Antidepressant treatment of depression in the Finnish general population.

Laukkala T, Isometsa E, Hamalainen J, Heikkinen M, Lindeman S, Aro H.

Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.

OBJECTIVE: Antidepressant use has increased in the last decade, but whether depression continues to be undertreated is unknown. The authors investigated the prevalence of antidepressant treatment and its predictors in a recent general population sample of depressed subjects. METHOD: As part of the Finnish Health Care Survey, in 1996 a representative sample of Finns (N=5,993) aged 15-75 years underwent a standardized face-to-face interview that used the DSM-III-R criteria for major depressive episode. RESULTS: Only 13% of subjects with a major depressive episode during the preceding 12 months (70 of 557) reported current use of an antidepressant. In logistic regression models, use of psychiatric services for depression, regular use of any other medication, more than 1 month of sick leave, and smoking were associated with antidepressant treatment. CONCLUSIONS: Most depressed subjects in 1996 in Finland were not receiving antidepressant treatment despite the several-fold increase in antidepressant use in the 1990s.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11729032&dopt=Abstract antidepressant




Altered dendritic spine density in animal models of depression and in response to antidepressant treatment.

Norrholm SD, Ouimet CC.

Program in Neuroscience, Department of Psychology, Florida State University, Tallahassee, Florida 32306-4340, USA.

Olfactory bulbectomy, neonatal clomipramine administration, and maternal deprivation have been employed as animal models of depression. Each model is unique with respect to the experimental manipulations required to produce "depressive" signs, expression and duration of these signs, and response to antidepressant treatments. Dendritic spines represent a possible anatomical substrate for the enduring changes seen with depression and we have previously shown that chronic antidepressant drug exposure alters the density of hippocampal dendritic spines in an enduring fashion. The purpose of the present study was to determine whether persistent alteration of hippocampal spine density is a common element in each of these different models of depression and whether such alterations could be reversed with chronic antidepressant treatment. The results show that olfactory bulbectomy reduced spine density in CA1, CA3, and dentate gyrus compared to sham-operated controls. Chronic treatment with amitriptyline, a tricyclic antidepressant, reversed the bulbectomy- induced reduction in dendritic spine density in CA1, CA3, and dentate gyrus, whereas treatment with mianserin, an atypical antidepressant, reversed this reduction only in dentate gyrus. On the other hand, neither neonatal clomipramine administration nor maternal deprivation affected hippocampal dendritic spine density. Repeated neonatal handling, however, as a control or as part of the maternal deprivation procedure, elevated spine density in dentate gyrus. These data suggest that long-lasting alterations in hippocampal dendritic spine density contribute to the neural mechanism underlying the olfactory bulbectomy model of depression, but not the neonatal clomipramine or maternal deprivation models. Copyright 2001 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11746712&dopt=Abstract antidepressant




The reductions in sweetened milk intake induced by interleukin-1 and endotoxin are not prevented by chronic antidepressant treatment.

Dunn AJ, Swiergiel AH.

Department of Pharmacology and Therapeutics, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA. adunn lsuhsc.edu

Administration of interleukin-1 (IL-1) and endotoxin (lipopolysaccharide, LPS) to rodents can decrease food intake, a behavioral response resembling the diminution of appetite observed in human depression. IL-1 and LPS are known to affect cerebral neurotransmission involving norepinephrine and serotonin, both of which have been implicated in feeding behavior and in the pharmacotherapy of depression in man. The ability of chronic antidepressant treatment to attenuate LPS-induced depressed feeding in rats has been cited as evidence that cytokines may be involved in human depression. Thus, we studied the effects of chronic treatment with the tricyclic antidepressant, imipramine, and the novel antidepressant, venlafaxine, on the sweetened milk intake challenged with intraperitoneally injected IL-1 beta and LPS. Chronic (from 2 to 8 weeks) treatment of the mice with imipramine (10 mg/kg once or twice daily) or venlafaxine (10 and 20 mg/kg/day) did not significantly alter the decreases in milk intake in response to mIL-1 beta or LPS. In some experiments, chronic imipramine slightly decreased body weight and slightly increased milk intake, but not food pellet intake. Venlafaxine had none of these effects. Analysis of variance did not indicate any significant interactions between the antidepressant and IL-1 or LPS treatments. These results indicate that chronic treatment with antidepressants does not significantly alter the responses to IL-1 or LPS in the mouse sweetened milk model of sickness behavior. Copyright 2001 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11752890&dopt=Abstract antidepressant




Antidepressant drug prescribing in Italy, 2000: analysis of a general practice database.

Pietraru C, Barbui C, Poggio L, Tognoni G.

Community Pharmacy, Department ASL 7, Chivasso, Torino, Italy.

OBJECTIVE: Databases of subjects receiving antidepressants provide evidence on the use of drugs in typical patients and settings under real-world conditions. This study analysed a general practice database to estimate the prevalence of antidepressant drug use, describe the use of these compounds by gender and age and estimate the prevalence of occasional versus non-occasional users. METHODS: The general practice database of Chivasso, a city near Turin in Piedmont, was analysed. The database includes all community (i.e. outside hospitals) prescriptions reimbursed by the National Health System in the population living in the study area. From the database, the total number of units of antidepressant drugs prescribed over a 6-month period was extracted. Using the general practice patient code, all records were converted into a sample of patients receiving one or more prescriptions of one or more antidepressants. RESULTS: During the 6 months surveyed, 12,930 antidepressant prescriptions were dispensed to 3751 patients, resulting in a prevalence of use of 19 patients per 1000 inhabitants (confidence interval 18.3, 19.5). The prevalence of use progressively increased with age and was more than double in females than males (female/male ratio 2.16). Paroxetine was the most prescribed compound, followed by amitriptyline and fluoxetine. However, in older subjects, the top two antidepressants were trazodone and amitriptyline. Nearly one-fourth of all dispensed antidepressants were prescribed on one occasion only; occasional users were slightly younger than non-occasional users. CONCLUSIONS: In Italy, databases have been used to monitor the prescription of medicines, but they have always provided aggregate data on drug sales and consumption. In this study, a sample of typical patients receiving antidepressants under real-world conditions was analysed to help clarify what happens in clinical practice. Databases of patients receiving antidepressants should be adopted to suggest public health priorities and generate original research hypotheses to be formally tested with experimental studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11758640&dopt=Abstract antidepressant




Dosage of antidepressant medication dispensed in Scotland.

Patience D.

Shawpark Resource Center, 41, Shawpark Street, Glasgow G20 9DR.

OBJECTIVES: To examine the daily doses of the more frequently prescribed antidepressants in Scotland and to assess the extent of adequate dosage and its relationship to drug type. DESIGN: Monthly random sample of all prescriptions dispensed in Scotland over 1 year. Antidepressants were categorised into 5 groups, older tricyclics, newer tricyclics, atypical antidepressants, selective serotonin uptake inhibitors (SSRI's) and monoamine oxidase inhibitors (MAOI's). Percentage of prescriptions at or above the minimum effective dose was calculated for each group. In addition the total number and rank order of all antidepressant prescriptions in 1995 were calculated in order to examine sampling bias. SETTING: Prescription data routinely collected by the Pharmacy Practices Division of the Common Services Agency of The NHS in Scotland. RESULTS: Older tricyclics continue to be the most frequently prescribed antidepressants (51%), followed by SSRI's (34%), newer tricyclics and atypicals (7% each) and MAOIs (1%). Only 18% (95% C.I. 13-23%) of the sample of older tricyclics were prescribed at or above the minimum therapeutic level, compared to 99% (95% C.I. 95-100%) for SSRIS' 76% (95% C.I. 55-93%) for atypicals and 74% (95% C.I. 52-96%) for lofepramine. CONCLUSIONS: Despite initiatives to improve the treatment of depressive illness in primary care, the majority of prescriptions continue to be for older tricyclic antidepressants at sub-therapeutic dosage. Incorporation of consensus statement guidelines about minimum effective doses for these drugs in the BNF may be an important and economical route to improving treatment of identified depressive illness.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11769112&dopt=Abstract antidepressant




Further characterisation of potential antidepressant action of flibanserin.

Borsini F, Cesana R.

Boehringer Ingelheim Pharma KG, CNS Department, Building J63, Birkendorfer Strasse 75, 88397 Biberach an der Riss, Germany. Franco.Borsini bc.boehringer-ingelheim.com

RATIONALE: Flibanserin has shown antidepressant-like properties in some animal models. In order to better define the probability that flibanserin may act as an antidepressant, its effects were tested in additional tests. OBJECTIVES: To assess the activity of flibanserin in the forced swimming test in rats, in the distress call frequency in isolated chicks, in the tail suspension test in mice and in muricidal rats. Flibanserin was also tested in mice performing an operant schedule of a food reinforcement fixed at an interval of 2 min. METHODS: Flibanserin was given intraperitoneally at a dose range between 0.5 and 32 mg/kg, 60 min before the muricidal test, 30 min before the tail suspension test, once (30 min) or three times (24, 5 and 1 h) before the forced swimming test, or just before testing (distress-induced calls in chicks). In the food reinforcement test in mice, flibanserin was given orally 60 min before testing. RESULTS: Flibanserin showed an antidepressant-like effect in the distress-induced calls in chicks (5 mg/kg) and in the muricidal test (16 and 32 mg/kg), but not in the tail suspension test (from 7.5 to 30 mg/kg). Flibanserin (8 and 16 mg/kg) increased immobility in the forced swimming test, either when administered once or for three times. Flibanserin increased the operant responses in the food reinforcement test (40 mg/kg). CONCLUSIONS: Flibanserin showed antidepressant-like effects in two out of four tests, and increased animal drive in the operant paradigm. These findings, together with others already published, may suggest that flibanserin will exert antidepressant activity in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11797071&dopt=Abstract antidepressant




Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database.

Khan A, Leventhal RM, Khan SR, Brown WA.

Northwest Clinical Research Center, Bellevue, Washington, USA. akhan nwcrc.net

Some studies suggest that more severely ill patients with depression respond well to antidepressants and poorly to placebo, whereas those who are mildly ill respond equally well to antidepressants and placebo. This notion has implications for the design of clinical trials. To further assess and substantiate these putative predictors of antidepressant and placebo response, we assessed the Food and Drug Administration database of 45 phase II and III antidepressant clinical trials. The frequency of statistically significant differences between antidepressants and placebo was higher in the trials that included patients with more severe depression. In the antidepressant-treated groups, the magnitude of symptom reduction was significantly related to mean initial Hamilton Rating Scale for Depression (HAM-D) score; the higher the mean initial HAM-D score, the larger the change. With placebo treatment, however, the higher the mean initial HAM-D score, the smaller the change. Early discontinuation was more frequent among patients whose mean initial HAM-D scores were higher. These data may help inform the design of future antidepressant clinical trials.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11799341&dopt=Abstract antidepressant