Treatment of Anxiolytics Flashcards
Types of Anxiety Disorders
1) GAD
- Excessive anxiety & worries > 6mths
2) Panic Disorder (PD)
- Anticipatory anxiety of recurrent panic attacks
3) Social anxiety disorder (SAD)
- Fear of being scrutinised/humiliated by others in public
4) OCD
- Obsessional thoughts/impulses, followed by compulsive behaviours
5) PTSD
- Re-experiencing of trauma, persistent avoidance, increased arousal
What is the “fear circuit” regulated by?
Amygdala
What is the “worry circuit” regulated by?
Cortico-stratial-thalamic-cortical (CSTC) loop
Neurotransmitters involved in Anxiety disorders
Serotonin (5-HT):
- Fear/anxiety due to over-activiation of amygdala
- -> Amygdala receives input from serotonergic neurons which can inhibit its outputs
GABA:
- Inhibitory neurotransmitter
- Benzodiazepines potentiate GABA
Norepinephrine
Medical conditions associated with Anxiety
CVS: Congestive HF
- Hypoxia will potentiate anxiety
Endocrine: Hyperthyroidism
- Rapid irregular heartbeat, nervousness, irritability, trouble sleeping, fatigue
Neurologic: Dementia, delirium
Pulmonary: Asthma, COPD
Drug classes that can potentiate drug-induced Anxiety
- Sympathomimetics
- Stimulants
- Corticosteroids
- Antidepressants
- Dopamine agonists
- Beta-adrenergic agonists
- Drug withdrawal
- Drug intoxication
Clinical presentation of Panic Attack
Discrete period of intense fear/discomfort, sxns develop abruptly & peaks w/in 10min (usually not more than 20-30min)
> =4:
- palpitations, pounding heart
- sweating
- trembling/shaking
- sensations of SOB
- feeling of choking
- chest pain/discomfort
- Nausea/ab distress
- Dizzy, lightheaded
- Derealization or feeling detached
- fear of losing control/going crazy
- fear of dying
- numbness or tingling sensation
- chills or hot flushes
Clinical presentation of GAD
Excessive anxiety & worry >=6mths
> =3:
- Restlessness or feeling keyed up or on the edge
- Easily fatigue
- Difficulty concentrating or mind going blank
- Irritability
- Muscle tension
- Sleep disturbance (insomnia, restless unsatisfying sleep)
- Sxns cause functional impairment
Clinical presentation of Panic disorder with or w/o Agoraphobia
1) Recurrent unexpected panic attacks
2) >= 1 of the panic attacks has been followed by >=1mth of >=1 of the following…
i) Persistent anticipatory anxiety
ii) Worry about implications of panic attacks
iii) Sig change in behaviour related to the panic attacks
Clinical presentation of Social Anxiety Disorder
- Marked & persistent fear of >=1 social/performance situations where there is possible scrutiny by others -> Humiliating/embarrassing
- Duration > 6mths
- Avoid situations that are feared
- -> Avoidance impairs functioning
Clinical presentation of OCD
Obsessions
- recurrent & persistent thoughts/impulses/images, intrusive & inappropriate
- recognises that obsessional thoughts are product of own mind (vs Schizoprenia)
Compulsions:
- Repetitive behaviours/ mental acts
- -> Acts aimed to prevent/reduce distress but not connected in realistic way, clearly excessive
- -> Time-consuming, causes marked distress (Take >= 1hr/day), impairs functioning
Clinical presentation of PTSD
- Person was exposed to stressor
- Intrusion symptoms (traumatic event persistently re-experienced)
- Avoidance (persistent effort to avoid situation)
- Negative alterations in cognitions and mood
- Alterations in arousal & reactivity
–> Persistence of symptoms cause distress/ functional impairment
Assessment of Anxiety Disorders (Clinician-rated & Clinical setting)
Clinician-rated: Hamilton Anxiety Scale (HAM-A) - Gold standard
Clinical setting:
- MSE + Formal structured psychiatric review
Non-Pharmacological Therapy of Anxiety Disorders
Cognitive Behavioural Therapy (CBT)
Relaxation therapies
GAD:
+ Psychotherapy, anxiety management
OCD:
+ Exposure & Response Prevention (ERP)
PTSD:
+ Psychotherapy, counselling
Pharmacological Agents for GAD
*SSRIs
Venlafaxine XR (reserve)
Pregabalin (reserve)
Pharmacological Agents for Panic Disorders
*SSRIs
TCA
Pharmacological Agents for Social Anxiety Disorders
*SSRIs
Pharmacological Agents for OCD
*SSRIs
Clomipramine (2nd line)
Venlafaxine (3rd line)
Highly recommended:
CBT + SSRI/Clomipramine
Pharmacological Agents for PTSD
- SSRIs
- CBT impt 1st line too
Dosing of Serotonergic Antidepressants
Starting dose: LOW
- Transient jitteriness in initial 1-2wks
- Consider +Benzodiazepine as adjunct
Maintenance Dose: HIGH
- Effective maintenance dosing are on the high end of the dose range
Serotonergic Antidepressant use & place in therapy in Anxiety Disorders
All useful for long-term management
- SSRIs, SNRIs (except in OCD), Clomipramine (OCD)
- Effective for “excessive worrying”
- Onset at least 1-2mths (downregulation of autoreceptors)
- Full response in ~3mths
- Duration of treatment at least 1-2yrs, typically long-term
Adjunctive Benzodiazepines in Anxiety Disorders (Therapeutic action, Dosing, tolerance & dependence, SE, Caution)
Therapeutic action:
- For physical/somatic symptoms (eg. muscle tension)
- Fast OOA (eg. Lorazepam within 30mins)
Options (High potency preferred)
- Clonazepam, Lorazepam, Alprazolam XR (for panic disorder)
Dosing: Short-term (3-4mths), PRN then taper
Side effects:
- Drowsiness, confusion, amnesia, impaired muscle co-ordination/weakness
Caution:
- Paradoxical excitement (children & elderly especially)
- Dependence & withdrawal symptoms
Tolerance & Dependence:
- Tolerance in anxiolytic action not common
- Gradual taper required
Pregabalin for GAD (alternative when other agents fail)
- GABA analogue, increases synaptic GABA
- Also acts on voltage-gated Ca2+ channels
- $$$
FDA-approved Benzodiazepines for GAD
Lorazepam (most common, int-acting):
- PO 1-3mg/day (2-3 divided doses),
Max: 6-8mg/day
- Short DOA
Diazepam (long-acting, sedating)
- Long DOA
Alprazolam:
- Initially PO 0.25mg TDS
- Short DOA
DDI of drugs used in Treatment of Anxiety Disorders
- Alcohol & CNS depressants
- MAOIs + SSRI/TCA
- -> Serotonin syndrome
Benzodiazepines:
- CNS depressants effect with alcohol & other CNS depressants
- Benzodiazepines + Opioids = Increased mortality (Increase cardiopulmonary depression***)
Long-term goals of treatment of Anxiety Disorders
GAD, Panic disorder, SAD, PTSD:
- Remission of core anxiety sxs
- Recovery of function
OCD:
- Complete resolution of sxs difficult to achieve
Early & long-term effects of Pharmacotherapy of Anxiety Disorders
Early:
- Possible increased anxiety with antidepressants during first 1-2wks
- Nausea, HA, Insomnia/sedation usually subsides after 2-3wks
Long-term:
- Sexual dysfunction & weight gain common with antidepressants
