Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects. Comparison of the effects of sertraline and its metabolite desmethylsertraline on blockade of central 5-HT reuptake in vivo. [Reports of suspected side effects of selective serotonin reuptake inhibitors in Belgium and The Netherlands] Rx drugs

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Int Clin Psychopharmacol. 1996 Sep;11(3):165-75.
Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects.

Menting JE, Honig A, Verhey FR, Hartmans M, Rozendaal N, de Vet HC, van Praag HM.

Department of Psychiatry and Neuropsychology, University of Limburg Maastricht, The Netherlands.

A qualitative analysis of studies on the efficacy and side-effects of selective serotonin reuptake inhibitors (SSRIs) for the treatment of elderly people with depression is presented. Only placebo-controlled or comparison studies of SSRI versus other antidepressants were included. The description and methodological quality of the analysed studies were important criteria in the outcome of the analysis. Quality was assessed by means of a blinded review approach. After excluding duplicate publications, 16 studies were analysed, of which six turned out to be of good quality. The results indicated that at the end of the treatment periods (4-8 weeks) all antidepressants were equally effective. Side-effects occurred less frequently with SSRIs than with tricyclics (TCAs), and different side-effect profiles were found. Significantly fewer SSRI-treated patients than TCA-treated patients dropped out both overall and due to side-effects.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8923095&dopt=Abstract

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Neuropsychopharmacology. 1996 Apr;14(4):225-31.
Comparison of the effects of sertraline and its metabolite desmethylsertraline on blockade of central 5-HT reuptake in vivo.

Sprouse J, Clarke T, Reynolds L, Heym J, Rollema H.

Department of Neuroscience, Pfizer Central Research, Groton, CT 06340, USA.

N-demethylation of the selective serotonin reuptake inhibitor sertraline to desmethylsertraline yields a compound with 10- to 20-fold less potency at blocking serotonin (5-HT) reuptake as measured in vitro. In the present study desmethylsertraline (DMS) was examined in two in vivo models of reuptake inhibition--elevation of extracellular 5-HT in the corpus striatum as measured by microdialysis and inhibition of firing of serotonin-containing dorsal raphe neurons. Whereas sertraline (1, 3.2, and 10 mg/kg s.c.) produced a dose-dependent increase in extracellular 5-HT and a decrease in 5-HIAA in rat striatum, desmethylsertraline was without effect on either parameter. In similar fashion, desmethylsertraline had no effect on dorsal raphe cell firing at a dose (1,000 micrograms/kg i.v.) nearly 20-fold the ED50 for sertraline (52 micrograms/kg). Taken together, these data suggest that DMS does not contribute to the blockade of central 5-HT reuptake produced by sertraline in vivo and therefore would be expected to play a negligible role in its clinical activity.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8924190&dopt=Abstract

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Ned Tijdschr Geneeskd. 1996 Sep 7;140(36):1817-20.
[Reports of suspected side effects of selective serotonin reuptake inhibitors in Belgium and The Netherlands]

[Article in Dutch]

Van Ermen AM, Ottervanger JP, Roisin T, Kurz X, Stricker BH.

Ministerie van Sociale Zaken, Volksgezondheid en Leefmilieu, Belgisch Centrum voor Geneesmiddelenbewaking, Brussel.

OBJECTIVE: To study the adverse drug reaction (ADR) profile of selective serotonin re-uptake inhibitors (SSRI) in Belgium and the Netherlands. DESIGN: Descriptive study. SETTING: The Belgian Pharmacovigilance Centre and the Dutch Drug Safety Unit. METHOD: All adverse reactions of fluoxetine, fluvoxamine, paroxetine and sertraline, reported between the moment of registration of these drugs and January 1st 1995, were assessed for causality. Possible, probable and certain adverse reactions were counted per drug and per country. RESULTS: At the national monitoring centres of Belgium and of the Netherlands adverse reactions were reported 78 and 537 times, respectively. Approximately 30% of the adverse reactions were well-established. Approximately 60% of the reactions were poorly documented or not serious. Less than 1% of the adverse reactions reported in Belgium and approximately 13% of the reactions reported in the Netherlands, were less established and/or serious. These reactions were: movement disorders and extrapyramidal reactions, convulsions, galactorrhoea, hyponatraemia and syndrome of inappropriate antidiuretic hormone secretion, and purpura. CONCLUSION: The ADR profile was compatible with the ADR profile in the medical literature, but not all ADR were similarly represented in the product information of the different SSRI. More adverse reactions were reported in the Netherlands than in Belgium.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8927144&dopt=Abstract

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