Anxiety and Depression

Gil C. Grimes, MD

September 2006

Outline

• Definitions

• Prevalence

• Risk Factors

• Complications

• Treatment

Anxiety Definition

• DSM-IV Criteria– Excessive anxiety and worry about a number

of events and activities– Duration at least 6 months– Patients find it difficult to control worry– Distress or impaired function

Anxiety Definition

– At least 3 of the follow 6 symptoms• Feeling restless, fidgety, jittery, keyed up, on edge,

or difficulty sitting still• Being easily fatigued• Difficulty concentrating or mind going blank• Irritable• Muscle tension, aches, or soreness• Trouble falling asleep, staying asleep, or restless

nonrestorative sleep

Anxiety Definition

• Rule out general medical condition, substance abuse, or other mental condition– Angina or MI– Hypoglycemia– Hyperthyroidism– Carcinoid syndrome– Drug Effects

• Acyclovir, anabolics, ACE inhibitors, Baclofen, and others (Medical letter 2002;44(1134):59)

• Street Drugs• Toxins like organophsotates, mercury, arsenic

Anxiety Definition

• Differentiation from depression– Feature favoring anxiety

• Difficulty falling asleep• Phobic avoidance behavior• Rapid pulse• Breathing disturbances• Apprehensive expectations• Tremors• Palpitations• Faintness• Depersonalizations• Derealization

Anxiety Definition

• Look for co-morbidities– Panic disorder– Social phobias or agoraphobia– Obsessive-compulsive disorder– PTSD– Acute stress disorder– Separation anxiety disorder

• Treatment will differ with these co-morbidities

Anxiety Diagnosis

• Chief Complaints– Manifold complaints– Psychological such as anxiety, tremor, dyspnea,

palpitations– Functional such as insomnia, inability to relax,

difficulty concentrating• ROS

– Motor- trembling, twitching, shaking, tense, restless, fatigued

– Autonomic- dyspnea, palpitations, tachycardia, sweating, clammy, dry mouth, light-headed, abdominal distress, flushes dysphagia

Anxiety Prevalence

• Onset age 20-30 years

• Lifelong illness

• Female:Male 2:1 (males may be more somatizers)

• Survey data– 3-3.3% over one year in 2 national survey’s 1

– 14.8% in urban FM office 2

– 28.8% lifetime prevalence nationally 3

1- Am J Psychietry 1999;156(12):1915 Level 2c2- Arch Fam Med 2000;9(9):876 Level Level 1c3- Arch Gen Psychiatry 2005;62(6):593 Level 1c

Anxiety Risk Factors

• Genetics– 32% heritability 1

• Meta-analysis of aggregate familial risk• 10-17% risk first degree relatives• 80-90% risk in monozygotic twins

– Co-morbid psychiatric disorders (depression)

1- Am J Psychiatry 2001;158(10):1568 Level 1a

Anxiety Complications

• Increased utilization of health care– Cohort 1232 patients– Followed 3 months prior and 12 months after

index visit– Twice the cost is anxiety present 1

• Increased risk for progression of disability 2

– Cohort of 1,002 women >65 with functional limitations

1- J Fam Pract 1999;48(10):769 Level 2b2- J Am Gerietri Soc 2005;53(1):34 Level 1b

Anxiety Complications

• Increased of suicidal ideation and attempts– 7.076 persons in Netherlands cross-sectional

study• 11.4% had SI 2.9% had attempt overall• 42% of GAD had SI OR 7.01• 12.1% of GAD had attempt OR 5.87

– Second study 4,796 persons• New SI 2% attempt 0.84% overall• 5.9% with GAD developed SI OR 4.23• 3% with GAD had Attempt OR 2.3

Arch Gen Psychiatry 2005;62(11):1249 Level 1b

Depression Definition

• Depressed mood with 5 or more of the following – Sleep disturbance – Psychomotor retardation or agitation – Appetite disturbance (or weight change) – Concentration difficulties – Energy low– Sleep disturbance – Psychomotor retardation or agitation – Appetite disturbance (or weight change) – Concentration difficulties – Energy low

Depression Definition

• Presenting complaints– 97% decreased energy– 90% anxiety– ~80% sleep disturbance, fatigue, or insomnia– Other common complaints

• Helplessness/hopelessness• Loss of energy or interest• Excessive self-criticism/guilt/low self-esteem• Delusions• Hypochonriasis

NEJM 1999;341(18):1329 Level 1c

Depression Definition

• Anxious subtype– Worries, tension, restlessness– Slower response to medications

• Atypical– Mood reactivity (increased appetite, weight gain, hypersomnia)– More common in females– Earlier onset, more frequent, more chronic

• Seasonal affective disorder– Increased appetite, carb craving, weight gain, hypersomnia

• Postpartum depression– Within 4 weeks of delivery– Depressed mood, tearfulness, labile mood

J Clin Psychiatry 1998;59(suppl 16):5 Level 5

Depression Definition

• PRIME-MD questions– 2-item screening sensitive not specific

• During the past month have you often been bothered by

• Anhedonia-little interest or pleasure in things you usually enjoy

• Depressed mood- feeling down, depressed or hopeless

• Study of 1000 adult patients

Arch Intern Med 1998;158(22):2649 Level 1b

Depression Definition

• Rule out mimics– Neuromuscular disease that affect facial expression– Degenerative neurological disease that causes

psychomotor retardation– Delirium– Drug withdrawal (amphetamine)– Thyroid disorders– Tertiary syphilis, AIDS etc.– Neoplasm – Screen and rule out of bipolar

Depression Definition

• Differentiation from Anxiety– Features favoring depression

• Early morning awakening• Hypersomnia• Diurnal variation• Sad downcast facial expression• Slowed speech• Slowed thought process• Sadness / guilt / hopelessness / despair

Depression Prevalence

• Common among US adults– Face to face survey >43K persons 1

• Diagnosis in prior year 5.28%• Lifetime 13.23%

– Face to face survey 9,090 persons 2

• 16.2% lifetime prevalence• 6.6% in the last 12 months

– NIH Survey 9,863 students (age 11-15) 3

• 25% females and 10% males depressed• Higher with substance abuse and bullying

1- Arch Gen Psychiatry 2005;62(10):1097 Level 2c2- JAMA 2003;289(23):3095 Level 2c3- Arch Pediatr Adolesc Med 2004;15 Level 2c

Depression Risk Factors

• Major depression in parents 1

– 2,427 adolescents and young adults followed 4 years

– In one parent OR 2.7– In both parents OR 3

• Alcohol dependence 2

– OR 4.2 for dependence but no association for abuse

• Alienation form parents in early teens 3

1- Arch Gen Pshychiatry 2002;59(4):365 Level 1c2- Arch Gen Psychiatry 2002;59(9):794 Level 2c3- J Am Acad Child Adolesc Psychaitry 2002;41(12):1478 Level 2c

Depression Risk Factors

• Some association of various strength– Bullying or being bullied– Separation or divorce– Adverse life events– History of physical abuse– Chronic illness– Chronic pain– Perimenopausal– Smoking cessation

Depression Complications

• Recurrent Depression– 50-80%experience second episode– 10-15% die by suicide– Maternal depression 1

• Increased antisocial behavior in children• Increase risk of psychiatric diagnosis if maternal

depression persisted

1- JAMA 2006;295(12):1389

Depression Complications

• Coronary Heart Disease– Increases incidence of CAD in both men and

women• Adjusted CAD RR 1.73 in women• Adjusted CAD RR 1.71 in men

– Increases CAD mortality in men• Adjusted death from CAD 2.34 in men

• Associated with increased risk of heart failure

Arch Intern Med 2000;160(9):1261 Level 2b and JAMA 2006;295(24):2874

Therapy for Anxiety

• Anxiety– Key is antidepressants for prophylaxis– Effective in Randomized controlled trials for

anxiety without depression– Benzodiazepines good short term (no long

term evidence)– Hydroxyzine works

Therapy for Anxiety

• Antidepressants– For anxiety NNT 5.15 Cochrane review 2005

• Venlafaxine (effexor) several RCT with good data various ages 1,2 doses up to 225 mg daily

– NNT3.2-10– NNH for side effects 10 nausea, somnolence, dry mouth

• Paroxitine (paxil) several RCT with good data BUT pregnancy cat D doses 20-50 mg 3,4

– NNT 4-10– Side effects asthenia, somnolence, nausea, decreased

libido

1- JAMA 2000;283(23):3082 Level 1b2- J Am Geriatr Soc 2002;50(1):18 Level 1b

3- Am J Psychiatry 2003;160(4):749 Level 1b4- J Clin Psychiatry 2001;62(5):350 Level 1b

Therapy for Anxiety

• Antidepressants– Sertraline (Zoloft) Two RCT adults and adolescents

various doses (50-150 adults, 50 adolescents)• NNT 4 adults no difference drop outs 1 • Significant improvement compared to placebo in adolescents

2

– Fluvoxamine (Luvox) children 6-17 with GAD dose 250-300 mg 3

• NNT 3 at 8 weeks• NNH 16

1- Am j Psychiatry 2004;161(9):642 Level 1b2- Am J Psychiatry 2001;158(12):2008 Level 1b3- N Engl J Med 2001;344(17):1279 Level 1b

Therapy for Anxiety

• Antidepressants– Fluoxetine (Prozac) 20 mg in children and

adolescents 1

• NNT 4 • Mild transient headaches and GI side effects (no

drop outs)

– Escitalopram (Lexapro) 10-20 mg in adults 2

• NNT 5• No significant difference in discontinuation

1- J Am Acad Child Adolesc Psychiatry 2003;42(4):415 Level 1b2- Depress Anxiety 2004;19(4):234 Level 1b

Therapy for Anxiety

• Benzodiazepines– All equally effective– Insufficient evidence for long term use 1

• Systematic review of 8 trial• Weak methodology prevents firm conclusions

– Many adverse effects, sedation, increased confusion, falls in elderly, ataxia, anterograde amnesia 2

– Associated with increased risk for first motor vehicle collision 3

1- Int Clin Psychopharmacol 2000;15(2):99 Level 2b2- J Am Geriatr Soc 2000;$*(6):682 Level 2b3- Lancet 1998;352(9137):1331 Level 2c

Therapy for Anxiety

• Hydroxyzine 1,2,3

– 3 randomized control trials– Dosages 12.5 to 50 mg daily– Most common side effects sleepiness, weight

gain, dry mouth, loss of concentration, and insomnia

1- J Cloin Psychaitry 2002;63(11):1020 Level 1b2- Psychopharmacology (Berl) 1998;139(4):402 level 1b3- Encephale 1994;20(6):785 level 1b

Therapy for Depression

• All antidepressants are equally effective– Efficacy typically seen in 1-4 weeks– Treat for at least 6 months– Do not discontinue during high stress period

• Counseling also works– Not as fast as medications– Equally effective as medications

Therapy for Depression

• TCAs or SSRI more effective than placebo– SR of 15 RCT – Meta-analyses of TC vs. Placebo

• NNT 8 • NNH 15

– Meta-analysis of SSRI vs. Placebo• NNT 7• NNH 39

Ann FAm Med 2005;3(5):449 Level 1a

Risk for Suicide

• Increased in SSRI – SR 702 RCT of SSRI– In 189 trials SSRI vs. Placebo NNH 708– In 115 trials SSRI vs. TCA no significant

difference– In 83 trials SSRI vs. other active comparator

NNH 437

BMJ 2005;330(7488):396 Level 1a

Risk for Suicide

• Risk is highest early after initiation

• Nested case-control study in UK 159,810 patients– Compared relative risk over 90 days– Days 1-9 4.07 for SI and 38 for suicide– Days 10-29 2.88 for SI and 5.1 for suicide– Day 30-89 1.53 for SI and 2 for suicide

JAMA 2004;292(3):338 Level 2b

Handouts and Questions