Anxiety Flashcards
What are the key symptoms in anxiety disorders?
- Severe, excessive, persistent anxiety and
- irrational fears
- that impair functioning of daily living
Anxiety is out of proportion to the actual danger/threat
Persists long after original trigger disappeared, typically >6m
Untreated anxiety can cause…
- Untreated anxiety if an independent high risk factor for suicide
- Untreated anxiety can increase risks for developing CVD, CBV, GI, and respiratory disorders (e.g., persistent tachycardia can cause ventricular hypertrophy and heart failure)
Anxiety circuits
Fear circuit - regulated by amygdala
Worry circuit - regulated by cortico-striatal-thalamic cortical (CSTC loop)
Neurotransmitter implicated in anxiety
Serotonin
GABA
Norepinephrine
Medical conditions associated with anxiety
- Cardiovascular (e.g., angina, arrhythmias, CHF, IHD, MI)
- Endocrine/Metabolic (e.g., Cushing’s disease, hyperthyroidism)
- Neurologic (e.g., Dementia, delirium, parkinson’s, seizures, stroke, neoplasms, inadequate pain control)
- Pulmonary (e.g., asthma, COPD, PE, pneumonia)
- Others: anemias, SLE, vestibular dysfunction
Impt to check troponin, ECG, FBG, thyroid levels etc. to rule out medical conditions
Drug-induced anxiety
(Similar to the drugs that induce mania)
- Sympathomimetics (e.g., pseudoephedrine)
- Stimulants (e.g., amphetamines, cocaine)
- Methylxanthines (e.g., caffeine, theophylline)
- Thyroid hormones (e.g., Levothyroxine)
- Corticosteroids (e.g., prednisolone - systemic)
- Antidepressants (e.g., SSRI, TCAs, esp with rapid dose escalation due to sudden increase in neurotransmitters)
- Dopamine agonists (e.g., Levodopa)
- Beta-adrenergic agonists (E.g., Salbutamol)
Other drug-related causes:
- Withdrawal (caffeine, alcohol, sedatives, BZDs, antidepressants, nicotine)
- Intoxication (e.g., anticholinergics, antihistamines, digoxin)
What is a panic attack?
Discrete period of intense fear/discomfort, with 4 or more of the following symptoms, developed abruptly, reached a peak within 10 min, usually lasts no more than 20-30min
May be expected or unexpected
- Palpitations, incr PR
- Sweating
- Trembling/shaking
- Sensations of shortness of breath
- Feeling of choking
- Chest pain/discomfort
- Nausea or abdominal distress
- Feeling dizzy, unsteady, lightheaded, faint
- Derealization or depersonalization
- Fear of losing control or going crazy
- Fear of dying
- Paresthesia (numbness, tingling sensation)
- Chills or hot flushes
Name the 5 anxiety disorders that are most amendable to drug treatment
- Panic disorder
- Social anxiety disorder (SAD)
- Generalized anxiety disorder (GAD)
- Obsessive compulsive disorder (OCD)
- Post traumatic stress disorder (PTSD)
Describe Generalized anxiety disorder (GAD)
(CIMSRF)
Excessive anxiety and worries 6m or more, over a pervasive spread of things, cause significant functional impairment
3 or more of the following symptoms:
- Restlessness
- Being easily fatigue
- Difficulty concentrating or mind going blank
- Irritability
- Muscle tension
- Sleep disturbance (insomnia, restless unsatisfying sleep)
Pharmacotherapy for GAD
SSRIs: Escitalopram, Paroxetine
SNRIs: Venlafaxine XR, Duloxetine
Pregabalin
Others: TCA, BB, hydroxyzine, buspirone etc.
Non-pharmacotherapy for GAD
Cognitive behavioral therapy
Psychotherapy
Relaxation
Anxiety management
Describe Panic disorder
Anticipatory anxiety of recurrent panic attacks:
- Recurrent unexpected panic attacks
AND
- > =1 of the panic attacks has been followed by >=1m of >=1 of the following:
- Persistent anticipatory anxiety about having panic attacks
- Worry about implications of panic attack
- Significant change in behavior related to panic attacks
May occur with or without agoraphobia
Pharmacotherapy for Panic Disorder
SSRIs: Fluoxetine, Paroxetine, Sertraline
SNRI: Venlafaxine
TCAs
Non-pharmacotherapy for Panic Disorder
CBT
Describe Social anxiety disorder (SAD)
Fear of being scrutinized or humiliated by others in public of >=1 social/performance situations, duration >6 months
The feared situations are avoided or endured with intense anxiety/distress, the avoidance or anxious anticipation or distress in the feared situation significantly impairs functioning
Pharmacotherapy for SAD
SSRIs: Fluvoxamine, Paroxetine, Sertraline
SNRI: Venlafaxine
Others: RIMA - Moclobemide or MAOi
Non-pharmacotherapy for Panic Disorder
Behavioral therapy
Describe Obsessive compulsive disorder (OCD)
Obsessional thoughts/impulses that causes anxiety, followed by compulsive behaviors to relieve that anxiety; person recognizes and is aware that the obsessions/compulsions are excessive and irrational and significantly impairs functioning (e.g., time-consuming >=1h a day)
- Obsession: recurrent and persistent thoughts/impulses/images, intrusive and inappropriate, causing marked anxiety/distress (e.g., contamination, dirt)
- Compulsion: repetitive behaviors or mental acts performed aimed at preventing/reducing the distress but NOT connected in a realistic way, and clearly excessive (e.g., washing hands)
Pharmacotherapy for OCD
SSRIs: Fluoxetine, Fluvoxamine, Paroxetine, Sertraline
Clomipramine - TCA (2nd line for OCD)
Non-pharmacotherapy for OCD
CBT
Exposure and response prevention (ERP)
Describe Post traumatic stress disorder (PTSD)
(SIANA)
Re-experiencing of trauma, persistent avoidance, increased arousal
- Stressor
- Intrusive symptoms - persistent re-experience
- Avoidance - of distressing trauma-related stimuli
- Negative alterations in cognition and mood
- Alterations (increase) in arousal and reactivity
Persistence of symptoms for >1 month, significant functional impairment
Pharmacotherapy for PTSD
SSRIs: Paroxetine, Sertraline
*DO NOT USE Benzodiazepines
- numbs the brain, sedating
- in PTSD, patient is encouraged to actively participate in sharing of traumatic event
Non-pharmacological for PTSD
CBT (1st line)
Psychotherapy
Counseling
Non-pharmacological in anxiety disorders should be used ________
Psychotherapy should be used in combination with medications
CBT/Psychotherapy is key (1st line), medications are adjunctive
Which drug is used for physical or worrying symptoms in anxiety?
Physical symptoms (tremors, tense, palpitation, sweating):
- Benzodiazepines
Worrying symptoms
- SSRIs
Which drugs used in acute stress disorder
- Benzodiazapines (short-course, PRN)
- Antihistamines (e.g., hydroxyzine)
What scale is used to assess anxiety?
Clinician-rated Hamilton Anxiety Scale (HAM-A)
Treatment goal for anxiety disorders:
- Remission of anxiety symptoms
- Functional recovery
Medications have a role for anxiety that is persistently severe and disabling
[Antidepressant in anxiety]
Which antidepressants can be used?
All serotonergic antidepressants can be useful for long-term management of GAD, PD, SAD, OCD, PTSD
- SSRIs > SNRIs > Clomipramine
- In OCD, 1st line SSRI, 2nd line Clomipramine, 3rd line Venlafaxine
[Antidepressant in anxiety]
Approach to dosing
Low starting dose
- transient jitteriness in initial 1-2 weeks due to increase in neurotransmitters
Consider BZD as adjunct for acute anxiety symptoms
- because antidepressants work slowly (gradual downregulation of presynaptic autoreceptors after chronic exposure to effects of the antidepressants)
High maintenance dose
- E.g., fluoxetine for anxiety start as 10mg/day but can increase to max maintenance dose of 60-80mg/day (VS in depression - 20mg/day)
[Antidepressant in anxiety]
Onset, efficacy, and duration of treatment
Onset: 1-2 months (recall 4-8 weeks for mood symptoms and anxiety)
- 6-12 weeks to achieve initial efficacy, max/full response may require 3 months
Efficacy: effective for worrying symptoms, not effective for physical symptoms (tense, tremors, palpitations)
Duration: at least 1-2 years, may be lifelong
[Adjuncts]
List the adjuncts used in anxiety disorders
- Benzodiazapine
- Antihistamine (hydroxyzine)
- Beta blockers (propranolol)
Pregabalin may be used as well - not adjunct
[Adjunctive benzodiazepines in anxiety]
Therapeutic action
Onset
BZDs effective for physical symptoms of anxiety (as an anxiolytic)
Fast onset of action, work vv fast to manage acute symptoms
- E.g., Lorazepam (fast onset within 30min)
They can be used in acute stress disorder or adjustment disorders
[Adjunctive benzodiazepines in anxiety]
Duration
Short-term 3-4 months of treatment, PRN dosing
*But typically supply only 2-4 weeks for short-term basis
[Adjunctive benzodiazepines in anxiety]
Choice of BZD in anxiety disorders
High potency agents preferred in anxiety disorders
- Clonazepam
- Lorazepam
- Alprazolam XR (for panic disorder) - short-acting therefore XR formulation, most potent, most abuse and death
[Adjunctive benzodiazepines in anxiety]
Short acting vs Long acting BZDs
Short-acting (~6h): Lorazepam, Alprazolam
Long-acting (~10h): Diazepam (less preferred as can cause drowsiness throughout the day, affect cognition, cause falls esp in elderly), Clonazepam
FYI: very short acting: Midazolam (~2h)
[Adjunctive benzodiazepines in anxiety]
Tolerance
Tolerance to anxiolytic action is less common
Tolerance to hypnotic actions more common, develops within days (same dose less effective overtime)
May develop if used continuously for >1-2 weeks
[Adjunctive benzodiazepines in anxiety]
Dependence, withdrawal
- Avoid abrupt cessation after weeks of continued use (withdrawal)
- Gradual taper required
BZD withdrawal symptoms:
- Incr HR
- Agitation
- Rebound Anxiety
- Tremors
- Insomnia
- Seizures
- Hallucinations
[Adjunctive benzodiazepines in anxiety]
Dosing (general principles)
- Lowest effective dose PRN for 1-2 weeks (prevent risk of dependence)
- Intermittently (once every 2 or 3 nights for insomnia)
[Adjunctive benzodiazepines in anxiety]
Cautions
- Paradoxical excitement/disinhibition - i.e., agitation, tachycardia (esp in children elderly, head injury)
- Dependence and withdrawal symptoms can occur esp in pt with history of drug dependence
[Adjunctive benzodiazepines in anxiety]
Doses of the following:
- Alprazolam
- Clonazepam
- Diazepam
- Lorazepam
Alprazolam (anxiety)
- 0.25mg - 0.5mg BD-TDS, max 4-6mg/day
- Short duration of action
- No major active metabolite
Clonazepam (anxiety)
- 0.5mg BD, max 4mg/day
Diazepam (anxiety, insomnia)
- 2-10mg BD-QDS
Lorazepam (anxiety, insomnia)
- 2mg/day (in divided doses), titrate to 2-3mg/day; max dose 6mg/day, do not exceed 10mg/day (elderly/debilitated - 0.5mg/day, max 2mg/day)
- short duration of action
- primarily hepatic metabolism: glucuronidation
- no interaction with cyp enzymes
- no active metabolites
[Adjunctive benzodiazepines in anxiety]
Lorazapam metabolism and CYP interaction
Lorazepam metabolized via hepatic glucuronidation, no active metabolites
Not a substrate of CYP enzymes (unlike other BZDs - CYP3A4 substrates)
[Adjunctive benzodiazepines in anxiety]
BZD use in panic disorder
Do not stop regular dosing, do not stop abruptly, or might go into withdrawal
[Other adjunctives - Antihistamines]
- Hydroxyzine
Sedating antihistamine - hydroxyzine (labelled for anxiety and insomnia)
- Does NOT cause dependence
- Watch for anticholinergic side effects
- Careful with doses, typically use 10-25mg; high doses of 100mg cause QTc prolongation (sudden cardiac death)
- Active metabolite: Cetirizine
[Other adjunctives - Beta blockers]
- Propanolol
Propanolol (non-selective BB)
- Caution in pt with history of asthma (bronchoconstriction)
[Other - Pregabalin] - GAD only
Also comment on its risk for dependence
Anticonvulsant - Pregabalin
- Indication: may be used as an anxiolytic in GAD only
- Onset: 1-2 weeks (doe not work immediately)
- Pregabalin can increase expression of enzymes that produce GABA (promote GABA transmission)
- Some potential for dependence
General DDIs to look out for:
- Alcohol and other CNS depressants: incr CNS depressant side effects of benzodiazepines and antidepressants
- Anticholinergic side effects
- MAOIs, SSRIs, TCAs => watch for serotonin syndrome (mental status change, autonomic instability, neuromuscular changes)
