Major Depressive Disorder in children and adolescents (MDD)

1. Prof. Debbie van der Westhuizen Head: Child- and Adolescent Units Weskoppies Hospital Major Depressive Disorder in children and adolescents (MDD)

2. Nobody loves me

3. Overall, the clinical picture and diagnosis of MDD in children is similar to that in adults: using DSM-IV-TR criteria

4. However, a few differences in clinical description exist • Due to child’s psychosocial developmental stage • Children tend to be more irritable and have more low frustration tolerance, temper tantrums, failure to make expected weight gains, somatic complaints, hallucinations, social withdrawal instead of verbalizing feelings of depression when compared to adolescents; • Adolescents usually have more melancholic symptoms and suicide attempts

5. Subtypes of MDD: prognostic & treatment implications • MDD with psychotic features: associated with family history of bipolar- and psychotic depression; more severe depression; greater long-term morbidity, resistance to antidepressant mono-therapy and an increased risk of bipolar disorder • MDD can manifest with atypical symptoms such as increased reactivity to rejection, lethargy, (leaded paralysis), increased appetite, craving for carbohydrates, and hyper-somnia

6. Subtypes of MDD: prognostic & treatment implications • Youth with seasonal affective disorder where symptoms of depression are mainly during the season with less daylight should be differentiated from depression being triggered by school stress • Less intense than MDD is dysthymic disorder (DD); a more chronic depression (1 year); often overlooked and misdiagnosed; consists of long-term change in mood; causing more psychosocial impairment

7. Why should childhood depressive disorders be early identified and treated ? • Major depression (MDD) and dysthymia (DD) are familial, recurrent, associated with significant psychosocial morbidity (school drop-outs, substance abuse) and mortality (suicide)

8. What is your role as GP? • No biological tests are available that guide diagnosis and treatment of depressed youth • Diagnosis is based on a comprehensive evaluation with the child and other informants; parents, teachers and after-care • Taking history with main complaint and MSE (mental status evaluation) should elicit specific signs and symptoms supported by decline in academic, interpersonal, self-care and hobbies • Academic performance: barometer for mental health

9. What do we know about epidemiology? • Prevalence of MDD is 2% in children and 8% in adolescence; 10% suffer from sub-syndromal symptoms • Single most predictive risk factor for MDD is high family loading; heritability of MDD is 60% (Cradock et al, 2005)

10. What do we know about risk factors and clinical description? • Genes predispose to react to stressful negative situations with depressive symptoms • Aetiology of MDD seems to be determined by interaction of certain: 1.Genes 2.environment (support) 3.cognitive-, 4.coping style

11. What do we know about risk factors and clinical description? • Onset and recurrences of MDD may be precipitated by: losses, abuse neglect, ongoing conflicts, exposure to violence, and frustrations • Effects of stress depend on cognitive- & coping styles (rumination and hopelessness), IQ, socio-economic- and family support Stressors Support

12. Diagnostic criteria for MDD A. Depressed mood and or lost of pleasure/interest for most of the day or subjective change from previous functioning during same 2-week period; children and adolescents irritable mood B. 1. depressed mood or subjective reports (feels sad and empty) or only irritable 2. marked diminished interest or pleasure in almost all daily activities most of the day 3. significant weight loss(when not dieting) or failure to make expected weight gains 4. insomnia or hypersomnia nearly every day

13. Diagnostic criteria for MDD • Depressed mood and or lost of pleasure/interest for most of the day or subjective change from previous functioning during same 2-week period; children and adolescents irritable mood: • 5. psychomotor agitation- or retardation 6. fatigue or loss of energy 7. feelings of worthlessness 8. diminished ability to think or concentrate 9. recurrent thoughts of death, recurrent suicidal ideation

14. Diagnostic criteria for MDD C. Symptoms do not meet criteria for mixed episode D. Symptoms cause clinically distress (social, school) E. Not due to direct psychological effects of a substance, other drug or medication or GMC F. Symptoms not better accounted for by bereavement

15. Co-morbidity • MDD and DD may occur together (so called “double depression”) and either can be accompanied by medical or neurological illness

16. Depressive disorder co-morbidity • 40-90% of youth have other psychiatric disorders • Up to 50% having two or more co-morbid diagnosis

17. Prevention of onset- or recurrence of depression • Improve risk factors such as sub-syndromal symptoms of depression, underlying psychiatric disorders (anxiety-), ongoing stressful situations, parental psychopathology, marital discord, substance abuse; treat depressed moms early and vigorously • Stop the cruel cycle of: depression; that makes child irritable;- increases interpersonal conflict; other distance themselves from depressed child; loneliness and lack of support worsens • Successful treatment of mothers with depression; fewer new diagnoses and remission rates • Maternal depression associated with less response to CBT

18. The cruel bidirectional relationship of stress, conflict & depression

19. Clinical course and outcome • Median duration of MDD in clinically referred youth is 8 months; although recover from 1st episode; recurrences 60% by 1-2 years after remission and up to 70% after 5 years; continue to have MDD episodes as adults • Childhood depression (DD); protracted course, mean episode length 3-4 years; increased risk for MDD; other behaviour disorder and substance abuse; impulsivity, aggression, exposure to negative life events (early pregnancy) 20-40% develop bipolar disorder • If untreated, negative emotional, cognitive and social skills that interfere with family relationships; suicide attempts and completed suicide

20. Be aware of the following when taking history • Comprehensive evaluation includes thorough knowledge of specific developmental stages of children and adolescents, sex, race, environmental conditions, cultural- and religious background

21. Evaluation: History + MSE

22. Instruments • Standardized structured and semi-structured interviews are available for evaluation psychiatric symptoms in children > 7 years • Typically too long to use in non-research settings • Use a mood diary and mood timeline in the assessment of onset and course of mood disorders; use school years and birthdays as anchors • Mood is rated from very happy (10) to very sad (0) or irritable to non-irritable. • Also note normative-, non-normative stressors and treatments • Parent and child self-report instruments or clinician-based scales: CDRS (Children’s Depression Rating Scale) to assess severity of depression before, during and after treatment

23. Three treatment phases • Main goal: to achieve response and ultimately full symptomatic remission • Divided in 3 phases: acute, continuation, and maintenance • Choice of treatment: age, cognitive development, severity and subtype of depression, chronicity, co-morbid conditions, family-, psychiatric history, family- and social environment, preferences, culture, religion, expertise in pharmacology available, and/or psychotherapy

24. Treatment phases: achieve response and ultimately full symptomatic remission

25. Frequent follow-ups during treatment • Frequent contacts with parents • Sufficient time to monitor clinical status:symptoms of depression, suicide ideation, development of mania or hypomania, co-morbid disorders • Treatment response is the absence of MDD or significant reduction in symptom severity (50%) • The goal is to restore function and not to reduce symptoms;-lack in progress in functioning is a clue that depression is incompletely treated; or due to a co-morbid psychiatric- medical disorder or environmental factor

26. Psycho education and adherence to medication • Evaluate presence of side-effects/explain possible side-effects that may contribute to poor compliance or early discontinuation • Establish child and parent’s belief about medication benefit • History of suicidal/homicidal ideation or somatic symptoms before starting • Safety: parents to lock away medication and give daily dosages under supervision

27. Psycho education (PE): supportive management for parents & school

28. Acute treatment: psychotherapy • CBT, and IPT (interpersonal therapy) have evidence of efficacy from RCT’s (specific depressed adolescents) • Overall effect of psychotherapy for acute treatment of depressed youth are modest • CBT is effective in MDD; can be delivered effectively at PHC settings • However, in history of sexual abuse or depressed parents, CBT is not so effective

29. Acute treatment: pharmacotherapy • Efficacy: Fluoxetine showed a larger difference between medication and placebo than other antidepressants (long half life may lessen the effect of poor adherence), or studies better designed including more severe depressed patients • Optimal pharmacological treatment may involve higher dose or longer duration treatment, the lack of treatment of co-morbid conditions, some children need to receive a combination of pharmacological and psychosocial interventions

30. Findings from the TADS (Treatment for Adolescents with Depression) indicate: fluoxetine is superior to placebo for the treatment of depression in youth but is not associated with greater decreases in suicidal ideation • All groups exhibit a significant decrease in suicidal ideation34

31. Anti-depressants in Children and adolescents • US FDA’s meta-analysis of short-term placebo-controlled trails of SSRIs and other antidepressants in youth indicated: increased risk of suicide ideation or attempt • Suicidality occurred early in treatment and consisted of increased or new-onset suicidal ideation, with very few suicide attempts and no suicide completions.

32. A recent meta-analysis supports the assertion that many more youth will show a good clinical response to SSRIs than will become suicidal • Side-effects: may trigger rarely hypomania in predispose child, or worsening or onset of suicidal ideation/attempt (more so in venlafaxine) • No suicide completions were reported

33. Tips for describing anti-depressants • Inform the patient and the family about the risks and benefits of selective serotonin reuptake inhibitors; discuss black box warning • Be sure to inform family members specifically about the risk of suicide behaviour • Therapy should be started at a low dose (equivalent of 5-10mg of fluoxetine) • If needed, dose increases should be considered every 2 weeks • The food and Drug Administration recommends weekly monitoring for the first 4 weeks of antidepressant therapy and after dose adjustment

34. Common warning signs for adolescent suicide • Sudden change in behaviour • Apathy • Withdrawal • Change in eating patterns • Unusual preoccupation with death or dying • The giving away of valued personal possessions • Signs of depression • Moodiness • Hopelessness

35. Continuation phase: • Monthly follow-up (depending on clinical status) • Assess: functioning (academic & interpersonal), support systems, environmental stressors, motivation for treatment, presence of co-morbid psychiatric and medical conditions • Assess internal; as well as external conflicts that may result in relapse • If taking antidepressants, continue to foster adherence, optimize dose, evaluate for side effects

36. Maintenance treatment

37. Use of antidepressants

38. Case: Everything bothers her • Sally is a 13-year old eight grader who lives with her parents and her bother • Chief complaint: Sally is "feeling really low and irritable due to trouble with her friends” • History of present illness: Sally reports that she has been feeling down since her 7th grade, after having a big fight with her best friend

39. She started to struggle in school during the semester; falling behind; her home work required more time and effort She began to have difficulty falling asleep at night, worried about school and friends History of present illness • Eventually they reconciled but Sally felt insecure in her relationships • When school started the next year she was worried that whether they would like her

40. PHCP explained she had a depression; by the time she was taking 20mg Prozac (started on 5-10mg daily) her mood had brightened and worries had been decreasing History • Difficulty to get out of bed, tired, stomachaches, bigger appetite, craving sweets and junk food; increased isolation, falling grades, sleep schedule

41. Sally had a tough time starting school: worried about her parents forgetting to pick her up at school, being shy with peers No contributing developmental problems, delivered 38 weeks c 'section History • Although Prozac was increased to 40mg daily with weekly supportive psychotherapy, she still experienced social problems, low self-esteem and attention and gained weight after months

42. Family history: MDD in Sally's mother, father, and sibling Socially: family moved several times (dad's job), enrolled at small private school for individual attention, sibling conflict younger brother • No contributing psychiatric: learning-, disruptive disorders; obsessive compulsive disorder, substance use disorder, personality or medical problems, not sexually active, good understanding of the risk of STD

43. Mental Status Examination • Sally presented as casually dressed, mildly overweight youngster, co-operative with interview • Her speech was normal in rate, tone and volume • Her psycho-motor status was marked by considerable fidgeting • Described her own mood as “good”

44. MSE • Sally's affect was euthymic • Her thoughts were logical and goal directed • No evidence of thought blocking, insertion or deletion, or ideas of reference • Sally's thought content was remarkable for themes noted above • No perceptual abnormalities, sensorium clear, cognitive functions grossly intact, insight preserved, denied current suicidality/homocidality

45. Screening Questionnaires • Sally and her parents filled out a set a rating scales in advance of their visit. On the Children's Depression Inventory (CDI; Kovacs 1985), Sally endorsed items indicating negative self-esteem and interpersonal conflict • On the Conner's Teaching Rating Scale the teacher endorsed items indicating ADHD • ADHD symptoms also endorsed by her parents rating on Conner's Parenting Rating Scale -Revised (Conner's et al. 1998)

46. Commentaries: Psychotherapeutic Perspective • Diagnostic formulation: Diagnoses to rule out for Sally are major depressive disorder, dysthymia, social anxiety, and /or generalized anxiety and ADHD • Fairly clear symptoms of MDD: predominant depressive mood, feeling down since 7th grade, anhedonia, social withdrawal, increase in appetite, difficulty falling asleep, diminished ability to think and concentrate, feelings of fatigue/low energy; • Fidgeting during interview (psyho-motor agitation)might be evidence of MDD or ADHD

47. Assessment • Self-report scales such as the Beck Depression Inventory (Beck et al 1986) or administered CDI are useful for screening and for gauging therapy progress, but have limited usefulness as diagnostic tools • Adult respondent instruments such as the Child Behavior Checklist (Achenbach and Edelbrock 1983) or Conners' Teacher/Parent Rating Scales have similar advantages and drawbacks • My primary diagnostic information would come from a clinical interview to gauge the presence, the severity (Impairing) and duration of the symptoms of the provisional diagnoses

48. Psychopharmacologic perspective • Prior history of primarily separation and social anxiety • Beginning in the 7th grade a minor depression • Multiple characteristics that makes this adolescent a risk for depression: family history of depression, co-morbid conditions (anxiety, ADHD, minor depression) • During 8th grade she had a MDD treated with SSRIs and supportive therapy resulting in partial remission of her depression • Illustrates the importance of accurate diagnoses, interaction of co-morbid disorders, cause and consequences of illness, need for rational, evidence-based approach to treatment

49. Psychopharmacologic treatment • Primary disorder: Depression • Treatment guidelines and algorithms for depression-, anxiety disorders and ADHD are available • Well-established physician-patient-family relationship • SSRI for MDD, medication management: side-effects like apathy, sleep disturbance, or appetite changes- versus ongoing worsening of symptoms of MDD versus insufficient treatment • For adolescents: 2 adequate trails of an SSRI, switch to non-SSRI or augment with lithium or bupropion

50. Co-morbid condition (ADHD) • Clinician should consider treatment of ADHD, using ADHD treatment guidelines • Using the most effective treatment being a stimulant • The question is which treatment to initiate first; if one initiates one intervention at a time- ADHD or depression?