Antidepressant drug choice for first users in two regions in The Netherlands.

Egberts AC, Veenstra M, de Jong-van den Berg LT.

Utrecht Institute for Pharmaceutical Sciences Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht, The Netherlands.

OBJECTIVE: To map the prescribing habits of physicians in two different regions in the Netherlands with respect to antidepressant drug choice for first users. DESIGN: Retrospective follow-up study. METHODS: All persons who received an antidepressant drug for the first time during October 1994 to September 1995 were identified from 29 community pharmacies situated in two regions in the Netherlands. Age, gender, type of prescriber, region and the concomitant use of certain groups of drugs as marker for certain diseases were evaluated as determinants for prescribing either a "classic" or a "second generation" antidepressant drug to first users using logistic regression analysis. RESULTS: We identified 4,637 first users during the study period corresponding with an overall incidence density of 16 per 1,000 person-years. For the majority of first users of both regions, the same five antidepressants were prescribed. However, the two regions differed markedly with regard to the frequency of prescription of the individual antidepressants. Region of living was identified as the most important determinant of prescribing a certain category of antidepressant drugs to first users (OR 2.9 [95% CI 2.5-3.3]). Just a few patient characteristics were associated with antidepressant drug choice. The elderly were more likely to receive a classic antidepressant, as were patients concomitantly using anti-epileptics (OR 0.4 [95% CI 0.3-0.6]). Patients concomitantly using cardiac glycosides were more likely to receive a second generation antidepressant (OR 1.8 [95% CI 1.2-2.1]). With respect to age and the other patient characteristics studied, the same pattern was observed in both regions. CONCLUSION: Regional differences contributed more to differences in prescribing habits than individual patient characteristics. In order to improve pharmacotherapy with antidepressant drugs relevant patient characteristics should more be taken into account.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10427583&dopt=Abstract antidepressant




Ethnicity and the prescribing of antidepressant pharmacotherapy: 1992-1995.

Sclar DA, Robison LM, Skaer TL, Galin RS.

Pharmacoeconomics and Pharmacoepidemiology Research Unit, College of Pharmacy, Washington State University, Pullman 99164-6510, USA.

Little is known about the prescribing pattern for antidepressant pharmacotherapy by ethnicity. The present study was designed to determine the rates of office-based visits documenting the utilization of antidepressant pharmacotherapy, a diagnosis of a depressive disorder, or both, among whites, blacks, and Hispanics age 20-79 years. Data from the National Ambulatory Medical Care Survey for 1992-93 and 1994-95 were utilized for this analysis. Comparing these time periods, we observed several trends: (1) The annualized mean rate per 100 US population of office-based visits documenting the use of antidepressant pharmacotherapy for any reason increased from 13.4 to 15.9 among whites (p < or = 0.0001) and from 6.5 to 7.7 among blacks (p < or = 0.0001), but remained unchanged at 7.3 for Hispanics (p > 0.05). (2) Documentation of a diagnosis of a depressive disorder increased for whites (10.9 to 12.0; p < or = 0.0001), for blacks (4.2 to 5.6; p < or = 0.0001), and for Hispanics (4.8 to 5.6; p < or = 0.0001). (3) The recording of a diagnosis of a depressive disorder in concert with the initial prescription or continuation of antidepressant pharmacotherapy also increased for whites (6.5 to 7.7; p < or = 0.0001), for blacks (2.6 to 3.4; p < or = 0.0001), and for Hispanics (3.0 to 3.2; p < or = 0.0001). We conclude that the rate of office-based visits documenting the utilization of antidepressant pharmacotherapy, a diagnosis of a depressive disorder, or both, was comparable among blacks and Hispanics by 1994-95, but was less than half the rate for whites in either time period examined. Further prospective research is required to discern the reasons for observed differences by ethnicity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10439303&dopt=Abstract antidepressant




Antidepressant-like effects of 5-hydroxytryptamine1A receptor agonists on operant responding under a response duration differentiation schedule.

Kinney GG, Griffith JC, Hudzik TJ.

Astra Arcus USA, Department of Biology, Rochester, NY 14602, USA. kinneyg BMS.com

A response duration differentiation schedule, where rats depress a lever for between 1.0 and 1.3 s to obtain a food reward, provides a useful measure for detecting antidepressant activity. It is known that 5-hydroxytryptamine1A (5-HT1A) receptor agonists exhibit antidepressant-like activity in multiple animal models of depression, however, compounds selective for this receptor have not been tested in this model to date. Thus, the present study sought to determine the effect of the full 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the partial 5-HT1A agonist, buspirone, on responding in the response duration differentiation task. The effects of these drugs were compared to the effects of the non-specific serotonergic agonist, lysergic acid diethylamide (LSD); the phenothiazine, chlorpromazine; the atypical antidepressant, trazodone; and the non-selective 5-HT1A antagonists, propranolol and alprenolol. It was found that propranolol, trazodone, and both the full (8-OH-DPAT) and partial (buspirone) 5-HT1A agonists produced increases in the mean response duration, which is typical of antidepressant activity. By contrast, with the exception of propranolol, compounds lacking antidepressant efficacy (e.g. chlorpromazine, LSD and alprenolol), failed to produce increases in mean response durations. Further, the effects of 8-OH-DPAT were inhibited by pretreatment with the 5-HT1A antagonist, (-)-alprenolol (3.0 and 30.0 mg/kg i.p.). The results of this study provide further support for the suggestion that 5-HT1A agonists may be useful for the treatment of clinical depression and that these effects are specifically mediated by 5-HT1A receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10065919&dopt=Abstract antidepressant




[Creation of a line of "depressed" mice from a selection of breeders exhibiting a behavioral helplessness]

[Article in French]

Vaugeois JM, Costentin J.

Unite de Neuropsychopharmacologie Experimentale UPRES-A 6036 CNRS-IFRMP n. 23, Faculte de Medecine et de Pharmacie de Rouen, Saint Etienne du Rouvray, France. jean-marie.vaugeois univ-rouen.fr

Antidepressants are used since 40 years. All presently used antidepressants have a slow onset of action and do not improve all patients; thus, there is an absolute need for new antidepressants. A variety of animal models, often based upon the monoaminergic theory of depressive disorders, has been used to screen the current antidepressants. In fact, the main focus of most of these animal models has been to predict the antidepressant potential i.e. to establish predictive validity. However, the evaluation of such animal models should also consider face validity, i.e. how closely the model resembles the human condition, and this should help to identify innovating medicines. Antidepressants, when taken by a healthy person, induce nothing more than side effects, unrelated to an action on mood, whereas they alleviate depressive symptomatology in depressed patients. We have speculated that genetically selected animal models would be closer to the human clinical situation than models based on standard laboratory strains. We have depicted here that marked differences exist between strains of mice in the amount of immobility i.e. "spontaneous helplessness" observed in the tail suspension test, a method used to screen potential antidepressants. We have studied the behavioural characteristics of mice selectively bred for spontaneous high or low immobility scores in the tail suspension test. Hopefully, these selectively bred lines will provide a novel approach to investigate behavioural, neurochemical and neuroendocrine correlates of antidepressant action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10101610&dopt=Abstract antidepressant




What factors influence the prescribing of antidepressant pharmacotherapy? An assessment of national office-based encounters.

Sclar DA, Robison LM, Skaer TL, Galin RS.

College of Pharmacy, Washington State University, Pullman, USA.

OBJECTIVE: This study was designed to identify: 1) predictors of antidepressant pharmacotherapy among patients diagnosed with depression; and 2) predictors of prescription for either a selective-serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). METHOD: Data from the 1995 National Ambulatory Medical Care Survey (NAMCS) were used to discern the number of office-based encounters documenting a diagnosis of depression (ICD-9-CM codes 296.2-296.36; 300.4; or 311) among patients eighteen years of age or older. Logistic regression-derived odds ratios (OR) and 95 percent confidence intervals (CI) were used to elucidate factors predictive of receipt of antidepressant pharmacotherapy, and, more specifically, factors predictive of receipt of an SSRI or an SNRI. Model variables included age (18-49 years as compared to > or = 50 years); race (white as compared to nonwhite, inclusive of Hispanics); gender; self-report of depression as a reason for the office-based encounter; and payer type (private insurance program as compared to public). RESULTS: Among the estimated 18,046,293 office-based visits resulting in a diagnosis of depression, 56.2 percent of patients self-reported depression as a reason for the office-based encounter; 67.5 percent were prescribed or continued a regimen of antidepressant pharmacotherapy; and 48.3 percent were prescribed an SSRI or an SNRI. Factors predictive of receipt of antidepressant pharmacotherapy included age less than fifty years (OR = 1.30, CI = 1.01-1.67); female gender (OR = 1.45, CI = 1.13-1.85); and self-report of depression as a reason for the office-based encounter (OR = 1.98, CI = 1.57-2.51). Factors predictive of receipt of an SSRI or an SNRI included age less than fifty years (OR = 1.31, CI = 1.03-1.65); female gender (OR = 1.55, CI = 1.23-1.95); and self-report of depression as a reason for the office-based encounter (OR = 1.56, CI = 1.25-1.95). In addition, having private insurance increased the likelihood of having been prescribed an SSRI or SNRI by 46 percent (OR = 1.46, CI = 1.13-1.89). CONCLUSIONS: Among patients with a diagnosis of depression, the pattern of prescribing antidepressant pharmacotherapy is influenced by a patient's age, gender, self-report of depression, and type of insurance coverage. Further research is required to discern the reasons for these observed effects and to advance clinically rational and equitable access to pharmacotherapeutic innovation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10207740&dopt=Abstract antidepressant




Nerve growth factor-induced neurite sprouting in PC12 cells involves sigma-1 receptors: implications for antidepressants.

Takebayashi M, Hayashi T, Su TP.

Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.

One theory concerning the action of antidepressants relates to the drugs' ability to induce an adaptive plasticity in neurons such as neurite sprouting. Certain antidepressants are known to bind to sigma-1 receptors (Sig-1R) with high affinity. Sig-1R are dynamic endoplasmic reticulum proteins that are highly concentrated at the tip of growth cones in cultured cells. We therefore tested the hypotheses that Sig-1R might participate in the neurite sprouting and that antidepressants with Sig-1R affinity may promote the neuronal sprouting via Sig-1R. The prototypic Sig-1R agonist (+)-pentazocine [(+)PTZ], as well as the Sig-1R-active antidepressants imipramine and fluvoxamine, although ineffective by themselves, were found to enhance the nerve growth factor (NGF)-induced neurite sprouting in PC12 cells in a dose-dependent manner. A Sig-1R antagonist N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE100) blocked the enhancements caused by these Sig-1R agonists. In separate experiments, we found that NGF dose and time dependently increased Sig-1R in PC12 cells. Chronic treatment of cells with (+)PTZ, imipramine, or fluvoxamine also increased Sig-1R. These latter results suggested that NGF induces the neurite sprouting by increasing Sig-1R. Indeed, the overexpression of Sig-1R per se in PC12 cells enhanced the NGF-induced neurite sprouting. Furthermore, antisense deoxyoligonucleotides directed against Sig-1R attenuated the NGF-induced neurite sprouting. Thus, when taken together, our results indicate that Sig-1R play an important role in the NGF-induced neurite sprouting and that certain antidepressants may facilitate neuronal sprouting in the brain via Sig-1R.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12438547&dopt=Abstract antidepressant




[A specific dosage method for the analysis of 24 antidepressants using gas chromatography-mass spectrometry (GC/SM)]

[Article in French]

Lacassie E, Ragot S, Gaulier JM, Marquet P, Lachatre G.

Service de Pharmacologie et Toxicologie, CHRU Dupuytren, Limoges, France.

A specific and sensitive method for the analysis of 24 antidepressants in human serum was developed using gas chromatography-mass spectrometry (GC/MS). This method allowed the simultaneous determination of antidepressants belonging to different classes: tricyclic antidepressants (TADs), selective serotonin reuptake inhibitors (SSRIs) and selective inhibitors of monoamine oxidase A (IMAOs). Antidepressants were submitted to liquid-liquid extraction at pH 9.5 using a mixture of heptane/isoamyl alcohol (98.5/1.5; v/v) without derivatization. Cyproheptadine was used as the internal standard (IS). Separation was obtained with a nonpolar PTE5 capillary column (30 m x 0.32 mm; film thickness 0.25 micron). Mass spectrometry consisted of electron impact ionisation (70 eV), and full scan acquisition. Extraction recoveries were over 60% for 22 antidepressants and between 35 and 95% for moclobemide and viloxazine. Limits of quantitation ranged from 20 to 100 ng/ml for most of the antidepressants, except for moclobemide and viloxazine for which it was 500 ng/ml. Intra-assay standard deviation was satisfactory. An excellent linearity was observed from the respective LOQs up to 1000 ng/ml for 22 antidepressants and up to 4000 ng/ml for moclobemide and viloxazine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10216976&dopt=Abstract antidepressant




Effect of mental health specialty care on antidepressant length of therapy.

Croghan TW, Melfi CA, Dobrez DG, Kniesner TJ.

Health Outcomes Evaluation Group, Eli Lilly and Company, Indianapolis, IN 46285, USA. thomasvwvcroghan lilly.com

OBJECTIVES: Treatment of depression with medications and psychotherapy clearly is efficacious, but not all patients require such intensive therapy. In this report, we examine the costs and effects of dual treatment on a population of employees and their families with depression. We sought to determine the costs and length of medication treatment consequences of providing mental health specialty care to antidepressant-treated individuals. RESEARCH DESIGN AND SUBJECTS: A quasi-experimental retrospective design was used to examine the administrative data of 2678 antidepressant users whose insurance claims are included in the MarketScan database. The primary measure used was joint cost-continuity of antidepressant medication. RESULTS: Patients receiving concurrent psychotherapy were more likely to achieve length of antidepressant treatment consistent with current recommendations. The cost-consequence ratio for concurrent treatment was $4062/1% improvement in the number of adequately treated individuals. CONCLUSION: Adding psychotherapy to treatment with medication appears to improve the efficacy of antidepressant treatment. The incremental costs suggest that it is a valuable addition in most cases and should be considered cost-effective.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10217389&dopt=Abstract antidepressant