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What Every Psychologist Should Know About the Food and Drug Administration's Black Box Warning Label for Antidepressants
Abstract
In 2004, the Food and Drug Administration released a black box warning label for all antidepressants, indicating an increased risk for suicidality in children and adolescents. The label was subsequently updated in 2007 to include those up to 24 years of age. Data have since emerged to indicate changes in clinical practice patterns of nonspecialists (i.e., nonpsychiatrists) prescribing medications. Among the changes reported in practice patterns are an increased likelihood of referral and a decreased willingness to prescribe antidepressants. Findings also indicate marked reductions in ambulatory visits for depression among children and adolescents, lower rates of diagnosis of depression in this age group, a spillover effect to adults, inaccurate understanding of the actual risk communicated on the warning label (on the part of primary care practitioners), and increased suicide rates among children and adolescents. Recent findings have important implications for practicing psychologists, and specific recommendations are offered. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
... A first fundamental step preceding the start of CBT-SP is the process of informed consent by which clinicians discuss with their patients about potential risks and benefits associated with treatment. Although most therapists engage in this process, they rarely talk openly and directly with patients about the frequency of suicidality among individuals who undergo outpatient mental healthcare [85]. The patient should be informed that the initiation of treatment has been associated with the emergence of suicidal risk, even though there is no causality in this relationship. ...
... A first fundamental step preceding the start of CBT-SP is the process of informed consent by which clinicians discuss with their patients about potential risks and benefits associated with treatment. Although most therapists engage in this process, they rarely talk openly and directly with patients about the frequency of suicidality among individuals who undergo outpatient mental healthcare [85]. The patient should be informed that the initiation of treatment has been associated with the emergence of suicidal risk, even though there is no causality in this relationship. ...
... Clinicians are therefore encouraged to discuss the possible benefits and risks of psychopharmacological treatment with each patient at the outset of CBT-SP as well as during the course of treatment. In addition, continual monitoring of psychiatric symptoms and potential side-effects is recommended (Rudd, Cordero, & Bryan, 2009). Agitation and psychomotor restlessness, in particular, warrant particular attention (Rihmer, 2007). ...
Accumulating evidence supports the efficacy of cognitive behavioral therapy for suicide prevention (CBT‐SP) as an empirically supported treatment approach for suicidal patients. In light of these findings, several procedures pulled from CBT‐SP have been recommended for standard care with suicidal patients. The present article provides an overview of the procedures used in CBT‐SP and discusses how these procedures meet, or even exceed, standard of care expectations for outpatient mental healthcare clinicians. Finally, the relevance of clinician fidelity to the CBT‐SP model when evaluating standard of care expectations is discussed.
... In addition, since the issuance of the boxed warning for SSRIs, the rate of completed suicide in children and adolescents increased significantly in Canada (Katz et al. 2008), the U.S. (Bridge et al. 2008) and the Netherlands (Gibbons et al. 2007), although Sammons (2009) noted that adolescent suicide rates were rising before the DSCs were issued. Rudd et al. (2009) concluded from a review of the literature that the 2004 boxed warning led to changes in practice patterns (i.e., fewer prescriptions for antidepressants and more referrals to psychiatrists by non-psychiatric prescribers), reduced outpatient visits for pediatric depression, lower rates of pediatric depression diagnoses, and inaccurate understanding of the risk of completed pediatric suicides following the suicidality warning. ...
To alert professionals and consumers about safety risks associated with approved drugs, the U.S. Food and Drug Administration (FDA) periodically issues Drug Safety Communications, or DSCs (previously known as advisories, warnings, and health care professional letters). This review consolidates balanced information from 22 DSCs issued over the last 15 years by the FDA for drugs with pediatric indications (for any disorder) that are used to treat pediatric emotional and behavioral disorders (ADHD drugs, antipsychotics, antidepressants, and antiepileptics/anticonvulsants). A single-source document of pediatric DSCs for these drugs was needed because none existed previously; finding DSC information on the FDA website can be challenging; and other information sources (e.g., manufacturer or advocacy websites, blogs, other media reports) may lack the objectivity or accuracy that the FDA is charged to maintain. This consolidation is intended to enable better informed risk-benefit analysis around treatment selection and drug safety monitoring. For the 22 DSCs, we summarize the safety concerns, the populations affected, and when available from the FDA, the incidence of the adverse events, precursors, and factors that may increase or mitigate the risk of these very serious (e.g., sudden death, life-threatening rash, liver failure), but typically low incidence (<1 %) adverse events (cardiometabolic complications with atypical antipsychotics and suicidality with antidepressants are more common). This review does not address the far more common, but usually less serious, side effects that also accompany these drugs. Implications of this review for research and practice are discussed.
... Despite available data, we are unaware of any publications addressing the need to include the potential risks of death or suicide attempt in the informed consent process. The recent Food and Drug Administration (FDA) black box warning label for antidepressant use with adolescents and young adults has amplified concerns about adverse events (including suicidal thoughts and attempts ) in the treatment of suicidal thoughts and behaviors (Posner, Oquendo, Gould, Stanley, & Davies, 2007; Rudd, Cordero, & Bryan, 2009). It is certainly arguable about the need to include this information in the consent process, with the most common argument against inclusion being that the risks are not a consequence of or secondary to treatment. ...
Informed consent is uniformly accepted as essential to the treatment process. However, the relevant literature has not discussed issues of risk specific to suicidal patients, nor has such information routinely been included in the informed consent process. The implications of including suicide-specific risk information in the informed consent process is discussed and examples provided. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
... Additionally, the authors found a 58% decrease in SSRI pharmacy claims subsequent to the black box warning. Rudd and colleagues 75 reviewed this decrease in the frequency of depression diagnoses and antidepressant prescribing, suggesting that decreased use of mental health services for depression in youth may be related to provider and family fear, coupled with public misunderstanding of the data underlying the warning. Marshall and colleagues 76 used the framework of risk perception and subsequent public behavior 77 to discuss the public health impact of the FDA black box warning regarding antidepresssants. ...
Nonadherence is the Achilles' heel of effective psychiatric treatment. It affects the resolution of mental health symptoms and interferes with the assessment of treatment response. The meaning of the term adherence has evolved over time and is now associated with a variety of definitions and measurement methods. The result has been a poorly operationalized and nonstandardized term that is often interpreted differently by providers and patients. Drawing extensively from the literature, this article aims to (1) describe changes in the concept of adherence, drawing from the mental health treatment literature, (2) present a more comprehensive definition of adherence that recognizes the role of patient-provider transactions, (3) introduce dynamic adherence, a six-phase model, which incorporates the role of transactional processes and other factors that influence patients' adherence decisions, and (4) provide recommendations for providers to improve adherence as well as their relationships with patients.
The following prerequisite interviewing skills need to be mastered before role-playing suicidal assessments: maintain a slow pace, elicit feelings, empathic summary, feeling response, self-awareness, clarify vague answers, open-ended inquiry, validity tools for increasing accuracy, and transitional statements.
Clinical Psychology is for students studying clinical psychology as part of an undergraduate programme in psychology, nursing, sociology or social and behavioural sciences. Undergraduate students who wish to know if postgraduate study in clinical psychology would be of interest to them will find this book particularly useful. The book will inform students about: •the profession of clinical psychology •how to get onto a clinical psychology postgraduate training programme •the way clinical psychologists work with children, adolescents and adults with common psychological problems •the main models of practice used by clinical psychologists, and •the scientific evidence for the effectiveness of psychological interventions. There is a focus on both clinical case studies and relevant research, and the book includes summaries, revision questions, advice on further reading and a glossaryof key terms, all of which make it an excellent student-friendly introduction to an exceptionally interesting subject.
Primary care is a critical setting for suicide prevention because it is often the first and only source of mental health care for the U.S. general population. It is also important because suicidal patients report a greater number of somatic complaints and make more frequent medical visits compared to nonsuicidal patients. Models for managing suicide within primary care have recently arisen, yet no models have been proposed for use within the patient-centered medical home (PCMH), a primary care model that integrates behavioral health into its practice. The authors suggest a chronic disease model for the management of suicide risk in the PCMH along with collaborative strategies that may include suicide screening and targeted assessment, warm hand-offs, cognitive-behavioral interventions, routine collaborative medication management, and means restriction counseling. The current paper advises how those within the PCMH can adapt and implement evidence-based practices to manage suicide. Finally, the authors discuss a case example illustrating these evidence-based and collaborative methods.
Introduction
Nonadherence is the Achilles heel of effective psychiatric treatment. The meaning of the term “adherence” has evolved over time and is now associated with a variety of definitions and measurement methods. This has resulted in a poorly operationalized and non-standardized term that is often interpreted differently by providers and patients.
Objectives/Aims
This abstract aims to: 1) describe changes in the concept of adherence; 2) present a more comprehensive definition of adherence which recognizes the influence of patient-provider transactions; 3) introduce dynamic adherence, a six-phase model, which incorporates the influence of transactional processes and econometrics on patients’ adherence decisions; and 4) provide recommendations for providers to improve their relationships with patients and in turn, medication adherence.
Methods
A review of the scientific mental health literature.
Results
Despite the prevalence, seriousness, and costs associated with medication nonadherence, the construct of adherence remains poorly operationalized and lacks cogent standardization. Drawing from psychiatric research, a dynamic model of medication adherence across six phases is presented.
Conclusions
This model of adherence highlights the importance of the patient-provider relationship and the transactional processes that comprise what is a dynamic developmental system. Dynamic adherence is intended to foster movement toward a more coherent and unified set of definitions and clinical strategies that will provide the potential to more fully elucidate the risk and protective mechanisms impacting adherence, and the subsequent development and refinement of best practices in increasing the odds of stable medication adherence.
Recently observed reductions in the use of antidepressant medication in youth come after a period that many have characterized as being marked by excessive reliance on such agents. The Food and Drug Administration advisory first issued in 2004 clearly influenced this change in clinical practice; however, other factors such as public and expert opinion, medicolegal considerations, and the behavior of pharmaceutical manufacturers also have had some effect. Some have speculated that a reduction in antidepressant use in youth is related to observed increases in suicide rates for this population. Although there has been an increase in the rate of adolescent suicide since 2003, such increases have also been seen in other age and demographic groups. The association between suicide rates and antidepressant use in adolescents or other groups is unclear, and is likely more correlational than causal. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
New effective, efficient, and accessible service delivery methods for cognitive–behavioral therapies for pediatric anxiety disorders are needed. Many anxious children do not receive needed treatment because of barriers such as limited availability of trained practitioners, costs of treatment, and time. A cognitive–behavioral therapy (CBT) stepped care approach that “steps up” care as needed from less intensive therapies with minimal therapist assistance to therapist-directed treatment may address barriers and provide more accessibility to treatment. A stepped care approach does not necessarily mean that traditional weekly face-to-face therapy sessions will not be needed. However, different service delivery methods that begin with CBT minimal therapist-assisted interventions may be a first line of treatment because not all children may need the full treatment package. This article provides an overview of the current research on CBT minimal therapist-assisted interventions (i.e., modified CBT protocols, computer-based therapy, bibliotherapy, telephone-based therapy, group treatment, and pharmacology) and information on how these first-line treatments may be incorporated into a stepped care model. Minimal therapist-assisted interventions within a stepped care model are in the early stages of development, although there is evidence that these types of treatment may be a viable first step to treating pediatric anxiety disorders. More research on minimal therapist-assisted interventions within stepped care models is needed, and challenges associated with disseminating and implementing stepped care need to be addressed. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The author questions the premise on which the M. D. Rudd, L. Cordero, and C. J. Bryan (see record
2009-11890-001) argument is based and delineates some of the risks of psychotropic medication for children and adolescents. The argument is made that the diagnosis of depression should be made by specialty care providers who have particular expertise pertaining to specific developmental issues of children and adolescents. Recommendations are made for the development of psychosocial interventions for children and adolescents that may prove efficacious for the management of depression in children and adolescents. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Recent advances in pharmacotherapy and changing health care environments have focused increased attention on trends in outpatient treatment of depression.
To compare trends in outpatient treatment of depressive disorders in the United States in 1987 and 1997.
Analysis of service utilization data from 2 nationally representative surveys of the US general population, the 1987 National Medical Expenditure Survey (N = 34 459) and the 1997 Medical Expenditure Panel Survey (N = 32 636).
Respondents who reported making 1 or more outpatient visits for treatment of depression during that calendar year.
Rate of treatment, psychotropic medication use, psychotherapy, number of outpatient treatment visits, type of health care professional, and source of payment.
The rate of outpatient treatment for depression increased from 0.73 per 100 persons in 1987 to 2.33 in 1997 (P<.001). The proportion of treated individuals who used antidepressant medications increased from 37.3% to 74.5% (P<.001), whereas the proportion who received psychotherapy declined (71.1% vs 60.2%, P =.006). The mean number of depression treatment visits per user declined from 12.6 to 8.7 per year (P =.05). An increasingly large proportion of patients were treated by physicians for their condition (68.9% vs 87.3%, P<.001), and treatment costs were more often covered by third-party payers (39.3% to 55.2%, P<.001).
Between 1987 and 1997, there was a marked increase in the proportion of the population who received outpatient treatment for depression. Treatment became characterized by greater involvement of physicians, greater use of psychotropic medications, and expanding availability of third-party payment, but fewer outpatient visits and less use of psychotherapy. These changes coincided with the advent of better-tolerated antidepressants, increased penetration of managed care, and the development of rapid and efficient procedures for diagnosing depression in clinical practice.
Previous reports suggesting that selective serotonin reuptake inhibitor (SSRI) use is associated with increased suicidal risk have not assessed completed suicides. The authors analyzed reports from randomized controlled trials to compare suicide rates among depressed patients assigned to an SSRI, other antidepressants, or placebo.
Food and Drug Administration (FDA) summary reports of the controlled clinical trials for nine modern FDA-approved antidepressants provided data for comparing rates of suicide.
Of 48,277 depressed patients participating in the trials, 77 committed suicide. Based on patient exposure years, similar suicide rates were seen among those randomly assigned to an SSRI (0.59%, 95% confidence interval [CI]=0.31%-0.87%), a standard comparison antidepressant (0.76%, 95% CI=0.49%-1.03%), or placebo (0.45%, 95% CI=0.01%-0.89%).
These findings fail to support either an overall difference in suicide risk between antidepressant- and placebo-treated depressed subjects in controlled trials or a difference between SSRIs and either other types of antidepressants or placebo.
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.
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.
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.
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.
All adolescent insurance members aged 12-18 years at first diagnosis of MDD.
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.
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.
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.
Little is known about trends in suicidal ideation, plans, gestures, or attempts or about their treatment. Such data are needed to guide and evaluate policies to reduce suicide-related behaviors.
To analyze nationally representative trend data on suicidal ideation, plans, gestures, attempts, and their treatment.
Data came from the 1990-1992 National Comorbidity Survey and the 2001-2003 National Comorbidity Survey Replication. These surveys asked identical questions to 9708 people aged 18 to 54 years about the past year's occurrence of suicidal ideation, plans, gestures, attempts, and treatment. Trends were evaluated by using pooled logistic regression analysis. Face-to-face interviews were administered in the homes of respondents, who were nationally representative samples of US English-speaking residents.
Self-reports about suicide-related behaviors and treatment in the year before interview.
No significant changes occurred between 1990-1992 and 2001-2003 in suicidal ideation (2.8% vs 3.3%; P = .43), plans (0.7% vs 1.0%; P = .15), gestures (0.3% vs 0.2%; P = .24), or attempts (0.4%-0.6%; P = .45), whereas conditional prevalence of plans among ideators increased significantly (from 19.6% to 28.6%; P = .04), and conditional prevalence of gestures among planners decreased significantly (from 21.4% to 6.4%; P = .003). Treatment increased dramatically among ideators who made a gesture (40.3% vs 92.8%) and among ideators who made an attempt (49.6% vs 79.0%).
Despite a dramatic increase in treatment, no significant decrease occurred in suicidal thoughts, plans, gestures, or attempts in the United States during the 1990s. Continued efforts are needed to increase outreach to untreated individuals with suicidal ideation before the occurrence of attempts and to improve treatment effectiveness for such cases.
In 2003, the U.S. Food and Drug Administration (FDA) issued a public health advisory about the risk of suicidality in pediatric patients taking selective serotonin reuptake inhibitors (SSRIs) for depression, and in 2005, the agency mandated a black box warning and medication guide indicating that pediatric and adult patients may be at risk. The authors examine the effects of this pediatric policy on treatment of adult depression in the community.
An adult cohort with newly diagnosed episodes of depression was created from a large national integrated claims database of managed care plans from October 1998 to September 2005 (N=475,838 unique episodes). Time-series analyses were used to compare the post-FDA advisory trends to the trends during the 5 years preceding the advisory.
The rate of diagnosed depression was significantly lower after the advisory than would have been expected on the basis of the preadvisory historical trend. The average percentage of adults with new (versus recurrent) depressive episodes was 88.6% in the preadvisory period (declining at an annual rate of 1.69%), and it decreased significantly to 77.5% (declining more rapidly, at an annual rate of 7.70%). The percentage of adults with depression who did not receive an antidepressant increased from an average of 20% (declining at 0.45% annually) before the policy action to an average of 30% (increasing at an annual rate of 20.6%). The data did not show any compensatory increases in psychotherapy or prescription of atypical antipsychotics or anxiolytics.
The FDA advisory had a significant spillover effect into community treatment for adults with depression, despite the focus of the policy on pediatric patients.
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.
The Food and Drug Administration (FDA) issued a public health advisory in October 2003 on the risk of suicide in pediatric patients taking antidepressants and advised maintaining "close supervision" of such patients. In this study, the authors compared trends in the frequency of provider contacts for patients with depression before and after the advisory was issued.
Retrospective cohorts of children (N=27,370) and adults (N=193,151) with new episodes of depression treated with antidepressants were created from a national claims database of managed care plans (1998-2005). Two standards were used in measuring patient monitoring: the Health Plan Employer Data and Information Set (HEDIS) quality-of-care criterion calling for three contacts in 3 months and the FDA-recommended contact schedule totaling seven visits in 3 months. Time-series models compared postadvisory trends to the expected trend based on preadvisory measures.
Less than 5% of all patients met FDA contact recommendations before the advisory, and the rate did not change after the advisory. A greater proportion of patients met the HEDIS contact criterion before the advisory (60% for children and 40% for adults), and the rate did not change after the advisory. A greater proportion of pediatric patients seen by a psychiatrist (80%) met the HEDIS criterion than those seen by a pediatrician (60%) or a non-pediatrician primary care physician (54%), and than adults seen by a psychiatrist (65%) or a primary care physician (37%). The proportions of pediatric patients who met the FDA recommendations did not differ by specialty.
Contrary to expectations, the frequency of visits by patients with new episodes of depression treated with antidepressants did not increase after the October 2003 FDA advisory was issued.
Regulatory bodies worldwide, including Health Canada, have issued warnings about prescribing antidepressants to children and adolescents. We sought to determine whether the Health Canada warning had the desired effects on prescribing patterns and outcomes and whether it had any unintended health consequences.
We examined data from prescription and health care databases representing more than 265 000 children, adolescents and young adults annually to determine changes in the rates of antidepressant prescription, use of health services and outcomes in these populations in the 9 years before and the 2 years after the Health Canada warning. We also examined the data for unintended changes in these rates among patients with anxiety disorders. We used young adults as the comparison group because they were not targeted by the warning.
Following the warning, the rate of antidepressant prescriptions decreased among children and adolescents (relative risk [RR] 0.86, 95% confidence interval [CI] 0.81-0.91) and among young adults (RR 0.90, 95% CI 0.86-0.93). Ambulatory visits because of depression decreased among children and adolescents (RR 0.90, 95% CI 0.85-0.96) and young adults (RR 0.91, 95% CI 0.87-0.96). The rate of completed suicides among children and adolescents rose significantly after the warning (RR 1.25, 95% CI 1.08-1.44; annual rate per 1000 = 0.04 before and 0.15 after the warning). There was no equivalent change in the rate of completed suicides among young adults (RR 1.01, 95% CI 0.93-1.10; annual rate per 1000 = 0.15 before and 0.22 after the warning). Among patients with an anxiety disorder, the prescription rates did not change among children and adolescents, except for a decrease in the use of selective serotonin reuptake inhibitors other than fluoxetine, but the rates among young adults changed similar to the pattern of changes in the overall prescribing of antidepressants. There was also a significant decrease in the rate of physician visits because of anxiety disorders among young adults after the warning.
Health advisories and warnings issued by regulatory bodies may have unintended consequences on the provision of care, delivery of health services and clinical outcomes. Further efforts are required to ensure that health warnings do not result in unexpected harm.
The objective of the present study was to examine if the change in the suicide rate is associated with individuals' use of antidepressants as has been suggested by ecological studies.
Decomposition of suicide rates by antidepressant treatment group.
Population-based record linkage.
All individuals aged 50 years and older living in Denmark between 1 January 1996 and 31 December 2000 (N = 2,100,808).
Suicide rates are calculated according to current antidepressant treatment status (no treatment, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), other antidepressants). The change in the suicide rate during 1996-2000 was decomposed by treatment group.
Only one in five older adults dying by suicide was in treatment at the time of death. Whereas the male suicide rate declined by 9.7 suicides per 100,000, recipients of antidepressants contributed to the decline by 0.9 suicides. Women redeeming antidepressant prescriptions accounted for 0.4 suicides of the observed reduction of 3.3 per 100,000. The average suicide rates for men receiving TCA and SSRI were 153.3 and 169.0 per 100,000 person-years, respectively. Among older women, both TCA and SSRI users had an average suicide rate of 68.8 per 100,000 over the period examined.
Just a small proportion of older adults dying by suicide were found to be in treatment with antidepressants at the time of death. Individuals in active treatment with antidepressants seem to account for 10% of the decline in the suicide rate. Nevertheless, suicides might be prevented by more effective treatment.
The evidence-base of psychosocial treatment outcome studies for depressed youth conducted since 1998 is examined. All studies for depressed children meet Nathan and Gorman's (2002) criteria for Type 2 studies whereas the adolescent protocols meet criteria for both Type 1 and Type 2 studies. Based on the Task Force on the Promotion and Dissemination of Psychological Procedures guidelines, the cognitive-behavioral therapy (CBT) based specific programs of Penn Prevention Program, Self-Control Therapy, and Coping with Depression-Adolescent are probably efficacious. Interpersonal Therapy-Adolescent, which falls under the theoretical category of interpersonal therapy (IPT), also is a probably efficacious treatment. CBT provided through the modalities of child group only and child group plus parent components are well-established intervention approaches for depressed children. For adolescents, two modalities are well-established (CBT adolescent only group, IPT individual), and three are probably efficacious (CBT adolescent group plus parent component, CBT individual, CBT individual plus parent/family component). From the broad theoretical level, CBT has well-established efficacy and behavior therapy meets criteria for a probably efficacious intervention for childhood depression. For adolescent depression, both CBT and IPT have well-established efficacy. Future research directions and best practices are offered.
Context Recent advances in pharmacotherapy and changing health care environments
have focused increased attention on trends in outpatient treatment of depression.Objective To compare trends in outpatient treatment of depressive disorders in
the United States in 1987 and 1997.Design and Setting Analysis of service utilization data from 2 nationally representative
surveys of the US general population, the 1987 National Medical Expenditure
Survey (N = 34 459) and the 1997 Medical Expenditure Panel Survey (N
= 32 636).Participants Respondents who reported making 1 or more outpatient visits for treatment
of depression during that calendar year.Main Outcome Measures Rate of treatment, psychotropic medication use, psychotherapy, number
of outpatient treatment visits, type of health care professional, and source
of payment.Results The rate of outpatient treatment for depression increased from 0.73
per 100 persons in 1987 to 2.33 in 1997 (P<.001).
The proportion of treated individuals who used antidepressant medications
increased from 37.3% to 74.5% (P<.001), whereas
the proportion who received psychotherapy declined (71.1% vs 60.2%, P = .006). The mean number of depression treatment visits
per user declined from 12.6 to 8.7 per year (P =
.05). An increasingly large proportion of patients were treated by physicians
for their condition (68.9% vs 87.3%, P<.001),
and treatment costs were more often covered by third-party payers (39.3% to
55.2%, P<.001).Conclusions Between 1987 and 1997, there was a marked increase in the proportion
of the population who received outpatient treatment for depression. Treatment
became characterized by greater involvement of physicians, greater use of
psychotropic medications, and expanding availability of third-party payment,
but fewer outpatient visits and less use of psychotherapy. These changes coincided
with the advent of better-tolerated antidepressants, increased penetration
of managed care, and the development of rapid and efficient procedures for
diagnosing depression in clinical practice.
Purpose: To explore the accuracy of primary care providers' understanding of the FDA black box warning label for SSRI antidepressants for children and adolescents. Methods: A total of 115 licensed primary care providers (PCPs) completed an email survey addressing the FDA black box warning label. Results: Despite self-reports of being well informed about the black box warning label, over 91% of PCPs incorrectly reported that the warning label states that patients died by suicide in the aggregated SSRI clinical trials for children and adolescents, in contrast to the actual reported risk for increased frequency of suicidal thinking and suicide-related behaviors (i.e. suicide attempts and deliberate self-harm). The majority of PCPs (90%) also reported providing verbal information to patients regarding the nature of risk. Conclusions: Efforts need to be made to improve PCPs' understanding of the risk communicated in the FDA black box warning label for children and adolescents, specifically that increased risk does not include risk for death by suicide.
As part of this special issue on psychology in primary care settings, we describe the Department of Veterans Affairs' (VA's) new approach to education for practice in the primary care setting and we concurrently address some general issues related to the education of clinical psychologists for practice in this setting. In this article we argue that the primary care psychologist, in parallel with the generalist in medicine, must have a strong generic background in clinical psychology in order to gain the broad range of clinical skills necessary to function effectively as an "in-depth generalist" (IDG) who is capable of addressing the variety of psychological issues that emerge in the primary care setting. The IDG model of professional practice, which we believe is best suited for primary care/managed care settings, requires extensive training in generic clinical skills and increased time devoted to its implementation at both the predoctoral and the postdoctoral levels.
Recently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs.
To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market.
Examination of the Physicians' Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black box warning).
Frequency of and time to a new black box warning or drug withdrawal.
A total of 548 new chemical entities were approved in 1975-1999; 56 (10.2%) acquired a new black box warning or were withdrawn. Forty-five drugs (8.2%) acquired 1 or more black box warnings and 16 (2.9%) were withdrawn from the market. In Kaplan-Meier analyses, the estimated probability of acquiring a new black box warning or being withdrawn from the market over 25 years was 20%. Eighty-one major changes to drug labeling in the Physicians' Desk Reference occurred including the addition of 1 or more black box warnings per drug, or drug withdrawal. In Kaplan-Meier analyses, half of these changes occurred within 7 years of drug introduction; half of the withdrawals occurred within 2 years.
Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years.
To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between different SSRIs and different tricyclic antidepressants.
Nested case-control study.
Primary care in the United Kingdom.
146,095 individuals with a first prescription of an antidepressant for depression.
Suicide and non-fatal self harm.
1968 cases of non-fatal self harm and 69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was 0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to 1.25) in people prescribed SSRIs compared with those prescribed tricyclic antidepressants. We found little evidence that associations differed over time since starting or stopping treatment. We found some evidence that risks of non-fatal self harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group (interaction P = 0.02). The adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared with users of tricylic antidepressants for those aged 18 or younger was 1.59 (1.01 to 2.50), but no association was apparent in other age groups. No suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs.
We found no evidence that the risk of suicide or non-fatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. We found some weak evidence of an increased risk of non-fatal self harm for current SSRI use among those aged 18 or younger. However, preferential prescribing of SSRIs to patients at higher risk of suicidal behaviour cannot be ruled out.
To investigate whether selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with an increased risk of suicide related outcomes in adults.
Meta-analysis of randomised controlled trials of SSRIs compared with placebo in adults submitted by pharmaceutical companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA).
Over 40,000 individuals participating in 477 randomised controlled trials.
Suicide, non-fatal self harm, and suicidal thoughts.
An estimated 16 suicides, 172 episodes of non-fatal self harm, and 177 episodes of suicidal thoughts were reported. We found no evidence that SSRIs increased the risk of suicide, but important protective or hazardous effects cannot be excluded (odds ratio 0.85, 95% credible interval 0.20 to 3.40). We found weak evidence of an increased risk of self harm (1.57, 0.99 to 2.55). Risk estimates for suicidal thoughts were compatible with a modest protective or adverse effect (0.77, 0.37 to 1.55). The relative frequency of reported self harm and suicidal thoughts in the trials compared with suicide indicates non-fatal end points were under-recorded.
Increased risks of suicide and self harm caused by SSRIs cannot be ruled out, but larger trials with longer follow up are required to assess the balance of risks and benefits fully. Any such risks should be balanced against the effectiveness of SSRIs in treating depression. When prescribing SSRIs, clinicians should warn patients of the possible risk of suicidal behaviour and monitor patients closely in the early stages of treatment.
Depressive disorders during youth occur frequently, are chronic and recurrent, and are associated with significant functional impairment, morbidity, and mortality. Two psychotherapeutic approaches-cognitive behavioural therapy and interpersonal therapy-are each better than wait-list or treatment-as-usual approaches. Several antidepressants have proven efficacious compared with placebo; however, more than half the studies comparing antidepressant treatment with placebo in children and adolescents with depression have not shown any benefit of the active compounds. Suicide rates are decreasing overall in adolescents, and there seems to be a correlation between the use of selective serotonin reuptake inhibitors (SSRIs) and a decrease in completed suicide. However, there was a signal for increase in suicide attempts and suicidal ideation in patients on acute antidepressant treatment when all antidepressants were assessed as a single group. Thus, there is substantial debate about the best approach to treat this serious disorder. Here, we discuss the treatment options for depression in children and adolescents.
In March 2004 the U.S. Food and Drug Administration (FDA) warned physicians and patients regarding increased risk of suicide with 10 newer antidepressant drugs. Available data leave considerable uncertainty regarding actual risk of suicide attempt and death by suicide during antidepressant treatment. The authors used population-based data to evaluate the risk of suicide death and serious suicide attempt in relation to initiation of antidepressant treatment.
Computerized health plan records were used to identify 65,103 patients with 82,285 episodes of antidepressant treatment between Jan. 1, 1992, and June 30, 2003. Death by suicide was identified by using state and national death certificate data. Serious suicide attempt (suicide attempt leading to hospitalization) was identified by using hospital discharge data.
In the 6 months after the index prescription of antidepressant treatment, 31 suicide deaths (40 per 100,000 treatment episodes) and 76 serious suicide attempts (93 per 100,000) were identified in the study group. The risk of suicide attempt was 314 per 100,000 in children and adolescents, compared to 78 per 100,000 in adults. The risk of death by suicide was not significantly higher in the month after starting medication than in subsequent months. The risk of suicide attempt was highest in the month before starting antidepressant treatment and declined progressively after starting medication. When the 10 newer antidepressants included in the FDA advisory were compared to older drugs, an increase in risk after starting treatment was seen only for the older drugs.
The risk of suicide during acute-phase antidepressant treatment is approximately one in 3,000 treatment episodes, and risk of serious suicide attempt is approximately one in 1,000. Available data do not indicate a significant increase in risk of suicide or serious suicide attempt after starting treatment with newer antidepressant drugs.
The aim of this study was to compare the incidence of suicidal ideation and behaviors observed with antidepressant drug treatment to the incidence with placebo, in randomized, controlled pediatric clinical trials.
Manufacturers of nine antidepressant drugs identified suicidal adverse events in randomized, placebo-controlled, pediatric clinical trials that they had sponsored. Events were found with an electronic search for adverse event descriptions, including key words suggesting suicidal ideation or self-injury, along with a manual review of all adverse events meeting the standard regulatory definition for seriousness. Incidence rate data for these events supplied by the manufacturers were combined across trials to yield Mantel-Haenszel combined risk estimates.
Data from 22 randomized, short-term, placebo-controlled, pediatric trials in various indications, involving nine different antidepressant drugs, were available for analysis. A total of 2298 pediatric subjects were exposed to active drug, and 1952 to placebo. Seventy eight (78) serious suicidal adverse events occurred in these trials (54 with active drug and 24 with placebo); there were no completed suicides. The combined incidence rate ratio across all trials for serious suicidal adverse events was 1.89 (95% Confidence Interval, 1.18-3.04).
In short-term, placebo-controlled, pediatric studies of antidepressants, active drug treatment was associated with a rate of serious suicidal events almost twice that of placebo.
After a decade-long decline, annual suicide rates in American children and adolescents increased in 2004. A report released in February 2007 described an 18% increase in the suicide rate in persons aged 1 through 19 years between 2003 and 2004. The incidence of suicide, the third-leading cause of death in 15 to 19-year-old Americans, increased from 7.3 to 8.2 per 100,000 persons in 2004. Language: en
In October 2003, the U.S. Food and Drug Administration (FDA) issued a public health advisory about the risk of suicidality in pediatric patients taking selective serotonin reuptake inhibitors (SSRIs) for depression. This study used data from a large national pediatric cohort to examine patterns of diagnosis of depression, prescription of antidepressants, prescription of pharmacological alternatives to antidepressants, and use of psychosocial care before and after the FDA advisory was issued.
A large pediatric cohort with newly diagnosed episodes of depression was created from a national integrated claims database of managed care plans from October 1998 to September 2005 (N=65,349). Time-series models were used to compare diagnosing and prescribing trends during the 2 years after the FDA advisory and the expected trends based on data from the 5-year period preceding the advisory.
From 1999 to 2004, pediatric diagnoses of depression increased from 3 to 5 per 1,000. After the FDA advisory was issued, the national rate decreased to 1999 levels, a significant deviation from the historical trend. Pediatricians and nonpediatrician primary care physicians accounted for the largest reductions in new diagnoses. Among patients with depression, the proportion receiving no antidepressant increased to three times the rate predicted by the preadvisory trend, and SSRI prescription fills were 58% lower than predicted by the trend. There was no evidence of a significant increase in use of treatment alternatives (psychotherapy, atypical antipsychotics, and anxiolytics).
The FDA advisory was associated with significant reductions in aggregate rates of diagnosis and treatment of pediatric depression.
Treating suicidal behavior
- M D Rudd
- T E Joiner
- M H Rajab
- M. D. Rudd
- T. E. Joiner
- M. H. Rajab
Rudd, M. D., Joiner, T. E., & Rajab, M. H. (2004). Treating suicidal
behavior. New York: Guilford Press.
Antidepressant use in children and adolescentsantidepressants/default.htm Food and Drug Administration Center for Drug Evaluation and Research Revisions to product labeling Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents
- Drug Food
- Administration
- Drug Center
- Evaluation
- R D Research
- C H Brown
- K Hur
- S M Marcus
- D K Bhaumik
- J A Erkens
Food and Drug Administration Center for Drug Evaluation and Research.
(2004). Antidepressant use in children and adolescents. Retrieved August 6,
2008, from http://www.fda.gov/cder/drug/antidepressants/default.htm
Food and Drug Administration Center for Drug Evaluation and Research.
(2007). Revisions to product labeling. Retrieved October 1, 2008, from
http://www.fda.gov/cder/drug/antidepressants/antidepressants_label_
change_2007.pdf
Gibbons, R. D., Brown, C. H., Hur, K., Marcus, S. M., Bhaumik, D. K.,
Erkens, J. A., et al. (2007). Early evidence on the effects of regulators'
suicidality warnings on SSRI prescriptions and suicide in children and
adolescents. American Journal of Psychiatry, 164, 1356 –1363.