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Frances L Lynch,
John F Dickerson,
Greg Clarke,
Benedetto Vitiello,
Giovanna Porta,
Karen D Wagner,
Graham Emslie,
Joan Rosenbaum Asarnow,
Martin B Keller,
Boris Birmaher, [......],
Taryn Mayes,
Lynn DeBar,
James T McCracken,
Michael Strober,
Robert L Suddath,
Anthony Spirito,
Matthew Onorato, Jamie Zelazny,
Satish Iyengar,
David Brent
[show abstract]
[hide abstract]
ABSTRACT: Many youth with depression do not respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and this is associated with higher costs. More effective treatment for these youth may be cost-effective.
To evaluate the incremental cost-effectiveness over 24 weeks of combined cognitive behavior therapy plus switch to a different antidepressant medication vs medication switch only in adolescents who continued to have depression despite adequate initial treatment with an SSRI.
Randomized controlled trial.
Six US academic and community clinics.
Three hundred thirty-four patients aged 12 to 18 years with SSRI-resistant depression.
Participants were randomly assigned to (1) switch to a different medication only or (2) switch to a different medication plus cognitive behavior therapy.
Clinical outcomes were depression-free days (DFDs), depression-improvement days (DIDs), and quality-adjusted life-years based on DFDs (DFD-QALYs). Costs of intervention, nonprotocol services, and families were included.
Combined treatment achieved 8.3 additional DFDs (P = .03), 0.020 more DFD-QALYs (P = .03), and 11.0 more DIDs (P = .04). Combined therapy cost $1633 more (P = .01). Cost per DFD was $188 (incremental cost-effectiveness ratio [ICER] = $188; 95% confidence interval [CI], -$22 to $1613), $142 per DID (ICER = $142; 95% CI, -$14 to $2529), and $78,948 per DFD-QALY (ICER = $78,948; 95% CI, -$9261 to $677,448). Cost-effectiveness acceptability curve analyses suggest a 61% probability that combined treatment is more cost-effective at a willingness to pay $100,000 per QALY. Combined treatment had a higher net benefit for subgroups of youth without a history of abuse, with lower levels of hopelessness, and with comorbid conditions.
For youth with SSRI-resistant depression, combined treatment decreases the number of days with depression and is more costly. Depending on a decision maker's willingness to pay, combined therapy may be cost-effective, particularly for some subgroups.
clinicaltrials.gov Identifier: NCT00018902.
Archives of general psychiatry 03/2011; 68(3):253-62. · 12.26 Impact Factor
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Maria A Oquendo,
Sarah Feldman,
Emily Silverman,
Dianne Currier,
Gregory K Brown,
Donna Chen,
Page Chiapella,
Ruth Fischbach,
Madelyn Gould,
Barbara Stanley,
David Strauss, Jamie Zelazny,
Jane Pearson
[show abstract]
[hide abstract]
ABSTRACT: Adverse events (AEs) and serious adverse events (SAEs) are important outcomes of any intervention study yet are under-researched. Vague and variable definitions and substantial underreporting make comparisons of risk between studies difficult and evaluation of the safety of a particular intervention almost impossible. These realities may deter researchers from studying at-risk populations. Suicidal behavior is an adverse event in any study, and potentially a very serious one. Thus the issues of reporting and definition are particularly salient for researchers who work with populations at risk for suicidal behavior, especially when the suicidal behavior is the outcome of interest. We conducted a qualitative study with experienced suicide researchers and intervention experts to delineate the issues related to reporting serious adverse events faced by investigators conducting trials in suicide prevention. Participants from multiple sites were interviewed by phone, interviews transcribed and coded for definition and reporting issues and suggested solutions. A narrative synthesis was prepared and validated by all participants. Participants highlighted the difficulties in defining AEs and SAEs and stressed the importance and complexity of ensuring the AE was related to the study and reported properly, and were in agreement about the consequences of AEs to both institutions and individuals. Participants identified the need for the development of clear and consistent AE definitions and reporting requirements. Clear and consistently applied definitions of adverse and serious adverse events and reporting requirements would enhance the comparability of intervention studies in suicidal populations.
Archives of suicide research: official journal of the International Academy for Suicide Research 01/2011; 15(1):29-42.
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Benedetto Vitiello,
Graham Emslie,
Gregory Clarke,
Karen Dineen Wagner,
Joan R Asarnow,
Martin B Keller,
Boris Birmaher,
Neal D Ryan,
Betsy Kennard,
Taryn L Mayes, [......],
John Dickerson,
Michael Strober,
Robert Suddath,
James T McCracken,
Anthony Spirito,
Matthew Onorato, Jamie Zelazny,
Giovanna Porta,
Satish Iyengar,
David A Brent
[show abstract]
[hide abstract]
ABSTRACT: We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive-behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while nonresponders were given open treatment.
For the current study, patients were reassessed 48 (n = 116) and 72 (n = 130) weeks from intake. Data were gathered from February 2001 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology, and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE]), and relapse, as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed-effects regression models were applied to estimate remission, relapse, and functional recovery.
By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRIs had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (P < .03). Participants with more severe depression, greater dysfunction, and alcohol or drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of nonremitters by the first 6 weeks of treatment (P < .001). Of the 130 participants in remission at week 24, 25.4% relapsed in the subsequent year.
While most adolescents achieved remission, more than one-third did not, and one-fourth of remitted patients experienced a relapse. More effective interventions are needed for patients who do not show robust improvement early in treatment.
clinicaltrials.gov Identifier: NCT00018902.
The Journal of Clinical Psychiatry 11/2010; 72(3):388-96. · 5.80 Impact Factor
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Graham J Emslie,
Taryn Mayes,
Giovanna Porta,
Benedetto Vitiello,
Greg Clarke,
Karen Dineen Wagner,
Joan Rosenbaum Asarnow,
Anthony Spirito,
Boris Birmaher,
Neal Ryan,
Betsy Kennard,
Lynn DeBar,
James McCracken,
Michael Strober,
Matthew Onorato, Jamie Zelazny,
Marty Keller,
Satish Iyengar,
David Brent
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome.
Adolescents (ages 12-18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were randomly assigned to either a medication switch alone (alternate SSRI or venlafaxine) or a medication switch plus cognitive-behavioral therapy (CBT). At week 12, responders could continue in their assigned treatment arm and nonresponders received open treatment (medication and/or CBT) for 12 more weeks (24 weeks total). The primary outcomes were remission and relapse, defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator.
Of 334 adolescents enrolled in the study, 38.9% achieved remission by 24 weeks, and initial treatment assignment did not affect rates of remission. Likelihood of remission was much higher (61.6% versus 18.3%) and time to remission was much faster among those who had already demonstrated clinical response by week 12. Remission was also higher among those with lower baseline depression, hopelessness, and self-reported anxiety. At week 12, lower depression, hopelessness, anxiety, suicidal ideation, family conflict, and absence of comorbid dysthymia, anxiety, and drug/alcohol use and impairment also predicted remission. Of those who responded by week 12, 19.6% had a relapse of depression by week 24.
Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients, similar to adults. Eventual remission is evident within the first 6 weeks in many, suggesting that earlier intervention among nonresponders could be important.
American Journal of Psychiatry 07/2010; 167(7):782-91. · 12.54 Impact Factor
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Ainsley K Burke,
Hanga Galfalvy,
Benjamin Everett,
Dianne Currier, Jamie Zelazny,
Maria A Oquendo,
Nadine M Melhem,
David Kolko,
Jill M Harkavy-Friedman,
Boris Birmaher,
Barbara Stanley,
John J Mann,
David A Brent
[show abstract]
[hide abstract]
ABSTRACT: Exposure to suicidal behavior in peers and relatives is thought to increase risk for suicidal behavior in vulnerable individuals, possibly as a result of imitation or modeling. This study examines exposure to suicidal behavior and likelihood of suicide attempt in a high-risk cohort of offspring of a depressed parent.
A total of 449 offspring of 255 probands with a mood disorder were enrolled in a family study. Probands and offspring were assessed for psychopathology and suicide attempt history, and offspring for suicide exposure. Generalized estimating equations (GEE) and generalized least squares models were used to compare suicide attempt history in exposed and nonexposed offspring as well as characteristics of exposure in exposed offspring suicide attempters and exposed nonattempters. GEE was used to compare exposure occurring before first attempt in attempter offspring and exposure occurring before the same age in matched nonattempter offspring.
Offspring reporting exposure to suicidal behavior were four times more likely to report a lifetime suicide attempt compared with unexposed offspring, controlling for age. Suicide attempt status was not associated with age at first exposure, total number or degree (attempt or threat) of exposures, or relationship. Analysis of exposure occurring before age at first suicide attempt found no association between exposure and suicide attempt.
Offspring exposed to suicidal behavior are more likely to report a lifetime suicide attempt than nonexposed offspring. However, when examining the temporal sequence of exposure and attempt, the association is no longer significant, suggesting that imitation is not sufficient explanation.
Journal of the American Academy of Child and Adolescent Psychiatry 02/2010; 49(2):114-21. · 4.98 Impact Factor
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David Brent,
Nadine Melhem,
Robert Ferrell,
Graham Emslie,
Karen Dineen Wagner,
Neal Ryan,
Benedetto Vitiello,
Boris Birmaher,
Taryn Mayes, Jamie Zelazny,
Matthew Onorato,
Bernie Devlin,
Greg Clarke,
Lynn DeBar,
Marty Keller
[show abstract]
[hide abstract]
ABSTRACT: The authors sought to assess the relationship between candidate genes and two clinical outcomes, namely, symptomatic improvement and the occurrence of suicidal events, in a sample of treatment-resistant depressed adolescents.
A subsample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) trial, 155 of whom were of European origin, were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression, treatment response, or suicidal events. Participants had not responded to a previous adequate trial with an antidepressant and were randomized to receive either another selective serotonin reuptake inhibitor or venlafaxine, with or without cognitive-behavioral therapy (CBT). Single-nucleotide polymorphism (SNP) analyses were conducted using PLINK with permutation procedures.
No relationship was observed between any polymorphism and response to treatment. The FKBP5 (which codes for a protein causing subsensitivity of the glucocorticoid receptor) rs1360780TT and rs3800373GG genotypes were associated with suicidal events (N=18), even after controlling for treatment effects and relevant covariates. These two SNPs were in significant linkage disequilibrium (r=0.91).
The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucocorticoid receptor subsensitivity. These results are consistent with those of other studies linking alterations in the hypothalamic-pituitary-adrenal axis with suicidal behavior. The small number of events and lack of a placebo condition make these results preliminary. Replication with a larger sample and a placebo condition is needed to assess whether these events are related to treatment.
American Journal of Psychiatry 12/2009; 167(2):190-7. · 12.54 Impact Factor
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Benedetto Vitiello,
David A Brent,
Laurence L Greenhill,
Graham Emslie,
Karen Wells,
John T Walkup,
Barbara Stanley,
Oscar Bukstein,
Betsy D Kennard,
Scott Compton, [......],
Mark Riddle,
Tina Goldstein,
John Curry,
Lisa Capasso,
Taryn Mayes,
Sa Shen,
S Sonia Gugga,
J Blake Turner,
Shannon Barnett, Jamie Zelazny
[show abstract]
[hide abstract]
ABSTRACT: To examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide.
Adolescents (N = 124), ages 12 to 18 years, with a 90-day history of suicide attempt, a current diagnosis of depressive disorder (96.0% had major depressive disorder), and a Children's Depression Rating Scale-Revised (CDRS-R) score of 36 or higher, entered a 6-month treatment with antidepressant medication, cognitive-behavioral therapy focused on suicide prevention, or their combination (Comb), at five academic sites. Treatment assignment could be either random or chosen by study participants. Intent-to-treat, mixed effects regression models of depression and other relevant ratings were estimated. Improvement and remission rates were computed with the last observation carried forward.
Most patients (n = 104 or 84%) chose treatment assignment, and overall, three fourths (n = 93) received Comb. In Comb, CDRS-R declined from a baseline adjusted mean of 49.6 (SD 12.3) to 38.3 (8.0) at week 12 and to 27.0 (10.1) at week 24 (p < .0001), with a Clinical Global Impression -defined improvement rate of 58.0% at week 12 and 72.2% at week 24 and a remission (CDRS-R ≤ 28) rate of 32.5% at week 12 and 50.0% at week 24. The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline (r = 0.43, p < .0001) and declined in parallel.
When vigorously treated with a combination of medication and psychotherapy, adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression.
Journal of the American Academy of Child and Adolescent Psychiatry 10/2009; 48(10):997-1004. · 4.98 Impact Factor
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Benjamin I Goldstein,
Wael Shamseddeen,
Anthony Spirito,
Graham Emslie,
Greg Clarke,
Karen Dineen Wagner,
Joan Rosenbaum Asarnow,
Benedetto Vitiello,
Neal Ryan,
Boris Birmaher,
Taryn Mayes,
Matthew Onorato, Jamie Zelazny,
David A Brent
[show abstract]
[hide abstract]
ABSTRACT: Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD.
Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial (N = 334) were enrolled in the Treatment of SSRI-Resistant Depression in Adolescents trial. Analyses examined substance use (via the Drug Use Severity Index) and changes therein in relation to treatment and depressive symptoms. Adolescents meeting substance use disorder criteria via the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version at baseline were excluded.
Substance use was common: 28.1% reported repeated experimentation at baseline. Substance-related impairment was associated with baseline depression severity, older age, physical/sexual abuse, family conflict, hopelessness, and comorbid oppositional defiant disorder/conduct disorder. There was significant improvement in substance-related impairment among adolescents who responded to MDD treatment. Baseline suicidal ideation was higher among the subjects who progressed to high substance-related impairment (≥ 75th percentile) versus those whose substance-related impairment remained low (< 75th percentile), and parental depressive symptoms predicted persistence of high substance-related impairment during the study. The MDD response was best among the adolescents with low 12 week substance-related impairment scores regardless of whether they had high or low baseline substance-related impairment. There were no significant differential effects of specific treatments, pharmacological or cognitive-behavioral therapy, on substance use.
Substance use is common among adolescents with treatment-resistant MDD. The subjects who had persistently low substance-related impairment or who demonstrated reduced substance-related impairment had better MDD treatment response, although the direction of this association is uncertain.
Journal of the American Academy of Child and Adolescent Psychiatry 10/2009; 48(12):1182-92. · 4.98 Impact Factor
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David A Brent,
Laurence L Greenhill,
Scott Compton,
Graham Emslie,
Karen Wells,
John T Walkup,
Benedetto Vitiello,
Oscar Bukstein,
Barbara Stanley,
Kelly Posner, [......],
Mark Riddle,
Tina Goldstein,
John Curry,
Shannon Barnett,
Lisa Capasso, Jamie Zelazny,
Jennifer Hughes,
Sa Shen,
S Sonia Gugga,
J Blake Turner
[show abstract]
[hide abstract]
ABSTRACT: To identify the predictors of suicidal events and attempts in adolescent suicide attempters with depression treated in an open treatment trial.
Adolescents who had made a recent suicide attempt and had unipolar depression (n =124) were either randomized (n = 22) or given a choice (n = 102) among three conditions. Two participants withdrew before treatment assignment. The remaining 124 youths received a specialized psychotherapy for suicide attempting adolescents (n = 17), a medication algorithm (n = 14), or the combination (n = 93). The participants were followed up 6 months after intake with respect to rate, timing, and predictors of a suicidal event (attempt or acute suicidal ideation necessitating emergency referral).
The morbid risks of suicidal events and attempts on 6-month follow-up were 0.19 and 0.12, respectively, with a median time to event of 44 days. Higher self-rated depression, suicidal ideation, family income, greater number of previous suicide attempts, lower maximum lethality of previous attempt, history of sexual abuse, and lower family cohesion predicted the occurrence, and earlier time to event, with similar findings for the outcome of attempts. A slower decline in suicidal ideation was associated with the occurrence of a suicidal event.
In this open trial, the 6-month morbid risks for suicidal events and for reattempts were lower than those in other comparable samples, suggesting that this intervention should be studied further. Important treatment targets include suicidal ideation, family cohesion, and sequelae of previous abuse. Because 40% of events occurred with 4 weeks of intake, an emphasis on safety planning and increased therapeutic contact early in treatment may be warranted.
Journal of the American Academy of Child and Adolescent Psychiatry 09/2009; 48(10):987-96. · 4.98 Impact Factor
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Benedetto Vitiello,
David Brent,
Laurence Greenhill,
Graham Emslie,
Karen Wells,
John Walkup,
Barbara Stanley,
Oscar Bukstein,
Betsy Kennard,
Scott Compton, [......],
Mark Riddle,
Tina Goldstein,
John Curry,
Lisa Capasso,
Taryn Mayes,
Sa Shen,
Sonia Gugga,
Blake Turner,
Shannon Barnett, Jamie Zelazny
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE:: To examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide. METHOD:: Adolescents (N = 124), ages 12 to 18 years, with a 90-day history of suicide attempt, a current diagnosis of depressive disorder (96.0% had major depressive disorder), and a Children's Depression Rating Scale-Revised (CDRS-R) score of 36 or higher, entered a 6-month treatment with antidepressant medication, cognitive-behavioral therapy focused on suicide prevention, or their combination (Comb), at five academic sites. Treatment assignment could be either random or chosen by study participants. Intent-to-treat, mixed effects regression models of depression and other relevant ratings were estimated. Improvement and remission rates were computed with the last observation carried forward. RESULTS:: Most patients (n = 104 or 84%) chose treatment assignment, and overall, three fourths (n = 93) received Comb. In Comb, CDRS-R declined from a baseline adjusted mean of 49.6 (SD 12.3) to 38.3 (8.0) at week 12 and to 27.0 (10.1) at week 24 (p <.0001), with a Clinical Global Impression-defined improvement rate of 58.0% at week 12 and 72.2% at week 24 and a remission (CDRS-R </=28) rate of 32.5% at week 12 and 50.0% at week 24. The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline (r = 0.43, p <.0001) and declined in parallel. CONCLUSIONS:: When vigorously treated with a combination of medication and psychotherapy, adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression.Clinical trial registration information-Treatment of Adolescent Suicide Attempters (TASA). URL: http://clinicaltrials.gov. Unique identifier: NCT00080158.
Journal of the American Academy of Child and Adolescent Psychiatry 09/2009; · 4.98 Impact Factor
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David A Brent,
Graham J Emslie,
Greg N Clarke,
Joan Asarnow,
Anthony Spirito,
Louise Ritz,
Benedetto Vitiello,
Satish Iyengar,
Boris Birmaher,
Neal D Ryan, [......],
Matthew Onorato,
Betsy Kennard,
Taryn L Mayes,
Lynn L Debar,
James T McCracken,
Michael Strober,
Robert Suddath,
Henrietta Leonard,
Giovanna Porta,
Martin B Keller
[show abstract]
[hide abstract]
ABSTRACT: The authors sought to identify predictors of self-harm adverse events in treatment-resistant, depressed adolescents during the first 12 weeks of treatment.
Depressed adolescents (N=334) who had not responded to a previous trial with an SSRI antidepressant were randomized to a switch to either another SSRI or venlafaxine, with or without cognitive behavior therapy. Self-harm events, i.e., suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants, and by systematic weekly assessment for the last 153 participants.
Higher rates of suicidal (20.8% vs. 8.8%) and nonsuicidal self-injury (17.6% vs. 2.2%), but not serious adverse events (8.4% vs. 7.3%) were detected with systematic monitoring. Median time to a suicidal event was 3 weeks, predicted by high baseline suicidal ideation, family conflict, and drug and alcohol use. Median time to nonsuicidal self-injury was 2 weeks, predicted by previous history of nonsuicidal self-injury. While there were no main effects of treatment, venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation. Adjunctive use of benzodiazepines, while in a small number of participants (N=10) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events.
Since predictors of suicidal adverse events also predict poor response to treatment, and many of these events occurred early in treatment, improving the speed of response to depression, by targeting of family conflict, suicidal ideation, and drug use may help to reduce their incidence. The relationship of venlafaxine and of benzodiazepines to self-harm events requires further study and clinical caution.
American Journal of Psychiatry 03/2009; 166(4):418-26. · 12.54 Impact Factor
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Beth S Brodsky,
J John Mann,
Barbara Stanley,
Adrienne Tin,
Maria Oquendo,
Boris Birmaher,
Laurence Greenhill,
David Kolko, Jamie Zelazny,
Ainsley Keller Burke,
Nadine M Melhem,
David Brent
[show abstract]
[hide abstract]
ABSTRACT: Self-reported childhood sexual abuse is associated with major depression and with suicidal behavior. The current study investigates the relationship between reported childhood abuse and the familial transmission of suicidal behavior and other related risk factors.
507 offspring of 271 parent probands with DSM-IV major depressive disorder were compared according to the reported childhood abuse history on demographic, diagnostic, and clinical variables related to risk for suicidal behavior. Both self-report and clinical interview measures assessed history of childhood physical and sexual abuse. The study was conducted from May 1997 to February 2004.
Reported childhood sexual abuse, but not physical abuse, in the proband correlated with suicide attempts, posttraumatic stress disorder, earlier onset of major depressive disorder, higher levels of impulsivity, and greater likelihood of childhood sexual abuse in the offspring and was rarely perpetrated by the affected parent. A reported history of childhood physical abuse was related to more lifetime aggression in the offspring.
Reported childhood sexual abuse is a risk factor for suicidal behavior in parent and offspring. Transmission of suicide risk across generations is related to the familial transmission of sexual abuse and impulsivity. Sexual abuse is not directly transmitted by the victim to the next generation and may be related to family dynamics related to sexual abuse.
The Journal of Clinical Psychiatry 05/2008; 69(4):584-96. · 5.80 Impact Factor
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David Brent,
Graham Emslie,
Greg Clarke,
Karen Dineen Wagner,
Joan Rosenbaum Asarnow,
Marty Keller,
Benedetto Vitiello,
Louise Ritz,
Satish Iyengar,
Kaleab Abebe, [......],
Lynn DeBar,
James McCracken,
Michael Strober,
Robert Suddath,
Anthony Spirito,
Henrietta Leonard,
Nadine Melhem,
Giovanna Porta,
Matthew Onorato, Jamie Zelazny
[show abstract]
[hide abstract]
ABSTRACT: Only about 60% of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor (SSRI). There are no data to guide clinicians on subsequent treatment strategy.
To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI.
Randomized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI, conducted at 6 US academic and community clinics from 2000-2006.
Twelve weeks of: (1) switch to a second, different SSRI (paroxetine, citalopram, or fluoxetine, 20-40 mg); (2) switch to a different SSRI plus cognitive behavioral therapy; (3) switch to venlafaxine (150-225 mg); or (4) switch to venlafaxine plus cognitive behavioral therapy.
Clinical Global Impressions-Improvement score of 2 or less (much or very much improved) and a decrease of at least 50% in the Children's Depression Rating Scale-Revised (CDRS-R); and change in CDRS-R over time.
Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate (54.8%; 95% confidence interval [CI], 47%-62%) than a medication switch alone (40.5%; 95% CI, 33%-48%; P = .009), but there was no difference in response rate between venlafaxine and a second SSRI (48.2%; 95% CI, 41%-56% vs 47.0%; 95% CI, 40%-55%; P = .83). There were no differential treatment effects on change in the CDRS-R, self-rated depressive symptoms, suicidal ideation, or on the rate of harm-related or any other adverse events. There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment.
For adolescents with depression not responding to an adequate initial treatment with an SSRI, the combination of cognitive behavioral therapy and a switch to another antidepressant resulted in a higher rate of clinical response than did a medication switch alone. However, a switch to another SSRI was just as efficacious as a switch to venlafaxine and resulted in fewer adverse effects.
clinicaltrials.gov Identifier: NCT00018902.
JAMA The Journal of the American Medical Association 03/2008; 299(8):901-13. · 30.03 Impact Factor
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Nadine M Melhem,
David A Brent,
Melissa Ziegler,
Satish Iyengar,
David Kolko,
Maria Oquendo,
Boris Birmaher,
Ainsley Burke, Jamie Zelazny,
Barbara Stanley,
J John Mann
[show abstract]
[hide abstract]
ABSTRACT: The authors sought to identify clinical predictors of new-onset suicidal behavior in children of parents with a history of mood disorder and suicidal behavior.
In a prospective study of offspring of parents with mood disorders, 365 offspring (average age, 20 years) of 203 parents were followed for up to 6 years. Offspring with incident suicide attempts or emergency referrals for suicidal ideation or behavior ("incident events") were compared with offspring without such events on demographic and clinical characteristics. Multivariate analyses were conducted to examine predictors of incident events and predictors of time to incident event.
Offspring of probands who had made suicide attempts, compared with offspring of parents with mood disorders who had not made attempts, had a higher rate of incident suicide attempts (4.1% versus 0.6%, relative risk=6.5) as well as overall suicidal events (8.3% versus 1.9%, relative risk=4.4). Mood disorder and self-reported impulsive aggression in offspring and a history of sexual abuse and self-reported depression in parents predicted earlier time to, and greater hazard of, an incident suicidal event.
In offspring of parents with mood disorders, precursors of early-onset suicidal behavior include mood disorder and impulsive aggression as well as parental history of suicide attempt, sexual abuse, and self-reported depression. These results suggest that efforts to prevent the familial transmission of early-onset suicidal behavior by targeting these domains could reduce the morbidity of suicidal behavior in high-risk youths.
American Journal of Psychiatry 10/2007; 164(9):1364-70. · 12.54 Impact Factor
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Maria Oquendo,
David A Brent,
Boris Birmaher,
Laurence Greenhill,
David Kolko,
Barbara Stanley, Jamie Zelazny,
Ainsley K Burke,
Sekip Firinciogullari,
Steven P Ellis,
J John Mann
[show abstract]
[hide abstract]
ABSTRACT: The purpose of the study was to determine if patients with a history of major depressive episode and comorbid posttraumatic stress disorder (PTSD) have a higher risk for suicide attempt and differ in other measures of suicidal behavior, compared to patients with major depressive episode but no PTSD. In addition, to explore how PTSD comorbidity might increase risk for suicidal behavior in major depressive episode, the authors investigated the relationship between PTSD, cluster B personality disorder, childhood sexual or physical abuse, and aggression/impulsivity.
The subjects were 230 patients with a lifetime history of major depressive episode; 59 also had lifetime comorbid PTSD. The demographic and clinical characteristics of subjects with and without PTSD were compared. Multivariate analysis was used to examine the relationship between suicidal behavior and lifetime history of PTSD, with adjustment for clinical factors known to be associated with suicidal behavior.
Patients with a lifetime history of PTSD were significantly more likely to have made a suicide attempt. The groups did not differ with respect to suicidal ideation or intent, number of attempts made, or maximum lethality of attempts. The PTSD group had higher objective depression, impulsivity, and hostility scores; had a higher rate of comorbid cluster B personality disorder; and were more likely to report a childhood history of abuse. However, cluster B personality disorder was the only independent variable related to lifetime suicide attempts in a multiple regression model.
PTSD is frequently comorbid with major depressive episode, and their co-occurrence enhances the risk for suicidal behavior. A higher rate of comorbid cluster B personality disorder appears to be a salient factor contributing to greater risk for suicidal acts in patients with a history of major depressive episode who also have PTSD, compared to those with major depressive episode alone.
American Journal of Psychiatry 04/2005; 162(3):560-6. · 12.54 Impact Factor
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David A Brent,
Maria Oquendo,
Boris Birmaher,
Laurence Greenhill,
David Kolko,
Barbara Stanley, Jamie Zelazny,
Beth Brodsky,
Nadine Melhem,
Steven P Ellis,
J John Mann
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ABSTRACT: Both mood disorder and suicidal behavior are familial. In this study, the authors examine the factors associated with the familial transmission of these two related conditions to learn which are shared or unique risk factors for familial transmission.
The 285 offspring of 141 probands with mood disorder were studied. Proband and offspring characteristics associated with offspring mood disorder were examined by univariate statistics, logistic and Cox regression, and path analysis.
Parental history of sexual abuse was associated with an increased risk of offspring mood disorder. The relationship between parent sexual abuse and offspring mood disorder was mediated by offspring impulsive aggression, sexual abuse, and anxiety disorder. In offspring, higher levels of impulsive aggression were associated with earlier age at onset of mood disorder. Offspring suicide attempt was mainly related to offspring mood disorder, with additional contributions from offspring sexual abuse and impulsive aggression.
The pathways associated with the familial transmission of mood disorder and of suicide attempt are similar but not identical. Prevention of early-onset mood disorder by targeting high- risk families may help to prevent the transmission of suicidal behavior. Because these data are cross-sectional, these results must be confirmed by prospective follow-up.
Journal of the American Academy of Child & Adolescent Psychiatry 11/2004; 43(10):1259-66. · 6.44 Impact Factor
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David A Brent,
Maria Oquendo,
Boris Birmaher,
Laurence Greenhill,
David Kolko,
Barbara Stanley, Jamie Zelazny,
Beth Brodsky,
Sekip Firinciogullari,
Steven P Ellis,
J John Mann
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ABSTRACT: The authors sought to determine 1) whether the risk for familial transmission of suicidal behavior is greater with increased family loading for suicide attempts, and 2) whether the transmission of suicidal behavior is mediated by impulsive aggression.
A reanalysis of a high-risk study compared the offspring of three mood disorder proband groups: suicide attempters with a sibling who also attempted suicide (N=19), suicide attempters whose siblings never made a suicide attempt (N=73), and nonsuicidal probands whose siblings also never engaged in suicidal behavior (N=73). Probands and offspring were assessed with respect to psychopathology, suicide attempt history, impulsive aggression, and exposure to familial adversity.
Offspring of suicide attempters with siblings concordant for suicidal behavior showed a higher risk of suicide attempt than did offspring of nonsuicidal probands and had an earlier age at onset of suicidal behavior than offspring of suicide attempters with siblings discordant for suicidal behavior. Probands from sibling pairs concordant for suicidal behavior and their offspring reported greater lifetime impulsive aggression compared with each of the other two proband/offspring groups. In the offspring, impulsive aggression was the most powerful predictor of early age at first suicide attempt.
Familial loading for suicide attempts may affect rates of transmission as well as age at onset of suicidal behavior, and its effect may be mediated by the familial transmission of impulsive aggression.
American Journal of Psychiatry 09/2003; 160(8):1486-93. · 12.54 Impact Factor
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David A Brent,
Maria Oquendo,
Boris Birmaher,
Laurence Greenhill,
David Kolko,
Barbara Stanley, Jamie Zelazny,
Beth Brodsky,
Jeffrey Bridge,
Steve Ellis,
J Octavio Salazar,
J John Mann
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ABSTRACT: Although adoption, twin, and family studies have shown that suicidal behavior is familial, the risk factors for familial transmission from parent to child remain unclear.
A high-risk family study was conducted comparing the offspring of 2 mood-disordered groups: suicide attempters and nonattempters. Recruited from 2 sites, probands were 81 attempters and 55 nonattempters, with 183 and 116 offspring, respectively. Offspring were assessed by investigators masked to proband status. Probands and offspring were assessed with respect to psychopathologic findings, suicide attempt history, impulsive aggression, and exposure to familial environmental stressors.
Offspring of attempters had a 6-fold increased risk of suicide attempts relative to offspring of nonattempters. Familial transmission of suicide attempt was more likely if (1) probands had a history of sexual abuse and (2) offspring were female and had a mood disorder, substance abuse disorder, increased impulsive aggression, and a history of sexual abuse.
The offspring of mood-disordered suicide attempters are at markedly increased risk for suicide attempts themselves. Familial transmission of suicidal behavior in families with mood disorders almost always requires transmission of a mood disorder and is also related to the offspring's impulsive aggression and the familial transmission of sexual abuse. Early treatment of mood disorders and targeting impulsive aggression and sexual trauma may be helpful in the prevention and treatment of suicidal behavior in families with mood disorders.
Archives of General Psychiatry 10/2002; 59(9):801-7. · 12.02 Impact Factor
