Variations in antidepressant prescribing practice: clinical need or market influences?

De Las Cuevas C, Sanz EJ, De La Fuente JA.

Department of Psychiatry, University of La Laguna, Tenerife, Canary Islands, Spain. ccuevas ull.es

OBJECTIVE: To assess the antidepressant prescribing patterns of community psychiatrists, and the prescriptions issued by general practitioners and private physicians during 1999 in order to analyse and discuss the intensity and sources of variations between doctors. METHODS: All reimbursed prescriptions for antidepressants written in 1999 by community psychiatrists and general practitioners working for the Canary Islands Health Service at Santa Cruz de Tenerife were collected from official sources. Prescriptions were available individualized for each psychiatrist but were collected globally for the others. Drugs were classified according to the Anatomic Therapeutic Chemical (ATC-1999 edition) System and use was quantified in terms of defined daily doses (DDDs). As an indicator of the quality of drug prescribing, the DU90% was used. RESULTS: The total use of antidepressant in Tenerife was 21.4 DDD/1000 inhabitants/day. The most frequently prescribed substances were fluoxetine, paroxetine and sertraline, which accounted for 58% of all prescriptions. Each psychiatrist used between 10 and 20 different substances and between 15 and 26 different trade names. Prescribing by general practitioners mirrored that of psychiatrist, and private doctors (mainly psychiatrist) were found to have a different pattern of prescribing with higher use of new and uncommon antidepressants. Psychiatrists acknowledge the pressures of promotion by the pharmaceutical industry and half of them recognize a personal relationship with some 'company representatives'. CONCLUSION: There is a remarkable degree of variation in antidepressant prescribing by psychiatrists and general practitioners, this is due to economic and social factors as much as to morbidity differences.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12426937&dopt=Abstract antidepressant




Plasma concentrations of neuroactive steroids before and after repetitive transcranial magnetic stimulation (rTMS) in major depression.

Padberg F, di Michele F, Zwanzger P, Romeo E, Bernardi G, Schule C, Baghai TC, Ella R, Pasini A, Rupprecht R.

Department of Psychiatry, Ludwig-Maximilian University, Nussbaumstr. 7, D-80336, Munich, Germany.

There is evidence for altered levels of neuroactive steroids in major depression that normalize after successful antidepressant pharmacotherapy. Currently it is not known whether this is a general principle of clinically effective antidepressant therapy or a pharmacological effect of antidepressants. Here, we investigated whether repetitive transcranial magnetic stimulation (rTMS) may affect plasma concentrations of neuroactive steroids in a similar way as antidepressant pharmacotherapy. Progesterone, 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta- tetrahydroprogesterone (3alpha,5beta-THP), 3beta,5alpha-tetrahydroprogesterone (3beta, 5alpha-THP) and dehydroepiandrosterone (DHEA) were quantified in 37 medication-free patients suffering from a major depressive episode before and after 10 sessions of left prefrontal rTMS. Plasma samples were analyzed by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. There was a significant reduction of depressive symptoms after rTMS. However, plasma concentrations of neuroactive steroids were not affected by rTMS and not related to clinical response. Clinical improvement after extended daily treatment with rTMS is not accompanied by changes in neuroactive steroid levels. Changes in neuroactive steroid levels after antidepressant pharmacotherapy more likely reflect specific pharmacological effects of antidepressant drugs and are not necessary for the amelioration of depressive symptoms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12431862&dopt=Abstract antidepressant




How well do antidepressants work in older people? A systematic review of Number Needed to Treat.

Katona C, Livingston G.

Department of Psychiatry and Behavioural Sciences, Royal Free and University College Medical School, Wolfson Building, 48 Riding House Street, London W1N 8AA, UK. c.katona ucl.ac.uk

OBJECTIVES: To make direct comparisons between studies of antidepressant treatment of older people using Number Needed to Treat (NNT) analysis. METHODS: Medline and Embase Search 1966-1999 and contact with manufacturers of antidepressant drugs asking for any relevant data on file; NNT analyses of outcome in terms of efficacy and adverse effects. RESULTS: Most antidepressant trials show efficacy; this is less clear for moclobemide and fluoxetine. Head-to-head comparisons between antidepressants showed significant superiority for paroxetine over fluoxetine and a trend in favour of SSRIs and venlafaxine over tricyclics. CONCLUSIONS: NNT analysis is one way of providing intelligible information on antidepressant efficacy and adverse effects which can inform clinical decisions. LIMITATIONS: Many studies do not present data in a form amenable to NNT analysis. Most head-to-head comparisons between antidepressants are underpowered.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12103451&dopt=Abstract antidepressant




Influence of resistance to antidepressant pharmacotherapy on short-term response to electroconvulsive therapy.

Pluijms EM, Birkenhager TK, Huijbrechts IP, Moleman P.

Department of Biological Psychiatry, Parnassia Psychomedical Centre, P.O. Box 53002, 2505 AA The Hague, The Netherlands.

BACKGROUND: Few studies assessing the influence of resistance to antidepressant pharmacotherapy on the response to subsequent electroconvulsive therapy (ECT) are found in the literature. Results are somewhat conflicting and may not be applicable to the population of depressed patients in The Netherlands. The aim of this study is to assess the influence of medication resistance on the short-term response to ECT in a population of severely depressed inpatients in The Netherlands, where ECT is an exceptional treatment, often used as a final treatment option. METHODS: We reviewed the records of 41 consecutive inpatients with major depression according to DSM-III-R criteria and rated each patients' antidepressant pharmacotherapy prior to ECT. We examined the extent to which medication resistance was related to short-term response to ECT. RESULTS: When a reduction of at least 50% on the Hamilton Rating Scale for Depression (HRSD) post-ECT compared to pre-ECT (partial remission) is used as response criterion, medication resistant patients and patients without established medication resistance were equally likely to respond to subsequent ECT. When a post-ECT HRSD score < or = 7 (full remission) is used as response criterion, medication resistant patients were less likely to respond to subsequent ECT (8/29=27.6%) than patients who did not receive adequate antidepressant pharmacotherapy prior to ECT (6/12=50.0%), although the difference in response rate was not statistically significant. LIMITATIONS: This study has a retrospective nature and a relatively small sample size. CONCLUSION: Antidepressant medication resistance does not seem to have an influence on the short-term response to subsequent ECT. However, when the number of patients achieving full remission is concerned, a substantial percentage of antidepressant medication resistant patients respond to ECT, although their response rate was nearly half compared to that of patients without prior adequate treatment with antidepressants. This difference in response rate was not statistically significant. ECT seems to be an effective treatment for both patients with and without prior adequate treatment with antidepressants in this Dutch population.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12103456&dopt=Abstract antidepressant




What are older peoples' experiences of taking antidepressants?

Prabhakaran P, Butler R.

Paterson Centre for Mental Health, St Mary's Hospital, 20 South Wharf Road, London W2 1PD, UK.

BACKGROUND: Antidepressants are prescribed widely to older people but little is known about older peoples' own reported experiences of taking them in routine practice. METHODS: A doctor interviewed 92 people, aged over 65, with a hospital diagnosis of depression, who had been prescribed an antidepressant in the past year. RESULTS: Most of the subjects were prescribed a selective serotonin reuptake inhibitor (SSRI), at a standard dose, for at least 8 weeks. Most people felt the antidepressants were helpful, although a third felt they made no difference. Two thirds of older people reported having adverse effects of which most were moderate or severe. The most common adverse effects were headache and dry mouth. Only a third said that they always took their tablets. LIMITATIONS: The sample was restricted to older people seen by hospital services. Interviews were carried out by a doctor and patients may not have been entirely truthful. CONCLUSIONS: Older people have important views about their treatment that they are prepared to tell a doctor. A lot of older people do not think their antidepressants are helpful, and the majority experience adverse effects. Many do not always take their medication. Doctors should routinely ask older people about their experiences of taking antidepressants. Copright 2002 Elsevier Science BV.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12128244&dopt=Abstract antidepressant




Effects of antidepressants in rats trained to discriminate centrally administered isoproterenol.

Crissman AM, O'Donnell JM.

Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA. acrissman utmem.edu

Previous work has shown that the discriminative stimulus effects of centrally administered isoproterenol are mediated primarily via beta1-adrenergic receptors. In the present study, this model was used to investigate the ability of antidepressant drugs displaying various pharmacological profiles to stimulate beta1-adrenergic receptors in vivo; this was assessed by determining whether they substituted for the discriminative stimulus effects of isoproterenol. Rats were trained to discriminate centrally administered isoproterenol (10 microg i.c.v.) from artificial cerebral spinal fluid using a water-reinforced, two-lever operant task (fixed ratio 10 schedule). After acquisition of the discrimination, drugs were tested for substitution (i.p.). The tricyclic antidepressants protriptyline and desipramine, the norepinephrine uptake inhibitor nisoxetine, the monoamine oxidase inhibitor phenelzine, and the atypical antidepressants bupropion, mirtazapine, and venlafaxine all produced greater than 90% isoproterenol-appropriate responding. The serotonin uptake inhibitor fluoxetine, the atypical antidepressants buspirone and trazodone, and the novel, putative antidepressants N(G)-nitro-L-arginine and N-acetyl-L-tryptophan 3,5-bis benzyl ester failed to substitute for isoproterenol at the dose ranges tested. Antagonism studies carried out with betaxolol for those drugs that fully generalized to isoproterenol's cue verified mediation by beta1-adrenergic receptors. The present results indicate that drugs with noradrenergic activity generalize to isoproterenol's discriminative stimulus. Although this suggests a role for central beta1-adrenergic receptors in the mechanism of action of certain antidepressant drugs, it does not seem that stimulation of these receptors is an effect shared by antidepressants from all pharmacological classes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12130722&dopt=Abstract antidepressant




Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis.

Hall WD, Mant A, Mitchell PB, Rendle VA, Hickie IB, McManus P.

Office of Public Policy and Ethics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.

OBJECTIVE: To examine the association between trends in antidepressant prescribing and suicide rates in Australia for 1991-2000. DESIGN: Analysis of databases of suicide and rates of antidepressant prescribing according to age and sex. SETTING: Australian Bureau of Statistics data, sales data from the Australian pharmaceutical industry, prescribing data in general practice. SUBJECTS: Men and women aged 15 years and over in 10 year age groups. MAIN OUTCOME MEASURES: Trends in suicide rates and trends in antidepressant prescribing. Association measured by Spearman's rank correlations. RESULTS: While overall national rates of suicide did not fall significantly, incidence decreased in older men and women and increased in younger adults. In both men (r(s)=-0.91; P<0.01) and women (r(s)=-0.76; P<0.05) the higher the exposure to antidepressants the larger the decline in rate of suicide. CONCLUSIONS: Changes in suicide rates and exposure to antidepressants in Australia for 1991-2000 are significantly associated. This effect is most apparent in older age groups, in which rates of suicide decreased substantially in association with exposure to antidepressants. The increase in antidepressant prescribing may be a proxy marker for improved overall management of depression. If so, increased prescribing of selective serotonin reuptake inhibitors in general practice may have produced a quantifiable benefit in population mental health.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12742921&dopt=Abstract antidepressant




Participation of the lateral septal nuclei (LSN) in the antidepressant-like actions of progesterone in the forced swimming test (FST).

Estrada-Camarena E, Contreras CM, Saavedra M, Luna-Baltazar I, Lopez-Rubalcava C.

Instituto de Neuroetologia, Universidad Veracruzana, Xalapa Ver, Mexico. clopez conacyt.mx

The possible participation of lateral septal nuclei (LSN) in the antidepressant-like actions of progesterone was evaluated. The effect of different concentrations of progesterone (0.001, 0.01 and 0.1 M) or saline solution injected directly into the LSN of ovariectomised rats was determined using the forced swimming test (FST). In addition, the temporal course of progesterone (0.1 M) antidepressant-like actions was compared with that of the classical antidepressant imipramine (0.1 M). Finally, in order to establish the possible participation of the GABA(A) receptor in the antidepressant-like action of progesterone, the effect of pre-treatment with the GABA(A) antagonist picrotoxin (0.125 mg/kg, i.p.) was evaluated. Intraseptally administered progesterone produced a concentration-dependent decrease in immobility behaviour but did not modify locomotor activity. These antidepressant-like actions lasted 4 h, while those of imipramine lasted 72 h. Finally, progesterone-induced anti-immobility effect could be blocked by the systemic injection of picrotoxin. Present results reveal that LSN play a role in the antidepressant-like actions of progesterone that appear to be mediated by the GABA(A) receptor. Copyright 2002 Elsevier Science B.V.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12191804&dopt=Abstract antidepressant