Biomedical subjects

Diane Warden

Publications and source records attributed to Diane Warden.

16 recordsLinked to original sources

PubMed2006

The Montgomery Asberg and the Hamilton ratings of depression: a comparison of measures.

The 17-item Hamilton Rating Scale for Depression (HRSD(17)) and the Montgomery Asberg Depression Rating Scale (MADRS) are two widely used clinician-rated symptom scales. A 6-item version of the HRSD (HRSD(6)) was created by Bech to address the psychometric limitations of the HRSD(17). The psychometric properties of these measures were compared using classical test theory (CTT) and item response theory (IRT) methods. IRT methods were used to equate total scores on any two scales. Data from two distinctly different outpatient studies of nonpsychotic major depression: a 12-month study of highly treatment-resistant patients (n=233) and an 8-week acute phase drug treatment trial (n=985) were used for robustness of results. MADRS and HRSD(6) items generally contributed more to the measurement of depression than HRSD(17) items as shown by higher item-total correlations and higher IRT slope parameters. The MADRS and HRSD(6) were unifactorial while the HRSD(17) contained 2 factors. The MADRS showed about twice the precision in estimating depression as either the HRSD(17) or HRSD(6) for average severity of depression. An HRSD(17) of 7 corresponded to an 8 or 9 on the MADRS and 4 on the HRSD(6). The MADRS would be superior to the HRSD(17) in the conduct of clinical trials.

Adolescent↗

PubMed2006

Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

BACKGROUND: After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. METHODS: We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). RESULTS: Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. CONCLUSIONS: After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.).

Adult↗

PubMed2006

Medication augmentation after the failure of SSRIs for depression.

BACKGROUND: Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. METHODS: We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). RESULTS: The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). CONCLUSIONS: Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (ClinicalTrials.gov number, NCT00021528.).

Adult↗

PubMed2006

Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.

OBJECTIVE: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHOD: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of or=11 (HRSD(17)>or=14) defined relapse. RESULTS: The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. CONCLUSIONS: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

Adolescent↗

PubMed2006

A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report.

OBJECTIVE: Few controlled studies have addressed the issue of which antidepressant medications should be recommended for outpatients who have not responded to multiple treatment trials. This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant (nortriptyline) following two prospective, consecutive, unsuccessful medication treatments for nonpsychotic major depressive disorder. METHOD: Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks (first step) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone (second step), adult outpatients (N=235) with nonpsychotic major depressive disorder were randomly assigned to 14 weeks of treatment with mirtazapine (up to 60 mg/day) (N=114) or nortriptyline (up to 200 mg/day) (N=121). The primary outcome, symptom remission, was defined a priori as a total exit score of </=7 on the 17-item Hamilton Rating Scale for Depression. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)), obtained at treatment visits, provided secondary outcomes of remission (score </=5 at exit) and response (>/=50% reduction in score from baseline). RESULTS: For mirtazapine, remission rates were 12.3% and 8.0% per the Hamilton and QIDS-SR(16) scores, respectively. For nortriptyline, remission rates were 19.8% and 12.4%, respectively. QIDS-SR(16) response rates were 13.4% for mirtazapine and 16.5% for nortriptyline. Neither response nor remission rates statistically differed by treatment, nor did these two treatments differ in tolerability or adverse events. CONCLUSIONS: Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (<20%) among patients with major depressive disorder.

Adult↗

PubMed2006

A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report.

OBJECTIVE: More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T(3)) augmentation as a third-step treatment for patients with major depressive disorder. METHOD: A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T(3) (up to 50 mug/day; N=73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score < or =7 on the 17-item Hamilton Depression Rating Scale. RESULTS: After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T(3) augmentation, although the difference between treatments was not statistically significant. Lithium was more frequently associated with side effects (p=0.045), and more participants in the lithium group left treatment because of side effects (23.2% versus 9.6%; p=0.027). CONCLUSIONS: Remission rates with lithium and T(3) augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. The lower side effect burden and ease of use of T(3) augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.

Adolescent↗

PubMed2006

Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report.

OBJECTIVE: The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials. METHOD: Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine (N=51). The primary outcome measure was whether patients achieved remission, which was defined as a score < or =7 at exit on the 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D was administered by telephone by raters to whom treatment was masked. RESULTS: Remission rates were not significantly different between the two treatment groups (6.9% for the tranylcypromine group and 13.7% for the venlafaxine plus mirtazapine group). The mean daily dose at exit for tranylcypromine was 36.9 mg (SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and for mirtazapine, 35.7 mg (SD=17.6). Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance. CONCLUSIONS: Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments.

Adult↗

PubMed2006

Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, but the rates, timing, and baseline predictors of remission in "real world" patients are not established. The authors' primary objectives in this study were to evaluate the effectiveness of citalopram, an SSRI, using measurement-based care in actual practice, and to identify predictors of symptom remission in outpatients with major depressive disorder. METHOD: This clinical study included outpatients with major depressive disorder who were treated in 23 psychiatric and 18 primary care "real world" settings. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks. The clinicians were assisted by a clinical research coordinator in the application of measurement-based care, which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures. Remission was defined as an exit score of or=50% in baseline QIDS-SR score. RESULTS: Nearly 80% of the 2,876 outpatients in the analyzed sample had chronic or recurrent major depression; most also had a number of comorbid general medical and psychiatric conditions. The mean exit citalopram dose was 41.8 mg/day. Remission rates were 28% (HAM-D) and 33% (QIDS-SR). The response rate was 47% (QIDS-SR). Patients in primary and psychiatric care settings did not differ in remission or response rates. A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment. Participants who were Caucasian, female, employed, or had higher levels of education or income had higher HAM-D remission rates; longer index episodes, more concurrent psychiatric disorders (especially anxiety disorders or drug abuse), more general medical disorders, and lower baseline function and quality of life were associated with lower HAM-D remission rates. CONCLUSIONS: The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials. The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results.

Adolescent↗

PubMed2006

Factors associated with health-related quality of life among outpatients with major depressive disorder: a STAR*D report.

OBJECTIVE: Major depressive disorder (MDD) is often chronic and is often associated with significant morbidity and mortality. The importance of assessing disability and health-related quality of life (HRQOL) in patients with MDD has only recently been recognized. The aim of this study was to examine sociodemographic and clinical correlates of HRQOL in a large cohort of outpatients with MDD. METHOD: Baseline assessments were completed for 1500 consecutive patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression trial, including sociodemographic characteristics and measures of depressive symptom severity, clinical features, and HRQOL. Multiple domains of HRQOL were assessed with the 12-item Short Form Health Survey, the Work and Social Adjustment Scale, and the Quality of Life Enjoyment and Satisfaction Questionnaire. The current analyses were conducted on HRQOL data available for 1397 of the 1500 subjects. RESULTS: Greater symptom severity was associated with reduced HRQOL by all measures. Even after age and symptom severity were controlled for, a number of clinical features and sociodemographic characteristics were independently associated with HRQOL in multiple domains, including age at onset of MDD, ethnicity, marital status, employment status, education level, insurance status, and monthly household income. CONCLUSION: Results strongly suggest the need to assess HRQOL in addition to symptoms in order to gauge the true severity of MDD. This study also highlights the necessity of measuring HRQOL in multiple domains. These results have implications for the assessment of remission and functional recovery in the treatment of MDD.

Adult↗

PubMed2005

Presenting characteristics of depressed outpatients as a function of recurrence: preliminary findings from the STAR*D clinical trial.

OBJECTIVES: Recurrent depression predicts risk for subsequent episodes, but it is unclear how it relates to demographic features, course of illness, and clinical presentation. METHODS: We report on the baseline data for the first 1500 patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org). Patients were required to have a DSM-IV diagnosis of nonpsychotic major depression and to score > or = 14 on the 17-item Hamilton rating scale for depression. Status with respect to recurrent depression and other aspects of illness course and demographic features were ascertained at intake, along with measures of depression and concurrent general medical illness. RESULTS: Patients with recurrent depression were older, had an earlier age of onset, and were more likely to have a positive family history of depression than first episode patients. However, recurrent patients were less likely to be chronic and reported shorter current episodes than first episode patients, something that was largely confined to females. Recurrent patients were more likely than first episode patients to report non-essential aspects of mood, cognition, and somatic symptoms, although largely as a consequence of greater overall depressive symptom severity. CONCLUSIONS: As compared to single episode depressions, recurrent depression was associated with greater symptom severity and illness characteristics suggestive of greater underlying risk, but not other demographic characteristics than age. Risk for recurrence appeared to be distinct from chronic depression. A subset of chronic first episode patients may lack the capacity to remit and may therefore be distinct from those with recurrent episodes.

Adolescent↗

PubMed2005

Quality improvement methods as applied to a multicenter effectiveness trial--STAR*D.

In multicenter clinical trials, important aspects of trial performance (e.g., the number of participants who enter the trial within the required time frame, the number of participants who remain in the trial, and/or the completeness of the outcome data collected) directly affect the extent to which the study can achieve its aims. Obtaining the maximum amount of data from the maximum number of participants at each step in the trial increases the likelihood of identifying real differences in outcome. These aspects of trial performance can, therefore, be considered intermediate performance goals of the study since success in achieving each of them is directly related to success in achieving study aims. A quality improvement system was introduced to improve efficiency and performance in the multicenter Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Four intermediate performance goals were targeted for quality improvement efforts: (1) initial enrollment of subjects, (2) collection of entry/exit primary outcome data, (3) retention of subjects to enter subsequent "levels" of the trial, and (4) collection of blood samples for genetics studies. The identification of numerical targets for these goals provides a basis for monitoring performance and for implementing attempts to improve performance, since success in achieving each goal is directly related to success in achieving the study aims. This paper describes the background, rationale, development, and potential utility of implementing a quality improvement system to improve the performance and efficiency of the trial.

Adolescent↗

PubMed2005

Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features.

BACKGROUND: This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). METHODS: Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. RESULTS: Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive-compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. LIMITATIONS: Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. CONCLUSIONS: Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD.

Adult↗

PubMed2004

Web-based communications and management of a multi-center clinical trial: the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project.

While efficient methods of communication are known to be essential in conducting large multicenter clinical trials, very little information is provided on actual methods that can be implemented to improve communication. An integrated technology-based communication system was developed for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project, which prospectively defines treatments that are most effective for participants with a diagnosis of a nonpsychotic major depressive disorder (MDD) who report an unsatisfactory clinical outcome to an initial and, if necessary, subsequent treatment(s). This web-based communication system is comprised of a multi-faceted study Web site, including a help desk, document sharing, a project directory and reports. In addition, automated reporting via e-mail and an online data correction mechanism are also available. The STAR*D communication system improves communication between study personnel and improves the quality of the study's data through the integration of system elements, the integration of those elements with traditional forms of communication,, by filling the gaps not addressed by those traditional methods and by reducing the staff workload burden.

Clinical Trials as Topic↗

PubMedDate not supplied

Clinical features of depressed outpatients with and without co-occurring general medical conditions in STAR*D.

BACKGROUND: A significant percentage of patients with major depressive disorder (MDD) suffer from concurrent general medical conditions (GMCs). OBJECTIVE: The objective of this preliminary report was to describe the rates of co-occurring significant GMCs and the clinical correlates and symptom features associated with the presence of GMCs. DESIGN: Baseline cross-sectional case-control study of patients enrolling in a prospective randomized multistage treatment study of MDD. SETTING: Fourteen regional U.S. centers representing 19 primary care and 22 psychiatric practices. PATIENTS: One thousand five hundred outpatients with DSM-IV nonpsychotic MDD. MEASUREMENTS: Sociodemographic status, medical illness ratings, psychiatric status, quality of life and DSM-IV depression symptom ratings. RESULTS: The prevalence of significant medical comorbidity in this population was 52.8% (95% CI 50.3-55.3%). Concurrent significant medical comorbidity was associated with older age, lower income, unemployment, limited education, longer duration of index depressive episode and absence of self-reported family history of depression. Somatic symptoms common in MDD were endorsed at a higher rate in those with GMCs. Those without a GMC had higher rates of endorsement of impaired mood reactivity, distinct mood quality and interpersonal sensitivity. CONCLUSIONS: Concurrent GMCs are common among outpatients with MDD in both primary care and specialty settings. Concurrent GMCs appear to influence the severity and symptom patterns in MDD and describe a vulnerable population with sociodemographic challenges to effective assessment and treatment.

Adolescent↗

PubMedDate not supplied

A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial.

PURPOSE: No study has directly compared the clinical features of depression for patients entering clinical trials using identical enrollment criteria at primary care (PC) and specialty care (SC) settings. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (http://www.star-d.org) provides a unique opportunity to provide this comparison for patients with a major depressive disorder (MDD) requiring treatment. SUBJECTS AND METHODS: We report baseline data for the first 1500 patients enrolled in this trial involving 41 clinic sites (18 PC, 23 SC). Broadly inclusive eligibility criteria required that patients have a DSM-IV diagnosis of nonpsychotic MDD, have not failed an adequate medication trial during their current episode and score>or=14 on the 17-item Hamilton Rating Scale for Depression (HAM-D17). Primary outcomes included the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) and the HAM-D17. RESULTS: Specialty care and PC patients had equivalent degrees of depressive severity (IDS-C30=35.8; HAM-D17=20.4). Specialty care patients were almost twice as likely to report a prior suicide attempt than PC patients (21% vs. 12%, P<.0001) and slightly less likely to endorse suicidal ideation in the past week (45.0% vs. 50.8%, P=.006). The only other distinguishing core symptoms were a slightly lower likelihood of PC patients endorsing depressed mood (95.2% vs. 97.7%, P=.032) or anhedonia (66.3% vs. 70.7%, P=.042, IDS-C30) and a lower likelihood of PC patients endorsing weight loss (IDS-C30). HAM-D17 results were identical. CONCLUSION: Depressive severity was not different, and symptomatic presentations did not differ substantially. Major depressive disorder is more similar than different among patients at SC and PC settings. Thus, similar clinical and research methods for screening, detecting and measuring treatment outcomes can be applied in both settings.

Ambulatory Care↗

PubMedDate not supplied

Substance use disorder comorbidity in major depressive disorder: a confirmatory analysis of the STAR*D cohort.

The demographics and clinical features were compared between those with (29.4%) and without concurrent substance use disorder (SUD) in 2541 outpatients with major depression (MDD) enrolled in the Sequenced Treatment Alternatives to Relieve Depression study. Compared to those without SUD, MDD patients with concurrent SUD were more likely to be younger, male, divorced or never married, and at greater current suicide risk, and have an earlier age of onset of depression, greater depressive symptomatology, more previous suicide attempts, more frequent concurrent anxiety disorders, and greater functional impairment (p = 0.048 to <0.0001). They were also less likely to be Hispanic and endorse general medical comorbidities (p = 0.006 and 0.002, respectively).

Adolescent↗