Hispanic ethnicity, physician-patient communication, and antidepressant adherence.

Sleath B, Rubin RH, Huston SA.

University of North Carolina at Chapel Hill School of Pharmacy and Cecil G. Sheps Center for Health Services Research, Chapel Hill, NC, USA.

The purpose of the study was to examine how Hispanic ethnicity influenced physician-patient communication about antidepressants and antidepressant adherence using a data set of audiotapes and transcripts of 98 medical visits and medical and pharmacy records. The data were collected in 1995 at the University of New Mexico's general medicine and family practice clinics. Physicians were more likely to state antidepressant information to non-Hispanic white patients than to Hispanic patients. Physicians were more likely to state information to patients who were prescribed new antidepressants. Physicians asked approximately one of five patients on continued therapy how well their antidepressants were working and only one of 10 patients if they were experiencing any side effects. Non-Hispanic white patients were significantly more likely to state information about their antidepressants than Hispanic patients. Younger patients and patients who were prescribed new antidepressants were more likely to ask questions about antidepressants. Hispanic patients and patients who were prescribed new antidepressants were significantly less adherent to their antidepressant therapy during the one hundred day period after their audio-taped visits than non-Hispanic white patients and patients on continued therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12764707&dopt=Abstract antidepressant




Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment.

Stout SC, Owens MJ, Nemeroff CB.

Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

In a series of experiments, we tested the hypothesis that chronic antidepressant drug administration reduces the synaptic availability of corticotropin-releasing factor (CRF) through one or more effects on CRF gene expression or peptide synthesis. We also determined whether effects of acute or chronic stress on CRF gene expression or peptide concentration are influenced by antidepressant drug treatment. Four-week treatment with venlafaxine, a dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor, and tranylcypromine, a monoamine oxidase inhibitor, resulted in an attenuation of acute stress-induced increases in CRF heteronuclear RNA (hnRNA) synthesis in the paraventricular nucleus (PVN). Trends toward the same effect were observed after treatment with the 5-HT reuptake inhibitor fluoxetine, or the NE reuptake inhibitor reboxetine. CRF mRNA accumulation in the PVN during exposure to chronic variable stress was attenuated by concurrent antidepressant administration. Basal CRF hnRNA and mRNA expression were not affected by antidepressant treatment in the PVN or in other brain regions examined. Chronic stress reduced CRF concentrations in the median eminence, but there were no consistent effects of antidepressant drug treatment on CRF, serum corticotropin, or corticosterone concentrations. CRF receptor expression and basal and stress-stimulated HPA axis activity were unchanged after antidepressant administration. These results suggest that chronic antidepressant administration diminishes the sensitivity of CRF neurons to stress rather than alters their basal activity. Additional studies are required to elucidate the functional consequences and mechanisms of this interaction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11861819&dopt=Abstract antidepressant




Effects of antidepressants on function and viability of human neutrophils.

Strumper D, Durieux ME, Hollmann MW, Troster B, den Bakker CG, Marcus MA.

Department of Anesthesiology, Pain Therapy and Home Ventilation, University Hospital Maastricht, Netherlands.

BACKGROUND: Antidepressants are frequently used in chronic pain therapy and are under investigation as long-acting local anesthetics. Because of the structural similarities between antidepressants and local anesthetics, the authors hypothesized that these compounds act similarly, and they investigated the effects of nortriptyline, amitriptyline, imipramine, and fluoxetine on priming and activation of human polymorphonuclear neutrophils (hPMNs). METHODS: Effects of 30-, 120-, and 240-min preincubation with nortriptyline (10(-7)-10(-4) M), amitriptyline (10(-6)-10(-3) M), imipramine (10(-6)-10(-3) M), or fluoxetine (10(-7)-10(-4) M) on O(2)- generation of platelet activating factor-primed (10-6 M) and/or formyl-methionyl-leucyl-phenylalanine-activated (10(-6) M) isolated hPMNs were determined. All data are reported as mean +/- SD (statistics: t test, P < 0.05). RESULTS: Brief incubation in low concentrations of nortriptyline, amitriptyline, or fluoxetine (all at 10(-5) M) did inhibit priming but not activation of hPMNs. Imipramine (10(-5) M) affected neither priming nor activation. Prolonged incubation in lower concentrations of all antidepressants influenced neither priming nor activation. However, at higher concentrations, all four compounds exerted cytotoxic effects: virtually all hPMNs were killed by amitriptyline and imipramine (both at 10(-3) M) or nortriptyline and fluoxetine (both at 10(-4) M). CONCLUSION: Antidepressants, in low concentrations, inhibited priming but not activation of hPMNs. However, at concentrations similar to those attained after local injection, and in marked contrast to local anesthetics, antidepressants are profoundly toxic to hPMNs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12766643&dopt=Abstract antidepressant




Secular trends in antidepressant prescribing in the UK, 1975-1998.

Middleton N, Gunnell D, Whitley E, Dorling D, Frankel S.

Department of Social Medicine, University of Bristol.

BACKGROUND: We have examined secular trends in age- and sex-specific prescribing of antidepressants to determine whether these mirror changes in other population measures of mental health. METHOD: An analysis was carried out of age- and sex-specific rates of antidepressant prescribing by a representative sample or panel of UK general practitioners (GPs) in the period 1975-1998. RESULTS: The number of antidepressant prescriptions issued increased more than twofold in the period 1975-1998 and, in 1998, a total of 23.4 million antidepressant prescriptions were issued by GPs in the United Kingdom. Rates of antidepressant prescribing increased markedly in all age and sex groups with as much as a threefold increase in the older age groups. With the exception of 12-19-year-olds, these increases have been more marked in males, although absolute levels of prescribing are still at least two times higher in females. CONCLUSIONS: Antidepressant prescribing has increased in all age and sex groups. This indicates either that there have been changes in the presentation, recognition and management of depression in general practice or that the prevalence of depression has increased, or a combination of these two phenomena. The higher prescribing rate in females is in keeping with evidence from psychiatric morbidity surveys suggesting that women experience higher levels of psychiatric morbidity than men. Decreases in the ratio of female to male prescribing, however, support other data indicating that, relative to females, the mental health of young males has declined in recent years. Changes in patterns of help-seeking may also contribute to the observed trends.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11873886&dopt=Abstract antidepressant




Hepatotoxicity associated with the new antidepressants.

Carvajal Garcia-Pando A, Garcia del Pozo J, Sanchez AS, Velasco MA, Rueda de Castro AM, Lucena MI.

Instituto de Farmacoepidemiologia de la Universidad de Valladolid, Spain. carvajal ife.uva.es

BACKGROUND: Safety profiles of classical and new antidepressants are well established. Hepatotoxicity is known to occur. Recently, several cases of severe hepatic injury associated with the new antidepressants have been reported, prompting us to quantify this risk. METHOD: To estimate the cumulative incidence of hepatic adverse reactions associated with antidepressants, we used cases of hepatic damage collected via spontaneous reporting and included in the Spanish Pharmacovigilance System database; for exposure, we have used data from drug sales to the Spanish National Health System. RESULTS: The estimated reported incidence did not show major differences for the antidepressants studied, ranging from 1.28 cases per 100,000 patient-years for sertraline to 4.00 for clomipramine, except for nefazodone, which was the agent that had the highest incidence with 28.96 cases per 100,000 patient-years. CONCLUSION: The reported incidence of hepatic adverse reactions to nefazodone seems to be higher than that estimated so far. Given the high prevalence of depression and the widespread use of antidepressants, physicians should be alert to the possibility that these medications cause hepatitis and consider early discontinuation of an antidepressant if the condition is suspected.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11874214&dopt=Abstract antidepressant




Influence of antidepressant therapies on weight and appetite in the elderly.

Thomas P, Hazif-Thomas C, Clement JP.

Hopital de Jour Geriatrique Louis Pasteur, 86036 Poitiers, France. p.thomas chu-poitiers.fr

OBJECTIVE: Determine the nutritional impact of antidepressant drugs in elderly. METHODS: The study included 139 independently mobile out-patients managed by the Poitiers geriatric day hospital for problems of loss of home support, rehabilitation and medical or psychological care, with a stable treatment for 3 months at the time of inclusion and over the 3 months of the study. The study addressed the time course of nutritional parameters from baseline to 3 months post-inclusion. The physical examination included monthly weighing of the patients, 3-monthly evaluation of nutritional status using the Mini Nutritional Assessment (MNA) instrument and serum albumin. RESULTS: 52 men (76.3 +/- 6.7 years [62-87]) and 87 women (81.0 +/- 7.2 years [65-100]) were included. Seventy-nine patients presented with dementia. Seventy-four patients were receiving an antidepressant, of which 54 serotonin reuptake inhibitors. The patients free from dementia and not receiving antidepressants had nutritional indices that did not vary over the study period. The dementia-free patients receiving antidepressants gained weight (1.44 kg) - 1.87 kg on serotonin reuptake inhibitors - showed an improvement in MNA of 0.76/30 and showed a significant improvement in serum albumin of 1.78 g/L. The demented patients not receiving antidepressants lost weight (-1.01 kg), MNA score fell and serum albumin significantly decreased. On antidepressants, the demented patients significantly gained weight (0.73 kg) while no deterioration in the other parameters reflecting undernutrition was observed. Conclusions. In the middle term, in elderly subjects, antidepressants do not induce undernutrition or weight loss. Irrespective of antidepressant type, those agents seem to prevent weight loss in elderly subjects presenting with dementia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12766794&dopt=Abstract antidepressant




Prevalence and patterns of concomitant use of selective serotonin reuptake inhibitors and other antidepressants in a high-cost polypharmacy cohort.

Kotzan JA, Maclean R, Wade W, Martin BC, Lami H, Tadlock G, Gottlieb M.

College of Pharmacy, University of Georgia, Athens 30605, USA. jkotzan rx.uga.edu

BACKGROUND: Concomitant antidepressant therapy for patients who do not respond to selective serotonin reuptake inhibitors (SSRIs) may be appropriate under close medical supervision. However, little is known about the prevalence or patterns of concurrent antidepressant therapy in a typical large health maintenance organization. OBJECTIVE: The purpose of this study was to determine the prevalence of concomitant SSRI-antidepressant therapy and to assess the relationship between concomitant SSRI therapy, patient demographic characteristics, and the use of multiple prescribers and pharmacies. METHODS: This was a retrospective analysis of administrative prescription and medical claims data from January 1998 through September 1999. Data were obtained on beneficiaries who had >15 prescriptions dispensed in either of the first 2 quarters of 1999 and/or patients who accrued >$1,000 in prescription costs in either or both of the quarters. Patients were defined as undergoing concomitant SSRI therapy if they had received > or = 14 days of concomitant treatment with 2 SSRIs, an SSRI and tricyclic antidepressant, an SSRI and benzodiazepine, or an SSRI and miscellaneous antidepressant. Contingency analysis and logistic regression were used to identify factors associated with concomitant SSRI therapy. RESULTS: The relative risk for concomitant SSRI-SSRI therapy for patients with multiple prescribers versus a single prescriber was 2.32; the relative risk for patients receiving prescriptions from multiple pharmacies versus a single pharmacy was 2.97. Female patients were 19.8% more likely than male patients to receive concomitant SSRI therapy. Use of multiple prescribers increased the odds for concomitant SSRI therapy by >3.0 across the 4 therapeutic combinations. Use of multiple pharmacies increased the odds for concomitant SSRI-SSRI therapy by 5.42. CONCLUSIONS: Prescription of concomitant SSRI therapy was strongly associated with changes in strength of dosage and products and with use of multiple prescribers and pharmacies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11911554&dopt=Abstract antidepressant




Altered regulation of CREB by chronic antidepressant administration in the brain of transgenic mice with impaired glucocorticoid receptor function.

Blom JM, Tascedda F, Carra S, Ferraguti C, Barden N, Brunello N.

Department of Psychology, Universita Vita-Salute San Raffaele, Via Olgettina 58, Milan, Italy. blom mailserver.unimi.it

Various effects of antidepressant drugs on gene transcription have been described and altered gene expression has been proposed as being a common biological basis underlying depressive illness. One target for the common action of antidepressants is a modifying effect on the regulation of postreceptor pathways and genes related to the cAMP cascade. Recent studies have demonstrated that long-term antidepressant treatment resulted in sustained activation of the cyclic adenosine 3',5'-monophosphate system and in increased expression of the transcription factor cAMP response element binding protein (CREB). A transgenic animal model of depression with impaired glucocorticoid receptor function was used to investigate the effect of chronic antidepressant treatments on CREB expression in different brain areas. Wild-type and transgenic mice received one administration of saline, desipramine, or fluoxetine, daily for 21 days. The effects of antidepressants on CREB mRNA were analyzed using a sensitive RNase protection assay. Antidepressant treatment resulted in a neuroanatomically and animal specific expression pattern of CREB. Our findings suggest that life-long central glucocorticoid receptor dysfunction results in an altered sensitivity with respect to the effects of antidepressants on the expression of CREB.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11927185&dopt=Abstract antidepressant