Lecture 7 Diagnostics & Therapeutics of Anxiety Disorders ... · disorder & generalized anxiety disorder o Short-term use of lowest effective dose • Acts as a central nervous system

Lecture 7 Diagnostics & Therapeutics of Anxiety Disorders Johal

GENERALIZED ANXIETY DISORDER:

DIAGNOSTIC CRITERIA:

• Excessive anxiety & worry lasting for at least 6 months

• Three of the following symptoms:

o Restlessness

o Easily fatigued

o Difficulty concentrating

o Irritability

o Muscle tension

o Sleep disturbance (insomnia)

o Significant distress or functional impairment

due to sx

• Sx not caused by a substance (cocaine, steroids) or a

medical condition

• Focus of the anxiety and worry are not caused by

another anxiety or psychiatric disorder

RISK FACTORS:

• Mean onset is 21 years

o 60% of pts have onset b/w 11 and early 20s

• Onset occurs earlier when GAD is the primary

presentation, and occurs later when GAD is secondary

to other psychiatric disorders

• 90.4% of patients reported having at least one other

lifetime mental health disorder

GENERALIZED ANXIETY DISORDER ASSESSMENT (GAD)-7:

• Screens for GAD and assesses severity

• Brief (5 minutes); self-rated

• 15 = severe anxiety; 10 = moderate; 5 = mild

TREATMENT FOR GAD:

• Initial therapy = medications, psychotherapy, or combo

o Both approaches efficacious, unclear if

combination is better

• First line = SSRI or SNRI

o Preferred as they are generally safer & better

tolerated than TCAs or MAOIs

o Some patients may require small initial doses for

the first week (1/2 of the recommended starting

dose) to prevent activation syndrome

• Non-response: unclear if it is better to increase dose,

augment, switch, or wait longer if partial response

o Switch to another SSRI or SNRI

o Augmentation with buspirone, BZD or pregabalin

• Psychological treatments

o Cognitive behavioral therapy (CBT) protocols

o Mindfulness-based cognitive therapy (MBCT)

TIMELINE FOR ANXIETY DISORDERS:

• Follow up with the patient at 2-week intervals with a

goal of remission at 8-12 weeks

o If no response, trial of different SSRI considered

• May take 4-6 weeks for impact on improvement

o Pharmacotherapy should be continued for at

least a year after response

• Improvement for anxiety disorders is typically > 25%

reduction in symptoms

BENZODIAZEPINES:

ADVERSE EFFECTS:

• Not effective for depressive sx

and may contribute to depression

with long-term administration

• Drowsiness, sedation

• Psychomotor impairment

• Impairment of memory & recall

• Abuse, dependence & withdrawal

• Rebound anxiety, relapse,

withdrawal

SEIZURES UPON WITHDRAWAL:

• Occur within 3 days of drug

discontinuation (short t1/2)

o Can occur up to 1 week after

stopping longer t1/2 agent

• Increased risk: higher dose, longer

durations, concurrent ingestion of

meds that lower seizure threshold

TAPERING PRINCIPLES:

• 25% per week reduction in dosage

until 50% dose is reduced, then

reduce 1/8th every 7 days

• Therapy:

> 8 wks = slow taper over 2-3 weeks

> 6 mo = slow taper over 4-8 weeks

> 1 yr = slow taper over 2-4 months

• Switching from short long-acting

BZD before gradual taper not

recommended in literature

USES:

• Low doses of high potency BZDs

used to abort initial panic attacks

& control high-frequency attacks

later in panic disorder

• Also used in social anxiety

disorder & generalized anxiety

disorder

o Short-term use of lowest

effective dose

• Acts as a central nervous system

depressant which essentially

calms things down

CONSIDER USING BZD:

• 2-4 weeks when initiating

treatment with an anti-

depressant to achieve more rapid

relief and mitigate potential anti-

depressant-induced anxiety

• Comorbid bipolar disorder

• Next-step monotherapy or

augmentation in pts who respond

poorly to antidepressants or CBT

PATIENT EDUCATION:

• Duration of therapy is 2-4 weeks,

with first-line antidepressant

• Consequences of ingestion with

alcohol & other CNS depressants

• Provides symptomatic relief but does

not treat underlying psychological

problems

DOSE EQUIVALENTS OF BZDS:

BZD T1/2 mg

Diazepam Long 5

Clonazepam Intermediate 0.25

Alprazolam 0.5

Lorazepam 1

Triazolam Short 0.25

BUSIPRONE:

• Second-line for GAD or augmentation onto SSRI/SNRI

• Delayed onset of effect (2 weeks or longer)

• Not useful in clinical situations requiring immediate anxiolysis

• BZD use within 1 month before buspirone associated with reduced efficacy

• Very short t1/2 (2.5 hours), requiring dosing 2-3 times/day

• Does not treat underlying depression symptoms

SPECIAL POPULATIONS:

• Pregnancy/lactation: BZDs associated with increased risk of cleft lip or palate, and

neonatal withdrawal symptoms

o Short-acting BZDs (alprazolam & lorazepam) safest to use in breastfeeding

• Children/adolescents: SSRI and CBT

• Elderly patients: most common anxiety disorder

o Citalopram, sertraline, CBT is best (due to drug interactions)

Lecture 7 Diagnostics & Therapeutics of Anxiety Disorders Johal

PANIC DISORDER:

DIAGNOSTIC CRITERIA:

• Panic attack = a distinct period of intense fear or discomfort

when 4 or more symptoms developed and achieve a peak

within 10 minutes

• Panic disorder = recurrent unexpected panic attacks with at

least one of the attacks being followed by >1 month of at

least one of the following:

a) Constant concern about having another attack

b) Being anxious about the implications of the attack

or its consequences

c) Maladaptive change in behavior designed to avoid

having panic attacks

SYMPTOMS:

Psychological Physical

• Fear of loosing control

• Fear of dying

• Fear of going crazy

• Chest pain

• Palpitations

• Nausea

• Tachycardia

• Sweating

RISK FACTORS:

• Females > males

• Environmental (context, triggers)

• Learned avoidance behavior

• Stressful life events

• Genetics (family member develops disorder before age 20 =

17x more likely)

TREATMENT RESPONSE:

• 1/3 of patients achieve remission

• 1/5 of patients follows an unremitting and chronic course

PREDICTORS OF LONG-TERM COURSE:

• Long duration of illness

• Agoraphobia

• Comorbidity with personality, mood, or other anxiety disorders

• Excessive sensitivity to physical anxious symptoms

• Anxiety sensitivity: belief that anxiety can cause deleterious physical,

social, and psychological consequences

• Maintenance of panic: acute fear that develops after initial panic attack

TREATMENT OF PANIC DISORDER:

• Initial therapy of PD can be with medications or psychotherapy

o SSRIs and venlafaxine

o BZDs for panic attacks (ex// lorazepam SL prn)

• Combination of pharmacotherapy and CBT is an option with patients who

continue to have symptoms with maximization of pharmacotherapy

SPECIAL POPULATIONS:

• Pregnancy/lactation: psychosocial treatment is preferred

o If pharmacotherapy needed, assess risks vs benefits of appropriate agent

• Adolescents: may present as fear of leaving home

• Elderly patients: exhibit fewer, less intense symptoms, and less avoidant behavior

POST-TRAUMATIC STRESS DISORDER (PTSD):

DOMAINS OF PTSD:

Re-experience Recurrent, intrusive, distressing memories of the trauma

Avoidance Avoidance of thoughts, feelings, or conversations about the trauma

Hyper-arousal Decreased concentration, hypervigilance, trouble sleeping, irritability, or angry outbursts

RISK FACTORS:

• Pre-traumatic: gender (women at higher risk during

childbearing years than men); genetics

• Peri-traumatic: magnitude of event/period

• Post-traumatic: follow-up

DURATION:

• 36 months with treatment, 5 years without

• 1/3 will develop chronic symptoms that do not remit

• Concurrent disorder: depression (80%); substance use (50%)

TREATMENT OF PTSD:

• General approach = exposure-based CBT or pharmacotherapy with SSRI/SNRI

• All guidelines recommend against BZD in PTSD

SSRI/SNRI:

• Paroxetine, sertraline, fluoxetine are first-line agents for PTSD

• Other SSRIs may also be beneficial (less evidence)

• Venlafaxine recommended as first-line option in some guidelines

o High dose (mean = 221.5 mg/day)

o Only re-experiencing/avoidance improved (not hyperarousal)

OTHER PHARMACOTHERAPY:

• Anti-convulsants: typically used as adjunctive agents with antidepressants

• 2nd-generation antipsychotics: not effective as monotherapy

• Prazosin: sleep-related sx and core symptoms of combat-related PTSD

o Insomnia & nightmares = core sx that can be made worse with SSRIs

• Clonidine: PTSD in children

o Decreased emotional lability, hyperarousal, nightmares

BZD USE IN PTSD:

• No evidence that BZDs reduce core symptoms

• Potentiate acquisition of fear response and worsen trauma recovery

• No positive long-term data

o Early BZD administration associated with higher incidence of PTSD at

1- and 6-month follow-up

SPECIAL POPULATIONS:

• Pregnancy/lactation: CBT first-line option

• Children: “at-risk samples”; re-enact traumatic events in play

o CBT, medications for target sx

• Elderly: common, especially older veterans

o Treatment similar to adults (monitoring)

Lecture 7 Diagnostics & Therapeutics of Anxiety Disorders Johal

OBSESSIVE COMPULSIVE DISORDER (OCD):

DIAGNOSTIC CRITERIA:

• Must have obsessions, compulsions or both

o Obsessions = persistent & recurrent thoughts or urges

that cause anxiety or distress

▪ Patients attempt to ignore or neutralize them

with a different thought/action (i.e. compulsion)

o Compulsions = repetitive behaviors or mental acts to

reduce anxiety (not connected in a realistic way)

• Obsessions and compulsions cause marked distress and:

o Are time consuming (>1 hour/day)

o Significantly interfere with a person’s normal routine,

occupational functioning, or usual social relationships

SPECIFIERS:

• Good or fair insight: recognizes OCD beliefs are definitely or

probably not true

• Poor insight: thinks OCD beliefs are probably true

• Absent insight (delusional beliefs): thinks OCD beliefs are true

CLINICAL COURSE:

• Often present to other physicians other than psychiatrists

o ex// dermatologists with chapped hands

• More than 50% have a sudden onset of symptoms

• Delay of 5-10 years before treatment because many patients

keep symptoms secret

• Comorbidity with depression occurs in one-third of patients

• Course is long and variable

TREATMENT:

• Pharmacotherapy with SSRI, or CBT

o 6-8 weeks, but sometimes 10-12 weeks, for symptom reduction

• With little or no response, trying another SSRI is recommended

o Clomipramine is recommended after a failure of two SSRIs

• NOTE: Canadian Anxiety Guidelines says bupropion NOT effective for OCD

SSRIs:

• Results of treatment trials suggest abnormalities in 5-HT neurotransmission

• Fluoxetine, fluvoxamine, paroxetine, sertraline

o More similar in efficacy to clomipramine, but more tolerable

• Higher doses produce a higher response rate and symptom relief

o Max dose – maintain for at least 4-6 wks before assessing response

CLOMIPRAMINE:

• Selective and potent inhibition of 5-HT reuptake in presynaptic neuron

• Response rates may lower in patients with depression

DOSE:

• 25 mg/day initial, increasing by 25 mg increments every 4-7 days up to

100 mg/day in first 2 weeks

• Dose to response (max 250 mg/day)

DRUG INTERACTIONS:

• Fluvoxamine, paroxetine, fluoxetine inhibit metabolism of clomipramine

o Case reports of sertraline interaction

• (Es)citalopram preferred agent if an SSRI is combined with clomipramine

ADVERSE EFFECTS:

• Anticholinergic effects

• Dizziness, drowsiness, headache, sedation

• Epilepsy = seizure risk

• Orthostatic hypotension

• Weight gain

• Elevated LFTs

• Cardiotoxic in overdose

SAFETY:

• ECG: obtain baseline in patients over 40 y/o or at risk of heart disease

• LFTs: obtain at baseline and periodically during therapy

• TDM: (desmethyl)clomipramine should be below 500 ng/Ml

o Asian pts at higher risk of toxicity due to decreased clearance

o Ultra-rapid CYP2D6 metabolizers may need unusually high doses

DURATION OF THERAPY:

• Continued for 1-2 years before tapering

• Relapse rates are very high (up to 89%)

• Treatment should continue indefinitely for most patients

MONITORING:

• During acute phase weekly for 4 weeks, then bi-weekly; then evaluate on monthly basis to monitor symptom change over time

o Can be extended to every 1-2 months during months 6-12

o Patients should keep a symptom diary

SPECIAL POPULATIONS: PREGNANCY

• CBT alone is recommended for women desiring to become

pregnant or breastfeeding

• OCD symptoms onset during pregnancy occurs in up to

12-39% of women

• OCD severity is usually unaffected by pregnancy

• Women with OCD are vulnerable to worsening during times of

hormone fluctuation (increased monitoring)

Lecture 7 Diagnostics & Therapeutics of Anxiety Disorders Johal

SOCIAL ANXIETY DISORDER (SAD):

DIAGNOSTIC CRITERIA:

• Marked fear or anxiety about 1 or more social situation

where the individual is exposed to possible scrutiny by others

o Social situations typically provoke fear/anxiety

o Anxiety/fear is out of proportion to actual threat or

socio-cultural context

• Persistent and lasts > 6 months

• The anxiety or avoidance causes clinically significant

impairment or distress

CLINICAL COURSE:

• Mean age of onset is 14-16 years

• Delay to treatment is typically 10 years

o Without txt, course is chronic, unremitting and lifelong

• 70-80% have history of concurrent anxiety, depression

and/or substance use

o Early detection, education, treatment

TREATMENT:

• Individual CBT specific for SAD

• Pharmacotherapy with an SSRI

o 10-12 weeks of SSRI (dose-response curve is relatively flat)

o Limited evidence behind citalopram

• Limited evidence supports augmentation for patients with partial response

o Changing to another SSRI or venlafaxine recommended

SIGNS AND SYMPTOMS:

• Fears

• Feared situations

• Physical symptoms

• Types (generalized vs. non-generalized)*

NON-GENERALIZED = performance related

BETA BLOCKERS

• Not effective in generalized SAD

• May be used in non-generalized performance-related SAD

o Decreases tremor, palpitations, and blushing

• Propranolol 10-80 mg or atenolol 25-50 mg 1-2 hours before performance

o Test dose to assess tolerability

ONSET/DURATION OF THERAPY:

• 6-8 weeks on antidepressant therapy

o Response as early as week 3 of therapy with venlafaxine

• Patients encouraged to keep a symptom diary

• 1 year or longer after response is attained to prevent relapse

o Relapse common after discontinuation

SPECIAL POPULATIONS:

• Children: early treatment is important to limit persistence to adulthood

o CBT and social skills training

• Elderly: unrecognized and underdiagnosed in this population

TREATMENT TIPS FOR ANXIETY DISORDERS:

Panic disorder (PD) • Agoraphobia = more severe cases

• BZDs for panic attacks

GAD • Buspirone and pregabalin are 2nd line options

PTSD • 3 domains of presentation

• Risk factors

• BZDs not indicated

OCD • Highly serotonergic reuptake needed = high dose SSRIs or clomipramine

SAD • B-blocker (propranolol) for symptoms of performance related anxiety)