sertraline, Zoloft
Determination of sertraline and desmethylsertraline in human serum using copolymeric bonded-phase extraction, liquid chromatography and gas chromatography-mass spectrometry.

Rogowsky D, Marr M, Long G, Moore C.

United Chemical Technologies, Bristol, PA 19007.

The determination of the new antidepressant drug sertraline and its main metabolite, desmethylsertraline, in human serum is described. A new solid-phase extraction method employing the dual functionality Clean Screen cartridge is presented followed by reversed-phase liquid chromatographic (LC) analysis. The sample preparation yielded extremely clean extracts and absolute recoveries in excess of 90% for both drugs from human serum. The response of the LC system was linear over the concentration range 0.01-2.5 mg/l for both sertraline and desmethylsertraline with a limit of detection of 0.01 mg/l. A gas chromatographic-mass spectrometric (GC-MS) system is also described should confirmation of the drugs be necessary.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8061822&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Selective serotonin reuptake inhibitor dose titration in the naturalistic setting.

Gregor KJ, Overhage JM, Coons SJ, McDonald RC.

Center for Pharmaceutical Economics, College of Pharmacy, University of Arizona, Tucson.

Little information exists regarding the use of selective serotonin reuptake inhibitors (SSRIs) in the naturalistic setting. The Regenstrief Medical Record System was used to analyze the dosing of SSRIs in the outpatient population of an urban teaching hospital. A cohort of 3350 patients was extracted, of whom 2859 had received fluoxetine and 460 sertraline. This cohort received 21,079 prescriptions. (The 31 patients who were prescribed paroxetine were eliminated from further analysis.) The mean daily dose for all patients receiving fluoxetine was 21 +/- 6 mg for the first prescription dispensed and 25 +/- 11 mg for the ninth. For fluoxetine-treated patients with depression included on their computerized medical problem list, the mean daily dose was 21 +/- 6 mg for the first prescription and 26 +/- 12 mg for the ninth. A mean of 5.0% of all patients continuing fluoxetine therapy had their daily dose increased with each prescription refill during the first nine prescriptions. The mean daily dose for all patients receiving sertraline was 59 +/- 28 mg for the first prescription and 117 +/- 66 mg for the ninth. For sertraline-treated patients with depression included on their computerized medical problem list, the mean daily dose was 57 +/- 25 mg for the first prescription and 110 +/- 65 mg for the ninth. A mean of 14.9% of all patients continuing sertraline therapy had their daily dose increased with each prescription refill during the first nine prescriptions. The frequency of sertraline dose increases was 2 to 3 times the rate for fluoxetine. Because increases in daily doses typically result from inadequate control of symptoms of depression, these findings may reflect fluoxetine's greater effectiveness in controlling symptoms during the initial stages of therapy in the naturalistic setting.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8062324&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Interface between authorship, industry and science in the domain of therapeutics.

Healy D, Cattell D.

North Wales Department of Psychological Medicine, University of Wales College of Medicine, Bangor, UK. Healy_Hergest compuserve.com

BACKGROUND: Changes in the character of medical authorship. Aims To compare the impact of industry-linked and non-industry linked articles. METHOD: We compared articles on sertraline being coordinated by a medical writing agency with articles not coordinated in this way. We calculated numbers of Medline-listed articles per author, journal impact factors, literature profiles and citation rates of both sets of articles. RESULTS: Non-agency-linked articles on sertraline had an average of 2.95 authors per article, a mean length of 3.4 pages, a mean Medline listing of 37 articles per author (95% CI 27-47) and a mean literature profile of 283 per article (95% CI 130-435). Agency-linked articles on sertraline had an average of 6.6 authors per article, a mean length of 10.7 pages, a mean Medline listing of 70 articles per author (95% CI 62-79) and a mean literature profile of 1839 per article (95% CI 1076-2602). The citation rate for agency articles was 20.2 (95% CI 13.4-27.0) and for non-agency articles it was 3.7 (95% CI 3.3-8.1). CONCLUSIONS: The literature profiles and citation rates of industry-linked and non-industry-linked articles differ. The emerging style of authorship in industry-linked articles can deliver good-quality articles, but it raises concerns for the scientific base of therapeutics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12835239&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Effect of chronic antidepressant treatment on responses to apomorphine in selectively bred rat strains.

Pucilowski O, Overstreet DH.

Skipper Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, School of Medicine 27599-7175.

The purpose of this study was to verify the dopamine-sensitizing behavioral effect of chronic antidepressant treatment in two selectively bred rat strains: the hypercholinergic Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL). Two antidepressants, desipramine HCl (DMI) and sertraline HCl, were injected IP in separate groups of FSL and FRL rats in a dose of 16.5 mumol/kg twice daily for 16 days. Twenty-four hours after withdrawal, locomotor and hypothermic responses to 0.2 mg/kg of apomorphine, SC, were examined. Attenuation of the effect of apomorphine was observed in the open field: FRLs withdrawn from sertraline were significantly less mobile than control FRLs, and the same trend was found in FSL rats. Chronic DMI resulted in similar changes in the locomotor activity. Sertraline treatment decreased apomorphine-induced hypothermia by almost half in FSLs, whereas slight hyperthermia was induced in FRL rats instead. The present results suggest that in these selectively bred strains, a serotonergic antidepressant such as sertraline may have sensitized dopaminergic autoreceptors and/or desensitized postsynaptic receptors. Apomorphine-induced hypothermia could be mediated by serotonergic neuron function that may have been altered by chronic sertraline but not DMI treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8221139&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Modification of the N-methyl-D-aspartate response by antidepressant sigma receptor ligands.

Bergeron R, Debonnel G, De Montigny C.

Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Sertraline, a selective serotonin reuptake inhibitor, and clorgyline, a monoamine oxidase inhibitor, both of which have high affinity for sigma receptors, were assessed in an electrophysiological model. In keeping with previous data obtained with other sigma receptor ligands, low doses of sertraline and of clorgyline potentiated selectively with a bell-shaped dose-response curve the effect of N-methyl-D-aspartate (NMDA) on pyramidal neurons in the CA3 region of the rat dorsal hippocampus. This potentiation was reversed by the sigma receptor ligands haloperidol and BMY-14802. The selective serotonin reuptake inhibitor paroxetine and the monoamine oxidase inhibitor tranylcypromine, both devoid of affinity for sigma receptors, had no effects on the NMDA response. These data suggest that the effects of sertraline and clorgyline on the NMDA response are due to their affinity for sigma receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8243549&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Lithium augmentation in sertraline-resistant depression: a preliminary dose-response study.

Dinan TG.

Department of Psychological Medicine, St Bartholomew's Hospital, London, United Kingdom.

Eleven patients with DSM-III-R major depression who were treatment-resistant to sertraline were allocated for lithium augmentation therapy. In conjunction with their sertraline, 6 received lithium carbonate 400 mg at night and 5 received 800 mg at night. A total of 7 patients responded within 1 week. The degree of response was not related to the serum lithium level. Patients with lithium levels as low as 0.3 mEq/l responded. No significant side effects were reported.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8256650&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Serotonin and cardiac morphogenesis in the mouse embryo.

Yavarone MS, Shuey DL, Tamir H, Sadler TW, Lauder JM.

Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599-7090.

The possible involvement of the neurotransmitter serotonin (5-HT) and its binding protein (SBP) in cardiac morphogenesis was studied using mouse whole embryo culture (together with immunocytochemistry or 3H-thymidine autoradiography) and a cell migration assay. Embryos were cultured before and during the period of endocardial cushion formation, embryonic (E) days 9-12, in the presence of 5-HT, the monoamine oxidase (MAO) inhibitor nialamide, or an uptake inhibitor (fluoxetine or sertraline). For the migration assay, cells from the outflow tracts of E12 embryos were dissociated and placed in a chemotaxis chamber together with different concentrations of 5-HT. E9 embryos cultured in the presence of 10 microM 5-HT and nialamide exhibited intense 5-HT immunoreactivity (5-HT IR) throughout the myocardium. This staining was greatly diminished by fluoxetine, sertraline, or the absence of nialamide. As morphogenesis proceeded, myocardial staining in embryos exposed to 5-HT became restricted to developing endocardial cushion forming regions and was more completely blocked by uptake inhibitors. No evidence for 5-HT synthesis by myocardium was found at any age studied using the precursor L-tryptophan. SBP was present in endocardial cushions in cultured and uncultured embryos. 3H-thymidine autoradiography demonstrated that both fluoxetine and sertraline inhibited proliferation of cardiac mesenchyme, endocardium, and myocardium. These effects were most pronounced when exposure began at E9 (prior to cushion formation). Dose-dependent effects of 5-HT on migration of outflow tract cells were also observed. Taken together, these results suggest that 5-HT may play a role in cardiac morphogenesis during endocardial cushion formation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8367830&dopt=Abstract sertraline Zoloft