Treatment for Adolescents With Depression Study (TADS)

Emslie, Graham J.; Kratochvil, Christopher J.; Vitiello, Benedetto; Silva, Sílvia Agostinho da; Mayes, Taryn L.; McNulty, Steven; Weller, Elizabeth B.; Waslick, Bruce; Casat, Charles D.; Walkup, John T.; Pathak, Sanjeev; Rohde, Paul; Posner, Kelly; March, John S.

doi:10.1097/01.chi.0000240840.63737.1d

Cited by 155 publications

(114 citation statements)

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“…[30] Fluoxetine plus CBT versus CBT alone: The RCT found a significantly greater reduction in self-reported physical symptoms for fluoxetine plus CBT compared with CBT alone after 12 weeks of treatment (mean PSC scores: 11.0 with combination therapy v 18.5 with CBT alone; P = 0.0036; PSC scores at start of treatment not reported). [40] The RCT found higher numbers of treatment-emergent physical adverse effects for fluoxetine plus CBT compared with CBT alone (61 with combination therapy v 9 with CBT alone; significance not assessed). There was a significant reduction in suicidal ideation scores for fluoxetine plus CBT compared with CBT alone at 12 weeks (mean SIQ scores: 10.9 with combination treatment v 11.3 with CBT alone; P = 0.04; scores at start of treatment not reported).…”

Section: Fluoxetine Plus Cbt Versus Fluoxetine Alonementioning

confidence: 99%

“…[40] The RCT found lower numbers of treatment-emergent physical adverse effects for fluoxetine plus CBT compared with fluoxetine alone (61 with combination therapy v 81 with fluoxetine; significance not assessed). It found no significant differences in the number of people reporting adverse effects between the three treatment groups receiving pills (37 with combination treatment v 35 with fluoxetine v 34 with placebo; reported as not significant).…”

Section: Fluoxetine Plus Cbt Versus Fluoxetine Alonementioning

confidence: 99%

“…[40] Fluoxetine plus CBT versus placebo: The RCT found no significant difference in reduction of self-reported physical symptoms for fluoxetine plus CBT compared with placebo after 12 weeks of treatment (mean Physical Symptom Checklist [PSC] scores: 11.0 with combination therapy v 12.3 with placebo; reported as not significant; P value not reported; PSC scores at start of treatment not reported). [40] The RCT found similar numbers of treatment-emergent physical adverse effects for fluoxetine plus CBT compared with placebo (61 with combination therapy v 60 with placebo; significance not assessed). It found no significant differences in the number of people reporting adverse effects between the three treatment groups receiving pills (37 with combination treatment v 35 with fluoxetine v 34 with placebo; reported as not significant; significance not assessed).…”

Section: Harmsmentioning

confidence: 99%

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Complementary, light, sleep deprivation and exercise therapies

2007

Treating Depression Effectively

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INTRODUCTION: Depression may affect 2-8% of children and adolescents, with a peak incidence around puberty. It may be self-limiting, but about 40% of affected children experience a recurrent attack, a third of affected children will make a suicide attempt, and 3-4% will die from suicide. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological, psychological, combination, and complementary treatments for depression in children and adolescents? What are the effects of treatments for refractory depression in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: citalopram, cognitive behavioural therapy (CBT) (individual or group, to prevent relapse), escitalopram, electroconvulsive therapy, family therapy, fluoxetine (alone or with cognitive therapy or CBT), fluvoxamine, group therapeutic support (other than CBT), guided self-help, individual psychodynamic psychotherapy, interpersonal therapy, lithium, mirtazapine, monoamine oxidase inhibitors (MAOIs), omega-3 polyunsaturated fatty acids, paroxetine, sertraline (alone or with CBT), St John's Wort (Hypericum perforatum), tricyclic antidepressants, and venlafaxine.

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Section: Fluoxetine Plus Cbt Versus Fluoxetine Alonementioning

confidence: 99%

Section: Fluoxetine Plus Cbt Versus Fluoxetine Alonementioning

confidence: 99%

Section: Harmsmentioning

confidence: 99%

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Complementary, light, sleep deprivation and exercise therapies

2007

Treating Depression Effectively

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“…5,6 Predictors of suicidal adverse events include previous suicidal behaviour and higher baseline levels of suicidal ideation, anger, and irritability. 5 In the Treatment of Adolescent Depression Study, 6 the rate of suicidal events was lower in the combination of antidepressant and CBT than in medication alone; however, in other clinical trials of more severely or chronically depressed youth, no protective effect was found for combination treatment. 6,7 No relation has been established among dosage, adherence pattern, medication type, and risk for events, and while some promising pharmacogenetic findings have been reported, there is currently no clinical applicability of these findings.…”

mentioning

confidence: 99%

“…2 However, other reports have shown similar rates of events, whether using usual adverse event reporting methods or by deriving the occurrence of events from systematically assessed measures of self-reported suicidal ideation. 5,6 Predictors of suicidal adverse events include previous suicidal behaviour and higher baseline levels of suicidal ideation, anger, and irritability. 5 In the Treatment of Adolescent Depression Study, 6 the rate of suicidal events was lower in the combination of antidepressant and CBT than in medication alone; however, in other clinical trials of more severely or chronically depressed youth, no protective effect was found for combination treatment.…”

mentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitors and Suicidality: A Guide for the Perplexed

Brent

2009

Can J Psychiatry

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T he rate of suicidal adverse events is elevated around 2-fold in drugs, relative to placeboes, in clinical trials of antidepressants in children, adolescents, and young adults. 1,2 Since the FDA's black box warning in [2003][2004], there has been a decline in the prescription rate of antidepressants, with no compensatory increase in referrals for psychotherapy in the United States. 3 Families, patients, and clinicians are uncertain about how to balance the benefits and risks of antidepressants. In this brief review, the clinical significance of suicidal events is discussed along with the factors that may increase or attenuate the risk, possible explanations for this phenomenom, the benefits and risks of antidepressants, the public health implications of a decline in the use of SSRIs, and recommendations for clinicians.Suicidal adverse events are treatment-emergent increases in suicidal ideation or an actual suicide attempt. In more than 4300 participants in pediatric antidepressant clinical trials, there have been no deaths by suicide, and most of these events were increases in suicidal ideation, rather than actual suicide attempts. The actual risk difference for the occurrence of an event is not large. While the FDA initially reported a risk difference of 2%, a more recent re-analysis included more recently conducted trials found a risk difference of only 0.9%, which translates to a NNH of 121. 1,2 Moreover, during the period of time when the rate of SSRI prescriptions was increasing, youth suicide rates were declining. 4 One cannot necessarily infer a causal relation between the increase in the use of SSRIs in adolescents and a decline in the adolescent suicide rate. However, if antidepressants were associated with an increased risk for suicide, one would have expected an increase in adolescent suicide, which clearly was not the case.The nature of assessment for suicidal events has also been questioned. In most clinical trials, suicidal events are not surveyed systematically, but are reported spontaneously. In fact, in the subset of clinical trials that had systematic assessment, there was no difference between medication and placebo regarding systematically assessed suicidal ideation. 2 However, other reports have shown similar rates of events, whether using usual adverse event reporting methods or by deriving the occurrence of events from systematically assessed measures of self-reported suicidal ideation. 5,6 Predictors of suicidal adverse events include previous suicidal behaviour and higher baseline levels of suicidal ideation, anger, and irritability. 5 In the Treatment of Adolescent Depression Study, 6 the rate of suicidal events was lower in the combination of antidepressant and CBT than in medication alone; however, in other clinical trials of more severely or chronically depressed youth, no protective effect was found for combination treatment. 6,7 No relation has been established among dosage, adherence pattern, medication type, and risk for events, and while some promising pharmacogenetic findings...

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Screening for Depression and Suicide Risk in Children and Adolescents

Viswanathan

Wallace

Middleton

et al. 2022

JAMA

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ImportanceDepression, suicidal ideation, and self-harm behaviors in youth are associated with functional impairment and suicide.ObjectiveTo review the evidence on screening for depression or suicide risk in children and adolescents to inform the US Preventive Services Task Force (USPSTF).Data SourcesPubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022.Study SelectionEnglish-language, randomized clinical trials (RCTs) of screening for depression or suicide risk; diagnostic test accuracy studies; RCTs of psychotherapy and first-line pharmacotherapy; RCTs, observational studies, and systematic reviews reporting harms.Data Extraction and SynthesisTwo reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted.Main Outcomes and MeasuresTest accuracy, symptoms, response, remission, loss of diagnosis, mortality, functioning, suicide-related events, and adverse events.ResultsTwenty-one studies (N = 5433) were included for depression and 19 studies (N = 6290) for suicide risk. For depression, no studies reported on the direct effects of screening on health outcomes, and 7 studies (n = 3281) reported sensitivity of screening instruments ranging from 0.59 to 0.94 and specificity from 0.38 to 0.96. Depression treatment with psychotherapy was associated with improved symptoms (Beck Depression Inventory pooled standardized mean difference, −0.58 [95% CI, −0.83 to −0.34]; n = 471; 4 studies; and Hamilton Depression Scale pooled mean difference, −2.25 [95% CI, −4.09 to −0.41]; n = 262; 3 studies) clinical response (3 studies with statistically significant results using varying thresholds), and loss of diagnosis (relative risk, 1.73 [95% CI, 1.00 to 3.00; n = 395; 4 studies). Pharmacotherapy was associated with improvement on symptoms (Children’s Depression Rating Scale–Revised mean difference, −3.76 [95% CI, −5.95 to −1.57; n = 793; 3 studies), remission (relative risk, 1.20 [95% CI, 1.00 to 1.45]; n = 793; 3 studies) and functioning (Children’s Global Assessment Scale pooled mean difference, 2.60 (95% CI, 0.78 to 4.42; n = 793; 3 studies). Other outcomes were not statistically significantly different. Differences in suicide-related outcomes and adverse events for pharmacotherapy when compared with placebo were not statistically significant. For suicide risk, no studies reported on the direct benefits of screening on health outcomes, and 2 RCTs (n = 2675) reported no harms of screening. One study (n = 581) reported on sensitivity of screening, ranging from 0.87 to 0.91; specificity was 0.60. Sixteen RCTs (n = 3034) reported on suicide risk interventions. Interventions were associated with lower scores for the Beck Hopelessness Scale (pooled mean difference, −2.35 [95% CI, −4.06 to −0.65]; n = 644; 4 RCTs). Findings for other suicide-related outcomes were mixed or not statistically significantly different.Conclusion and RelevanceIndirect evidence suggested that some screening instruments were reasonably accurate for detecting depression. Psychotherapy and pharmacotherapy were associated with some benefits and no statistically significant harms for depression, but the evidence was limited for suicide risk screening instruments and interventions.

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Treatment for Adolescents With Depression Study (TADS)

Cited by 155 publications

References 25 publications

Complementary, light, sleep deprivation and exercise therapies

Complementary, light, sleep deprivation and exercise therapies

Selective Serotonin Reuptake Inhibitors and Suicidality: A Guide for the Perplexed

Screening for Depression and Suicide Risk in Children and Adolescents

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