Calcitonin-induced impairment in conditioning is antagonized by chronic antidepressant drug treatment.

Aboufatima R, Chait A, Dalal A, de Beaurepaire R.

Unite d'Ecophysiologie, Faculte des Sciences Semlalia, Universite Cadi Ayyad, Marrakech, Maroc.

The purpose of this study was to test the effect of calcitonin, when injected into the lateral ventricle, on conditioning behaviour and to see whether antidepressant drug treatment can antagonize calcitonin-induced impairment of this behaviour. Conditioned response by conditional stimulus (CS) was compared in control rat (CO) and in rats that received intraventricular perfusion of calcitonin (CA), acute antidepressant drug treatment (ADa), acute antidepressant drug treatment + calcitonin (ADa + CA), chronic antidepressant drug treatment (21 days) + calcitonin the day after (ADc + CA). Control rats acquired easily the conditioned response, the CA group and ADa + CA had problems in making the correlation between CS and unconditional stimulus (US), and consequently did not acquire a conditioned response, but in the ADc + CA group, rats exhibited more conditioned responses. The results indicate that calcitonin disrupts conditioning processes and chronic but not acute antidepressant drug treatment can reverse the effects of calcitonin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10667092&dopt=Abstract antidepressant




Central nervous system active medications and risk for fractures in older women.

Ensrud KE, Blackwell T, Mangione CM, Bowman PJ, Bauer DC, Schwartz A, Hanlon JT, Nevitt MC, Whooley MA; Study of Osteoporotic Fractures Research Group.

Department of Medicine and Center for Chronic Disease Outcomes Research, VA Medical Center, Minneapolis, MN 55417, USA. ensru001 umn.edu

BACKGROUND: Use of central nervous system (CNS) active medications may increase the risk for fractures. Prior studies are limited by incomplete control of confounders. METHODS: To determine whether use of CNS active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases fracture risk in elderly, community-dwelling women, we examined use of these 4 categories of medications in a cohort of 8127 older women and followed the participants prospectively for incident nonspine fractures, including hip fractures. Current use of CNS active medications was assessed by interview with verification of use from containers between 1992 and 1994 and between 1995 and 1996. Use was coded as a time-dependent variable. Incident nonspine fractures occurring after the initial medication assessment until May 31, 1999, were confirmed by radiographic reports. RESULTS: During an average follow-up of 4.8 years, 1256 women (15%) experienced at least one nonspine fracture, including 288 (4%) with first hip fractures. Compared with nonusers, women taking narcotics (multivariate hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.83) and those taking antidepressants (multivariate HR, 1.25; 95% CI, 0.99-1.58) had increases in the risks for any nonspine fractures. Women taking tricyclic antidepressants and those using selective serotonin reuptake inhibitors (SSRIs) had similar fracture rates. There were no independent associations between benzodiazepine use or anticonvulsant use and risk for nonspine fracture. Women taking antidepressants compared with nonusers had a 1.7-fold increase in the risk for hip fracture (multivariate HR, 1.65; 95% CI, 1.05-2.57). We did not observe independent associations between use of any of the other 3 classes of CNS active medications and risk of hip fracture. CONCLUSIONS: Community-dwelling older women taking narcotics have an increased risk for any nonspine fracture, and those taking antidepressants have a greater risk for nonspine fractures, including hip fracture. Rates of fracture were similar in women taking tricyclic antidepressants and those using SSRIs. Benzodiazepine use and anticonvulsant use were not independently associated with an increased risk of nonspine fractures, including hip fracture.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12719205&dopt=Abstract antidepressant




Factors affecting prescribing of the newer antidepressants.

Garrison GD, Levin GM.

Albany College of Pharmacy, Union University, NY, USA.

OBJECTIVE: To survey various prescriber types and specialties to determine whether differences exist in prescribing patterns for the newer antidepressants. DESIGN, SETTING, AND PARTICIPANTS: A survey about prescribing of the newer antidepressants was mailed to 1,500 New York state licensed prescribers who were randomly selected from membership rosters. Nurse practitioners; physician assistants and physicians in family medicine, primary care, general practice, and internal medicine; and psychiatrists were included. MAIN OUTCOME MEASURES: Prescriber responses regarding factors involved with choosing among the newer antidepressants. RESULTS: A total of 508 surveys (36%) were returned, of which 398 (29%) were acceptable for analysis. In choosing among the newer antidepressants, most prescribers ranked patient diagnosis and past success as a high priority, and free drug samples and drug-representative detailing as a low priority. The majority of each prescriber type preferred fluoxetine for major depression and depression associated with fatigue; paroxetine for concomitant anxiety and depression, as well as for panic disorder; and sertraline for geriatric patients and patients with suicidal ideation. Differences existed between the prescriber groups when asked whether prescribing habits for the newer antidepressants were based on familiarity with a particular agent (p = 0.0009) and on labeled indications (p = 0.002). CONCLUSIONS: This is the first study to demonstrate prescribing preferences for the newer antidepressants among different prescriber groups. Additional studies are needed to determine predictors of patient response to newer antidepressants and clinical guidelines for their use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10669179&dopt=Abstract antidepressant




Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.

Malberg JE, Eisch AJ, Nestler EJ, Duman RS.

Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, Connecticut 06508, USA.

Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11124987&dopt=Abstract antidepressant




Antidepressant prescribing practices of nurse practitioners.

Shell RC, Smith PL, Moody NB.

College of Nursing, East Tennessee State University, Johnson City, USA. rshell planetc.com

Depression is considered a highly treatable illness, yet often it is inadequately treated by physicians in primary care settings. The economic and human cost of inadequate treatment is well documented. The purpose of this pilot study was to explore the antidepressant prescribing practices among a convenience sample of nurse practitioners (NPs) and to use the findings to refine the antidepressant therapy questionnaire for further use. A self-administered questionnaire was completed by 26 NPs. Results of the survey revealed that NPs in primary care settings frequently treat a wide variety of common mental health problems and prescribe antidepressant medications for a number of these disorders as well as for nonpsychiatric problems. Factors that influence the NPs' decision-making process in the selection of a particular antidepressant were found to vary among the NPs surveyed. Although 65% of the NPs felt that they were sufficiently informed about the available antidepressants to select the most appropriate drug for their clients, 77% believed they needed additional education on antidepressant medications, and all but one respondent reported willingness to attend continuing educational offerings on antidepressant medications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10455575&dopt=Abstract antidepressant




Treatment of C6 glioma cells and rats with antidepressant drugs increases the detergent extraction of G(s alpha) from plasma membrane.

Toki S, Donati RJ, Rasenick MM.

Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612-7342, USA.

Results from previous studies suggested that chronic treatment of rats or C6 glioma cells with antidepressants augments the coupling between Gs and adenylyl cyclase. As these effects on C6 glioma cells are seen in the absence of presynaptic input, several antidepressant drugs may have a direct "postsynaptic" effect on their target cells. It was hypothesized that the target of antidepressant action was some membrane protein that may regulate coupling between G proteins and adenylyl cyclase. To test this, C6 glioma cells were treated with amitriptyline, desipramine, iprindole, or fluoxetine for 3 days. Chlorpromazine served as a control for these treatments. Membrane proteins were extracted sequentially with Triton X-100 and Triton X-114 from C6 glioma cells. Triton X-100 extracted more G(s alpha) in membranes prepared from antidepressant-treated C6 glioma cells than from control groups. In addition, cell fractionation studies revealed that the amount of G(s alpha) in caveolin-enriched domains was reduced after antidepressant treatment and that adenylyl cyclase comigrated with G(s alpha) in the gradients. These data suggest that some postsynaptic component that increases availability of Gs to activate effector molecules, such as adenylyl cyclase, might be a target of antidepressant treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10461902&dopt=Abstract antidepressant




A 20-year longitudinal observational study of somatic antidepressant treatment effectiveness.

Leon AC, Solomon DA, Mueller TI, Endicott J, Rice JP, Maser JD, Coryell W, Keller MB.

NIMH Collaborative Program on the Psychobiology of Depression, USA. aclean med.cornell.edu

OBJECTIVE: This observational study examined the effectiveness of somatic antidepressant treatments as administered in the community. METHOD: The study group consisted of 285 subjects with an intake diagnosis of major depressive disorder who had entered the National Institute of Mental Health Collaborative Depression Study as early as 1978, had at least one additional affective episode, and had been followed for up to 20 years, as recently as 1999. The characteristics that distinguished subjects receiving various levels of somatic antidepressant treatment were accounted for in what was called a propensity for treatment intensity model. The effectiveness of somatic antidepressant treatment during major affective episodes was then examined. RESULTS: Those who received higher levels of antidepressant treatment tended to have more prior episodes, more severe depressive symptoms, and more intensive somatic therapy during prior episodes and prior well intervals than those who received lower levels. Treatment effectiveness analyses that were stratified by propensity for treatment intensity demonstrated that those who received higher levels of antidepressant treatment were significantly more likely to recover from affective episodes. In contrast, those treated with lower levels were no more likely to recover than those who did not receive somatic treatment. CONCLUSIONS: Despite the indications of more severe depressive illness, those who received higher levels of somatic antidepressant treatment were more likely to recover from recurrent affective episodes. Results from this observational study extend the generalizability of reports from randomized clinical trials of antidepressants to a wider, more representative group of individuals who suffer from major depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12668362&dopt=Abstract antidepressant




A survey of antidepressant prescribing in the terminally ill.

Lloyd-Williams M, Friedman T, Rudd N.

LOROS Hospice, Leicester, UK.

Depression is a symptom in a quarter of patients admitted to a palliative care unit, but little is known of how depression in terminally ill patients is treated. We reviewed 1046 consecutive patient admissions, of whom 106 (10%) were prescribed antidepressant medication while under the care of a palliative care team. Of these patients, 21 were prescribed antidepressants when under the care of the home care team, but 80 patients (76%) were started on medication during the final 2 weeks of life. There was consequently insufficient time for the medication to have any therapeutic effect. Seventeen patients were discharged home on antidepressant medication. Three patients were referred for a psychiatric assessment. Patients prescribed antidepressants were significantly younger (P = 0.002) than those who were not. There were no prescriptions for psychostimulants. Although the numbers of patients prescribed antidepressant medication were low in all disease groups, it was notable that patients with breast cancer were prescribed antidepressant medication more frequently than any other patient group. We conclude that there appears to be a need for a coordinated approach to both the assessment and the treatment of depression in terminally ill patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10474711&dopt=Abstract antidepressant