Regional variation in anti-depressant dispensings in New Zealand: 1993-1997.

Roberts E, Norris P.

Health Services Research Centre, Institute for Policy Studies, Victoria University of Wellington. eroberts hist.umn.edu

AIMS: To examine regional differences in the prescribing of anti-depressants in New Zealand from 1993 to 1997, and to examine the composition and dynamics of these differences. METHODS: Data on every subsidised dispensing of anti-depressant drugs 1993 to 1997 were obtained from PHARMAC and analysed using SAS. Each dispensing was allocated to a regional council area on the basis of the location of the dispensing pharmacy. RESULTS: Prescribing of anti-depressants increased with time in all regions. However, there was substantial regional variation in prescribing rates per-capita, the highest being 2.28 to 2.49 times the lowest in every year. Regions also varied substantially in the mix of newer and older drugs used, although newer drugs became increasingly important in every region. CONCLUSIONS: Regional differences in anti-depressant prescribing are large. Further research with different data sources is required to explore the reasons for this variation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11277471&dopt=Abstract antidepressant




Anti-depressant prescribing patterns for prison inmates with depressive disorders.

Baillargeon J, Black SA, Contreras S, Grady J, Pulvino J.

Department of Pediatrics, University of Texas Health Science Center, San Antonio, TX 78284-7802, USA. baillargeon uthscsa.edu

BACKGROUND: Although prison inmates are reported to exhibit elevated rates of depressive disorders, little is known about anti-depressant prescribing patterns in correctional institutions. METHODS: The study population consisted of 5305 Texas Department of Criminal Justice (TDCJ) inmates who were diagnosed with one of three depressive disorders: major depression, dysthymia, and bipolar disorder (excluding those with manic episodes only). Information on medical conditions, sociodemographic factors, and pharmacotherapy was obtained from an institution-wide medical information system. RESULTS: In 1998, 78.2% of all inmates diagnosed with depressive disorders were treated with antidepressant medication. Of these, 47.3% were treated exclusively with tricyclic anti-depressants (TCA); 30.9% were treated with selective serotonin re-uptake inhibitors (SSRI); and 21.8% were not treated with any form of anti-depressant medication. Prescribing patterns varied substantially according to a number of sociodemographic factors under study. LIMITATIONS: Because the present study relied on retrospective, clinical data, the investigators had limited ability to assess: specific symptomatology for each diagnosed depressive condition under study; socio-economic status, pre-incarceration access to health care; and the overall reliability and validity of the data. CONCLUSION: The proportion of prison inmates with depressive disorders who receive appropriate medication management is substantially higher than that reported among similarly diagnosed nonincarcerated samples. It will be important, however, for future investigators to examine the sources of sociodemographic variation in treatment patterns found in the present study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11246100&dopt=Abstract antidepressant




Anti-depressant action of melatonin in chronic forced swimming-induced behavioral despair in mice, role of peripheral benzodiazepine receptor modulation.

Raghavendra V, Kaur G, Kulkarni SK.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India.

The possible antidepressant effect of physiological and pharmacological doses of melatonin was investigated in the Porsolt forced swimming-induced behavioral despair test. The duration of immobility period of BALB/c and C57BL/6J mice during a 6-min swim test was measured at noon (11:00-12:00 h), early dark (20:00-21:00 h) and at midnight (1:00-2:00 h), respectively. The circadian time cycle did not alter the duration of immobility in either strains of mice. Similarly, exogenously administered melatonin (10-1000 microg/kg congruent with 50 nM to 5 microM/mouse), a dose that could act on high affinity melatonin receptors, did not modify the duration of immobility period at any of the time intervals studied in either strains of the mice. This suggested that neither circadian variation influenced the duration of immobility period of BALB/c and C57BL/6J mice nor at physiological doses melatonin showed any anti-depressant action. Acute administration of higher doses of melatonin (2.5-10 mg/kg) failed to induce any anti-depressant activity in mice which were subjected to forced swimming test for the first time. However, daily administration of melatonin (2.5-10 mg/kg) prior to swimming test significantly reversed the increase in immobility period that was observed on chronic exposure to swimming test. This effect was comparable with the effect of GABA-benzodiazepine (BZ) receptor agonists. Similarly, like GABAergic drugs, acute administration of melatonin also showed anti-depressant activity in a mice which were exposed to chronic forced swimming test. The anti-depressant action of melatonin was sensitive to reversal by peripheral BZ receptor antagonist, PK11195. Whereas, flumazenil failed to reverse the anti-depressant action of melatonin, thereby suggesting that central BZ receptor were not involved in its action. In conclusion the study showed that at pharmacological doses melatonin has anti-depressant action in chronic forced swimming-induced despair behavior by an action involving peripheral BZ receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11115737&dopt=Abstract antidepressant




Enhancing the technology of clinical trials and the trials model to evaluate newly developed, targeted antidepressants.

Katz MM, Halbreich UM, Bowden CL, Frazer A, Pinder RM, Rush AJ, Wheatley DP, Lebowitz BD.

Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. mkbsk Worldnet.ATT.net

Concern about disappointing results from recent multi-center trials of new antidepressants prompted several ACNP workshops on "improving the technology of clinical trials." The workshops focused on technical problems, such as patient screening, reliability of clinical ratings, and the role of the placebo control. They aimed to determine how to more effectively apply the current clinical trials model for evaluating antidepressant drugs. The problems confronting the field of clinical trials, however, extend beyond technology. They also included conceptual issues concerning changes in the understanding of depressive disorders and of the multiple actions of antidepressant drugs. Such problems have been further complicated by the rapidly changing field of drug development itself, which is continually refining the targeting of new antidepressant agents. Drugs are increasingly being developed to try to change specific behavioral facets more rapidly and may be less likely, therefore, to act initially on "whole" disorders. To address such issues, a symposium was held in Rhodes in 2000 that focused on such conceptual changes with the goal of developing recommendations to revise the clinical evaluation model. Its purpose was to integrate new knowledge on depression and the mechanisms of action of antidepressant drugs toward developing more efficient methods of drug development. Since the evaluation process will eventually require changes in governmental policy, senior staff from the National Institute of Mental Health (NIMH) , Unites States and Food and Drug Administration (FDA), Unites States participated as well as members of academia, industry and clinical practice. Recommendations for altering clinical trial methodology were made in four areas: patient selection, methodology of evaluation, measuring onset of action, and FDA and NIMH perspectives on current practice. This article discusses these four areas and presents the consensus of the panel participants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12225690&dopt=Abstract antidepressant




[Risk factors associated with the consumption of antidepressant agents]

[Article in Spanish]

Rispau Falgas A, Soler Vila M, Garcia Bayo I, Carames Duran E, Espin Martinez A, Garcia Pulido C.

Centro de Salud Gava II, Barcelona.

OBJECTIVES: To find the profile of the consumer of anti-depressants, identify risk factors and calculate the prevalence of the under-diagnosis of depression in our milieu. DESIGN: Case-control study. SETTING: Gava II Health Centre, Barcelona. PARTICIPANTS AND METHODS: The study covered 134 consumers of anti-depressants and 274 controls with no treatment (one group from the Centre, the other from the community) paired for sex, age and general practitioner. The Zung-Conde self-applied depression) scale was administered. MEASUREMENTS AND MAIN RESULTS: 88% of those surveyed were women, with an average age of 50. The prescribing doctor was, in 55% of cases, their general practitioner. The anti-depressants prescribed were mainly (70.9%) from the group of selective inhibitors of serotonin uptake. There were more divorced and widowed people among the cases (p < 0.05). The pathology most often associated with the cases was digestive (31%, p < 0.02). 63% of cases had suffered some event they thought important in the 6 months before prescription. Average score on the Zung test was 51.5% in the cases, and 40% in the controls (p < 0.0001). Using 50 on the Zung scale as the cut-off point, we classified 56% of the cases and 17% of the controls as depressed. CONCLUSIONS: The profile of the consumer of anti-depressants is a women of about 50, living as one of a couple, house-wife, with primary education only, and medium to low social and economic level. The prevalence in the controls of depressive illness neither detected nor treated is similar to that found in other studies. We need to find some instrument to measure attitude, in order to reduce the number of patients who are underdiagnosed in the consulting room.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9842082&dopt=Abstract antidepressant




Affective disorder and epilepsy comorbidity: implications for development of treatments, preventions and diagnostic approaches.

Jobe PC.

Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, PO Box 1649, Peoria, Illinois 61656-1649, USA. pcj uic.edu

Concepts pertaining to affective disorder and epilepsy comorbidity are contributing appreciably to improvements in patient care. Several antiepileptic treatments have become important components of the management of bipolar affective disorder. In contrast, little progress has emerged in developing clinical applications of the anticonvulsant properties of the antidepressants in the treatment of the epilepsies. The slow onset of action of the antidepressants remains a major impediment to fully effective treatment of depressive episodes. Nevertheless, studies from experimental epileptology demonstrate that the anticonvulsant effects of the antidepressants occur rapidly and as a consequence of noradrenergic and/or serotonergic activation. These studies also demonstrate that adequate initial doses of the antidepressants are essential to rapid onset of anticonvulsant action. Pharmacokinetically valid loading dose paradigms are seemingly avoided with antidepressant drugs in humans because of potential toxicities and/or patient unacceptability. However, substantial progress has been made in reducing the adverse effect liability of the antidepressants. No longer is convulsive liability considered to stem from the therapeutic mechanisms of the anti-depressants. Rather, noradrenergic and serotonergic influences have demonstrable anticonvulsant properties. Other side effects may also be separable from the anticonvulsant and antidepressive effects of antidepressive treatments. The concept that the protracted process of antidepressant-induced beta-noradrenergic down-regulation is an essential prelude to the onset of mood benefit is no longer a sustainable premise. Nevertheless, increasing evidence underlies the possibility that knowledge of serotonergic and noradrenergic regulatory processes can be used to design strategies that will hasten the onset of antidepressive action. Similar optimism pervades efforts to determine the possibility that dual inhibition of serotonin and norepinephrine transporters will hasten onset of antidepressive action. Moreover, because noradrenergic and serotonergic systems are determinants of predisposition to seizures and to dysfunctional affective episodes, augmentation strategies may also be applicable to the use of antidepressant drugs in epilepsy and to the use of antiepileptic drugs such as carbamazepine in mood disorders. Recent studies have demonstrated that, in part, the therapeutic effectiveness of carbamazepine may stem from its marked capacity to elevate serotonin concentrations in the extracellular fluid of the brain via mechanisms that differ from those of the membrane reuptake inhibitors. Evidence suggests that the epilepsies and affective disorders may arise from a multiplicity of neurobiological abnormalities. A disorder in one individual may arise via different mechanisms than a phenomenologically similar disorder in another individual. Thus, diagnostic tools are needed to make mechanistic distinctions among individuals so that treatments can be appropriately developed and selected. In terms of epileptogenesis and affective disorder progression, neuroprotective paradigms for one individual may differ from those needed for another. Moreover, diagnostic technologies that are adequate to detect genetically and/or experientially determined vulnerability before the onset of a seizure or dysfunctional affective episode may be valuable steps toward achieving goals of prevention.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15112464&dopt=Abstract antidepressant




Are bipolar I depressive patients less responsive to treatment with antidepressants than unipolar depressive patients? Results from a case control study.

Bottlender R, Rudolf D, Jager M, Strauss A, Moller HJ.

Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstr. 7, 80336 Munich, Germany. bottlend psy.med.uni-muenchen.de

The increasing evidence that bipolar and unipolar affective disorders have different biological etiologies and courses of illness has been associated with an intensifying interest in specific treatment regimens for both disorders during the last decade. In this context, the question arose whether antidepressants exert similar efficacy in the acute treatment of bipolar compared to unipolar depression. Although the clinical impression does not indicate substantial differences in the efficacy of antidepressants between these groups of patients, empirical databases concerning this topic are rare. The present study compared the efficacy of antidepressants in 50 unipolar and 50 bipolar depressed inpatients (ICD-9 criteria) under naturalistic treatment conditions. Both groups of patients were matched for age, gender and duration of illness. Clinical assessments of status at the time of admission and at discharge were used to rate response to antidepressant treatment. Analyses of the data revealed that both groups of patients needed the same time for treatment response and did not show any significant differences in outcome measures at discharge. These findings do not concur with the hypothesis formulated by some experts in the field of affective disorders that antidepressants are less effective in the acute treatment of bipolar depressed patients compared to unipolar depressed patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12231265&dopt=Abstract antidepressant




Discontinuation of use and switching of antidepressants: influence of patient-physician communication.

Bull SA, Hu XH, Hunkeler EM, Lee JY, Ming EE, Markson LE, Fireman B.

Division of Research, Kaiser Permanente Medical Care Program, 2000 Broadway, Oakland, CA 94612-2304, USA. scott.bull alza.com

CONTEXT: Although current depression treatment guidelines recommend continuing antidepressant therapy for at least 4 to 9 months, many patients discontinue treatment prematurely, within 3 months. OBJECTIVES: To investigate the relationship between patient-physician communication and the continuation of treatment with antidepressants and to explore the demographics, adverse effects, therapeutic response, and frequency of follow-up visits. DESIGN, SETTING, AND PATIENTS: A total of 401 telephone interviews of depressed patients being treated with selective serotonin reuptake inhibitor (SSRI) therapy between December 15, 1999, and May 31, 2000, were conducted and 137 prescribing physicians completed written surveys from Northern California Kaiser Permanente health maintenance organization outpatient clinics. MAIN OUTCOME MEASURES: Patient-physician communication about therapy duration and about adverse effects; therapy discontinuation or medication switching within 3 months after start of SSRI therapy. RESULTS: Ninety-nine physicians (72%) reported that they usually ask patients to continue using antidepressants for at least 6 months, but 137 patients (34%) reported that their physicians asked them to continue using antidepressants for this duration and 228 (56%) reported receiving no instructions. Patients who said they were told to take their medication for less than 6 months were 3 times more likely to discontinue therapy (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.21-8.07) compared with patients who said they were told to continue therapy longer. Patients who discussed adverse effects with their physicians were less likely to discontinue therapy than patients who did not discuss them (OR, 0.49; 95% CI, 0.25-0.95). Patients who reported discussing adverse effects with their physicians were more likely to switch medications (OR, 5.60; 95% CI, 2.31-13.60). Fewer than 3 follow-up visits for depression, adverse effects, and lack of therapeutic response to medication were also associated with patients' discontinuing therapy. CONCLUSIONS: Discrepancies exist between instructions that physicians report they communicate to patients and what patients remember being told. Explicit instructions about expected duration of therapy and discussions about medication adverse effects throughout treatment may reduce discontinuation of SSRI use. Our finding that patients with 3 or more follow-up visits were more likely to continue using the initially prescribed antidepressant medication suggests that frequent patient-physician contact may increase the probability that patients will continue therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234237&dopt=Abstract antidepressant