The impact of unrecognized bipolar disorders for patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) program.

Shi L, Thiebaud P, McCombs JS.

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.

BACKGROUND: This study compares hospital use, suicide risk and health care costs of antidepressant patients with recognized bipolar disorders (recognized-BP) and unrecognized bipolar disorders (unrecognized-BP) with non-bipolar (non-BP) patients. METHODS: Data from the California Medicaid (Medi-Cal) program were used to identify 25,460 adults with a new episode of antidepressant therapy. Recognized-BP patients received either a bipolar (BP) diagnosis or a mood stabilizer (MS) on or before the initiation of antidepressant therapy. Unrecognized-BP patients received a BP diagnosis or MS therapy after antidepressant initiation. Non-BP patients had no BP diagnosis and no MS use. Multivariate models were used to estimate marginal risks and costs across groups. RESULTS: Recognized-BP and unrecognized-BP represented 14.9% and 6.2% of all antidepressant users, respectively. Less than half of recognized-BP patients used a MS medication in conjunction with their antidepressant. Unrecognized-BP patients were nearly four times more likely to attempt suicide and 50% more likely to be hospitalized than non-BP patients. Recognized-BP patients were at lower risk for attempted suicide and hospitalization relative to unrecognized-BP patients. Unrecognized-BP patients experienced higher 1-year total costs relative to non-BP patients (USD 995, p<0.01) and recognized-BP patients (USD 682, p<0.05). LIMITATIONS: Clinically relevant medical records data were not available making the classification of patients as unrecognized-BP, recognized-BP and non-BP imprecise. CONCLUSIONS: Unrecognized-BP is both common and costly. More than half of all recognized-BP patients do not use an MS at the time they initiated antidepressant therapy. More effort is needed to provide early and correct diagnosis and effectively treat both recognized-BP and unrecognized-BP patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15555688&dopt=Abstract antidepressant




Antidepressant drug use in Lombardy, Italy: a population-based study.

Percudani M, Barbui C, Fortino I, Petrovich L.

Health Care Directorate, Region of Lombardy, Milan, Italy. mauro_percudani regione.lombardia.it

BACKGROUND: The patterns of antidepressant drug prescribing have rarely been studied in large and geographically defined catchment areas. In the present study, we examined the prevalence and distribution of antidepressant prescribing in Lombardy, a northern Italy region of nine million inhabitants. METHODS: This study used the Regional Administrative Database of Lombardy. This database includes all prescriptions reimbursed by the National Health System in the population living in this region. All antidepressant prescriptions dispensed from the 1st January to the 31st December 2001 were extracted and prevalence data calculated by dividing antidepressant users by the total number of male and female residents in each age group. RESULTS: During the study period, 404,238 individuals were dispensed antidepressants, yielding a prevalence of use of 2.85 (95% confidence interval 2.84, 2.87) per 100 males and 5.92 (95% confidence interval 5.90, 5.94) per 100 females. The prevalence of use progressively rose with age in both sexes, with the highest rates in old and very old individuals. The majority of individuals received a pharmacological treatment with selective-serotonin reuptake inhibitors only, slightly more than 12% received a treatment with tricyclic antidepressants. General practitioners issued the majority of antidepressant prescriptions. CONCLUSIONS: The very high rates of antidepressant drug prescribing detected in late life suggest the need of characterising these individuals in terms of medical and psychiatric characteristics, needs and quality of life. It also suggests the need for pragmatic clinical trials, carried out in the general practice, with the aim of assessing whether antidepressants are effective in these conditions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15555710&dopt=Abstract antidepressant




Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants.

Meijer WE, Heerdink ER, Nolen WA, Herings RM, Leufkens HG, Egberts AC.

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, The Netherlands.

BACKGROUND: Serotonin plays a role in platelet aggregation. Because antidepressants influence blood serotonin levels, their use may be associated with an increased risk of abnormal bleeding. However, previous studies were inconclusive regarding this association. The aim of this study was to estimate the risk of abnormal bleeding associated with the use of antidepressants and to establish the relationship between serotonin reuptake inhibition and the risk of bleeding. METHODS: We used data collected from 1992 through 2000 to conduct a nested case-control study of a cohort of more than 64 000 new antidepressant users. Cases were identified as all patients hospitalized for a primary diagnosis of abnormal bleeding, and they were matched with controls for age and sex. We classified exposure according to the degree (high, intermediate, or low) of serotonin reuptake inhibition and performed logistic regression analysis to calculate odds ratios. RESULTS: There were 196 cases of abnormal bleeding. The risk of hospitalization increased with the use of inhibitors providing intermediate (odds ratio, 1.9; 95% confidence interval, 1.1-3.5) and high degrees of serotonin reuptake inhibition (odds ratio, 2.6; 95% confidence interval, 1.4-4.8). CONCLUSIONS: In a large population of new antidepressant users we found a significant association between degree of serotonin reuptake inhibition by antidepressants and risk of hospital admission for abnormal bleeding as the primary diagnosis. An increased risk of abnormal bleeding was strongly associated with the degree of serotonin reuptake inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15557417&dopt=Abstract antidepressant




Bipolar depression: relationship between episode length and antidepressant treatment.

Frankle WG, Perlis RH, Deckersbach T, Grandin LD, Gray SM, Sachs GS, Nierenberg AA.

BACKGROUND: The role of antidepressant medications in bipolar depression remains controversial, mainly due to a lack of research in this area. In this study the authors examined the episode length in bipolar depression and the relationship between antidepressant therapy and episode length. METHOD: A retrospective chart review of 165 subjects identified 50 (30%) with bipolar illness who experienced a major depressive episode between 1 January 1998 and 15 December 2000. Data gathered utilized a structured instrument completed by the clinician at each visit. This instrument includes modified SCID mood modules as well as continuous ratings for each associated symptom of depression and mood elevation. Survival analysis was employed to calculate the median length of the depressive episodes for the entire group. Further survival analysis compared the episode length for subjects treated with antidepressants during the depression (N = 33) with those who did not receive antidepressants (N = 17). The rate of switch into elevated mood states was compared for the two groups. RESULTS: The survival analysis for the entire sample demonstrated 25%, 50% and 75% probability of recovery at 33 (S.E. 8.7), 66 (S.E. 17.9) and 215 (S.E. 109.9) days, respectively. Comparing those who received (N = 33) and those who did not receive (N = 17) antidepressants during the episode did not reveal any difference in the length of the depressive episode. Switch rates were not significantly different between those receiving antidepressants and those not taking these medications (15.2% v. 17.6%, respectively). CONCLUSIONS: Over the past 20 years little progress has been made in reducing the length of depressive episodes in those with bipolar illness. This is despite increasing pharmacological options available for treating depression. Clinicians treating bipolar depression should discuss with their patients the likelihood that the episode will last between 2-3 months. Our results also suggest that antidepressant treatment may not reduce the length of depressive episodes, neither did it appear to contribute to affective switch in our sample.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12455940&dopt=Abstract antidepressant




Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: a propensity-adjusted retrospective cohort study.

Valuck RJ, Libby AM, Sills MR, Giese AA, Allen RR.

Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Denver, Colorado 80262, USA. robert.valuck uchsc.edu

CONTEXT: The US FDA has issued an advisory warning of a possible link between antidepressant treatment for paediatric patients with major depressive disorder (MDD) and an increased risk of suicidal behaviour. A large database of paid health insurance claims for adolescents with MDD provided the opportunity to examine this possible relationship.OBJECTIVE: To examine the potential empirical link between antidepressant treatment and suicide attempts among adolescents aged 12-18 years using a community sample of managed care enrollees across the US.DESIGN: A retrospective longitudinal cohort using paid insurance claims for all healthcare and prescription fills for adolescents who were newly diagnosed with MDD and had at least 6 months of follow-up data. A multivariate Cox proportional hazards regression analysis was used to test the hypothesis that antidepressant use increased the risk of suicide attempt, adjusting for propensity for allocation to each treatment group and for demographic and clinical characteristics.SETTING: Managed care plans including both commercial and Medicaid plans in the east, midwest, south and western regions of the US from January 1997 to March 2003.PARTICIPANTS: All adolescent insurance members aged 12-18 years at first diagnosis of MDD.MAIN OUTCOME MEASURES: Suicide attempts as indicated by medical utilisation with International Classification of Diseases (9th edition) [ICD-9] or 10th edition (ICD-10) codes in any healthcare setting or by any covered provider.RESULTS: 24 119 adolescents met inclusion criteria (63% female). Crude suicide attempt rates ranged from 0.0-2.3% by index treatment group. Treatment with SSRIs (hazard ratio) [HR] = 1.59; CI 0.89, 2.82), other antidepressants (HR = 1.03; CI 0.43, 2.44), or multiple antidepressants (HR = 1.43; CI 0.70, 2.89) after index MDD diagnosis resulted in no statistically increased risk of suicide attempt. Treatment with antidepressant medication for at least 180 days (6 months) reduced the likelihood of suicide attempt compared with antidepressant treatment for <55 days (8 weeks) [HR = 0.34; CI 0.21, 0.55]. Other variables that were independently associated with greater risk of suicide attempts included female gender, severity of illness indicators, younger age at time of MDD diagnosis, and living in the midwest or west.CONCLUSIONS: Antidepressant medication use had no statistically significant effect on the likelihood of suicide attempt in a large cohort of adolescents across the US after propensity adjustment for treatment allocation and controlling for other factors. The relationship between suicidal behaviour and antidepressant medication use is complex and requires further investigation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15581382&dopt=Abstract antidepressant




Is dopamine a limiting factor of the antidepressant-like effect in the mouse forced swimming test?

Renard CE, Dailly E, Nic Dhonnchadha BA, Hascoet M, Bourin M.

EA 3256 Neurobiologie de l'Anxiete et de la Depression, Faculte de Medecine, BP 53508, 1 rue Gaston Veil, Nantes Cedex 01 44035, France.

To study the role of dopamine (DA) in antidepressant-like effect in the forced swimming test (FST), the relationship between the magnitude of the antidepressant-like effect of drugs [citalopram, fluoxetine, paroxetine (selective serotonin reuptake inhibitors), desipramine (tricyclic antidepressant), maprotiline (tetracyclic antidepressant), bupropion (DA reuptake inhibitor), and tranylcypromine (inhibitor of monoamine oxidase)] and the corresponding concentration of DA in the whole brain of mice was investigated. A trend for an inversely proportional linear relationship [(magnitude of the antidepressant-like effect) = -0.0145 x (concentration of DA in the whole brain) +34.773 (r = 0.276)] was observed between the magnitude of the antidepressant-like effect and the concentrations of DA in the whole brain, but this correlation was not significant. This result suggests that the high concentration of DA in the whole brain could be a limiting factor for the antidepressant-like effect of antidepressants such as tranylcypromine and seems to play a minor role in the antidepressant-like activity of another antidepressant such as bupropion in the FST.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15588751&dopt=Abstract antidepressant




5-HT1A receptors are differentially involved in the anxiolytic- and antidepressant-like effects of 8-OH-DPAT and fluoxetine in the rat.

De Vry J, Schreiber R, Melon C, Dalmus M, Jentzsch KR.

CNS Research, Bayer HealthCare, Aprather Weg 18a, 42096 Wuppertal, Germany. Jean.DeVry Grunenthal.de

Fluoxetine, a selective serotonin reuptake inhibitor, shows moderate efficacy and potency in the rat forced swimming depression test and the shock-induced ultrasonic vocalization anxiety test, whereas the 5-HT(1A) receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is highly efficient and potent in both models. Whereas the 5-HT(1A) receptor antagonist WAY 100,635 abolishes the effect of 8-OH-DPAT in both models, it only attenuates the antidepressant-like effect of fluoxetine. Pretreatment with the 5-HT-depleting agent parachlorophenylalanine attenuates the antidepressant-like effect of fluoxetine, but not that of 8-OH-DPAT. This suggests that the antidepressant-like effect of fluoxetine and 8-OH-DPAT results from indirect (via increased synaptic availability of 5-HT) and direct stimulation of postsynaptic 5-HT(1A) receptors, respectively; whereas the anxiolytic-like effect of fluoxetine is not mediated by 5-HT(1A) receptors. The data support the hypothesis that the antidepressant- and anxiolytic-like effect of 8-OH-DPAT is predominantly mediated by post- and presynaptic 5-HT(1A) receptors, respectively, and that 5-HT(1A) receptors are only partially involved in the antidepressant-like effect of fluoxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15589388&dopt=Abstract antidepressant




Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials.

Khan A, Brodhead AE, Kolts RL, Brown WA.

Northwest Clinical Research Center, Bellevue, MA, USA. akhan nwcrc.net

Although increased pre-treatment severity of depressive symptoms is thought to suggest better outcome with tricyclic antidepressants, it is unclear if such a pattern exists among those depressed patients treated with newer antidepressants. If such a pattern with newer antidepressants were observed, it would have implications for the design and conduct of future antidepressant trials. We reviewed the data from 329 depressed adult patients that were part of 15 multi-center, randomized, double blind, placebo-controlled antidepressant clinical trials at our center. Based on patients' pre-treatment scores on the 17-item Hamilton Depression Rating Scale (HAM-D), patients were sub-grouped to one of four severity of depression groups: low moderate, high moderate, moderately severe, and severe. The effect size was 0.51 in the low moderate group, 0.54 in the high moderate group, 0.77 in the moderately severe group and 1.09 in the severe group. An analysis of variance revealed a statistically significant interaction between treatment and severity of depressive symptoms. A correlational analysis revealed that in the group of depressed patients assigned to antidepressants, higher levels of pre-treatment depressive symptoms were significantly associated with greater changes in response to antidepressant treatment. Although a similar pattern was seen among the depressed patients assigned to placebo, it did not reach statistical significance. The results of this study suggest that antidepressant-placebo differences may be larger among those depressed outpatients with higher pre-treatment HAM-D scores compared to those depressed outpatients with lower pre-treatment scores. These findings may help in the design of future antidepressant clinical trials.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15589562&dopt=Abstract antidepressant