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