sertraline, Zoloft
Serum sertraline and N-desmethylsertraline levels in breast-feeding mother-infant pairs.

Wisner KL, Perel JM, Blumer J.

Division of Pediatric Pharmacology and Critical Care, Case Western Reserve University, Cleveland, OH 44106, USA. klw6 po.cwru.edu

OBJECTIVE: The authors' goal was to study the serum sertraline levels of breast-feeding mothers and their infants. METHOD: They obtained serum levels of sertraline and N-desmethylsertraline in nine mother-infant pairs. RESULTS: Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or less) in seven of the nine infants. One infant had a high level of N-desmethylsertraline, and one infant had unusual serum sertraline and N-desmethylsertraline values (half of its mother's levels). All infants were thriving. CONCLUSIONS: Most breast-feeding infants whose mothers were taking sertraline had very low serum levels of both sertraline and N-desmethylsertraline, consistent with published reports. The authors discuss in detail the one infant with unusually high levels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9585724&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
[Pattern of usage of new antidepressants in clinical practice]

[Article in Spanish]

Montejo AL, Gilaberte I, Fombellida C, Hylan TR, Sacristan JA.

Centro de Salud La Alamedilla, Hospital Clinico Universitario de Salamanca.

INTRODUCTION: Data from naturalistic studies have reported differences in the clinical use of antidepressants referring to the need for adjusting doses, treatment duration, tolerability and use of concomitant medication. These differences could be considered as an indicator of the effectiveness of antidepressants in clinical practice settings. OBJECTIVES: It is a naturalistic, retrospective, observational study which objective is to evaluate and compare the pattern of antidepressant use (fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine) and to establish if there is a relation between the different pattern of use and the effectiveness of them. DATA AND METHODS: A retrospective dataset of patients who initiated therapy on fluoxetine, fluvoxamine, paroxetine, sertraline, or venlafaxine with a follow-up period of 6 months was used. Information about clinical characteristics of patients and antidepressant pattern of use were collected. Pattern of antidepressant use were defined as: "initial doses", "upward dose titration", "augmentation strategy", "switching" and "early interruption of treatment". The efficacy of the therapy was assessed by the CGI-improvement. RESULTS: Fluoxetine was the antidepressant more associated with a statistical significance (p = 0.001) to an stable pattern of use (initial doses without upward dose titration, switching or augmentation). After controlling for other observed baseline characteristics, patients who remained on their initial antidepressant therapy, with a stable pattern of use were 1.61 times more likely than patients who had an adjustment to therapy to experience a treatment response. Patients who initiated treatment with sertraline or venlafaxine were 2.155 and 4.831 times less likely, respectively, to experience a response relative to patients who initiated therapy on fluoxetine. CONCLUSIONS: The need to upward dose titration, switching or augmentation in the treatment could be indicated a worse therapeutic control of the symptoms. Patients treated with fluoxetine are in a stable pattern of use more likely than patients in the other antidepressants, this fact is related with better global therapeutic results.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9595820&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Preclinical toxicological evaluation of sertraline hydrochloride.

Davies TS, Klowe WM.

Pfizer Central Research, Groton, CT 06340, USA.

The toxicity profile of the antidepressant drug sertraline was determined in a series of preclinical studies in mice, rats, rabbits and dogs. Acute, subchronic, reproductive, chronic and carcinogenicity studies were conducted by the oral route. The highest doses tested in these studies were the maximum tolerated doses based on clinical signs, decreased food consumption, body weight effects, organ weight changes or clinical/anatomical pathology findings. Genetic toxicity studies were also performed. The liver was identified as a target organ in the mouse, rat and dog. The observed liver findings were consistent with hepatic xenobiotic-metabolizing enzyme induction and included hepatomegaly, hepatocellular hypertrophy, slightly increased serum transaminase activity and proliferation of smooth endoplasmic reticulum. Hepatocellular fatty change, a minimal toxic effect, was seen in mice and rats. There was no teratogenicity in studies conducted at maternally toxic doses in rats and rabbits. Decreased neonatal survival and growth observed in these studies have been previously reported in reproduction studies with other serotonin reuptake inhibitors. Sertraline was not genotoxic in an extensive battery of tests. Carcinogenicity tests were negative in rats, while benign liver tumors were slightly increased in drugtreated male mice. Liver tumors were considered secondary to the enzyme inducing potential of sertraline and not indicative of human risk.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9598298&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Cocaine and selective monoamine uptake blockers (sertraline, nisoxetine, and GBR 12935) prevent the d-fenfluramine-induced head-twitch response in mice.

Darmani NA.

Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501, USA.

Serotonin release subsequent to 5-HT precursor loading mainly occurs via exocytosis. Acute cocaine or sertraline administration promote the ability of 5-HT precursors (e.g. L-tryptophan) to induce the 5-HT2A receptor-mediated head-twitch response (HTR) in rodents. The 5-HT releaser, d-fenfluramine, at behaviorally active doses, can induce the head-twitch response in rodents by releasing cytoplasmic 5-HT via the serotonin uptake carrier working in reverse. The purpose of the present study was to utilize the d-fenfluramine-induced HTR to determine the serotonergic and nonserotonergic components of cocaine's actions on the d-fenfluramine-sensitive pool of cytoplasmic 5-HT. Because a dramatic differential potentiation in HTR frequency is obtained when cocaine is administered prior relative to after L-tryptophan injection, the effects of varying doses of cocaine and the selective serotonin (sertraline), dopamine (DA) (GBR 12935), and norepinephrine (NE) (nisoxetine) uptake blockers were investigated on the d-fenfluramine-induced behavior in two experimental protocols. Thus, each uptake inhibitor was administered either 10 min following (protocol 1) or 10 min prior to (protocol 2) d-fenfluramine injection. All the tested uptake inhibitors attenuated the d-fenfluramine-induced HTR in a dose-dependent manner in both experimental protocols. However, their order of potency in either protocol 1 (nisoxetine > GBR 12935 > cocaine > sertraline) or protocol 2 (cocaine > GBR 12935 > nisoxetine = sertraline) does not agree with in vitro affinity of these drugs for the 5-HT transporter. In addition, the potency order for cocaine and nisoxetine in protocol 1 was significantly reversed in protocol 2. The inhibitory effects of the cited drugs on the d-fenfluramine-induced HTR are discussed in terms of: 1) high doses of selective monoamine uptake blockers may not exhibit as much selectivity for their target uptake sites as indicated by in vitro tests; and 2) possible pharmacokinetic interactions between d-fenfluramine and the monoamine uptake blockers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9610928&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
The functional sensitisation of sigma receptors following chronic selective serotonin reuptake inhibitor treatment.

Faherty CJ, Harkin AJ, Leonard BE.

Department of Pharmacology, National University of Ireland, Galway.

The purpose of the present study was to investigate the potential impairment of normal motor function following chronic selective serotonin reuptake inhibitor treatment that may result from sensitisation of sigma receptors. Rats were chronically treated with either sertraline, citalopram, paroxetine or fluvoxamine and a selective sigma receptor ligand, di-o-tolylguanidine (DTG), for 28 days. All animals then received an acute intra-rubral injection of either DTG or saline. Following the direct injection of DTG into the red nucleus, rats chronically treated with DTG exhibit a maximal behavioural response characterised as a pronounced dystonia. Animals chronically treated with sertraline and citalopram elicited a response similar to that of control animals following the acute DTG challenge, whereas chronic treatment with paroxetine and fluvoxamine significantly decreased and increased the dystonic response, respectively. Facial spasticity and vacuous chewing movements were associated with, and reflected the extent of, the DTG-induced dystonia. Changes in regional biogenic amine concentrations were also determined. The concentrations of serotonin and noradrenaline were determined in the brain stem and cerebellum following the intra-rubral injection of either saline or DTG in animals that had been chronically treated with a selective serotonin reuptake inhibitor or DTG. There was a significant increase in serotonin concentration in the brain stem as a result of chronic DTG and fluvoxamine treatments. The increase in serotonin correlated with the reported potentiation of dystonia in animals that received 28 days treatment with these drugs. The potentiation of dystonia following chronic DTG and fluvoxamine treatments suggests that these drugs sensitise the sigma2 receptors, an effect that does not appear to be shared by citalopram, sertraline or paroxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9617747&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Sertraline: new indication. May help children with obsessive-compulsive disorder.

[No authors listed]

(1) The choice of treatment for children with obsessive-compulsive disorder is difficult. Behaviour therapy and antidepressants have not been assessed adequately in this setting, and their efficacy seems limited. Clomipramine was the first antidepressant to show a degree of efficacy. (2) Sertraline is the first drug to be licensed in France for children aged from 6 to 17 years with obsessive-compulsive disorder. (3) According to our literature search, the evaluation file on sertraline in this indication mainly contains data from a double-blind placebo-controlled trial involving 187 children. After 3 months of treatment, sertraline was significantly more effective than placebo, although most children remained symptomatic. Direct comparison is lacking, but sertraline seems as effective as clomipramine. (4) However, 13% of children receiving sertraline left this trial because of adverse events (3% on placebo; p = 0.02). The short-term safety profile of sertraline in children is the same as in adults, i.e. mainly nausea, agitation, headache, insomnia and tremor. (5) We have no data on the effects of prolonged sertraline therapy in children, particularly on neuropsychological development. (6) The first-line treatment of obsessive-compulsive disorder is behaviour therapy. Sertraline, like clomipramine, is an option when behaviour therapy fails or is unfeasible. The choice between sertraline and clomipramine should be discussed case by case, according to their safety profiles; however, we have more experience with clomipramine, which should therefore be preferred over sertraline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12068839&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Platelet serotonin transporter in depressed children and adolescents: 3H-paroxetine platelet binding before and after sertraline.

Sallee FR, Hilal R, Dougherty D, Beach K, Nesbitt L.

Medical University of South Carolina, Charleston, USA.

OBJECTIVE: To evaluate serotonin transporter protein (5HTPR) binding in platelets from children and adolescents with major depression (MDD) compared to normal controls using the selective ligand 3H-paroxetine. METHOD: Children and adolescents with MDD (n = 24) defined by DSM-III-R criteria and normal controls (n = 22) were compared by platelet 5HTPR kinetic analysis with the hypothesis that 5HTPR is reduced in MDD. A subset of MDD subjects (n = 18) continued to participate in a fixed-dose, open-label sertraline trial for 6 weeks followed by drug-free washout and repeated 5HTPR analysis. RESULTS: Sex, prepubertal status, and age had no effect on 5HTPR. Medication-free MDD subjects differed from controls in reduced binding capacity (Bmax) (p < .001). Sertraline therapy decreased binding affinity from baseline non-selectively (p < .05), and Bmax elevation from baseline was associated with nonresponse and suicide attempt history. CONCLUSION: Earlier literature in this population is replicated with regard to reduced platelet 5HTPR Bmax in MDD. Findings support a continuum of 5HTPR involvement in MDD across the developmental spectrum.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9666634&dopt=Abstract sertraline Zoloft