PICO SEARCH ASSIGNMENT WORKSHEET                   

Brief description of patient problem/setting:

A 9 year old male presents to the pediatric psychiatry unit after an act of self-harm the day prior following an interaction with a classmate where he made a negative comment to the classmate’s sibling and felt the urge to punish himself after. The patient notes that ever since moving to America from Colombia, he’s been having feelings of isolation, low mood, and self-blame over not fitting in. He also endorses passive suicidal ideations which have been held at bay due to fear of the pain and notes that currently he is without a clear plan. There are no reported prior psychiatric hospitalizations but his symptoms have been worsening and intensifying. He currently lives with his mother who has noticed increasing sadness and despair.

Search Question:

In children with suicidal ideation or self-harm behaviors, is CBT more effective than antidepressant pharmacotherapy in reducing recurrent self-harm and suicidal thoughts?

Question Type:

☐Prevalence			☐Screening		☐Diagnosis
☐Prognosis			X Treatment		☐Harms

In the event that meta-analyses or systematic reviews are not available to answer a question on clinical treatment such as the efficacy of cognitive behavioral therapy compared to pharmacotherapy the next best choice would be RCT’s. It has been well established that RCT’s are the strongest study design for treatment related questions and more importantly they allow for a direct comparison between the two treatment methods while reducing bias. The next logical choice would be cohort studies as they offer a chance to track patients over long periods of time and compare the outcomes of their treatment regimens. Although my question isn’t particularly targeted towards adverse events, cohort studies can pick up the rarest of these events effectively. These choices are further supported by the natural hierarchy of study designs which upholds meta-analyses & systematic reviews at the top followed by RCT’s and cohort studies.

PICO search terms:  

P	I	C	O
Children	Cognitive behavioral therapy	Pharmacotherapy	Reduced suicidal ideations
Pediatric	Behavioral therapy	Antidepressants	Reduced self-harm
Youth	CBT	SSRI	Suicide prevention
Adolescents	Psychotherapy	Drug therapy	Suicidal thoughts
School-age		Medication
Kids		Fluoxetine

Search tools and strategy used:  

Database	Search terms used	Number of results	Filters Applied
Cochrane Library	Children AND Cognitive BehavioralTherapy OR CBT AND Suicide	74	Review type: intervention, Topic: Child Health
Ebsco	Children AND Anti-depressant AND Suicide	20	English, Child: 6-12, Adolescent: 13-18, USA, United States, Full Text, All child: 0-18 years, English, Past 10 years
Pubmed	Children OR adolescents AND CBT AND suicide	36	Last 10 years, Free full text, Meta-Analysis, RCT, Systematic Review

 When conducting my research, I used 3 different databases as these are the ones I’m most comfortable with, these include Cochrane Library, Ebsco, and Pubmed. I strategically used each database in conjunction with my search terms, and I intentionally used the terms that I thought would yield the most relevant results hence why I went for terms like “Children, CBT, Anti-depressants, and Suicide”. I didn’t want to overcomplicate my searchers and miss valuable pieces of info. I also used filters such as “child health” which was a topic choice offered by Cochrane library, English & USA to keep it relevant to the pediatric population here, and last 10 years to yield info as recent as possible. Additionally, I used filters to select for RCT’s, meta-analysis, and systematic reviews again all in an effort to yield the highest quality evidence. From there I paid keen attention to the titles of each result and if it seemed to be of use, I would then look at the abstract and results. By doing so I was able to narrow down my results to the 3 that I have chosen which I believe offer the best and most useful information to help answer my PICO question.

Results found:  

1. Esposito‐Smythers, Christianne, et al. “Family‐Focused Cognitive Behavioral Treatment for Depressed Adolescents in Suicidal Crisis with Co‐Occurring Risk Factors: A Randomized Trial.” Journal of Child Psychology and Psychiatry, vol. 60, no. 10, 21 July 2019, pp. 1133–1141, https://doi.org/10.1111/jcpp.13095.

1. Study Type: Randomized Control Trial
2. Abstract:

1. Objectives/Background: Suicide is the second leading cause of death among adolescents. The purpose of this study was to test a family-focused outpatient cognitive-behavioral treatment (F-CBT) protocol for depressed adolescents following psychiatric hospitalization for a suicide attempt or suicidal ideation, and who had a co-occurring risk factor (suicidal behavior prior to the index admission, non-suicidal self-injury, and/or a substance use disorder), in a randomized Phase 2 efficacy trial
2. Method: One-hundred forty-seven adolescents (Mean age = 14.91 years; 76.2% female, 85.5% White) and their families, recruited primarily from an inpatient psychiatric hospitalization program, were randomly assigned to F-CBT or enhanced treatment-as-usual (E-TAU). A suicide attempt was the primary outcome variable. Depression, suicidal ideation and non-suicidal self-injury are also reported here. Assessments were completed at pre-treatment as well as 6, 12, and 18-months post-randomization.
3. Results: In the sample as a whole, rates of attempts decreased from 20% at 6 months to 9% at 12-months to 7% at 18-months. There was no evidence of a significant difference between treatment arms in rates of suicide attempts, major depressive disorder, suicidal ideation, or non-suicidal self-injury at any of the post-randomization assessment points.
4. Conclusion: Though F-CBT was associated with reductions in suicidality, depression, and non-suicidal self-injury, E-TAU showed an equally strong effect. Greater frequency of F-CBT treatment sessions, particularly at the start of care, and alternative approaches to transitioning to care at 12 months, may be necessary when using F-CBT with this population.
5. Keywords: Suicide, cognitive-behavioral therapy, adolescent, clinical trial
6. Key points:

1. This randomized controlled trial compared Family-Focused CBT to Enhanced Treatment As Usual (E-TAU), the F-CBT approach is a 12-month interventional process involving one to one adolescent CBT sessions, parent training sessions, and joint family sessions. It focuses on safety planning, cognitive restructuring, behavioral activation, problem-solving and parent involvement in efforts to improve monitoring and communication. On the other hand, E-TAU is comprised of a referral-based system that connects individuals to outpatient community resources after hospitalization such as medication management and therapy.
2. The results demonstrate that in both treatment groups there were noticeable reduction in suicide attempts, depressive symptoms and ideations, and self-injury considered non-suicidal over the course of 18 months. They found no significant differences between the two treatment groups, however.
3. Overall, the study shows that CBT-based interventions are indeed associated with reductions in suicidal behaviors. Furthermore, treatment methods such as E-TAU which emphasize more structured and intensive care with sustained follow-up treatment seem to be quite effective.

4. Why I chose this study: I chose this study because of its high-quality evidence being an RCT first and foremost. More importantly, it directly addresses the effectiveness of CBT in reducing suicidal behavior in adolescents. I also was intrigued by how the study included long-term follow-ups over the course of 18 months and measured depression severity in addition to looking at highly relevant outcomes such as suicide attempts, ideation, and self-injury. The study also makes a valuable comparison to another form on CBT in ETAU highlighting the multifaceted and flexible nature of CBT to fit different needs. Furthermore, I was also able to identify various elements of the studies design that improve its validity such as concealed allocation and assessor blinding.
5. Link to study: https://pmc.ncbi.nlm.nih.gov/articles/PMC6742562/

2. Hetrick, Sarah E, et al. “New Generation Antidepressants for Depression in Children and Adolescents: A Network Meta-Analysis.” Cochrane Database of Systematic Reviews, vol. 2021, no. 5, 24 May 2021, https://doi.org/10.1002/14651858.cd013674.pub2.

1. Study Type: Systematic Review
2. Abstract:

1. Background: Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well‐being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications.
2. Objective: To investigate, via network meta‐analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide‐related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician‐rated depression (CDRS‐R) and suicide‐related outcomes.
3. Method/Criteria: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020. Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs).
4. Analysis: Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self‐rated), functioning, suicide related outcomes and overall adverse outcomes. Random‐effects network meta‐analyses were conducted in a frequentist framework using multivariate meta‐analysis. Certainty of evidence was assessed using Confidence in Network Meta‐analysis (CINeMA). We used “informative statements” to standardise the interpretation and description of the results.
5. Results: Twenty‐six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a “small and unimportant” reduction in depression symptoms on the CDRS‐R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD ‐1.43, 95% CI ‐3.90, 1.04; vilazodone: MD ‐0.84, 95% CI ‐3.03, 1.35; desvenlafaxine MD ‐0.07, 95% CI ‐3.51, 3.36; moderate certainty evidence: sertraline: MD ‐3.51, 95% CI ‐6.99, ‐0.04; fluoxetine: MD ‐2.84, 95% CI ‐4.12, ‐1.56; escitalopram: MD ‐2.62, 95% CI ‐5.29, 0.04; low certainty evidence: duloxetine: MD ‐2.70, 95% CI ‐5.03, ‐0.37; vortioxetine: MD 0.60, 95% CI ‐2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were “small and unimportant” differences between most antidepressants in reduction of depression symptoms (high‐ or moderate‐certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self‐harm or suicide was an exclusion criterion for the study. Proportions of suicide‐related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide‐related outcomes compared with placebo. There is low certainty evidence that escitalopram may “at least slightly” reduce odds of suicide‐related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may “at least slightly” increase odds of suicide‐related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an “at least slightly” increased odds of suicide‐related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants.
6. Conclusions: Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first‐line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide‐related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.
7. Key points:

1. Most antidepressants revealed only a small and modest reduction in depressive symptoms compared with the placebo. The researchers used the terms “ small and unimportant” emphasize the limited impact of their effect.
2. No specific antidepressant greatly outperformed any of the others in the reduction of depressive symptoms.
3. As stated earlier, the evidence that was obtained regarding the effectiveness of antidepressants in reducing suicidal outcomes was deemed unreliable. A lot the trials excluded high-risk youth that were actively suicidal and furthermore the confidence intervals were wide.
4. The researchers placed a strong emphasis on close monitoring for potential suicidal ideations and behaviors when attempted to prescribe antidepressants to at risk youth. They also made mention of CBT being a very important first-line option in accordance with guidelines.

4. Why I chose this study: As a systematic review this study contains a very high level of evidence and confidence in its data. The prior study looked at CBT and its effects on suicide reduction and this study now focuses on newer-generation antidepressants and how they help to alleviate depression which as we know is strongly associated with suicidal ideation and self-harm. It provided me with solid evidence that most antidepressants provide only a modest reduction in depressive symptoms, and the data is even more uncertain in terms of suicide-related outcomes. This is in part due to many high-risk youths being excluded from trials thus creating gaps in the available evidence. The study was also performed quite rigorously as it examined multiple antidepressants and pulled evidence from a series of databases.
5. Link to study: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013674.pub2/full?highlightAbstract=cognitiv%7Ccognit%7Ctherapy%7Csuicide%7Csuicid%7Cbehavioural%7Ccbt%7Ccognitive%7Cchildren%7Cbehavioral%7Ctherapi%7Cbehaviour%7Cbehavior%7Cchild
6. Ignaszewski, M. J., & Waslick, B. (2018). Update on Randomized Placebo-Controlled Trials in the Past Decade for Treatment of Major Depressive Disorder in Child and Adolescent Patients: A Systematic Review. Journal of Child & Adolescent Psychopharmacology, 28(10), 668–675. https://doi-org.york.ezproxy.cuny.edu/10.1089/cap.2017.0174

1. Study Type: Systematic Review
2. Abstract:

1. Objectives: Antidepressant treatment for major depressive disorder (MDD) has been a topic of continued interest with a number of placebo randomized-controlled trials (RCTs) being published in the past decade. We review the updated literature since the 2007 Bridge meta-analysis, and reassess safety data looking at signals of treatment-emergent suicidality with the Columbia Suicide Severity Rating Scale (CSSR-S).
2. Methods: PubMed literature review was performed searching for RCTs published since the 2007 article and supplemented with manual search.
3. Results: Findings from seven trials (five industry sponsored, one NIMH funded, and one other) were included in this systematic review, which showed high medication and placebo response rates, with only fluoxetine and escitalopram treatment reaching statistical significance. Fluoxetine was also shown to prevent relapse of MDD with continued treatment with an odds ratio of 3.2 for prevention of relapse compared with placebo. There were no increases in treatment-emergent suicidality associated with antidepressant medication in any trial measuring suicidality systematically using the CSSR-S.
4. Conclusions: Depressed pediatric patients respond similarly in these trials to antidepressant intervention and placebo, with recent studies showing that newer agents did not clearly demonstrate benefit above placebo. The evidence continues to support fluoxetine and escitalopram as first-line treatment and demonstrated effect to prevent relapse. Use of newer rating scales reveals similar rates of treatment-emergent suicidality in patients on antidepressants as placebo, in contrast to increased suicide signal suggested by past research using adverse events data. Antidepressant treatment is generally safe and well tolerated in this age group.
5. Key Points:

1. This systematic review was done in association with 7 different placebo RCT’s on children & adolescents with MDD, it found high response rates to placebos. It also mentions that fluoxetine and escitalopram were the only SSRI’s that showed any significant benefit over placebo.
2. Another key point is that despite the general consensus that anti-depressants provide relatively modest reduction in suicidality, there was no significant increase in treatment associated suicidality. It was further mentioned that suicide risk associated with SSRI’s may be better explained by how suicidality is measured.
3. The overall message is that despite newer agents not blatantly outperforming placebos, the risk to benefit profile nonetheless upholds fluoxetine and escitalopram as the clear best pharmacologic options when deemed necessary. The study furthermore stresses the importance of close monitoring early on in treatment and of course going forwards.

4. Why I chose this study: I chose this study because it provides a different perspective from the prior article on the effectiveness of pharmacologic options in reducing suicidality in children. Specifically, it looks at treatment-induced suicidality using a certain tool called the Columbia suicide severity rating scale which adds greater reliability to the data. Adding this study furthermore allows me to include a structured suicidality assessment as evidence in the form of this tool. It also reiterates the point that despite the overall modest reduction in suicidality offered by pharmacotherapy certain options such as fluoxetine do indeed offer considerable reduction.
5. Link to study: https://journals-sagepub-com.york.ezproxy.cuny.edu/doi/full/10.1089/cap.2017.0174

Clinical bottom line:

Across the studies that I have chosen which include one randomized controlled trial and two systematic reviews, the overall evidence is there to suggest that both CBT and antidepressants produce reductions in depressive symptoms and suicidality in adolescents. What the studies fail to clarify however is which is the superior method of reducing these negative symptoms. The first article emphasized the role of structured and sustained follow-up as a key driver of psychotherapy success as seen with family-focused CBT’s considerable reduction in suicide attempts over 18 months. This idea of CBT’s efficacy is further emphasized in the following systematic review obtained from the Cochrane database; it found that anti-depressants again only offer modest reductions and come with a warning of potential increased odds of suicidality. Commentary from these researchers even explain that CBT is indeed the first line in accordance with guidelines. Finally, even when compared to a placebo antidepressants failed to provide convincing results apart from the two recognized options of fluoxetine and escitalopram. Collectively, this evidence suggests that CBT is the first line in reducing suicidality in children and if necessary pharmacotherapy with fluoxetine or escitalopram can be added but never psychotherapy as a stand alone therapy. Pharmacotherapy poses risks of increased suicidality especially early on in treatment and adherence issues are always a concern when considering pharmacotherapy in the pediatric population.