Antidepressants and Mood Disorders Youth to Maturity
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Antidepressants and Mood Disorders
Youth to Maturity
Kansas Osteopathic Conference April 2008
CindyRuttan DO
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If depression is creeping up and must be faced, learn something about the nature of the beast: You may escape without a mauling.
Dr. R. W. Shepherd
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Objectives Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Major Depressive Disorder (MDD)is Classified as a Mood Disorder
Mood disorders are:• Disorders that have a disturbance in mood as the
predominant feature
Mood disorders include:• Depressive disorders
• Bipolar disorders
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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Mood Disorders Can be Depressive or Bipolar
Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Mood Disorders Can be Depressive or Bipolar
Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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It's a recession when your neighbor loses his job; it's a depression when you lose yours.
Harry S Truman33rd president of the United States, 1884-1972
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Summary:Major Depressive Disorder (MDD)
MDD is a mood disorder• Diagnostic criteria include both emotional and physical symptoms
MDD is often not detected and often under-treated• MDD is prevalent in the United States
• MDD is costly to employers and children, and increases healthcare costs in the elderly
Remission is the goal of treatment• Treating all symptoms (emotional and physical) is associated with better
long-term outcomes
• Residual symptoms are often physical
Untreated MDD is associated with increased morbidity and mortality
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MDD: SIGECAPSS Sleep D/O I InterestsG Guilt E Energy
C ConcentrationA AppetiteP PsychomotorS Suicide
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Serotonin (5HT) and Norepinephrine (NE) Pathways in the Human Brain
• Most serotonin tracts originate in the raphe nuclei located in the midbrain. • Most norepinephrine tracts originate in the nuclei of the locus coeruleus located in the midbrain.
Corpus Callosum
Cingulate Gyrus
Prefrontal Cortex(Orbitofrontal Cortex)
Amygdala
Hippocampus
Raphe Nuclei
Locus Coeruleus
Thalamus
Hypothalamus
Ascending tracts for 5HT and NE
Descending tracts for 5HT and NE
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MDD (continued) Must have Depressed Mood and/or
Anhedonia, or may just be Irritability in Children for a minimum of 2 weeks with additional 4 of the 8 symptoms
Recurrent means 2 months symptom-free between episodes.
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Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
Mood Disorders Can be Depressive or Bipolar
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DSM-IV-TR Associated Symptoms of A Major Depressive Episode (MDE)
Tearfulness Irritability Brooding or obsessive rumination Anxiety or phobias Excessive worry over physical health Complaints of Pain
• Headaches
• Joint pain
• Abdominal pain
• Other pains
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:352.
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MDDCharacteristics Developmental differences:
endogenicity, melancholia, psychosis,suicide attempts, lethality of suicide attempts, and functional impairment increase with age.
Separation anxiety, phobias, somatic complaints, and behavioral problems increase with children.
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MDDCharacteristics (continued)
Psychosis•Children have more Auditory
Hallucinations*
•Adolescents and Adults exhibit more Delusions**
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Mood Disorders Can be Depressive or Bipolar
Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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DysthymiaA AppetiteC ConcentrationH HopelessE EnergyW WorthlessS Sleep D/O
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Dysthymia (continued)
Two of the six criteria and a Depressed mood for two years with no more than one month of feeling normal. Children require only one year and may just have irritable mood.
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Dysthymic DisorderCharacteristics Feelings of unresolved love, anger,
somatic, self deprecation, anxiety and disobedience.
Fewer Melancholic features compared to MDD
About 70% estimate will go on to have MDD. Both MDD / DD diagnosis is called DOUBLE DEPRESSION.
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Mood Disorders Can be Depressive or Bipolar
Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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Mood Disorders Can be Depressive or Bipolar
Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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Manic Episode/ Hypomania
D Distraction I IndiscretionsG GrandioseF Flight of ideas
A ActivityS SleepT Talkative
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Mania/Hypomania(continued)
3 of the 7 criteria with an elevated mood for one week.
4 of the 7 criteria with irritability for one week.
Hypomania: symptoms last at least four days
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Mood Disorders Can be Depressive or Bipolar
Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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Cyclothymia Depressive symptoms, yet does not
meet criteria for MDD and Hypomanic type symptoms for two years. Children: one year.
During the duration, one can not be without the symptoms for more than two months at a time.
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Mood Disorders Can be Depressive or Bipolar
Major Depressive Disorder
• Single / Chronic / Recurrent• Atypical
• Melancholic
• Catatonic
• Psychotic
• Postpartum onset
• Seasonal Dysthymic Disorder Depressive Disorder NOS
Bipolar I Disorder
• Manic / Mixed episodes
Bipolar II Disorder
• Hypomanic + Major Depression
Cyclothymic Disorder
• Hypomanic + Depressive
Bipolar Disorder NOS
Depressive Disorders Bipolar Disorders
Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
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All diagnoses must include:
Can not be accounted for by other Mental Health disorders
Not caused by a substance or GMCMust clinically cause significant
distress or impairment in social, occupational, or other important areas of function
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Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Epidemiology Depression in youth Estimated between
.4 and 2.5% Prepubertal
.4-8.3 % Adolescent(1:1/2:1 F/M)
Lifetime prevalence rate of MDD for adolescents is 15-20%(comparable to adults)
DD prevalence rate is .6-1.7% for children,1.6%-8.0% for adolescents
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Course of Disorder in Youth Mean MDD length 7-9 months 90% of MDD remit in 1.5-2 years; 6-10%
protracted MDD is recurrent: possibility of returning
is 40% within 2 years and 70% by 5 years.
BADI / II: 20-40% of adolescents with MDD develop BADI within 5 years after the onset of Depression
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Course of Disorder(continued - from youth on)
DD protracted course with mean length 4 years. Associated with inc. MDD 70%, Bipolar 13%, and Substance Abuse 15%
First episode of MDD is usually about 2-3 years after DD.
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Factors associated with Onset of MDD50% transmission in adult
twin studies suggest genetic connection. Subsequently, genetic studies point to environmental issues.
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Family Aggregation studies
• MDD
• DD Family/Environmental Stressful events Neg. Cognitive style
Biologic markers
• GH
• Serotonin
• Hypothalamic/Pit.
• Dexamethasone suppression
• ACTH Sleep
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Sequelae in youth Affects daily living MDD occurs 4-5 years prior to the onset of
substance abuse. Early identification of MDD can help prevent future substance abuse.
After recovery children and adolescents still show subclinical symptoms.
Adolescents with 2+ episodes have worse outcome.
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1. Kessler RC, et al. J Affect Disord 1993;29:85-96.2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:345-428.
Who Gets Major Depressive Disorder (MDD)? Nearly twice as prevalent in females 1
Risk factors for MDD include:2
• family history of MDD
• post partum period
• medical comorbidity
• stressful life events
• current substance abuse
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Major Depressive Disorder (MDD) is a Common Disorder in the United States
14.9% lifetime prevalence of MDD in the U.S.
• 18.6% lifetime prevalence of MDD in women
• 11.0% lifetime prevalence of MDD in men
8.6% 12-month prevalence of MDD in the U.S.
• 11.0% 12-month prevalence of MDD in women
• 6.1% 12-month prevalence of MDD in men
The prevalence of 12-month and lifetime MDD is significantly more for women vs. men (p < .05)
Kessler RC, et al. Br J Psychiatry Suppl 1996:17-30.Kessler RC, et al. Arch Gen Psychiatry 1994;51:8-19.
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Major Depression is a Major Cause of Disability World-Wide
Rank 1990 2020 (Estimated)
1 Lower respiratory infections Ischemic heart disease
2 Perinatal conditions Major Depressive Disorder
3 HIV/AIDS Road traffic accidents
4 Major Depressive Disorder Cerebrovascular disease
5 Diarrheal diseases Chronic obstructive pulmonary disease
Adapted from: Murray CJ, Lopez AD. Science 1996;274:740-743.
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Cultural Variations in the Clinical Presentation of Patients with Major Depressive Disorder (MDD) May Obscurethe Diagnosis of MDD
Psychological distress may be expressed through somatic symptoms in many cultural groups including Latinos1, African Americans2, and Asian-Americans3
These groups may be more likely to report:• Poor general health
• Impairment in physical functioning
• Multiple physical symptoms or bodily complaints
1. Escobar JI, et al. Arch Gen Psychiatry 1987;44:713-718. 2. Brown C, et al. J Affect Disord 1996;41:181-191.3. Yeung A, et al. Acta Psychiatr Scand 2002;105:252-257.
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Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Comorbidity MDD 40-70% of depressed children & adolescents
have comorbid psychiatric disorders. 20-50% have 2 or more comorbid diagnoses.
• DD and Anxiety D/O (both 30-80%)
• Disruptive D/O (10-80%)
• Substance abuse (20-30%)*
• Personality D/O (Borderline 30%)**
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Depressed Mood May Be Secondary to Another Condition Specified general medical conditions
• Prominent, persistent disturbance in mood
• Direct physiological consequence of the medical condition• Degenerative neurological conditions
• Cerebrovascular disease
• Metabolic conditions
• Endocrine conditions
• Autoimmune conditions
• Viral or other infections
• Cancer
Medication or other substance use• Prominent, persistent disturbance in mood
• Direct physiological consequence of:• Medication
• Drug Abuse
• Toxin Exposure
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:352.
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Comorbidity DD 70% have MDD 50% have pre-existing psych. history.
• 40% anxiety
• 30% conduct
• 24% ADHD
• 15% enuresis and encopresis 15% have 2 or more comorbid etio.
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Major Depressive DisorderMay Be Associated with Neuroanatomic Changes Depressed vs. Non-depressed Elderly Patients1
• Smaller hippocampal volume in depressed
• Smaller prefrontal cortex volume in depressed
Severely Depressed Patients vs. Normal Controls• Reduced hippocampal volume in depressed2
• Reduced hippocampal volume in depressed patients in remission for 4-7 months2
• Longer time that depression was untreated was significantly related to reduced total hippocampal gray matter volume3
Postmortem Studies From Depressed Patients2
• Loss and shrinkage of neurons in the prefrontal cortex
1. Bell-McGinty S, et al. Am J Psychiatry 2002;159:1424-1427. 2. Sapolsky RM. Arch Gen Psychiatry 2000;57:925-935. 3. Sheline Y, et al. Am J Psychiatry 2003;160:1516-1518.
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Patients With Major Depressive Disorder (MDD) May Deny Emotional Symptoms
50% of MDD patients in primary care settings complain of multiple unexplained somatic symptoms
11% deny psychological symptoms in primary care settings
Simon GE, et al. N Engl J Med 1999;341:1329-1335.
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Major Depressive Episodes (MDEs) Can Be Chronic and Recurrent
70
90
0
20
40
60
80
100
2 Previous MDEs 3 Previous MDEs
Ch
ance
of
Su
bse
qu
ent
Maj
or
Dep
ress
ive
Ep
iso
des
(%
)
1. Graph adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:372.
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Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Zung WW, et al. J Fam Pract 1993;37:337-344.
Clinically Significant Depressive Symptoms are Prevalent Among Primary Care Patients in the U.S.
20.9% of primary care patients have clinically significant depressive symptoms
Only 1.2% of primary care patients cited depression as the reason for their visit
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Major Depressive Disorder (MDD) is Still Largely Untreated
Kessler RC, et al. JAMA 2003;289:3095-3105.
• Only 21.6% of all MDD patients in this study received adequate treatment.
Patients with MDD in Patients with MDD in the last 12 monthsthe last 12 months
48.4% of 48.4% of patients with patients with MDD did not MDD did not receive any receive any treatmenttreatment
51.6% of patients 51.6% of patients with MDD with MDD
received some received some treatmenttreatment
58.1 % of treated 58.1 % of treated patients received patients received
inadequate inadequate treatmenttreatment
41.9 % of treated 41.9 % of treated patients received patients received
minimally adequate minimally adequate treatmenttreatment
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1. Simon GE, et al. N Engl J Med 1999;341:1329-1335. 2. Kirmayer LJ, et al. Am J Psychiatry 1993;150:734-741.
69%Present only
with physical symptoms
31%Present with psychological
and physical symptoms
Patients with Major Depressive Disorder (MDD) May Present WithOnly Physical Chief Complaints
• In an international study of 1146 patients with major depression, 69% reported only physical symptoms as the reason for their physician visit 1
• In another study, 76% of patients diagnosed with depression or anxiety made “somatic presentations” (physical complaints)2
Primary Reason for Clinical Visit as Reported by Depressed Patients1
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Adapted from: Kroenke K, et al. Arch Fam Med 1994;3:774-779.
More Physical Symptoms are Associated With a Higher Likelihood of Depressive Disorders
60%
44%
23%
12%
2%
0
20
40
60
80
0-1 2-3 4-5 6-8 9+
% o
f P
rim
ary
Car
e P
atie
nts
W
ith
Dep
ress
ive
Dis
ord
ers
Number of Physical Symptoms (N=1000)
• Common physical symptoms included fainting, menstrual problems, headache, chest pain, dizziness, palpitations, sexual problems, GI symptoms (nausea, vomiting, gas, or indigestion, constipation, diarrhea), abdominal pain, dyspnea, fatigue, insomnia, joint or limb pain, and back pain.
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Major Depressive Disorder Increases Morbidity and Mortality From Other Medical Conditions
Increased mortality after stroke1
• Comorbid depression increased the risk of death by 13%
Reduced survival after heart failure2
• Comorbid depression doubled the death rate
Risk factor for cardiac mortality and morbidity3
• Comorbid depression was associated with a fourfold increase in the risk of mortality in the 6 months post myocardial infarction
1. Williams LS, et al. Am J Psychiatry 2004;161:1090-1095. 2. Faris R, et al. Eur J Heart Fail 2002;4:541-551.3. Carney RM, et al. J Psychosom Res 2002;53:897-902.
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Major Depressive Disorder (MDD) in Adults is Costly to Children MDD mothers were more likely than non-MDD
mothers to:1
• Report that children have serious emotional problems (3 times as likely)
• Not have children treated for problems (4 times more likely)
• Have discord with their children (10 times more likely)
Maternal depression in prenatal and postnatal period predicts poorer growth in a community sample of infants2
1. Weissman MM, et al. J Affect Disord 2004;78:93-100.2. Rahman A, et al. Arch Gen Psychiatry 2004;61:946-952.
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Treating Major Depressive Disorder (MDD) Reduces Health Care Costs in Elderly Treating elderly patients for diagnosed MDD
reduced the cost of medical services1
Treating elderly patients for all diagnosed mental health disorders lowered inpatient costs for patients admitted for non-psychiatric medical or surgical services2
1. Unutzer J, et al. JAMA 1997;277:1618-1623.2. Kominski G, et al. Med Care 2001;39:500-512.
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The 2002 U.S. Preventive Services Task Force Report Recommended Screening Adults For Depression
Screening for depression will:• Improve detection
• Improve patient outcomes
A simple two-question depression screener is a helpful tool for identifying depression
• In the past 2 weeks, how often have you been bothered by any of the following problems?
• Little interest or pleasure in doing things
• Feeling down, depressed, or hopeless
Thibault JM, et al. Am Fam Physician 2004;70:1101-1110.
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Assessment summary
Evaluate symptoms: labs recommended Interview patient and other contacts Becks Depression Inventory, Children’s
Depressive Inventory---screeners for symptoms.
NO BIOLOGIC TEST USEFUL TO DIAGNOSE MDD OR DD
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Major Depressive Disorder is Costly to U.S. Employers
$31 billion in total lost productive time per year1
• $27 billion lost productive time due to reduced performance while at work (presenteeism)
• $4 billion lost productive time due to absenteeism
Workers with depression use more short term disability than the average for all other causes2
1. Stewart WF, et al. JAMA 2003;289:3135-3144.2. Greenberg PE, et al. J Clin Psychiatry 2003;64 (Suppl 7):17-23.
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Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Treatment OptionsPsychosocial InterventionsPsychopharmacology
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Drug/CBT Combo(Psychiatric News vol. 39 #7 9/3/2004 again March 2,2007)
TADS (NIMH Treatment of Adolescent Depression Study) Appears that CBT helps as a buffer to suicidal thoughts which were thought to be increased by some SSRIs alone.
All patients must be monitored closely if prescribed a medication.
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Treatment OptionsPsychosocial InterventionsPsychopharmacology
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Phases of Treatment Response in Major Depressive Disorder (MDD)
Kupfer DJ. J Clin Psychiatry 1991;52 (Suppl):28-34.
RelapseReturn of
symptoms meeting the
criteria for MDD prior to recovery
Mo
od
Imp
rove
men
t
Asymptomatic
Symptoms
Syndrome Response50% Improvement
from Baseline
RemissionMinimal Symptoms,Normal Functioning
RecoveryLong-term Remission
RecurrenceNew Episode
of MDD
Treatment Phases: Acute 12 weeks
Continuation4-9 Months
Maintenance >1 Years
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Remission of Major Depressive Disorder is the Goal of Treatment
Remission is:
• Minimal to no residual symptoms • Low scores on scales used to track depression
severity in research settings 17-item HAMD 7
MADRS < 10
• Function restored
Depression Guideline Panel. Depression in Primary Care: Vol 2. Treatment of Major Depression: Clinical Practice Guideline Number 5. Rockville, MD: AHCPR, US Department of Health and Human Services; 1993:23.
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Remission With No Residual Symptoms Reduces the Risk of Relapse for Major Depressive Disorder (MDD)
For Patients Achieving Remission of MDD (as measured by Research Diagnostic Criteria)
• Patients with residual symptoms relapsed 3 times as fast compared to those who were asymptomatic at remission
• Almost 3 times as many patients without residual symptoms at remission remained well compared to those with residual symptoms
Judd LL, et al. J Affect Disord 1998;50:97-108.
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Treatment Options for Major Depression Include Pharmacological and Non-Pharmacological Therapies Pharmacological Therapy
• Selective Serotonin Reuptake Inhibitors (SSRI)
• Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRI)
• Mixed Reuptake Inhibitors (bupropion)
• Mixed Selective Serotonin Reuptake Inhibitors and Receptor Blockers (mirtazepine, nefazodone)
• Tricyclic Antidepressants (TCA)
• Monoamine Oxidase Inhibitors (MAOI)
Non-Pharmacological Therapy• Psychotherapy
• Cognitive Behavioral Therapy (CBT)
• Interpersonal Therapy (IPT)
Hales RE, Yudofsky SC, eds. Textbook of Clinical Psychiatry, 4th ed. Arlington, VA: American Psychiatric Publishing, Inc; 2003:491-503.
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Antidepressant Rx Patterns in Children and Adolescents
Nationwide database retrospective exam from 1998-2002 looking at antidepressant use.
Ambulatory claims for random sample of more than 1.9 million life years of commercially insured ages 18 and younger.
Overall increase from 1.6% in 1998 to 2.4% in 2002
Higher among girls (68%) than boys (34%)
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Antidepressant Rx Patterns(continued)
The trend seems to be driven by the use of SSRIs. The use of TCAs dropped by 29%
Conclusion: Use prevalence continues to grow and is similar to the rate of increase seen in second generation antidepressants.
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No antidepressant except Prozac has been FDA approved in children
or adolescentsfor depression diagnosis
All other medications discussed will be off label
use.
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TCA in youth 60-80% respond. However, all controlled double blind studies
showed no statistical difference between Placebo and TCA, except one study by Preskorn.
Geller’s study found 31% respond to Nortriptyline and 17% to placebo; other trials found 50% response to both TCA and Placebo.
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FDA WARNING 3/22/2004 Requested pharmaceutical companies to
modify labels on the following medications for close observation of adults and children taking these medications.
Concerned with worsening of depression and suicidality initially in treatment and during modification in dosage.
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Could the warnings cause the rise in adolescent suicide?Psychiatric News Vol.42 No.5 March 2,2007
Suicide in Youth ages 1-19yrs increased from 2003 to 2004 by 18.2%
Media started to talk about med side effects in 2003 thus noted a 20% decline in meds written for this age group.
CDC reported suicide from ages 1-19yrs in ‘03 = 2.2 per 100,000 or 1737 deaths
’04 = 2.6 per 100,000 or 1,985 deaths
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Suicide info continued from ’03-’04 Ages 10-14 increased by 8.3%
1.2 per 100,000 (244 suicides) to
1.3 per 100,000 (283 suicides) Ages 15-19 increased by 12.3%
7.3 per 100,000 (1487 suicides) to
8.2 per 100,000 (1700 suicides)
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FDA panel should Specify Benefits as Well as Risks
Psychiatric News vol. 42 #2Jan19,2007
PDAC recommended Increased age range to about 25
related to suicide risks Protective effect for older patients
particularly over 65 Danger of untreated mental illness
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Clinical Trial Controversy Psychiatric News Vol. 39 #14 7/16/2004
Ongoing controversy surrounding SSRIs in child psychiatry is threatening the foundation of clinical research regarding all drugs physicians prescribe. Not limited to Mental Health meds.
Selective data, skewed profiles, and integrity of the researcher have all been in question.
No immediate resolution in sight. The only known information is from trials which favor the drugs, not placebos. Failed trials don’t necessarily mean drugs are not effective.
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SSRI Prozac (fluoxetine) Paxil (paroxetine) Zoloft (sertraline) Luvox (fluvoxamine #) Celexa (citalopram) Lexapro (escitalopram)
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Other Antidepressants
Wellbutrin (buproprion)Effexor (venlafaxine)Serzone (nefazadone)Remeron (mirtazapine)MAOI (EMSAM,Nardil,etc.)
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MAOI (transdermal patch)
Only the 6mg dose possibly may not require dietary restrictions.
IF it STINKS don’t eat it !! (see the info on package insert)
Drug to Drug or Drug to OTC med interactions. Contraindications: sympathomimetics, carbamazepine, oxcarbazepine and various others…
Waiting periods to stop and start use of drug trial which could be contraindicated if used at the same time. (see package insert)
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Other MedicationsLithiumDepakoteTegretolNeurontinLamictalTrileptal
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Other Medications (continued)
Hormone Replacement TherapyThyroidAtypical/Typical Antipsychotic
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Start low, go slow with any upward or
downward titrations.
Taper off dosages; try not to just stop the medications-
provide the smallest quantity
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Various New Warning Labels Recommended by FDA
All drug manufacturers must submit data to the FDA on post-marketing adverse events in pediatric population.
No conclusive link to fetal toxicity. However, due to neurological, neuromuscular and autonomic effects in newborns subjected to: Prozac, Paxil, Celexa,Zoloft, Luvox and Effexor…
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Infants experienced symptoms of possible withdrawal
Excited agitation, irritability, trouble feeding, sleep problems.
Respiratory distress, cyanosis, apnea, seizures, hypertonia, hyperreflexia and tremor.
So far, no public advisory is recommended. More research is needed. Do not want to scare pregnant patients into not being treated. Yet, the committee voted for ALL SSRIs and SNRIs to have words like ….
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Suggested labeling as such…(Psych NewsVol.39No#14 7-16-04 pg.33)
Neonates exposed to SSRIs/SNRIs late in third trimester may develop adverse events (AE) requiring longer hospitalization, respiratory support, tube feeding. These AE may arise immediately after delivery.
Recommended to taper the dose of meds during the last trimester so the fetus receives no drug via placenta for 7-10 days prior delivery.
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Indications for Referral to a Specialist for the Treatment of Major Depressive Disorder Active suicidality
• Requires emergency treatment
• Requires hospitalization
Unclear diagnosis Severe psychotic or severe bipolar depression Complex comorbid psychiatric conditions Failure to respond or remit Psychotherapy needed Electroconvulsive Therapy (ECT) Needed
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Definitions Characteristics/Symptoms Epidemiology Comorbidity/Clinical course Assessment/Evaluation Treatment Options SUICIDE UPDATE
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Suicidewww.teenscreen.org
3rd leading cause of death among adolescents in 2001 behind accidents and homicide. Incidence of suicidal ideation is much greater.
Nearly two-thirds of those who kill themselves showed psychiatric symptoms more than one year prior to their death.
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Suicides/Attempts Adolescent rate has quadrupled since 1950. This
represents 12% of total mortality in this age group.
Attempts have increased to have one year and lifetime rates of 1.7 to 5.9%, and 3.0 to 7.1% respectively.
Predisposing factors: Anxiety, disruptive behavior, bipolar, substance abuse, personality D/O, family history of mood D/O, previous attempts, impulsivity, available methods….
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Suicide Questions (Current Psychiatry Vol. 3 #7 July, 2004)
What method used?• Purchase or use something
available
• Take all or only a portion. Why did they stop?
• What did they expect to happen? What amount used? What treatment was needed? Planned or impulsive? Risk-Rescue ratio… Thoughts about attempt…
Past attempts?
Mental state of patient.. angry,relaxed…
Access to weapons Contract for safety Social, MH support,
changed situation? Intoxication Willingness to contract Attention seeking Borderline
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Take Home Message
Do a complete evaluation
interview with various informants when possible
Baseline labs ---don’t overlook a GMC
Review all present meds including OTC and HERBAL Use what you are familiar with and do a adequate medication trial
SSRI’s min.30 days at reasonable dose
TCA’s obtain levels and EKG’s ASK Questions regarding Suicide or Homicide and Self mutilation----if yes
refer to hospital. Educate the client and Family about the diagnosis –realize with a child/adol.
there maybe more than one diagnosis and some maybe” provisional “. Llimited medication is FDA approved for Child/Adol. MDD/DD.
REFER to a psychiatrist if in doubt !!
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The Bluebird of Happiness long absent from his life, Ned is visited by the Chicken of Depression.
Gary Larson
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References The Psychiatric Interview (Carlat) Clinical Psychiatric News April 2004 pg. 43
(Steve Perlstein) DSM IV Child and Adolescent Psychiatry 2nd ed.
(Dulcan and Martini) Journal of Child and Adolescent Psychiatry
Nov. 1996, 35:11, and Dec. 1996 35:12
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References Cont- AACAP Member Notice Regarding FDA
• Internet resource
Psychiatric News• Vol, 39 no. 5 3/5/2004
• Vol. 39 no. 6 4/16/2004
Clinical Psychiatry News• Vol. 32 no. 4 April 04
• Vol. 32 no. 5 May 2004
FDA Talk Paper 10/27/2003 FDA Public Health Advisory 10/27/2004
• Internet resource
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References Cont- Psychiatric Times
• Sept. 1999 Vol. XVI Issue 9 Psychiatric Services
• Vol. 55 No. 4 pgs. 387-391 Current Psychiatry
• Vol. 3 no. 3 Mar 2004 pgs. 83-89 AACAP News
• April 2004 Vol.35 Issue 2 pgs.49-51 Lillymedical.com (selected MDD slides)
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References cont. Reviews in child and adolescent psychiatry
Chapters 5 and 6 pgs(35-54) reprint from AACAP journal 1998
Psychopharmacology of Antidepressants
Stephen Stahl MD PHD reprint 1998 Child and Adolescent clinical
psychopharmacology 3rd ed. Wayne Hugo Green 2001
Clinical Child Psychiatry Klykylo Kay Rube 1998