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Biomedical subjects

Madhukar H Trivedi

Publications and source records attributed to Madhukar H Trivedi.

At least 19 recordsLinked to original sources

Remission status in persistent depressive disorder following acute treatment with psychotherapy plus medication or medication alone: A 2-year naturalistic follow-up.

OBJECTIVE: Long-term benefits of acute-phase treatments for persistent depressive disorder (PDD) are unclear. Treatment guidelines disagree on the efficacy of cognitive behavioral analysis system of psychotherapy (CBASP). We examined whether acute CBASP protected against recurrence in PDD patients over two years of naturalistic follow-up. METHODS: An observational study evaluated major depressive episode (MDE) recurrences in patients completing the Research Evaluating the Value of Augmenting Medication with Psychotherapy (REVAMP) trial. Enrollees 18-75 years had PDD: current chronic MDE, recurrent MDEs with incomplete recovery, or double depression. All received open-label antidepressant medication (ADM) for 12 weeks. Non-remitters, continuing on ADM, were randomized (2:2:1) to 12 weeks of 1) CBASP, 2) brief supportive therapy (BSP), or 3) ADM alone (MEDS). Patients completing this 12-week randomized phase were offered two-year follow-up. Blinded raters assessed the primary outcome, remission status, using the Longitudinal Interval Follow-up Evaluation and Hamilton Depression Rating Scale at 3-month intervals. Analyses evaluated group differences and non-specific predictors of remission status. RESULTS: Of 323 participants entering follow-up, 203 (62.8%) met current MDE criteria during follow-up, without between-group differences: BSP: 83 (65.3%), CBASP: 85 (60.2%), MEDS: 35 (63.6%), Chi-square = 0.75; p = 0.69. Remission after acute treatment, lack of comorbid anxiety disorder, and female gender were significantly associated with lower recurrence risk. CONCLUSION: Similar to the acute phase outcomes, no group differences emerged over the 2-year follow-up, suggesting no long-term benefit of a 12-week CBASP treatment with ADM over other PDD treatments. Findings underscore the difficulty of PDD treatment and the importance of acute treatment remission. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00057551.

Antidepressant↗

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n&#xa0;=&#xa0;75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p&#xa0;=&#xa0;0.02 to p&#xa0;<&#xa0;0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans↗

Peripheral immune markers and choroid plexus volumes as predictors of change in depressive symptoms: Insights from the EMBARC study.

Changes in choroid plexus (ChP) volume and peripheral inflammation have been associated with Major Depressive Disorder (MDD), yet their individual and combined impact on depressive symptoms is unclear. This study investigated whether baseline immune markers and ChP volumes predict changes in depressive symptoms during the 8-week treatment period among Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study participants who received either sertraline or placebo. Adults (n&#x202f;=&#x202f;222) with MDD with peripheral blood samples were included. Circulating chemokines and cytokines were examined using a 40-plex assay. Depressive symptoms were assessed over 8 weeks using the Hamilton Depression Rating Scale (HAMD-17). Principal component analysis (PCA) was used for dimension reduction. Mixed-effects models were used to examine whether immune profiles and ChP volumes, and their interaction predicted HAMD-17, adjusting for demographic/clinical covariates and baseline depression severity. PCA identified three immune profiles. One profile, characterized by higher levels of cytokines and chemokines including IL-6, TNF-&#x3b1;, and IL-1&#x3b2;, was associated with greater depression severity, higher BMI, age, and CRP at baseline. Higher levels of these immune markers were associated with less improvement in depressive symptoms at 8 weeks (estimate = 1.211, p&#x202f;=&#x202f;0.018) in models adjusting for right and left ChP volume (right ChP model: estimate = 1.034, p&#x202f;=&#x202f;0.005; left ChP model: estimate = 0.993, p&#x202f;=&#x202f;0.007). Interactions between immune markers and ChP volumes were not significant. Future investigations are warranted to examine the relationships between immune markers and ChP volume beyond structural changes in the context of depression symptoms.

Adult↗

ADHD in Youth With Major Depressive Disorder in the Texas Youth Depression and Suicide Research Network (TX-YDSRN): Clinical Correlates and Moderators.

OBJECTIVE: Depression is a major public health concern with a 19% lifetime prevalence in youth, often precipitating other concerns, including suicidal behavior, poor school performance, and worsened peer relationships. ADHD is also common among youth and frequently presents alongside major depressive disorder (MDD), with this comorbidity associated with increased impairment. More research is needed to elucidate the clinical characteristics of this comorbidity (MDD&#x2009;+&#x2009;ADHD), especially as it relates to youth with MDD and no ADHD (MDD&#x2009;-&#x2009;ADHD). The present study examined the clinical correlates of MDD&#x2009;+&#x2009;ADHD in youth and the presence of an ADHD diagnosis as a moderator of the relationship between depressive symptoms and suicidality, peer relationships, and school functioning, respectively. METHODS: Our sample included 797 youth with MDD ages 8 to 20&#x2009;years (Mage&#x2009;=&#x2009;15.5&#x2009;years) with and without ADHD. RESULTS: Youth with MDD&#x2009;+&#x2009;ADHD experienced more severe depressive symptoms, higher levels of suicidality, impulsivity, and irritability, and worse academic performance compared to those with MDD&#x2009;-&#x2009;ADHD. ADHD diagnosis did not moderate the relationships between depression severity and suicidality, peer relationships, or school functioning, respectively, suggesting that having an ADHD diagnosis may not affect these outcomes in depressed youth in this way. CONCLUSION: Findings shed light on the impact of ADHD in depressed youth, which may allow for earlier and more tailored intervention efforts aimed at identifying and targeting depression, suicidality, peer relationships, and school functioning.

Humans↗

Symptom features of postpartum depression: are they distinct?

The clinical features of postpartum depression and depression occurring outside of the postpartum period have rarely been compared. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)) provides a means to assess core depressive symptoms. Item response theory and classical test theory analyses were conducted to examine differences between postpartum (n=95) and nonpostpartum (n=50) women using the QIDS-SR(16). The two groups of females were matched on the basis of age. All met DSM-IV criteria for nonpsychotic major depressive disorder. Low energy level and restlessness/agitation were major characteristics of depression in both groups. The nonpostpartum group reported more sad mood, more suicidal ideation, and more reduced interest. In contrast, for postpartum depression sad mood was less prominent, while psychomotor symptoms (restlessness/agitation) and impaired concentration/decision-making were most prominent. These symptomatic differences between postpartum and other depressives suggest the need to include agitation/restlessness and impaired concentration/decision-making among screening questions for postpartum depression.

Adult↗

Assessing physicians' use of treatment algorithms: Project IMPACTS study design and rationale.

Effective treatments for major depressive disorder have been available for 35 years, yet inadequate pharmacotherapy continues to be widespread leading to suboptimal outcomes. Evidence-based medication algorithms have the potential to bring much-needed improvement in effectiveness of antidepressant treatment in "real-world" clinical settings. Project IMPACTS (Implementation of Algorithms using Computerized Treatment Systems) addresses the critical question of how best to facilitate integration of depression treatment algorithms into routine care. It tests an algorithm implemented through a computerized decision support system using a measurement-based care approach for depression against a paper-and-pencil version of the same algorithm and non-algorithm-based, specialist-delivered usual care. This paper reviews issues related to the Project IMPACTS study rationale, design, and procedures. Patient outcomes include symptom severity, social and work function, and quality of life. The economic impact of treatment is assessed in terms of health care utilization and cost. Data collected on physician behavior include degree of adherence to guidelines and physician attitudes about the perceived utility, ease of use, and self-reported effect of the use of algorithms on workload. Novel features of the design include a two-tiered study enrollment procedure, which initially enroll physicians as subjects, and then following recruitment of physicians, enrollment of subjects takes place based initially on an independent assessment by study staff to determine study eligibility. The study utilizes brief, easy-to-use symptom severity measures that facilitate physician decision making, and it employs a validated, phone-based, follow-up assessment protocol in order to minimize missing data, a problem common in public sector and longitudinal mental health studies. IMPACTS will assess the success of algorithm implementation and subsequent physician adherence using study-developed criteria and related statistical approaches. These new procedures and data points will also allow a more refined assessment of algorithm-driven treatment in the future.

Algorithms↗

Clinical differences among depressed patients with and without a history of suicide attempts: findings from the STAR*D trial.

BACKGROUND: This study sought to determine whether a history of suicide attempts among outpatients diagnosed with nonpsychotic major depressive disorder (MDD) is correlated with any difference in clinical presentation that should influence patient care. METHODS: Baseline data from the Sequenced Treatment Alternatives to Relieve Depression (STAR()D) trial on outpatients with MDD treated in primary and specialty care settings were used to model significant demographic and clinical correlates of suicide attempter status. RESULTS: Altogether, 16.5% of participants (n=667) reported prior suicide attempts. Controlling for age, gender, and depressive symptom severity, previous attempters had more current general medical conditions (micro=3.2 vs. 2.9, p<.0001), more current alcohol/substance abuse (p<.0001), and more work hours missed in the past week (26.2% vs. 18.2%, p<.0001) than non-attempters. On average, for the previously suicidal, the onset of MDD occurred 8.9 years earlier in life (p<.0001) and had included 1.2 additional depressive episodes (p=0.001) compared to those without prior suicidal behavior. Previous attempters also reported more current suicidal ideation (61.3% of previous attempters, adjusted OR 1.6, vs. 45.5% of nonattempters, p<.0001). LIMITATIONS: Presence or absence of a history of suicide attempts was determined only through self report. CONCLUSIONS: Those with a history of suicidal behavior suffer a greater burden of depressive illness. Earlier intervention and ongoing, aggressive care, including maintenance-phase pharmacotherapy, may be critical to mitigating the long-term consequences associated with this increased disease burden.

Absenteeism↗

Report by the ACNP Task Force on response and remission in major depressive disorder.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Clinical Trials as Topic↗

The Montgomery Asberg and the Hamilton ratings of depression: a comparison of measures.

The 17-item Hamilton Rating Scale for Depression (HRSD(17)) and the Montgomery Asberg Depression Rating Scale (MADRS) are two widely used clinician-rated symptom scales. A 6-item version of the HRSD (HRSD(6)) was created by Bech to address the psychometric limitations of the HRSD(17). The psychometric properties of these measures were compared using classical test theory (CTT) and item response theory (IRT) methods. IRT methods were used to equate total scores on any two scales. Data from two distinctly different outpatient studies of nonpsychotic major depression: a 12-month study of highly treatment-resistant patients (n=233) and an 8-week acute phase drug treatment trial (n=985) were used for robustness of results. MADRS and HRSD(6) items generally contributed more to the measurement of depression than HRSD(17) items as shown by higher item-total correlations and higher IRT slope parameters. The MADRS and HRSD(6) were unifactorial while the HRSD(17) contained 2 factors. The MADRS showed about twice the precision in estimating depression as either the HRSD(17) or HRSD(6) for average severity of depression. An HRSD(17) of 7 corresponded to an 8 or 9 on the MADRS and 4 on the HRSD(6). The MADRS would be superior to the HRSD(17) in the conduct of clinical trials.

Adolescent↗

Clinical vs. self-report versions of the quick inventory of depressive symptomatology in a public sector sample.

OBJECTIVES: Recent work using classical test theory (CTT) and item response theory (IRT) has found that the self-report (QIDS-SR(16)) and clinician-rated (QIDS-C(16)) versions of the 16-item quick inventory of depressive symptomatology were generally comparable in outpatients with nonpsychotic major depressive disorder (MDD). This report extends this comparison to a less well-educated, more treatment-resistant sample that included more ethnic/racial minorities using IRT and selected classical test analyses. METHODS: The QIDS-SR(16) and QIDS-C(16) were obtained in a sample of 441 outpatients with nonpsychotic MDD seen in the public sector in the Texas Medication Algorithm Project (TMAP). The Samejima graded response IRT model was used to compare the QIDS-SR(16) and QIDS-C(16). RESULTS: The nine symptom domains in the QIDS-SR(16) and QIDS-C(16) related well to overall depression. The slopes of the item response functions, a, which index the strength of relationship between overall depression and each symptom, were extremely similar with the two measures. Likewise, the CTT and IRT indices of symptom frequency (item means and locations of the item response functions, b(i) were also similar with these two measures. For example, sad mood and difficulty with concentration/decision making were highly related to the overall depression severity with both the QIDS-C(16) and QIDS-SR(16). Likewise, sleeping difficulties were commonly reported, even though they were not as strongly related to overall magnitude of depression. CONCLUSION: In this less educated, socially disadvantaged sample, differences between the QIDS-C(16) and QIDS-SR(16) were minor. The QIDS-SR(16) is a satisfactory substitute for the more time-consuming QIDS-C(16) in a broad range of adult, nonpsychotic, depressed outpatients.

Adult↗

Making clinicians lives easier: guidance on use of the QIDS self-report in place of the MADRS.

BACKGROUND: The ability to convert total scores from one scale to another facilitates the interpretation of research findings and facilitates the use of systematic measurement in clinical practice. METHODS: Item Response Theory methods were used to convert total scores between the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) and the Montgomery Asberg Depression Rating Scale (MADRS) total scores. Data were obtained from a sample of 233 outpatients with highly treatment-resistant, nonpsychotic major depressive episodes participating in a one-year open label study of vagus nerve stimulation to augment psychotropic medication treatment. RESULTS: MADRS total scores averaged 31.9 (SD = 6.7) at baseline and 21.9 (SD = 11.0) at one year. QIDS-SR16 total scores averaged 17.6 (SD = 3.6) at baseline and 12.5 (SD = 5.8) at one year. Based on one-year data (or exit if the patient did not complete one year), corresponding QIDS-SR16 and MADRS total scores were presented for each possible QIDS-SR16 and MADRS total score. A QIDS-SR16 total score of 5 was comparable to a MADRS total score of 7 or 8 (7.5). LIMITATION: The degree to which these results generalize to less treatment-resistant samples is unknown. CONCLUSION: The conversion of QIDS-SR16 and MADRS total scores provides a basis for clinicians who wish to use the QIDS-SR16 to understand what MADRS total scores reported in clinical trials approximate QIDS-SR16 total scores obtained with their patients.

Adult↗

Family history of mood disorder and characteristics of major depressive disorder: a STAR*D (sequenced treatment alternatives to relieve depression) study.

INTRODUCTION: Clinicians routinely ask patients with major depressive disorder (MDD) about their family history. It is unknown, however, if patients who report a positive family history differ from those who do not. This study compared the demographic and clinical features of a large cohort of treatment-seeking outpatients with non-psychotic MDD who reported that they did or did not have at least one first-degree relative who had either MDD or bipolar disorder. METHODS: Subjects were recruited for the STAR( *)D multicenter trial. Differences in demographic and clinical features for patients with and without a family history of mood disorders were assessed after correcting for age, sex, race, and ethnicity. RESULTS: Patients with a family history of mood disorder (n=2265; 56.5%) were more frequently women and had an earlier age of onset of depression, as compared to those without such a history (n=1740; 43.5%). No meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. CONCLUSIONS: Women were twice as likely as men to report a positive family history of mood disorder, and a positive family history was associated with younger age of onset of MDD in the proband. Consistent with prior research, early age of onset appears to define a familial and, by extension, genetic subtype of major depressive disorder.

Adolescent↗

Prevention of missing data in clinical research studies.

Missing data is a problem that is ubiquitous to all clinical studies and a source of multiple problems from an analytic point of view (reduced statistical power, increased the type I error, bias) Statistical approaches have been developed to analyze data collected from trials with missing data. Understanding and implementing the appropriate statistical technique is essential but should be differentiated from preventive approaches that are designed to reduce rates of missing data In this article, we draw attention to these preventive efforts. Seven steps to minimizing the amount of missing data are defined as documentation, training, monitoring reports, patient contact, data entry and management, pilot studies, and communication. Although the implementation of these approaches is time consuming and costly, the overall quality of the study is increased. Despite efforts devoted to areas, no study is without missing data. Once the study is completed, it is essential to assess the pattern of missing data and apply the appropriate statistical analysis.

Bias↗

Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

BACKGROUND: After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. METHODS: We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). RESULTS: Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. CONCLUSIONS: After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.).

Adult↗

Medication augmentation after the failure of SSRIs for depression.

BACKGROUND: Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. METHODS: We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). RESULTS: The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). CONCLUSIONS: Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (ClinicalTrials.gov number, NCT00021528.).

Adult↗

Remissions in maternal depression and child psychopathology: a STAR*D-child report.

CONTEXT: Children of depressed parents have high rates of anxiety, disruptive, and depressive disorders that begin early, often continue into adulthood, and are impairing. OBJECTIVE: To determine whether effective treatment with medication of women with major depression is associated with reduction of symptoms and diagnoses in their children. DESIGN: Assessments of children whose depressed mothers were being treated with medication as part of the multicenter Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial conducted (between December 16, 2001 and April 24, 2004) in broadly representative primary and psychiatric outpatient practices. Children were assessed by a team of evaluators not involved in maternal treatment and unaware of maternal outcomes. Study is ongoing with cases followed at 3-month intervals. SETTING AND PATIENTS: One hundred fifty-one mother-child pairs in 8 primary care and 11 psychiatric outpatient clinics across 7 regional centers in the United States. Children were aged 7 to 17 years. MAIN OUTCOME MEASURES: Child diagnoses based on the Kiddie Schedule for Affective Disorders and Schizophrenia; child symptoms based on the Child Behavior Checklist; child functioning based on the Child Global Assessment Scale in mothers whose depression with treatment remitted with a score of 7 or lower or whose depression did not remit with a score higher than 7 on the Hamilton Rating Scale for Depression. RESULTS: Remission of maternal depression after 3 months of medication treatment was significantly associated with reductions in the children's diagnoses and symptoms. There was an overall 11% decrease in rates of diagnoses in children of mothers whose depression remitted compared with an approximate 8% increase in rates of diagnoses in children of mothers whose depression did not. This rate difference remained statistically significant after controlling for the child's age and sex, and possible confounding factors (P = .01). Of the children with a diagnosis at baseline, remission was reported in 33% of those whose mothers' depression remitted compared with only a 12% remission rate among children of mothers whose depression did not remit. All children of mothers whose depression remitted after treatment and who themselves had no baseline diagnosis for depression remained free of psychiatric diagnoses at 3 months, whereas 17% of the children whose mothers remained depressed acquired a diagnosis. Findings were similar using child symptoms as an outcome. Greater level of maternal response was associated with fewer current diagnoses and symptoms in the children, and a maternal response of at least 50% was required to detect an improvement in the child. CONCLUSIONS: Remission of maternal depression has a positive effect on both mothers and their children, whereas mothers who remain depressed may increase the rates of their children's disorders. These findings support the importance of vigorous treatment for depressed mothers in primary care or psychiatric clinics and suggest the utility of evaluating the children, especially children whose mothers continue to be depressed.

Adult↗

Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment.

Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed. In a split-sample design, a selection of 68 candidate genes was genotyped, with 768 single-nucleotide-polymorphism markers chosen to detect common genetic variation. We detected significant and reproducible association between treatment outcome and a marker in HTR2A (P range 1 x 10(-6) to 3.7 x 10(-5) in the total sample). Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele. The A allele was over six times more frequent in white than in black participants, and treatment was less effective among black participants. The A allele may contribute to racial differences in outcomes of antidepressant treatment. Taken together with prior neurobiological findings, these new genetic data make a compelling case for a key role of HTR2A in the mechanism of antidepressant action.

Adult↗

Self-rated global measure of the frequency, intensity, and burden of side effects.

No standard side-effect measure currently available can be easily used in clinical practice for patients receiving treatment for depression. The Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) Scale was developed to document these three domains of side effects in patients treated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project. This article presents data on the reliability and validity of the FIBSER. The STAR*D prospectively enrolled 4,041 outpatients with nonpsychotic major depressive disorder (MDD) who were seeking medical care (as opposed to symptomatic volunteers recruited via advertisements). The patients were treated with citalopram. Clinical assessments, including the FIBSER, were completed at 2, 4, 6, 9, 12, and, if necessary, 14 weeks after enrollment. The FIBSER was shown to be reliable, with high correlations between observations taken a short time apart, and correlations decreasing as time between observations increased. There were also consistent relationships between items over time. The FIBSER has both face and construct validity. Thus, the FIBSER is a reliable and valid self-report measure of side effects in a population receiving treatment for depression. Although it does not measure the impact of specific side effects, it does measure three domains of impact: frequency, intensity, and burden of the side effects. Its brevity makes it a useful tool for routine clinical practice. These advantages are not available in other side-effect measures.

Adult↗