sertraline, Zoloft
Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia.

Henry TB, Kwon JW, Armbrust KL, Black MC.

Department of Environmental Health Science, University of Georgia, Athens, Georgia 30602, USA. thenry uga.edu

Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac; fluvoxamine, Luvox; paroxetine, Paxil; citalopram, Celexa; and sertraline, Zoloft) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15379001&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Serotonin (5-HT) enhances the activity of amphotericin B against Aspergillus fumigatus in vitro.

Heller I, Leitner S, Dierich MP, Lass-Florl C.

Institute of Hygiene and Social Medicine, Leopold-Franzens University of Innsbruck, Fritz Pregl-Strasse 3/III, 6020 Innsbruck, Austria.

We investigated the in vitro synergistic antifungal potential of combining serotonin (5-HT) and sertraline with amphotericin B and itraconazole against clinical isolates of Aspergillus spp. Synergy tests were performed using the chequerboard microdilution method. Activity was measured against Aspergillus fumigatus (n = 7), Aspergillus flavus (n = 3) and Aspergillus terreus (n = 2), and compared with that for Candida albicans and Candida parapsilosis. The fractional inhibitory concentration (FIC) indices ranged between 0.25 and 3 for the various isolates tested. 5-HT was shown to enhance the activity of amphotericin B against Aspergillus spp. Combination studies with 5-HT and itraconazole and with sertraline and itraconazole or amphothericin B showed different activities for the various strains, including synergism (FIC < 1.0), additivity (FIC = 1), and indifference (FIC between 1.0 and 2.0). 5-HT and sertraline showed antagonistic activity (FIC > 2) with amphotericin B and itraconazole against C. parapsilosis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15380269&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Influence of sertraline on the antinociceptive effect of morphine, metamizol and indomethacin in mice.

Pakulska W.

Department of Pharmacodynamics, Medical University of Lodz, Poland.

Interaction between analgesic and various psychotropic drugs constitute a subject of many research investigations. Literature data considering this issue are often inconsistent. Sertraline is one of the most potent drugs in the family of selective serotonine reuptake inhibitors (SSRIs). The influence of sertraline (5 mg/kg) on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg or 1.4 mg/kg) was investigated in a mouse model using the tail-flick and hot-plate tests. All drugs were injected intraperitoneally. Sertraline was administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after sertraline administration. The research studies were futher conducted with multiple (14 days) drug dosage. Sertraline after single dose increased the antinociceptive effect of morphine (in the hot-plate test) and metamizol and indomethacin (only in the tail-flick test). Sertraline after 14 day administration decreased analgesic effect of morphine (only in the hot-plate test). Sertraline applied for 14 days increased the antinociceptive effect of indomethacin. Sertraline alone after multiple doses increased pain reaction time. The results of experiments suggest the role of sertraline in nociception and possibility of interaction between sertraline and analgesic drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15493299&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
A comparison of the direct costs and cost effectiveness of serotonin reuptake inhibitors and associated adverse drug reactions.

Sullivan PW, Valuck R, Saseen J, MacFall HM.

Pharmaceutical Outcomes Research Program, Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Patrick.Sullivan UCHSC.edu

BACKGROUND: The economic burden of depression is known to be high and was estimated to be USD 83.1 billion in 2000. Serotonin reuptake inhibitors (SRIs), including both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), have a superior adverse effect and safety profile relative to traditional agents (e.g. TCAs), and as a result have demonstrated superior cost effectiveness. Although efficacy across the SRIs is similar, the incidence of adverse drug reactions (ADRs) within SRIs remains significant and varies by agent. Patients who experience ADRs from SRIs may seek medical care, require additional treatment, and even discontinue treatment altogether, leading to increased utilisation and cost of therapy. OBJECTIVE: This study estimates the direct cost and cost effectiveness, taking into account the impact of treatment-related ADRs, of eight currently marketed SRIs (citalopram, escitalopram, generic fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, venlafaxine and venlafaxine extended release [XR]) used as initial treatment for depression. METHODS: A decision analytic model with a 6-month treatment goal was used to estimate the direct cost and cost effectiveness of treatment from the managed care/payer perspective. Estimates of SRI-related ADRs, associated treatments and costs were derived from the US FDA-approved prescribing information and published literature. Efficacy was assumed to be similar across all SRIs. Effectiveness was measured using quality-adjusted life years (QALY) based on EuroQol EQ-5D scores derived from the 2000 Medical Expenditure Panel Survey (MEPS). Censored least absolute deviations (CLAD) regression analysis was used to derive age-adjusted estimates of utility for all health states. Univariate and Bayesian second-order multivariate probabilistic sensitivity analyses were conducted to examine the impact of uncertainty in the parameter estimates. RESULTS: The expected direct cost and cost effectiveness of treatment from least to most expensive were: escitalopram (USD 3891; 0.341), citalopram (USD 3938; 0.340), generic fluoxetine (USD 4034; 0.335), venlafaxine XR (USD 4226; 0.336), sertraline (USD 4250; 0.335), generic paroxetine (USD 4385; 0.332), paroxetine CR (USD 4440; 0.332) and venlafaxine (USD 4613; 0.326). Monte Carlo simulation results suggested that escitalopram was the most likely (77%) to be cost effective for a willingness to pay < or = USD 50,000 per QALY, followed by citalopram (22%), generic fluoxetine (0.3%) and all other SRIs (0%). Sensitivity analyses indicated that the results of the study were robust to the assumptions underpinning the model. CONCLUSIONS: SRI-related ADRs have a significant impact on the direct cost and cost effectiveness of treatment. Escitalopram, with the lowest ADR rate of the SRIs, had the lowest expected treatment cost and greatest effectiveness when compared with citalopram, generic fluoxetine, generic paroxetine, paroxetine CR, sertraline, venlafaxine and venlafaxine XR.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15521793&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Itch and skin rash from chocolate during fluoxetine and sertraline treatment: case report.

Cederberg J, Knight S, Svenson S, Melhus H.

Department of Clinical Chemistry and Pharmacology, Uppsala Academic Hospital, Uppsala, Sweden. jonas.cederberg medsci.uu.se

BACKGROUND: The skin contains a system for producing serotonin as well as serotonin receptors. Serotonin can also cause pruritus when injected into the skin. SSRI-drugs increase serotonin concentrations and are known to have pruritus and other dermal side effects. CASE PRESENTATION: A 46-year-old man consulted his doctor due to symptoms of depression. He did not suffer from any allergy but drinking red wine caused vasomotor rhinitis. Antidepressive treatment with fluoxetine 20 mg daily was initiated which was successful. After three weeks of treatment an itching rash appeared. An adverse drug reaction (ADR) induced by fluoxetine was suspected and fluoxetine treatment was discontinued. The symptoms disappeared with clemastine and betametasone treatment. Since the depressive symptoms returned sertraline medication was initiated. After approximately two weeks of sertraline treatment he noted an intense itching sensation in his scalp after eating a piece of chocolate cake. The itch spread to the arms, abdomen and legs and the patient treated himself with clemastine and the itch disappeared. He now realised that he had eaten a chocolate cake before this episode and remembered that before the first episode he had had a chocolate mousse dessert. He had never had any reaction from eating chocolate before and therefore reported this observation to his doctor. CONCLUSIONS: This case report suggests that there may be individuals that are very sensitive to increases in serotonin concentrations. Dermal side reactions to SSRI-drugs in these patients may be due to high activity in the serotonergic system at the dermal and epidermo-dermal junctional area rather than a hypersensitivity to the drug molecule itself.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15522120&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Analytical method for the quantitation of sertraline hydrochloride stereoisomers by electrokinetic chromatography.

Zhou MX, Foley JP.

Department of Chemistry, Drexel University, Philadelphia, PA 19104, USA.

Sertraline is a basic compound and of pharmaceutical application for antidepressant treatment. The compound has two chiral centers. Separation of the three enantiomeric impurities from the parent compound is challenging. In this study, we successfully separated all four stereoisomers by electrokinetic chromatography using highly sulfated gamma-cyclodextrin and highly sulfated alpha-cyclodextrin as the chiral selectors. The two chiral selectors provided different selectivity and therefore affected the overall separation profiles. This may be due to the size difference between the dichlorophenyl moiety end and naphthalenamine moiety end, resulting in two different types of inclusion complexes with the different cyclodextrins. For routine analysis, highly sulfated gamma-cyclodextrin was better than highly sulfated alpha-cyclodextrin. For each stereoisomeric impurity, the method using sulfated gamma-cyclodextrin provided a limit of quantitation at or lower than 0.1% of the drug substance with adequate resolution. The critical resolution at this concentration level was not less than 4.0. Experimental data suggested that an internal standard was necessary for the purpose of quantitation, and the practical linearity range for analysis of sertraline stereoisomeric impurities was of about two orders of magnitude.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15527116&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
A sertraline-intoxicated driver.

Rohrig TP, Goodson LJ.

Regional Forensic Science Center, 1109 North Minneapolis, Wichita, Kansas 67214, USA.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is chemically unrelated to other SSRIs, tricyclic antidepressants, and other currently available antidepressant medications. This report documents a case of driving under the influence of sertraline. The subject was involved in a motor vehicle accident. Upon contact by law enforcement, the subject was confused and could neither stand nor walk. The officer noted mumbled speech, droopy eyes, and that the subject seemed sleepy. No alcohol was present in the vehicle, and no odor of alcohol was detected on the subject's breath. The subject was determined to be under the influence of some intoxicating substance. Toxicological analysis revealed only the presence of sertraline. Sertraline was extracted from the blood sample utilizing solid-phase extraction and identified and quantitated by gas chromatography-mass spectrometry. The blood sertraline concentration was determined to be 1285 microg/L.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15538966&dopt=Abstract sertraline Zoloft