lecture 7 diagnostics & therapeutics of anxiety disorders ... · disorder & generalized...
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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)