Children's Depression Rating Scale-Revised Total Score Research Articles

Safety and Efficacy of Levomilnacipran Extended Release in Pediatric Patients Aged 7-17 Years with Major Depressive Disorder: Results of Two Phase 3, Randomized, Double-Blind Studies.

Objective: Major depressive disorder (MDD) presents a significant psychosocial burden, and there is an unmet need for additional treatment options in pediatric patients. Here, we report the results of two phase 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies evaluating the efficacy and safety of levomilnacipran extended release in children and adolescents with MDD. Methods: In the first study, LVM-MD-11, patients aged 12-17 years received daily doses of levomilnacipran 40 mg (n = 134), levomilnacipran 80 mg (n = 138), fluoxetine 20 mg (n = 134), or placebo (n = 141). In the second study, LVM-MD-14, patients aged 7-17 years received levomilnacipran 40 to 80 mg (n = 166), fluoxetine 20 mg (n = 166), or placebo (n = 160) daily. Primary and secondary efficacy endpoints were changes in Children's Depression Rating Scale-Revised (CDRS-R) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively. Results: In LVM-MD-11, there were no significant differences in change in CDRS-R total score between patients treated daily with placebo (least squares mean [LSM] change in CDRS-R total score -22.9) versus levomilnacipran 40 mg (-23.3; p = 0.8035) or 80 mg (-22.6; p = 0.8681). Similarly, in LVM-MD-14, there were no significant differences in LSM change in CDRS-R total score with placebo (-21.3) versus levomilnacipran 40 to 80 mg daily (-23.0; p = 0.2215). There were also no significant differences between the fluoxetine and placebo groups in either study for changes in CDRS-R total score. Changes in CGI-S score were not significant between placebo and levomilnacipran 40 to 80 mg daily or between placebo and fluoxetine. Levomilnacipran was generally well tolerated. Conclusions: The high placebo response in this study prevented the detection of an effect of levomilnacipran in children and adolescents. Clinical Trial Registration numbers: NCT02431806 and NCT03569475.

Item Response Analyses of the Children's Depression Rating Scale-Revised Using Data from Clinical Studies.

Objective: We aimed to identify which of the 17 items comprising the Children's Depression Rating Scale-Revised (CDRS-R) can sensitively capture changes in depression severity. Methods: We used data from four studies involving two antidepressants. For each of the 17 CDRS-R items, we conducted item response analyses to identify and evaluate those that reflect changes in depression severity. We created plots of the item characteristic curves (ICCs) estimated by the graded response model, and option characteristic curves and ICCs using nonparametric item response theory. The change from baseline in the CDRS-R subscale score with specified reflective items by item response analyses and the effect size between the treatment group and placebo group were calculated and compared with those of the CDRS-R total score. Results: CDRS-R items #2 (difficulty having fun), #3 (social withdrawal), #10 (low self-esteem), #11 (depressed feelings), and #15 (depressed facial expression) have favorable profiles that reflect disease severity. Changes from baseline in the CDRS-R total score (least square mean ± standard error) at week 8 were -22.3 ± 0.7 and -23.9 ± 0.7 in the placebo group and treatment group, respectively (difference, -1.5; estimated effect size, -0.113), changes from baseline in the CDRS-R5 (CDRS-R subscale consisting of the specified reflective items [#2, #3, #10, #11, and #15]) score at week 8 were -8.4 ± 0.3 and -9.6 ± 0.3 in each group, respectively (difference, -1.2; effect size, -0.202). Conclusions: The item response analyses clarified the properties of 17 items of the CDRS-R for major depressive disorder in children and adolescents. The CDRS-R5 might optimize the assessment of changes in overall depression severity and differentiation of treatment responses.

Efficacy and Safety of Duloxetine in Children and Adolescents with Major Depressive Disorder in Japan: A Randomized Double-Blind Placebo-Controlled Clinical Trial Followed by an Open-Label Long-Term Extension Trial.

Objective: The goal of this study was to evaluate the efficacy and safety of duloxetine in children and adolescents (9-17 years of age) with major depressive disorder (MDD) in Japan. Methods: This study consists of two clinical trials. First, a 6-week, randomized double-blind placebo-controlled clinical trial (RCT) was conducted. The primary endpoint of RCT was the change in Children's Depression Rating Scale-Revised (CDRS-R) total scores from baseline. Following RCT, an open-label long-term extension trial (OLE) was conducted to investigate the longer-term safety of duloxetine for ∼1 year. Results: In RCT, CDRS-R total score changes from baseline to 6 weeks after the start of administration (primary endpoint) were -21.03 in the duloxetine group (n = 74) and -22.42 in the placebo group (n = 74). No significant difference was observed in the primary endpoint between the groups (p = 0.5587). In addition, no significant difference was observed in secondary endpoints such as CDRS-R response rates. The proportion of patients with ≥1 treatment-emergent adverse event (TEAE) in RCT was significantly higher in the duloxetine group (78.7%) than in the placebo group (62.2%), and most were mild or moderate in severity. Changes in CDRS-R total scores during OLE, in consecutive patients from the duloxetine group in RCT (n = 63), or placebo group (n = 59) in RCT, and newly enrolled patients (n = 28), were -12.1, -11.3, and -17.8, respectively. The proportion of patients with ≥1 TEAE in OLE was 90.5%, 88.1%, and 89.3% in the respective groups, and most of them were mild or moderate in severity. Conclusions: Duloxetine did not show superiority to placebo in efficacy in children and adolescents with MDD in Japan. Overall reported TEAEs were consistent with the currently available duloxetine safety profile and no new safety finding was observed in the two clinical trials.

Second-Generation Antipsychotics in Management of Acute Pediatric Bipolar Depression: A Systematic Review and Meta-analysis.

Objectives: To evaluate the efficacy in reduction of depressive symptoms, and safety and tolerability of second-generation antipsychotics (SGAs) to manage pediatric bipolar depression (PBD). Methods: We conducted a systematic review for randomized clinical trials (RCTs) for PBD in MEDLINE, Scopus, and EMBASE. Four (quetiapine: 2, lurasidone: 1, olanzapine-fluoxetine combination [OFC]: 1) out of 569 studies met the criteria for inclusion in meta-analysis. RevMan was used for statistical analysis, and the mean difference (MD) between mean children's depression rating scale-revised (CDRS-R) score was used to measure treatment difference between SGA and placebo. Results: Lurasidone displayed a significant reduction in depressive symptoms (MD -5.70, 95% confidence interval [CI] -8.67 to -2.73) in PBD, followed by OFC (MD -5.00, 95% CI -8.64 to -1.36) and quetiapine (MD -2.30, 95% CI -6.80 to 2.20; MD 1.00, 95% CI -9.88 to 11.88). The response was significantly higher for lurasidone (59.5% vs. 36.5%; p < 0.001) and OFC (78.2% vs. 59.2%, p = 0.003) compared with placebo. There was no statistically significant MD in treatment and response rates between quetiapine and placebo in all RCTs. The weighted mean CDRS-R total score difference was -4.58 (95% CI -6.59 to -2.56) and overall effect was significant (p < 0.00001). Importantly, the p value for heterogeneity was 0.46, which indicated that there was no heterogeneity between outcomes of the studies. The number needed to treat (NNT) for lurasidone was 4.3, followed by OFC (NNT = 5.3) and quetiapine (NNT = 12.5; NNT = 25). Conclusion: Our findings showed lurasidone and OFC were more efficacious than placebo for acute depressive episodes in PBD. RCTs of treatments for PBD remain scarce pressing the need for more research.

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Vilazodone in Adolescents with Major Depressive Disorder

BackgroundMajor depressive disorder (MDD) is a serious illness in children and adolescents. Vilazodone is a selective serotonin reuptake inhibitor approved for MDD in adults. This study evaluated the efficacy, safety, and tolerability of vilazodone in adolescent patients, ages 12–17 years, with MDD (NCT01878292).MethodsThis double-blind, randomized, placebo-controlled, parallel-group, fixed-dose study was conducted at 56 study centers in the United States and was 10 weeks in duration (a 1-week screening period, an 8-week double-blind treatment period, and a 1-week double-blind down-taper period). Outpatients with an MDD diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria were included in the study. Clinical inclusion criteria required a Children’s Depression Rating Scale–Revised (CDRS-R) total score of ≥ 40 and Clinical Global Impressions–Severity (CGI-S) score of ≥ 4. Patients were randomized 1:1:1 to 8 weeks of double-blind treatment with placebo (n = 174), vilazodone 15 mg/day (n = 175), or vilazodone 30 mg/day (n = 180). The primary and secondary efficacy parameters were change from baseline to week 8 in CDRS-R total score and CGI-S score, respectively. Safety parameters included adverse events (AEs); clinical laboratory, vital sign, and electrocardiogram parameters; and the Columbia-Suicide Severity Rating Scale.ResultsApproximately 86% of patients completed double-blind treatment. There was no statistically significant difference between vilazodone 15 mg/day or 30 mg/day and placebo in change from baseline in CDRS-R score. Change in CGI-S score was not significant after adjustment for multiple comparisons. The most common treatment-emergent AEs were nausea, upper abdominal pain, vomiting, diarrhea, nasopharyngitis, headache, and dizziness. Reports of suicidal ideation (placebo, 33.3%; vilazodone 15 mg/day, 36.0%; vilazodone 30 mg/day, 31.1%) and suicidal behavior (placebo, 1.8%; vilazodone 15 mg/day, 1.1%; vilazodone 30 mg/day, 1.1%) were similar between treatment groups. There were no deaths in the study.ConclusionsThe efficacy of vilazodone for the treatment of MDD in adolescent patients could not be confirmed in this study. Vilazodone was generally safe and well tolerated, with treatment-emergent AEs similar to those in adult patients.Clinical Trial RegistrationNCT01878292.Electronic supplementary materialThe online version of this article (10.1007/s40272-018-0290-4) contains supplementary material, which is available to authorized users.

Efficacy and Safety of Lurasidone in Children and Adolescents With Bipolar I Depression: A Double-Blind, Placebo-Controlled Study

To evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression. Patients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary endpoint was change frombaseline to week 6 in the Children's Depression Rating Scale-Revised (CDRS-R) total score,evaluated by amixed-model repeated-measures analysis. A total of 347 patients were randomized and received at least 1 dose of lurasidone (n= 175; mean age 14.2 years; mean dose 33.6 mg/day) or placebo (n= 172; mean age 14.3 years). At week 6, treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score (-21.0 versus-15.3; p< .0001; effect size 0.45). Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score (key secondary measure) and in measures of anxiety, quality of life, and global functioning. Study completion rates were 92.0% in the lurasidone group and 89.7% in the placebo group; discontinuation rates due to adverse events were the same for the 2 groups (1.7%). The 2 most common adverse events on lurasidone were nausea and somnolence. Treatment with lurasidone was associated with few effects on weight and metabolic parameters. In this placebo-controlled study, monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly decreased depressive symptoms in children and adolescents with bipolar depression. Lurasidone was well tolerated, with minimal effects on weight and metabolic parameters. Clinical trial registration information-Lurasidone Pediatric Bipolar Study; http://Clinicaltrials.gov; NCT02046369.

Factors associated with depression severity in adolescence

IntroductionSevere depression is greatly impairing during adolescence and involves a high risk for suicidal behaviors.Objectives and aimsIdentify clinical and demographic factors associated with severity of depression in adolescents diagnosed with a major mood disorder so as to improve clinical treatment and prevent suicidal behaviors.MethodsWe analyzed factors associated with depression severity in 145 severely ill adolescents diagnosed with a major affective disorder using the K-SADS (Kiddie-Schedule for Affective Disorders and Schizophrenia) at the Mood Disorder Outpatient Program of Bambino Gesù Children's Hospital (Rome). Depressive and manic symptoms were rated with the CDRS-R (Children's Depression Rating Scale-Revised) and K-SADS-MRS (Mania Rating Scale), respectively. Bivariate comparisons were followed by multivariable linear regression modeling.ResultsDepression severity was greater among females than males (mean CDRS scores: 53.0 vs. 42.8; P &lt; 0.0001) and with major depressive versus bipolar disorder diagnosis (50.4 vs. 45.4; P = 0.001). Manic symptoms, including irritability, mood lability, crowded thoughts, delusions, and insomnia, were more likely with more severe depression; their number and severity correlated with CDRS-R total score (respectively, β = 1.53 and 5.44;both P &lt; 0.0001). Factors independently and significantly associated with CDRS-R depression score in multivariate modeling were:– presence of suicidal ideation;– absence of ADHD;– female sex;– greater number of manic symptoms.ConclusionsSevere depression was associated with manic symptoms and with suicidal ideation among adolescents diagnosed with either bipolar or major depressive disorders. This relationship should be considered in treatment planning and suicide prevention, including consideration of mood-stabilizing and antimanic agents in the treatment of severe adolescent depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Olanzapine/Fluoxetine Combination in Children and Adolescents With Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

To assess the efficacy and safety of olanzapine/fluoxetine combination (OFC) for the acute treatment of bipolar depression in children and adolescents. Patients 10 to 17 years of age with bipolar I disorder (BP-I), depressed episode, baseline Children's Depression Rating Scale-Revised (CDRS-R) total score≥40, Young Mania Rating Scale (YMRS) total score≤15, and YMRS-item 1≤2 were randomized to OFC (6/25-12/50 mg/day olanzapine/fluoxetine; n= 170) or placebo (n= 85) for up to 8 weeks of double-blind treatment. The primary efficacy measure was mean change in CDRS-R using mixed-model repeated-measures methodology. Baseline-to-week-8 least-squares mean change in CDRS-R total score was greater for OFC-treated patients than for placebo-treated patients (-28.4 versus-23.4, p = .003; effect size= .46), with between-group differences statistically significant at week 1 (p= .02) and all subsequent visits (all p< .01). Rates of and times to response and remission were statistically significantly greater for OFC- than for placebo-treated patients. The most frequent treatment-emergent adverse events in the OFC group were weight gain, increased appetite, and somnolence. Mean weight gain at patient's endpoint was significantly greater for OFC- than for placebo-treated patients (4.4 kg versus 0.5 kg, p< .001). Treatment-emergent hyperlipidemia was very common among OFC-treated patients. Abnormal increases in hepatic analytes, prolactin, and corrected QT interval (QTc) were also common or very common but generally not clinically significant. In this study, OFC was superior to placebo, and has been approved by the US Food and Drug Administration (FDA) for the acute treatment of bipolar I depression in patients 10 to 17 years of age. Benefits should be weighed against the risk of adverse events, particularly weight gain and hyperlipidemia. Clinical trial registration information-A Study for Assessing Treatment of Patients Ages 10-17 with Bipolar Depression; http://clinicaltrials.gov; NCT00844857.

A double-blind, placebo-controlled study of selegiline transdermal system in depressed adolescents.

A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12-17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features. Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I). Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial. These data demonstrated that the STS was safe and well tolerated in this adolescent sample. However, both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms (CDRS-R total score) over the length of the study, without statistical superiority by either group.

Efficacy and safety of extended-release quetiapine fumarate in youth with bipolar depression: an 8 week, double-blind, placebo-controlled trial.

Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10-17 years of age, with acute bipolar depression. This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150-300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates. Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: -29.6 (SE, 1.65) with quetiapine XR and -27.3 (SE, 1.60) with placebo, a between-treatment group difference of -2.29 (SE, 1.99; 95% CI, -6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event potentially related to diabetes mellitus occurred in 3.3% of the quetiapine XR versus no adverse events in the placebo group. Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression. Quetiapine XR was generally safe and well tolerated.

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥ 40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤ 28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study drug. AEs suggestive of self-harm occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128) for placebo and 14.5% (19/131) for escitalopram. Extended use of escitalopram was generally safe and resulted in modest improvement in efficacy in adolescents with MDD.

Psychometric Properties of the Children's Depression Rating Scale–Revised in Adolescents

The aim of this study was to present the reliability and validity of the Children's Depression Rating Scale-Revised (CDRS-R) in the adolescent age group. Adolescents with symptoms of depression were assessed using the CDRS-R and global severity and functioning scales at screening, baseline, and after 12 weeks of fluoxetine treatment. Global improvement was also assessed at week 12 (or exit). Reliability and validity were analyzed using Classical Test Theory (item-total correlations and internal consistency) and correlations between the CDRS-R and other outcomes. Adolescents (n = 145) were evaluated at screening; 113 (77.9%) met criteria for major depressive disorder, 8 (5.5%) had subthreshold depressive symptoms, and 24 (16.6%) had minimal depressive symptoms. Ninety-four adolescents had a baseline visit after 1 week, and 88 were treated with fluoxetine. Internal consistency for the CDRS-R was good at all three visits (screening: 0.79; baseline: 0.74; exit: 0.92), and total score was highly correlated with global severity (r = 0.87, 0.80, and 0.93; p < 0.01). Only exit CDRS-R score was significantly correlated with global functioning (Children's Global Assessment Scale; r = -0.77; p < 0.01). Reductions on the CDRS-R total score were highly correlated with improvement scores at exit (Clinical Global Impressions-Improvement; r = -0.83; p < 0.01). The results demonstrate good reliability and validity in adolescents with depression.

The short-term safety and efficacy of fluoxetine in depressed adolescents with alcohol and cannabis use disorders: a pilot randomized placebo-controlled trial

BackgroundThe objective of this study was to examine whether fluoxetine was superior to placebo in the acute amelioration of depressive symptomatology in adolescents with depressive illness and a comorbid substance use disorder.MethodsEligible subjects ages 12–17 years with either a current major depressive disorder (MDD) or a depressive disorder that were also suffering from a comorbid substance-related disorder were randomized to receive either fluoxetine or placebo in this single site, 8-week double-blind, placebo-controlled study. The primary outcome analysis was a random effects mixed model for repeated measurements of Children's Depression Rating Scale-Revised (CDRS-R) scores compared between treatment groups across time.ResultsAn interim analysis was performed after 34 patients were randomized. Based on the results of a futility analysis, study enrollment was halted. Twenty-nine males and 5 females were randomized to receive fluoxetine (n = 18) or placebo (n = 16). Their mean age was 16.5 (1.1) years. Overall, patients who received fluoxetine and placebo had a reduction in CDRS-R scores. However, there was no significant difference in mean change in CDRS-R total score in those subjects treated with fluoxetine and those who received placebo (treatment difference = 0.19, S.E. = 0.58, F = 0.14, p = .74). Furthermore, there was not a significant difference in rates of positive urine drug toxicology results between treatment groups at any post-randomization visit (F = 0.22, df = 1, p = 0.65). The main limitation of this study is its modest sample size and resulting low statistical power. Other significant limitations to this study include, but are not limited to, the brevity of the trial, high placebo response rate, limited dose range of fluoxetine, and the inclusion of youth who met criteria for depressive disorders other than MDD.ConclusionFluoxetine was not superior to placebo in alleviating depressive symptoms or in decreasing rates of positive drug screens in the acute treatment of adolescents with depression and a concomitant substance use disorder.

Long-Term, Open-Label Venlafaxine Extended-Release Treatment in Children and Adolescents with Major Depressive Disorder

Because major depressive disorder (MDD) is often chronic and recurrent, even pediatric patients who are treated successfully during an acute episode may need longer-term treatment. Yet, data on long-term treatment with antidepressants in pediatric MDD are limited. To evaluate long-term effectiveness and safety of treatment with venlafaxine extended-release (ER) in children and adolescents with MDD. Subjects (n=86) 7-17 years of age with MDD entered a multicenter, open-label study of flexible-dose venlafaxine ER for 6 weeks of acute treatment, followed by continuation treatment for up to 6 months total treatment. The primary efficacy variable was the Children's Depression Rating Scale-Revised (CDRS-R) total score (intent-to-treat population). Mean CDRS-R total score decreased from 60.1+/-10.0 at baseline to 36.3+/-13.1 at week 6, and to 33.8+/-15.0 at 6 months (last observation carried forward). Among completers (n=36), the mean CDRS-R total score was 24.3+/-7.6 at the end of 6 months of treatment. The most frequent treatment-emergent adverse events were headache (53%), nausea (26%), infection (24%), abdominal pain (22%), vomiting (21%), and pharyngitis (19%). Fifteen (17%) participants discontinued due to adverse events, 9 of whom did so within the first 6 weeks. Serious adverse events (suicide attempt [two], hostility [two], hallucinations, depression, and pharyngitis) occurred in seven patients. There were no suicides. Most improvement with venlafaxine ER occurs during the first 6 weeks of treatment. Prescribers should be alert to signs of suicidal ideation and hostility in pediatric patients.

Differentiating Depression in Medically Ill Children and Adolescents

Abstract The overlap between ratings of functional impairment and depressive symptomatology in children and adolescents with cancer was examined. Twenty-four pediatric oncology patients referred for psychiatric consultation were assessed on the Children's Depression Rating Scale-Revised (CDRS-R), a Global Rating of Depression, and the Pediatric Performance Scale (PPS). Results indicated significant overlap between the severity of depression (CDRS-R total score) and the degree of functional impairment (PPS). Elimination of the CDRS-R items assessing somatic symptoms of depression yielded a scale that was not correlated with functional impairment but was still significantly correlated with clinical judgment of depression severity (Global Rating of Depression).