Anxiety And DepressionDennis Mungall , Pharm.D.Director,Virtual Education, Non traditional Doctor of Pharmacy ProgramAssociate Professor , Pharmacy PracticeOhio State University/ College of Pharmacy

Learning ObjectivesUnderstand the various anxiety disorders , Depression and how each disorder presentsUnderstand the treatment strategies for each disorderUnderstand the signs and symptoms of each disorderUnderstand the consequences to the health care system of anxiety and depression

History of DepressionIt is thought that ancient man saw mental illness as possession by supernatural forces. Ancient human skulls have been found with large holes in them, a process that has become known as trepanning. The accepted theory is that it was an attempt to let evil spirits out. We cannot be certain of this, but we do know that again and again human kind has returned to the idea of mental illness being caused by evil forces.

History of DepressionAnd yet in certain of these cases there is mere anger and grief and sad dejection of mindthose affected with melancholy are not every one of them affected according to one particular form but they are suspicious of poisoning or flee to the desert from misanthropy or turn superstitious or contract a hatred of life. Or if at any time a relaxation takes place, in most cases hilarity supervenes. The patients are dull or stern, dejected or unreasonably torpidthey also become peevish, dispirited and start up from a disturbed sleep. Arateus (AD 150)

History of DepressionHippocrates (460-377 BC) lived at the time of Hellenic enlightenment, when great advances were made in all areas of knowledge. He applied Empedocles theory to mental illness and was insistent that all illness or mental disorder must be explained on the basis of natural causes. Unpleasant dreams and anxiety were seen as being caused by a sudden flow of bile to the brain, melancholia was thought to be brought on by an excess of black bile4, and exaltation by a predominance of warmth and dampness in the brain. Temperament was thought to be choleric, phlegmatic, sanguine or melancholic depending on the dominating humor

History of DepressionBy the end of the fifteenth century psychological problems were greatly entwined with legal and religious issues and were not seen alone. The devil was seen as the cause of all ills .Mental disorder was equated with sin. They also stated that where doctors could find no cause for a disease and where the disease did not respond to traditional treatment it was caused by the devil. A witch was stripped and her pubic hair was shaved before presentation to judges, so that the devil would have nowhere to hide. On being found guilty a witch would be burnt at the stake. Literally hundreds of thousands of women and children suffered this fate and probably many of the mentally ill.

History of DepressionRobert Burtons anatomy of melancholy appeared for the first time in 1621.2 He described in detail the psychological and social causes (such as poverty, fear and solitude) that were associated with melancholia and seemed to cause it In Early nineteenth century Heinroth believed that sin was the causal factor in mental illness. Not sin in the theological sense, but the offending of an individuals morals by their own thoughts. He was referring to an internal conflictThe man who exemplified the hard-nosed scientific feel of this era was the German psychiatrist Wilhelm Griesinger (1817-1868). For him mental diseases were somatic diseases6, and the cause of mental illness was always to be found in the brain. He firmly believed that psychiatry and neuropathology were one

History of DepressionFreud successfully realised was that neurophysiological and psychological knowledge need not be contradictory. Psychoanalysis predominated until the 1970s, which was followed by renewed interest in genetic, biochemical and neuropathological causes of mental disorder which came to be known as biological psychiatry

Introduction

Lifetime Prevalence of Depression and Anxiety Disorders

Comparision with Other Medical Conditions

Sx Overlap of Anxiety and Depression

Sx Overlap ( cont.)

Physical SymptomsRisk Of Psychiatric DisorderPercentKroenke et al. Arch Fam Med. 1994;3:774.Physical Symptoms (#)

Somatic Symptoms In Mood And Anxiety DisordersKroenke et al. Arch Fam Med. 1994;3:774.

Lifetime Rates Of Anxiety Disorders InAlcohol-Dependence*****

Mood/Anxiety DisorderOccurring Prior To Substance DependenceMerikangas et al. Psychologic Med. 1998;28:773.PercentAlcohol DependenceDrug Dependence

Primary Care Presentation

Anxiety and Depression in Primary Care

Depression and Gender

Days Lost from Work

Costs of Depression in the United StatesCosts of Depression in the United States Cost CenterAmount ($ billion) Direct costs Inpatient care8.3 Outpatient care2.8 Partial care0.1 Pharmaceuticals1.2 Total direct costs12.4 Indirect costs Absenteeism11.7 Decreased productivity 2.1 Suicide 7.5 Total indirect costs31.3

Recovery Rates

Relapse Rates

Utilizers of Medical Care

Depression

Case Study

Depression Prevalence

Morbidity and Mortality

Morbidity and Mortality

Suicide

Depression : DSM IV

Major Depressive Episode:Criteria

Criteria (cont.)

Hamilton Rating Score for Depression

Interview TechniquesDepressed or DownRestlessFatiguedGuiltyInability to Concentrate

Associated Features

Associated Features (cont.)

Depression Risk Factors Prior episodesFamily historyPrior suicide attemptsFemale genderRecent childbirth Medical comorbidityAlcohol or substance abuseRecent separation or bereavementDepression Guideline Panel. Depression in Primary Care: Volume 1. Detection and Diagnosis.Clinical Practice Guideline, Number 5. Rockville, MD. U.S. Department of Health and Human Service,Public Health Service, Agency for Health Care Policy and Research. AHCPR Publication No. 93-0550. April 1993.

Recurrent Depression Risk FactorsInadequate treatment Poor medication complianceFrequent +/- multiple episodesPreexisting dysthymiaOnset after age 60Long duration or severe index episodeSeasonal patternFamilial mood disordersComorbid anxiety or substance abuse disorder

Factors Complicating Diagnosis OfLate Life DepressionComorbid general medical/neurologic illnessCognitive declineMultiple losses/bereavement

Disease Management

Depression Treatment OutcomeThe Five RsKupfer. J Clin Psychiatry. 1991;52(Suppl 5):28.RemissionxxxSymptomsSyndromeResponseRelapseRecoveryRecurrenceTreatment PhasesAcute 6-12Weeks Continuation4-9 MonthsMaintenance 1 Year

Response to Therapy

Relapse

Compliance

Guidelines

Criteria For An Adequate Trial Of Antidepressant TreatmentAccurate diagnosisAppropriate antidepressantAdequate dose/duration

Initial Approach to RX

Initial Approach to RX

Initial Approach to RX

Choosing an Antidepressant

Long Term Treatment Strategies

Rules of Dosing

Serotonin Side Effects

Pharmacokinetics of Antidepressants

Drug Interactions

Treatment Choices

Treatment Choices ( cont.)

Treatment Choices ( cont.)

Treatment Summary

Strategies In Treatment Resistant DepressionMaximize doseAugmentation:Thyroid hormone (T3 > T4) Lithium (levels 0.7 mEq/mL)Combination therapy: eg, SSRI/TCAOther: MAOIs- venlafaxineECT

SSRIs And Sexual DysfunctionCommon, class effectAffects men and womenReduced libidoDysfunctional orgasmdelayed ejaculationinability to ejaculateanorgasmiaKeller-Ashton et al. J Sex Marital Ther. 1997;23:165.Segraves. J Clin Psychiatry. 1998;59(Suppl 4):48.

SSRI - Related Sexual DysfunctionTolerate sexual dysfunction in favor of optimal therapeutic response Dose (or consider drug holiday), but monitor for relapseBeneficial in case reports: bupropion, buspirone, amantadine, bromocriptine, methylphenidate, yohimbine, gingko bilobaConsider alternate antidepressant

Keller-Ashton et al. J Sex Marital Ther. 1997;23:165. Rothschild. Am J Psychiatry. 1995;152:1514.Segraves. J Clin Psychiatry. 1998;59(Suppl 4):48.Potential Management Strategies

Antidepressants And Weight GainWeight gain associated with TCAs, MAOIs, SSRIs, and newer antidepressants Appetite, weight loss associated with depression; therapeutic response may increase weight to normalWeight gain during SSRI therapy has not been systematically studied

TCAs: Enhanced Side Effects In The ElderlySedationAnticholinergic effectsOrthostatic hypotensionCardiac toxicity

Anticancer Drugs Associated With DepressionMassie et al. J Pain Symptom Manage. 1994;9:325.CorticosteroidsInterferonAsparaginaseCyproteroneVinblastineVincristineProcarbazineTamoxifen

Risk Factors For Suicide In Cancer PatientsMassie et al. J Pain Symptom Manage. 1994;9:325.Current or prior suicidalityDepressionPsychosis/irrational thinkingSubstance abuseRecent lossPoor social supportOlder maleUncontrolled painAdvanced diseasePoor prognosisCancer site (head/neck, lung, GI, urogenital, breast)Exhaustion/fatigue

Dysthymia: Criteria

Treatment of Dysthymia

Generalized Anxiety Disorder: Excessive Chronic Anxiety and Worry

DSM IV Classification

Case Studies : GADAcute AnxietyChronic AnxietyUncontrolled Anxiety

Symptom Overlap In GAD And DepressionRoy-Byrne et al. J Clin Psychiatry. 1997;58(Suppl 3):34.InterestAppetiteEsteemSuicideDepressionAgitationDysphoriaSleepFatigueConcentrationRestlessnessTensionIrritabilityWorryGAD

Criteria

GABA

Benzodiazepines

Rx of GAD

Treatment

Rx of GAD

Social Phobia/Social Anxiety Disorder : Fear of Scrutiny

Case Study: Social Anxiety

DSM-IV Social Anxiety DisorderFear/avoidance of social situationsFeared situations avoided or endured with intense anxiety or distressFear recognized as excessive or unreasonableFear/avoidance interferes with work, social, family activitiesAmerican Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC, American Psychiatric Association, 1994.

Prevalence Of Social Anxiety Disorder* Magee et al. Arch Gen Psychiatry. 1996;53:159.**Weiller et al. Br J Psychiatry. 1996;168:169.Prevalence(%)

Common Somatic ComplaintsBeidel. J Clin Psychiatry. 1998;59(Suppl 17):27.PalpitationsTrembling/ShakingBlushingSweatingButterflies

Social Anxiety Disorder And AgoraphobiaDifferential DiagnosisSocialAnxietyDisorderDisorderFear of negative evaluation or humiliation in social or performance situationsCommon FearPublic scrutinyKey ConcernsAvoids speaking, eating, drinking, writing, or using restrooms only in publicExampleAgora-phobiaFear that help wont be available or escape wont be possibleBeing caught in situation where escape may be difficultAvoids being alone or away from home; being in a crowd; traveling in a car, bus or airplane; or being on a bridge or in an elevator

Social Anxiety Disorder And Panic DisorderDifferential DiagnosisSocialAnxietyDisorderDisorderFear of negative evaluation or humiliation in social or performance situationsCommon FearPublic scrutinyKey ConcernsAvoids speaking, eating, drinking, writing, or using restrooms only in publicExamplePanicDisorderFear of having a heart attack, dying, or going crazySudden, unexpected panic attacks alone or in public; not exclusively limited to social situationsDiscrete attacks about 10 minutes, including chest pain, fear of dying, or smothering sensations/avoids places where attacks have occurred

Social Anxiety Disorder And GADDifferential DiagnosisSocialAnxietyDisorderDisorderFear of negative evaluation or humiliation in social or performance situationsCommon FearPublic scrutinyKey ConcernsAvoids speaking, eating, drinking, writing, or using restrooms only in publicExampleGeneralizedAnxietyDisorderFear of everyday routine, life circumstances, e.g. job, finances, health, or minor mattersAnxiety/worry shifting from one concern to another - no fear of social situationsWorries almost constantly about routine, everyday matters

Screening Questions For Social Anxiety Disorder In Primary CareAre you afraid of being scrutinized in public?Do you fear speaking to others?Do you avoid social situations or events?

Social Anxiety DisorderParticipating in small groupsEating, drinking, writing in publicTalking to authority figuresPerforming or giving a talkAttending social eventsWorking while being observedMeeting strangers or datingUsing public bathroomBeing center of attentionCommon Fears

Social Anxiety DisorderDistinguishable from other anxiety disordersVery common, but undiagnosed, undertreated, costlyEffectively treated with SSRIs +/- psychotherapyEasily screened with patient self-rated questionnaire

Social Anxiety Disorder Treatment GoalsReduce anxiety/phobic avoidanceReduce disabilityTreat depression/other comorbidities Choose therapy that is tolerable over long-termDavidson. J Clin Psychiatry. 1998;59(Suppl 17):47.

Treatment

Benzodiazepine Treatment Of Social Anxiety DisorderCan be effectivePotential problems in patients with alcohol/substance abuse Not effective for comorbid depressionSide effectsdisruption of cognitive function/sedationtolerance/dependence/withdrawal

Fluvoxamine Treatment Of Social Anxiety Disordervan Vliet et al. Psychopharmacology. 1994;115:128.Responders(%)Treatment Group (N = 30)

Sertraline Treatment Of Social Anxiety DisorderKatzelnick et al. Am J Psychiatry. 1995;152:1368.Responders(%)Treatment Group (N = 12)

Paroxetine Treatment Of Social Anxiety Disorder* P

Monoamine Oxidase Inhibitor Treatment OfSocial Anxiety DisorderIrreversible, nonselectiveeffective poorly toleratedhazardousReversible, selectivemoderate effectivenesswell toleratednot available in US

MAOI: Diet

-Blocker Treatment Of Social Anxiety DisorderEffective for mild, occasional performance anxietyNot effective in generalized social anxiety disorderWill not treat comorbid conditionsVery limited role

Tricyclic Antidepressant Treatment OfSocial Anxiety Disorder Doubtful efficacyPoor side effect profilesedation, tremor, dry moutheffects on cognitive functionsexual dysfunctionweight gainconstipation

Conclusions: Social Anxiety DisorderFrequently undiagnosed and untreatedPresents as marked and persistent fear of social or performance situations or with physiologic symptomsTreatment options: psychosocial and pharmacologicSSRIs show most promise

Panic Disorder: Spontaneous panic attacks

Case Study : Panic

Criteria For Panic Attacks

Other Causes of Panic Sx

Other Causes of Panic Sx

Rx: Panic Disorder

Benzodiazepines

Clonazepam

Benzodiazepines (cont.)

Antidepressants

Antidepressants (cont.)

Post Traumatic Stress Disorder

PTSD : Case Study

Prevalence Of PTSDMalesFemales

Core Features Of PTSD Intrusive symptomsAvoidance behaviorNumbingHyperarousal symptomsTrauma

Criteria

Non-Combat Related Trauma Associated With PTSDKessler et al. Arch Gen Psychiatry. 1995;52:1048.Incidence(%)MalesFemales

Diagnosis Of PTSD In Primary CareMust specifically ask about traumaAssess presence of core symptoms Patient self-rated scales (eg Impact of Event Scale, MINI)Assess comorbidity (depression, substance use disorders, anxiety disorders)

Treatment Of PTSDEducationSupportAnxiety management pharmacotherapypsychotherapyLifestyle modification

Non-Combat Related PTSD:SSRI Treatment StudiesVan Der Kolket al. 1994Author64*NFlu vs. Pbo;5 weeksRegimenSignificant symptoms with FluOutcomeDavidson et al. J Trauma Stress. 1991;4:419.Marshall et al. J Clin Psychopharmacol. 1998;18:10.Davidsonet al. 19915Flu;8 - 32 weeks Intrusive and avoidant symptomsRothbaumet al. 19967Ser;12 weeks Symptoms in 4/5 respondersMarshallet al. 199819Par;12 weeksSignificant all core symptoms* Including 31 cases of combat related PTSDRothbaum et al. J Trauma Stress. 1996;9:865.Van Der Kolk et al. J Clin Psychiatry. 1994;55:517.

Treatment