The relationship between plasma β-endorphin levels and severity of depression

S151

I?!] Affectioe disorders and antidepressants there were no statistically or clinically significant differences between the groups. 44 Patients in the fluvoxamine group and 42 in the clomipramine group were evaluable for safety. Fluvoxamine was better tolerated than clomipramine. The overall incidence of drug-related adverse events was lower with fluvoxamine than with clomipramine. Most notably, however, the pattern of adverse events was quite different for the two groups; this reflects the different pharmacology of the drugs. Clomipramine was associated with considerably more anticholinergic effects including dry mouth (52% vs 21%), tremor (41% vs 9’/), constipation (27% vs 9%), dizziness (26% vs 7%) and sweating (17% vs 7%). Special senses were affected to a greater extent by clomipramine than fluvoxamine, including accommodation abnormalities (7% vs O%), amblyopia (14% vs 2%) and tinnitus (12% vs 0%). In contrast, fluvoxamine was associated with a somewhat higher incidence of nausea (30% vs 19%): asthenia (9% vs 5%) and vomiting (5% vs 0%). There were no reports of sexual dysfunction in the fluvoxamine group. In addition, the percentage of patients who withdrew prematurely due to adverse events was more than twice as high in the clomipramine group than in the fluvoxamine group (24% vs 11%). In conclusion, fluvoxamine is equally as effective as clomipramine in severe depression but is considerably better tolerated.

CAS scores declined progressively during treatment in both the tluvoxamine and fluoxetine groups. This reflected a reduction in anxiety associated with depression. Scores on the Beck’s Scale for Suicidal Ideation also diminished progressively, with no consistent differences between the fluvoxamine and fluoxetine treated groups. Mean Sleep Evaluation scores improved consistently during treatment. Although the improvement between baseline and day 14 was similar in each group, thereafter sleep improved more in the fluvoxamine group than in the fluoxetine group (7.9 vs 3.3 at day 28 and 10.3 vs 5.2 at day 42). However, these differences did not achieve statistical significance.

Fluvoxamine Fluoxetine

Baseline

Day 7

Day 14

30.9 jz 7.6 31.8 & 7.3

27.1 i 7.7 29.3 f 7.2 0.27

23.0 i 27.1 i 0.096

P (Wilcoxon) 0.8

Day 28 9.5 8.7

Day 42

19.3 zk 10.8 18.6 + II.9 23.4i 10.4 21.1 i 10.5 0.48 0.2

In conclusion, analysis of the secondary efficacy variables in this study reveal interesting differences between fluvoxamine and fluoxetine which merit further investigation.

References [I] Kasper S, Miiller H-J, Montgomery SA, Zondag E (1995) Antidepressant efficacy in relation to item analysis and severity of depression: a placebocontrolled trial of fluvoxamine versus imipmmine. International Clinical Psychopharmacology 9 (Suppl4), 3-12. [2] Mendlewicz J. (I 992) Efficacy of fluvoxamine in severe depression. Drugs 43 (Suppl 2), 32-39. [3] Ottevanger EA. ( 1995) Fluvoxamine and clomipramine in severely depressed hospitalised patients: a randomised, double-blind study. L’Encephale 21, 317321.

[P.1.051]

Fluvoxamine and fluoxetine in the treatment depression; similarities and differences

J. Dalery.

Hopital Neum-Chir, Pierre Wertheimer, Lyon, France

of

Because of the paucity of published comparative studies between different selective serotonin reuptake inhibitors (SSRls), there has been a tendency for these drugs to be considered to be equivalent in all aspects (or for clinical differentiation to be based on anecdotal data). However, they are chemically diverse and a varied pharmacology would be expected. Although some attempts have been made to make distinctions between these drugs (DeVane, 1995; van den Berg, 1995), there are few direct clinical comparisons. The current study was designed to compare the efficacy and tolerability/safety profile of fluvoxamine and fluoxetine under rigorous doubleblind, randomised conditions. The overall efficacy and safety/tolerability results of this study have been presented elsewhere and the two treatments were shown to be broadly equivalent; this presentation will focus on the secondary efficacy variables. Patients meeting DSM-1IIR criteria for Major Depressive Episode, and with a baseline 17-item Hamilton Depression Rating Scale (HAMD-17) score of 17 or more, were eligible for inclusion. Patients were randomised to receive fluvoxamine (50 mg/day for days 1-7, then 100 mgiday for the subsequent 35 days) or fluoxetine (20 mg/day for 42 days). The primary efficacy variable was the HAMD-17, but patients were also evaluated using the Clinical Anxiety Scale (CAS), Irritability, Depression and Anxiety Scale (IDAS), Beck’s Scale for Suicidal Ideation and Sleep Evaluation Scores. IDAS total score fell progressively in both groups at each evaluation; however, the reduction in the fluvoxamine group was consistently greater than that in the fluoxetine group (see Table 1). Although none of the differences were statistically significant, that at day 14 approached significance. Similarly, the mean reduction IDAS anxiety, depression and irritation subscores was greater in the fluvoxamine than in the fluoxetine group at all assessments. The differences were statistically significant at days 7, 14 and 28 for the depression subscore.

References

[ 1]

DeVane CL (1995). Comparative safety and tolerabihty of selective serotonm reuptie inhibitors. Human Psychopharmacology 10, S185-S193. [2] van den Berg SJ (1995). Comparing SSRk: from chemistry to clinical choice. Human Psychopharmacology 10, S199-S209.

-1

The relationship between plasma fi-endorphin levels and severity of depression

M. Ba$iirk, S. Muhtaroglu’, M.F. Karaaslan, A. O&z, A. SimSek, M. Reyhancan. Erciyes University School of Medicine.Departments of Psychiatry; ‘Biochemistry, Kayseri 38039, Turkey Objective: Endorphins are synthesized in the cells of pituitary gland of the hypothalamus and released from the pituitary gland into the peripheral circulation. The role of endorphins in the pathogenesis of psychiatric disorders has stimulated considerable interest in recent years. Although several studies performed on depressed patients have showed a deficiency in endorphin activity, plasma studies of endorphins in depressive disorders have produced conflicting results so far. Risch et al (1982) reported plasma fi-endorphin levels to be higher in patients with depressive and schizoaffective disorders compared to controls. Alexopoulos et al (1983) found no difference between depressed and normal subjects. In this study, we investigated plasma @-endorphin levels in patients with major depressive disorder (MDD) in relation to their severity of illness. Methods: Thirty-six drug free (at least for 2 weeks) patients with MDD (17 females, 19 males; mean f SD age: 48.60 & 13.20) who met DSM-IV criteria for major depressive disorder (APA 1994) and 13 healthy subjects (6 females, 7 males; mean ZIISD age: 38.70 & 10.00) chosen among the hospital staff were included in the study. The severity of depression were evaluated with Hamilton Depression Rating Scale (HAM-D) and Montgomery Asberg Depression Rating Scale (MADRS). Venous blood was collected at 08.00 a.m. and plasma p-endorphin level was determined by using standard RIA (Nichols Instiute Diagnostics P-endorphin B.N kits. ND). Results: Mean values (i SD) of plasma P-endorphin were 132.76 * 28.78 pg/ml in the depressed group and 116.06 i 21.26 pg/ml in the control group. There was a significant difference between the depressed and the control groups in plasma fi-endorphin levels (t = 2.66 p < 0.05). There was also a significant correlation between plasma p-endorphin levels and HAM-D and MADRS scores (r = 0.5 p < 0.05 and r = 0.5 p < 0.05, respectively). Conclusion: Our data showing that plasma b-Endorpin levels are higher in patients with MDD compared to controls and they correlate

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