sertraline, Zoloft
Rapid and simple methods for quantitative analysis of some antidepressant in pharmaceutical formulations by using first derivative spectrophotometry and HPLC.

Erk N.

Department of Analytical Chemistry, Faculty of Pharmacy, University of Ankara, 06100 Ankara, Turkey. erk pharmacy.ankara.edu.tr

Two rapid, simple and accurate first derivative spectrophotometry and HPLC method for the determination of nefazodone hydrochloride and sertraline hydrochloride in pharmaceutical formulations are discussed. The first one is a derivative spectrophotometric procedure and the second one is based on a HPLC method with a UV detector. In the first method, first derivative spectrophotometry, nefazodone hydrochloride or sertraline hydrochloride by measurement of their first derivative signals at 241.8-256.7 nm (peak-to-peak amplitude), or 271.6-275.5 nm (peak-to-peak amplitude), respectively. Calibration graphs were established for 10.0-42.0 microg ml(-1) nefazodone hydrochloride, or 8.0-46.0 microg ml(-1) sertraline hydrochloride. In the other method, HPLC, the UV detection was carried out at 265.0 nm (nefazodone hydrochloride) and 270.0 nm (sertraline hydrochloride). The samples were chromatographed on a Supercosil RP-18 column. The mobile phases were methanol:acetonitrile:phosphate buffer at pH 5.5 (10:50:40 v/v/v) (nefazodone hydrochloride) and methanol:phosphate buffer at pH 4.5 (20:80 v/v) (sertraline hydrochloride). The results obtained from first derivative spectrophotometric method were comparable with those obtained by using HPLC. It was concluded that both the developed methods are equally accurate, sensitive, and precision could be applied directly and easily to the pharmaceutical formulations of nefazodone hydrochloride and sertraline hydrochloride, respectively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14630230&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Sex differences in the pituitary-adrenal response following acute antidepressant treatment in sheep.

Broadbear JH, Hutton LC, Clarke IJ, Canny BJ.

Department of Physiology, Monash University, 3800, Victoria, Australia.

RATIONALE: Depression is more prevalent in women than in men, and therapeutic responses may also differ between the sexes. In addition, abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is more common in depressed women. OBJECTIVES: To further examine these phenomena, the present study was designed to investigate whether sex differences exist in the HPA axis responses of male and female sheep following acute antidepressant administration. METHODS: Two commonly prescribed antidepressants, imipramine (a tricyclic antidepressant, TCA; 2.0 and 5.0 mg/kg) and sertraline (a selective serotonin reuptake inhibitor, SSRI; 0.5, 2.0 and 5.0 mg/kg) were administered to gonadectomized male and female sheep via acute subcutaneous injection. Treatment order was randomized. Jugular blood was sampled for the measurement of prolactin, adrenocorticotropin (ACTH), and cortisol by radioimmunoassay. RESULTS: Treatment with sertraline resulted in a comparable increase in prolactin secretion in male and female sheep. However, sertraline stimulated ACTH and cortisol secretion in females but not in males, a sexually dimorphic effect that was independent of circulating sex steroids. Treatment with imipramine had no effect on prolactin, ACTH or cortisol levels in male or female sheep. CONCLUSIONS: These data suggest that the HPA axes of females are more sensitive to the stimulatory effects of serotonin following acute treatment with the SSRI, sertraline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14634712&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Predictors of response in generalized social phobia: effect of age of onset.

Van Ameringen M, Oakman J, Mancini C, Pipe B, Chung H.

Anxiety Disorders Clinic, McMaster University Medical Centre, McMaster University, Hamilton, Ontario, Canada. vanamer mcmaster.ca

Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the pharmacological treatment of generalized social phobia (GSP). However, little is known about the predictors of response to treatment. Two hundred and four outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20-week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d. Response was defined as the percentage of patients with a Clinical Global Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much improved). Outcome analyses were conducted using regression models including treatment group as a categorical predictor and study visit as a repeated measure. Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several possible predictors of response to treatment including DSM-IV comorbidity, age, sex, age of onset of GSP, and duration of illness. Patients with later-onset (especially adult-onset) GSP tend to have a better response to treatment than those with earlier-onset GSP. This result generally appears in our analyses as a 2-way interaction, where the association with response is greatest for patients with adult-onset GSP (in contrast to those with child or adolescent onset). This finding is most robust for symptom measures, but is still apparent for the Sheehan measure of disability at work. This advantage for later-onset GSP can be accounted for neither by severity of illness nor by duration of illness. Superior treatment outcome for later-onset GSP may be mediated by the degree of social and family disability.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14709946&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Comparison of managed care charges among patients treated with selective serotonin reuptake inhibitors for premenstrual dysphoric disorder.

Endicott J, McLaughlin TP, Grudzinski AN.

New York State Psychiatric Institute, New York, NY, USA.

OBJECTIVE: To determine the impact on managed care charges of selecting citalopram, fluoxetine, paroxetine, or sertraline as first-line pharmacotherapy for newly diagnosed premenstrual dysphoric disorder (PMDD). METHOD: This retrospective study analyzed administrative claims data from 14 managed care plans in the United States. The study population was identified from an integrated outcomes database for the period Jan. 1, 1998, to Dec. 31, 1999. Patients aged 18 years or older, newly diagnosed with PMDD, and initiating therapy with a selective serotonin reuptake inhibitor (SSRI) within 30 days of the diagnosis were eligible for analysis. To date, there is no specific ICD-9 diagnosis code for PMDD; thus, patients were required to have an ICD-9 diagnosis of premenstrual tension syndrome (ICD-9 625.4). Patients with documented previous psychiatric disorders/treatment were excluded. All inpatient, outpatient, and pharmacy claims incurred by each patient during the study period were included in the analysis. PMDD-related treatment charges for the 6-month period following treatment initiation were compared using multivariate regression. RESULTS: A total of 1413 patients met the study criteria. Fluoxetine and sertraline were the most common agents selected as first-line therapy. After differences in age, managed care plan, pretreatment resource utilization, physician specialty, index prescription year, treatment charges, presence of mental health and nonmental health comorbid conditions, and changes in medication were controlled for, patients taking paroxetine and citalopram had significantly higher PMDD-related treatment charges than sertraline patients (paroxetine, p =.0430; citalopram, p =.0226). Fluoxetine patients also had higher treatment charges than sertraline patients, though statistical significance was not reached. CONCLUSIONS: Sertraline, as first-line therapy for PMDD, was associated with lower PMDD-related treatment charges compared with other SSRIs during the first 6 months after treatment initiation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14728114&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
HPLC determination of sertraline in bulk drug, tablets and capsules using hydroxypropyl-beta-cyclodextrin as mobile phase additive.

Chen D, Jiang S, Chen Y, Hu Y.

China Pharmaceutical University, 24 Tongjia Lane, Nanjing 210009, China.

A sensitive and stereospecific high-performance liquid chromatography (HPLC) method for determination of sertraline in bulk drug, tablets and capsules was developed. Chromatography resolution of the sertraline enantiomeric forms and trans diastereoisomers was performed on Alltima C18 (250 mm x 4.6mm i.d., 5 microm) column with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as mobile phase additive. The composition of the mobile phase was 68:32 (v/v) aqueous 170 mM phosphate buffer, pH 3.0 (adjusted with 85% phosphoric acid) containing 18 mM HP-beta-CD/acetonitrile at a flow rate of 1.0 ml x min(-1). The UV detector was set at 225 nm. Calibration curves were linear (r=0.9999, n=9) in the range of 1-120 microgml (-1) for sertraline. Limit of detection and quantitation for sertraline was 0.029 and 0.097 microg x ml (-1). The values of R.S.D. of repeatability and intermediate precision for bulk drug, tablets and capsules of sertraline hydrochloride were less than 1.0%.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14738940&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Fluoxetine, but not sertraline or citalopram, potentiates the locomotor stimulant effect of cocaine: possible pharmacokinetic effects.

Fletcher PJ, Sinyard J, Salsali M, Baker GB.

Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada. Paul_Fletcher camh.net

RATIONALE: The selective serotonin reuptake inhibitor (SSRI) fluoxetine enhances some of the behavioural effects of cocaine, including locomotor stimulation. While this effect has often been interpreted as evidence for a serotonergic component to the behavioural effects of cocaine, direct evidence for this hypothesis is lacking. One alternative explanation is that fluoxetine, by inhibiting cytochrome P450 (CYP) enzymes, interferes with the metabolism of cocaine. OBJECTIVES: These experiments were undertaken to: 1) compare the effects of fluoxetine with those of two other SSRIs, sertraline and citalopram, on cocaine-induced locomotor activity, 2) examine the effects of fluoxetine on cocaine-stimulated locomotion in rats depleted of serotonin (5-hydroxytryptamine; 5-HT), and 3) determine the effect of fluoxetine on cocaine levels in the brain. METHODS: Locomotor activity was measured, using photocell based activity monitors, in rats habituated to those monitors. Depletion of 5-HT was achieved by injecting 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei. Cocaine levels in whole brain were measured using high-performance liquid chromatography with ultraviolet detection. RESULTS: In experiment 1, 5 mg/kg fluoxetine enhanced the ability of 10 and 15 mg/kg cocaine to increase locomotor activity. Neither citalopram nor sertraline (5 and 10 mg/kg) altered the stimulant effect of 10 mg/kg cocaine. Experiment 2 showed that this effect of fluoxetine was also apparent in rats with large and widespread depletion of brain 5-HT levels. The 5-HT depletion also failed to alter the response to cocaine itself. In experiment 3, brain levels of cocaine were elevated in rats pretreated with fluoxetine compared with rats that received cocaine alone. CONCLUSION: Fluoxetine enhanced the ability of cocaine to increase locomotor activity. This effect appears not to depend upon increasing 5-HT function since fluoxetine was also effective in rats with substantial 5-HT depletions, and two other SSRIs did not alter the effects of cocaine. Fluoxetine-treated rats had higher brain levels of cocaine than rats treated with cocaine alone. This effect suggests that fluoxetine slows the metabolism of cocaine, perhaps by inhibition of CYP enzymes involved in metabolizing cocaine. The results also indicate that 5-HT reuptake inhibition may not play a prominent role in mediating the stimulant effects of cocaine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14740149&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
A comparison of characteristics of depressed patients and efficacy of sertraline and amitriptyline between Japan and the West.

Ohishi M, Kamijima K.

Biometrics, Pfizer Pharmaceuticals Inc., Mitsui Building, 2-1-1, Nishi-Shinjuku, Shinjuku-ku, 163-0461, Tokyo, Japan. masahiko.ohishi japan.pfizer.com

BACKGROUND: This study was conducted to investigate the differences and similarities of the profile of depressed patients and the efficacy of the antidepressants, sertraline and amitriptyline, between Japan and the West (United States, Europe), using the Hamilton Depression Rating Scale (HAM-D) score of the individual patients. METHODS: Using common selection criteria, 680 patients from three regional clinical studies were chosen for this investigation. Factor analysis of the HAM-D scores for each regional group was carried out to compare the profile of depressed patients. Analysis of covariance was used to compare the efficacy of sertraline and amitriptyline between the regions. RESULTS: Factor analyses clearly showed three main factors (major depressive symptoms, anxiety and sleep disturbance) to be common across all three geographic regions. Higher HAM-D component scores of "Work and interests" and "Retardation" and lower ones of "Depressed mood" and "Feeling of guilt" were observed for the Japanese patients compared to the Western patients. Improvement of anxiety symptoms was marked for the Japanese amitriptyline treated patients. LIMITATIONS: Although the patient data used in these analyses were restricted by using identical selection criteria, there still remains some methodological shortcomings due to the original study design differences. CONCLUSIONS: Overall, the three main factors of depression and their magnitudes were similar between Japan and the West. The presentation of major depressive symptoms in Japanese patients differed from Western patients; this could be related to social, cultural and religious differences. Marked sedative effect for Japanese patients appeared to be due to the factor of anxiety being the strongest of the three main factors in Japanese depressed patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12117628&dopt=Abstract sertraline Zoloft