Increased use of antidepressants in Canada: 1981-2000.

Hemels ME, Koren G, Einarson TR.

Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada. m.hemels utoronto.ca

OBJECTIVE: To provide a descriptive analysis of Canadian utilization (prescriptions, cost, cost per prescription) of antidepressants (ATC-code: N06A). METHODS: IMS Canada provided prescription volumes and costs from 1981 to 2000. We analyzed time trends for antidepressants in general and 4 subclasses (tricyclic antidepressants [TCAs], selective serotonin-reuptake inhibitors [SSRIs], dual action antidepressants [DAAs], and monoamine oxidase inhibitors [MAOIs]). Costs were discounted using the consumer price index, adjusting for population growth using data from Statistics Canada. RESULTS: Between 1981 and 2000, total prescriptions increased from 3.2 to 14.5 million. Market share of TCAs (23.7%) and MAOIs (2.1%) remained constant, despite the introduction of the first SSRI, fluoxetine, in 1989. SSRI prescriptions increased to 6.7 million (market share 46.3%). DAA use increased gradually after 1994 to 3.5 million prescriptions (23.9% market share) in 2000. The number of prescriptions expanded (possibly due to SSRIs) by 238%, with an increased cost of 2.7 billion dollars. Total expenditures for antidepressants increased exponentially, from 31.4 million dollars in 1981 to 543.4 million dollars in 2000 (y = 4E - 130e(0.1556x) [R(2) = 0.99]). Cost per prescription increased linearly from 9.85 dollars in 1981 to 37.44 dollars in 2000 (y = 1.72x + 7.92 [R(2) = 0.96]). CONCLUSIONS: Utilization and costs of pharmacotherapy for depression have increased above the inflation rate and are expected to exceed 1.2 billion dollars (50 dollars per prescription) in 2005. Increased costs may be due to increased availability of new products with increased safety, efficacy, and acquisition cost; increased number of users; and increasing costs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12196054&dopt=Abstract antidepressant




The identification of depression and the coverage of antidepressant drug prescriptions in Italian general practice.

Bellantuono C, Mazzi MA, Tansella M, Rizzo R, Goldberg D.

The Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Ospedale Policlinico, 37134, Verona, Italy. bellant galactica.it

BACKGROUND: Studies on antidepressant prescriptions in general practice need to assess the level of prescriptions relative to the need for them ('coverage'), and the variability among doctors. METHODS: Two different cut-off scores on a screening test for depression (the Personal Health Questionnaire, PHQ) are used to predict rates for depression, and rates for depressive patients thought likely to benefit from antidepressants (according to a severity criterion) in primary care patients. These two rates are compared with assessments by 11 GPs of recognised depression, as well as with rates of drug prescribed. RESULTS: The rate for depression thought likely to be treated with antidepressants estimated with the PHQ is broadly comparable with the rate for conspicuous depressive illness, and much lower than that predicted by the PHQ for depression. There was great variability between GPs in their ability to detect depression, and their preparedness to prescribe antidepressants. Antidepressants were only prescribed for 3.5% of the patients, compared to the 8.9% thought to need them. However, antidepressants, mostly SSRIs, are much more likely to be prescribed than tranquillisers. LIMITATIONS: The limitations of the study are that the PHQ is able to estimate 'coverage' but not 'focusing' (the proportion of those receiving antidepressants who needed them). CONCLUSIONS: Although the rate for conspicuous depression is similar to that for depressions thought to be treated with antidepressants, the 'coverage' of antidepressants was only 39.3%. The variability between physicians confirm the need of good practice guidelines and training packages for the identification and management of depression. Large epidemiological studies are needed to overcome the current lack of clinically relevant data on the quality of antidepressant prescriptions in general practice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12204317&dopt=Abstract antidepressant




Just keep taking the tablets: adherence to antidepressant treatment in older people in primary care.

Maidment R, Livingston G, Katona C.

Royal Free and University College Medical School, London, UK.

BACKGROUND: poor adherence to antidepressant medication may account for a significant proportion of treatment failures. Adherence levels and factors associated with adherence have not previously been studied in older people. OBJECTIVES: to report the prevalence and correlates of adherence to antidepressants in people > or = 65 years of age in a primary care setting. METHOD: sixty-seven patients currently being prescribed antidepressants from a single rural general practice were assessed using a range of questionnaires measuring adherence to antidepressants, severity of depression, specific health education about antidepressants, level of side-effects, insight, positive and negatives beliefs about medication in general and antidepressants in particular, level of intellectual functioning (past and present), a past history of recovery from depression, type of antidepressant, complexity of prescriptions, age and living arrangements. RESULTS: forty-five participants (67.2%) were fully adherent; seven (10.4%) mostly adherent, three (4.5%) adhered sometimes, three rarely and nine (13.4%) never. Backwards linear regression found that adherence increased with information given and cognitive impairment and decreased with concerns about taking antidepressants and severity of side-effects. CONCLUSIONS: non-adherence to antidepressant medication is a significant problem in older patients. Our study probably overestimated adherence as it was self-report, which usually overestimates adherence and the refusals are more likely to have been people not taking tablets but still found nearly one third of the patients were non-adherent. An intervention comprising education, eliciting and addressing specific concerns about antidepressant medication and using medication, which minimises side effects, may be helpful. Copyright 2002 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12211126&dopt=Abstract antidepressant




Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats.

Pilc A, Klodzinska A, Branski P, Nowak G, Palucha A, Szewczyk B, Tatarczynska E, Chojnacka-Wojcik E, Wieronska JM.

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland. nfpilc cyf-kr.edu.pl

Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic and antidepressant drugs. The involvement of group I mGlu receptors in anxiety and depression has also been proposed. In view of the recent discovery of anxiolytic- or antidepressant-like effects of acute injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective and brain penetrable mGlu5 receptor antagonist, we designed the present study to examine anxiolytic- and/or antidepressant-like effects of multiple administrations of this drug. The anxiolytic-like effects of MPEP were evaluated in rats using the conflict drinking test. The antidepressant-like effect was estimated using the rat olfactory bulbectomy model of depression. Seven subsequent injections of MPEP (1 mg/kg) significantly (by 320%) increased the number of shocks accepted during the experimental session in the Vogel test. MPEP given once daily at a dose of 10 mg/kg, restored the learning deficit of bulbectomized rats after 14 days of treatment, remaining without any effect in the sham-operated animals. N-methyl-D-aspartic acid (NMDA)-induced convulsions in mice were not affected by a single injection of MPEP (30 mg/kg) indicating that at this dose MPEP did not block NMDA receptors. The results indicate that the prolonged blockade of mGlu5 receptors exerts anxiolytic- and antidepressant-like effects in rats. No tolerance to anxiolytic-like action occurs. The previously mentioned results further indicate that antagonists of group I mGlu receptors may play a role in the therapy of both anxiety and depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12213272&dopt=Abstract antidepressant




Antidepressant treatments induce the expression of basic fibroblast growth factor in cortical and hippocampal neurons.

Mallei A, Shi B, Mocchetti I.

Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA.

New experimental evidence suggests that the mechanism of action of antidepressants includes the induction of neurotrophic factor synthesis in selected brain areas. The present study is aimed at establishing whether prolonged antidepressant treatments increase the expression of basic fibroblast growth factor (FGF2), a polypeptide growth factor that has a broad neurotrophic activity in the adult central nervous system. Rats received a single dose or long-term (3 weeks) administration of desipramine (DMI), fluoxetine (FLU), and mianserin (MIA), then were sacrificed at 5 and 24 h after the last injection. RNase protection assay and Western blot analysis revealed that all antidepressant drugs elicited an anatomically specific increase in FGF2 mRNA and protein. The increase in FGF2 mRNA after a single injection was seen only at 5 h after the injection and was restricted to the entorhinal cortex, whereas the effect of the long-term treatments lasted up to 24 h and occurred in the entire cortex and hippocampus. Immunohistochemical analysis of FGF2 immunoreactivity was carried out to investigate which cell types responded to the antidepressant treatments. DMI and MIA increased FGF2 proteins predominantly in neurons of layer V throughout the cerebral cortex and in some neurofilament-positive cells of the hippocampus. FLU increased FGF2 immunoreactivity mainly in neurofilament-positive cells of the hippocampus. These findings may explain the therapeutic efficacy of antidepressants in affective disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11961119&dopt=Abstract antidepressant




Association between antidepressant drug use and hyponatraemia: a case-control study.

Movig KL, Leufkens HG, Lenderink AW, van den Akker VG, Hodiamont PP, Goldschmidt HM, Egberts AC.

Hospital Pharmacy Midden-Brabant, TweeSteden and St Elisabeth Hospital, Tilburg, The Netherlands. kmovig zamb.tsz.nl

AIMS: To estimate the risk of, and risk factors for, hyponatraemia associated with the use of selective serotonin reuptake inhibitors (SSRIs) compared with the use of other antidepressant drugs. METHODS: A case-control study of psychiatric in- and out-patients on antidepressant drugs performed in the mid-southern part of The Netherlands over a 2 year period. Cases (n=29) were all using antidepressant drugs with a serum sodium concentration of < or = 130 mmol l(-1) while controls (n=78) were patients on antidepressants with a normal sodium concentration (136-144 mmol l(-1)). Information on blood sodium concentrations was obtained from clinical chemistry data while information on drug use was obtained from community and hospital pharmacy databases. Medical records were used to ascertain possible risk and confounding factors. Unconditional multivariate logistic regression was used to estimate odds ratios for hyponatraemia in patients on SSRIs compared with patients on other antidepressant drugs. RESULTS: SSRIs were associated with an increased risk of hyponatraemia (OR 3.3; 95% CI 1.3, 8.6) compared with other classes of antidepressant drugs. Stratified and interaction analyses revealed that elderly patients using diuretics concomitantly with SSRIs were at the highest risk of experiencing hyponatraemia (OR 13.5; 95% CI 1.8, 101). CONCLUSIONS: SSRIs are more frequently associated with hyponatraemia than other classes of antidepressant drugs. This adverse drug reaction was more common in older patients (> or = 65 years) and in those using diuretics.

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Antidepressant treatment for depression: total charges and therapy duration*

Dobrez DG, Melfi CA, Croghan TW, Kniesner TJ, Obenchain RL.

Institute for Health Services Research and Policy Studies of Northwestern University, Evanston, IL, USA.

BACKGROUND: The economic costs of depression are significant, both the direct medical costs of care and the indirect costs of lost productivity. Empirical studies of antidepressant cost-effectiveness suggest that the use of selective serotonin reuptake inhibitors (SSRIs) may be no more costly than tricyclic antidepressants (TCAs), will improve tolerability, and is associated with longer therapy duration. However the success of depression care usually involves multiple factors, including source of care, type of care, and patient characteristics, in addition to drug choice. The cost-effective mix of antidepressant therapy components is unclear. AIMS OF THE STUDY: Our study evaluates cost and antidepressant-continuity outcomes for depressed patients receiving antidepressant therapy. Specifically, we determined the impact of provider choice for initial care, concurrent psychotherapy, and choice of SSRI versus TCA-based pharmacotherapies on the joint outcome of low treatment cost and continuous antidepressant therapy. METHODS: A database of private health insurance claims identifies 2678 patients who received both a diagnosis of depression and a prescription for an antidepressant during 1990-1994. Patients each fall into one of four groups according to whether their health care charges are high versus low (using the median value as the break point) and by whether their antidepressant usage pattern is continuous versus having discontinued pharmacotherapy early (filling fewer than six prescriptions). A bivariate probit model controlling for patient characteristics, co-morbidities, type of depression and concurrent treatment is the primary multivariate statistical vehicle for the cost-effective treatment situation. RESULTS: SSRIs substantially reduce the incidence of patients discontinuing pharmacotherapy while leaving charges largely unchanged. The relative effectiveness of SSRIs in depression treatment is independent of the patient's personal characteristics and dominates the consequences of other treatment dimensions such as seeing a mental health specialist and receiving concurrent psychotherapy. Initial provider specialty is irrelevant to the continuity of pharmacotherapy, and concurrent psychotherapy creates a tradeoff through reduced pharmacotherapy interruption with higher costs. DISCUSSION: Longer therapy duration is associated with SSRI-based pharmacotherapy (relative to TCA-based pharmacotherapy) and with concurrent psychotherapy. High cost is associated with concurrent psychotherapy and choice of a specialty provider for initial care. In our study cost-effective care includes SSRI-based pharmacotherapy initiated with a non-specialty provider. Previous treatment history and other unobserved factors that might affect antidepressant choice are not included in our model. IMPLICATIONS FOR HEALTH CARE PROVISION: The decision to use an SSRI-based pharmacotherapy need not consider carefully the patient's personal characteristics. Shifting depressed patients' pharmacotherapy away from TCAs to SSRIs has the effect of improving outcomes by lowering the incidence of discontinuation of pharmacotherapy while leaving largely unchanged the likelihood of having high overall health care charges. Targeted use of concurrent psychotherapy may be additionally cost-effective. IMPLICATIONS FOR HEALTH POLICIES: The interaction of various components of depression care can alter the cost-effectiveness of antidepressant therapy. Our results demonstrate a role for the non-specialty provider in initiating care and support increased use of SSRIs as first-line therapy for depression as a way of providing cost-effective care that is consistent with APA guidelines for continuous antidepressant treatment. IMPLICATIONS FOR FURTHER RESEARCH: Further research that improves our understanding of how decisions regarding provider choice, concurrent psychotherapy, and drug choice are made will improve our understanding of the effects treatment choices on the cost-effectiveness of depression care. We have suggested that targeted concurrent psychotherapy may prove to be cost-effective; research to determine groups most likely to benefit from the additional treatment would further enable clinicians and healthcare policy makers to form a consensus regarding a model for treating depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11967455&dopt=Abstract antidepressant




Cost-effectiveness of antidepressant medications.

Croghan TW, Melfi CA, Crown WE, Chawla A.

Eli Lilly and Company, Department of Health Services and Policy Research, Lilly Corporate Center, Indianapolis, IN 46285, USA.

BACKGROUND: Antidepressant medications have been shown to effectively relieve symptoms, improve interpersonal and occupational functioning and reduce disability from coexisting medical conditions. Although the newer selective serotonin reuptake inhibitors (SSRIs) have improved tolerability, are easier to take and are associated with longer lengths of therapy when compared with the tricyclic antidepressants (TCAs), the relative cost-effectiveness of alternative antidepressants remains unclear. AIMS OF THE STUDY: This study seeks to determine (i) the probability that relapse or recurrence of depression can be prevented by appropriate antidepressant choice, (ii) the cost associated with relapse or recurrence of depression and (iii) the relative cost-effectiveness of alternative antidepressants. METHODS: We use a quasi-experimental design to compare claims from a state Medicaid plan for TCA and SSRIs users. RESULTS: Premature discontinuation of antidepressant medication is the strongest predictor of relapse and recurrence. Antidepressant choice was not an independent predictor of relapse or recurrence. The effect of relapse and recurrence on expenditures is complex, with a non-significant trend toward lower expenditures for those who had longer periods between episodes of depression two years after initiation of treatment for the first episode. We were unable to replicate prior research results regarding the impact of SSRIs on duration of therapy in this Medicaid plan. CONCLUSIONS: Premature discontinuation of antidepressant treatment is associated with a high probability of relapse and recurrence. Health care expenditures are not altered by preventing relapse and recurrence. We suggest that antidepressant medications associated with reduced probability of premature discontinuation should be considered cost-effective. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: There are very few variables which health care providers can use to improve the outcomes and associated economic consequences of depression. Among these factors, treatment choice and adherence to the prescribed treatment are likely candidates. In this paper, we suggest that adherence to antidepressant medication results in substantial improvement in the time to relapse or recurrence of depression. Choice of an SSRI may thus improve treatment outcome by lengthening remission. In addition, this choice is not associated with higher costs. IMPLICATIONS FOR HEALTH POLICY FORMULATION: Depressive illnesses are associated with high rates of health service use and functional impairment. Thus, the societal burden is quite high. This paper furthers the debate regarding the relative cost-effectiveness of antidepressant medications, and our findings suggest several ways that policy makers can improve the care of depressed individuals at little additional cost. Specifically our findings highlight the importance of adherence to current recommendations regarding the length of antidepressant treatment and suggest several methods for improving this important outcome. IMPLICATIONS FOR FURTHER RESEARCH: The relative cost-effectiveness of alternative antidepressant medications continues to be an important and unsolved issue. We suggest the need for future research in this area using a variety of research designs appropriate to the question. The quasi-experimental approach outlined here seems promising in this regard.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11971150&dopt=Abstract antidepressant