scores decreased by 13.03 points for f luvoxamine and by 11.61 points for sertraline (vislt-w~se analysis) over the 7-week period There were no statistically significant differences between groups at any visit and at end-point for the primary efficacy variable (HAM-D 21-item total score) Secondary and supportive measures confirmed the results obtained wi:h the HAM-D

Neither treatment was associated with any clinically important changes in laboratory values or vital s~gns. There were more overall complaints as- sociated with sertraline than with f luvoxamine (93.5% of sertraline patients reported adverse events versus 85.7% with f luvoxamme) Although more fluvoxamine-treated patients discontinued owing to adverse events (nine f luvoxamine vs. one sertraline, p 0.016). there was no clear pattern to the reasons. In evaluating overall reports of adverse events, there was little difference between the two treatments with the majority occurring in the body as a whole (e.g, headache, asthenia), digestive (e.g., nausea, diar rhea), and nervous (eg., insomnia, somnolence) systems. Sertraline was associated with more sexual dysfunction complaints (libido decrease, ser traline 19.57% vs. f luvoxamine 6.12% p = 0.049: ejaculatory abnormality, ser t ra l ine22.22%vs f luvoxamine5.26%)thanf luvoxamine. No patient was rated as worse in suicidal ideation at the end of the study.

References Wilde, M, PIosker, G L , Benfield, R Fluvoxamme: an updated review of its pharm acologv

and therapeutic use in depressive illness (!993) Drugs 46 (5), 895 924 Delgado PL, Price, LH, Charney, D S, Henlnger, GR Efficacy of fluvoxamme m

treatment-refractory depression (1988) J Affective Dis 15.55~60

Comparison of fluvoxamine and fluoxetine in major depression

M. Rapaport 1. E Coccaro 2,Y.Shel ine 3, P Holland 4 . T Perse 5 . L Fabre 6 1 UmversJty of California, San Diego, CA, 2 Medical College of Pennsylvania, Philadelphia, PA, 3 Washington Universi~, St. Louis, MO, 4 Boca Raton Psychiatry Group, Boca Raton, FL, 5 NFPC, Edmonds, WA, 6 Research Testing, Inc., Houston, TX

Fluvoxamine maleate (LUVOX'") is a potent and specdic inhibitor of sere

tonm reuptake with demonstrated antidepressant activity in a number of clinical trials This is a report from a randomized, double-blind, parallel group study of the efficacy and safety of f iuvoxamine and fluoxetine (Prozae ®) in major depressive disorder. Based on previous studies, we postulated that: (1) f luvoxamine and fluoxetine would have comparable efficacy; and (2) flu- voxamme would be associated with fewer treatment emergent signs and symptoms (TESS) than fiuoxetine, in particular, less problems with insom- nia, agitation, nervousness, restlessness, and anxiety.

After a one-to-two week placebo run-in, patients received double-blind treatment with either f luvoxamine (50-150 mg/day) or f luoxetine (20-80 rag/day) for seven weeks. The Hamilton Depression Rating Scale (HAM-D) was the primary efficacy measure and secondary efficacy measures in- cluded HAM-D factor scores, the Clinical Global Impression Scale (CGI), the Hamilton Psychiatric Rating Scale for Anxiety (HAM-A), the Raskin- Covi Scale and the SCL-56 Vital signs, clinical hematology and biochem- istry tests, adverse events, concomitant medication, and scales for suici- dal ideation (Modified Scale for Suicidal Ideation). and akathisia (Barnes Akathisia Scale) comprised the safety evaluations.

One hundred fifteen patients were screened for the study, with 100 patients randomized: 51 to LUVOX'" and 49 to Prezac ®. The patient charac- tenstics bid not differ between groups and represented a sample of a typical depressed outpatient population. The mean age and gender for f luvoxamine and fluoxetine were 40 and 38.6 years and 60 and 63.8% female, respec- tively. The mean decrease in HAM-D 21-item total score from baseline to week 7 was 15.52 for f luvoxamine (2515 to 9.63) and 15.85 for f luoxetine (25.57 to 972) (p = 0.641 ). There were no statistically significant differences between groups at any visit, including end-point, for the primary efficacy variable (HAM-D 21-item total score). Secondary and supportive measures confirmed the results obtained with the HAM-D.

Sixteen patients did not complete the study (eight in each group), how- ever, only 4 patients discontinued due to adverse events. Clinical laboratory results and vital signs did not reveal any clinically significant changes. In spite of a rather high incidence of treatment emergent adverse events, (100% of fluoxetine patients and 94% of f luvoxamine patients reported at least one adverse event) treatments were well-tolerated, with few drop-outs due to adverse events, The most common adverse events for the fluoxe- tine treated group were headache (53%), nausea (43%). insomnia (28%), diarrhea (28%). and nervousness (23%). The most common adverse events for the f luvoxamine treated group were headache (50%). insomnia (36%}, and nausea (22%). Patients treated with fluoxetine experienced significantly more problems with nausea (p = 0.03). Very few patients were rated as hav- ing measurable suicidal ideation at baseline, and there was no significant change in suicidal ideation at endpoint.

As postulated, f luvoxamine and fluoxetine were equally efficacious for the management of outpatients with major depression. Although we did not find that fluoxetine caused statistically more agitation by rating scale, subjects did report more feelings of nervousness and had significantly more problems with nausea. This suggests that f luvoxamine may afford some benefit in terms of a slightly more favorable side effect profile.

References Lapierre. J et al Treatment of major affective disorder with fluvoxamine (1987). J Clin

Psychiatry, 48, 65~8 Cohn, J B, Wilcox, C. A comparison of fluoxetine, imipramine, and placebo patients with

major affective disorder (1985) J Clin Psychiatry. 45, 26-31.

Safety and tolerability of fluvoxamine in adolescent depression

M Alfonso 1, R. Ferrer 1 , R Such 2. 1 Department of PsychJatm/ Hospita/ de San Rafael, Vail d'Hebrdn, 107, 08035 Barcelona, Spain," 2 Medical Department, So/vay Duphar, Diagonal, 507, 08029 Barcelona, Spain

The study was planned as a double blind pilot study to evaluate the safety and tolerability of two different doses of f luvoxamine (50 mg and 100 rag) during eight weeks of treatment (1 week wash-out period, 7 weeks active treatmentl. Patients of both sexes, with ages between 12 and 18 years diagnosed of major depression, dysthymia, or adaptive disorder with depressed mood according to DSM-III-R were included in the study. Patients in treatment with MAOIs or other SSRIs during the previous two weeks, or lithium during the previous week, and those with systemic disease of clinical relevance were excluded. The patients selected for the study fol lowed a single blind phase of 3 weeks, receiving placebo in the first week (wash- out period), f luvoxamine 25 mg in the second week and f luvoxamine 50 mg m the third week. After this period the patients were allocated in the 50 mg or 100 mg group, receiving this doses for the next 5 weeks. The