sertraline, Zoloft
The extent and determinants of changes in CYP2D6 and CYP1A2 activities with therapeutic doses of sertraline.

Ozdemir V, Naranjo CA, Herrmann N, Shulman RW, Sellers EM, Reed K, Kalow W.

Psychopharmacology Research Program, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.

The extent of changes in CYP2D6 and CYP1A2 activities with higher therapeutic dosages (>50 mg/day) of sertraline is not well established in vivo. This study assessed the extent and determinants of changes in CYP2D6 and CYP1A2 isozyme activities after treatment with clinically relevant doses of sertraline. Patients and healthy volunteers aged 19 to 85 years (N = 21) were treated with sertraline for 5 to 55 days. The dosage of sertraline ranged from 25 to 150 mg/day (93.5+/-26.4 mg/day; mean +/- SD). All subjects had an extensive metabolizer phenotype for CYP2D6 and received a single oral dose of dextromethorphan (30 mg) and caffeine (100 mg) before and after sertraline treatment. The log O-demethylation ratio (ODMR) of dextromethorphan and the caffeine metabolic ratio (CMR) in overnight urine were used as in vivo indices of the CYP2D6 and CYP1A2 isozyme activities, respectively. Concurrent medications and lifestyle habits (e.g., smoking and diet) were monitored during the study. Baseline log ODMR (-2.33+/-0.45) but not CMR (5.1+/-1.9) (mean +/- SD) significantly changed after sertraline treatment (-2.19+/-0.62; 4.5+/-1.6, respectively) (p: ODMR = 0.04, CMR = 0.10). There was no significant effect of age, dose, duration of treatment, gender, sertraline and/or desmethylsertraline plasma concentration, subject type (patient or volunteer), and weight on the extent of changes in log ODMR or CMR (p > 0.05). In conclusion, sertraline treatment at a mean daily dosage of 94.0 mg did not significantly change CYP1A2 activity and resulted in a modest inhibition of CYP2D6 activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9472843&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
[The effect of sertraline on cognitive functions in patients with obsessive-compulsive disorder]

[Article in Polish]

Borkowska A, Pilaczynska E, Araszkiewicz A, Rybakowski J.

Katedra i Klinika Psychiatrii AM w Bydgoszczy.

The aim of this study was to assess the effect of sertraline on psychopathological symptoms and cognitive functions and in patients with obsessive compulsive disorder (OCD). The investigated group consisted of 25 patients with OCD (12 male, 13 female) aged 17-47 (mean 29 +/- 9) years, duration of illness was 1-15 (mean 4 +/- 2) years. After treatment with sertraline, a significant improvement in OCD symptoms measured by YBOCS and in neuropsychological "frontal" tests were observed. Little correlation was found between the effect of sertraline on OCD symptoms and on cognitive dysfunctions. This may suggest that these two effects may be connected with different pharmacological properties of the drug. The effect of sertraline on OCD symptoms, similarly like other drugs inhibiting serotonin transporter (clomipramine, other SSRI) is associated with its influence on serotonergic system. On the other hand, the effect of sertraline on dopaminergic neurotransmission may be related to its favorable action on cognitive functions connected with the activity of frontal lobe.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12647451&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Withdrawal reactions with selective serotonin re-uptake inhibitors as reported to the WHO system.

Stahl MM, Lindquist M, Pettersson M, Edwards IR, Sanderson JH, Taylor NF, Fletcher AP, Schou JS.

Pharmacoepidemiology Unit, Medical Products Agency (MPA), Uppsala, Sweden.

OBJECTIVE: The present study was performed both to investigate whether there might be a difference between the selective serotonin re-uptake inhibitors, (SSRIs) with regard to the incidence of withdrawal reactions, and to describe the associated symptoms. From the WHO database, therefore, all case reports from the year of introduction for each of the SSRIs, fluoxetine, paroxetine and sertraline, were retrieved. Sales figures were obtained from Intercontinental Medical Statistics International. The reporting rates were calculated as the number of reports per million defined daily doses (DDDs) sold per year. RESULTS: The reporting rate of withdrawal reactions for paroxetine was found to be higher than that for sertraline and fluoxetine in each of the countries selected for detailed analyses (US, UK and Australia), as well as for all 16 countries combined. Moreover, using the WHO system of organ classification, the ratio of central nervous system to psychiatric withdrawal symptoms was 1.9 and 2.1 for paroxetine and sertraline, respectively, whereas that for fluoxetine was 0.48, indicating a possible qualitative difference between the SSRIs with respect to the nature of the withdrawal syndrome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9476026&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Sertraline does not inhibit cytochrome P450 3A-mediated drug metabolism in vivo.

Preskorn SH, Alderman J, Greenblatt DJ, Horst WD.

Psychiatric Research Institute, Wichita, KS 67214, USA.

The in vivo effect of sertraline on oxidative drug metabolism mediated by cytochrome P450 (CYP) 3A was assessed by coadministration with alprazolam, carbamazepine, and terfenadine in three separate studies. Sertraline at doses of 50 to 200 mg/day for 10 to 20 days did not alter the pharmacokinetics of these CYP3A substrates/drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9493476&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Inhibition of P-glycoprotein by newer antidepressants.

Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE.

Department of Internal Medicine VI, Clinical Pharmacology, and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany. Johanna_weiss med.uni-heidelberg.de

Pharmacokinetic drug-drug interactions often occur at the level of P-glycoprotein (Pgp). To study possible interactions caused by the newer antidepressants we investigated citalopram, fluoxetine, fluvoxamine, paroxetine, reboxetine, sertraline, and venlafaxine and their major metabolites desmethylcitalopram, norfluoxetine, paroxetine-metabolite (paroxetine-M), desmethylsertraline, N-desmethylvenlafaxine, and O-desmethylvenlafaxine for their ability to inhibit Pgp. Pgp inhibition was studied by a fluorometric assay using calcein-acetoxymethylester as Pgp substrate and two different cell systems: L-MDR1 cells (model for human Pgp) and primary porcine brain capillary endothelial cells (pBCECs, model for the blood-brain barrier). Both cell systems proved to be suitable for the evaluation of Pgp inhibitory potency of drugs. All antidepressants tested except O-desmethylvenlafaxine showed Pgp inhibitory activity with sertraline, desmethylsertraline, and paroxetine being the most potent, comparable with the well known Pgp inhibitor quinidine. In L-MDR1 cells fluoxetine, norfluoxetine, fluvoxamine, reboxetine, and paroxetine-M revealed intermediate Pgp inhibition and citalopram, desmethylcitalopram, venlafaxine, and N-desmethylvenlafaxine were only weak inhibitors. The ranking order was similar in pBCECs. The fact that some of the compounds tested exert Pgp inhibitor effects at similar concentrations as quinidine suggests that pharmacokinetic drug-drug interactions between the newer antidepressants and Pgp substrates should now be thoroughly studied in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12649369&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Sertraline in diabetic neuropathy: preliminary results.

Goodnick PJ, Jimenez I, Kumar A.

Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Florida 33136, USA.

Previous research has shown that antidepressants have been useful in the treatment of pain, particularly diabetic neuropathy. This study was an initial open investigation into the use of sertraline in diabetic neuropathy. Eight patients with diabetic neuropathy but not depression were treated with increasing doses of sertraline to a maximum of 150 mg/day for 8 weeks. Sertraline treatment led to significant reductions in mean visual analog scale (VAS) ratings, e.g., pain from 71.2 to 23.1 (t = 3.74, p < .01) and paresthesias from 53.8 to 15.0 (t = 4.15, p < .01). Baseline platelet serotonin (5HT) content also correlated significantly with improvement in pain (r = 0.70,p =. 05). Plasma sertraline (SRT) correlated with improvement in paresthesias (r = 0.70). Conclusion: This preliminary result indicates the potential application of sertraline to treatment of diabetic neuropathy. A replication is now underway.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9511950&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Effects of imipramine and sertraline on protein kinase activity in rat frontal cortex.

Tadokoro C, Kiuchi Y, Yamazaki Y, Oguchi K, Kamijima K.

Department of Psychiatry, School of Medicine, Showa University, Tokyo, Japan.

Three-week administration of sertraline or imipramine to rats (10 mg/kg, intraperitoneally, twice a day) increased ex vivo cyclic AMP-dependent protein kinase activity in the soluble but not in the particulate fraction of the frontal cortex. However, cyclic AMP-dependent protein kinase activity was not affected in either fraction of the parietotemporal cortex and hippocampus. Neither antidepressant altered protein kinase C activity in the soluble and particulate fractions or Ca2+/calmodulin-dependent protein kinase II activity in the frontal cortex. Therefore, sertraline and imipramine both selectively enhance cyclic AMP-dependent protein kinase activity in the frontal cortex. This enhancement might be involved in their biochemical mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9544792&dopt=Abstract sertraline Zoloft