Use Of Antidepressants In Children Research Articles

Escitalopram for the treatment of major depressive disorder in youth

Introduction:Major depressive disorder (MDD) is a serious public problem, affecting 4 – 6% of adolescents at any one time. Although adolescent MDD needs early and appropriate intervention, concerns regarding the risk of suicidality associated with antidepressant treatment and efficacy of pharmacotherapy have led to decreased use of antidepressants in children and adolescents. After the approval of fluoxetine in 2003, escitalopram received FDA approval in 2009 for the acute and maintenance treatment of MDD in adolescent patients.Areas covered:The paper addressed the following questions: Is escitalopram effective for adolescent MDD? How large is the magnitude of effectiveness? Does escitalopram treatment have any benefit in adolescents compared with the risk of suicidal behavior and treatment-emergent adverse events?Expert opinion:The efficacy of escitalopram in adolescent MDD was demonstrated in a double-blind, randomized, controlled trial and extrapolated from a similar citalopram trial. The optimal dose is 10 mg/day and the magnitude of the antidepressant effect is modest. Escitalopram treatment is generally well tolerated by adolescents, but treatment-emergent agitation, suicidal behavior and manic symptoms should be closely monitored. Escitalopram can be used as one of the first-line treatment options for moderate to severe MDD in adolescents.

Impact of Food and Drug Administration (FDA) paediatric antidepressant warnings on stock prices of pharmaceutical manufacturers

Objectives The objective was to investigate the impact of the Food and Drug Administration (FDA) paediatric antidepressant warnings in 2004 on the magnitude and the systematic risk associated with stock returns of antidepressant manufacturers. Methods Center for Research in Security Prices (CRSP) daily stock-price data for 2003–2006 were used to examine the FDA warning impact. The beta coefficient from the capital asset pricing model was used as a measure of systematic risk. The CRSP New York Stock Exchange 500 value-weighted daily return was used as the market return. A multivariate regression model framework was employed in which an equation was estimated simultaneously for each of the five firms (Eli Lilly, Forest Laboratories, GlaxoSmithKline, Pfizer and Wyeth) affected by the warnings. The periods 2 February to 23 March 2004 and 14 September to 18 October 2004 were defined as the warning periods. A seemingly unrelated regression model was used with daily stock return as the dependent variable and warning period as the primary independent variable. The unit of analysis was each trading day between 1 January 2003 and 31 December 2006. Key findings In the period of uncertainty and warnings (2003–2004) the beta coefficient increased by an average of 0.296 (95% confidence interval 0.103, 0.489) across the five firms. The FDA warnings had no significant impact on the magnitude of the stock returns. Conclusions The 2004 FDA warnings on antidepressant use in children led to an increase in the systematic risk associated with antidepressant drug manufacturers' stocks with no corresponding change in stock returns, suggesting that investors did not change their perception of the value of these firms, but did perceive increased risk. This increase in risk makes it more costly for the manufacturers to raise capital.

Does treatment effect depend on control event rate? Revisiting a meta-analysis of suicidality and antidepressant use in children

Weisberg et al. (Clin Trials 2009, 6: 109-18) illustrate that entry criteria in randomized trials can lead to results that are biased for the target population. Presenting data from a previously published meta-analysis of the effect of antidepressants in children on suicidality, they suggest a relationship between the control event rate and relative risk. Our purpose is threefold: (1) to show that natural methods of demonstrating a relationship between the control event rate and relative treatment benefit are fraught with danger, (2) to develop better methods, and (3) to assess whether there is evidence of such a relationship in the suicidality meta-analysis. We propose an improved graphical method and an exact and approximate test of whether the treatment effect increases (or decreases) with the control event rate. The apparent relationship in the naive plot of relative risk against control rate is actually no stronger than what would be expected by chance. Results of our test do not support the conclusion that the odds ratio for suicidality varies with the control rate (one-sided p = 0.39). We are not able to apply the exact test to this data set. Simulation results indicate that the relationship would have to be very strong to detect it with these sample sizes and control event rates. The difficulty in showing that the treatment effect in clinical trials differs by control rate is caused by 3 factors: (1) artificial correlation between a relative risk and control rate, (2) regression dilution bias because the independent variable - the control proportion - is subject to random variability, and (3) low power because we are trying to detect an interaction. Our graph and test are useful tools. Using them, we found no support for a relationship between the control event rate and treatment effect on suicidality.

Use of Antidepressants in Children: Is It Time for a Comparative Effectiveness Trial?

Use of Antidepressants in Children: Is It Time for a Comparative Effectiveness Trial?

Commentary on ‘Forum: use of antidepressants in children and adolescents’

Commentary on ‘Forum: use of antidepressants in children and adolescents’

Commentary on ‘Forum: use of antidepressants in children and adolescents’

Commentary on ‘Forum: use of antidepressants in children and adolescents’

Commentary on ‘Forum: use of antidepressants in children and adolescents’

Commentary on ‘Forum: use of antidepressants in children and adolescents’

Antidepressant Use in Children and Adolescents Diagnosed with Major Depressive Disorder: What Can We Learn from Published Data?

The consequences of major depression disorder (MDD) in youths are likely to be devastating for both the patient and his/her family. Thus, this review analyzes systematically the effectiveness of antidepressant drugs (ADDs) in managing such patients. Medical literature reporting primary data on use of ADDs in children and adolescents was identified through searches (1966-January 2010) of MEDLINE/PubMed, EMBASE, SCOPUS, and The Cochrane Library databases. Additional studies were manually identified from the reference lists of published articles. Search terms (variously combined) were: children, childhood, adolescents, adolescence, MDD, mood/affective disorders, depression, tricyclic antidepressants (TCAs) SSRIs, Serotonin-Norepinephrine Reuptake inhibitors (SNRIs), noradrenergic/specific serotoninergic antidepressants (NaSSA). A separate search was conducted to complete the profile of effectiveness of each single antidepressant agent. 43 peer-reviewed articles met the inclusion criteria. Reviewed information does not definitively support the use of antidepressants in children younger than 10 years old. In contrast, robust information suggests that fluoxetine should be considered as first-line agent in depressed adolescents whose clinical conditions require psychopharmacological approach. Depressed children should be primarily approached with non-pharmacological interventions that should include the evaluation of potential parental psychiatric disorders. In adolescents with MDD, the decision to use fluoxetine should be associated with specific social and health protocols focused to reinforce self-esteem, improve the quality of relationships with parents and peers, facilitate healthy life-style changes, and identify the potential onset/worsening of suicidality.

Citalopram efficacy study; interstitial 15q11‐q13 duplication mouse

Citalopram efficacy study; interstitial 15q11‐q13 duplication mouse

Early Evidence on the Effects of Regulators’ Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents

Objective.In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they

Treating Depressed Children With Antidepressants: More Harm than Benefit?

Since the FDA held hearings in February 2004 on the safety of antidepressants in children, there has been a great deal of controversy regarding the use of antidepressants in children, culminating in the well publicized black box warnings about increased risk of suicidal behavior in children and young adults (up to age 25) caused by these medications. Using questions that a parent might ask, the current article attempts to summarize the efficacy and safety data on the use of antidepressants in children so that psychologists, with or without prescription privileges, may be able to inform parents of young patients about the science behind this treatment. This article is based on a presentation at the 2007 American Psychological Association conference by the author in acceptance of the 2006 APAHC Bud Orgel Award for Distinguished Achievement in Research. Much of the information described in this article is drawn from the recent APA Report of the Working Group on Psychoactive Medications for Children and Adolescents. (Brown et al. 2006; available at www.apa.org/pi/cyf/childmeds.pdf ) culminating in a book by the same authors (Brown et al., Childhood mental health disorders: Evidence base and contextual factors for psychosocial, psychopharmacological, and combined interventions 2007).

Early Evidence on the Effects of Regulators’ Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents

In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression. The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings. SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979. In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents.

Effect of Regulatory Warnings on Antidepressant Prescribing for Children and Adolescents

To evaluate the effect of UK and US warnings placed in response to reports of suicidal thinking in pediatric patients receiving selective serotonin reuptake inhibitor and selective norepinephrine reuptake inhibitor antidepressants on antidepressant prescribing for children and adolescents. Interrupted time-series analysis of antidepressant prescriptions. Tennessee's Medicaid program, January 1, 2002, through September 30, 2005. A mean of 405,000 children and adolescents aged 2 to 17 years qualified each month. Main Exposure Piecewise linear regression models were used to estimate the cumulative effect of the warnings, which were considered the exposure of interest. Monthly proportions of study children and adolescents who were new users of antidepressants, had discontinuity in antidepressant use, or were users of other psychotropic drugs. During the 2 years preceding the UK warning, there was no trend in the monthly proportions of new antidepressant users, with 23 new users per 10 000 persons per month. This proportion subsequently decreased 33% (95% confidence interval, 23% to 41%; P < .001) by 21 months following the UK warning. The reduction was most pronounced for the nonfluoxetine selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, where initiations decreased 54% (95% confidence interval, 46% to 62%; P < .001). In contrast, new users of fluoxetine increased 60% (95% confidence interval, 9% to 135%; P = .02). There was no increase in discontinuations of antidepressants, and there was no evidence of substitution of other psychotropic drugs. The regulatory warnings led to decreased use of antidepressants in children and adolescents, but the clinical and public health consequences of this change are unknown.

Antidepressant use and off‐label prescribing in children and adolescents in Dutch general practice (2001–2005)

To study the use of antidepressants in children and adolescents in Dutch general practice in 2001 and 2005 and to determine off-label prescribing. Data were obtained from the Netherlands Information Network of General Practice (LINH) that comprised 97 practices in 2001 and 73 practices in 2005. General practitioners (GPs) recorded prescriptions with their indication in the medical records of the patients during one calendar year. We selected boys and girls aged 0-17 years (n = 83 442 in 2001; n = 62 969 in 2005) and identified those who got prescribed antidepressants (N06A). Prevalence of use, indications and percentage of off-label prescriptions were compared between 2001 and 2005. The prevalence of selective serotonin reuptake inhibitor (SSRI) use decreased from 1.2 to 1.1 per 1000 children and adolescents between 2001 and 2005. The use of tricyclic antidepressants (TCAs) and other antidepressants also decreased (0.8 to 0.7 and 0.3 to 0.2, respectively). TCAs were often prescribed for nocturnal enuresis, but in patients aged 12-17 years hyperactivity was the leading indication in both years. GPs continued to prescribe SSRIs for depression (about half of the prescriptions) after the safety warnings, while venlafaxine prescribed for depression decreased in favour of anxiety. Off-label prescribing of SSRIs increased from 16.7% to 34.4% and that of venlafaxine from 22.2% to 58.3%. All SSRI and venlafaxine prescriptions were unlicensed for age. The decreased use of SSRIs and venlafaxine suggests an impact of the safety warnings. A point of concern is the enlarged off-label prescribing and insight in the underlying reasons and its appropriateness is needed.

Merits of psychotherapies

I wish to highlight 2 issues regarding the article on the use of antidepressants in children and adolescents.[1][1] First, the majority of the main measures used in the 16 studies failed to support the drug over placebo. Ten of these studies were unpublished (all of which were industry-sponsored)

Antidepressant Use in Children and Adolescents in Germany

The expanded use of antidepressants in youth has been the subject of numerous studies and some concerns in recent years. This study describes prescription patterns of antidepressants (ATD) for youths in Germany for the years 2000-2003 and includes prescription use of St. John's Wort. Prescription data from a health insurance organization with 1.4 million members per year across Germany, of whom approximately 280,000 were under 20 years of age, were accessed. Total age- and gender-specific ATD yearly utilization rates were computed. Prevalence was defined as the dispensing of 1 or more prescriptions for an ATD per calendar year per 1000 continuously enrolled youth. ATD prevalence was 3.43 per 1000 (95% Confidence Interval [CI], 3.21-3.65) in 2000 and 3.74 per 1000 (3.25-3.97) in 2003. St John's Wort products, which are approved for antidepressant use by the German drug agency, and tricyclic antidepressants (TCAs), accounted for more than 80% of antidepressant use. Although selective serotonin reuptake inhibitors (SSRIs) represented only 15% of antidepressant use, there was a doubling of its use over the 4-year period. Adolescent girls (age, 15-19 years) had utilization rates ranging from 11.44 to 13.82 per 1000, and accounted for most ATD use. Overall, females were twice as likely as males to get an antidepressant. Among users, there were low rates of multiple medication use (5.6% used more than one class of ATD, and 6.7% more than one drug). Prescription patterns in Germany reveal predominate use of St. John's Wort and TCAs, which contrasts sharply with U.S. patterns, wherein SSRIs predominate. Also, in the United States, unlike Germany, 5-9- and 10-14 year olds receive sizable proportions of ATDs. Labeling status (only herbal hypericum preparations and TCAs are labeled for the treatment of depression in children and adolescents in Germany) and cost restrictions appear to influence the prescribing pattern of doctors in Germany. Recent treatment recommendations of national and international regulatory agencies need to take into account the different national situations.

Do SSRIs cause suicide in children? The evidence is underwhelming

After regulatory agencies in the United Kingdom and United States recommended severe restrictions on antidepressant use in children, many lessons were learned, although one was not that these drugs cause suicide. We learned that pharmaceutical companies selectively released data that reflected positively on their products and that combining suppressed and published data suggested that most of these medications had questionable efficacy. We also learned that the studies lacked uniformity both in which age groups constituted children and which behavior was considered suicidal. Several recent, large nonindustry studies indicated that rates of suicide and suicidal behavior were actually reduced in children who used antidepressants, despite piteous anecdotal tales in the popular press purporting that selective serotonin reuptake inhibitors (SSRIs) caused children to kill themselves. Patients in pharmaceutical trials probably do not represent typical patients in routine clinical practice. Emerging implications are that suicidal behavior-if it does occur-is most likely soon after starting antidepressant use and that prescribers must be both vigilant in educating patients and families about warning signs and available to manage worrisome behavior.

New Data Show Declines In Antidepressant Prescribing

New Data Show Declines In Antidepressant Prescribing

APA Office Is Your Partner In Delivering Quality Care

APA Office Is Your Partner In Delivering Quality Care

Gag Clauses in Clinical-Trial Agreements

Gag clauses in clinical-trial agreements prevent investigators from examining the data independently or submitting a manuscript for publication without first obtaining the consent of the sponsor. Sponsors with a financial interest in the outcome of clinical research can suppress negative results. They can also interfere with the publication of unfavorable data on safety, as it was recently alleged that Merck officials did in the company-sponsored “Advantage” study of rofecoxib for the treatment of osteoarthritis published in 2003.1 Some of the hidden data, like those related to cyclooxygenase-2 inhibitors and the use of antidepressants in children, may eventually become public, but . . .