6/15/21

1 Anxiety Disorders
Contributor: Carl Salzman
2 NEUROBIOLOGY OF PANIC DISORDER*
• Decreased 5-HT in dorsal periacqueductal grey matter (DPAG)
–Electrical stimulation causes panic symptoms
• Caffeine causes panic attacks in panic disorder patients
• SSRIs can enhance 5-HT in DPAG
–Is the mechanism of antipanic properties of antidepressants and
Xanax
–Buspirone does not enhance DGAG 5-HT and is ineffective in panic
3 EARLY USE OF ANTIDEPRESSANTS FOR PANIC DISORDER*
• TCAs and MAOIs have robust anti-panic disorder effects:
–Commonly prescribed with a BZ for rapid response
• Decline in use due to unacceptable side effects and dietary
restrictions; highest drop out rates
4 SSRI TREATMENT OF PANIC DISORDER*
• Are the primary drugs for treatment of panic disorder
• Commonly prescribed with benzodiazepines in early, acute phase of
treatment
• May lose efficacy over time
• Unacceptable side effects; higher drop out rate than BZs
• Recent data: clonazepam superior to paroxetine for long-term
treatment of panic disorder
5 LONG-TERM TREATMENT OF PANIC & AGORAPHOBIC
DISORDERS
• Many treatment responders show further improvement over time;
• Continuing antidepressant therapy is effective in preventing relapse;
• Beneficial effects can last 1-3 years (or more);
• Antidepressants may lose efficacy over time;
• Antidepressants may have unacceptable side effects and higher drop
out rates than BZ treatment alone;
•
• Similar findings occur with benzodiazepines (alprazolam &
clonazepam).
6 LONG-TERM PHARMACOTHERAPY IN PANIC & AGORAPHOBIC
DISORDERS-

1
6 LONG-TERM PHARMACOTHERAPY IN PANIC & AGORAPHOBIC
DISORDERS-
• Many studies show significant likelihood that panic attacks and
agoraphobic symptoms will resume after a period of drug-free
remission.
–15-30% relapse for agoraphobic symptoms1;
–>30% relapse after 2 years of MAOI or TCA treatment2;
–Nearly all patients who responded to alprazolam relapse after
gradual drug discontinuation3,4.
•
7 DROP OUT RATES FROM LONG-TERM TREATMENTS OF PANIC
DISORDER: BENZODIAZEPINES AND ANTIDEPRESSANTS
Meta-analysis of antidepressant treatment with/without adjunct
benzodiazepines (N=679):
–AD-BZ group 37% less likely to drop out of treatment than AD alone
group;
–Combined group treatment response: 63%; AD group alone
response: 38%.

8 LONG-TERM PHARMACOTHERAPY IN PANIC & AGORAPHOBIC

DISORDERS
• Antidepressants may lose efficacy over time;
• Antidepressants may have unacceptable side effects and higher drop
out rates than BZ treatment alone:
–Sexual dysfunction
–Weight gain
• Combining LOW doses of both an antidepressant and a BZ may
diminish side effect frequency and severity and decrease drop-out
rates.
•
9

Possible Mechanisms of Anxiety-I

Hypothesis: Underactive Inhibitory Neurons*
• Anxiety is related to insufficient:
– inhibitory neurotransmitter (GABA)
– GABAA receptor function

10

11

12
10 GABAA Receptor
11 BZ Receptor
Normally in “agonist sensitivity” position: enhances GABAA
opening of Cl– channel
12 LIGANDS FOR BZ RECEPTOR*
• Agonist – (diazepam) –activates receptor
• Partial agonist – only partially activates receptor or receptors
• Inverse agonist (diazepam binding inhibitor; beta-carboline)- activates
receptor but causes opposite effect
• Antagonist – (Flumazenil)- blocks all receptors (agonist and inverse
agonist)
13 Possible Mechanisms of Anxiety-I:
GABAA- BZ Dysfunction*
• Dysfunctional GABA receptors
– Subsensitive to GABA
• Insufficient GABA (unlikely)
• Dysfunctional BZ receptors
– Decreased endogenous BZ agonist
– Subsensitive to endogenous BZ agonist
14 Possible Mechanisms of Anxiety II:
Possible Role of Inverse Agonist*
• Increased endogenous BZ inverse agonist
• BZ receptors shift from agonist sensitivity to inverse agonist
sensitivity
•
•
15 Possible Mechanisms of Anxiety III-Neuronal Excitation: *
Role of Glutamate
• Excitatory amino acid neurotransmitter
– Mediates excitatory neurotransmission
– Interacts with most synapses
• Stress activates cortical and limbic glutamate neurotransmission
• Increased neurotransmission is through NMDA receptor
16
17 Possible Mechanisms of Anxiety-IV:
ROLE OF OTHER NEUROTRANSMITTERS: NOREPINEPHRINE*
16
17 Possible Mechanisms of Anxiety-IV:
ROLE OF OTHER NEUROTRANSMITTERS: NOREPINEPHRINE*
• Fear and anxiety can be produced by electrical stimulation of locus
ceruleus
• Anxiety and panic are produced by α2 antagonists
• α2 agonist clonidine is anxiolytic
• Noradrenergic antidepressants may increase anxiety
18 ROLE OF OTHER NEUROTRANSMITTERS:
SEROTONIN*
• Serotonin transporter (5-HTT) regulates duration and intensity of
serotonin effects at synapse in cortex and limbic regions
• Short variant allele of 5-HTT is associated with higher anxiety and
neuroticism scores
•
19 Possible Mechanisms of Anxiety-V
ROLE OF CORTICOTROPHIN-RELEASING FACTOR*
• Is the major physiologic regulator of the HPA axis, release of pituitary
ACTH and controls activation of glucocorticoid synthesis
• CRF modulates stress:
–Increases epinephrine and norepinephrine
–Increases heart rate, BP, glucose concentration, behavioral arousal
• CRF release is inhibited by GABA and opioids
•
20 Mechanism of Anxiety
Corticotrophin Releasing Factor*
• Anxiolytics reverse stress-induced behavior and HPA activation
• Benzodiazepines decrease hypothalamic CRF concentration
• Benzodiazepines decrease CRF in locus coeruleus
• CRF1 receptor antagonists may have anxiolytic properties
21 MECHANISMS OF ANXIETY: CRF –II*
• CRF mediates anxiogenic responses by activating CRF1 receptors in
limbic brain regions.
• Anxiety is further modulated by the endogenous cannabinoid (eCB)
system that attenuates the synaptic effects of stress.
–Anandamide and 2-AG are endogenous cannabinoids that interact
with each other and play a role in reducing anxiety and stress.
• Pathological anxiety and stress hypersensitivityt are driven by
increases in CRF1 signalling.

22
 • Pathological anxiety and stress hypersensitivityt are driven by
increases in CRF1 signalling.
•
22 ROLE OF AMYGDALA IN ANXIETY*
• Amygdala is activated by fear
–Has arousal receptors: Norepinephrine and dopamine which
increase CREB in the nucleus
–Glutamate also stimulates CREB in central nuclei of the amygdala
• NE, DA, Glutamate--->activate and increase output from amygdala to
HPA axis and cortex--->anxiety and depressive disorders
23
Possible Mechanism of Anxiety-VI
ROLE OF OTHER NEUROTRANSMITTERS ADENOSINE*
• Functions in postsynaptic second messenger systems
–Has sedative and hypnotic effects
–Has myorelaxant properties
• Adenosine antagonists (theophyllin and caffeine) increase anxiety
(inhibit BZ binding to GABAA – BZ – Cl- ionophore
• NO CAFFEINE for those with anxiety disorders
24

Possible Mechanism of Anxiety-VII

ROLE OF OTHER NEUROTRANSMITTERS:
Peptides*
•
• Each may play a role
– Cholecystokinin
– Corticotropin-releasing factor
– Neuropeptide Y
– Tachykinins
– Endogenous opiates
25 Social Anxiety Disorder
26 DSM-5 Social Anxiety Disorder (SAD)
l Believes performance will be negatively evaluated with resulting
embarrassment or humiliation
l
l Exposure to feared situation predictably elicits anxiety
l
26

l Exposure to feared situation predictably elicits anxiety

l
l Avoids or endures feared social situation(s) with distress
l
l Fear is out of proportion to the actual threat posed
l
l Impairs occupational, social, or family roles
l
l Not better explained by drug of abuse, medication, or medical or
mental disorder, e.g., major depression (social reticence),
Parkinson’s Disease, obesity, burns, stuttering

l
27 SAD Differential Diagnosis
l Avoidant Personality Disorder *
l Panic Disorder / Agoraphobia
l Generalized Anxiety Disorder
l Depression-related social avoidance
l Separation anxiety disorder
l Body Dysmorphic Disorder
l Schizotypal / Schizoid Personality Disorder
l Medical conditions, e.g., tremor
28 Social Anxiety Disorder in Adolescents
l May present with or as:
– Depression
– Conduct Problems (truancy, etc.)
– Substance or ETOH Abuse
29 DSM-5 SAD Subtype Characteristics
1 Generalized
(~70%)
l Pervasive social fears, avoidance
l Early onset
l Familial
l >80% comorbidity
l More impairment
l Lower remission Rate
l Extended treatment needed
2 DSM-5 Performance only
 l Extended treatment needed
2 DSM-5 Performance only
(~30%)
l Few social fears (mostly public speaking)
l Later onset
l Not familial
l Less comorbidity
l Limited impairment
l Remission common
l PRN treatment usually adequate
30 Typical Feared Social Situations
1 Generalized
l Attending Social Events
l Conversing in a Group
l Speaking on Telephone (esp. in public)
l Interacting with Authority Figures
l Making Eye Contact
l Ordering Food in a Restaurant
2 Performance Only
l Public Speaking
l Eating in Public
l Writing a Check
l Using a Public Toilet
l Taking a Test
l Trying on Clothes in a Store
l Speaking up at a Meeting
l Athletic, musical, or dance performance
31 Social Anxiety Disorder Symptoms*
1 l Physical
l
l
l
l
l
l
l

l Cognitive

2
 l Cognitive
l
l

l Behavioral
2 l Tachycardia
l Trembling*
l Blushing*
l Shortness of Breath
l Sweating*
l Abdominal Distress
l Socially-Cued Panic Attacks
l
l Perceived scrutiny and certainty of negative evaluation
l Misinterpretation or failure to note social cues

l Avoidance
l Freezing
l
l
l
32 The Course of SAD*
33

• Lower educational status

•Are less likely to graduate high school
•Work in less skilled occupations
• Lower income and socioeconomic status
• Lower likelihood of marrying
• Higher likelihood of divorce
• Impeded leisure activities
l
34 Social Anxiety Disorder: Neurobiological Aspects*

l Familial Transmission: GSAD risk 10x gen’l population

l 5-HT Function
34

l Familial Transmission: GSAD risk 10x gen’l population

l 5-HT Function
– Genetic polymorphism in 5-HT transporter (SLC6A4)
– Reduced 5-HT1a receptor density
– Tryptophan depletion reverses SSRI benefits
l DA function
– Low striatal dopamine D2 binding in generalized SAD (SPECT)
– Decreased DA reuptake site density in the striatum
– Catechol-O-methyl transferase (COMT) polymorphism
l Children with Behavioral Inhibition
– As adults, are more likely to have anxiety, especially SAD
– Behavioral inhibition is possibly learned from parental behavior
Fox AS, Kalin NH. Am J Psychiatry 2014;171:1162-73
35 Fear Circuit in SAD*
Brain areas implicated in SAD include:
– Amygdala
– Prefrontal cortex
– Insula
– Hippocampus
– Striatum
–
Fox AS, Kalin NH. Am J Psychiatry. 2014;171:1162-73
36
37

38 SAD: Comorbidity*
More often seen in generalized SAD
In the Epidemiological Catchment Area study and the National
Comorbidity Survey study:
– 80% of those with DSM-III-R SAD reported at
least one other psychiatric disorder
– SAD usually occurred first
SAD onset before age 15 is associated with greater risk of subsequent
major depression, alcoholism, agoraphobia or generalized anxiety
disorder than is onset after age 15.*

39 SAD: Comorbidity*
Schneier FR, et al. Arch Gen Psychiatry. 1992;49:282-8

40

41
39
Schneier FR, et al. Arch Gen Psychiatry. 1992;49:282-8

40

41
Generalized SAD: Pharmacotherapy*

Recommended First-Line = SSRI or SNRI

• Initial dose for 2-4 weeks, then é if needed
• Should see some benefit in 2 - 4 weeks
• May require up to 2x dose needed for MDD
• 40-60% respond to any one SSRI / SNRI
42 After 6-8 weeks…

• For partial response to SSRI-

—Increase dose as tolerated
—augment with BZ or CBT
• For non-response
—Try a second SSRI
—Switch to an SNRI
—Switch to CBT
43

Generalized SAD: Pharmacotherapy

• Typical pattern:
—Continued improvement over several months
—May take ≥ 1 yr for optimal response
• Continue medication after gains maximized to allow for resumption of
psychosocial development
• Relapse after D/C medication alone is high

44 Treatment of Children and Adolescents

with Anxiety Disorders
Contributor: John T. Walkup, MD
45
44

Contributor: John T. Walkup, MD

45 Anxiety in DSM 5
nDuration criteria increased to 6 months!?
nAnxiety disorders removed from “Disorders First Diagnosed in
Infancy, Childhood and Adolescence”
n

n
46 Anxiety Disorders DSM 5
nSpecific phobia
nSelective mutism
nSeparation anxiety disorder
nGeneralized anxiety disorder
nSocial anxiety disorder
nPanic disorder
nAgoraphobia

nAnxiety disorder associated with another medical condition

nSubstance-induced anxiety disorder
nUnspecified anxiety disorder
n
47 Anxiety Disorders and Phobias
nSpecific Phobia, not Simple Phobia
nSeparation Anxiety Disorder wording change
nOver 18 years can now get SepAD
nSo avoidance of school or work.
nAdults have to have the problem for 6 months or more.
nCan still make the diagnosis with acute separation distress in kids.
nSocial Anxiety Disorder is the preferred name for Social Phobia
nSelective Mutism now classified as an Anxiety Disorder
n
n
48 Anxiety Disorders and Phobias
nPanic Attack
nExpected and unexpected to capture the idea that some are
triggered and some are spontaneous
nPanic Disorder
nPretty much unchanged
48

nPanic Disorder
nPretty much unchanged
nAgoraphobia
nUnlinked from Panic Disorder
nNeed 2 environments so not confused with avoidance from other
anxiety disorders
n
49 Treatment of Anxiety Disorders in Children and Adolescents
50 Bottom Line*
nAntidepressants work extremely well
nSSRIs medication of choice
nAtypical antidepressant should be considered second line, but
considered
nSome limited data on augmentation strategies
nLimited data for benzodiazepines
nNo reason to expect that buspirone or bupropion should be
effective
nTo do a good job will have to prescribe ‘off label’
nCBT also extremely effective when done by an experienced
professional
nOutstanding med management and CBT principles are wonderfully
complementary
51 Ages of Onset Risk
nASDs – 0-3 years or later for mild
nADHD - 4-7 or later for mild, but differential is broader
nAnxiety – 6-12 years
nDepression – 13-16 years
nBipolar and psychosis - > 16 years
nDisruptive behavior – almost anytime
52 Anxiety Disorders in Children and Adolescents
nSpecific Phobia
nSeparation Anxiety Disorder
nGeneralized Anxiety Disorder
nSocial Anxiety Disorder
nAcute Stress Disorder
nPost-traumatic stress disorder
nPanic Disorder
n
53
 nPanic Disorder
n
53 Anxiety is not a great term
nOther terms capture the anxiey better
nHome sickness (separation)
n“Worry worts” (generalized)
nSelf-conscious or shyness (social anx)
nExcessive interpersonal sensitivity
nFear
nApprehension
nDread
nWorry
n
54 Characteristics Common to All Anxiety Disorders
nHypervigilant
nReactive to novel stimuli
nThreat bias
n
nAvoidance coping
nCatastrophic reactions
nParental accommodation
nMidline physical symptoms
n
n
n
n
n
n
55

56 What to look for*

nMidline physical complaints – headaches, stomach aches, dramatic
presentations of pain.
nProblems with falling asleep and middle of the night awakening,
nEating problems – over and under
nExcessive need for reassurance –bedtime, school, storms, bad things
happening
nInattention and poor performance at school
nExplosive outbursts

57
 nInattention and poor performance at school
nExplosive outbursts
nAvoidance of outside and interpersonal activities – school, parties,
camp, sleepovers, safe strangers
nNot necessarily pervasive
57 Assessment Strategies
nGlobal scales with anxiety subscales
nChild Behavior Checklist
nBehavioral Assessment System for Children
nMASC
nSCARED
nChild version
nhttp://www.psychiatry.pitt.edu/sites/default/files/Documents/asses
sments/SCARED%20Child.pdf
nParent on child version
nhttp://www.psychiatry.pitt.edu/sites/default/files/Documents/asses
sments/SCARED%20Parent%20with%20scoring.pdf
n
58 Epidemiology
nVery common up to 8-10% of kids
nUnder diagnosed
nUnder treated
nNeed to look for it
nProbably the most common childhood disorder and the prepubertal
mood disorder
59 Serotonin Reuptake Inhibitors
US FDA Approvals
nApproved for OCD
nClomipramine > 10 yrs
nFluvoxamine > 8 yrs
nSertraline > 6 yrs
nFluoxetine > 7 yrs
nApproved for Depression
nFluoxetine > 12 yrs
nEscitalopram > 12 yrs
nApproved for Non-OCD Anxiety
nDuloxetine for GAD 7-17 years
60

61

1
2
 nDuloxetine for GAD 7-17 years
60 Anxiety Disorders in Later Life

61 Does Aging Increase or Decrease the Likelihood of Anxiety

Symptoms?
1 Less Vulnerability
2 • Negative affect decreases with age (though increases in the mid-
70’s)1
• Life experience offers stress inoculation 2
• Aging locus coeruleus becomes less responsive3
•
3 Greater Vulnerability
4 • Distress of chronic illnesses
• Burden of disability
• Accumulated losses
• Degeneration of dorsolateral prefrontal cortex (DLPFC)4
62 Epidemiology
• Prevalence of anxiety disorders in later life requires further
investigation
• Estimated at 3.2 to 14.2%
• Current view:
–GAD as common as in younger adults
–Specific phobias common, general uncommon
–OCD and Panic Disorder uncommon in later life
–PTSD: Little is known
•
63 6 Month Prevalence of
Anxiety Disorders in Older Men
64 6 Month Prevalence of
Anxiety Disorders in Older Women
65 Age at onset
• Controversy: Are anxiety disorders in later life recurrent or of late
onset?
• Best current answer: “Yes”
–Half have onset in childhood/adolescence
–One third begin at or after age 50
66
65

–Half have onset in childhood/adolescence

–One third begin at or after age 50
66 Etiology*
• Same or different as with younger adults?
–Psychological:
•Conditioning (classical, instrumental)
•Anxiety related to dependence, fears (e.g. falling)1
–Biological:
•Changes in neurotransmitter/endocrine regulation
•Disease burden including cardiopulmonary2
•Medication burden
•Anxiety associated with cognitive impairment3
–
67 A Dire Consequence of Anxiety: Increased Suicide Risk*
• Presence of anxiety disorder* boosts mixed age annual rates of
suicide attempts and suicides
–Suicide attempts: 1350/100,000
–Completed suicides: 193/100,000
• In elderly, presence of anxiety symptoms increases suicide risk.
68 Does Anxiety in Older
Adults Look Different?*
• In general, anxiety symptoms in later life look like those of younger
adults
• Aging diminishes panic symptoms and increases somatization
• Some specific “geriatric anxiety syndromes”:
• Fear of falling
• Fear of dementia
• Hoarding
• Anxiety as a prodrome of cognitive impairment
• “Organic “ (secondary) anxiety
69 Medical Comorbidity*
• 80-86% of adults ≥ 65 years have at least one chronic medical
condition
–Greater comorbidity with increasing age
–36% of older cardiac patients had anxiety disorder
–18-50% of older COPD patients had anxiety disorder
–42% of patients with vestibular symptoms feared falling
–40-43% of PD patients experienced anxiety symptoms

70
 –42% of patients with vestibular symptoms feared falling
–40-43% of PD patients experienced anxiety symptoms
–5-21% of patients with dementia showed anxiety symptoms
• Anxiety increases medical mortality
•
70 Why Do Clinicians Miss Anxiety
in Older Adults?
• Patients may minimize symptoms or not seek treatment
• Patients’ words may mislead, e.g. “concern” rather than “anxiety”
• Patients may forget they have symptoms
• Clinicians may attribute anxiety symptoms to normal aging or a
disease
–Age-specific disorders (fear of falling, hoarding) may be
missed/under-diagnosed).
71 Typical Labs in Geriatric Work-Up*
–CBC with diff
–Metabolic panel: electrolytes, BUN, creatinine, glucose, calcium,
magnesium, LFTs
–B12, folate, homocysteine
–Thyroid: TSH, T3, T4
–ESR
–STD tests as indicated (RPR, HIV)
–Urinalysis
–ECG
–Neuroimaging
•
72 Anxiety Disorder Due to GMC*
• Prominent anxiety, panic attacks, obsessions-compulsions
• Evidence from history, labs, physical exam that the anxiety is a direct
physiological consequence of a GMC
• Severity: causes significant distress or dysfunction
• Exclusions:
• Not better accounted for by another mental disorder
• Does not occur only during a delirium
• Specify if:
• With Generalized Anxiety
• With Panic Attacks
• With Obsessive-Compulsive Symptoms
73
 • With Panic Attacks
• With Obsessive-Compulsive Symptoms
73 Medical Conditions Causing Anxiety*
• Endocrine: hyper and hypothyroidism, pheo-chromocytoma,
Cushing's Syndrome, hypoglycemia
• Cardiac: congestive heart failure, pulmonary embolism, arrhythmia
• Respiratory: COPD, hyperventilation, asthma
• Metabolic: B12 Deficiency, porphyria
• Neuro: encephalitis, tumors, TLE
74 Secondary Anxiety: Treatment
• Treat the underlying medical condition
• Remove the offending agent
• May need to wean gradually, e.g., SSRI
• Provide Symptomatic Treatment
• If anxiety does not resolve quickly consider short term anxiolytic
therapy
75 GAD in Older Adults*
• One of the most common psychiatric disorders in elderly –
• Prevalence: 1% - 7.3%1,2
• High in medical settings
• Course:
• GAD More chronic than depressive episodes (20-30 yr hx at
presentation)3
• Remission is rare
• Diagnostic pitfall: Theme of worry may seem “reasonable”
• Health, relationships, money
• Patients seek medical, not mental health, specialists
• Attend to intensity and functional impairment
!
76 GAD: Epidemiology & Course
• Prevalence in Community Samples
• 1.2 – 7.3%1
• Elderly 1 month prevalence: 1.9%
• Women: 55-60% of patients
• Bottom Line: GAD remains common in elderly
• Onset age of GAD in elderly patients
• 2/3 in childhood or adolescence
• 1/3 onset at ≥ 50 years of age

77
 • 2/3 in childhood or adolescence
• 1/3 onset at ≥ 50 years of age
• Course: chronic – may persist for decades
77 GAD: Psychotherapy
• CBT
• Cognitive Restructuring
• Relaxation Training
• Psychodynamic
• Anxiety signals unconscious conflict or impulses
• Resolve conflict
• Increase ego mastery of remaining anxiety
• Supportive Therapy
• Reduce stress and improve coping skills
• Psychoeducation
78 GAD: Pharmacotherapy*
• SSRI: Several are FDA-indicated for GAD treatment
• Start low, go slow to avoid increase in anxiety
• Consider escitalopram:
•escitalopram: starting dose 5-10 mg daily; if lack response => 15-
20 mg daily
–Paroxetine in common use despite some limitations:
•paroxetine: starting dose 10-20 mg qd; target dose 40-60 mg qd;
CYP2D6 and CYP3A4 inhibitor: avoid with TCAs (may lead to
toxicity) and thioridiazine

"
79 GAD: Pharmacotherapy…*
• SNRI: venlafaxine, duloxetine (FDA-approved)
-- venlafaxine (Effexor and Effexor XR): starting dose 75 mg
daily; may titrate up to 225 mg daily; risk of hypertension at higher
doses (225 mg daily and higher); moderate hepatic impairment:
reduce dose by 50%; mild-moderate renal impairment: reduce by
25%
-- duloxetine: starting dose 20 mg daily, may titrate up gradually to
60 mg daily total dose, in qd or bid schedule; avoid in hepatic
insufficiency or end stage renal disease

"
80
 "
80 GAD: Pharmacotherapy…*
• Buspirone1
• More effective in psychic than somatic anxiety
• 10-45 mg daily in divided doses; relatively benign side effect profile
• Benzodiazepines
• clonazepam: long half life without fast / high peak levels
• Other meds (without FDA indication for GAD)
• Other antidepressants: TCA, MAOIs
• benzodiazepines, pregabalin2 (small evidence-base when anxiety
measured as a secondary outcome in the treatment of pain/spinal
cord injury), antihistamines
•
1.Majercsik E et al. Progress in Neuro-Psychopharmacology and
Biological Psychiatry 2004; 1161-1169; 2. Mehta S et al. Arch Phys
Med Rehabil 2014; 95(11): 2180-6.
2.
2.
2.
2.
"
81 Benzodiazepine Use?*
• Acute, time-limited use may be of help
• Not first line anxiety treatment
• Consider antidepressants first; other medications
• Older adults have increased sensitivity to side effects/adverse events
and lowered metabolism
–Dizziness, weakness, sedation (interfering with driving, operating
machinery), falls and fractures
82 Benzodiazepine use?...*
• Benzodiazepines heavily prescribed in elderly
• Appear efficacious in elderly (1 small study)
• Induce falls and cognitive impairment…
–At a LOWER dose than that effective for anxiety
–Short-acting are not safer
–Favor benzodiazepines with non-hepatic metabolism, though risk
remains
83
 remains
83 Benzodiazepine Use?...*
–If need is documented, consider short-term use with low doses and
with shorter duration benzos (half-lives) to minimize side effects
(though risk remains)
–*Note: avoid abrupt/rapid discontinuation (especially if use has been
chronic) => withdrawal syndrome (rebound anxiety and insomnia,
tachychardia, diaphoresis, restlessness, tremor, seizures)
–
84 Benzodiazepine Use?...*
• Generally start with ½ dose as would be used in younger adults (or
less than ½ in frail older adults)
--lorazepam (Ativan): 0.5–2 mg daily, in divided doses
--oxazepam (Serax) 15-60 mg daily, in divided doses
--clonazepam (Klonopin) 0.25-1 mg daily, in single dose
--alprazolam (Xanax) 0.5-2 mg daily, in divided doses
85 Specific Phobia: Diagnosis DSM 5
• Symptoms
• Marked fear or anxiety about specific object or situation
• Feared object/situation almost always provokes anxiety
• Avoidance or endurance with anxiety
• Anxiety out of proportion to danger
• Lasts 6 months or more
• Clinically significant distress/impairment
• Exclusion: not another mental disorder
• Specifier: animal/environment/blood/situation/other
86 Specific Phobia: Common in Elderly
• Lifetime Prevalence: 3.1-10.2%1
• Prevalence in elderly: 4.8%
• Detection complicated by:
• Lifestyle accommodations
• “Reasonableness” of fears
• Example: Fear of falling
• Important in elderly: Fear of memory loss
!
87 Specific Phobias: Course
• Predisposing Factors
87 Specific Phobias: Course
• Predisposing Factors
• Traumatic events experienced or observed, panic attacks,
parental warnings
• Phobias: 30% concordance for phobias in identical female twins
• Course
• Usually begin in childhood or early adolescence
• May begin anytime, triggered by traumatic events
88 Specific Phobia: Treatment
• Exposure Therapy
• Main form of treatment
• Cognitive Restructuring
• Meds (sometimes helpful):
• SSRIs
• Benzodiazepines (e.g. lorazepam 1-2mg taken 30 minutes prior to
airplane flight)
89 Social Anxiety Disorder: DSM 5
• Marked fear/anxiety of 1 or more social situations involving possible
scrutiny
• Fear of negative evaluation
• Social situations almost always provoke fear/anxiety
• Avoidance or anxious endurance
• Out of proportion
• 6 months or more
• Clinically significant stress/impairment
• Not substance, mental, medical
• Specify if “performance only”
90 Social Anxiety: Psychosocial Tx
• Psychotherapy is first line treatment
–Cognitive Behavioral Therapy
•Cognitive Restructuring
•Exposure Response Prevention
•Individual or Group format
–Social Rehabilitation
•Social skills training
•Communication and assertiveness training
•Role playing
•Joining clubs
91
 •Role playing
•Joining clubs
91 Social Anxiety: Med Treatments*
• SSRIs: First Line meds
–Sertraline: start 25-50 mg qd; target up to 200 mg qd
–Paroxetine (less preferred): start 10-20 mg qd; target dose 40-60
mg qd; CYP2D6 and CYP3A4 inhibitor: avoid with TCAs (may lead
to toxicity) and thioridazine
• SNRI: Venlafaxine
–Starting dose 75 mg daily; may titrate up to 225 mg daily; risk of
hypertension at higher doses (225 mg daily and higher); moderate
hepatic impairment: reduce dose by 50%; mild-moderate renal
impairment: reduce by 25% ; interdose rebound anxiety can
complicate treatment.

92 Social Anxiety: Med Treatments…*

• MAOIs1: effective but more complex to use and less safe because of
adverse effects and drug interactions:
–Serotonergic syndrome (avoid MAOIs with SSRIs, SNRIs and other
serotonergic agents
–Hypertensive Crisis (Noradrenergic Syndrome): avoid
MAOIs with sympathomimetics
• b Blocker: for Specific Social Anxiety Syndromes
–Focused on specific social triggers rather than generalized fear of
contact (e.g. public speaking)
93 Social Anxiety: Med Treatments…*

• Augmenters / alternatives
–Benzodiazepines1 (consider adverse effects, risk for misuse)
–Anticonvulsants: less robust evidence base; evidence specific to
older adults is lacking2: gabapentin3, pregabalin, levetiracetam4,5
94 Panic Disorder in DSM 5
• Symptoms:
• Recurrent unexpected Panic Attacks (4 or more of: palpitations,
sweating, trembling, SOB, choking, chest pain, nausea, dizzy, chills,
paresthesias, derealization, fear lose control, fear dying)
• 1 month or more of persistent worry about attacks or significant

95
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paresthesias, derealization, fear lose control, fear dying)

• 1 month or more of persistent worry about attacks or significant
maladaptive attack-avoiding behavior
• Not substance or medical
• Not other mental disorder

95 Agoraphobia: A Separate Dx in DSM 5

• Marked fear/anxiety about 2 or more of: public transportation, open
spaces, closed places, crowds/lines,outside home alone
• Fear/avoidance because escape might be difficult or help unavailable
• Agoraphobic situations almost always provoke fear/anxiety
• Active avoidance or endurance with fear
• Out of proportion
• At least 6 months
• Clinically significant distress/impairment
• Not medical, or other mental disorder
• Can be co-diagnosed with Panic Disorder
96 Panic Disorder: Epidemiology*
• Mixed adult lifetime prevalence: 1.5 - 5%
• In the elderly, prevalence is lower. Why?
• Stress inoculation
• Decreased physiological response mounted
• Premature death of those with panic disorder
• In elderly, fewer symptoms and less avoidance
• Chronic course
97 Panic Disorder Treatment*
• Lack of evidence specific to elderly populations, so recommendations
are by analogy:
• First line: SSRI or SNRI (fluoxetine, sertraline, citalopram,
escitalopram, fluvoxamine, paroxetine); SNRI: venlafaxine XR,
duloxetine
•Antidepressant preferred over benzodiazepine – also treats
common comorbid depression
•Benzodiazepines avoided due to age-related adverse effects but
adjunctive short-term use may be helpful
--clonazepam, lorazepam
• Second line: TCA (imipramine, desipramine, nortriptyline), MAOI
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 • Second line: TCA (imipramine, desipramine, nortriptyline), MAOI
98 Panic Disorder Treatment…*
• Treatment resistant:
–Possible augmentation with an additional non-serotonergic
antidepressant such as mirtazapine, gabapentin, benzodiazepine
• Frequent initial follow-up is important
–Side effects are common
–Nonadherence is common