Depression in adolescents and young adults: Evidence review

Depression in adolescents and young adults: Evidence review

On behalf of

January 2010
http://www.beyondblue.org.au/index.aspx?link_id=

Researchers:

Skye Newton Stynke Docter Edith Reddin Tracy Merlin Janet Hiller

Senior Research Officer Research Officer Research Officer Manager Director

Adelaide Health Technology Assessment Discipline of Public Health School of Population Health and Clinical Practice University of Adelaide With special thanks to Eliana Della Flora, George Mnatzaganian, Elizabeth Buckley, Claude Farah, Debra Gum, and Hong Ju for their assistance.

Depression in adolescents and young adults 3

Table of contents Executive summary ........................................................................................................................... 13Introduction ................................................................................................................................... 17

Aim of the systematic review ....................................................................................................... 17Objectives / Research questions ...................................................................................................... 17

How do we develop clinical practice guidelines? ......................................................................... 17Risk factors and protective factors .................................................................................................. 19

Risk factors from developmental stages/ inherent to child ........................................................... 27Genetic and Environmental interaction ................................................................................. 27Pregnancy ............................................................................................................................ 30Biological .............................................................................................................................. 30 Child ..................................................................................................................................... 33Psychological factors............................................................................................................ 33 Childhood abuse .................................................................................................................. 40 Adolescence ......................................................................................................................... 42Pubertal/ normal crisis: biological factors ............................................................................ 42 Puberty/ normal crisis: Psychological factors ...................................................................... 46 Puberty/ normal crisis: Eating and weight control ............................................................... 57Puberty/ normal crisis: Social factors .................................................................................. 61Puberty/ abnormal crisis: biological .................................................................................... 67Pubertal/ abnormal crisis: psychological factors ................................................................. 72Pubertal/ abnormal crisis: Life events ................................................................................. 85 Risky behaviour .................................................................................................................... 89 Child/ adolescence ............................................................................................................... 99

Risk with systemic origins .......................................................................................................... 108Parental/ family origin ......................................................................................................... 108Societal .............................................................................................................................. 130School ................................................................................................................................ 132

Interacting Risk Factors for both adolescents and young adults ................................................ 134Mediator factors for both adolescents and young adults ........................................................... 141

Prevention ................................................................................................................................. 148Universal prevention strategies in children and adolescents ..................................................... 149

Psychosocial interventions ................................................................................................. 149Comparison of psychosocial interventions ......................................................................... 161Parent training .................................................................................................................... 165

Universal prevention strategies in young adults ........................................................................ 167Counselling of parents ........................................................................................................ 167Classroom behaviour management ................................................................................... 168Psychosocial interventions ................................................................................................. 169Transition training ............................................................................................................... 174Meditation ........................................................................................................................... 175Vitamins ............................................................................................................................. 176

Selective prevention strategies in children and adolescents ..................................................... 179Psychosocial interventions ................................................................................................. 179

4 Depression in adolescents and young adults

Family focused intervention ................................................................................................ 191Dialectical behaviour therapy skills training group .............................................................. 196Exercise therapy ................................................................................................................ 197

Selective prevention strategies in young adults ......................................................................... 199Early educational child care ............................................................................................... 199Psychosocial interventions ................................................................................................. 200Writing ................................................................................................................................ 207

Indicated prevention strategies in children and adolescents ..................................................... 209Cognitive behavioural interventions .................................................................................... 209Interpersonal Psychotherapy Adolescent Skills Training ................................................. 226Bibliotherapy ...................................................................................................................... 227

Indicated prevention strategies in young adults ......................................................................... 229Cognitive behavioural interventions .................................................................................... 229Interpersonal psychotherapy .............................................................................................. 231Adventure based therapy ................................................................................................... 232Exercise therapies .............................................................................................................. 233

Psychosocial and physical therapies ............................................................................................ 236For treating major depressive disorder or dysthymia in adolescents ......................................... 236

Cognitive Behavioural Therapy versus wait-list .................................................................. 237Cognitive Behavioural Therapy versus usual care ............................................................. 242Cognitive Behavioural Therapy versus placebo ................................................................. 244Cognitive Behavioural Therapy versus Interpersonal Psychotherapy ................................ 247Cognitive Behavioural Therapy maintenance versus no treatment .................................... 249Cognitive Behavioural Therapy versus Systemic-Behavioural Family Therapy and Nondirective Supportive Therapy ....................................................................................... 253Cognitive Behavioural Therapy versus Life Skills Training ................................................. 256Cognitive Behavioural Therapy versus Relaxation Training ............................................... 260Interpersonal Psychotherapy versus wait-list ..................................................................... 262Interpersonal Psychotherapy (IPT) versus usual care ........................................................ 266Family interventions versus wait-list ................................................................................... 269Family interventions versus usual care .............................................................................. 272Therapeutic Support Group versus Social Skills Group ..................................................... 274

For treating major depressive disorder or dysthymia in young adults ........................................ 277Cognitive Behavioural Therapy (CBT) versus wait-list ....................................................... 277Yoga versus no treatment .................................................................................................. 279Bright Light Therapy versus placebo .................................................................................. 282

For treating bipolar depression in adolescents and young adults .............................................. 284Electroconvulsive Therapy versus usual care .................................................................... 284Family Focused Therapy (FFT) versus Enhanced Care (EC) ............................................ 286

Pharmacological therapies ............................................................................................................. 289For treating major depressive disorder or dysthymia in adolescents ......................................... 289

SSRIs versus placebo ........................................................................................................ 289SSRIs vs placebo for maintenance .................................................................................... 309Selective serotonin reuptake inhibitor (SSRIs) versus tricyclic anti-depressants ................ 312Selective serotonin reuptake inhibitor (SSRIs) versus selective serotonin and noradrenergic reuptake inhibitor (SNRIs), with/without cognitive behavioural therapy .............................. 319Variable dose fluoxetine versus fixed dose fluoxetine in previous nonresponders to fluoxetine

........................................................................................................................................... 321


Serotonin norepinephrine reuptake inhibitor (SNRI) vs placebo ......................................... 323Tricyclic antidepressants versus placebo ........................................................................... 325Reversible inhibitor of monoamine oxidase A (RIMA) vs placebo ...................................... 333

For treating major depressive disorder or dysthymia in young adults ........................................ 335SSRI vs TCA ...................................................................................................................... 335Antidepressants vs placebo ............................................................................................... 340

For treating bipolar depression in adolescents .......................................................................... 343Anticonvulsant vs placebo for manic or mixed episodes .................................................... 343Anticonvulsant vs Antipsychotic for manic or mixed episodes ............................................ 346Anticonvulsant plus atypical antipsychotic vs anticonvulsant plus placebo ........................ 349Antipsychotic vs placebo .................................................................................................... 351Lithium vs placebo ............................................................................................................. 353Maintenance with Lithium vs placebo ................................................................................. 355Lithium + ginseng vs lithium + fluoxetine ............................................................................ 357

For treating bipolar depression in young adults ......................................................................... 359Comparisons of psychological vs pharmacological therapies or combined ............................. 360

For treating major depressive disorder or dysthymia in adolescents ......................................... 360Cognitive Behavioural Therapy versus Selective Serotonin Reuptake Inhibitors (SSRIs) .. 360Cognitive Behavioural Therapy plus SSRIs versus SSRIs alone ....................................... 366Sequentially added SSRIs and CBT versus SSRIs alone .................................................. 378Cognitive Behavioural Therapy plus SSRIs versus SSRIs alone for maintenance therapy in proven responders to SSRIs .............................................................................................. 380SSRI or SNRI in combination with CBT versus SSRI or SNRI alone in nonresponders to one SSRI ................................................................................................................................... 382Cognitive Behavioural Therapy plus SSRIs versus placebo ............................................... 384Cognitive Behavioural Therapy plus SSRIs versus CBT alone .......................................... 389

Prognosis ................................................................................................................................. 393Prognostic factors in adolescents for whom treatment of major depressive disorder or dysthymia is not specified .............................................................................................................................. 393

Psychological factors .......................................................................................................... 396Risky behaviour .................................................................................................................. 403Family origin ....................................................................................................................... 404Social origin ........................................................................................................................ 406

Prognostic factors in adolescents treated for major depressive disorder or dysthymia ............. 407Predictors of outcomes in adolescents receiving fluoxetine, CBT, fluoxetine plus CBT or placebo (TADS) .................................................................................................................. 407Predictors of outcomes in adolescents receiving CBT ....................................................... 409Predictors of outcomes in adolescents receiving CBT, systemic-behavioural family therapy or supportive therapy .............................................................................................................. 411Predictors of outcomes in adolescents receiving CBT or life skills tutoring ........................ 412

Appendix A Methodology ........................................................................................................... 414Literature search and selection criteria ...................................................................................... 414Study selection criteria .............................................................................................................. 418Validity assessment ................................................................................................................... 426Data extraction and analysis ..................................................................................................... 430Assessing the body of evidence and formulating recommendations ......................................... 430

Appendix B Health Technology Assessment Agencies .......................................................... 433Appendix C Study quality critical appraisal checklists ........................................................... 435


Appendix D Evidence tables ...................................................................................................... 441Risk factors ................................................................................................................................ 441Prevention ................................................................................................................................. 621Psychotherapy ........................................................................................................................... 769Pharmacotherapy ...................................................................................................................... 845Prognosis .................................................................................................................................. 927

Appendix E NHMRC Evidence statement form ........................................................................ 965Risk factors ................................................................................................................................ 965Prevention ............................................................................................................................... 1116Psychosocial and physical therapies ....................................................................................... 1174Pharmacotherapy .................................................................................................................... 1210Comparisons of psychological vs pharmacological therapies or combined ............................. 1245 Prognosis ................................................................................................................................ 1258

Appendix F Excluded studies ................................................................................................. 1292Excluded publications from Risk Factors ................................................................................. 1292Excluded publications from prevention .................................................................................... 1295Excluded publications from psychotherapy ............................................................................. 1295Excluded publications from Pharmacotherapy ........................................................................ 1296Excluded publications from Prognosis ..................................................................................... 1296

References ............................................................................................................................... 1298

Tables Table 1 Predictive value of gender for (symptoms of) depression, suicidal ideation or suicide

attempt .............................................................................................................................. 21 Table 2 Predictive value of age for depressive symptoms and suicide attempt ............................. 23 Table 3 Predictive value of ethnicity for depressive symptoms ...................................................... 26 Table 4 Predictive value of genotype for depression and depressive symptoms ............................ 29 Table 5 Predictive value of neonatal health problems for major depressive disorder and depression

.......................................................................................................................................... 31 Table 6 Predictive value of birth weight for depression and symptoms of depression ................... 32 Table 7 Predictive value of disruptive behaviour for depression, depressive symptoms and suicide

attempt .............................................................................................................................. 35 Table 8 Predictive value of social competence for depressive symptoms, suicidality and suicide

attempt .............................................................................................................................. 37 Table 9 Predictive value of child-parent attachment for major depressive disorder, depressive

symptoms and suicide attempt .......................................................................................... 38 Table 10 Predictive value of childhood sexual abuse for depression, depressive symptoms, suicidal

attempt and suicide ideation.............................................................................................. 40 Table 11 Predictive value of childhood physical abuse for major depression, suicidal attempt and

suicide ideation ................................................................................................................. 42 Table 12 Predictive value of hormone levels for major depressive disorder ..................................... 43 Table 13 Predictive value of maturation for major depressive disorder and suicides attempt ........... 44 Table 14 Predictive value of sexual orientation for suicide attempt .................................................. 45 Table 15 Predictive value of self esteem for depression and depressive symptoms ........................ 47


Table 16 Predictive value of body image for depression, symptoms of depression, depressive mood and suicide attempt ........................................................................................................... 49

Table 17 Predictive value of physical activity for depressive symptoms, bipolar disorder and dysthymia .......................................................................................................................... 51

Table 18 Predictive value of cognitive and attributional style for major depressive disorder, dysthymia and depressive symptoms ............................................................................... 53

Table 19 Predictive value of school performance for major depressive episode and dysthymia, depression and depressive symptoms and depressive mood ........................................... 55

Table 20 Predictive value of overweight and obesity for depressive symptoms and depressive mood .......................................................................................................................................... 58

Table 21 Predictive value of eating disorder and symptoms of eating disorder for depression and depressive symptoms ....................................................................................................... 59

Table 22 Predictive value of dieting for depressive symptoms, suicide attempt and suicidal ideation .......................................................................................................................................... 61

Table 23 Predictive value of quality of relationships for major depressive disorder, depression, depressive symptoms, depressed mood, suicide ideation and suicide attempt ................ 63

Table 24 Predictive value of romantic involvement for depressive symptoms, depressive mood and suicide attempt .................................................................................................................. 66

Table 25 Predictive value of health problems for major depressive disorder, (major) depression, depressive symptoms and suicidal ideation ...................................................................... 69

Table 26 Predictive value of sleeping problems for major depressive disorder, depression and depressive symptoms ....................................................................................................... 71

Table 27 Predictive value of mental disorders for major depressive disorder, depression and depressive symptoms ....................................................................................................... 72

Table 28 Predictive value of suicide attempt for major depressive disorder, suicide attempt and suicide ideation ................................................................................................................. 74

Table 29 Predictive value of suicidal ideation for major depressive disorder, suicide attempt and suicide ideation ................................................................................................................. 76

Table 30 Predictive value of depressive symptoms for major depression, depression, depressive symptoms, suicidal attempt and suicide ideation .............................................................. 79

Table 31 Predictive value of internalising problems for depressive symptoms and suicide attempt . 82 Table 32 Predictive value of aggression for depressive symptoms .................................................. 83 Table 33 Predictive value of hypomania and mania for hypomania and major depression .............. 85 Table 34 Predictive value of peer or family suicide for major depressive disorder, suicide attempt

and suicide ideation .......................................................................................................... 86 Table 35 Predictive value of parental death for depression and depressive symptoms .................... 88 Table 36 Predictive value of adolescence sexual abuse for short term depressive symptoms ......... 88 Table 37 Predictive value of substance use for major depressive disorder, depression, depressive

symptoms, suicidality ........................................................................................................ 90 Table 38 Table 39 Predictive value of alcohol use for major depressive disorder, depressive symptoms and

suicide attempt .................................................................................................................. 93

Predictive value of smoking for major depressive disorder and depressive symptoms ...... 91

Table 40 Predictive value of cannabis use for depressive symptoms, suicide attempt and suicide

ideation ............................................................................................................................. 95 Table 41 Predictive value of other drug use for depressive symptoms, suicide attempt and suicide

ideation ............................................................................................................................. 96 Table 42 Predictive value of pregnancy for major depressive disorder and depressive symptoms .. 98 Table 43 Predictive value of having problems with the law for depressive symptoms ...................... 99


Table 44 Predictive value of life events for depression, depressive symptoms and suicidal ideation ........................................................................................................................................ 101

Table 45 Predictive value of temperament, personality and emotional regulation for depressive symptoms and (single) suicide attempt ........................................................................... 104

Table 46 Predictive value of anxiety for (major) depression and single suicide attempt ................. 107 Table 47 Predictive value of family psychopathology for major depressive disorder, depression and

depressive symptoms ..................................................................................................... 110 Table 48 Predictive value of parental divorce for depressive symptoms ........................................ 112 Table 49 Predictive value of parental education level for depressive symptoms ............................ 114 Table 50 Predictive value of parental support for major depressive disorder, depression, depressive

symptoms, depressive mood, suicide attempt and suicidality ......................................... 116 Table 51 Predictive value of parenting style for major or minor depression, depressive symptoms

and suicide attempt ......................................................................................................... 119 Table 52 Predictive value of family functioning for major depressive disorder, depressive symptoms,

depressed mood and suicide ideation ............................................................................. 121 Table 53 Predictive value of family composition for major depressive disorder, depression and

suicide ideation ............................................................................................................... 124 Table 54 Predictive value of family role for major depressive disorder and depression .................. 125 Table 55 Predictive value of family social economic status for depressive symptoms .................... 127 Table 56 Predictive value of mothers role satisfaction for depressive symptoms .......................... 129 Table 57 Predictive value of residential situation for (short term) depressive symptoms and first time

bipolar disorder ............................................................................................................... 130 Table 58 Predictive value of family and peer delinquency for depressive symptoms ..................... 131 Table 59 Predictive value of school size for depressive symptoms and suicide attempt ................ 132 Table 60 Predictive value of specific school program for depressive symptoms and suicide attempt

........................................................................................................................................ 133 Table 61 Predictive value of stress and attribution style for major depressive disorder and

depressive symptoms ..................................................................................................... 134 Table 62 Predictive value of stress, attribution style and self esteem for major depressive disorder

and depressive symptoms .............................................................................................. 135 Table 63 Predictive value of friends suicide and depressive affect for suicide attempt .................. 136 Table 64 Predictive value of life event and cognitive style for depressive symptoms ..................... 137 Table 65 Predictive value of depressive symptoms and behaviour for depressive symptoms ........ 138 Table 66 Predictive value thinking difficulties and fatigue for major depressive disorder ................ 139 Table 67 Predictive value of primary caregivers inductive reasoning and neighbourhood disorder for

depressive symptoms ..................................................................................................... 140 Table 68 Rumination as a mediator between negative cognitive style, self criticism, neediness and

number of past MDEs and future MDEs .......................................................................... 141 Table 69 Child high cognitive risk as a mediator between parental feedback and depression ....... 142 Table 70 Stress burden as a mediator between early childhood adversities and depression ......... 143 Table 71 Parental rejection as a mediator between childhood harsh parenting and depression .... 144 Table 72 Dieting as a mediator between body dissatisfaction and depressive symptoms .............. 145 Table 73 Family relations as a mediator between single parent household and depressive mood . 146 Table 74 Financial problems as a mediator between single parent household and depressive mood

........................................................................................................................................ 146 Table 75 Life events as a mediator between single parent household and depressive mood ........ 147 Table 76 Studies included on universal prevention in children/adolescents: psychosocial

interventions versus no treatment, wait-list or placebo .................................................... 150


Table 77 Studies included on universal prevention in children/adolescents: comparison of psychosocial interventions .............................................................................................. 163

Table 78 Study assessing universal prevention of depression with parent training ........................ 166 Table 79 Study included for counselling of parents as a universal intervention .............................. 167 Table 80 Study included on classroom behaviour management .................................................... 168 Table 81 Studies included on universal prevention of depression using psychosocial interventions in

young adults .................................................................................................................... 171 Table 82 Study included on universal prevention of depression using transition training in young

adults .............................................................................................................................. 175 Table 83 Study included on universal prevention of depression with meditation in young adults ... 176 Table 84 Study included on universal prevention of depression with vitamins in young adults ...... 177 Table 85 Studies included assessing psychosocial interventions as selective prevention for

children/adolescents ....................................................................................................... 181 Table 86 Study assessing psychosocial intervention in adolescents with diabetes ........................ 184 Table 87 Study included assessing a psychosocial intervention in adolescents with minority status

and low income as risk factor .......................................................................................... 186 Table 88 Study included assessing cognitive behavioural intervention in those with personality as

risk factor ........................................................................................................................ 188 Table 89 Study included assessing cognitive behavioural intervention with residing in shelter as a

risk factor ........................................................................................................................ 190 Table 90 Studies included for family focused interventions for selective prevention for children /

adolescents ..................................................................................................................... 193 Table 91 Study on dialectical behaviour therapy skills training group for selective prevention in

adolescents ..................................................................................................................... 196 Table 92 Study on exercise for selective prevention in adolescents ............................................... 197 Table 93

Table 94 Studies included for assessment of psychosocial interventions for selective prevention for young adults .................................................................................................................... 202

Studies included for early educational child care as selective prevention for young adults ........................................................................................................................................ 199

Table 95 Study assessing cognitive behavioural intervention in those with body image concerns as

risk factor ........................................................................................................................ 204 Table 96 Study included assessing a social problem solving intervention in incarcerated youth, at

risk as suicidal, under protection, or being bullied ........................................................... 206 Table 97 Studies included for assessment of writing as selective prevention for young adults ...... 207 Table 98 Studies on cognitive behavioural interventions for indicated prevention in children /

adolescents ..................................................................................................................... 210 Table 99 Diagnosis of depression after cognitive behavioural intervention and control as indicated

prevention in adolescents ............................................................................................... 216 Table 100 Quality of life after cognitive behavioural interventions and control as an indicated

prevention strategy in adolescents .................................................................................. 221 Table 101 Study on interpersonal psychotherapy skills training for indicated prevention in children /

adolescents ..................................................................................................................... 226 Table 102 Study on bibliotherapy for indicated prevention in adolescents ....................................... 228 Table 103 Studies on cognitive behavioural interventions as an indicated prevention strategy in

young adults .................................................................................................................... 229 Table 104 Studies included for assessment of interpersonal psychotherapy for indicated prevention

for young adults............................................................................................................... 231 Table 105 Study on adventure based therapy as an indicated prevention strategy in young adults . 233


Table 106 Studies on exercise as indicated prevention in young adults ........................................... 234 Table 107 Studies included assessing CBT vs wait-list ................................................................... 238 Table 108 Study included assessing CBT vs usual care.................................................................. 243 Table 109 Variables that moderate depressive symptoms (CDRS-R) in TADS study ...................... 244 Table 110 Study included assessing CBT vs placebo ..................................................................... 245 Table 111 Adverse events related to CBT vs placebo ...................................................................... 246 Table 112 Studies included assessing Cognitive Behavioural Therapy versus Interpersonal Therapy ..

..................................................................................................................................... 248 Table 113 Studies included assessing CBT maintenance versus no treatment ............................... 251 Table 114 Studies included assessing CBT versus other Systemic-Behavioural Family Therapy and

Nondirective Supportive Therapy .................................................................................... 255 Table 115 Study included assessing CBT versus Life Skills Training .............................................. 258 Table 116 Study included assessing CBT versus Relaxation Training ............................................ 261 Table 117 Studies included assessing Interpersonal Therapy (IPT) versus wait-list or clinical

monitoring ....................................................................................................................... 262 Table 118 IPT versus wait-list on global functioning ......................................................................... 263 Table 119 IPT versus usual care or wait-list on remission of depressive symptoms ........................ 264 Table 120 Studies included assessing Interpersonal Therapy (IPT) versus usual care .................... 267 Table 121 Studies included assessing Attachment Based Family Therapy versus wait-list ............. 271 Table 122 Studies included assessing Family intervention versus usual care ................................. 273 Table 123 Studies included assessing Therapeutic Support Group versus Social Skills Group ...... 276 Table 124 Remission of depressive symptoms in studies comparing CBT versus wait-list .............. 278 Table 125 Study included assessing Yoga with no treatment .......................................................... 281 Table 126 Study included assessing Bright Light Therapy versus placebo ...................................... 283 Table 127 Electroconvulsive Therapy versus usual care .................................................................. 285 Table 128 Study included assessing Family Focused Therapy versus Enhanced Care .................. 287 Table 129 Studies included assessing SSRIs vs placebo in adolescents ......................................... 291 Table 130 SSRIs vs placebo on functioning ..................................................................................... 298 Table 131 Variables that moderate depressive symptoms (CDRS-R) in TADS study ...................... 302 Table 132 SSRIs vs placebo adverse events over the treatment period ....................................... 305 Table 133 Cost-effectiveness of SSRIs vs placebo in adolescents .................................................. 308 Table 134 Study included assessing fluoxetine vs placebo in adolescents who achieved remission of

depressive symptoms with fluoxetine .............................................................................. 311 Table 135 Functioning after SSRIs vs TCAs .................................................................................... 312 Table 136 Studies included on SSRIs vs TRAs ............................................................................... 313 Table 137 SSRI vs tricyclic antidepressants on depressive symptoms ............................................ 315 Table 138 SSRIs vs tricyclic antidepressants adverse events ....................................................... 316 Table 139 Study included assessing SSRI CBT vs SNRI CBT .................................................. 320 Table 140 Study included comparing two doses of fluoxetine .......................................................... 322 Table 141 Study included assessing SNRI vs placebo ..................................................................... 324 Table 142 Studies included assessing tricyclic antidepressants and placebo .................................. 326 Table 143 Tricyclic antidepressants vs placebo adverse events ................................................... 330 Table 144 Study included assessing reversible inhibitor of monoamine oxidase A and placebo ...... 334 Table 145 Studies included for SSRIs vs TCAs in young adults ....................................................... 337 Table 146 Systematic reviews included on antidepressants vs placebo in young adults .................. 341 Table 147 Studies included assessing anticonvulsants vs placebo in manic or mixed episodes ...... 344 Table 148 Study included assessing anticonvulsants vs atypical antipsychotic for mixed or manic

episodes .......................................................................................................................... 347


Table 149 Study assessing an anticonvulsant with the addition or either atypical antipsychotic or placebo for a manic episode ........................................................................................... 350

Table 150 Study included assessing an atypical antipsychotic and placebo for manic episodes ..... 352 Table 151 Study assessing lithium and placebo for acute treatment of bipolar disorder .................. 354 Table 152 Study assessing lithium vs placebo for maintenance after response to lithium ................ 356 Table 153 Study assessing the addition of ginseng or fluoxetine to lithium in depressive episodes in

adolescents with bipolar disorder .................................................................................... 358 Table 154 CBT vs SSRIs on functioning........................................................................................... 361 Table 155 Studies included assessing CBT versus Selective Serotonin Reuptake Inhibitors (SSRIs)

........................................................................................................................................ 362 Table 156 CBT vs SSRIs on depressive symptoms ......................................................................... 363 Table 157 Variables that moderate depressive symptoms (CDRS-R) in TADS study ...................... 364 Table 158 CBT vs SSRIs on suicidal ideation .................................................................................. 364 Table 159 CBT vs SSRIs on psychiatric adverse events over the treatment period ........................ 365 Table 160 Cost-effectiveness of CBT vs placebo and SSRIs vs placebo in adolescents ................. 365 Table 161 Variables that moderate depressive symptoms (CDRS-R) in TADS study ...................... 368 Table 162 Studies included assessing combined CBT plus SSRIs versus SSRIs alone ................. 369 Table 163 Adverse effects of SSRI versus combined SSRI plus CBT .............................................. 374 Table 164 Cost / Cost effectiveness of SSRI versus combined SSRI plus CBT .............................. 376 Table 165 Studies included assessing CBT plus SSRIs versus SSRIs alone .................................. 379 Table 166 Studies included assessing relapse prevention CBT plus SSRIs versus SSRIs alone ... 381 Table 167 Study included assessing SSRI or SNRI with CBT vs SSRI or SNRI .............................. 383 Table 168 CBT + SSRIs versus placebo on functioning .................................................................. 384 Table 169 Studies included assessing CBT plus SSRIs versus placebo .......................................... 386 Table 170 CBT + SSRIs versus placebo on depressive symptoms .................................................. 387 Table 171 CBT plus SSRIs versus placebo on psychiatric adverse events over the treatment period

........................................................................................................................................ 387 Table 172 CBT plus SSRI versus placebo on suicidal ideation ........................................................ 388 Table 173 Cost effectiveness of CBT plus SSRIs versus placebo .................................................... 388 Table 174 Study included assessing CBT + SSRIs vs CBT ............................................................. 390 Table 175 Variables that moderate depressive symptoms (CDRS-R) in TADS study ...................... 391 Table 176 Adverse events related to CBT + SSRIs vs CBT ............................................................. 391 Table 177 Predictive value of gender for the prognosis of recurrent major depressive disorder and

depression ...................................................................................................................... 394 Table 178 Predictive value of age of onset for the prognosis of depression (recurrent depression, and

time to recovery) ............................................................................................................. 395 Table 179 Predictive value of characteristics of depressive episodes for the prognosis of depression

(staying well, recurrent major depressive disorder, and time to recovery)....................... 397 Table 180 Predictive value of personality disorder symptoms or Axis II diagnosis for the prognosis of

depression (subsequent major depressive disorder, pure depression and staying well) . 398 Table 181 Predictive value of suicidality severity for the prognosis of depression (suicide) ............. 399 Table 182 Predictive value of global functioning for the prognosis of depression (recovery) ............ 400 Table 183 Predictive value of anxiety for the prognosis of depression, recurrent major depressive

disorder, suicide attempt and depression ........................................................................ 401 Table 184 Predictive value of anger for the prognosis of depression (suicide) ................................. 402 Table 185 Predictive value of self devaluation for the prognosis of depression (persistent major

depression) ..................................................................................................................... 403


Table 186 Predictive value of substance use for the prognosis of depression (depression at follow-up) ........................................................................................................................................ 404

Table 187 Predictive value of family history of recurrent depressive disorder for the prognosis of depression (recurrent major depressive disorder and staying well) ................................ 405

Table 188 Predictive value of harsh discipline for the prognosis of a major depressive episode (relapse) .......................................................................................................................... 405

Table 189 Predictive value of perceived social support for the prognosis of a major depressive episode (relapse) ............................................................................................................ 406

Table 190 Predictors of treatment efficacy ....................................................................................... 408 Table 191 Comorbidities as a predictor of outcomes in adolescents receiving CBT (with/without

parental involvement) ...................................................................................................... 409 Table 192 Predictors of outcomes in adolescents receiving CBT (with/without parental involvement) ..

..................................................................................................................................... 410 Table 193 Predictors of treatment efficacy in those receiving CBT, systemic-behavioural family

therapy or supportive therapy.......................................................................................... 411 Table 194 Predictors of time to recovery .......................................................................................... 412 Table 195 Bibliographic databases ................................................................................................... 414 Table 196 Additional sources of literature......................................................................................... 415 Table 197 Search terms for evaluation of risk factors ....................................................................... 416 Table 198 Search terms for evaluation of prevention strategies for depression ............................... 416 Table 199 Search terms for evaluation of non-pharmacological management of depression ........... 417 Table 200 Search terms for evaluation of pharmacological management of depression .................. 418 Table 201 Inclusion criteria for risk factor studies ............................................................................. 422 Table 202 Inclusion criteria for prevention studies ............................................................................ 423 Table 203 Inclusion criteria for evaluation of non-pharmacological interventions ............................. 424 Table 204 Inclusion criteria for evaluation of pharmacological interventions .................................... 425 Table 205 Inclusion criteria for evaluation of how risk factors affect prognosis ................................ 426 Table 206 Evidence dimensions ....................................................................................................... 427 Table 207 NHMRC levels of evidence .............................................................................................. 428 Table 208 Clinical impact grading for NHMRC body of evidence matrix ........................................... 430 Table 209 Body of evidence matrix .................................................................................................. 431 Table 210 Definition of NHMRC grade of recommendations ............................................................ 432


Executive summary This document outlines the results of a series of systematic reviews, performed to determine what are the risk factors and protective factors for depression, how can depression be prevented, how can it be treated, and how do risk factors impact on outcomes, in the population of adolescents and young adults. The evidence collected was then used to form the basis for a series of evidence statements, which were translated into recommendations by the Working Committee. The full guideline document is published elsewhere. A summary of the evidence statements that were graded A or B is provided below: Risk factors Females have a substantial increased risk for depression, symptoms of depression, suicidal ideation and suicide attempts during adolescence and young adulthood compared to males. (Grade B) From the evidence it can be stated that neonatal health problems, in particular in males, is a predictive factor for major depressive disorders and depression in adolescence and young adulthood. (Grade B) Depression and depressive symptoms in female adolescents and young adults might be predicted by low birth weight. (Grade B) Incubator care in the early stage of life is a protective factor for major depressive disorder in young female adults. (Grade B) Depression, symptoms of depression and suicide attempts in adolescence and young adulthood can be predicted by disruptive behaviour (e.g. including conduct problems, disruptive behaviour disorders, rebelliousness, oppositional disorders, being under-controlled and showing antisocial behaviour). (Grade B) Adolescents and young adults with low self esteem are at an increased risk for developing depression, depressive symptoms or suicide attempts compared to their peers with high self esteem. High self esteem is a protective factor for depression, depressive symptoms or suicide attempts. (Grade B) There is evidence for low quality relationships as a predictor and high quality relationships as a protector for the development of major depressive disorder, depression, depressive symptoms, suicidal ideation and suicide attempt in adolescence and young adulthood. (Grade B) The evidence suggests that sleeping problems might be a predictor for major depressive disorder, depression or symptoms of depression in adolescence. (Grade B) The existence of mental disorders in adolescents increases the likelihood of developing major depressive disorder, depression and depressive symptoms in adolescence and young adulthood. (Grade B) Adolescents with a history of suicide attempts are more likely to be diagnosed with depression, attempt suicide and have suicidal ideation in adolescence and young adulthood. (Grade B)


The evidence indicates that suicidal ideation in adolescents is a predictor of major depression, suicidal ideation and suicide attempt later in adolescence and during young adulthood. (Grade B) Childhood and adolescent depressive symptoms is a good predictor of clinical depression, depressive symptoms, suicide attempts and suicide ideation in adolescence and young adulthood. (Grade B) The evidence indicates that adolescents exposed to a completed suicide or suicide attempt of a friend or family member have a substantial risk for the development of major depressive disorder and their own suicide attempt in adolescence and young adulthood. (Grade B) The evidence suggests that stressful negative life events, such as family conflict, loss of a friend or relative and traumatic experiences, are predictive factors for depression, depressive symptoms and suicide ideation in adolescence and young adulthood. (Grade B) The occurrence of psychopathology in parents increases the risk of major depressive disorder, depression and depressive symptoms in adolescent and young adult offspring. (Grade A) The majority of the evidence indicates that parental support is a protective factor for the development of major depressive disorder, depression, depressive symptoms, depressive mood, and suicidality in adolescence and young adulthood. (Grade B) Prevention

Universal prevention of depression in adolescents There is evidence that psychosocial interventions are not an effective universal prevention strategy for preventing the onset of major depressive disorder in the adolescent population. Small reductions in depressive symptoms were observed immediately post-intervention, but not after 12 months. (Grade A) There is insufficient evidence to recommend one form of universal psychosocial intervention over another, to reduce depressive symptoms in the adolescent population. (Grade B)

Selective prevention of depression in adolescents There is evidence that family focused interventions, given to the child at risk of depression and their parent(s), are effective for reducing the frequency of newly diagnosed major depressive disorder or depressive symptoms during adolescence. (Grade B)

Indicated prevention of depression in adolescents There is good quality evidence that cognitive behavioural interventions might effectively reduce depressive symptoms in the short term. The benefits of cognitive behavioural interventions at 12 months after the sessions have concluded are not consistent. (Grade B) There is insufficient evidence to recommend the use of cognitive behavioural interventions as a method of preventing the transition to a major depressive disorder in adolescents with depressive symptoms. (Grade B)


There is good quality evidence that cognitive behavioural interventions might effectively reduce depressive symptoms in the short term. The benefits of cognitive behavioural interventions at 12 months after the sessions have concluded are not consistent. (Grade B) Psychosocial and physical therapies

For treating major depressive disorder in adolescents There is evidence from a large number of studies that CBT is beneficial compared to wait-list for reducing depressive symptoms and improving functioning when measured immediately post-treatment, in adolescents with major depressive disorder or dysthymia. (Grade B) There is evidence from a small number of studies (relative to CBT) that IPT is beneficial compared to wait-list immediately post-treatment for treating depressive symptoms and depression in adolescents with major depressive disorder or dysthymia. (Grade B)

Pharmacological therapies

For treating major depressive disorder in adolescents Fluoxetine is more effective than placebo at reducing depression and depressive symptoms and improving functioning in the short term, in adolescents diagnosed with major depressive disorder without suicidal ideation nor deemed at high risk of suicide at baseline. (Grade B) The published evidence on paroxetine reported that it is more effective than placebo at reducing depression and depressive symptoms in adolescents diagnosed with major depressive disorder (Grade B), however, conclusions cannot be made on the basis of the published evidence, due to the presence of selective reporting and publication bias. SSRIs1

are associated with a higher risk of side effects and adverse events than placebo in adolescents being treated for major depressive disorder. (Grade B)

In adolescents with major depressive disorder without suicidal ideation nor deemed at high risk of suicide at baseline, SSRIs increase the rate of suicidal ideation or attempts compared to placebo by a factor of two to three (from a low very base rate). No completed suicides were reported. (Grade B)

For treating major depressive disorder in young adults There is evidence from a large sample size of a non-statistically significant effect on increased suicidal ideation from antidepressants compared to placebo in young adults with psychiatric indications. (Grade B) There is an increased risk of suicidal behaviour (preparatory acts, suicide attempts, or completed suicides) from antidepressants compared to placebo in young adults with psychiatric indications (including major depressive disorder). Completed suicides were a very rare event. (Grade A)

1 SSRIs assessed included fluoxetine, paroxetine, sertraline and citalopram


Comparisons of psychological vs pharmacological therapies or combined

For treating major depressive disorder in adolescents There is evidence to suggest that CBT plus SSRI is superior to placebo for reducing suicidal ideation, reducing depressive symptoms and improving functioning in adolescents with major depressive disorder (Grade B). Prognosis

Prognostic factors in adolescents for whom treatment of a major depressive disorder is not specified Recurrence of depressive disorder and depression in adolescence and young adulthood is more likely in females than males, although there is some inconsistency in the evidence on the statistical significance of this relationship. (Grade B) Adolescents and young adults with major or minor depressive disorders have better prognostic outcomes if they are younger at the age of onset, have had fewer previous depressive episodes, have a minor depressive disorder rather than major depressive disorder, have a shorter depressive episode have lower severity of depressive symptoms, and no significant depressed mood. (Grade B) The presence of an Axis II diagnosis (personality disorders or intellectual disability) or a high level of borderline or anti social personality disorder symptoms, in current or formerly depressed adolescents increases the risk for recurrent MDD and depression. (Grade B) Adolescents with a current or previous episode of depressive disorder and an anxiety disorder are more likely to have recurrent major depressive disorder, attempt suicide or develop pure depression in adolescence and young adulthood, than those without comorbid anxiety. (Grade A)


Introduction

Aim of the systematic review The primary aim of this systematic review is to provide the evidence base for the 2010 NHMRC clinical practice guidelines Depression in adolescents and young adults to cover young people aged 13 to 24 years old.

Objectives / Research questions To identify biopsychosocial risk factors and protective factors for the development of

depression in adolescents and young adults and their impact upon its course and outcomes. To evaluate preventive strategies for depression in adolescents and young adults. To evaluate management strategies for treating, monitoring and preventing recurrence of

depression in adolescents and young adults.

The abovementioned objectives are central to informing the beyondblue NHMRC Clinical Practice Guidelines: Depression in Adolescents and Young Adults Working Committee in their task of completing their objective to develop current clinical practice guidelines which make recommendations for the prevention, identification, treatment and management of the symptoms of depression in adolescents and young adults. The aim of this is to:

improve health outcomes and prevent the incidence of further depressive episodes and ongoing depression for adolescents and young adults who have experienced depressive symptoms, or been diagnosed with depression; and

for those with a diagnosis of depression, to promote effective treatment, limit illness duration, advise on strategies if treatment resistant and help prevent relapse.

How do we develop clinical practice guidelines? Clinical practice guidelines are systematically developed statements that assist clinicians, consumers and policy makers to make appropriate health care decisions. Such guidelines present statements of best practice based on a thorough evaluation of the evidence from published research studies in the form of systematic literature reviews on the outcomes of treatment or other health care procedures (NHMRC 2000a). Systematic literature reviews use explicit, systematic methods to limit bias and reduce the effect of chance in the review, and therefore provide more reliable and consistent results upon which to draw conclusions. This enables the development of evidence-based clinical practice guidelines. The National Health and Medical Research Council (NHMRC) have published a series of Guidelines for Guidelines handbooks to assist developers with the process of producing and disseminating clinical practice guidelines (NHMRC 1999; NHMRC 2000a; NHMRC 2000b; NHMRC 2000c; NHMRC 2001). A checklist outlining the minimum requirements for formulating NHMRC evidence-based guidelines has also been developed and is based on these handbooks (NHMRC 2007). This guideline followed the process recommended by NHMRC, which is based on the following nine key principles (NHMRC 2007):

1. the guideline development and evaluation process should focus on outcomes;


2. the guidelines should be based on the best available evidence and include a statement concerning the strength of recommendations;

3. the method to synthesise the evidence should be strongest applicable; 4. the guideline development group should be multidisciplinary and including consumers early in

the development process; 5. guidelines should be flexible and adaptable to varying local conditions; 6. guidelines should consider resources and should incorporate an economic appraisal; 7. guidelines are developed for dissemination and implementation among their target audiences; 8. the implementation and impact of the guidelines should be evaluated; and 9. guidelines should be updated regularly.

Further details on the methodology are provided in Appendix A, page 414.


Risk factors and protective factors Research question: What are the biopsychosocial risk factors and protective factors for depression in adolescents and young adults? Box 1 Inclusion criteria for risk factor studies

Parameter Inclusion criteria

Population

At inception: children, adolescents and young adults (aged 24 years) without a diagnosis of clinical depression At follow-up: adolescents (aged 13 18 years) and young adults (aged 19 24 years)

Intervention Biopsychosocial risk factors and protective factors for depression (eg biological or genetic factors, environmental factors such as rural and remote location, social factors such as ethnicity, social isolation, family functioning, attachment relationships, personality factors such as problem solving style, optimistic thinking style, exposure factors such as abuse, trauma, bullying or bereavement, substance abuse disorders, medical illness, comorbidities, or the interaction of two or more of the above factors)

Outcomes Primary outcome: development of depression (unipolar, bipolar, or depression with comorbidities) defined according to clinically derived diagnostic criteria Secondary outcomes: development of symptoms of depression, suicidal ideation, suicide

Study design Prospective cohort studies or systematic reviews of prospective cohort studies*

Language Non-English language articles will be excluded unless they appear to provide a higher level of evidence than the English language articles identified. Translation of such articles will significantly increase the timeframe of the review.

Publication date 1966 11/2008

Limitations Human

* The protocol was varied to allow for retrospective cohort studies, case-control studies and cross-sectional studies to be included to assess genetics as a risk factor for depression. A total of 119 studies met the inclusion criteria outlined in Box 1. Due to the volume of literature available assessing risk factors for depression, depressive symptoms or suicidal ideation/suicide, the summary below is limited to those factors where a significant risk or protective effect was reported. Studies which presented nonsignificant results for which there were other studies reporting significant results, were mentioned in the text, but have not been included in the tables, as studies rarely reported size of effect of nonsignificant findings. There appeared to be no risk factors/protective factors that were exclusive to one age subgroup (adolescents or young adults) so the results are presented together. Studies are presented in order of outcome measures (diagnosed depression, depressive symptoms then suicidal ideation/suicide attempts), study quality, followed by study size. Good and average quality studies are presented in the tables and discussed in the text, while poor quality studies are presented in the tables but have not been discussed. While the strength of evidence on different risk factors and protective factors may be examined, the relative importance of the different factors is not easily assessed, and no attempt has been made to report this.


Gender Thirty one studies- three of good quality and twenty-eight average quality studies reported on gender as a predictive factor for depression, symptoms of depression, suicidal ideation or suicide attempts (see Table 1). Gourion et al (2008), in their good quality study, reported in their final predictive model that males are less likely to develop a major depressive disorder compared to females (OR=0.4, 95%CI 0.3, 0.7) (Gourion et al 2008). The good quality study by (Patton et al 2001,) reported that females are at an increased risk, with nearly 8 times the odds of developing depression compared to males (OR=7.7, 95%CI 3.1, 19). The average quality study by Galambos et al (2004) reported similar results indicating that females have 3 times the odds of developing a major depressive disorder than males. This was supported by Fergusson et al (2002a) who found a significant association between depression and female gender (=0.62, p


Table 1 Predictive value of gender for (symptoms of) depression, suicidal ideation or suicide attempt Study Quality N Risk factor Outcome

measure 95%CI or p-value

Outcome

Gourion, 2008 ++ 1212 Male OR 0.4 0.3, 0.7 MDD (DSM-III-R)

Patton, 2001 ++ 2032 Female OR 7.7 3.1, 19 Depression (ICD- 10)

Galambos, 2004 + 1322 Female OR 2.93


Box 2 Evidence statement matrix for gender as a predictor of MDD, depressive symptoms, suicidal ideation or suicide attempt

Component Rating Description Evidence base A Three level II studies with a low risk of bias and 28 level II studies with a moderate risk of bias

Consistency B Sixteen studies showed that female gender is a significant predictor for depression, symptoms of depression, suicidal ideation and suicide attempt. Similar results were found by the studies that examined male gender. Nine studies did not find a significant result. The difference can be explained by the other risk factors that had been included in the models.

Clinical impact B Eight studies indicated results of an OR between 1.4 and 2 for female gender compared to male. Four studies reported an OR >2 for females. The regression coefficients also indicated a substantial increased risk for female gender. The reverse was found for males (OR 0.3- 0.5).

Generalisability B Most studies included children from urban, suburban or rural secondary, middle or high schools, two studies took a sample from a birth cohort, one from a neighbourhood and one study took a sample from a medical university. Natsuaki et al (2007) only include African Americans in their study, which is not generelisable.

Applicability A The studies were conducted in several countries; one from Australia (so directly applicable), plus three from Canada, three from New Zealand, and one from the UK, which all have similar social and cultural contexts compared to Australia and results can therefore sensibly applicable. Additional studies were from Scandinavia and the United States, and the results are likely to be applicable.

Evidence statement Females have a substantial increased risk for depression, symptoms of depression, suicidal ideation and suicide attempts during adolescence and young adulthood compared to males. (Grade B)

Age Sixteen average and one poor quality study reported on the prospective relationship between age and depressive symptoms or the frequency of suicide attempts (see Table 2). Brown et al (2007) examined the role of age for different ethnic groups in terms of the change in depressive symptoms from adolescence to young adulthood. Levels of baseline depressive symptoms were positively associated with age across all ethnic groups and both genders (ie the older the participants were at baseline, the higher their average level of depressive symptoms). However, the authors found a negative association between older females and change in depression. White, Hispanic and Asian older females had a greater decrease in depressive symptoms over time (=-0.03, p


developing depressive symptoms. For males, the author did not find a significant relationship between age and depressive symptoms (Choi et al 1997). Warren (2008) reported in his dissertation that female adolescents were more likely to have short-term depressive symptoms, the older they were (unadjusted OR=1.20, 95%CI 1.10, 1.30). However, in adolescents who had experienced pregnancy (wanted or unwanted), age was a protective factor against short-term depressive symptoms (unadjusted OR=0.81, 95%CI 0.52, 1.26). In univariate analyses, age was not a significant predictor of long-term depressive symptoms across all the female adolescents (OR=0.96, 95%CI 0.87, 1.06), whereas it was a significant protective factor in those who had become pregnant (OR=0.54, 95%CI 0.32, 0.90). In multivariate analyses (controlling for the effects of ethnicity, prior depressive symptoms, religion, and prior pregnancy), Warren (2008) reported that risk of developing long term depressive symptoms for the first time decreased with age (OR=0.86, 95%CI 0.78, 0.95). Multivariate analyses showed no significant relationship between age and short term depressive symptoms (Warren 2008). Wichstrom (2000) reported that older adolescents had more often made a suicide attempt at baseline. After controlling for the effects of previous suicide attempts and suicidal ideation in multivariate analyses, increasing age was a protective factor (OR=0.78, 95%CI 0.78, 0.93), i.e., younger adolescents were more likely than older adolescents to attempt suicide for the first time (Wichstrom 2000). A further 15 studies reported non-significant results for age in the multivariate analyses for depressive symptoms and suicide attempt for at least one ethnicity/gender (Albers & Biener 2002; Alloy et al 2006; Brown et al 2007; Choi et al 1997; Duncan & Rees 2005; Gore et al 2001; Natsuaki et al 2007; O'Donnell et al 2005; Skitch & Abela 2008; Undheim & Sund 2005; Van Voorhees et al 2008a; Watt 2003; Young et al 2005). Overall, the majority of the evidence reported non-significant results, signalling that an adolescents age at baseline is not a reliable factor on which to base predictions about how their levels of depressive symptoms are likely to change over time. However, the studies that reported statistically significant results were reasonably consistent in reporting that increasing age is a protective factor against further depressive symptoms. Box 3 summarises the body of evidence according to NHMRC criteria. Table 2 Predictive value of age for depressive symptoms and suicide attempt Study Quality N Risk factor Outcome


Outcome

Brown, 2007 + 20 126 Older age, white female -0.02


Wichstrom, 2000 + 9 679 Older OR 0.85 0.78, 0.93 Suicide attempt

Watt, 2003 + 13 568 Older, female OR 0.72 14 years OR 2.02 0.9, 4.53 Symptoms of depression

Undheim, 2005 + 2465 Age, male -0.31 NS Symptoms of depression Age, female -0.18 NS Symptoms of depression

Eamon, 2002 + 898 Age - NS Symptoms of depression Natsuaki, 2007 + 897 Age - NS Symptoms of depression Albers, 2002 + 522 Age OR 0.92 0.71, 1.20 Symptoms of depression Skitch, 2008 + 161 Age 0.01 NS Symptoms of depression Gore, 2001 - 1036 Age, male -0.05 NS Depressed mood Age, female -0.04 NS Depressed mood Watt, 2003 + 13 568 Older, male OR 1.04 NS Suicide attempt

ODonnell, 2005 + 769 Age, male OR 1.34 0.93, 1.92 Suicidality Age, female OR 0.75 0.55, 1.01 Suicidality ++ = good quality study; + = average quality study; OR = Odds Ratio, = regression coefficient; NS=not significant Box 3 Evidence statement matrix for age as a predictor of depressive symptoms or suicide attempt Component Rating Description Evidence base C Sixteen level II studies with moderate risk of bias and one level II study with high risk of bias

Consistency C All significant results were consistent, except for Watt et al (2003) where older men had a small increased risk. There were 12 studies that did not find a predictive association between age and the outcome depression and therefore there is some uncertainty about age as an independent predictive factor.

Clinical impact C The three studies that present odds ratios are within the range of 0.72-0.86, which can represent a moderate clinical impact.

Generalisability B The majority of studies included either schoolchildren or a sample from the community which had good generalisability. Natsuaki et al (2007) only included African American children, ODonnell (2005) included Latino and African American children from economically disadvantaged areas, and Warren (2008) only studied females.


Applicability B The majority of studies came from the US, two from Norway and one Canada, therefore the results are applicable to the Australian context.

Evidence statement The majority of the evidence reported that age was not a significant predictor of change in depressive symptoms. From those studies reporting significant results, there was relatively consistent evidence that depressive symptoms and suicide attempts are more likely to occur for the first time in younger adolescents than older adolescents for both males and females. (Grade C)

Ethnicity Two good and 12 average quality studies investigated ethnicity as a predictive factor for depressive symptoms (see Table 3).The study by Watt (2003) indicated that there is an association between ethnic minority status in males and depressive symptoms. Compared to white males, males in a minority group had a small increased risk (=0.07, p


The good quality Australian study by Alati et al found no significant results for Asian or Aboriginal and Torrens Strait Islanders compared to Caucasian ethnicity in their univariate analysis (Alati et al 2007). Being of Asian or multi-ethnic heritage was not reported to be a significant risk factor or protective factor for depressive symptoms in multivariate analyses by Gore & Aseltine (2003), and Van Voorhees et al (2008). The significant results suggest that being black or Hispanic increases the risk for depressive symptoms, although ethnicity should be seen in a wider context, as being black or Hispanic is strongly related to other social demographic factors. Most of the included studies that reported on ethnic minority status as a risk factor were performed in the United States, and it is unknown to what extent the result are generalisable to minority ethnic groups within Australia. Furthermore, there is also evidence from 14 studies that ethnicity is neither a predictor nor a protective factor for the outcomes under investigation. Box 4 provides an overall assessment of the body of evidence reporting on ethnicity as a risk factor. Table 3 Predictive value of ethnicity for depressive symptoms Study Quality N Risk factor Outcome


Outcome

Gore, 2003 ++ 1093 Black vs white 0.10


Eamon, 2002 + 898 Hispanic - NS Symptoms of depression Albers, 2002 + 522 White vs non-white OR 0.42 0.18, 1.00 Symptoms of depression Watt, 2003 + 13568 Minority, male OR 1.10 NS Suicide attempt Minority, female OR 1.03 NS Suicide attempt

Garrison, 1991 + 1083 Ethnicity - NS Suicidal ideation ODonnell, 2005 + 769 Hispanic vs black,

male OR 0.64 0.31, 1.31 Suicidality

Hispanic vs black, female

OR 0.88 0.53, 1.45 Suicidality

+ = average quality study; OR = Odds Ratio, = regression coefficient Box 4 Evidence statement matrix for ethnicity as a predictor of depressive symptoms Component Rating Description Evidence base A Two level II studies with low risk of bias and 12 level II studies with moderate risk of bias

Consistency C The evidence reflects genuine uncertainty around this factor.The significant results are mostly consistent, although 14 studies reported non-significant results for ethnicity.

Clinical impact C The studies by Watt (2003) and Gore (2001) showed a slight clinical impact with beta coefficient < 0.2. The study by Warren et al (2008) reported increased odds between 1.38 and 1.82, which can be considered as a moderate clinical impact.

Generalisability A The majority of studies had good generalisability, using school or community samples. Eamon et al (2002) had oversampled minority groups from disadvantaged areas. Warren et al (2008) only studied a female population.

Applicability B Thirteen studies came from the US and one from Norway which have a fairly similar social and cultural context to Australia.

Evidence statement The majority of the evidence reported that ethnicity was not a significant predictor of depression or depression-related outcomes. However, the evidence was consistent in reporting that being of black or Hispanic ethnicity in the United States may put adolescents and young adults at an increased risk of having depressive symptoms compared to white adolescents and young adults (although not always to a statistically significant degree). (Grade C)

Risk factors from developmental stages/ inherent to child

Genetic and Environmental interaction Two good and two average quality studies examined the impact of genetics, and their interaction with environmental factors, on the development of depression and depressive symptoms in adolescence and young adulthood (see Table 4). The included studies assessed two dopamine related genes (the dopamine transporter gene DAT-1 and monoamine oxidise inhibitor A, MAOA), polymorphisms in the serotonin transporter gene (5-hydryoxytryptamin; 5HT), and an enzyme involved in the biosynthesis of 5HT (tryptophan hydroxylase; TPH). Haeffel et al examined the role of three polymorphisms of the dopamine transporter gene (DAT-1; rs40184, rs6347 and rs2652511) and assessed how they interact with maternal rejection for the development of depression in male adolescents and young adults. The authors found no significant interaction between rs6347 or rs2652511 and maternal rejection, whereas there was for rs40184 (G(2)=11.49, p=0.003). To investigate this effect further, the authors examined the interaction between


the different genotypes (CC, CT and TT) of the rs40184 polymorphism and maternal rejection. Their results indicated that those males with a TT genotype who had experienced maternal rejection had an increased likelihood of depression compared to their peers who had also experienced maternal rejection, but who were genotyped as CT or CC on the rs40184 polymorphism (Wald=7.11, p=0.005; Wald=7.11, p=0.008, respectively). CC vs TT, CT vs TT and maternal rejection on their own were not found to be significant predictors of depression (Haeffel et al 2008). Eley et al assessed the impact of three polymorphisms of 5-HT (5-HTTLPR, 5-HT2A, 5-HT2C), plus MAOA and TPH and environmental risk on depressive symptoms in adolescence. Environmental risk was assessed by the Social Problems Questionnaire, a question relating to parental education level, and the List of Threatening Events. The authors found that genotype 5-HTTLPR with a short allele predicted a decrease in depression in females (OR=0.56, 95%CI 0.32, 0.96). Similarly, in female adolescents the interaction between genotype 5-HTTLPRs short allele and environmental risk resulted in an increase of depressive symptoms (OR=2.82, 95%CI 1.12, 7.12). These results were not found in males. For genotype 5-HT2C, the authors indicated that with each additional T allele the odds of severe depressive symptoms rose with 1.61 (OR=1.61, p=0.02). There was no significant interaction between 5-HT2A and environmental risk. For both 5-HT2C and MAOA, neither the main effect nor the interaction with environmental risk was statistically significant. For the enzyme TPH, allele 5 was found to be protective in males. With each additional allele 5 the odds of developing high depressive symptoms decreased by almost half after adjusting for sex and environmental risk (OR=0.49, p=0.02). However, the interaction between allele 5 and environmental risk in males was found to be a predictor for an increase in depressive symptoms (OR=4.99, 95%CI 1.03, 24.26). It should be noted that these results came from a small group of males in the TT genotype group, and caution should be used in their interpretation (Eley et al 2004). Sjberg et al supported the results of Eley et al. The authors examined the interaction between genotype 5-HTTLPR, gender and psychosocial risk factors for depressive symptoms (Sjoeberg et al 2006). Across both sexes, levels of depressive symptoms were significantly influenced by the interaction between 5-HTTLPR and psychosocial risk (p=0.004), however, the authors noted that short 5-HTTLPR alleles

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Depression in adolescents and young adults: Evidence review

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