sertraline, Zoloft
Sertraline, a selective serotonin reuptake inhibitor modulates extracellular noradrenaline in the rat frontal cortex.

Thomas DN, Nutt DJ, Holman RB.

University of Bristol, Psychopharmacology Unit School of Medical Sciences, UK.

The selective action of selective serotonergic reuptake inhibitors (SSRIs) on 5-hydroxytryptamine (5-HT) neurotransmission underlies the therapeutic effectiveness of this class of drugs. Yet there is increasing evidence that changes in extracellular 5-HT content may result in changes in the regulation of other neurotransmitter systems. The present study examines the effects of acute and chronic administration of the SSRI sertraline on release of endogenous noradrenaline (NA) in the frontal cortex and hippocampus of the rat using in vivo microdialysis. Acute administration of sertraline did not significantly alter NA release in either the cortex or the hippocampus. However, 24 h after chronic (14 days) administration of the drug (10 mg/kg i.p. once daily), NA release in the cortex but not hippocampus was significantly enhanced. The lack of an effect on NA release following a challenge with the alpha2-antagonist idazoxan suggests that chronic drug treatment has reduced the sensitivity of cortical pre-synaptic alpha2-adrenoceptors, activation of which would normally inhibit further NA release. The possible mechanisms underlying the regional specificity of the effect of chronic and not acute sertraline administration and the implications of these results for our understanding of depression are discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10065910&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
A comparison of the effects of different serotonin reuptake blockers on sexual behaviour of the male rat.

Mos J, Mollet I, Tolboom JT, Waldinger MD, Olivier B.

Department of Pharmacology, Solvay Pharmaceuticals, Weesp, The Netherlands.

In human males, SSRIs differentially affect (premature) ejaculation; paroxetine and fluoxetine markedly and sertraline, moderately inhibited ejaculation latency, whereas fluvoxamine did not inhibit this parameter (Waldinger, M.D., Hengeveld, M.W., Zwinderman, A.H., Olivier, B., The effect of SSRI antidepressants on ejaculation: a double-blind, randomised, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine and sertraline. J. Clin. Psychopharmacol. (in press)). The present studies tried to investigate, using sexual behaviour in male rats, whether such differences could also be found in animal paradigms of sexual behaviour. In a series of three experiments we compared various specific serotonin reuptake inhibitors (SSRIs) for their ability to suppress sexual behaviour in male rats. In the first experiment sexually experienced rats were tested 60 min after oral administration of clomipramine, fluvoxamine, fluoxetine (all in a range of 0, 3, 10 and 30 mg/kg p.o.), sertraline or paroxetine (both in a range of 0, 1, 3 and 10 mg/kg p.o.). Clomipramine, paroxetine and fluvoxamine did not significantly inhibit male sexual behaviour, although some trends were observed. Sertraline inhibited sexual behaviour at 3 and 10 mg/kg p.o., the effects being stronger at 3 mg/kg p.o. Fluoxetine (3 mg/kg p.o.) facilitated sexual behaviour, while at 30 mg/kg p.o. a modest increase in the postejaculatory interval was noted. In the second experiment, sexual behaviour of sexually naive male rats was slightly inhibited by paroxetine 10 mg/kg p.o., but sertraline (range 1-10 mg/kg p.o.), fluvoxamine and fluoxetine (both in a range of 3-30 mg/kg p.o.) were ineffective. In the last experiment the effects of paroxetine (0-10 mg/kg p.o.), fluvoxamine and fluoxetine (both 0-30 mg/kg p.o.) were studied during an exhaustion design in sexually experienced male rats. As rats get more 'sluggish' when they have had multiple ejaculations, we hoped to see stronger inhibitory effects in the last cycle prior to exhaustion. None of the drugs dose-dependently inhibited the pattern of sexual behaviour during the first sexual cycle. In the last cycle the patterning of sexual behaviour differed, but only paroxetine (10 mg/kg p.o.) inhibited sexual behaviour significantly. The total number' of ejaculations during the test was not reduced by any of the SSRIs tested. Contrary to human findings, we did not find major inhibitory effects of SSRIs on male rat sexual behaviour at non-sedative doses. The only differentiation that could be made is that paroxetine and sertraline had slightly stronger effects than the other 5-HT reuptake inhibitors. Masculine sexual behaviour in rats does not constitute a suitable model to investigate the differential mechanism of sexual inhibition of SSRIs that have been described in human males.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10082238&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
A cost-effective approach to the use of selective serotonin reuptake inhibitors in a Veterans Affairs Medical Center.

Singletary T, North DS, Weiss M, Marman G.

Denver VA Medical Center, Denver, CO 80220, USA.

In light of the tremendous expansion in the number of selective serotonin reuptake inhibitors available to the clinician, the Pharmacy and Therapeutics Committee of the Denver Veterans Affairs Medical Center considered the advantages and disadvantages of fluoxethine, paroxetine, and sertraline, to determine which agent or agents would be carried on the formulary. The committed recommended sertraline as the preferred agent for the treatment of depression, panic disorders, and obsessive-compulsive disorders. The purpose of this retrospective study was to assess the economic outcome of that decision. The study population consisted of patients at the medical center who were receiving selective serotonin reuptake inhibitors during January through March of 1994 and those were receiving these agents between September 1995 and January 1996. The expanded collection period in 1995-96 was due to a relatively new medical center policy to offer 90-day fills on medication to reduce costs. The extended collection period assured a 100% sample of patients receiving these agents. The 1994 fluoxetine to sertraline dosage equivalency ratio was 20 mg:55.6 mg, based on average daily doses of fluoxetine and sertraline of 32.7 and 90.9 mg, respectively. The cost to the medical center for an average daily dose of fluoxetine was $1.86; sertraline cost $1.22 per day. The 1996 fluoxetine to sertraline dosage equivalency ratio (20 mg:51.3 mg) had not changed significantly since 1994, indicating that the dose of 20 mg of fluoxetine remained very close to a 50-mg dose of sertraline. The average daily doses of fluoxetine and sertraline (34.9 mg and 89.7 mg, respectively) were not significantly different than the 1994 doses. Only 33 patients had been prescribed paroxetine (average daily dose, 32.4 mg). On the basis of these values, the average daily cost of fluoxetine to the medical center was $2.01, compared with $1.18 for sertraline and $1.24 for paroxetine. This $0.83 per patient per day drug acquisition cost difference between fluoxetine and sertraline results in a drug cost reduction of $302,674 per year.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10169244&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Regulation of CCK mRNA expression in the rat brain by stress and treatment with sertraline, a selective serotonin re-uptake inhibitor.

Giardino L, Bettelli C, Pozza M, Calza L.

Institute of Otolaryngology II, University of Milano, Milan, Italy.

In this paper, we have investigated the regulation of CCK mRNA expression in the brain after restraint stress with and without long-term treatment with the selective serotonin reuptake inhibitor sertraline. Stress alone increases CCK mRNA levels in the hippocampus, whereas no changes were found in the cerebral cortex, amygdaloid complex and thalamus. CCK mRNA expression decreases in the hippocampus, increases in the thalamus and was not modified in the cerebral cortex and amygdaloid complex after sertraline alone. CCK mRNA content was unchanged in all investigated areas after stress plus sertraline compared to control rats. Copyright 1999 Published by Elsevier Science B.V.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10196464&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Fluoxetine and sertraline dosages in major depression.

Cantrell R, Gillespie W, Altshuler L.

Department of Psychiatry, UCLA, CA 90095-7057, USA.

In a retrospective study, we sought to determine medication dosages usually prescribed to obtain euthymia in 59 outpatients with a diagnosis of major depression treated with fluoxetine or sertraline. Charts of veterans admitted to the outpatient mental health clinic at the West Los Angeles Veterans Hospital with a diagnosis of major depression and treated with either fluoxetine or sertraline were reviewed. Progress notes were analyzed for a 6-month time period after the initiation of the medication treatment, and improvement was rated by a physician blind to the drug used for treatment. No significant differences were found in overall response rates between the fluoxetine (81% responders) and sertraline (76% responders) groups. Eighty-one percent of the fluoxetine responders compared to 32% of sertraline responders were at the manufacturer's recommended starting dose (MRSD) at the time of clinical response. One-third of patients receiving sertraline were started on or rapidly titrated to more than 50 mg/day. When only those patients receiving an adequate trial of sertraline at 50 mg were considered, 47% required a dose increase to achieve a remission. These data suggest that 50 mg of sertraline may be inadequate for some patients to achieve a resolution of symptoms of major depression and that many clinicians currently prescribe in a manner suggesting that they believe the MRSD is a suboptimal dosage.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10207663&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Possible alteration of tryptophan metabolism following repeated administration of sertraline in the rat brain.

Nakayama K, Katsu H, Ando T, Nakajo R.

Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan. kazu-n yb3.so-net.ne.jp

The levels of tryptophan and the serotonin (5-HT) turnover were examined in various brain regions of rats after single or repeated treatment with the selective 5-HT uptake inhibitor, sertraline. A single administration of sertraline (10mg/kg, i.p.) increased tryptophan and 5-HT levels in all the brain regions investigated. The levels of 5-hydroxyindolacetic acid (5-HIAA) decreased in various brain regions. The 5-HIAA/5-HT ratio as turnover index was significantly decreased by a single administration of sertraline in all the brain regions investigated. Daily treatment with sertraline (10mg/kg) for 21 days did not affect tryptophan and 5-HT levels in various brain regions 1h after last injection. The 5-HT turnover was not changed in any of the brain regions investigated by a repeated administration of sertraline. In conclusion, the data show that the increase in tryptophan levels and the decrease in 5-HT turnover in rat brain are attenuated by repeated treatment of sertraline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12464401&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
The potentiating effect of sertraline and fluoxetine on amphetamine-induced locomotor activity is not mediated by serotonin.

Sills TL, Greenshaw AJ, Baker GB, Fletcher PJ.

Biopsychology Section, Centre for Mental Health and Drug Addiction, Toronto, Canada. terrence paych.toronto.edu

Sertraline dose-dependently increased the locomotor stimulating effect of amphetamine. At the highest dose, 20 mg/kg sertraline had a biphasic effect on amphetamine-induced hyperactivity, producing an initial reduction in amphetamine-induced hyperactivity that was later followed by an augmentation of amphetamine-induced hyperactivity in the last hour of the 3-h test. Sertraline, at doses of 5 and 10 mg/kg, produced an augmentation of amphetamine-induced hyperactivity over the last 2 h of the 3-h test session. Further, there was an increase in the concentration of amphetamine in the brain in rats pretreated with 5 mg/kg sertraline. Both sertraline (5 mg/kg) and fluoxetine (5 mg/kg) produced an augmentation of amphetamine-induced hyperactivity that was unaltered by a serotonergic lesion of the median and dorsal raphe nuclei that resulted in a greater than 90% depletion of serotonin in hippocampus, striatum, and nucleus accumbens. Further, both sertraline and fluoxetine inhibited spontaneous locomotor activity and this effect was also unaltered by the depletion of serotonin. Thus, serotonergic neurotransmission is not essential for the effects of sertraline and fluoxetine on spontaneous and amphetamine-induced locomotion. It is probable that sertraline and fluoxetine augment the locomotor stimulatory effect of amphetamine by decreasing the metabolism of amphetamine, perhaps via actions on cytochrome P450 isozymes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10367561&dopt=Abstract sertraline Zoloft