Treatment of war related adolescent depression
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Treatment of war related adolescent depression Treatment of war related adolescent depression Document Transcript

  • ORIGINAL CONTRIBUTION Interventions for Depression Symptoms Among Adolescent Survivors of War and Displacement in Northern Uganda A Randomized Controlled Trial Paul Bolton, MBBS Context Prior qualitative work with internally displaced persons in war-affected north- Judith Bass, PhD ern Uganda showed significant mental health and psychosocial problems. Theresa Betancourt, ScD Objective To assess effect of locally feasible interventions on depression, anxiety, and conduct problem symptoms among adolescent survivors of war and displace- Liesbeth Speelman, MA ment in northern Uganda. Grace Onyango, MA Design, Setting, and Participants A randomized controlled trial from May 2005 Kathleen F. Clougherty, MSW through December 2005 of 314 adolescents (aged 14-17 years) in 2 camps for inter- nally displaced persons in northern Uganda. Richard Neugebauer, PhD Interventions Locally developed screening tools assessed the effectiveness of in- Laura Murray, PhD terventions in reducing symptoms of depression and anxiety, ameliorating conduct Helen Verdeli, PhD problems, and improving function among those who met study criteria and were ran- domly allocated (105, psychotherapy-based intervention [group interpersonal psy- T HE WAR IN NORTHERN UGANDA chotherapy]; 105, activity-based intervention [creative play]; 104, wait-control group remains one of the most violent [individuals wait listed to receive treatment at study end]). Intervention groups met andpersistentcomplexhumani- weekly for 16 weeks. Participants and controls were reassessed at end of study. tarian emergencies in the world. Main Outcome Measures Primary measure was a decrease in score (denoting im- Over 1.8 million individuals, mainly eth- provement) on a depression symptom scale. Secondary measures were improvements in nicAcholi,havebeeninternallydisplaced scores on anxiety, conduct problem symptoms, and function scales. Depression, anxiety, during 20 years of conflict between the and conduct problems were assessed using the Acholi Psychosocial Assessment Instru- government of Uganda and the Lord’s ment with a minimum score of 32 as the lower limit for clinically significant symptoms Resistance Army.1 The Lord’s Resistance (maximum scale score, 105). Army has been accused of human rights Results Difference in change in adjusted mean score for depression symptoms be- abusesincludingmassviolence,rape,and tween group interpersonal psychotherapy and control groups was 9.79 points (95% the abduction of more than 25 000 chil- confidence interval [CI], 1.66-17.93). Girls receiving group interpersonal psycho- therapy showed substantial and significant improvement in depression symptoms com- dren.1 Local populations have crowded pared with controls (12.61 points; 95% CI, 2.09-23.14). Improvement among boys into internally displaced persons camps was not statistically significant (5.72 points; 95% CI, −1.86 to 13.30). Creative play where they face threats to their health showed no effect on depression severity (−2.51 points; 95% CI, −11.42 to 6.39). There and well being.1 Prior research on chil- were no statistically different improvements in anxiety in either intervention group. dren affected by armed conflicts docu- Neither intervention improved conduct problem or function scores. ments increased risk of mental health Conclusions Both interventions were locally feasible. Group interpersonal psycho- problems ranging from adjustment dif- therapy was effective for depression symptoms among adolescent girls affected by ficulties to depression and anxiety dis- war and displacement. Other interventions should be investigated to assist adoles- orders, including posttraumatic stress cent boys in this population who have symptoms of depression. disorder.2-4 Governmental and nongov- Trial Registration Identifier: NCT00280319 ernmental organizations (NGOs) inter- JAMA. 2007;298(5):519-527 vene to address these problems, yet few interventionshavebeenrigorouslyevalu- Western societies that have included mony intervention5 nor a clinic-based ated using a randomized controlled trial nonpharmaceutical treatments have gen- counseling and problem-solving treat- (RCT) design, either in northern Uganda erated mixed results.5-9 Neither a ment7 have so far proved superior to the or elsewhere.4 The few RCTs in non- community-based single-session testi- control condition. In contrast, trials of Author Affiliations are listed at the end of this article. Bloomberg School of Public Health, 615 N Wolfe For editorial comment see p 567. Corresponding Author: Paul Bolton, MBBS, Center for St, Room E8646, Baltimore, MD, 21205 (pbolton Refugee and Disaster Response, Johns Hopkins ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, August 1, 2007—Vol 298, No. 5 519 Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA Box. Symptoms of Locally Described Syndromes and Chores/Activities Used to Generate Local Depression Symptom and Functional Impairment Scales Depression-Like Syndromes Anxiety-Like Syndromes Par a Ma Lwor Has lots of thoughts, wants to be alone, is easily annoyed, Clings to elders, thinks of self as having no future, constantly runs, holds head, drinks alcohol, thinks about suicide, doesn’t dislikes noise, has fast heart rate, fears being alone, has loss of greet people, sits alone, has lots of worries, does not appetite, wants to be alone, does not sleep at night, drinks alco- think straight, cannot do anything to help self, does hol, doesn’t greet people, thinks people are chasing him/her not trust, mutters to self, insults friends, is disobedient, Syndrome of Maladaptive Socially Unacceptable Behaviors is weak, cries continuously, loses concentration in Kwo Maraco school b Two Tam a Fights, uses bad language, is disrespectful, misbehaves, drinks alcohol, uninterested, deceitful, a rough person, uses drugs, dis- Has lots of thoughts, constantly worries, experiences body obedient, loses interest in school b pain, feels that brain isn’t functioning, thinks of self as being of no use, thinks about suicide, talks about problems, Play and Chore Activities by Function and Sex sits alone, has headaches, feels sad, does not care about liv- Girls ing or dying, thinks of bad things, doesn’t feel like talking, is Fetching water, washing clothes, digging, washing utensils, play- forgetful, is weak, cries continuously, loses interest in ing ball, sweeping house, smearing floor with mud, cooking school b food, traditional dance Kumu a Boys Has loss of appetite, feels pain in the heart, sits with cheek in Fetching water, digging, playing games, sweeping compound, palm, cries when alone, does not sleep at night, talks about prob- playing football lems, lies down all the time, has lots of worries, has head- aCombined to create the composite depression scale. The final scale aches, feels cold, is weak, does not feel like talking, is disobe- dient included 35 signs and symptoms. bThe 2 school-related items were excluded from the final scales be- cause many of the students were not school-going. a cognitive behavioral therapy,9 a psy- for internally displaced persons near Gulu previous randomized trial we con- choeducation treatment program,6 and town in northern Uganda. Each camp has ducted, which found such syndromes a previous trial in southwestern Uganda a population exceeding 20 000. Eco- to be amenable to treatment provided (conducted by the authors of this article nomic activity and organized social and by one of our collaborating partners with an intervention also from this ar- cultural life are minimal, although chil- (World Vision).8 The fourth local syn- ticle),8 all found significant improve- dren have some access to schools. drome is ma lwor, which appears to be ments in the psychological symptoms an anxiety-like syndrome and kwo ma- studied. However, these trials focused Symptom Assessment raco, the fifth local syndrome, is a com- on adults. RCTs of mental health inter- We developed local symptom assess- bination of maladaptive or socially un- ventions to assist children and adoles- ment measures based on a prior quali- acceptable behaviors (B OX ). The cents affected by war are also needed. tative study in both camps (P.B., T.B., remaining 2 problems, one referring to This article describes an RCT in 2 and L.S., unpublished data, 2004). In a cluster of posttraumatic stress reac- camps for internally displaced persons that study, we identified 7 important tions with psychotic features and the in northern Uganda. We investigated mental health and psychosocial prob- other to a legitimate fear of future Lord’s whether a therapy-based intervention lems affecting children and adoles- Resistance Army attacks, were not in- (interpersonal psychotherapy for groups, cents from the viewpoint of the youths vestigated further because our NGO [IPT-G]) and an activity-based interven- themselves, their caregivers (mothers partners and the research team felt that tion (creative play, [CP]) were effective or other adult relatives), and other these problems were unlikely to be af- for relieving mental health and psycho- knowledgeable local individuals. fected by the NGOs’ current or planned social problems resulting from war and Among these problems, the research interventions, including the interven- displacement among adolescents. team and NGO staff selected 5 prob- tions tested in this study. lems judged amenable to interven- Problems of alcohol abuse and METHODS tions within the NGOs’ capacity. Three sexual violence were widely reported— Site and Population of these 5 problems—two tam, kumu, symptoms related to the use of alcohol Study participants were Acholi adoles- and par—are local depression-like syn- are present in 3 of the 5 locally described cents aged 14 to 17 years living in 2 camps dromes and were selected because of a syndromes and sexual aggression is rep- 520 JAMA, August 1, 2007—Vol 298, No. 5 (Reprinted) ©2007 American Medical Association. All rights reserved. Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA resented under the locally described tions of the cardinal Diagnostic and Sta- ously in a variety of cultures, is a gen- conduct syndrome of ma lwor. How- tistical Manual of Mental Disorders eral screening instrument for child emo- ever, our purpose was to study the (Fourth Edition) symptoms of depres- tional and behavioral problems.13-15 It effects of interventions on locally sion and related symptoms.11 Accord- provides a determination of probable defined syndromes, and distinct syn- ingly, we developed a local depression ‘caseness’ (based on scores)16 but is not dromes referring to these problems were symptom scale based on the summed designed as a measure of treatment out- not identified in the qualitative study. scores on all items comprising the 3 syn- comes.17 We compared the APAI scores Note, however, that while symptoms of dromes (35 individual signs and symp- for those individuals with positive psychosis, posttraumatic stress disor- toms). Scale reliability and validity were screening results for the trial with their der, drug and alcohol use, and trauma evaluated for a subsample (n = 178) of scores on the Strengths and Difficulties were not among the foci of the assess- the adolescents interviewed for trial eli- Questionnaire emotional problems sub- ment, individuals who had these symp- gibility (N=667). Cronbach (a mea- scale (for which scores of 7-10 points in- toms were not excluded from the study. sure of internal reliability) was 0·92. dicate probable “caseness”)16 to test As in a previous study10 we explored Mental health professionals familiar with whether the APAI and the cutoff crite- whether any existing instruments the local culture were not available to ria were identifying adolescents with sig- matched the local descriptions of these make clinical diagnoses. Therefore, we nificant mental health problems accord- 5 selected problems. Because no extant used an alternative method of explor- ing to a standard measure (the Strengths instruments proved suitable, we cre- ing criterion validity.10 We identified in- and Difficulties Questionnaire). ated a local instrument consisting of ques- dividuals among this group for whom tions on all the symptoms of all 5 local youth-caregiver pairs concurred that the Functional Assessment problems: the Acholi Psychosocial youth had at least 2 of the 3 local de- We also developed a local function mea- Assessment Instrument (APAI). APAI pression-like syndromes (cases) and pairs sure based on the qualitative data, using respondents were asked about the fre- concurring that the youth had none of an approach similar to that used else- quency of each symptom occurrence dur- these syndromes (noncases). The APAI where.18 The measure has 2 gender- ing the previous week. Responses were depression symptom scale (mean [SD]) specific scales, each reflecting com- coded on a 4-point Likert scale ranging was substantially and significantly higher mon activities judged important for from 0 (never) to 3 (constantly). Ques- for the cases (45.3, [13.6]) than for the children and adolescents by youths and tions were added regarding symptom noncases (15.6, [11.2]), thereby sup- adult camp residents (Box). Impair- duration, sociodemographics, duration porting concurrent validity. The trial eli- ment was rated on a Likert scale rang- of camp residence, and whether the ado- gibility threshold was derived from these ing from 0 (no more difficulty than lescent was ever abducted. scores: 32, which is approximately 1 SD most other boys/girls of the same age) Given the predominance of depres- below the case mean. A convenience sub- to 4 (frequently unable). An overall sion-like syndromes in the qualitative sample of 30 individuals were readmin- function score comprised the sum of the data and the effectiveness of IPT-G for istered the APAI 3 to 5 days later. Test- individual item scores, and ranged from treating depression symptoms else- retest reliability for the depression 0 to 36 for girls (9 activities) and 0 to where in Uganda,8 introducing and test- symptom scale was 0.84. 20 for boys (5 activities). ing IPT-G in this population seemed ap- propriate. Both the research team and our Clinical Significance of Scale Scores Study Eligibility, Screening, NGO partners also believed that an ex- The trial eligibility symptom threshold Consent, and Randomization isting intervention, CP, was potentially was derived from the comparison of Screening and baseline assessments effective for these same problems (and mean depression symptom scale scores were conducted in the summer of 2005. for the conduct syndrome of kwo ma- for cases and noncases, operational- Both interventions lasted from August raco). Therefore, we designated the de- ized in the manner described in the pre- 2005 through December 2005. Assess- pression problems as the primary study vious section. The threshold of 32 (1 SD ments were conducted pre- and post- outcomes: two tam, kumu, and par (Box). less than the case mean) was selected as intervention and change calculated for Because the anxiety (ma lwor) and con- a reasonable lower bound for clinically the local depression symptom scale. duct (kwo maraco) syndromes were also significant presence of symptoms (maxi- Sample size calculations were based on thought amenable to both IPT-G and mum scale score, 105). To evaluate the an expected 10-point difference in this CP, measures of these problems were clinical significance of this threshold change between either of the treat- retained as secondary outcomes. from a Western clinical perspective, the ment groups and the controls. One hun- scale scores were compared with re- dred adolescents per group provided Instrument Development, sults for the Strengths and Difficulties greater than 80% power (P = .05), as- Reliability and Validity Questionnaire, 12 administered to- suming SDs of less than 25 points. Di- The 3 local depression problems con- gether with the APAI. The Strengths and rect comparisons between interven- tain varying (but incomplete) combina- Difficulties Questionnaire, used previ- tion groups were inappropriate given ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, August 1, 2007—Vol 298, No. 5 521 Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA ized trial. On this occasion informed con- Figure. Flowchart of Study Participants sent included advising each youth of the 667 Adolescents screened study group to which he or she had been for eligibility allocated. Our NGO partners had pre- viously agreed to provide/continue on a 329 Excludeda permanent basis whichever interven- tion proved effective. Individuals assigned 300 Met initial eligibility criteria 38 Met expanded eligibility criteriab to the wait-control group were told they would be first to receive whichever inter- 338 Randomized 24 From expanded eligibility group vention (if any) proved effective. excluded (target study size met) Of the total sample screened (N=667), 300 individuals met original inclusion 105 Randomized to receive 105 Randomized to receive group 104 Randomized to control group criteria, were stratified by camp and sex, creative play interpersonal psychotherapy 102 Enrolled and randomized to a study group. Of 99 Enrolled 103 Enrolled 1 Did not consent 3 Did not consent 1 Did not consent 1 Could not be found these 300, 290 were enrolled in the study. 2 Could not be found 1 Could not be found Of the remaining 10 individuals, 1 was 1 Already participating an a creative play program already involved in the CP program in a neighboring camp, 4 could not be lo- 11 Lost to follow-up at end 7 Lost to follow-up at end 14 Lost to follow-up at end cated, and 5 refused. To meet our origi- of trial of trial of trial 6 Could not be found 3 Could not be found 9 Could not be found nal sample size (300), we randomized an 3 Away from camp 1 Away from camp 2 Away from camp additional 38 individuals whose depres- 2 Moved to another camp 3 Moved to another camp 2 Moved to another camp 1 Died sion symptom scores were between 28 and 31 points. This relaxation of a trial 82 Attended ≥1 session and 89 Attended ≥1 session and 90 Completed postintervention eligibility criterion is acceptable when completed postintervention completed postintervention assessment study design consequences are mini- assessment assessment mal.19 The first 14 individuals all con- 105 Included in primary analysis 105 Included in primary analysis 104 Included in primary analysis sented and therefore, the remainder were not approached. The participation rate a Did not meet inclusion criteria (described in Study Eligibility, Screening, Consent, and Randomization). was 96.8% (304 enrolled of 314 re- b Expanded eligibility criteria included reducing the cutoff score on the depression-severity screener. cruited; FIGURE). differences in the size and sex ratio that on the depression symptom scale Postintervention Assessment made up the intervention groups. Con- and greater than 0 on the function scale, The study instrument was re-adminis- sequently, the study was not powered had symptoms for at least 1 month, and tered to 282 (90%) of the original 314 for between-intervention comparisons. resided in the camps during the pre- participants within 1 month of com- Trial eligibility was based on a 2-stage ceding month. Exclusion criteria were pleting both interventions. Interview- screening process. In stage 1, 10 inter- inability to be interviewed due to a cog- ers were blinded to interviewees’ inter- viewer supervisors contacted local lead- nitive or physical disability, or severe vention status. ers, teachers, community workers, and suicidal ideation or behavior. adolescents to create a list of youths be- Informed consent was initially Interventions lieved to have at least 1 of the local de- obtained only for the screening interview. Both interventions comprised 16 weekly pression-like problems. In stage 2, the in- Eligible youths were then randomly group meetings, lasting 1.5 to 2 hours strument was administered to these assigned to a study group. Random each. These were preceded by 1 or 2 indi- youths by 20 trained interviewers. Su- allocation was done by computer- vidual meetings in which the interven- pervisors observed 10% of interviews, re- ized generation of a random number tion was explained and (in the case of viewed all completed instruments, and between 1 and 400 for each eligible par- the IPT-G intervention) a treatment plan visited all adolescents not interviewed to ticipant, ordering them by number and was generated by the IPT-G facilitators. confirm unavailability or refusal. Inter- assigning the first third to IPT-G, the sec- Interpersonal psychotherapy, a time- viewers were used (rather than self- ond third to CP and the final third to the limited, manualized intervention, was completion of forms) because of con- wait-control group. Each eligible youth developed in the United States for ambu- cerns about the rate of literacy among the was then visited by a facilitator (if allo- latory, nonpsychotic unipolar depres- respondents, given frequent interrup- cated to IPT-G or CP) or other NGO staff sion20 and later adapted for use with ado- tions in schooling due to the war. (if allocated to controls) and a second lescents with depression, individually21 Trial-eligible interviewees were aged informed consent process was done, this and in groups.22 Interpersonal psycho- 14 to 17 years, scored greater than 32 time for participation in the random- therapy assumes that depressive epi- 522 JAMA, August 1, 2007—Vol 298, No. 5 (Reprinted) ©2007 American Medical Association. All rights reserved. Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA sodes are triggered by difficulties in 1 or manual accordingly. For example, if the Analysis more of 4 interpersonal areas: grief, inter- goal is to build trust with peers, the ac- Baseline characteristics of the study personal disputes, role transitions, and tivities may require the adolescents to groups were compared using 2 tests for interpersonal deficits. Interpersonal psy- work collaboratively. After the activities, categorical data and t tests for continu- chotherapy focuses on improving depres- facilitators lead discussions on what the ous data. The primary outcome measure sive symptoms and functioning by iden- participantsandfacilitatorsthoughtabout of intervention effectiveness was within- tifying the interpersonal problem(s) most the activity as a means of drawing real-life subject change in the depression symp- relevant to the current depression and lessons. CP was provided to 4 groups (2 tom scale scores between baseline and then assisting the individual in building groups/camp; both sexes represented in postintervention assessment. The sec- skills to manage those problems. Treat- each group; 25-30 adolescents in each ondary outcome measures were the cor- ment using IPT-G was first facilitated in group), consistent with its routine imple- responding scale scores for the local anxi- Africa among adults with depression in mentation.Thesame2individuals(1man, ety and conduct syndrome symptoms southwest Uganda.8 Based on this expe- 1woman)fromWarChildHollandjointly and the function measure. We compared rience and our preliminary qualitative facilitated all CP sessions for all groups. separately the mean within-subject work in northern Uganda(P.B., T.B., and Supervision was provided weekly or bi- change in the symptom and function L.S., unpublished data, 2004 [available monthly by the War Child Holland psy- scores between the wait-list control from authors at request]), IPT-G’s focus chosocial specialist who regularly shared group and the individual interventions. on interpersonal triggers and group rela- supervision reports with the US-based Stata statistical software version 9.0 tionship building seemed compatible study personnel. These reports were re- (STATACorp, College Station, Texas) with Acholi culture. viewedanddiscussedwithstudystaffdur- was used for descriptive analyses and SAS The IPT-G intervention was imple- ing bimonthly phone meetings to ensure version 9.1 (SAS Institute Inc, Cary, mented by World Vision Uganda. There adherence to the treatment model and to North Carolina) for grouped analyses. were 12 IPT-G groups, each led by a fa- monitor human subjects protection. We used a random effects model to esti- cilitator with 2 weeks of on-site training When implementing CP in different mate intervention effect on change in by Columbia University faculty (K.F.C.). countries, some War Child Holland pro- scale scores, adjusting for the clustering A treatment manual specifying IPT-G grams have added to the basic CP model within intervention groups by control- strategies and techniques was adapted for by including various therapy-based ele- ling for within-group correlated obser- local use(K.F.C., H.V., and Myrna Weiss- ments in the postactivity discussion, vations and between group variabil- man, PhD, Columbia University, New according to local capacity. War Child ity.24 Regression coefficients and P values York State Psychiatric Institute, unpub- Holland staff in northern Uganda had were computed for continuous mea- lished data, 2006). Groups consisted of originally planned to do this as well. sures. Statistical significance was set at 6 to 8 adolescent boys or girls and a fa- However, for this study, it was decided P .05, 2-tailed and expressed as a 95% cilitator of the same sex. Facilitators re- to use only the standard activity-based confidence interval (CI). ceivedweeklydirectsupervisionbyWorld CP model in which postactivity group Analyses are presented for the intent- Vision Uganda staff with prior IPT-G discussions focus on building skills. In to-treat samples (n = 314), which in- experience. These supervisors in turn re- this way, the study maximized the con- cludes all trial-eligible individuals ran- ceivedweeklyphonesupervisionfromthe trast between a psychotherapy-based domized to one of the trial conditions US-based trainer and were in weekly con- intervention (IPT-G) and one focusing and approached for inclusion, whether tact with study personnel. IPT-G super- on group activities (CP). Participants or not they consented. For individuals visorsalsoprovidedweeklywrittenreports could discuss their problems with the CP who were not reinterviewed, baseline that were reviewed and discussed with facilitators after the group meetings and scores were used as their postinterven- study staff during the phone meetings for this occurred on a few occasions for dis- tion scores, thereby imputing no adherence to the treatment model and to tressed participants (a young woman change. Analyses were also conducted monitor human subjects protection. whose baby had died, and a boy who had on a completer sample (n=261), which Use of CP refers to the creative play lived with rebels in the bush), but these included only individuals interviewed format developed by War Child Holland discussions were not a routine part of the before and after the intervention and for war-affected youth. Its premise is that intervention. Otherwise, the nature of the who (for the intervention groups) at- a youth’s resilience will be strengthened standard CP intervention was the same tended any sessions. This was done to by verbal and nonverbal expression of as that typically used by War Child Hol- determine if the results were substan- thoughts and feelings through age- land in other countries with 2 excep- tially different for completers and as a appropriate creative activities such as, tions: (1) inclusion of adolescents as old check on whether our imputation songs, art, role plays, music, sports, as aged 17 years (usually limited to 15 method for noncompleters resulted in games and debates.23 Each activity serves years); and; (2) limiting CP participa- underestimates in sample variance. specific psychosocial goals and activities tion, normally open to all children, to The study was approved by the Bos- are selected from the War Child Holland adolescents with depression symptoms. ton University Institutional Review ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, August 1, 2007—Vol 298, No. 5 523 Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA Table 1. Study Sample Characteristics at Trial Baseline (n = 314) Group Interpersonal Psychotherapy Creative Play Wait-List Controls Characteristic (n = 105) (n = 105) (n = 104) P Value a No. (%) of participants Girls 60 (57) 61 (58) 59 (57) .98 Currently enrolled in school 69 (66) 71 (68) 71 (68) .88 History of abduction 42 (40) 48 (46) 41 (39) .59 Mean (SD) Age, y 15.0 (1.1) 14.7 (1.0) 15.2 (1.2) .01 Education, y 5.0 (1.5) 5.1 (1.4) 5.3 (1.3) .47 Time in camp, y 5.0 (3.0) 5.5 (3.6) 5.0 (3.2) .33 Local depression symptom, score b 43.5 (10.1) 44.2 (11.2) 44.2 (10.8) .85 Function for girls, score c 11.8 (7.0) 11.3 (6.5) 10.7 (6.9) .69 Function for boys, score c 6.8 (3.8) 7.1 (4.0) 8.2 (4.1) .20 a Analysis of variance used to evaluate mean differences across groups for continuous variables and 2 used for categorical data. b Depression symptom score generated by summing the 35 items referring to symptoms of the 3 local depression-like problems. c Function scale for girls comprises 9 activities; function scale for boys comprises 5 activities. These include sex-specific play and chore activities. Board and by the Ugandan National among the wait control group were inter- We also assessed change in the local Council on Science and Technology in viewed postintervention (87% of the total anxiety problem (ma lwor) and con- Kampala, Uganda. 104 wait-list control sample). Fourteen duct problems (kwo maraco) symptom adolescents (13%) assigned to IPT-G and scores as secondary outcomes. The ad- RESULTS 21 (20%) assigned to CP did not attend justed difference in mean within- Baseline Characteristics any sessions. Both sets of nonattendees subject decline between the IPT-G and Of 314 adolescents approached for en- had the same mean depression scores and wait-list control groups for ma lwor was rollment, 172 (55%) were in Awer camp ages as the attendees but were more likely small but significant: 2.16 points (95% and 142 (45%) in Unyama. At base- to be girls, to not attend school, and to CI, 0.84-3.48) while that for kwo ma- line, 180 (57%) were girls, 211 (67%) have a history of abduction. raco was not: 0.74 points (95% CI, -0.15- were enrolled in school, and 131 (42%) 1.63) . The CP group showed a slight reported a history of Lord’s Resistance Changes in Symptom Severity nonsignificant increase (0.2 points) and Army abduction. Mean duration of All 3 study groups demonstrated a de- decrease (0.4 points) for ma lwor and kwo camp residence was 5.2 years. Except cline in mean depression symptom scores maraco, respectively. for a slightly older age among wait-list between baseline and postintervention Exploratory analyses examined controls, the 3 study groups did not (TABLE 2). The decline in the depres- whether the effectiveness of either in- vary significantly (TABLE 1). The aver- sion symptom scale among the IPT-G tervention varied by sex, age, abduc- age Strengths and Difficulties Ques- group was substantially and signifi- tion history, and duration of camp resi- tionnaire emotional problems sub- cantly greater than the wait-list control dence. In stratified analyses, among scale score was 8.1 points without group. The adjusted difference in mean girls, IPT-G was greatly superior to the difference by sex and group assign- within-subject decline between the wait-list control condition in reduc- ment and 256 (81.5%) scored 7 or more IPT-G and wait-list control groups was ing symptom severity, while the re- points, the cutoff for probable ‘case- 9.79 points (95% CI, 1.66-17.93) for the sults for boys were not statistically sig- ness’. Results are presented unad- entire intent-to-treat sample and 10.71 nificant (TABLE 3). This effect also held justed for age as adjustment resulted in points (95% CI, 4.02-17.40) for the com- for the completer sample, where girls’ no appreciable difference. pleters only (Table 2). The CP group evi- mean scores were 16.6 points lower denced a small decline in the depres- (95% CI, 9.93-22.13) for those who re- Attendance sion symptoms scale, not differing ceived IPT-G compared with controls Of the 105 adolescents assigned to IPT-G, significantly from that of wait-list con- and IPT-G boys had scores 5.01 points 91 attended at least 2 sessions (mean of trols. The intraclass correlation coeffi- lower (95% CI, -1.89-11.90) com- 14.1 sessions; SD, 2.6) of whom 89 (86% cient for depression scale scores was pared with controls. No significant dif- of the total IPT-G sample) were assessed 0.099. Variances of the outcome mea- ferences emerged for the other vari- postintervention. Of the 105 youth sure among the intent-to-treat sample ables or in any of the CP analyses. assigned to CP, 84 attended at least 3 ses- differed only slightly from that among the sions (mean of 10·4 sessions; SD, 2.9) Completer sample (Table 2), indicating Recovery and Remission of whom 82 (83% of the total CP sample) that the imputation scheme did not ma- Recovery was defined as a reduction of were reassessed. Ninety individuals terially influence the risk of type I error. 50% or more of an individual’s baseline 524 JAMA, August 1, 2007—Vol 298, No. 5 (Reprinted) ©2007 American Medical Association. All rights reserved. Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA Table 2. Effectiveness of Interventions Compared With Controls in Reducing Depression Symptom Scores Among Intent-to-Treat and Completer Samples Intent-to-Treat Group Interpersonal Control Psychotherapy P Creative Play P Score Type (n = 104) (n = 105) Value (n = 105) Value Baseline depression symptom score, mean (SD) a 44.2 (10.8) 43.5 (10.1) .62 44.2 (11.2) .99 Follow-up depression symptom score, mean (SD) 37.3 (15.9) 27.8 (17.2) 40.6 (15.7) Difference from baseline to follow-up, mean (SD) 6.9 (16.0) 15.7 (17.0) 3.6 (18.2) Difference in adjusted mean score change 9.79 (4.15) [1.66 to 17.93] .02 −2.51 [−11.42 to 6.39] .58 (SE) [95% confidence interval] b Completers only (n = 90) (n = 89) (n = 82) Baseline depression symptom score, mean (SD) a 44.1 (10.6) 42.9 (10.3) .45 44.1 (11.4) .99 Follow-up depression symptom score, mean (SD) 36.1 (16.1) 24.9 (16.5) 39.6 (15.7) Difference from baseline to follow-up, mean (SD) 8.0 (17.0) 18.0 (16.5) 4.5 (19.0) Difference in adjusted mean score change 10.71 (3.4) [4.02 to 17.40] .002 −3.90 (3.7) [−11.17 to 3.37] .29 (SE) [95% confidence interval] b a P value refers to significance of difference in baseline scores between intervention and control groups. b Estimates of difference between intervention change score and control change score and associated confidence intervals and p values calculated using random effects model adjusting for clustering and baseline depression scale scores. Intraclass correlation coefficient calculated at 0.099. symptom severity score and remission Table 3. Interventions Compared With Control in Reducing Depression Symptom Scores as being at or less than a predefined cut- Among Intent-to-Treat Samples off score of 15.6 points (the mean score Difference in Scores (95% Confidence Interval) a of the noncases in the validation study). Among wait-list controls, 14 individu- Group Interpersonal Psychotherapy vs Wait-List Controls Creative Play vs Wait-List Controls als (13.5%) met criteria for recovery and Girls 12.61 (2.09 to 23.14) −1.61 (−12.51 to 9.29) 9 of total (8.9) met criteria for remission. Boys 5.72 (−1.86 to 13.30) −3.40 (−11.17 to 4.36) The corresponding numbers for the CP a Data presented as estimate of difference (95% confidence interval), calculated using random effects model adjusting and IPT-G groups were 13 (12.4%) and for clustering and baseline scores. 39 (37.1%) for recovery and 7 of total (6.7%) and 30 of total (29.1%) for remis- sion, respectively. Among the IPT-G Change in Function Effect of Using the Dunnett sample, 25 (42%) of the girls and 14 Mean within-subject function scores de- Adjustment (31%) of the boys met recovery criteria clined (ie, function improved) simi- Proschan and Fullman have recom- while 20 (33.9%) of the girls and 10 larly across all 3 study groups among mended using the Dunnet adjustment for (22.7%) of the boys met remission cri- girls and boys. Among the individuals statistical analysis of multiple compari- teria. Among ‘completers’, 14.6% and in the control group, the girls experi- sons for the same reasons that the bon- 7.3% of the CP participants and 42.7% enced a mean 1.9-point reduction (95% ferroni adjustment is used.25 While that and 34.5% of the IPT-G participants re- CI, −0.11 to 3.97) in their functional im- article refers to more comparisons than spectively, met the recovery and remis- pairment scores and the boys experi- we conducted in this study, we never- sion criteria. enced a 0.8-point mean reduction (95% theless tested the effect of including the CI, −0.39 to 2.07). This was similar to adjustment. We found no differences in Attendance and Group Leader Effects the amounts experienced by the CP par- the data and the adjustment factor itself The number of IPT-G sessions attended ticipants with a mean 1.3-point reduc- was not significant. was associated with greater symptom tion for girls (95% CI, −0.73 to 3.23) and reduction ( =1·3; P=.001). No asso- 0.5-point reduction for boys (95% CI, COMMENT ciation was found between number of CP −0.69 to 1.66). The IPT-G participants This study found IPT-G (a psycho- sessions attended and symptom change. reported greater reductions but the over- therapy-based intervention) superior to IPT-G effectiveness did not vary signifi- all differences compared with controls a wait-list control condition in reduc- cantly by group facilitator but the lim- did not reach statistical significance. ing depressive symptoms among this ited number of groups (12) constrained Among the IPT-G girls, the mean re- adolescent population. Statistically sig- analytic power. Facilitator effects could duction was 3.2 points (95% CI, 1.51- nificant improvement was limited to the not be examined for CP because both 4.87) while the boys’ mean score was 1.3 girl participants in this study. CP was facilitators worked with all 4 groups. points (95% CI, −0.02 to 2.93). not superior to the wait-list control con- ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, August 1, 2007—Vol 298, No. 5 525 Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA dition. Neither IPT-G nor CP was ef- proved functioning.27,28 Another pos- groups and because those groups were fective in improving anxiety, conduct sibility is that functional improve- larger and of mixed gender, both of problems, or functioning among boys ment occurred sometime later, a result which would reduce these effects. As or girls, according to our measures. that characterizes some interpersonal a result, we cannot speculate by com- Girls derived much greater improve- psychotherapy trials in industrialized parison with CP what it was about ment in depression symptoms from countries,29 or that the lack of improve- IPT-G that was effective; whether it was IPT-G than did boys. The amount of ment reflected a limitation in our mea- the psychotherapy, the effect of meet- change among boys was not statisti- sures (see Study Limitations section). ing in small groups, or the nonspecific cally significant when compared with The IPT-G group also showed a small attention of the facilitator. controls, however the study was not but significant improvement in anxiety The lack of improvement in function originally powered to detect gender- symptoms compared with controls, among any of the study groups may be specific differences. Previous studies of which is consistent with the improve- due, at least in part, to limitations in our IPT-G among adolescents in Western ment in depression symptoms and the measures. The items were taken solely countries have included too few boys to close relationship between anxiety and from the qualitative data and limited to know whether this finding reflects the depression. There was no such improve- activities that were possible given the situation elsewhere.22 It may be that boys ment among the CP group and con- environment (a camp for internally dis- are less willing to talk about emotional duct symptoms showed no improve- placed persons). This resulted in func- problems, particularly in a group for- ment in either group compared with tion scales containing only a few items mat. The different comorbidity profiles controls. Given that validity testing of (9 for girls and 5 for boys) and empha- among the boys and girls (boys had more the APAI focused on the depression syn- sizing activities and tasks and not cap- substance use and posttrauma symp- dromes, and that participants were turing other types of interpersonal or toms) may also have affected the effect screened into the study on the basis of social functioning targeted by the IPT-G of IPT-G, which has been shown to be depression symptoms only, we con- and CP interventions. less effective in individuals with depres- sider these results to be suggestive only. In our prestudy power calculations, sion and comorbid anxiety disorders.26 Further investigation is required. we did not take clustering into ac- The lack of improvement among the The consent process for the random- count, possibly resulting in some un- CP group may be because it was origi- ized trial differed from standard RCT pro- derestimation of the required sample nally designed for younger ages ( 15 cedures, where full consent precedes size. However, the intraclass correla- years) than our study population, who random allocation. Our approach was tion coefficient analysis suggests mini- may be more like adults than children based on prior experience among less- mal variance due to the clustering of in- in this culture and context. This may educated populations in Sub-Saharan dividuals within intervention groups. also explain the effectiveness of an adult Africa, where the concept of random To our knowledge, this is the first RCT intervention like IPT-G. The absence assignment is not well understood and of psychosocial or mental health inter- of effectiveness among the CP group can result in withdrawal from the study ventions among African adolescents af- was unexpected, particularly since the by those allocated to the control group. fected by war, and one of only a few RCTs CP facilitators received many positive Instead, we randomized potential par- of psychological treatments for depres- comments from participants, caretak- ticipants after the screening and then in- sion symptoms conducted in a develop- ers, and teachers. Perhaps the partici- formed them of their allocation as part ing country. In addition to our previ- pants wanted to please the facilitators, of the trial-consent process. In this way, ous trial of IPT-G in southwestern or were referring to other improve- we expected to reduce both refusals and Uganda,8 are RCTs by Patel et al in In- ments of which the nature was not cap- drop-outs—as long as refusals and drop- dia,7 Araya et al in Chile,6 and Igreja et tured with our measures, or they were outs were minimal, selection bias would al5 in Mozambique; all focusing on referring to the same natural improve- not be significant. Only 10 individuals adults. Two of these studies used indi- ment that occurred among the control randomized in this way did not partici- vidual-based psychotherapy treat- group (but which they may have at- pate. Of these, 5 were refusals. All 10 ments5,7 and reported no effectiveness, tributed to the intervention). What- were included in the intention-to-treat whereas the 2 group-based studies found ever the reason, we note that an activity- analyses by assuming no change be- active treatment superior to controls. The based intervention did not produce tween pre- and postassessments. current study also supports the poten- significant improvement in the out- tial of group-based therapies. comes assessed in the present study. Study Limitations Despite the differences between the The lack of improvement in func- While the lack of improvement among current study population and that of our tion for both interventions is in agree- the CP groups might suggest that the previous study8 of IPT-G (different cul- ment with reviews that note that re- facilitator and group effects were not ture, language, and ethnicity; adults vs duction in depressive symptoms does important, we cannot conclude this be- adolescents; war-affected and displaced not necessarily translate into im- cause the same facilitators ran both vs nondisplaced and at peace) there were 526 JAMA, August 1, 2007—Vol 298, No. 5 (Reprinted) ©2007 American Medical Association. All rights reserved. Downloaded from on February 21, 2008
  • DEPRESSION INTERVENTION IN ADOLESCENT SURVIVORS OF WAR IN NORTHERN UGANDA similarities in the results. IPT-G proved tute, Columbia University College of Physicians and Sur- 8. Bolton P, Bass J, Neugebauer R, et al. Results of a geons, and Gertrude H. Sergievsky Center, Faculty of clinical trial of a group intervention for depression in feasible in both sites in that acceptance Medicine, College of Physicians and Surgeons, Colum- rural Uganda. JAMA. 2003;289(23):3117-3124. was high, as was attendance through- bia University, New York, New York (Dr Neugebauer); 9. Sumathipala A, Hewege S, Hanwella R, Mann AH. Teachers College, Columbia University (Dr Verdeli); Dr Randomized controlled trial of cognitive behaviour out the intervention period. In both sites Bolton is now with the Center for Refugee and Disas- therapy for repeated consultations for medically un- there was significant overall improve- ter Response, and Dr Bass is now with the Department explained complaints: a feasibility study in Sri Lanka. ment in depression symptoms, com- of Mental Health, Johns Hopkins Bloomberg School of Psychol Med. 2000;30(4):747-757. Public Health, Baltimore, Maryland. 10. Bolton P. Cross-cultural validity and reliability test- pared with controls, with females im- Author Contributions: Dr Bolton had full access to all ing of a standard psychiatric assessment instrument proving substantially more than males. of the data in the study and takes responsibility for the without a gold standard. J Nerv Ment Dis. 2001; integrity of the data and the accuracy of the data analysis. 189(4):238-242. The extent of overall symptom improve- Study concept and design: Bolton, Betancourt, Bass. 11. American Psychiatric Association. Diagnostic and ment was less in this study than among Acquisition of data: Bolton, Bass, Betancourt. Statistical Manual of Mental Disorders. 4th ed. Wash- Analysis and interpretation of data: Bolton, Bass, ington, DC: American Psychiatric Association; 2000. the adults and function did not signifi- Betancourt, Clougherty, Neugebauer, Murray, Verdeli. 12. Goodman R. Strengths and difficulties questionnaire. cantly improve as it did among the adults. Drafting of the manuscript: Bolton, Bass, Betancourt, J Child Psychol Psychiatry. 1997;38(5):581-586. Speelman, Onyango, Clougherty, Neugebauer, Mur- 13. Kashala E, Lundervold A, Sommerfelt K, Tylleskar While this may be due to the study limi- ray, Verdeli. T, Elgen I. Co-Existing Symptoms and Risk Factors Among tations as described previously, it may Statistical analysis: Bass, Betancourt, Neugebauer. African School Children with Hyperactivity-Inattention also suggest that IPT-G is more suited for Study supervision: Bolton, Betancourt, Speelman, Symptoms in Kinshasa [published online]. Congo, Africa: Onyango, Clougherty, Murray, Verdeli. Eur Child Adolesc Psychiatry; 2006. mature participants and more suited to Financial Disclosures: None reported. 14. Samad L, Hollis C, Prince M, Goodman R. Child and girls across the age groups. Funding/Support: This project was solely funded by adolescent psychopathology in a developing country. Int World Vision and War Child Holland. Dr Neugebauer’s J Methods Psychiatr Res. 2005;14(3):158-166. The failure of both IPT-G and CP to contributions were funded by the Ruth and David 15. Thabet AA, Tischler V, Vostanis P. Maltreatment and significantly assist boys in this study Levine Foundation. coping strategies among male adolescents living in the Role of Sponsors: Both organizations also provided Gaza Strip. Child Abuse Negl. 2004;28(1):77-91. raises the question of whether other in- material support including local staff time to conduct 16. Goodman R, Renfrew D, Mullick M. Predicting type terventions may be needed to assist war- and supervise the interventions, assist in the logistical of psychiatric disorder from Strengths and Difficulties affected boys with depression symp- aspects of both the study design and interventions, Questionnaire (SDQ) scores in child mental health clin- and assisted in supervision of the interviewers. Nei- ics in London and Dhaka. Eur Child Adolesc Psychiatry. toms. Since both group psychotherapy ther organization was involved in the management or 2000;9(2):129-134. and activity-based interventions were analysis of the data but did offer suggestions as to the 17. Goodman R, Scott S. Comparing the Strengths and interpretation of the results. These staff also re- Difficulties Questionnaire and the Child Behavior Check- not effective, some form of individual viewed and approved the manuscript. list: is small beautiful? J Abnorm Child Psychol. 1999; psychotherapy or an entirely different Additional Contributions: We wish to thank those staff, 27(1):17-24. local leaders, and the communities who welcomed us 18. Bolton P, Tang AM. An alternative approach to cross- type of intervention may be indicated to work with them. Further, we wish to thank both cultural function assessment. Soc Psychiatry Psychiatr as the basis for a future trial. organizations for their commitment to improving the Epidemiol. 2002;37(11):537-543. impact of their humanitarian efforts. Both organiza- 19. Friedman LM, Furberg CD, DeMets DL. Fundamen- This study suggests that effective psy- tions have already begun to use the results of this study tals of Clinical Trials. 3rd ed. New York, NY: Springer; chological interventions can be feasible to inform their current programs in northern Uganda. 1998:151. in poor, rural, and illiterate communi- While not funding the study directly, the methodol- 20. Weissman M, Markowitz J, Klerman G. Compre- ogy described in this article was developed with the hensive Guide to Interpersonal Psychotherapy. New ties (even those affected by war) as are support of the US Agency for International Develop- York, NY: Basic Books; 2000. formal trials of such interventions. Where ment’s Torture Victims Fund. 21. Mufson L, Weissman MM, Moreau D, Garfinkel humanitarian and treatment programs R. Efficacy of interpersonal psychotherapy for depressed REFERENCES adolescents. Arch Gen Psychiatry. 1999;56(6):573-579. screen on the basis of symptom sever- 22. Mufson L, Gallagher T, Dorta KP, Young JF. A group ity, normal fluctuations in severity over 1. Coalition to Stop the Use of Child Soldiers. Child adaptation of interpersonal psychotherapy for depressed Soldiers Global Report 2004. http://www.reliefweb adolescents. Am J Psychother. 2004;58(2):220-237. time, and regression to the mean will .int/rw/lib.nsf/db900SID/LHON-66UJKU/$FILE 23. Kalksma-van Lith B. State of the Art in Psychoso- ensure apparent improvement regard- /child_soldiers_CSC_nov_2004.pdf?OpenElement Ac- cial Interventions with Children in War-affected Areas. cessed July 9 2007. War Child Holland 2005. less of true intervention effectiveness. 2. Barenbaum J, Ruchkin V, Schwab-Stone MS. The /uploadedfiles/979.pdf. Accessed February 3, 2007. Such programs, therefore, require con- psychosocial aspects of children exposed to war. J Child 24. Omar RZ, Thompson SG. Analysis of a cluster ran- Psychol Psychiatry. 2004;45(1):41-62. domized trial with binary outcome data using a multi- trolled study designs to accurately deter- 3. Lustig SL, Kia-Keating M, Grant Knight W, et al. Re- level model. Stat Med. 2000;19(19):2675-2688. mine effectiveness. view of child and adolescent refugee mental health. 25. Proschan MA, Follmann DA. Multiple compari- J Am Acad Child Adolesc Psychiatry. 2004;43(1):24-36. sons with control in a single experiment versus sepa- Author Affiliations: Applied Mental Health Research 4. Stichick T. The psychosocial impact of armed con- rate experiments: why do we feel differently? Am Stat. Group, Center for International Health and Develop- flict on children. Child Adolesc Psychiatr Clin N Am. 1995;49:144-149J. ment, Boston University School of Public Health, Bos- 2001;10(4):797-814. 26. Young JF, Mufson L, Davies M. Impact of co- ton, Massachusetts (Drs Bolton, Bass, and Murray); De- 5. Igreja V, Kleijn WC, Schreuder B, Van Dijk JA, Ver- morbid anxiety in an effectiveness study of interper- partment of Mental Health, Johns Hopkins Bloomberg schuurM.Testimonymethodtoamelioratepost-traumatic sonal psychotherapy for depressed adolescents. J Am School of Public Health, Baltimore, Maryland (Dr Bass); stress symptoms. Br J Psychiatry. 2004;184(3):251-257. Acad Child Adolesc Psychiatry. 2006;45(8):904-912. Department of Population and International Health, 6. Araya R, Rojas G, Fritsch R, Gaete J, Simon G, Pe- 27. Hirschfield RM, Montgomery SA, Keller MB, et al. Francois-Xavier Bagnoud Center for Health and Hu- ¸ ters TJ. Treating depression in primary care among low- Social functioning in depression: a review. J Clin man Rights, Harvard University School of Public Health, income women in Santiago, Chile: a randomized, con- Psychiatry. 2000;61(4):268-275. Boston, Massachusetts (Dr Betancourt); War Child Hol- trolled trial. Lancet. 2003;361(9362):995-1000. 28. Lin EH, VonKorff M, Russo J, et al. Can depres- land, Gulu, Uganda, (Ms Speelman); World Vision 7. Patel V, Chisholm D, Rabe-Hesketh S, Dias- sion treatment in primary care reduce disability? Arch Uganda, Kampla, Uganda (Ms Onyango); New York Saxena F, Andrew G, Mann A. Efficacy and cost- Fam Med. 2000;9(10):1052-1058. State Psychiatric Institute, Columbia University, New effectiveness of a drug and psychological treatment 29. Weissman MM, Klerman GL, Prusoff BA, Sho- York, New York (Ms Clougherty and Dr Verdeli); Divi- for common mental disorders in general health care lomskas D, Padian N. Depressed outpatients. Arch Gen sion of Epidemiology, New York State Psychiatric Insti- in Goa, India. Lancet. 2003;361(9351):33-39. Psychiatry. 1981;38(1):51-55. ©2007 American Medical Association. All rights reserved. (Reprinted) JAMA, August 1, 2007—Vol 298, No. 5 527 Downloaded from on February 21, 2008