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Larry J. Witmer, D.O.
C.O.R.E. Clinical Professor
of Family Medicine
UH Aurora Family Medicine
A Modern Epidemic:A Modern Epidemic:Depression and Depression and
AnxietyAnxiety
ObjectivesObjectivesReview the definition and diagnostic Review the definition and diagnostic
signs and symptoms of GAD/MDDsigns and symptoms of GAD/MDDReview HAMD scale for depressionReview HAMD scale for depressionReview prevalence and comorbidities Review prevalence and comorbidities
of GAD/MDDof GAD/MDDReview neurobiology of GAD/MDDReview neurobiology of GAD/MDDDiscuss effective medical, non-Discuss effective medical, non-
medical, and alternative medical, and alternative management of GAD/MDDmanagement of GAD/MDD
DEPRESSIONDEPRESSION
DSM-IV Definition of DepressionDSM-IV Definition of Depression(“SIG E CAPS”)(“SIG E CAPS”)
Sleep disturbance that includes Sleep disturbance that includes insomnia or hypersomniainsomnia or hypersomnia
Interest diminished or lack of Interest diminished or lack of pleasure in almost all activities most pleasure in almost all activities most of the day, nearly every dayof the day, nearly every day
Guilt or feelings of worthlessnessGuilt or feelings of worthlessness Energy is lacking nearly dailyEnergy is lacking nearly daily
DSM-IV Definition of DepressionDSM-IV Definition of Depression(“SIG E CAPS”)(“SIG E CAPS”)
Concentration lacking with a diminished Concentration lacking with a diminished ability to think, or indecisivenessability to think, or indecisiveness
Appetite change or unintentional weight Appetite change or unintentional weight loss or gain (≥5% of body weight in a loss or gain (≥5% of body weight in a month)month)
Psychomotor agitation or retardationPsychomotor agitation or retardation Suicidal ideation that can include recurrent Suicidal ideation that can include recurrent
thoughts of deaththoughts of death
Diagnosing DepressionDiagnosing Depression
• Major Depression Major Depression ((>> 2 weeks) 2 weeks)
• Minor Depression Minor Depression ((>> 2 weeks) 2 weeks)
• Dysthymia ((>> 2 years) 2 years)
• ≥5 depressive symptoms, including depressed mood or inability to experience pleasure, causing significant impairment in social, occupational, or other important areas of functioning
• 2 to 4 depressive symptoms, including depressed mood or inability to experience pleasure, causing significant impairment in social, occupational, or other important areas of functioning
• 3 or 4 dysthymic symptoms, including depressed mood, causing significant impairment in social, occupational, or other important areas of functioning
Depression Depression –– The Physical PresentationThe Physical Presentation
Somatic symptoms frequently Somatic symptoms frequently accompany depressionaccompany depression
Depressed patients can present Depressed patients can present with ONLY somatic symptomswith ONLY somatic symptoms
90% depressed patients report 90% depressed patients report comorbid anxiety symptomscomorbid anxiety symptoms
Reference:1. Simon GE, et al. N Engl J Med. 1999;341(18):1329-1335.
Depression Depression –– The Physical PresentationThe Physical Presentation
In primary care, physical symptoms are often the chief complaint in depressed patients
N = 1146 Primary care patients with major depression
In a New England Journal of Medicine study, 69% of diagnosed depressed patients reported unexplained physical symptoms as their chief compliant1
Depression Assessment ToolsDepression Assessment Tools
Patient AdministeredPatient Administered Beck Depression Inventory-II (BDI-II)Beck Depression Inventory-II (BDI-II) Inventory of Depressive Symptomatology (IDS)Inventory of Depressive Symptomatology (IDS) Quick Inventory of Depressive Symptomatology (QIDS)Quick Inventory of Depressive Symptomatology (QIDS) Zung Self-Rating Depression Scale (SDS)Zung Self-Rating Depression Scale (SDS)
Physician AdministeredPhysician Administered Hamilton Rating Scale for Depression (HAMD)Hamilton Rating Scale for Depression (HAMD) Montgomery-Asberg Depression Rating Scale (MADRS)Montgomery-Asberg Depression Rating Scale (MADRS) Cornell Dysthymia Rating Scale (CDRS)Cornell Dysthymia Rating Scale (CDRS) Center for Epidemiologic Studies Depression Scale Center for Epidemiologic Studies Depression Scale
(CES-D)(CES-D)
The Hamilton Rating Scale forDepression
17-item and 14-item versions of symptoms covering:depressed mood, feelings of guilt, suicide, early insomnia, middle insomnia, late
insomnia, difficulty with work & activitiespsychomotor retardation, agitation,
psychologicalanxiety, somatic anxiety, change in appetite,somatic symptoms (backache, headache,
muscle aches, heaviness in limbs) loss of energy, genital symptoms loss of weight, insight, diurnal variation
The Hamilton Rating Scale forDepression
Scoring is on a 3-point to a 5-point scale; add all items for a total score
The higher the score, the worse the depression:10 to 13 = mild14 to 17 = mild to moderate>17 = moderate to severe
ANXIETYANXIETY
DSM-IV Definition of Anxiety DSM-IV Definition of Anxiety
Persistent worry that is excessive and Persistent worry that is excessive and that the patient finds hard to controlthat the patient finds hard to control
work responsibilities, money, health, safety, work responsibilities, money, health, safety, car repairs, and household chores car repairs, and household chores
3 of 6 symptoms usually present3 of 6 symptoms usually present1.1. High levels of muscle tensionHigh levels of muscle tension2.2. IrritabilityIrritability3.3. Difficulty concentratingDifficulty concentrating4.4. Sleep disturbancesSleep disturbances5.5. RestlessnessRestlessness6.6. Easily fatiguedEasily fatigued
DSM-IV Definition of AnxietyDSM-IV Definition of Anxiety
Interference with work, family life, social Interference with work, family life, social activities, or other areas of functioningactivities, or other areas of functioning
Worry is out of proportion in its duration Worry is out of proportion in its duration or intensity to the actual likelihood or or intensity to the actual likelihood or impact of the feared situation or event impact of the feared situation or event
Frequently develop stress related Frequently develop stress related physical illnesses such as:physical illnesses such as:
1.1. IBSIBS2.2. TMJTMJ3.3. Bruxism (grinding teeth during sleep)Bruxism (grinding teeth during sleep)4.4. HTNHTN
Onset of AnxietyOnset of Anxiety Insidious onset that can begin relatively Insidious onset that can begin relatively
early in life, although it can be early in life, although it can be precipitated by a sudden crisis at any precipitated by a sudden crisis at any age above 6-7 years of ageage above 6-7 years of age
Many will say that they cannot Many will say that they cannot remember a time in their lives when remember a time in their lives when they were not worried about somethingthey were not worried about something
Not unusual for people to develop GAD Not unusual for people to develop GAD in their early adult years or even later in their early adult years or even later in reaction to chronic stress or anxiety-in reaction to chronic stress or anxiety-producing situations producing situations
Onset of AnxietyOnset of Anxiety
Disorders typically develop in childhood or Disorders typically develop in childhood or adolescenceadolescence
By the age of 16 years, approximately By the age of 16 years, approximately 10% of young people will have an anxiety 10% of young people will have an anxiety disorder of some type, with most occurring disorder of some type, with most occurring in femalesin females
Those who already have comorbid social Those who already have comorbid social anxiety disorder and MDD are nearly 9x anxiety disorder and MDD are nearly 9x more likely to have a recurrence of MDD more likely to have a recurrence of MDD and are 6x more likely than the general and are 6x more likely than the general population to attempt suicidepopulation to attempt suicide
157th Annual Meeting of the American Psychiatric AssociationConference Dates: 2004-05-02 to 2004-05-06
Location: New York, NY,USA
AnxietyAnxiety
Incidence rising in the U.S.Incidence rising in the U.S. Worse over past several years due to Worse over past several years due to
economyeconomy One of the most common mental health One of the most common mental health
problemsproblems Significant public health implicationsSignificant public health implications
Frequency with which they occurFrequency with which they occur Persistence of some associated Persistence of some associated
conditionsconditions Disability associated with themDisability associated with them
Comorbidity and Its Comorbidity and Its RelevanceRelevance
Depression comorbid with Depression comorbid with AnxietyAnxietyMask GAD symptomsMask GAD symptomsHamper GAD diagnosis and Hamper GAD diagnosis and
treatmenttreatmentExacerbate GAD symptomsExacerbate GAD symptoms
157th Annual Meeting of the American Psychiatric Association
Conference Dates: 2004-05-02 to 2004-05-06Location: New York, NY,USA
Comorbidity of GAD/MDDComorbidity of GAD/MDD
Psychiatric comorbidity is a concern Psychiatric comorbidity is a concern because it is associated with greater because it is associated with greater functional impairment and more functional impairment and more extensive utilization of health extensive utilization of health servicesservices
People with comorbid anxiety and People with comorbid anxiety and depression are slower to respond to depression are slower to respond to both psychotherapy and both psychotherapy and pharmacologic interventionpharmacologic intervention
Neurobiology of Neurobiology of Depression and Depression and
AnxietyAnxiety
SerotoninSerotonin5HT5HT and and NorepinephrineNorepinephrineNENE in the brain in the brain
Limbic System
Locus Ceruleus (NE Source)
Prefrontal Cortex
Raphe Nuclei (5-HT source)
Cooper JR, Bloom FE. The Biochemical Basis of Neuropharmacology. 1996.
The neurotransmitter The neurotransmitter pathwaypathway
Adapted from References:
1. Stahl SM. J. Clin Psych. 2002;63:203-220.
2. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.
3. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.
Dysregulation of Serotonin (5HT) Dysregulation of Serotonin (5HT) and Norepinephrine (NE) in the and Norepinephrine (NE) in the brain are strongly associated with brain are strongly associated with depression depression
Dysregulation of 5HT and NE in Dysregulation of 5HT and NE in the spinal cord may explain an the spinal cord may explain an increased pain perception among increased pain perception among depressed patientsdepressed patients1-31-3
Imbalances of 5HT and NE may Imbalances of 5HT and NE may explain the presence of both explain the presence of both emotional and physical symptoms emotional and physical symptoms of depression.of depression.
It’s not all in your head
Descending Pathway
Ascending Pathway
AscendingPathway
DescendingPathway
NeurobiologyNeurobiology
One hopeful aspect of the treatment of One hopeful aspect of the treatment of anxiety disorders is that some anxiety disorders is that some antidepressant treatments, which may be antidepressant treatments, which may be used in patients with comorbid anxiety used in patients with comorbid anxiety and depression, promote neurogenesisand depression, promote neurogenesis
Primates have reduced levels of Primates have reduced levels of neurogenesis throughout life, so the neurogenesis throughout life, so the neurogenic potential of certain therapies neurogenic potential of certain therapies has implications for the treatment of has implications for the treatment of anxietyanxiety
There are at least two sides There are at least two sides to the neurotransmitter storyto the neurotransmitter story
Sex
Appetite
Aggression
Concentration
Interest
Motivation
Depressed Mood
Anxiety
Irritability
Thought process
References:
1. Adapted from: Stahl SM. In: Essential Psychopharmacology: Neuroscientific Basis and Practical Applications: 2nd ed. Cambridge University Press 2000.
2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.
3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35.
4. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.
Norepinephrine (NE)
• Both serotonin and norepinephrine mediate a broad Both serotonin and norepinephrine mediate a broad spectrum of depressive symptomsspectrum of depressive symptoms
Serotonin (5-HT)
Vague Aches and pain
Functional domains of Serotonin and Norepinephrine1-4
Neurobiology of Anxiety and Neurobiology of Anxiety and DepressionDepression
Summary:Summary: Anxiety disorders commonly lead to MDD Anxiety disorders commonly lead to MDD
and MDD is frequently comorbid with GADand MDD is frequently comorbid with GAD Functional anatomy of anxiety and Functional anatomy of anxiety and
depression involves (among others) the depression involves (among others) the interaction between multiple areas of the interaction between multiple areas of the brain which are complex for which studies brain which are complex for which studies continuecontinue
Neurochemistry of GAD/MDD involves Neurochemistry of GAD/MDD involves brainstem 5-HT and NE systemsbrainstem 5-HT and NE systems
Optimal Treatment of Optimal Treatment of Depression and Depression and
AnxietyAnxiety
MedicationsMedicationsPsychotherapyPsychotherapy
Importance of Long Term Importance of Long Term TreatmentTreatment
33% of patients discontinue 33% of patients discontinue therapy within the first monththerapy within the first month
44% of patients discontinue 44% of patients discontinue therapy within the first 3 monthstherapy within the first 3 months
Masand, Clin Ther. 2003; Hamilton, Br J Clin PharmacolMasand, Clin Ther. 2003; Hamilton, Br J Clin Pharmacol
SSRI Treatment for MDD and SSRI Treatment for MDD and GADGAD
DepressionDepression Citalopram (Celexa)Citalopram (Celexa) Escitalopram Escitalopram
(Lexapro)(Lexapro) Venlafexine (Effexor)Venlafexine (Effexor) Duloxetine (Cymbalta)Duloxetine (Cymbalta) Paroxetine (Paxil)Paroxetine (Paxil) Fluoxetine (Prozac)Fluoxetine (Prozac) Sertraline (Zoloft)Sertraline (Zoloft) Vilazodone (Viibryd)Vilazodone (Viibryd) Fluvoxamine (Luvox)Fluvoxamine (Luvox)
AnxietyAnxiety Escitalopram Escitalopram
(Lexapro)(Lexapro) Venlafexine Venlafexine
(Effexor)(Effexor) Paroxetine (Paxil)Paroxetine (Paxil) Fluoxetine (Prozac)Fluoxetine (Prozac) Sertraline (Zoloft)Sertraline (Zoloft)
Is there a need to protect patients from Is there a need to protect patients from treatments only proven to have short-term treatments only proven to have short-term
efficacy?efficacy? Effective medications are frequently discontinued over Effective medications are frequently discontinued over
relatively short time periodsrelatively short time periods Most patients using medications long-term are those who Most patients using medications long-term are those who
responded acutely and either perceive continued benefit responded acutely and either perceive continued benefit or have suffered recurrence when attempting to taperor have suffered recurrence when attempting to taper
Based on Altshuler et al. AJP.
2003
Discontinues afteracute response
Lack of efficacy
Continues long-termtreatment
Few get long-term treatment in the real world
Alternative and complementary Alternative and complementary therapies of MDD/GADtherapies of MDD/GAD
1.1. Hypnotherapy/music therapyHypnotherapy/music therapy2.2. Osteopathic manipulative therapyOsteopathic manipulative therapy
2001 JAOA study in postpartum women, 8 2001 JAOA study in postpartum women, 8 weeks of OMT revealed 100% improvement weeks of OMT revealed 100% improvement with follow up evaluationwith follow up evaluation
3.3. Ayurvedic medicine Ayurvedic medicine Holistic system of healing which evolved in Holistic system of healing which evolved in
ancient India some 3000-5000 years ago ancient India some 3000-5000 years ago focusing on life energies and balancefocusing on life energies and balance
4.4. YogaYoga5.5. Religious practiceReligious practice6.6. Guided imagery meditationGuided imagery meditation
Alternative and complementary Alternative and complementary therapies of MDD/GADtherapies of MDD/GAD
In the United States, over 40% of In the United States, over 40% of consumers used a complementary consumers used a complementary therapy over the course of the last yeartherapy over the course of the last year
BiofeedbackBiofeedback and and relaxation techniquesrelaxation techniques to lower physiologic arousalto lower physiologic arousal
Massage therapy, hydrotherapy, shiatsu, Massage therapy, hydrotherapy, shiatsu, and acupuncture have been reported to and acupuncture have been reported to relieve muscle spasms or soreness relieve muscle spasms or soreness
An herbal remedy that has been used in An herbal remedy that has been used in clinical trials for treating GAD is clinical trials for treating GAD is passionflowerpassionflower ( (Passiflora incarnataPassiflora incarnata))
Alternative and complementary Alternative and complementary therapies of MDD/GADtherapies of MDD/GAD
St. Johns WortSt. Johns Wort May be effective in helping to support May be effective in helping to support
depressed mood and mood fluctuations by depressed mood and mood fluctuations by maintaining the balance of Serotonin, maintaining the balance of Serotonin, Norepinephrine, Dopamine and GABANorepinephrine, Dopamine and GABA
ZincZinc An essential mineral found in almost every An essential mineral found in almost every
cell cell Depression may be connected with low blood-Depression may be connected with low blood-
zinc levels zinc levels Studies involving zinc supplementation in Studies involving zinc supplementation in
depressed patients suggest that zinc has a depressed patients suggest that zinc has a strong anti-depressant activity strong anti-depressant activity
Alternative and complementary Alternative and complementary therapies of MDD/GADtherapies of MDD/GAD
Electroconvulsive Therapy (ECT)Electroconvulsive Therapy (ECT)Procedure in which electric currents are passed
through the brain, intentionally triggering a brief seizure
Cause changes in brain chemistry that can quickly reverse symptoms of certain mental illnesses
Valerian RootValerian Root Direct sedative effect on the Central Nervous Direct sedative effect on the Central Nervous
System System Used as a calming agent to reduce headaches, Used as a calming agent to reduce headaches,
nervousness and insomnianervousness and insomnia
SummarySummary ““SIG E CAPS” SIG E CAPS” mnemonicmnemonic to help interview to help interview
those patients you suspect may have those patients you suspect may have depressiondepression
90% of patients with MDD will have 90% of patients with MDD will have underlying GADunderlying GAD
5HT and NE are thought to be integral in 5HT and NE are thought to be integral in pathway that leads to symptoms related to pathway that leads to symptoms related to GAD/MDDGAD/MDD
Many medical and non medical therapies Many medical and non medical therapies available that should include psychotherapyavailable that should include psychotherapy
Ensure compliance with routine follow up Ensure compliance with routine follow up visits as this can hamper efficacy of therapyvisits as this can hamper efficacy of therapy
REFERENCESREFERENCES