Clinical Features and Burden Scores in Japanese Pediatric Migraines With Brainstem Aura, Hemiplegic Migraine, and Retinal Migraine.

BACKGROUND: Migraines are a broad spectrum of disorders classified by the type of aura with some requiring attentive treatment. Vasoconstrictors, including triptans, should be avoided in the acute phase of migraines with brainstem aura, in hemiplegic migraine, and in retinal migraine. This study investigated the characteristics and burden of these migraines. METHODS: Medical charts of 278 Japanese pediatric patients with migraines were retrospectively reviewed. Migraine burden of migraines with brainstem aura, hemiplegic migraines, and retinal migraine was assessed using the Headache Impact Test-6™ (HIT-6) and the Pediatric Migraine Disability Assessment scale (PedMIDAS). RESULTS: Of 278 patients screened, 12 (4.3%) patients with migraines with brainstem aura (n = 5), hemiplegic migraines (n = 2), and retinal migraine (n = 5) were enrolled in the study. All patients had migraine with/without typical aura, whereas some patients had coexisting migraine with another type of headache (chronic tension-type headache in 3 patients, and 1 each with frequent episodic tension-type headache, headache owing to medication overuse, and chronic migraine). Migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients with coexisting headaches had higher HIT-6 or PedMIDAS scores, whereas migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients without coexisting headache did not show high HIT-6 or PedMIDAS scores. CONCLUSION: All migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients experienced migraine with or without typical aura, and some patients having other coexisting headaches also had high PedMIDAS and HIT-6 scores. PedMIDAS and HIT-6 should not be considered diagnostic indicators of migraines with brainstem aura, hemiplegic migraines, or retinal migraine. In clinical practice for headaches in children, careful history taking and proactive assessment of the aura are needed for accurate diagnosis of migraines with brainstem aura, hemiplegic migraines, and retinal migraine.

Prostate cancer and antidepressants: A nationwide population-based nested case-control study.

BACKGROUND: We aimed to evaluate the association between antidepressant and prostate cancer by comparing exposures to antidepressants between those with and without prostate cancer. METHODS: A nationwide insurance claims database was used to identify our case subjects. Age- and gender-matched controls were selected at a 1:5 ratio. Conditional logistic regression model was used. RESULTS: 11,515 patients with prostate cancer were identified and matched with 55,373 controls. No increased associations between prostate cancer and most classes of antidepressants were found. However, a positive association with adjusted odds ratios ranged from 1.20 to 1.35 was noted in different doses of imipramine. Nevertheless, this association became statistically insignificant at higher cumulative doses. CONCLUSIONS: Our results indicate that there is no association between mechanistically dissimilar antidepressants and increased hazard for prostate cancer.

Análisis de costo-efectividad del escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento para pacientes con trastorno de pánico en Colombia / nalysis cost-effectiveness of escitalopram compared to paroxetine, sertraline, fluoxetine, imipramine and fluvoxamine as maintenance therapy for patients with panic disorder in Colombia

PROBLEMA DE INVESTIGACIÓN: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento en adultos con diagnóstico de trastorno de pánico en Colombia. TIPO DE EVALUACIÓN ECONÓMICA: Análisis de costo-efectividad. POBLACIÓN OBJETIVO: Adultos colombianos con diagnóstico de trastorno de pánico. INTERVENCIÓN Y COMPARADORES: Intervención: escitalopram; Comparadores: paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina. HORIZONTE TEMPORAL: 32 semanas. PERSPECTIVA: SGSSS de Colombia. TASA DE DESCUENTO: No aplica. ESTRUCTURA DEL MODELO: Se estructuró un árbol de decisión, teniendo en cuenta modelos publicados en la literatura. FUENTES DE DATOS DE EFECTIVIDAD Y SEGURIDAD: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS; Ensayos clínicos aleatorizados. DESENLACES Y VALORACIÓN: Ausencia de crisis de pánico; Semanas libres de crisis de pánico. COSTOS INCLUIDOS: Costo de los medicamentos; Costo de procedimientos; Costo de los eventos adversos. FUENTES DE DATOS DE COSTOS: SISMED; Manual tarifario ISS 2001. RESULTADOS DEL CASO BASE: Para el caso base, escitalopram, fluvoxamina y fluoxetina e imipramina fueron tecnologías dominadas por sertralina y paroxetina. El costo adicional por crisis de pánico evitada en tratamiento con paroxetina comparado contra sertralina se estimó en $4.814.953. ANÁLISIS DE SENSIBILIDAD: Los análisis de sensibilidad y el diagrama de tornado muestran a la probabilidad de lograr ausencia de crisis de pánico y la probabilidad de recaída, como a las variables con mayor impacto sobre las estimaciones de la razón de costo-efectividad. CONCLUSIONES Y DISCUSIÓN: De acuerdo con los hallazgos aquí presentados, paroxetina, ofrece mayor razón de costo-efectividad, respecto a sus comparadores. No obstante, es necesario tener en cuenta que cualquiera de las alternativas aquí estudiadas, puede ser costo-efectiva, debido a que las pequeñas variaciones en la probabilidad de ausencia de crisis de pánico pueden cambiar el resultado. La principal limitación de este estudio es la ausencia de información proveniente de estudios de investigación clínica, que muestre el desempeño comparativo entre las tecnologías, así como el seguimiento de los participantes en los estudios, en escenarios de más largo plazo que los existentes al momento de elaborar este documento.(AU)

Análisis de costo-efectividad del escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento para pacientes con trastorno de pánico en Colombia / Cost-effectiveness analysis of escitalopram compared to paroxetine, sertraline, fluoxetine, imipramine and fluvoxamine as maintenance therapy for patients with panic disorder in Colombia

Problema de investigación: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento en adultos con diagnóstico de trastorno de pánico en Colombia. Tipo de evaluación económica: Análisis de costo-efectividad. Población objetivo: Adultos colombianos con diagnóstico de trastorno de pánico. Intervención y comparadores: Intervención: escitalopram, Comparadores: paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina. Horizonte temporal: 32 semanas. Perspectiva: SGSSS de Colombia. Tasa de descuento: No aplica. Estructura del modelo: Se estructuró un árbol de decisión, teniendo en cuenta modelos publicados en la literatura. Fuentes de datos de efectividad y seguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayo s clínicos a leatorizados. Desenlaces y valoración: Ausencia de crisis de pánico, Semanas libres de crisis de pánico. Costos incluidos: Costo de los medicamentos, Costo de procedimientos, Costo de los eventos adversos. Fuentes de datos de costos: SISMED, Manual tarifario ISS 2001. Resultados del caso base: Para el caso base, escitalopram, fluvoxamina y fluoxetina e imipramina fueron tecnologías dominadas por sertralina y paroxetina. El costo adicional por crisis de pánico evitada en tratamiento con paroxetina comparado con trasertralina se estimó en $4.814.953. Análisis de sensibilidad: Los análisis de sensibilidad y el diagrama de tornado muestran a la probabilidad de lograr ausencia de crisis de pánico y la probabilidad de recaída, como a las variables con mayor impacto sobre las estimaciones de la razón de costo-efectividad. Conclusiones y discusión: De acuerdo con los hallazgos aquí presentados, paroxetina, ofrece mayor razón de costo-efectividad, respecto a sus comparadores. No obstante, es \r\nnecesario tener en cuenta que cualquiera de las alternativas aquí estudiadas, puede ser costo-efectiva, debido a que las pequeñas variaciones en la probabilidad de ausencia de crisis de pánico pueden cambiar el resultado. La principal limitación de este estudio es la ausencia de información roveniente de estudios de investigación clínica, que muestre el desempeño comparativo entre las tecnologías, así como el seguimiento de los participantes en los estudios, en escenarios de más largo plazo que los existentes al momento de elaborar este documento.(AU)

Fluoxetine and imipramine: are there differences in cost-utility for depression in primary care?

RATIONALE: Depressive disorders generate severe personal burden and high economic costs. Cost-utility analyses of the different therapeutical options are crucial to policy-makers and clinicians. Previous cost-utility studies, comparing selective serotonin reuptake inhibitors and tricyclic antidepressants, have used modelling techniques or have not included indirect costs in the economic analyses. OBJECTIVE: To determine the cost-utility of fluoxetine compared with imipramine for treating depressive disorders in primary care. METHODS: A 6-month randomized prospective naturalistic study comparing fluoxetine with imipramine was conducted in three primary care centres in Spain. One hundred and three patients requiring antidepressant treatment for a DSM-IV depressive disorder were included in the study. Patients were randomized either to fluoxetine (53 patients) or to imipramine (50 patients) treatment. Patients were treated with antidepressants according to their general practitioner's usual clinical practice. Outcome measures were the quality of life tariff of the European Quality of Life Questionnaire: EuroQoL-5D (five domains), direct costs, indirect costs and total costs. Subjects were evaluated at the beginning of treatment and after 1, 3 and 6 months. Incremental cost-utility ratios (ICUR) were obtained. To address uncertainty in the ICUR's sampling distribution, non-parametric bootstrapping was carried out. RESULTS: Taking into account adjusted total costs and incremental quality of life gained, imipramine dominated fluoxetine with 81.5% of the bootstrap replications in the dominance quadrant. CONCLUSION: Imipramine seems to be a better cost-utility antidepressant option for treating depressive disorders in primary care.

Trans-species assessment of antidepressant activity in a rodent model of depression.

Olfactory bulbectomy (OB), a preclinical model of depression, has most often been performed and validated in rats, but not as comprehensively in other rodent species. This study demonstrated that bulbectomy induced a hyperactive response in the open field test in three rodent species, namely the rat, mouse and hamster. OB, in all species, produced an increase in the distance travelled in the perimeter of the arena. The OB mouse was the only species to demonstrate increased distance travelled in the central part of the arena. These behavioral disturbances were attenuated in all species following chronic treatment with the antidepressant imipramine.

The impact of cost sharing on antidepressant use among older adults in British Columbia.

OBJECTIVE: Antidepressant therapies are underused among older adults and could be further curtailed by patient cost-sharing requirements. The authors studied the effects of two sequential cost-sharing policies in a large, stable population of all British Columbia seniors: change from full prescription coverage to 10-25 dollars copayments (copay) in January 2002 and replacement with income-based deductibles and 25% coinsurance in May 2003. METHODS: PharmaNet data were used to calculate monthly dispensing of antidepressants (in imipramine-equivalent milligrams) among all British Columbia residents age 65 and older beginning January 1997 through December 2005. Monthly rates of starting and stopping antidepressants were calculated. Population-level patterns over time were plotted, and the effects of implementing cost-sharing policies on antidepressant use, initiation, and stopping were examined in segmented linear regression models. RESULTS: Implementation of the copay policy was not associated with significant changes in level of antidepressant dispensing or the rate of dispensing growth. Subsequent implementation of the income-based deductible policy also did not lead to a significant change in dispensing level but led to a significant (p=.02) decrease in the rate of growth of antidepressant dispensing. The copay policy was associated with a significant (p=.01) drop in the frequency of antidepressant initiation among persons with depression. Income-based deductibles reduced the rate of increase in antidepressant initiation over time. Implementation of the copay and income-based deductible policies did not have significant effects on stopping rates. CONCLUSIONS: Introducing new forms of medication cost sharing appears to have the potential to reduce some use and initiation of antidepressant therapy by seniors. The clinical consequences of such reduced use need to be clarified.

The creation of the concept of an antidepressant: an historical analysis.

The concept of an "antidepressant" implies a drug that acts in a disease specific way to reverse the neuropathological basis of the symptoms of depression. However, there is little scientific research that could confirm this view. This paper reports an historical study of the emergence of the concept of the antidepressant and the social forces that influenced its adoption. Historical literature documents the increasing importance of the specificity of medical treatments in the 20th century and the increased power that they conferred on medical practitioners. In the case of depression, stimulants were used as treatment from the 1940s. During the 1950s the anti-tuberculous drugs iproniazid and isoniazid started to be portrayed as more specific than stimulants, even though their stimulant effects were well documented. When imipramine was suggested to be effective in depression, it was presented solely as acting in a disease specific way and it was soon referred to as an "antidepressant". The idea that some drugs have a specific action on the underlying basis of depression caught on rapidly and was well established by the 1960s before any evidence was available to support this view. Forces that could have driven the adoption of this view include the psychiatric profession's desire to integrate with general medicine to improve its social status and to move away from the asylum into the community. Physical interventions and drug treatments helped to boost its medical credentials and antidepressant drugs provided a convenient form of medical treatment for community-based distress. They also helped the profession to counter attacks from the antipsychiatry movement. The pharmaceutical industry too helped to establish and disseminate the view of antidepressants as disease specific treatments in order to distinguish them from non-specific drugs. This study raises questions about the view that psychiatry was transformed into a modern medical enterprise in the 1950s and 1960s by the introduction of disease specific drugs.

Cost-efficacy of individual and combined treatments for panic disorder.

OBJECTIVE: The objective of this study was to examine the relative cost-efficacy of empirically supported treatments for panic disorder. As psychosocial, pharmacologic, and combined treatments have all demonstrated efficacy in the treatment of panic disorder, cost-efficacy analysis provides an additional source of information to guide clinical decision making. METHOD: Cost-efficacy was examined based on results from the Multicenter Comparative Treatment Study of Panic Disorder, a randomized controlled trial of treatment for panic disorder (DSM-III-R). The trial was conducted from May 1991 to April 1998. Cost-efficacy ratios representing the cost per 1-unit improvement in Panic Disorder Severity Scale mean item score were calculated for 3 monotherapies (cognitive-behavioral therapy [CBT], imipramine, and paroxetine) and 2 combination treatments (CBT-imipramine and CBT-paroxetine) at the end of acute, maintenance, and follow-up phases. RESULTS: Results demonstrated consistently greater cost-efficacy for individual over combined treatments, with imipramine representing the most cost-efficacious treatment option at the completion of the acute phase (cost-efficacy ratio = $972) and CBT representing the most cost-efficacious option at the end of maintenance treatment (cost efficacy ratio = $1449) and 6 months after treatment termination (cost-efficacy ratio = $1227). CONCLUSION: In the context of similar efficacy for combined treatments, but poorer cost-efficacy, current monotherapies should be considered the first-line treatment of choice for panic disorder. Additionally, CBT emerged as the most durable and cost-effective monotherapy and, hence, should be considered as a particularly valuable treatment from the perspective of cost accountability.

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

PURPOSE: To study the use of antidepressants in children and adolescents in Dutch general practice in 2001 and 2005 and to determine off-label prescribing. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods.

OBJECTIVE: Up to 15% of depression patients eventually present with treatment-resistant or refractory depression (TRD), a condition that causes significant social and economic burdens. Our paper aims to summarize the current medical literature on the conceptual and methodologic issues involved in the definition, assessment, and staging of TRD. METHOD: We reviewed the recently published medical literature to identify papers that specifically discuss TRD. For this, we searched MEDLINE, EMBASE, and PsycINFO for potentially relevant English-language articles published between January 1996 and June 2006. RESULTS: Recent methodologic and conceptual advances have contributed to the achievement of an acceptable level of theoretical consensus on the general meaning of TRD. Accordingly, depression is usually considered resistant or refractory when at least 2 trials with antidepressants from different pharmacologic classes (adequate in terms of dosage, duration, and compliance) fail to produce a significant clinical improvement. Regarding diagnostic assessments, an accurate and systematic evaluation should be made to elicit the potential role of several contributing factors, such as medical and psychiatric comorbidity. CONCLUSION: Recently, 3 staging methods for TRD have been described, but they currently require extensive empirical support. Future research on TRD should include prospective studies addressing the validity of the proposed criteria, the impact of depression comorbid with other psychiatric disorders and (or) physical conditions, and the possible predictors o treatment outcome. There is an important and clear need for studies that empirically test current definitions, assessment strategies, and staging methods of TRD.

Effectiveness and cost-effectiveness of antidepressant treatment in primary health care: a six-month randomised study comparing fluoxetine to imipramine.

BACKGROUND: Over the past decade, studies of the effectiveness of pharmacological treatment for depression have often been based on research designs intended to measure efficacy, and for this reason the results are of limited generalizability. Research is needed comparing the clinical and economic outcomes of antidepressants in day-to-day clinical practice. METHODS: A six-month randomised prospective naturalistic study comparing fluoxetine to imipramine carried out in three primary care health centres. Outcome measures were the Montgomery Asberg Depression Rating Scale (MADRS), direct costs, indirect costs and total costs. Subjects were evaluated at the beginning of treatment and at one, three and six months thereafter. RESULTS: Of the 103 patients, 38.8% (n = 40) were diagnosed with major depressive disorder, 14.6% (n = 15) with dysthymic disorder, and 46.6% (n = 48) with depressive disorder not otherwise specified. Patients with major depressive disorder or dysthymic disorder achieved similar clinical improvement in both treatment groups (mean MADRS ratings decrease in major depressive disorder from baseline to 6 months of 18.3 for imipramine and 18.8 for fluoxetine). For patients with major depressive disorder and dysthymic disorder, the imipramine group had fewer treatment-associated costs (imipramine 469.66 Euro versus fluoxetine 1,585.93 Euro in major depressive disorder, p < 0.05; imipramine 175.39 Euro versus fluoxetine 2,929.36 Euro in dysthymic disorder, p < 0.05). The group with depressive disorder not otherwise specified did not experience statistically significant differences in clinical and costs outcomes between treatment groups. LIMITATIONS: Exclusion criteria, participating physicians may not represent GPs. CONCLUSIONS: In a primary care context, imipramine may represent a more cost-effective treatment option than fluoxetine for treating major depressive disorder or dysthymic disorder. There were no differences in cost-effectiveness in the treatment of depressive disorder not otherwise specified.

Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder.

OBJECTIVE: To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]). METHOD: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filter criteria ("equity", "strength of evidence", "feasibility" and "acceptability to stakeholders") is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs). RESULTS: Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater. CONCLUSIONS: Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.

The overactive bladder: a nursing perspective.

Symptoms of urgency and increased frequency of micturition and nocturia, with or without urge incontinence, are the hallmarks of a condition that afflicts millions of Americans. Several new drug therapies, as well as behavioral approaches, provide keys to management.

Bayesian model selection: analysis of a survival model with a surviving fraction.

We describe a methodology for model comparison in a Bayesian framework as applied to survival with a surviving fraction. This is illustrated using a case study of a randomized and controlled clinical trial investigating time until recurrence of depression. Posterior distributions are simulated using Metropolis-within-Gibbs Markov chain methods. Models reflecting the effects of covariates on the log odds of being in the surviving fraction, the log of the hazard rate, as well as both and neither are compared. Bayes factors for comparing the models are obtained by using the bridge sampling method of calculating normalizing constants.

Mood disorders in children and adolescents: psychopharmacological treatment.

Mood disorders are the leading causes of morbidity and mortality in children and adolescence. As a result, many adolescents are treated with psychopharmacologic agents such as antidepressants and mood stabilizers. To date, research into the safety and efficacy of these medications has lagged behind clinical practice. Several controlled trials of antidepressants in this population have recently been completed or are ongoing, yet few controlled trials of mood stabilizers have been conducted. Although acute efficacy of antidepressants is being addressed, many questions remain about pharmacological treatment of early-onset mood disorders. This article will focus on unmet research needs for the psychopharmacologic treatment of child and adolescent mood disorders.

Antidepressant efficacy and safety of low-dose sertraline and standard-dose imipramine for the treatment of depression in older adults: results from a double-blind, randomized, controlled clinical trial.

This study compared the efficacy and tolerability of 150 mg/day imipramine and 50 mg/day sertraline for the treatment of a major depressive episode (DSM-IV) in older adults (N = 55) in an 8-week, randomized, double-blind, controlled clinical trial. Intention-to-treat analysis (last observation carried forwards) showed a reduction of 50% or more on the baseline scores of the Montgomery-Asberg Rating Scale (MADRS) in 60.7% and 55.6% of patients receiving imipramine and sertraline, respectively (p = .698). Full remission of symptoms (MADRS < 9) was observed in 50.0% and 51.8% of patients, respectively (p = .891). Side effects were more frequent among patients treated with imipramine (86.7%) than among patients treated with sertraline (42.1%) (p = .008). Dropout rates were high in both groups (46.4% and 29.6% respectively, p =.200). These results indicate that imipramine and sertraline are equally effective for the treatment of major depression in later life, although adverse reactions are more frequent among subjects treated with imipramine than with sertraline.

Social functioning in depression: a review.

OBJECTIVE: This article reviews the available data on social functioning in depression and provides clinical guidelines and opinion on this important and expanding field. DATA SOURCES: A MEDLINE search was conducted to identify all English-language articles (1988-1999) using the search terms depression and social functioning, depression and social adjustment, depression and psychosocial functioning, and social functioning and antidepressant. Further articles were obtained from the bibliographies of relevant articles. DATA SYNTHESIS: Depressive disorders are frequently associated with significant and pervasive impairments in social functioning, often substantially worse than those experienced by patients with other chronic medical conditions. The enormous personal, social, and economic impact of depression, due in no small part to the associated impairments in social functioning, is often underappreciated. Both pharmacologic and psychotherapeutic approaches can improve social impairments, although there is a lack of extended, randomized controlled trials in this area using consistent assessment criteria. CONCLUSION: Despite this lack, it is becoming clear that not all treatments are equally effective in relieving the impaired social functioning associated with depressive disorders. Furthermore, efficacy in relieving the core symptoms of depression does not necessarily guarantee efficacy in relieving impaired social functioning.

Lost human capital from early-onset chronic depression.

OBJECTIVE: Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. METHOD: The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. RESULTS: Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. CONCLUSIONS: Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

History and evolution of the monoamine hypothesis of depression.

The symptoms of depression can be improved by agents that act by various mechanisms to increase synaptic concentrations of monoamines. This finding led to the adoption of the monoamine hypothesis of depression, first put forward over 30 years ago, which proposes that the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic and/or serotonergic systems and that targeting this neuronal lesion with an antidepressant would tend to restore normal function in depressed patients. The hypothesis has enjoyed considerable support, since it attempts to provide a pathophysiologic explanation of the actions of antidepressants. However, in its original form it is clearly inadequate, as it does not provide a complete explanation for the actions of antidepressants, and the pathophysiology of depression itself remains unknown. The hypothesis has evolved over the years to include, for example, adaptive changes in receptors to explain why there should be only a gradual clinical response to antidepressant treatment when the increase in availability of monoamines is rapid. Still, the monoamine hypothesis does not address key issues such as why antidepressants are also effective in other disorders such as panic disorder, obsessive-compulsive disorder, and bulimia, or why all drugs that enhance serotonergic or noradrenergic transmission are not necessarily effective in depression. Despite these limitations, however, it is clear that the development of the monoamine hypothesis has been of great importance in understanding depression and in the development of safe and effective pharmacologic agents for its treatment.