Major Depressive Disorder in children and adolescents MDD

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

Nobody loves me

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

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

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

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

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)

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 aftercare • 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

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)

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

What do we know about risk factors and clinical description? Stressors Support • 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

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

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. 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

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

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

Depressive disorder co-morbidity • 40 -90% of youth have other psychiatric disorders • Up to 50% having two or more co-morbid diagnosis 1 st Anxiety disorders 2 nd Disruptive behaviour disorders 3 rd ADHD, substance use disorders

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

The cruel bidirectional relationship of stress, conflict & depression Stress- others distance themselves, more lonely Interpersonal conflict increases Depression makes child irritable

Clinical course and outcome • Median duration of MDD in clinically referred youth is 8 months; although recover from 1 st 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

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 Race Child’s developmental stage Culturalbackground Sex Environmental conditions Religiousbackground Psych evaluation

Evaluation: History + MSE Exclude pregnancy (females), HIV, STDs substance abuse: ucannabis, party screen on blood, effects of steroids Exclude general medical conditions: hypothyroidism, mononucleosis, anemia, cancer, autoimmune, premenstrual dysphoric disorder Co-morbid psychiatric conditions; psychosis; reactions to bereavement and other stressors Knowledge of signs and symptoms of MDD in children and adolescents Evaluate suicidal- selfharm-, homicidal risk; with child & parents; and need for hospitalization

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 nonirritable. • 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

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

Treatment phases: achieve response and ultimately full symptomatic remission Acute: to achieve response Continuation: consolidate response, avoid relapses Maintenance: to avoid recurrences or new episodes

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

Psycho education and adherence to medication • Evaluate presence of side-effects/explain possible sideeffects 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

Psycho education (PE): supportive management for parents & school Parent counselling & training, support groups Improves families of depressed parents ability to solve problems Educate family and school about depression Advocate school to accommodate child until better; workload Collaborate parent, child, teachers as part of MDT

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

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

• 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 ideation 34

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.

• 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

Tips for describing antidepressants • 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 510 mg 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

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

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

Maintenance treatment MDD+DD, subsyndromal symptoms of depression, other psychiatric or medical conditions, psychosis Asymptomatic for 6 -12 months: which therapy and how long >2 episodes of depression or severe chronic depression for one year or longer Availability of physician suicidality, past or ongoing stressors (abuse, divorce, conflicts)

Use of antidepressants Dosages similar to adults, weekly visits first 4 w Clinical response 4 -6 weeks Youth with MDD; monitor for suicide, mania in +family Start low dose, increase slowly, taper slowly SSRIs; shorter halflives; once daily withdrawal

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 7 th grade, after having a big fight with her best friend

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

History Although Prozac was increased to 40 mg daily with weekly supportive psychotherapy, she still experienced social problems, low self-esteem and attention and gained weight after months 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

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 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

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”

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

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 symptoms also endorsed by her parents rating on Conner's Parenting Rating Scale -Revised (Conner's et al. 1998)

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 7 th 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

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

Psychopharmacologic perspective Prior history of primarily separation and social anxiety Beginning in the 7 th 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 8 th 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, evidencebased approach to treatment

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

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?

Continuation treatment Recommended continuation treatment for depression is 69 months During continuation therapy aggressive treatment of residual symptoms is recommended because of an increased chance of relapse Treatment of residual symptoms: pharmacological plus CBT or IPT Accurate diagnosis and assessment are essential, treatment should be rational, systematic, sequential, integrating different modalities to optimize outcome

Integrative perspective Medical approach: Sally meets the DSM-IV-TR diagnostic criteria for MDD symptoms have been present for 6 months; prominent mood symptoms include a depressed mood most of the day; an irritable mood when stressed or provoked; prominent neurovegetative symptoms include weight gain, insomnia, diminished ability to think or concentrate, fatigue; experiencing the symptoms at home, school and with peers

Depression and anxiety interact Diagnostic interview also establishes that Sally meets criteria for anxiety disorder NOS- she is intolerant of being alone and when she feels anxious she tries to relief emotional stress by excessive social interaction with friends by “harassing” them and driving them away; which in turn drives isolation Lastly, she meets criteria for previously undiagnosed ADHD

Treatment recommendations Built around the need for additional assessments, recommendations for psychosocial interventions, medication management, and both educational- and behavioral interventions in school Importantly, interventions of choice are explicitly evidence-based

Psychotherapy Empirical literature strongly suggests that Sally will do best if symptom picture is skillfully addressed using proven psycho-social interventions; tightly linked to their target symptoms The therapist in this model functions as a coach or mentor to implement a treatment that operates both at psychological level and on the somatic substrate: CBT (cognitive restructuring and conflict reduction) for depression and anxiety management training (exposure, cognitive restructuring, positive reinforcement) Participate in social activities (drama club or sport) Parent management training to modify negative reinforcement

Medications Unlikely to make any significant progress even with skillful CBT without psychopharmaco-therapy Careful attention to time response and dose-response A trail of atomoxetine for ADHD (medication should cover both depression and anxiety); Facilitate the implementation of CBT

Academic performance Sally was doing well at school; work has been more challenging because of her poor attention With permission of her family, therapist should update the school about her treatment so teachers will be aware and might help with cognitive-behavioral interventions

Major depressive disorder and death of a loved one • Death of significant other or close family member: • Assess the grieving parent to determine whether he/she has adequately coped with the loss of the wife/husband can adequately deal with son’s grief • If adolescent is suffering from MDD and complicated bereavement; started with SSRI and psychotherapy • Depressed children start with self-medication (drugs) • Suicidal ideation/ attempts are generally rare among children with uncomplicated bereavement but may occur as a feature of complicated bereavement

The End Any questions?