Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new sertraline research articles will be listed here shortly after becoming available to us.
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Medical research on sertraline
Fatal intoxication with milnacipran.
J Forensic Leg Med. 2008 Aug; 15(6): 388-90
Fanton L, Bévalot F, Grait H, Meur CL, Gaillard Y, Malicier D
The antidepressant milnacipran is a double serotonin/noradrenalin reuptake inhibitor. The low reported incidence of intoxication indicates excellent tolerance in comparison with tricyclic and second generation antidepressants. We report a fatal intoxication associating milnacipran, at blood levels (femoral=21.5mg/l, cardiac=20mg/l) 40-fold higher than the usual treatment concentration, and six other molecules (fluoxetine, norfluoxetine, sertraline, cyamemazine, nordazepam and oxazepam) at therapeutic levels. To the best of our knowledge, this is the first reported fatal intoxication involving milnacipran.
J Pharm Biomed Anal. 2008 May 17;
Youdim KA, Lyons R, Payne L, Jones BC, Saunders K
The current study focused on the development of an automated IC(50) cocktail assay in a miniaturized 384 well assay format. This was developed in combination with a significantly shorter high pressure liquid chromatography (HPLC) separation and liquid chromatography-mass spectrometry (LC-MS/MS) run-time; than those currently reported in the literature. The 384-well assay used human liver microsomes in conjunction with a cocktail of probe substrates metabolized by the five major CYPs (tacrine for CYP1A2, diclofenac for CYP2C9, (S)-mephenytoin for CYP2C19, dextromethorphan for CYP2D6 and midazolam for CYP3A4). To validate the usefulness of the automated and analytical methodologies, IC(50) determinations were performed for a series of test compounds known to exhibit inhibition across these five major P450s. Eight compounds (sertraline, disulfuram, ticlopidine fluconazole, fluvoxamine, ketoconazole, miconazole, paroxetine, flunitrazepam) were studied as part of a cocktail assay, and against each CYPs individually. The data showed that the IC(50)s generated with cocktail incubations did not differ to a great extent from those obtained in the single probe experiments and hence unlikely to significantly influence the predicted clinical DDI risk. In addition the present method offered a significant advantage over some of the existing cocktail analytical methodology in that separation can be achieved with run times as short as 1min without compromising data integrity. Although numerous studies have been reported to measure CYP inhibition in a cocktail format the need to support growing discovery libraries not only relies on higher throughput assays but quicker analytical run times. The current study reports a miniaturized high-throughput cocktail IC(50) assay, in conjunction with a robust, rapid resolution LC-MS/MS end-point offered increased sample throughput without compromising analytical sensitivity or analyte resolution.
Seizures induced by the combination treatment of methylphenidate and sertraline.
J Child Adolesc Psychopharmacol. 2008 Jun; 18(3): 301-3
Schertz M, Steinberg T
Exercise fails to improve neurocognition in depressed middle-aged and older adults.
Med Sci Sports Exerc. 2008 Jul; 40(7): 1344-52
Hoffman BM, Blumenthal JA, Babyak MA, Smith PJ, Rogers SD, Doraiswamy PM, Sherwood A
PURPOSE:: Although cross-sectional studies have demonstrated an association between higher levels of aerobic fitness and improved neurocognitive function, there have been relatively few interventional studies investigating this relationship, and results have been inconsistent. We assessed the effects of aerobic exercise on neurocognitive function in a randomized controlled trial of patients with major depressive disorder (MDD). METHODS:: Two-hundred and two sedentary men (n = 49) and women (n = 153), aged 40 yr and over and who met diagnostic criteria for MDD, were randomly assigned to the following: a) supervised exercise, b) home-based exercise, c) sertraline, or d) placebo pill. Before and after 4 months of treatment, participants completed measures of: Executive Function (Trail Making Test B-A difference score, Stroop Color-Word, Ruff 2 & 7 Test, Digit Symbol), Verbal Memory (Logical Memory, Verbal Paired Associates), and Verbal Fluency/Working Memory (Animal Naming, Controlled Oral Word Association Test, Digit Span). Multivariate analyses of covariance were performed to test the effects of treatment on posttreatment neuropsychological test scores, with baseline neuropsychological test scores, age, education, and change in depression scores entered as covariates. RESULTS:: The performance of exercise participants was no better than participants receiving placebo across all neuropsychological tests. Exercise participants performed better than participants receiving sertraline on tests of executive function but not on tests of verbal memory or verbal fluency/working memory. CONCLUSIONS:: We found little evidence to support the benefits of an aerobic exercise intervention on neurocognitive performance in patients with MDD.
Osteoporosis after combined use of a neuroleptic and antidepressants.
Pharm World Sci. 2008 Jun 24;
Laekeman G, Zwaenepoel L, Reyntens J, de Vos M, Casteels M
Bone mineral density may be negatively influenced by hyperprolactinemia, which can be caused by atypic neuroleptics and antidepressants. Case description The present paper reports about a spontaneous rib fracture in a female patient (age 52) taking neuroleptics (mainly risperidone), antidepressants (mainly sertraline), and anxiolytics (mainly lorazepam). At the time of the fracture a severe osteoporosis and a strongly enhanced plasma prolactin level (117 ng/ml; normal values: 3-24 ng/ml) were detected. The latter one normalized 2 months after abandoning sertraline and risperidone. After this normalization, the patient did not report further accidents up to now. Discussion Enhancement of plasma prolactin levels is linked to the mechanism of action of risperidone. Mammoplasia and increased plasma prolactin can occur during SSRI (Selective Serotonin Reuptake Inhibitors) or trazodone administration. The role of anxiolytics is less clear. The causal relationship between osteoporosis and long-term use of neuroleptics and antidepressants was assessed using probability scores, more particularly the Naranjo probability scale and the Bradford-Hill criteria of causality. A score of 6/13 (probable) was obtained with the Naranjo scale, whereas all 9 Bradford-Hill criteria were fulfilled. Conclusion Although this case could not be fully explored, attention should be paid to bone mineral density loss in depressed patients taking a combined therapy of atypic antipsychotics and antidepressants.
Ecotoxicol Environ Saf. 2008 Jun 19;
Minagh E, Hernan R, O'Rourke K, Lyng FM, Davoren M
Sertraline hydrochloride is a selective serotonin reuptake inhibitor (SSRI) widely prescribed to patients suffering from psychiatric disorders. Pharmaceutical products such as sertraline have been identified in environmental waters. This study describes the evaluation of sertraline using a battery of freshwater species representing four trophic levels. The species most sensitive to sertraline were Daphnia magna 21d reproduction test, Pseudokirchneriella subcapitata 72h growth inhibition, and Oncorhynchus mykiss 96h mortality, with the Microtox assay being the least sensitive assay. The D. magna 21d reproduction test was approximately two orders of magnitude more sensitive than the other bioassays. These results show the advantages of having a tiered approach within a test battery. The presented results indicate that sertraline hydrochloride adversely affects aquatic organisms at levels several orders of magnitude higher than that reported in municipal effluent concentrations, however adverse effects may result from lower concentration exposures, further research into chronic toxicity is therefore advocated.
Eur J Pharmacol. 2008 May 23;
Takahashi E, Katayama M, Niimi K, Itakura C
The main clinically used antidepressant drugs are selective monoamine reuptake inhibitors, including selective serotonin reuptake inhibitors (citalopram, sertraline), selective dopamine reuptake inhibitor (nomifensine) and selective noradrenaline reuptake inhibitor (reboxetine), but they have various side effects. Because cannabinoid CB(1) receptor antagonists (SR141716A, AM251) enhance monoamine release, they might be beneficial in the therapy of affective disorders. We hypothesized that the use of monoamine reuptake inhibitors in combination with cannabinoid CB(1) receptor antagonists would allow a lower dose of monoamine reuptake inhibitors to be used in the therapy of depression, thereby reducing or eliminating the side effects. To test this hypothesis, we examined the combination of SR141716A or AM251 with citalopram, sertraline, nomifensine or reboxetine at subthreshold doses to see whether these combinations would show an additive effect in the forced swimming test and the tail suspension test with mice. Subthreshold doses of cannabinoid CB(1) receptor antagonist and selective serotonin reuptake inhibitors, which separately had no effect on the immobility of mice in the tests, showed a clear effect when the drugs were administered at 40 and 30 min, respectively, before the tests, without any change of motor activity. Therefore, the use of subthreshold doses of these agents in combination might be useful to enhance mainly serotonergic neurotransmission, and to reduce or eliminate the side effects of citalopram and sertraline.
J Psychopharmacol. 2008 Jun 18;
Wann BP, Bah TM, Kaloustian S, Boucher M, Dufort AM, Le Marec N, Godbout R, Rousseau G
Abstract Depression is diagnosed in 15-30% of patients following myocardial infarction (MI) and this may also be observed in the rat. We measured the effects of the antidepressant sertraline on behavioural and biochemical events following MI in a rat model. Following surgery, MI rats and sham controls were treated with sertraline (10 mg/kg, i.p.) or saline. Subgroups of rats were tested for behavioural depression 14 days after surgery. Apoptosis was estimated in other rats by measuring caspase-3 activity and TUNEL positive cells (3 days after surgery) in limbic structures (amygdale, hippocampus, hypothalamus, frontal and prefrontal cortices). Bax/Bcl-2 ratio was measured 14 days after surgery. Behavioural signs of depression (decreased sucrose intake and forced swimming time) were found in saline-treated MI rats but not in sertraline-treated rats. Compared with controls, caspase-3 activity and TUNEL positive cells were significantly increased in most limbic structures of MI rats. High prefrontal Bax/Bcl-2 ratio in MI rats correlated with low forced swimming time. Apoptosis was not found in sertraline-treated MI rats. These results establish the bases of a rat model of depression following MI and show for the first time that a selective serotonin reuptake inhibitor prevents both behavioural and biochemical markers in this model.
Management Strategies for Premenstrual Syndrome/Premenstrual Dysphoric Disorder (July/August) (CE).
Ann Pharmacother. 2008 Jun 17;
Jarvis CI, Lynch AM, Morin AK
OBJECTIVE: To evaluate the current nonpharmacologic and pharmacologic treatment options for symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). DATA SOURCES: Literature was obtained through searches of MEDLINE Ovid (1950-March week 3, 2008) and EMBASE Drugs and Pharmacology (all years), as well as a bibliographic review of articles identified by the searches. Key terms included premenstrual syndrome, premenstrual dysphoric disorder, PMS, PMDD, and treatment. STUDY SELECTION AND DATA EXTRACTION: All pertinent clinical trials, retrospective studies, and case reports in human subjects published in the English language were identified and evaluated for the safety and efficacy of pharmacologic and nonpharmacologic treatments of PMS/PMDD. Data from these studies and information from review articles were included in this review. DATA SYNTHESIS: Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication. Suppression of ovulation using hormonal therapies is an alternative approach to treating PMDD when SSRIs or second-line psychotropic agents are ineffective; however, adverse effects limit their use. Anxiolytics, spironolactone, and nonsteroidal antiinflammatory drugs can be used as supportive care to relieve symptoms. Despite lack of specific evidence, lifestyle modifications and exercise are first-line recommendations for all women with PMS/PMDD and may be all that is needed to treat mild-to-moderate symptoms. Herbal and vitamin supplementation and complementary and alternative medicine have been evaluated for use in PMS/PMDD and have produced unclear or conflicting results. More controlled clinical trials are needed to determine their safety and efficacy and potential for drug interactions. CONCLUSIONS: Healthcare providers need to be aware of the symptoms of PMS and PMDD and the treatment options available. Treatment selection should be based on individual patient symptoms, concomitant medical history, and need for contraception.
Anal Chem. 2008 Jun 14;
Lajeunesse A, Gagnon C, Sauvé S
A novel analytical method has been developed for the determination of six basic antidepressants (venlafaxine, sertraline, paroxetine, citalopram, amitriptyline, and fluoxetine) and four of their metabolites ( O-desmethylvenlafaxine, desmethylsertraline, nortriptyline, and norfluoxetine) in raw sewage and roughly primary-treated wastewater. For analytical development purposes, two ion exchange solid-phase extraction cartridges were compared. Extracts were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive-mode electrospray (+ESI) and selected reaction monitoring transitions. The choice of a basic mobile phase significantly improved the instrumental sensitivity (by up to 14-fold for norfluoxetine) relative to common +ESI acidic mobile phases. In addition to the remarkable gain in sensitivity, negligible matrix effects were also observed in the raw sewage samples. Analyte recoveries ranged from 80 to 103% and effluent detection limits from 0.048 to 0.10 ng/L. Samples collected at the Montreal Wastewater Treatment Plant showed the unequivocal presence of all the target compounds at concentrations of 2-346 ng/L. The target antidepressants were also detected in samples taken from the effluent receiving waters (i.e., the St. Lawrence River) but at lower concentrations (0.41-69 ng/L). The highly sensitive proposed method constitutes one of the best means for monitoring the environmental occurrence of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and some of their metabolites.