Explaining variation in antidepressant prescribing rates in east London: a cross sectional study.

Hull SA, Aquino P, Cotter S.

Centre for General Practice and Primary Care, Institute of Community Health Sciences, Queen Mary's School of Medicine and Dentistry, University of London, Medical Sciences Building, Mile End Road, London E1 4NS, UK. s.a.hull qmul.ac.uk

BACKGROUND: Rates of depression and anxiety in south Asian populations are lower than expected. It remains uncertain whether this reflects a real difference in prevalence or differences in case recognition and management. OBJECTIVE: To examine whether concordance of culture or ethnicity between doctors and patients affects the prescribing rates for antidepressant and anxiolytic medications in general practice populations, taking into account demography, practice size and organization. METHOD: A cross-sectional general practice study, using practice and demographic data from primary care trusts, doctors' place of qualification from the General Medical Council, combined with practice level prescribing data from the prescription pricing authority (PACT) for the period 2000-2002. Set in 139 practices in the east London primary care trusts (PCTs) of Tower Hamlets, Hackney and Newham, multiethnic areas with large populations of south Asian residents and doctors. The main outcome measure was the annual prescribing rates for each group of drugs, calculated as the mean of two years average daily quantities (ADQs) for each medication, divided by the practice population. RESULTS: In east London the median prescribing rate (ADQs) for all antidepressants was 7.97 (inter-quartile range 4.91-10.76), for all anxiolytics and hypnotics 2.27 (interquartile range 1.11-3.96). There were significant differences in prescribing rates between practices with UK trained GPs and practices with south Asian trained GPs, with the highest rates of antidepressant prescribing in practices with UK trained GPs and low proportions of south Asian patients. No differences were found in anxiolytic and hypnotic prescribing rates between these practices. 57% of the variation in prescribing between practices could be explained by a model including the place of GP qualification, the proportion of registered women, older (>65) patients, and the list size per full time GP. CONCLUSIONS: Compared with previous studies prescribing rates for antidepressants have almost doubled over five years, the greatest increase being for selective serotonin re-uptake inhibitors (SSRIs). There is a modest fall in prescribing rates for anxiolytics and hypnotics. Concordance between south Asian practice populations and doctors from similar south Asian cultures is not associated with an increase in antidepressant prescribing. Lower rates of prescribing in practices with south Asian trained doctors occur regardless of the ethnic composition of the practice population. Reasons for these differences are uncertain, but may include differences in explanatory models for presenting symptoms, and management strategies which rely less on a biomedical paradigm.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15640295&dopt=Abstract antidepressant




A time-series analysis of the effect of increased copayments on the prescription of antidepressants, anxiolytics, and sedatives in Sweden from 1990 to 1999.

Ong M, Catalano R, Hartig T.

University of California, San Francisco, Division of General Internal Medicine, Ambulatory Care Center, 400 Parnassus Avenue, Box 0320, San Francisco, CA 94143-0320, USA. mong medicine.ucsf.edu

BACKGROUND: Outpatient prescription medication spending in Sweden has increased sharply since 1974. The Swedish government has raised copayments to reduce medication consumption and limit the growth of medication spending. OBJECTIVE: The aim of this study was to examine the effect of the 1995 and 1997 copayment increases on Swedish consumption of antidepressants, anxiolytics, sedatives. METHODS: Monthly drug-use data for July 1990 through December 1999 for these 3 pharmaceutical classes were obtained from Apoteket AB (Stockholm, Sweden). Data were provided for both sexes in units of defined daily doses per 1000 inhabitants. These series were analyzed with the use of Box-Jenkins autoregressive, integrated, moving-average time-series modeling methods. RESULTS: Dispensing of all 3 drugs classes increased immediately before copayment changes, with the exception of male sedative use at the time of the 1997 reform. Permanent increases in male antidepressant and sedative use occurred before the 1995 copayment reform. Only female antidepressant use was permanently reduced following the 1997 copayment reform. CONCLUSIONS: Our findings suggest that Swedish patients' valuation of mental health medications exceeds the enacted price increases. The permanent increases in male antidepressant and sedative use, beginning in 1995, may have been the result of previous undertreatment. The permanent reduction in female antidepressant use, beginning in 1997, suggests that the price levels reached a threshold that matched or exceeded Swedish women's valuation of these modific

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12809972&dopt=Abstract antidepressant




Antidepressant xerogenic medications and restoration rates.

Rindal DB, Rush WA, Peters D, Maupome G.

HealthPartners Research Foundation, 8100 34th Avenue S., Bloomington, MN 55425, USA. d.brad.rindal healthpartners.com

OBJECTIVES: This report examines the association between xerogenic antidepressant medication use and dental restorations (a proxy for dental caries). METHODS: Data for this study was collected from the electronic databases of two large dental group practices associated with two managed care organizations. The population examined was at least 55-year-old on the reference date and had at least 48 months of concurrent dental, medical and pharmacy coverage. We identified 915 individuals whose only exposure to a xerogenic medication was to an antidepressant. This group was compared with a group not on any medications and to a group on medications without any known xerostomic side effect. RESULTS: Poisson regression was used to compare restoration occurrence and restoration rates among the three groups. The antidepressant medication and the no xerogenic medication groups were more likely to have restorations than the no medication group but there was no difference in restoration rates between the two medication groups. The mean restoration rates were significantly different between the three groups with the antidepressant group having the highest restoration rate. The no xerogenic group also had a higher rate than the no medication group but not as high as the antidepressant group rate. CONCLUSIONS: This study provides objective quantification of the long-term effects that anti-depressant medications have on restoration use. Copyright Blackwell Munksgaard, 2005.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15642049&dopt=Abstract antidepressant




Facilitation of spontaneous glutamate release by antidepressant drugs in rat locus coeruleus.

Ishibashi H, Eto K, Kajiwara M, Noda M.

Department of Bio-signaling Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. h-ishi psysiol2.med.kyushu-u.ac.jp

The effects of antidepressant drugs on spontaneous excitatory postsynaptic currents (EPSCs) were investigated in the mechanically dissociated rat locus coeruleus (LC) neurons which had their presynaptic nerve terminals attached. The membrane currents were recorded by the whole-cell patch-clamp technique. Desipramine, a tricyclic antidepressant, reversibly and concentration-dependently increased the frequency of spontaneous EPSCs, but did not alter their amplitude distribution. The inhibitors of high-voltage-activated Ca2+ channels failed to block the facilitatory action of desipramine, while they inhibited the high K+-induced facilitation of spontaneous EPSC frequency. The desipramine action was also observed in the absence of extracellular Ca2+. Pretreatment of thapsigargin in Ca2+-free solution fully inhibited the desipramine action, thus suggesting the involvement of Ca2+ release from intracellular Ca2+ stores at glutamatergic presynaptic nerve terminals. Imipramine and nortriptyline, other tricyclic antidepressants, and amoxapine, mianserin and fluoxetine, non-tricyclic antidepressants, also increased the EPSC frequency, while tranylcypromine, an inhibitor of monoamine oxidase, did not increase the glutamate release. The present results indicate that modulation of spontaneous glutamatergic transmission by tricyclic- and non-tricyclic-antidepressant drugs may regulate the excitability of LC neurons.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15644283&dopt=Abstract antidepressant




Comparative assessment of Yale Single Question and Beck Depression Inventory Scale in screening for depression in multiple sclerosis.

Avasarala JR, Cross AH, Trinkaus K.

Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA. avasaralaj neuro.wustl.edu

OBJECTIVES: To examine if depression in multiple sclerosis (MS) can be accurately recognized using the Yale Single Question (YSQ) screen as compared with the Beck Depression Inventory (BDI), a 21-item self-report rating scale for depression. In addition, we sought to assess the sensitivity, specificity the positive predictive value (PPV) and the negative predictive value (NPV) of the YSQ. BACKGROUND: Depression associated with MS is a major contributor to morbidity. Screening for depression in patients with MS currently includes the BDI, which measures characteristic attitudes and symptoms of depression. However, in a busy outpatient clinic, the BDI might not be the most appropriate instrument, particularly if depression screening can be assessed accurately using simpler techniques that are easy to administer and consume less time. We compared the accuracy of the YSQ screen response against the BDI to screen for depression in MS patients, in an outpatient setting. METHODS: This is a comparative outcome study of two 'instruments' used for screening depression in MS patients in an academic outpatient setting. All patients were initially screened for depression by asking patients the YSQ--'Do you frequently feel sad or depressed?', followed by BDI administration. Depression was defined as a score of > or = 13 on the BDI. One hundred and twenty successive patients who presented to the MS clinic at Washington University School of Medicine and met the criteria for diagnosis of MS were screened for depression. All patients diagnosed as having MS, regardless of type, were included in the study. RESULTS: Of the 120 patients studied, a total of 49 of 120 were clinically depressed as defined by a BDI cut-off of > or = 13; 71 of 120 were not. The sensitivity of the YSQ was 32 of 49 = 65.3% with a 95% confidence interval (0.50, 0.78), specificity was 62 of 71 = 87.3% (0.77, 0.94), PPV was 32 of 41 = 78.0% (0.62, 0.89) and NPV was 62 of 79 = 78.5% (0.68, 0.87). Of the 49 patients depressed by BDI criteria, 17 responded 'no' to the YSQ, yielding a false-negative rate of 34.7% (0.22, 0.50). The Wilcoxon-Mann-Whitney test for difference in age among those on antidepressants compared with those who were not showed no statistical difference (P = 0.35). For patients on antidepressants, the mean BDI score was 16.0+/-8.9 (mean+/-SD) and 9.5+/-8.7 for those not on antidepressants. Differences in BDI scores among patients on antidepressants versus those who were not were statistically significant (P < 0.0001). Patients on antidepressants had significantly higher BDI scores. CONCLUSIONS: Our results show that the YSQ cannot replace the BDI as a screening instrument for depression in MS. The YSQ could not identify 34.7% of patients who were depressed by BDI criteria. However, as reported in a published study, BDI missed 30% of cases with early depression in MS when a cut-off of > or = 13 was used. The YSQ appears to be specific in ruling out depression when a patient is not depressed. MS is a chronic disease and since prevalence of depression varies, it is important to screen patients repeatedly over time so as not to miss the diagnosis. That BDI scores were higher among those taking antidepressants underscores the fact that this subset of patients need to be on medication, but the higher scores could also represent a sampling error since the duration of antidepressant use was not studied.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12814181&dopt=Abstract antidepressant




A role for galanin in antidepressant actions with a focus on the dorsal raphe nucleus.

Lu X, Barr AM, Kinney JW, Sanna P, Conti B, Behrens MM, Bartfai T.

Department of Neuropharmacology and The Harold L. Dorris Neurological Research Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. xiaoying scripps.edu

Selective serotonin reuptake inhibitors, such as fluoxetine (FLX), are the most commonly used drugs in the treatment of major depression. However, there is a limited understanding of their molecular mechanism of action. Although the acute effect of selective serotonin reuptake inhibitors in elevating synaptic serotonin concentrations is well known, the clinical amelioration of depressive symptoms requires 14-21 days of treatment, suggesting that numerous other rearrangements of function in the CNS must take place. In the present study, we demonstrated that 14 days of FLX treatment up-regulated galanin mRNA levels by 100% and GalR2-binding sites by 50%, in the rat dorsal raphe nucleus, where galanin coexists with serotonin. Furthermore, a galanin receptor antagonist, M40, attenuated the antidepressant-like effect of FLX in the forced swim test, a rodent preclinical screen commonly used to evaluate antidepressant-like efficacy. Direct activation of galanin receptors by a galanin receptor agonist, galnon, was found to produce an antidepressant-like effect in the same task. Two other antidepressant treatments also affected the galaninergic system in the monoaminergic nuclei: Electroconvulsive shock elevated galanin mRNA levels in dorsal raphe nucleus, whereas sleep deprivation increased galanin mRNA levels in the locus coeruleus, further underlining the connection between activation of the galaninergic system and antidepressant action of various clinically proven treatments.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15647369&dopt=Abstract antidepressant




Complexity of medication use in the Veterans Affairs healthcare system: Part II. Antidepressant use among younger and older outpatients.

Silkey B, Preskorn SH, Golbeck A, Shah R, Neff M, Jones TL, Choi J.

Via Christi Research Institute, Wichita, KS, USA.

CONTEXT: A previous study, described in Part I of this report, found that 71% of a sample of 5,003 general outpatients in the Veterans Affairs healthcare system were receiving a unique drug regimen (i.e., total specific drug entities regardless of dose, formulation, or administration schedule). The simplest regimens contained only one drug, while the most complex regimens exceeded 20 different drugs. The purpose of the present study was to determine if patients receiving a specific therapeutic class of medications (e.g., antidepressants) have more homogeneous drug regimens. OBJECTIVE: to examine the extent and complexity of multiple medication use in younger and older adult outpatients receiving antidepressants compared with those not receiving antidepressants. The study focused on drugs that act systemically or gastrointestinally and hence have the potential to interact. DESIGN, SETTING, AND PARTICIPANTS: Two subsets of stratified random samples of outpatients selected from prescription databases of U.S. Veterans Integrated Service Network 15. The first group involved 1,991 patients deemed to be on antidepressants (AD patients): 891 aged < 60 years and 1,100 aged > or = 60 years. The second group involved 3,732 patients who had received no antidepressants within the previous 365 days but who had a supply of at least one other current prescription (NoAD patients): 1,195 aged < 60 years and 2,535 aged > or = 60 years; 2 missing age information. MAIN OUTCOME MEASURES: number of drugs, frequency of drug regimens, level of multiple medication use including and excluding antidepressants. RESULTS: Younger AD patients received 3 more drugs than younger NoAD patients. 23.6% of younger AD patients, versus 5.9% of younger NoAD patients, received > or = 8 drugs. Older AD patients received 2 more drugs than older NoAD patients. 37.6% of older AD patients, versus 12.8% of older NoAD patients, received > or = 8 drugs. In both the AD and NoAD groups, 62%-96% of patients of all ages were receiving unique drug regimens. Each drug regimen containing 2 or more drugs occurred in fewer than 1% of patients. CONCLUSIONS: AD patients were receiving more complex drug regimens and had a higher frequency of unique drug regimens than NoAD patients, even when the results were adjusted for age group and number of prescribers. The high prevalence of unique drug combinations in all patient groups in this study indicates that clinicians in this system have only limited experience with the total effects of all of the medications their patients are receiving and thus cannot rely on experience to guard against adverse multi-drug interactions. This fact is a particular concern with psychiatric medications because adverse DDIs involving these medications can mimic psychiatric symptoms and may therefore be more difficult to detect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15650618&dopt=Abstract antidepressant




Combined use of SSRIs and NSAIDs increases the risk of gastrointestinal adverse effects.

de Jong JC, van den Berg PB, Tobi H, de Jong-van den Berg LT.

Department of Social Pharmacy and Pharmacoepidemiology, Groningen University Institute for Drug Exploration, University Centre for Pharmacy, Groningen, The Netherlands.

AIMS: To investigate the relationship between the use of antidepressants with or without NSAIDs and the risk of gastrointestinal side-effects. METHODS: This was a population-based cohort study. Medication data of 180,000 patients from 16 pharmacies in The Netherlands were studied. The subjects were a group of 15 445 new users of antidepressants with or without NSAIDs. A review of patient profiles for cases of gastrointestinal adverse effects caused by first time use of antidepressants with or without NSAIDs was carried out. The number of first prescriptions for peptic ulcer drugs (Anatomical Therapeutic Chemical classification A02B) in the period from day 2 after starting antidepressants with or without NSAIDs until 10 days after the last dose was the main outcome measure. RESULTS: In the reference group of 619 new users of nonselective antidepressants (TCAs), the incidence of first prescriptions for peptic ulcer drugs was 0.051 (95% confidence interval 0.021, 0.105). The use of SSRIs (n = 1181) caused a slightly higher incidence rate ratio (IRR) of 1.2 (0.5, 2.8). The combined use of SSRIs and NSAIDs (n = 86) increased the IRR to 12.4 (3.2, 48.0). In contrast, the combination of nonselective antidepressants and NSAIDs (n = 74) increased the IRR to 2.5 (0.3, 20.3). CONCLUSIONS: SSRIs increase the risk of gastrointestinal adverse effects in first time users as compared with nonselective antidepressants. The combined use of SSRIs and NSAIDs strongly increases the risk of gastrointestinal adverse effects and should be avoided. The combination of nonselective antidepressants and NSAIDs does not have this effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12814454&dopt=Abstract antidepressant