Psychotherapy for depression in college students

Abstract Background: Depression is a disease with a high incidence and easy to relapse. It not only affects the work and life of patients, but also brings a heavy economic burden. University is the peak of depression, and the prevalence of depression among college students is much higher than that of ordinary people. The purpose of this research is to evaluate depression symptoms, life satisfaction, self-confidence, substance use, social adjustment, and dropout rates of the use of psychological intervention for college students. Methods: We will identify relevant trials from systematic searches in the following electronic databases: PubMed, Embase, Web of Science and The Cochrane Library. We will also search Clinical Trials.gov, the WHO International Clinical Trials Registry Platform for unpublished data. Additional relevant studies will be searched through search engines (such as Google), and references included in the literature will be tracked. All relevant randomized controlled trials (RCTs) will be included. There are no date restrictions. Use Cochrane Collaboration's Risk of bias tool to conduct risk of bias analysis. Use the Grades of Recommendation, Assessment, Development, and Evaluation to assess the quality of evidence. All statistical analysis will be performed using Stata (V.15.0.) and Review Manager (V.5.2.0). Results: A total of 6238 records were obtained by searching the database and 27 records were obtained by other sources. After removing duplicate records, there are 4225 records remaining. We excluded 3945 records through abstract and title, leaving 280 full-text articles. Conclusion: This will be the first study to compare the effects of different psychological treatments on depression in college students. We hope that this study will guide clinical decision-making of psychotherapy to better treat depression in college students. Protocol Registration: INPLASY202070134.


Introduction
Depression is a common mental health disorder, which is mainly manifested by significant and lasting depression, slow thinking, sleep disturbance, loss of appetite, etc. In severe cases, suicide attempts or behaviors may occur. [1] Each episode of depression lasts at least two weeks. In severe cases, it may last for several years. This has a serious impact on work and life, and has caused a heavy financial burden. According to the World Health Organization, more than 350 million people worldwide suffer from depression. [2] The current incidence of depression in China is 6.1%. [3] By 2020, depression may become the second largest disease after heart disease. [4] And depression has become the main reason for people's loss of social function and ranks third in the global burden of disease. [5] Studies have shown that in the United States alone, the annual cost exceeds $43.7 billion. [6,7] College students are faced with the pressure from interpersonal communication, arduous learning tasks and adaptation to the new environment and lifestyle, which makes them prone to produce strong psychological conflicts and lead to depression. [8] Therefore, compared with their peers, college students have a higher risk of depression. [9] At present, the treatment of depression is mainly divided into medication and psychotherapy. Drug therapy mainly includes selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin norepinephrine reuptake inhibitors (SNRIs), etc. [10] Psychotherapy is to establish a relationship with the patient through a structured and purposeful connection and use a series of specific techniques to improve the patient's mental state. [11] It plays an important role in the treatment of depression. At present, the common psychotherapy in clinical treatment methods include cognitive behavior therapy, group psychotherapy, interpersonal behavior therapy, mindfulness therapy, etc. Previous studies showed that there are few systematic reviews and meta-analysis of depression in college students. However, the relevant evidence for the effectiveness of psychotherapy is still unclear, and there is no evidence to directly compare different psychological interventions. Therefore, this field urgently needs a Bayesian network meta-analysis (NMA) method that combines direct evidence with indirect evidence from multiple treatment comparisons to estimate the correlation between all treatments. [12] In this study, we will conduct a systematic review and NMA to evaluate depression symptoms, life satisfaction, self-confidence, substance use, social adjustment, and dropout rates of the use of psychotherapy for college students.

Methods
2.1. Eligibility criteria 2.1.1. Type of study. We will include all relevant randomized controlled trials (RCTs) including crossover trials. There are no language restrictions.
2.1.2. Type of patient. The patients we will include are college students diagnosed with depression according to any diagnostic criteria, such as Diagnostic and Statistical Manual of Mental Disorders (DSM)-III, [13] DSM-IV, [14] and International Classification of Diseases, 10th Revision (ICD-10). [15] Studies in which participants have a diagnosis of bipolar disorder, psychotic depression will be excluded. In addition, studies where participants are not clearly diagnosed with depression will also be excluded.
2.1.3. Type of interventions. We will include RCTs comparing one psychological intervention with another control conditions for depression in college students. For psychotherapy, mindfulness therapy, cognitive-behavioral therapy (CBT), meditation therapy, comprehensive self-control training (CSCT), [16] acceptance and commitment therapy (ACT), [17] and behavioral activation (BA) will be included. There will be no limit to the treatment session. In terms of control conditions, waiting-list control (WLC), [18] non-treatment control, physical exercise, bibliotherapy, [19] treatment as usual (TAU) will be included.

Type of outcomes. Primary outcome
Depression symptoms that mean the change in severity of depression from baseline to end point which is measured by the depression scale, such as Beck Depression Inventory (BDI), [20] The Center for Epidemiologic Studies Depression Scale (CESD-R), [21] Hamilton Rating Scale for Depression (HRSD). [22] Second outcomes 1. self-confidence, life satisfaction was assessed using visual rating scale 2. social adjustment was assessed using the Social Adaptation Self Evaluation Scale (SASS) [23] and the Social Adjustment Scale-Self Report for Youth. [24] 3. substance use was measured with 10 items to assess the use of eight substances, quantity per drinking and smoking day. [25] 4. Dropout rates from the beginning of the study to the end of the intervention.

Data source
We will identify relevant trials from systematic searches in the following electronic databases: PubMed, Embase, Web of Science and The Cochrane Library. We will also search Clinical Trials. gov, the WHO International Clinical Trials Registry Platform for unpublished data. The search terms will include "depression", "depressive disorder", "students", "university student", "college student". Additional relevant studies will be searched through search engines (such as Google), and references included in the literature will be tracked. There is no date restriction. Detail of search strategy of PubMed is shown in Table 1 as well as detail of search strategy of Embase is shown in Table 2.

Study selection
All records identified in the databases will be collected in the reference management software EndNote X8 for data screening. Two (MMN and PFM) reviewers will use data extraction tables to extract data from the original report independently, including research characteristics (such author information, publication year, journal and country), patient characteristics, intervention and outcome. Any disagreements will be resolved by the third member of our review team.

Risk of bias analysis
According to Cochrane Collaboration's Risk of bias tool, we will assess risk of bias as 'low risk', 'unclear risk' or 'high risk'. [26] The following items will be evaluated: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, incomplete outcome data and selective outcome reporting and other sources of bias. [27] The evaluation Zhang et al. Medicine (2020) 99:39 Medicine will be conducted by two independent raters (PFM and LD). Any disagreements will be resolved by a third review author.
2.5. Statistical analysis 2.5.1. Pairwise meta-analysis. We will use Review Manager (V.5.2.0) to perform traditional pairwise meta-analysis. Dichotomous data will be expressed as relative risk (RR) with 95% confidence interval (CI), and continuous outcomes will be expressed as standard mean difference (SMD) with 95% CI. [28] 2.5.2. Network meta-analysis. To simultaneously assess the comparative effects of more than 2 psychotherapy, an NMA will be performed. An NMA synthesizes direct and indirect comparisons over an entire network of psychotherapy, allowing for all available evidence to be considered in one analysis. Based on the network development process as outlined above, the outcome variable for the NMA is the standardized mean change in the DSST (measured using Hedge's G) from baseline to end of study. The standardization is based on the pooled (across treatment arms within study) estimate of the SDs. The NMA will be carried out using a frequentist's approach, and a 2-way ANOVA model is used. As the residual variances between treatment groups are known, it is possible for random effect estimates to be produced, which account for the between-trial heterogeneity. The model is used to perform ordinary pairwise meta-analysis comparing the different psychotherapy based on direct evidence from the clinical studies. Ranking probabilities will be calculated based on the joint distribution of the estimates of relative efficacy. [29] Consistency will be addressed through the principle of node splitting by using a network meta-regression model. The purpose of node-splitting is to investigate if the relative effect of 2 psychotherapy based on direct comparisons is comparable with the same effect based on indirect comparisons. Statistically, the model is an extension of the NMA, which allows for a different relative effect between the 2 psychotherapy that are being split in head-to-head trials compared with all other trials. NMA will be implemented by the mvmeta software package in Stata (15.0; Stata Corporation, College Station, TX, USA Stata), [30] If P value <.1 and I 2 > 50%, it is considered that there is heterogeneity in the study, and sensitivity analysis or subgroup analysis will be performed to detect the source of heterogeneity. Funnel plot and Egger linear regression analysis will be used to assess publication bias. Using Review Manager (V.5.2.0) to analyze the risk of bias in the included studies, where the green, yellow, and red in the image represent low, unclear, and high risks, respectively. [31,32] 2.5.3. Subgroup analysis. If statistical heterogeneity is evident, we will analyze the causes of heterogeneity, if there is enough data (such as differences between sexes, comparison between different countries, studies sponsored versus not sponsored by companies).

Sensitivity analysis.
We will use the exclusion method to conduct sensitivity analysis:    Overall mean change scores on BDI Overall mean change scores on SASS The score of visual rating scales ACT = acceptance and commitment therapy, BDI = Beck Depression Inventory, Cl = confidence interval, SASS = Social Adaptation Self Evaluation Scale, SE = standard error, SMD = standardized mean difference, WLC = waiting-list control. GRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. * The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparision group and the relative effect of the intervention (and its 95% Cl). † The assumed and the corresponding risk was calculated from the SMD to SE. (1) exclude low-quality studies; (2) exclude studies with comorbid physical or mental illnesses; (3) exclude trials with missing data.

Quality of evidence
We will use Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the quality of evidence for the primary outcomes. [33,34] The quality of evidence is assessed as 'high', 'moderate', 'low' or 'very low'. The following item will be evaluated: limitations, inconsistency, imprecision, indirectness, and publication bias. [35] 2.7. Summary of findings A "summary of finding" table will be created for the major outcome. We will also add absolute and relative percentage changes to the "summary of finding". For detailed information, see Table 3; we have listed partial summary of findings for the main comparison.

Results of the search
A total of 6238 records were obtained by searching the database and 27 records were obtained by other means. After removing duplicate records, there are 4225 records remaining. We excluded 3945 records through abstract and title, leaving 280 full-text articles. The document screening flowchart is shown in Figure 1.

Characteristic of included studies
In a preliminary trial, we included 8 studies. The average age of patients was 18 to 26, with a maximum sample size of 181 and a minimum sample size of 32. The research period ranges from one month to 12 months. For more detailed information, see Table 4.

Discussion
At present, although some studies have evaluated the intervention effects of psychotherapy, there is no NMA to compare the therapeutic effects of different psychological interventions for college students. Therefore, this systematic review and NMA will summarize the direct comparison and indirect comparison evidence to evaluate different psychological interventions. We hope that this study will help guide clinical decision-making for psychotherapy to better treat depression in college students.  Hamdan-Mansour, 2009 [37] No report 46/38 44 40 CBT no treatment Depression symptoms 3 months ACT = acceptance and commitment therapy, BA = behavioral activation, CBT = cognitive-behavioral therapy, CSCT = comprehensive self-control training, TAU = treatment as usual, WLC = waiting-list control.