Table 1.

Studies Included in This Review (by Author's Last Name)

Author (year)	Intervention	Inclusion criteria	Study design	Sample size	Age (mean)	Duration	Drug (mean endpoint dose)	Side effects	Outcome and measures	Effect size attendance SMD (SE)	Conclusions	Limitations
Bernstein et al. (1990)	Alprazolam + school reentry program vs. imipramine + school reentry program	Not described	Open-label study, randomization not described	17	9.5–17 (14.17)	8 weeks	Alprazolam (1.43 mg/day) Imipramine (135.42 mg/day)	Alprazolam and imipramine: sedation, occipital headache, lightheadedness, gastrointestinal discomfort, and dry mouth	Attendance: scale from 1 to 5 (1 = complete refusal, 5 = complete return) from unclear source Anxiety: none Depression: none Global: clinician global improvement scale (none, mild, moderate, and marked)	Not applicable	Attendance = in between group Δ NS Anxiety: n/a Depression: n/a Global: in between group Δ NS	Randomization not described Not blinded Specific SRB eligibility criteria not described Subjective measure of attendance and SRB Nonstandardized psychological intervention
Bernstein et al. (1990)	Alprazolam + school reentry program vs. imipramine + school reentry program vs. placebo + school reentry program	Diagnosis of an anxiety and/or depressive disorder School refusal (not defined)	Double blind and placebo controlled	24	7–18 (14.12)	8 weeks	Alprazolam (1.82 mg/day) Imipramine (164.29 mg/day)	Alprazolam and imipramine: abdominal pain, headaches, drowsiness, blurred vision, constipation, dry mouth, and dizziness, dizziness with standing	Attendance: scale from 1 to 5 (1 = complete refusal, 5 = complete return) from unclear source Anxiety: ARC, RMCAS Depression: CDI, CDRS Global: none	1.14 (0.93)*	Attendance: in between group Δ NS Anxiety: significant decrease in anxiety on ARC in alprazolam > imipramine > placebo (p = 0.03) RMCAS: in between group Δ NS Depression: in between group Δ NS Global: none	Specific SRB eligibility criteria not described Subjective measure of attendance and SRB Nonstandardized psychological intervention Short duration of intervention
Bernstein et al. (2000)	Imipramine + CBT vs. placebo + CBT	≥20% absence in 4 weeks Diagnosis of depression or anxiety disorder	RCT (double blind)	63 started 47 completed	12–18 (13.9)	8 weeks	Imipramine (187 mg/day)	Not described	Attendance: Parent report of percentage of hours attended/week Successful return to school: ≥75% attendance) Anxiety: ARC-C (Remission <5) and RCMAS Depression: BDI and CDRS-R (remission <35)	1.27 (0.28)	Attendance: imipramine group improved at a faster rate and more at the end of the intervention (p < 0.001) Successful return to school: greater for imipramine (54.2% vs. 16.7%, p < .01) Anxiety: between group Δ NS Depression: Improved in between groups on the CDRS-R favoring imipramine (p < 0.01)	Relatively short duration of treatment
Berney et al. (1981)	Clomipramine + individual therapy/casework with parents vs. placebo + individual therapy/casework with parents	SRB defined as “the association of a neurotic disorder with a marked reluctance to go to school, which had persisted for at least four weeks” No truancy	RCT double blind, randomized stratified by gender	52 randomized 46 completed	9–14 (not given)	12 weeks	Clomipramine (mean dose not given) 9–10 y/o: 40 mg/day 11–12 y/o: 50 mg/day 13–14 y/o: 75 mg/day	Not described	Attendance: clinician-rated 14-item questionnaire, 4-point scale Anxiety: clinician-rated 14-item questionnaire, 4-point scale Depression: clinician-rated 14-item questionnaire, 4-point scale Global: clinician-rated 14-item questionnaire, 4-point scale	Unable to calculate	Attendance: in between group Δ NS Anxiety: in between group Δ NS Depression: in between group Δ NS Overall: in between group Δ NS Conclusion: This trial fails to show that Clomipramine is better than placebo for improving ability to attend school, decrease severity of anxiety, depression, and overall severity.	Specific SRB and comorbid eligibility criteria poorly described Unvalidated measure of attendance and SRB, depression, anxiety, and global improvement Nonstandardized psychological intervention Short duration of intervention Arbitrary and low clomipramine dose selection
Gittelman-Klein et al. (1971)	Imipramine + multidisciplinary therapy vs. placebo + multidisciplinary therapy	Absence or difficulty attending school for 2 weeks and anxiety symptoms	RCT (double blind and placebo controlled)	35 completed	6–14 (10.8)	6 weeks	Imipramine (152 mg/day)	Imipramine: including most commonly drowsiness, dry mouth, constipation, dizziness, and nausea	Attendance: Mother's report on a 7-point Likert scale Successful return to school: Mother's report on Likert scale dichotomized into “Not back to school” and “Back to school” Anxiety: Lorr IMPS, PIRF, and mother's rating of child's behavior questions Depression: Lorr IMPS, PIRF, CBQ, and mother's rating of child's behavior questions Global: Clinician, parent, and child report on a 7-point Likert scale from “Very Much Worse” to “Completely Well”	0.87 (0.43)	Attendance: higher for imipramine (81% vs. 47%, p < 0.05). Anxiety: lower in imipramine vs. placebo in IMPS anxiety item (p < 0.01) Depression: lower in imipramine group vs. placebo in mother ratings of child's depressive symptoms (p < 0.05) and IMPS (p < 0.01) Overall: in between group significant global impression changes on clinician, parent, and child rating favoring imipramine (p < 0.005). Conclusion: Imipramine was better than placebo at improving attendance, and depression and anxiety symptoms	Specific SRB eligibility criteria not described Subjective measure of attendance and SRB Nonstandardized and unvalidated measurements of anxiety and depression Nonstandardized psychological intervention Short duration of intervention Significant dropout in the imipramine arm
Melvin et al. (2017)	CBT vs. CBT + placebo vs. CBT + fluoxetine	Absence from school for >2 weeks in 4 weeks (>50% of time) Anxiety disorder No antisocial behaviors	RCT (double blind for medication groups)	62	11–16.5 (13.6)	12 CBT sessions variable in duration	Fluoxetine (22.5 mg/day)	Fluoxetine: difficulty falling asleep, difficulty arousing in the morning, anger outbursts, headache, lethargy, and apathy CBT+ placebo: 1 suicide attempt	Attendance: school records Successful return to school: ≥80% of school time in school over 4 weeks. Anxiety: ADIS-C, RCMAS Depression: CDI Overall: GAF, CGI Others: SEQSS, CBCL, SRP-CSQ	0.34 (0.31)**	Attendance: in between group Δ NS Anxiety: in between group Δ NS Depression: in between group Δ NS Overall: in between group Δ NS Satisfaction: higher with CBT + fluoxetine (p < 0.05). Conclusion: this trail failed to support hypothesis that augmentation of CBT + fluoxetine improves attendance, anxiety, and depression.	Sample size small for three comparison groups
Wu et al. (2013)	CBT + fluoxetine vs. CBT	Absence from school for >2 weeks in 4 weeks (>50% of time) School refusal due to mood disorder No antisocial behaviors	Randomized, nonplacebo controlled, and nonblinded	82 randomized 75 completed	6–18 (13.44)	12 weeks	Fluoxetine 20–60 mg/day (mean dose not provided)	Fluoxetine: dry mouth, dizziness, attention problems, nausea, sleep disturbances, sleepiness, headache, increased appetite, and bellyache	Attendance: percentage of school attendance (source not specified). Successful return to school: ≥80% of school time in school in 4 weeks. Anxiety: SAS Depression: SDS Overall: CGI-S	0.24 (0.24)	Attendance: in between group (82.1% vs. 72.22%, NS) Anxiety: in between group Δ NS Depression: in between group Δ NS Overall: in between group Δ NS Conclusion: This trial fails to show that fluoxetine can further show efficacy of CBT for school refusal	No placebo controls. Not blinded No intent to treat analysis

CBCL, Child Behavior Checklist; CBQ, Rutter's Children's Behavior Questionnaire; CDI, Children's Depression Inventory; CDRS, Children's Depression Rating Scale; CDRS-R, Children's Depression Rating Scale-Revised; CGI, Clinical Global Impression; CGI-S, Clinical Global Impression Severity of Illness; Lorr IMPS, Lorr Inpatient Multidimensional Psychiatric Scale; NS, nonsignificant; PIRF, Psychiatric Interview Rating Form; RCMAS, Revised Children's Manifest Anxiety Scale; SAS, Self-rating Anxiety Scale; SDS, Self-rating Depression Scale; SEQSS, Self-Efficacy Questionnaire for School Situations; SRP-CSQ, School Refusal Program Consumer Satisfaction Questionnaire; SRB, School Refusal Behavior. ^*Effect size for both the imipramine + school reentry program versus placebo + school reentry program and the alprazolam + school reentry program versus placebo + school reentry. ^**Effect size for CBT + fluoxetine compared to CBT + placebo; RCT, randomized controlled trials; CBT, Cognitive Behavioral Therapy; SE, standard error; SMD, standard mean difference.