POST-TRAUMATIC STRESS DISORDER Comorbidity and Treatment Thomas A. Mellman, M.D. Howard University,...

POST-TRAUMATIC STRESS DISORDER

Comorbidity and Treatment

Thomas A. Mellman, M.D.Thomas A. Mellman, M.D.

Howard University, Washington DC Howard University, Washington DC

Major Teaching Points

• PTSD develops in a substantial minority of individuals PTSD develops in a substantial minority of individuals exposed to severe traumaexposed to severe trauma

• PTSD is highly comorbid with other psychiatric PTSD is highly comorbid with other psychiatric disordersdisorders

• SSRI medications have FDA approval for PTSD and SSRI medications have FDA approval for PTSD and efficacy for some PTSD subpopulationsefficacy for some PTSD subpopulations

• Other antidepressants, new generation antipsychotic Other antidepressants, new generation antipsychotic medications, noradrenergic antagonists, and mood medications, noradrenergic antagonists, and mood stabilizers have a role in treating some PTSD casesstabilizers have a role in treating some PTSD cases

• Cognitive behavioral therapy is an important Cognitive behavioral therapy is an important evidence-based intervention for PTSD evidence-based intervention for PTSD

Pre-Lecture ExamQuestion 1

True or False:

1. The prevalence of PTSD is higher in women than men.


True or False:

1. All individuals exposed to severely threatening trauma will develop PTSD.


True or False:

1. Cortisol activity in chronic PTSD is similar to major depression.

Question 4

1. The psychosocial PTSD treatment with the strongest evidence for efficacy is:

A. EDMR

B. Breathing relaxation

C. Exposure

D. Thought-stopping

Question 5

1. The weakest evidence for efficacy for PTSD is for which class of pharmacological agents:

A. SSRI’s

B. TCA’s

C. MAOI’s

D. Benzodiazepines

E. Risperidone

Overview

I.I. EpidemiologyEpidemiology

II.II. DiagnosisDiagnosis

III.III. Psychiatric ComorbidityPsychiatric Comorbidity

IV.IV. TreatmentTreatment

Post-Traumatic Stress Disorder (PTSD)

Lifetime prevalence in community of 1% to 14%, Lifetime prevalence in community of 1% to 14%, recent estimates from NCS of 7-8% recent estimates from NCS of 7-8%

PTSD is associated with sexual abuse, physical PTSD is associated with sexual abuse, physical assault, military combat, torture, accidental assault, military combat, torture, accidental trauma, natural or man-made disasters, diagnosis trauma, natural or man-made disasters, diagnosis of threatening illnessof threatening illness

American Psychiatric Association, 1994Kessler et al., ’95, 05


A characteristic set of symptoms following A characteristic set of symptoms following exposure to extreme traumatic stressexposure to extreme traumatic stress

1.1. experience, witness, or confronted with experience, witness, or confronted with actual or threatened death or injuryactual or threatened death or injury

2.2. Response involves intense fear, Response involves intense fear, helplessness, or horrorhelplessness, or horror

Duration more than one monthDuration more than one monthSignificant functional impairmentSignificant functional impairment


Re-experiencing symptoms (need 1)Re-experiencing symptoms (need 1)

1.1. intrusive recollectionsintrusive recollections

2.2. trauma-related nightmarestrauma-related nightmares

3.3. flashbacksflashbacks

4.4. psychological distress with reminderspsychological distress with reminders

5.5. physiologic reactivity with remindersphysiologic reactivity with reminders


Avoidance symptoms (need 3)Avoidance symptoms (need 3)

1.1. avoid thoughts/feelings/conversationsavoid thoughts/feelings/conversations

2.2. avoid activities, places, peopleavoid activities, places, people

3.3. inability to rememberinability to remember

4.4. diminished interestdiminished interest

5.5. feelings of detachmentfeelings of detachment

6.6. restricted affectrestricted affect

7.7. foreshortened futureforeshortened future


Arousal symptoms (need 2)Arousal symptoms (need 2)

1.1. impaired sleep initiation/maintenanceimpaired sleep initiation/maintenance

2.2. irritabilityirritability

3.3. concentrationconcentration

4.4. hypervigilancehypervigilance

5.5. exaggerated startleexaggerated startle

PTSD

Associated Features

1.1. Alcohol/drug problemsAlcohol/drug problems

2.2. Aggression/violenceAggression/violence

3.3. Suicidal ideation, intent, attemptsSuicidal ideation, intent, attempts

4.4. DissociationDissociation

5.5. DistancingDistancing

6.6. Problems at workProblems at work

7.7. Marital problemsMarital problems

8.8. HomelessnessHomelessness

Lifetime Prevalence of DSM-III-RMajor Psychiatric Disorders

NCS Data

Mood DisordersMood Disorders

Major depressive episodeMajor depressive episode 17.117.1DysthymiaDysthymia 6.46.4Manic episodeManic episode 1.61.6

Anxiety DisordersAnxiety DisordersSocial phobiaSocial phobia 13.313.3Simple phobiaSimple phobia 11.311.3PTSDPTSD 7.87.8Agoraphobia without panicAgoraphobia without panic 5.35.3GADGAD 5.15.1Panic disorderPanic disorder 3.53.5

Substance Use DisordersSubstance Use DisordersAlcohol abuse/dependenceAlcohol abuse/dependence 23.523.5Drug abuse/dependenceDrug abuse/dependence 11.911.9

Adapted from: Kessler et al. Arch Gen Psychiatry. 1994;51:8–19.Adapted from: Kessler et al. Arch Gen Psychiatry. 1994;51:8–19.Kessler et al. Arch Gen Psychiatry. 1995;52:1048–1060.Kessler et al. Arch Gen Psychiatry. 1995;52:1048–1060.

%%

PTSD Risks of Specific Traumas

in the US PopulationP

erc

enta

ge

Pe

rcen

tag

e

Natural Natural DisasterDisaster

RapeRapeCombatCombatCriminalCriminalAssaultAssault

MenMen

WomenWomen

Kessler RC et al. Kessler RC et al. Arch Gen PsychiatryArch Gen Psychiatry. 1995;52:1048–1060.. 1995;52:1048–1060.

N/AN/A

PTSD

Risk Factors for PTSD

Severity of trauma (i.e., threat, duration, injury, loss)Severity of trauma (i.e., threat, duration, injury, loss)

Prior traumaPrior trauma

GenderGender

Prior mood and/or anxiety disordersPrior mood and/or anxiety disorders

Family history of mood or anxiety disordersFamily history of mood or anxiety disorders

Low EducationLow Education

PTSD

Rates Related to Specific TraumasP

erc

enta

ge

Pe

rcen

tag

e

Natural Natural DisasterDisaster

RapeRapeCombatCombatCriminalCriminalAssaultAssault

MenMen

WomenWomen


00

2525

5050

7575

100100

11 22 33 44 55 66 77 1010

PTSD

Persistence Over Time


YearsYears

% W

ith

ou

t R

eco

very

% W

ith

ou

t R

eco

very

(Untreated Group)(Untreated Group)

PTSD

Function and Quality of LifeIn VietnamVeterans With and Without PTSD

Pe

rcen

tP

erc

ent

Not Not WorkingWorking

PhysicalPhysicalLimitationLimitation

ReducedReducedWell-Well-BeingBeing

Fair orFair orPoorPoor

HealthHealth

Zatzick DF et al. Zatzick DF et al. Am J PsychiatryAm J Psychiatry. 1997;154:1690–1695.. 1997;154:1690–1695.

Violent Violent BehaviorBehaviorPast YearPast Year

PTSDPTSD

Non-PTSDNon-PTSD

DepressionDepression 48 48 1212 48481919

ManiaMania 12 12 11 6611

Panic DisorderPanic Disorder 7 7 22 131344

Social PhobiaSocial Phobia 28 28 1111 28281414

GADGAD 17 17 33 151566

Alcohol Abuse/DependencyAlcohol Abuse/Dependency 52 52 3434 28281313

Substance Abuse/DependencySubstance Abuse/Dependency 34 34 1515 272788

Any DiagnosisAny Diagnosis 88 88 5555 79794646


Lifetime Rates (%)Lifetime Rates (%)

Men Men Women Women

PTSD Non-PTSD PTSD Non-PTSDPTSD Non-PTSD PTSD Non-PTSD

PTSD

Psychiatric Comorbidity

Comorbidity in PTSDNational Comorbidity Study

1 Other Diagnoses 2 Other Diagnoses 3 Other Diagnoses No Other Diagnosis

1 Other Diagnoses 2 Other Diagnoses 3 Other Diagnoses No Other Diagnosis

MEN

WOMEN

0

20

40

60

80

PTSD

Impact of Comorbid PTSD in Subjects With Other Anxiety Disorders

(%)

Ra

tes

(%)

Ra

tes

38

48

30

6

30

21

AlcoholAlcoholProblemsProblems

HospitalizedHospitalizedAttemptedAttemptedSuicideSuicide

Anxiety DisorderAnxiety DisorderWith PTSDWith PTSD

Anxiety DisorderAnxiety DisorderWithout PTSDWithout PTSD

Warshaw MG et al. Warshaw MG et al. Am J PsychiatryAm J Psychiatry. 1993;150:1512–1516.. 1993;150:1512–1516.

DIAGNOSTIC SPECTRADIAGNOSTIC SPECTRA

PTSDPTSD

DepressionDepression

PanicPanicDisorderDisorder

DissociationDissociation

SubstanceSubstanceUseUse

DisordersDisorders

PersonalityPersonalityDisorderDisorder

PsychosisPsychosis

SomatizationSomatizationObsessiveObsessive

CompulsiveCompulsiveDisorderDisorder

PTSD

Model Sequence of Comorbidity

PTSDSubstance

AbuseGAD

MDDPANIC

AgeAge 2323 2424 2525 3030

Davidson JR et al. Davidson JR et al. Compr PsychiatryCompr Psychiatry. 1990;31:162–170.. 1990;31:162–170.Mellman TA et al. Mellman TA et al. Am J PsychiatryAm J Psychiatry. 1992;149:1568–. 1992;149:1568–1574.1574.

Disability--->Disability--->

Lifetime History of Suicidal Attempts by Anxiety Disorder

20

2523 23

33

16

0

4

0

5

10

15

20

25

30

35

Panic(n=86)

Pan/Ag(n=111)

Agora(n=22)

Social(n=158)

PTSD(n=170)

GAD(n=127)

MAD(n=12)

GenPop

General US population lifetime rates of suicide attempts range from 2.9% to 4.6%.General US population lifetime rates of suicide attempts range from 2.9% to 4.6%.

Kessler RC, Kessler RC, Archives of General PsychiatryArchives of General Psychiatry. 1999; Moscicki EK, . 1999; Moscicki EK, Yale Journal of Biology and Yale Journal of Biology and MedicineMedicine. 1988. 1988

%

Disability Weights (Rating Scale)

psych

osis

blindnes

s

parap

legia

opioid

dep

enden

ce

seve

re d

epre

ssio

n

anore

xia

nervo

sa

PTSD

agora

phobia

bipola

r dis

order

moder

ate

depre

ssio

n

panic

dis

order

border

line

PD0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Score

Sanderson K and Andrews G, Australian and New Zealand Jnl of Psych 2001

640 36

PTSD

Impact of Treatment on Recovery


TreatedTreated

UntreatedUntreated

Median Months to RecoveryMedian Months to Recovery

(N = 459)(N = 459)

PTSD

Treatment Options

PsychotherapyPsychotherapy

PharmacotherapyPharmacotherapy

Combined treatmentsCombined treatments

PTSD

Considerations for Psychotherapy

1.1. Capacity to tolerate distress with Capacity to tolerate distress with exposureexposure

2.2. Motivation/preferenceMotivation/preference

3.3. Ability to participate and follow Ability to participate and follow structurestructure

4.4. Problems with interpersonal Problems with interpersonal adjustmentadjustment

Cognitive Restructuring and Combination Treatments

Study Population Comparison Results

Marks et al., 1998

87 civilian trauma victims

Relaxation vs E vs cognitive restructuring (CR) vs combination

All superior to relaxation

Resick et al. 2002

120 F, sexual assault

Cognitive processing Tx (CPT) (elements of CR and E) vs E vs minimal contact

CPT = E > MC CPT superior for guilt

Monson et al., 2007

60 Male veterans

Cognitive processing CPT vs Present Centered (PC)

CPT superior to PC

EXPOSURE STUDIES

Study Population Comparison Results

Keane et al., 1989 24 Vietnam veterans

E vs WL

Exposure group more improved, especially re-experiencing

Foa et al., 2005 179 Women civilian trauma

E vs E+CR vs WL E superior effective with all Sx clusters

Schnurr et al., 2007

Women veterans

E vs PC E superior to PC

*E = exposure-based treatment WL = wait list control SIT = stress inoculation training

PTSD

Treatment of PTSD by Exposureand/or Cognitive Restructuring

Marks I et al. Marks I et al. Arch Gen PsychiatryArch Gen Psychiatry. 1998;55:317–325.. 1998;55:317–325.

IES

Sco

res

IES

Sco

res

TreatmentTreatment1 mo1 mo 3 mos3 mos 6 mos6 mos

r = relaxationr = relaxationc = cognitive restructuringc = cognitive restructuringe = prolonged exposuree = prolonged exposureec = e + cec = e + crr

cc

ecec

ee

Follow UpFollow Up

Conclusions of the IOM report on the Treatment of PTSD (2007)

““The evidence is sufficient to conclude The evidence is sufficient to conclude the efficacy of (psychotherapy that the efficacy of (psychotherapy that utilize) exposure therapies in the utilize) exposure therapies in the treatment of PTSD” (PE, CPT)treatment of PTSD” (PE, CPT)

PHARMACOTHERAPYNeurobiological factorsNeurobiological factors

Evidence of efficacyEvidence of efficacy

What respondsWhat respondsPTSDPTSDrelated pathologyrelated pathology

Who respondsWho respondsType of traumaType of traumacomorbiditycomorbiditygendergender

PTSD: Neurobiological Alterations of Memory Processing

Greater physiologic reactivity to trauma-related stimuli Greater physiologic reactivity to trauma-related stimuli

Selective attention to trauma stimuliSelective attention to trauma stimuli

Fragmentary trauma narrativesFragmentary trauma narratives

Deficits in standard tests of verbal memoryDeficits in standard tests of verbal memory

Suggested abnormalities from structural and functional brain imaging Suggested abnormalities from structural and functional brain imaging

PTSD: Hormones and Neurotransmitters

Cortisol: reduced secretion and increased sensitivity Cortisol: reduced secretion and increased sensitivity to feedback inhibition with PTSD (to feedback inhibition with PTSD (Yehuda et al., 1993)Yehuda et al., 1993)

Role of noradrenergic activity in fear-enhanced Role of noradrenergic activity in fear-enhanced learning (learning (Cahill, 1997Cahill, 1997))

Noradrenergic and serotonergic probes stimulate Noradrenergic and serotonergic probes stimulate panic and flashback symptoms in combat-related panic and flashback symptoms in combat-related PTSD (PTSD (Southwick et al., 1997)Southwick et al., 1997)

Ross et al., 1994; Mellman et al., 1997, 2002, Breslau et al., 2004

PTSD: Dysregulated sleep SubjectiveSubjective

Trauma-related nightmaresTrauma-related nightmares

Insomnia/nonrestorative sleepInsomnia/nonrestorative sleep

Objective (EEG findings)Objective (EEG findings)

Mixed findings regarding sleep maintenance and Mixed findings regarding sleep maintenance and duration duration

Increased REM density/ Disrupted REM sleep Increased REM density/ Disrupted REM sleep continuity continuity

Increased motor activityIncreased motor activity

AIMS OF PHARMACOTHERAPY

Reduce core symptomsReduce core symptoms

Reduce associated symptomsReduce associated symptoms

Facilitate other therapyFacilitate other therapy

Medication Treatment for PTSD: Nature of the Evidence

At least 7 published RCTs supporting efficacy of At least 7 published RCTs supporting efficacy of SSRIs for acute Rx of PTSDSSRIs for acute Rx of PTSD

Mean N participants = 236.3 (range: 47-551)Mean N participants = 236.3 (range: 47-551)

FDA approval for sertraline (’99), paroxetine (’01)FDA approval for sertraline (’99), paroxetine (’01)

Maintenance efficacy established for sertraline for Maintenance efficacy established for sertraline for up to 52 weeks up to 52 weeks (Davidson et al. ‘01)(Davidson et al. ‘01)

Improvement in all 3 sx clusters and QOL Improvement in all 3 sx clusters and QOL measures, treatments safemeasures, treatments safe


Additional RCTs not demonstrating Additional RCTs not demonstrating benefit for SSRIs. Some are benefit for SSRIs. Some are underpowered. The one large and well underpowered. The one large and well designed negative study featured designed negative study featured male combat veterans with chronic male combat veterans with chronic PTSD treated in VA settings PTSD treated in VA settings (Friedman et al., 2007)(Friedman et al., 2007)


Efficacy supported by smaller RCTsEfficacy supported by smaller RCTs

TCAs, MAOIs, TCAs, MAOIs, lamotrigine; adjunctive lamotrigine; adjunctive olanzapine and risperidone, prazosin for olanzapine and risperidone, prazosin for sleep disturbancessleep disturbances

Efficacy Efficacy notnot supported by trials supported by trials

benzodiazepinesbenzodiazepines

Benefits suggested in open trialsBenefits suggested in open trials

Other SSRIs, Novel APs, AEDs, trazodone, Other SSRIs, Novel APs, AEDs, trazodone, nefazodone, noradrenergic nefazodone, noradrenergic suppressor/antagonists suppressor/antagonists

Medication Treatment for PTSD:Recommendations

11stst Line Line

SSRIs (sertraline, paroxetine, SSRIs (sertraline, paroxetine, fluoxetine) fluoxetine)

22ndnd Line Line

other novel and traditional ADs; other novel and traditional ADs; noradrenergic agents; noradrenergic agents; anticonvulsant/mood stabilizers; novel anticonvulsant/mood stabilizers; novel AP medicationsAP medications

Not recommendedNot recommended

traditional APs, benzodiazepines*traditional APs, benzodiazepines*

Friedman et al., 2000

DOES COMORBID PERSONALITY DISORDER AFFECT THE RESPONSE TO

AN SSRI?

0

25

50

75

FLUFLU PBOPBO

PDPD No PDNo PD

FLUFLU PBOPBOp=0.002p=0.002 nsns

DOES COMORBID DEPRESSION AFFECT THE RESPONSE TO AN SSRI?

0

10

20

30

40

50

60

70

MDD No MDD

FluoxetinePlacebo

p=0.003p=0.003 nsns

6060

00

Brady KT et al. Brady KT et al. J Clin Psychiatry.J Clin Psychiatry. 1995;56:502–505. 1995;56:502–505.

IES

IES

Sc

ore

Sc

ore

PTSD Treatment With SSRIs

Open-Label Sertraline in Comorbid PTSDand Alcoholism

PrePre PostPost

IESIES

PrePre PostPost

Alcohol UseAlcohol Use

140140

00

Sta

nd

ard

Sta

nd

ard

Drin

ks/W

eekD

rink

s/Week

(n = 9)(n = 9)

00

1010

3030FluoxetineFluoxetine

Davidson JR et al. Davidson JR et al. Int Clin PsychopharmacolInt Clin Psychopharmacol. 1997;12:291–296.. 1997;12:291–296.

Fin

al D

TS

Fin

al D

TS


Effect of Fluoxetine in Symptom Clusters

2020

PP = 0.02 = 0.02

IntrusiveIntrusive

PP = 0.08 = 0.08

AvoidantAvoidant

PP = 0.01 = 0.01

NumbingNumbing

PP = 0.01 = 0.01

HyperarousalHyperarousal

PlaceboPlacebo

6.76.7

13.513.5

3.03.0

6.36.3 6.26.2

15.115.1

9.09.0

17.317.3

Total (N = 53)Total (N = 53)

EFFECT OF FLUOXETINE ON QUALITY OF LIFE (SF36) IN PTSD:

Pre- to Post-Treatment

0

25

50

75

100

FLU PBO FLU PBO

Davidson et al., 1997 Davidson et al., 1997

General HealthGeneral Health Mental HealthMental Health

PrePre PostPost PrePre PrePre PrePrePostPost PostPost PostPost

p=0.006p=0.006 nsns

IMPROVEMENT IN DISABILITY:Fluoxetine vs Placebo

0

5

10

15

Total Work Family Social/Leisure

FluoxetinePlacebo

p=0.02p=0.02 p=0.02p=0.02 p=0.02p=0.02 p=0.01p=0.01


WHICH SYMPTOMS RESPOND TO AN SSRI?

0

1

2

RIR PhysDistress

Detach Numbing Concn Startle

FluoxetinePlacebo

P=0.006P=0.006 P=0.01P=0.01 P=0.02P=0.02 P=0.02P=0.02 P=0.005P=0.005 P=0.002P=0.002


SEQUENCE OF SYMPTOM IMPROVEMENT WITH FLUOXETINE

(SIP)Week

4 8 12

Startle ** * **

Concentration ** **

Intrusive recollections ** **

Physiological symptoms ** **

Estrangement *

Numbing *

*p<0.05 *p<0.01

SEQUENCE OF SYMPTOM IMPROVEMENT WITH FLUOXETINE

(DTS)Week

2 4 6 8 10 12

Hypervigilance ** *** *** * ** ***

Poor concentration ** *** *** * *** **

Upset by reminders * * * *

Estrangement ** ** * ** **

Anhedonia * **

Avoid thoughts * *

Foreshortened future *

*p<0.05 **p<0.01 ***p<0.001


4040

100100

00

2020

8080

FluoxetineFluoxetine

van der Kolk BA, Fisler RE. van der Kolk BA, Fisler RE. Prim CarePrim Care. 1993;20:417–. 1993;20:417–432.432.

CA

PS

C

AP

S

To

tal S

co

reT

ota

l Sc

ore

Effect of Trauma PopulationEffect of Trauma Population


Effect of Fluoxetine

PlaceboPlacebo

PrePre PostPost

6060

Trauma Clinic (n = 23)Trauma Clinic (n = 23)

PrePre PostPost PrePre PostPost

VA (n = 24)VA (n = 24)

PrePre PostPost

Paroxetine in PTSD

Sertraline vs Placebo in Non-Combat-related PTSD

-40

-35

-30

-25

-20

-15

-10

-5

0

0 2 4 6 8

SertralinePlacebo

WeekWeek

Brady et al.. JAMA 2000Brady et al.. JAMA 2000

ADVANTAGES AND DISADVANTAGES OF

SSRIs

Advantages Disadvantages

Effective on all PTSD symptoms

Unproven in Combat Veterans

Abuse-free GI, sexual, activating side effects

Once daily Medication interactions

Alprazolam (n = 10)Alprazolam (n = 10)

Braun P et al. Braun P et al. J Clin PsychiatryJ Clin Psychiatry. 1990;51:236–238.. 1990;51:236–238.

IES

IES

30.930.9

Effect of AlprazolamEffect of Alprazolam

26.626.630.030.0

28.828.8

PTSD

Treatment With Benzodiazepines

2020

4040

00

Placebo (n = 10)Placebo (n = 10)

1010

3030

PrePre PostPost PrePre PostPost

ADVANTAGES AND DISADVANTAGES OF BZDs


Acute relief of non-specific anxiety

No evidence of efficacy for PTSD

Possible disinhbition

Possible dependence

AmitriptylineAmitriptyline

PlaceboPlacebo

Davidson J et al. Davidson J et al. Arch Gen PsychiatryArch Gen Psychiatry..1990;47:259-266.1990;47:259-266.

% R

esp

on

der

s%

Res

po

nd

ers

4747

Studies Comparing Amitriptyline and Imipramine With PlaceboStudies Comparing Amitriptyline and Imipramine With Placebo

n = 22n = 22

1919

6565

2828

PTSD

Treatment With Tricyclics

5050

100100

00n = 18n = 18 n = 18n = 18n = 23n = 23

ImipramineImipramine

PlaceboPlacebo

Kosten TR et al. Kosten TR et al. J Nerv Ment DisJ Nerv Ment Dis..1991;179:366–370.1991;179:366–370.

ADVANTAGES AND DISADVANTAGES OF TCAs


Effective in PTSD Numerous side effects

Abuse-free Poorly tolerated

Once daily Dangerous in overdose

Hypnotic effects Wide dose range

Kosten TR et al.Kosten TR et al.J Nerv Ment DisJ Nerv Ment Dis..1991;179:366–370.1991;179:366–370.

Studies Comparing Phenelzine and Brofaromine With PlaceboStudies Comparing Phenelzine and Brofaromine With Placebo

PTSD

Treatment With MAOIs

PhenelzinePhenelzinePlaceboPlacebo

% R

esp

on

der

s%

Res

po

nd

ers 6868

n = 19n = 19

2828

6060

39395050

100100

00n = 18n = 18

BrofaromineBrofarominePlaceboPlacebo

2626

5555

n = 55n = 55 n = 58n = 58 n = 22n = 22 n = 23n = 23

BrofaromineBrofarominePlaceboPlacebo

Baker DG et al.Baker DG et al.PsychopharmacologyPsychopharmacology.. 1995;122:386–389. 1995;122:386–389.

Katz RJ et al.Katz RJ et al.AnxietyAnxiety..1994–95;1:169–174.1994–95;1:169–174.

ADVANTAGES AND DISADVANTAGES OF MAOIs


Effective in PTSD Numerous side effects

Poor tolerance

Dietary & other restrictions

May be particularly useful in complex cases

Dangerous in overdose

Antipsychotic Medications• Support for risperidone as add on Rx (Bartzokis et al.,

2005; Reich et al., 2004

• olanzapine 1 small study supporting adjunct efficacy, benefit to sleep (Stein et al., 2002)

• Traditional Antipsychotic medications “not recommended” – (Friedman et al. ISTSS Treatment Guidelines, 2000)

Mood Stabilizers• Carbamazepine

– Open clinical trial: decreased intrusions, flashbacks, insomnia, irritability, impulsivity, and violent behavior (Lipper et al., Psychosomatics, 1986)

• Valproic acid – Open trial: decreased hyperarousal and avoidance

(Stein, J Clin Psych, 1995)

• Lamotrigine– Small controlled trial: decreased re-experiencing,

numbing and avoidance (Hertzberg et al., Biol Psychiatry, 1999)

Medication Treatments for Traumatic Nightmares (None are FDA

approved for indication)

Prazosin (controlled trial)Prazosin (controlled trial)11

Cyproheptadine Cyproheptadine —— (positive results, open label; pilot (positive results, open label; pilot placebo-controlled study,negative)placebo-controlled study,negative)2,32,3

TrazodoneTrazodone44

Nefazodone Nefazodone —— (changes in qualitative features of dream (changes in qualitative features of dream recall)recall)55

Clonidine/guanfacine Clonidine/guanfacine —— (have been used in children) (have been used in children)6,76,7

Novel antipsychotics (adjunct use improves sleep)Novel antipsychotics (adjunct use improves sleep)88

5.Mellman TA, et al. Depress Anxiety. 1999;9:146-148. 6.Kinzie JD, et al. J Nerv Ment Dis. 1994;182:585-587.7. Horrigan JP, JAA CAP. 1996;35:975-976.8. Stein MB et al., Am J Psychiatry. 2002; 159:1777-1779

1. Raskind MA, et al. A J Psychiatry. 2002;160:371-3. 2. Brophy MH. Mil Med. 1991;156:100-101.3. Jacobs-Rebhun S, et al. Am J Psych. 2000;157:1525-64. Ashford, Miller. 1996.

PTSD

Summary

1.1. PTSD is commonPTSD is common

Usually chronicUsually chronic

Presentations varyPresentations vary

Comorbidity is the ruleComorbidity is the rule

2.2. Comprehensive assessment of patients is Comprehensive assessment of patients is critical to develop an individualized critical to develop an individualized treatment plantreatment plan

3.3. Treatment often involves multiple Treatment often involves multiple modalitiesmodalities

CONCLUSIONS

PTSD prevalent and PTSD prevalent and treatabletreatable disorder disorder

CBT effectiveCBT effective

Antidepressant agents effectiveAntidepressant agents effective

SSRI, MAOI, TCASSRI, MAOI, TCA

Combined CBT & pharmacotherapy Combined CBT & pharmacotherapy trial neededtrial needed

Few Are Treated

% untreated 50% 90% 75% 80% 50% 30%

PTSD: Unmet Medical Need

0

2

4

6

8

10

12

14

16

18

% Lifetime Prevalence

Untreated

Treated

Depression Social phobia

PTSD GAD Panic disorder

OCD

Question 1

True or False:

1. The prevalence of PTSD is higher in women than men.

Question 2

True or False:

1. All individuals exposed to severely threatening trauma will develop PTSD.

Question 3

True or False:

1. Cortisol activity in chronic PTSD is similar to major depression.

Question 4

1. The psychosocial PTSD treatment with the strongest evidence for efficacy is:

A. EDMR

B. Breathing relaxation

C. Exposure

D. Thought-stopping

Question 5

1. The weakest evidence for efficacy for PTSD is for which class of pharmacological agents:

A. SSRI’s

B. TCA’s

C. MAOI’s

D. Benzodiazepines

E. Risperidone

Answers to Pre & PostCompetency Exams

1. True

2. False

3. False

4. C

5. D

POST-TRAUMATIC STRESS DISORDER Comorbidity and Treatment Thomas A. Mellman, M.D. Howard University,...

Documents

Transcript of POST-TRAUMATIC STRESS DISORDER Comorbidity and Treatment Thomas A. Mellman, M.D. Howard University,...