Early discontinuation of antidepressants in general practice: association with patient and prescriber characteristics.

Hansen DG, Vach W, Rosholm JU, Sondergaard J, Gram LF, Kragstrup J.

Research Unit of General Practice, University of Southern Denmark, Odense, Denmark. DGilsaa health.sdu.dk

BACKGROUND: Most antidepressant treatment is initiated and continued in general practice but, despite current guidelines, treatment duration is often short among patients with depression. Discontinuation may, however, be caused by a complexity of factors, but so far research has focused on drug effects, adverse effects and drug regimens. OBJECTIVE: Our aim was to analyse whether early discontinuation of first-time antidepressant treatment in general practice may be predicted by (i) social position and psychiatric history of the patient; and (ii) demography, practice activity and the general prescribing behaviour of the GP. METHODS: Early discontinuation, i.e. that patients do not purchase antidepressants in the 6 months following first prescription, was analysed using established databases. Among patients presenting in 174 general practices in Funen County, Denmark, 4860 adult first-time users of antidepressants were identified (regardless of diagnosis). The inclusion period was January 1998-June 1999. RESULTS: One in three patients did not purchase antidepressants in the 6 months following first prescription, but rates were higher among those prescribed tricyclic compared with new generation antidepressants. Patients' age and sex did not have an influence, but early discontinuation was more frequent among patients of low socio-economic status and patients prescribed in practices characterized by high prescribing rates. No association with psychiatric history was observed. CONCLUSION: Early discontinuation is frequent in general practice, and patients of low social status are at greater risk. Adherence-promoting strategies should pay attention to the high prescribing doctors. Further studies may answer the question of whether the association between doctors' prescribing behaviour and early discontinuation is a feature specific to antidepressants or a more general phenomenon.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15520034&dopt=Abstract antidepressant




High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation.

Caldarone BJ, Harrist A, Cleary MA, Beech RD, King SL, Picciotto MR.

Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.

BACKGROUND: A wide variety of antidepressants act as noncompetitive antagonists of nicotinic acetylcholine receptors (nAChRs), but the relationship between this antagonism and the therapeutic effects of antidepressants is unknown. METHODS: Antidepressant properties of the noncompetitive nAChR antagonist mecamylamine in the forced swim test were tested alone and in combination with the tricyclic antidepressant amitriptyline. Mice lacking high-affinity nAChRs were tested in three behavioral models to determine whether these receptors are required for behavioral effects of amitriptyline in common models of antidepressant action. Finally, the brains of wild-type and knockout animals treated with amitriptyline were examined to determine whether high-affinity nAChRs are required for antidepressant-induced increases in hippocampal cell proliferation. RESULTS: Inhibition of nAChRs by mecamylamine had antidepressant-like effects in the forced swim test and potentiated the antidepressant activity of amitriptyline when the two drugs were used in combination. Mice lacking high-affinity nAChRs showed no behavioral response to amitriptyline. Finally, after chronic treatment with amitriptyline, nAChR knockout mice did not show the increase in hippocampal cell proliferation seen in wild-type mice. CONCLUSIONS: These data support the hypothesis that antagonism of nAChRs is an essential component of the therapeutic action of antidepressants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15522249&dopt=Abstract antidepressant




[Evolution of the utilization of antidepressant drugs in the Rioja and Zamora health districts throughout the 1997-2001 period]

[Article in Spanish]

Sainz de Rozas Aparicio C, Ruiz Clavijo Diez MT, Diaz Madero A.

Servicio de Farmacia, Complejo Hospitalario San Millan San Pedro, Logrono. csainz hsm.seris.es

BACKGROUND: Due to the high increase in the utilization of antidepressant drugs and the change in the prescription profile within this group, this study is aimed at discovering the evolution of the utilization of antidepressant drugs (NO6A subgroup) outside of the hospital setting in the Rioja and Zamora health districts throughout the 1997-2001 period and to evaluate the impact of the new drugs. METHODS: A study was made of the utilization of drugs included in the NO6A treatment subgroup under the Anatomical Therapeutic Chemical (ATC) classification. The data on the utilization of each specialty was taken from the pharmacy management (SIFAR) software applications and has been stated for each active ingredient in Daily Dose per Inhabitant (DDI). RESULTS: In the period under study, there was an increase in the total utilization of antidepressants in the two areas (Zamora 55% and Rioja 93%) due mainly to the increase in selective serotonin reuptake inhibitors (SSRI) (Zamora 80% and Rioja 143%) and in the new heterocyclic antidepressants (Zamora 82% and Rioja 78%). CONCLUSIONS: There has been an increase in the utilization of antidepressants, all of which has taken place in conjunction with a change in the prescription profile. There is a clear shift toward the utilization of the SSRI's and some heterocyclic antidepressants (venlafaxine, trazodone, reboxetine), the utilization of tricyclic antidepressants and IMAO's having decreased.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15535011&dopt=Abstract antidepressant




Antidepressants and risk of first-time hospitalization for myocardial infarction: a population-based case-control study.

Monster TB, Johnsen SP, Olsen ML, McLaughlin JK, Sorensen HT.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus and Aalborg, Denmark. t.monster home.nl

PURPOSE: Several studies have found an increased risk of myocardial infarction among depressed patients. Selective serotonin reuptake inhibitors (SSRIs) appear to lack the arrhythmic adverse effects of tricyclic antidepressants, and are thought to inhibit platelet aggregation. We examined whether use of different antidepressant classes is associated with a lower risk of first-time hospitalization for myocardial infarction, as compared with nonuse. METHODS: We identified 8887 cases of first-time hospitalization for myocardial infarction and 88,862 age- and sex-matched population-based controls during 1994-2002, using data from North Jutland County, Denmark. Cases and controls were stratified according to history of cardiovascular disease. All prescriptions for antidepressants before hospitalization for myocardial infarction were identified using a prescription database. Conditional logistic regression was used to estimate odds ratios of myocardial infarction associated with antidepressant use, adjusted for possible confounding factors. RESULTS: In patients with a history of cardiovascular disease, we found indications of a lower risk of myocardial infarction among those who used SSRIs (adjusted odds ratio [OR] = 0.85; 95% confidence interval [CI]: 0.62 to 1.16), nonselective serotonin reuptake inhibitors (adjusted OR = 0.83; 95% CI: 0.50 to 1.38), and other antidepressants (adjusted OR = 0.55; 95% CI: 0.31 to 0.97). There were no such associations among persons without a history of cardiovascular disease. CONCLUSION: Antidepressant use may be associated with a decreased risk of hospitalization for myocardial infarction among persons with a history of cardiovascular disease, although it remains uncertain whether there are differences by class of antidepressant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15541322&dopt=Abstract antidepressant




Effect of chronic antidepressant treatment on beta-receptor coupled signal transduction cascade. Which effect matters most?

Holoubek G, Noldner M, Treiber K, Muller WE.

Department of Pharmacology, Biocenter, University of Frankfurt, 60439 Frankfurt, Germany.

BACKGROUND: Beta-receptor down-regulation has been described as a common biochemical effect of chronic treatment with many but not all antidepressant drugs. Beta-receptor activation leads to elevated intracellular levels of cAMP followed by the activation of several protein kinases which in turn activate various transcription factors. One of those, CREP has received increasing interest as an relevant component within the antidepressant drug modulated signal cascade as it represents a down-stream signal not only of the beta-receptor but also of serotonin receptor activation. Chronic treatment with many antidpressant drugs has been shown to alter CREP levels in several brain regions. While beta-receptor down-regulation by chronic antidepressant treatment has been a consistent finding, alterations of CREP levels have been observed in both direction. Similarly divergent findings have been reported for BDNF a major gene targeted of CREB, where most but not all findings suggest up-regulation at least at the message level following chronic antidepressant treatment. METHODS: Because of these rather divergent data, we investigated the possible effects of chronic treatment (9 or 19 days) with three different antidepressant drugs (reboxetine, citalopram, imipramine) on the individual parameters of the beta-receptor coupled signal transduction cascade. All animals were also tested for possible antidepressant effects using the forced swimming test. RESULTS: While beta-receptor density was down-regulated by reboxetine and imipramine but not citalopram, CREB protein was only mildly elevated after 9 days, and not changed or slightly reduced after 19 days. BDNF protein levels were not or only slightly enhanced, but only for the 9 days treatment. Citalopram was most active. Under the conditions chosen, all three drugs were active in the forced swimming test. CONCLUSION: Taken together, the findings reported make it difficult to identify one single component of the beta-receptor coupled signal transduction cascade as common final target of chronic antidepressant treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15546062&dopt=Abstract antidepressant




Effects of pharmaceutical promotion on adherence to the treatment guidelines for depression.

Donohue JM, Berndt ER, Rosenthal M, Epstein AM, Frank RG.

Department of Health Policy and Management, University of Pittsburgh, Pennsylvania 15261, USA. jdonohue pitt.edu

OBJECTIVES: We sought to examine the impact of direct-to-consumer advertising (DTCA) and pharmaceutical promotion to physicians on the likelihood that (1) an individual diagnosed with depression received antidepressant medication and that (2) antidepressant medication was used for the appropriate duration. RESEARCH DESIGN AND SUBJECTS: A quasiexperimental design was used to examine treatment patterns of 30,621 depressed individuals whose insurance claims were included in the MarketScan database from 1997 through 2000. The main explanatory variables were spending on DTCA, detailing to physicians, and free samples for 6 antidepressant medications. RESULTS: Individuals diagnosed with depression during periods when class-level antidepressant DTCA spending was highest (cumulative spending more than US 18.5 million dollars) had 32% higher relative odds of initiating medication therapy compared with those diagnosed during periods when DTCA spending was lowest (P < 0.0001). Free samples of medications dispensed to physicians had no effect on odds of initiating antidepressant use. Class-level DTCA spending on antidepressants had a small positive effect on the duration of antidepressant use, whereas DTCA spending for the specific medication taken by an individual had no effect on treatment duration. Detailing spending at the class or product level had no significant effect on duration of treatment with an antidepressant medication. CONCLUSIONS: Our results suggest that DTCA of antidepressants was associated with an increase in the number of people diagnosed with depression who initiated medication therapy. DTCA was associated with a small increase in the number of individuals treated with antidepressants who received the appropriate duration of therapy. Promotion to physicians was not associated with either the initiation of treatment with an antidepressant or with the duration of therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15550797&dopt=Abstract antidepressant




Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction.

Schlienger RG, Fischer LM, Jick H, Meier CR.

Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology & Toxicology, University Hospital Basel, Basel, Switzerland.

BACKGROUND: It has been suggested that increased platelet activation increases the risk of acute myocardial infarction (AMI) in patients with depression. Selective serotonin reuptake inhibitors (SSRIs) may attenuate platelet activation by serotonin depletion in platelets. Observational studies have shown discrepant results of AMI risk associated with the use of SSRIs. OBJECTIVE: The aim of this study was to evaluate the association of exposure to different groups of antidepressants, including SSRIs, and the risk of AMI. The study also assessed in more detail the influence of timing of the exposure to antidepressants in a general adult population (<90 years of age), with or without diagnosed risk factors for AMI. STUDY DESIGN/METHODS: We conducted a population-based case-control analysis on the UK General Practice Research Database (GPRD). The study included 8688 patients (<90 years of age), with a first-time AMI between 1995 and 2001, and 33 923 controls, who were matched by age, sex, calendar time, and general practice. Conditional logistic regression was used to estimate odds ratios (ORs). RESULTS: Current use of an antidepressant was defined as a supply of the last prescription for an antidepressant that lasted up to the index date or beyond. Recent past use was defined as a supply of the last prescription for an antidepressant that ended 1-29 days before the index date. SSRIs investigated were citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine. Non-SSRIs investigated were amitriptyline, clomipramine, dosulepin, doxepin, imipramine, lofepramine, nefazodone, trazodone and trimipramine. Other antidepressants included were amoxapine, desipramine, lithium, maprotiline, mianserin, moclobemide, nortriptyline and protriptyline. Adjusted ORs (with 95% CI) for the current use of SSRIs, non-SSRIs, or other antidepressants, compared with non-use of antidepressants, were 0.63 (95% CI 0.43, 0.91; p=0.02), 0.92 (95% CI 0.77, 1.09; p=0.32) and 0.59 (95% CI 0.29, 1.20; p=0.14), respectively. The adjusted OR of recent past use of SSRIs compared with non-use of SSRIs was 1.42 (95% CI 1.02, 1.97; p=0.04). CONCLUSION: The present analysis provides further evidence that the current use of SSRIs is associated with a slightly decreased risk for AMI.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15554748&dopt=Abstract antidepressant




Antidepressants and suicide risk in the United States, 1985-1999.

Grunebaum MF, Ellis SP, Li S, Oquendo MA, Mann JJ.

Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA. mfg14 Columbia.edu

BACKGROUND: The role of antidepressants in suicide prevention is a major public health question. An association was hypothesized between the increase in the use of non-tricyclic antidepressant medications in the United States and the decline in the suicide rate during the years 1985-1999. METHOD: The relationships between the suicide, antidepressant prescription, unemployment, and alcoholic beverage consumption rates were studied using generalized linear models. Suicide rates by antidepressant overdose were compared in selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). RESULTS: From 1985 to 1999, the suicide rate fell 13.5%, with a greater decline among women, and antidepressant prescription rates increased over 4-fold, with the increase mostly due to SSRIs. Prescription rates for SSRIs and other second-generation antidepressants were both inversely associated with suicide rates (p = .03 and p = .02, respectively). In a multivariable analysis adjusting for unemployment and alcoholic beverage consumption rates, SSRI antidepressant prescription rates remained inversely associated with the national suicide rate (p = .03). Females received twice as many antidepressant prescriptions compared with males. The commonest prescription indication was mood disorders, the condition most often associated with suicide. SSRIs were associated with a lower risk of suicide by antidepressant overdose compared with TCAs. CONCLUSION: The decline in the national suicide rate (1985-1999) appears to be associated with greater use of non-tricyclic antidepressants. Treatment of a greater proportion of mood disorders with SSRIs and other second-generation non-tricyclic antidepressants may further reduce the suicide rate. Controlled studies of the antisuicidal properties of antidepressants are needed in high-risk depressed patient populations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15554756&dopt=Abstract antidepressant