Anxiolytics CA2 Flashcards
Brief description of anxiety-related disorders
Generalised Anxiety Disorder: excessive anxiety and worries for >6 months
Panic disorder: anticipatory anxiety and recurrent panic attacks
Obsessive Compulsive Disorder (OCD): occasional thoughts/impulses that cause anxiety, followed by compulsive behaviours to relieve that anxiety.
Post-traumatic stress disorder (PTSD): re-experiencing of trauma, persistent avoidance and increased arousal.
Etiology and pathophysiology of anxiolytics
- Fear circuit is regulated by the amydala
- Worry circuit is regulated by the cortico-striatal-thalamic cortical (CSTC) loop.
- Neurotransmitters involved:
» Serotonin
»> Pathological fear/anxiety is related to the over-activation of the amygdala.
»> High serotonin output -> increased anxiety
» GABA
»> Inhibitory neurotransmitter
»> Low levels -> high anxiety
Medical conditions associated with anxiety
cardiovascular: heart failure
endocrine: hyperthyroidism
neurologic: dementia, delirium
pulmonary: asthma, COPD
Clinical presentation of GAD
- Excessive anxiety and worry ≥ 6 months
- 3 or more of the following symptoms:
1. Restlessness or feeling on edge
2. Being easily fatigued
3. Difficulty concentrating or mind going blank
4. Irritability
5. Muscle tension
6. Sleep disturbance (insomnia, restless unsatisfying sleep) - Can cause significant functional impairment
Clinical presentation of panic disorder
- Recurrent unexpected panic attacks, and ≥1 of the panic attacks has been followed by ≥1 month of ≥1 of the following:
» Persistent anticipatory anxiety of having additional panic attacks
» Worry about the implications of the panic attack
» Significant change in behaviour related to the panic attacks.
Clinical presentation of social anxiety disorder
- Marked and persistent fear of ≥1 social/performance situations, where the person is exposed to unfamiliar people or possible scrutiny by other. He/she acts in a way that will be humiliating or embarrassing.
- Duration: >6 months
- Social situations are avoided, impairs functioning.
Clinical presentation of PTSD
- Person is exposed to a major stressor: e.g. death, threatened death, violence
- Traumatic experience is persistently re-experienced by the person
- Persistent, effortful avoidance of distressing, trauma-related stimuli post event
- Negative alterations in mood and cognitions
- Trauma-related alterations in arousal or reactivity
» Irritable and aggressive behavior
» Self-destructive etc. - Persistence of symptoms, could lead to functional impairment
Assessment of anxiety disorder
- Clinician-rated: Hamilton Anxiety Scale (HAM-A)
» Significant anxiety: Score 18-20
» Response= 40-50% reduction
» Recovery = score <7
» Pros: gold standard, Cons: takes a long time to be administered, and has to be by someone trained. - Self-rated :
» Beck Anxiety Inventory (BAI)
» Zung Self-rated Anxiety Scale - Identify target symptoms for each type of anxiety disorders
- Keep detailed diary to record fear levels, physical symptoms, cognitions and anxiety behaviors.
Treatment for GAD
Pharmacotherapy:
- SSRI
- Venlafaxine XR
- Pregabalin
Non-pharmacological:
- CBT
Treatment for Panic Disorder
Pharmacotherapy:
- SSRI
Non-pharmacological:
- CBT
Treatment for Social Anxiety Disorder
Pharmacotherapy:
- SSRI
Non-pharmacological:
- Behavioural therapy
OCD
Pharmacotherapy:
- SSRI, clomipramine
Non-pharmacotherapy:
- CBT
- Exposure and prevention therapy
PTSD
Pharmacotherapy:
- SSRI
Non-pharmacotherapy:
- CBT, psychotherapy, counselling
Treatment principles of antidepressants
- All serotonergic antidepressants can be used for long-term management of anxiety disorders, OCD, PTSD
- Approach to dosing: titrate upwards
- Serotonergic antidepressant: effective for excessive worrying types of disorders. Onset at least 1-2 months, to see the full impact must wait for 3 months.
Different types of antidepressants (SSRI)
escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
Different types of antidepressants (SNRI)
Venlafaxine XR, duloxetine
Different types of antidepressants (TCA)
Clomipramine
Different types of anxiolytics (benzodiazepines)
Alprazolam, clonazepam, diazepam, lorazepam
Different types of anxiolytics (antihistamines)
hydroxyzine
Different types of anxiolytics (beta blockers)
propanolol
Anticonvulsant
pregabalin
Treatment: Adjunctives:
A. Benzodiazepines
- Not recommended for monotherapy
- Therapeutic action: effective for physical symptoms of anxiety
» Fast onset of action: can be within 30 minutes
- Aim for short term treatment
- Gradual taper required
- High potency, therefore preferred for anxiety disorders
- E.g. Clonazepam, lorazepam, alprazolam XR (panic disorder)
B. Pregabalin (GAD
Significant drug-drug interactions
- General:
» Alcohol and other CNS depressants
» Anticholinergic agents
» MAOIs and SSRIs/TCAs combinations: serotonin syndrome - Antidepressant drug-drug interactions
- Benzodiazepines DDI
» CNS depressant effects with alcohol and other CNS depressants
» Benzodiazepines + opioids = increased morality
What are the long-term treatment goals of anxiety disorders?
- GAD, Panic disorder, SAD, PTSD
» Remission of core anxiety symptoms, recovery of function - OCD :
» Complete resolution of symptoms is often difficult to achieve
» Relapse rates are very high with poor medication adherence
Recommended duration of all medication treatment
- At least 1 year for all anxiety disorders
- At least 1-2 year for OCD
What are some early and long-term adverse effects to pharmacotherapy?
- Early:
» Possible increased anxiety with antidepressants during first 1-2 weeks - Long-term:
» Sexual dysfunction and weight gain are common with antidepressants, may lead to discontinuation of treatment
escitalopram dose
10mg/day, 10-20mg/day max
PD, SAD: 5mg/day
fluoxetine dose
20mg/day, 80mg max
PD: 5mg
paroxetine dose
20mg/day
max: 40-60mg/day
sertraline dose
25mg/day, 200mg total
venlafaxine dose
37.5mg-75mg
PD, PTSD: 37.5mg
total: 75-225mg
clomipramine dose
25mg, 100-250mg total
Alprazolam dose
- 5-4mg/day
max: 10mg
clonazepam dose
- 5-1mg/day
max: 4mg/day
diazepam dose
4-15mg/day
max: 40mg / day
lorazepam
1-3mg/day
max: 8mg/day
