Anxiety NBT Flashcards
what is an anxiety disorder?
- severe, excessive, persistent anxiety and irrational fears that impairs functioning w everyday living
anxiety is out of proportion to the actual danger or threat of the situation
5 types of anxiety disorders listed in the DSM-5 that are most amendable to drug treatment
- Generalised Anxiety Disorder (GAD)
- Panic disorder
- Social Anxiety Disorder (SAD)
- Obsessive Compulsive Disorder (OCD)
- Post traumatic stress disorder (PTSD)
what is GAD
- excessive anxiety and worries >= 6months
- associated with >= *3 of the following sx (where some of these sx present on more days):
1. Restlessness or feeling keyed up/ or on edge
- being easily fatigue
- difficulty concentrating or mind going blank
- irritability
- muscle tension
- sleep disturbance (insomnia, restless unsatisfied sleep)
- sxs can cause sig functional impairment
what is panic disorder
- anticipatory anxiety of a possible recurrent panic attacks
Panic attack definition: >= 4 sxs developed abruptly and peaks within 10min (lasts 20-30min) a. palpitations b. sweating c. trembling d. feel like SOB e. feel like choking f. nausea g. dizzy h. chills or hot flushes i. feel like things are unreal j. fear of going crazy, dying k. numbness/tingling (paresthesia)
- recurrent unexpected panic attacks where >= 1 panic attack has been followed by >= 1 mth of >=1 of the following:
- -> persistent anticipatory anxiety of having additional panic attacks
- -> worry about the implications of panic attack
- -> sig change in behaviour related to the panic attacks
what is social anxiety disorder?
- fear of being scrutinized or humiliated by others in public
- fear of >= 1 social/performance situtations
- duration > 6mths
- avoiding, anxious anticipation or distress significantly impairs functioning
What is obsessive-compulsive disorder (OCD)
obsessional thoughts/impulses that causes anxiety, followed by compulsive behaviours to relieve that anxiety
- person knows that the obsessional thoughts are a product of his own mind
- the repetitive behaviours or mental acts (repeating words silently) are aimed to reduce the distress but not connected in a realistic way (clearly excessive)
- time-consuming, impairs functioning
What is post traumatic stress disorder (ptsd)
re-experiencing of trauma, persistent avoidance, increased arousal
- stressor
- intrusion sx = persistently re-experienced
- avoidance
- negative alteration in cognition and mood
- alterations in arousal and reactivity
- at least 6 mths after trauma
- functional impairment
which anxiety& related disorders are less amendable to medication therapy?
phobias
what is the pathophysiology of anxiety>
- fear circuit regulated by amygdala
- worry circuit regulated by cortico-striatal-thalamic-cortical (CSTC) loop
what neurotransmitters are involved in anxiety
NE & serotonin
inhibitory neurotransmitter - GABA
drug choice focus more on serotonergic effect than on GABA
what medical conditions are associated with anxiety?
- cardiovascular: CHF, IHD, MI, angina, arrhythmias
- endocrine: hyperthyroidism
- neurologic: dementia, delirium
- pulmonary: asthma, COPD
drugs that can induce anxiety?
- sympathomimetics: pseudoephedrine
- stimulants: amphetamines, cocaine
- methylxanthines: theophylline, caffeine (theophylline 1a2 substate + anti dep (fluvoxamine 1a2 inhibitor ==> increase theophylline)
- thyroid hormone: levothyroxine
- corticosteroids
- antidepressants: SSRIs, TCAs (initiation or rapid dose escalation)
- dopamine agonist: levodopa
- beta-adrenergic agonist: salbutamol
- drug withdrawal (caffeine, alcohol, bzds, antidepressants, nicotine, sedatives)
- drug intoxication (anticholinergic, anti-H, digoxin)
how is anxiety diagnosed?
usually a mental status exam is done and formal structure psychiatrist interview documented
in RCTs gold standard: Hamilton Anxiety Scale (HAM-A)
treatment for GAD
- SSRIs
- venlafaxine XR
- pregabalin
- TCAs
+ cognitive behavioural therapy
treatment for panic disorder
- SSRIs*
- TCAs
+ CBT
treatment for SAD
- SSRIs
+ Behavioral therapy
treatment for OCD
- CBT** (impt first line tx)
+ SSRI** or Clomipramine
(as pharmacotx alone is v difficult to achieve complete remission)
CBT is a
non-pharmacologic therapy
what are the serotonergic antidepressants that are useful for long term management of anxiety disorders, ocd, ptsd?
1, SSRIs
- SNRIs
- Clomipramine
but in OCD: 1st line SSRI >2nd Clomipramine > 3rd Venlafaxine
how do we approach dosing?
starting dose must be LOW
- due to the transient jitteriness in the initial 1-2 weeks of starting anti-depressants
- can consider BZD as an adjunct
- but for maintenance dose, it can be at the high end of the range
- e.g. fluoxetine 60-80mg/day vs 20mg/day as a starting dose
when are the serotonergic antidepressant effective?
they are effective for EXCESSIVE WORRYING type of symptoms
- onset at least 1-2 months
- full response generally 3 months
- duration of treatment at least 1-2 yrs, typically long-term
when are adjunctive BZDs effective for anxiety?
- effective for physical symptoms of anxiety (e.g. muscle tension)
- -> fast onset of action; can be within 30min (e.g. lorazepam)
–> aim for short term (3-4 months) of treatment, PRN dosing, then taper
(usually used before the effect of the anti-depressant takes effect)
how common is tolerance developed when adjunct BZD is used?
- tolerance to hypnotic actions common, develops within days
- tolerance to the bzd anxiolytic action is less common
how to avoid dependence on BZDs
avoid abrupt cessation after weeks of continued used
gradual taper required
what type of BZDs are preferred in anxiety disorders?
- high potency* agents
e. g. clonazepam, lorazepam, alprazolam XR (alprazolam XR ONLY for *panic disorder)
take note: paradoxical excitement in children and elderly*
dependence and withdrawal sx can occur esp patient w hx of drug dependence
what are the names of the SSRIs?
Main:
- escitalopram (mainly GAD)
- fluoxetine (PD, OCD)
- fluvoxamine (SAD, OCD)
- paroxetine (all 5)
- sertraline (all 5)
- citalopram (2nd line OCD)
what are the names of the SNRIs?
- venlafaxine XR (GAD, PD, SAD)
- duloxetine (GAD)
what are the names of the TCAs?
clomipramine (GAD)
imipramine (?)
Names of the adjunct BZDs?
- alprazolam* (PD) (usually extended-release form)
- clonazepam (PD)
- lorazepam* (commonly used)
- diazepam* (not usually used as long acting)
- FDA approved treatment for general anxiety
What is the drugs under the others?
pregabalin (for use in GAD if SSRI/SNRI or other serotonergic drugs are not working)
- expensive
What is the anti-histamine drug used for anxiety
hydroxyzine (GAD)
what is the beta-blocker used for anxiety?
propranolol: for tachycardia and hand tremors
- but not commonly used
what are the sig DDI we need to avoid when using BZDs and anti-depressants
- alcohol and other CNS depressant AVOIDED w BZDs and anti-dep —> due to increase CNS depressant SE
- anticholinergic agents causes excessive anticholinergic effects (as anti-depressants alr have anticholinergic se)
- MAOIs and SSRIs/TCAs combination
- -> serotonin syndrome
- -> *restlessness, diaphoresis (sweating), tremor, shivering, myoclonus (jerking), confusion, convulsions, death) - Anti-depressants DDI (p450 enzymes inhibition) - refer to depression notes
- BZDs DDI:
- CNS depressant + alcohol/ other CNS depressant (counselling: do not take medication at the same time as alcohol, separate then 4-6hrs apart)
- BZDs + opioids = increased mortality (CNS depression)
- -> avoid combination or limit dose and duration
- PK: BZDs don’t induce microsomal enzymes but most are metabolised by cyp 3a4 (except lorazepam)
summary slides: which anxiety disorders can achieve remission of core anxiety sxs, recovery of function?
GAD, PD, SAD, PTSD
summary slides: which anxiety disorder is difficult to achieve complete resolution of sxs?
OCD
summary slides: how do we treat anxiety disorders?
objective assessment of outcomes
- psychiatric rating scales
- identify target sxs for each type of anxiety disorders
- keep detailed diary to record fear levels, physical sxs, cognitions and anxious behaviours
summary slide: what are the non-pharmacological management?
- OCD = CBT + (either SSRI or Clomipramine); as pharmacotherapy alone is v difficult to achieve complete remission
summary slide: what is the recommended duration of medication treatment?
- at least 1 year for all anxiety disorders
- at least 1-2 years for OCD
summary slide: which anti-depressants we use and why?
all antidepressants that promote 5-HT transmissions have efficacy for anxiety disorders
- effective for “worrying/apprehension” type of symptoms
summary slide: how do we start the anti-dep dose?
- initiate at very low doses, gradually titrate up to maximum dose range
summary slide: what is the time to respond to anti-dep?
may take 6-12 weeks
max response may take 3 months
e.g. OCD may take 2-3 mths to respond to tx
summary slide: how to discontinue anti-dep?
gradual taper to avoid discontinuation sx
e.g. decrease dose by 10-25% every 1-2weeks
summary slide: when is BZDs used?
- not recommended for monotx
- effective for “physical/somatic” aspect of symptoms
- quick onset of effect during initial weeks
summary slide: how to start on BZDs
limited duration of treatment is preferred (avoid use in persons w substance-use disorders)
summary slide: how to discontinue BZDs?
gradual taper to avoid rebound anxiety
summary slide: what are the bzds DDI?
- CNS depression w alcohol and other CNS depressants
- BZDs + opioids = increased mortality risks
summary slide: what are the early AE of pharmacotherapy?
- possible increased anxiety with antidepressants during first 1-2 weeks; where nausea, headache, insomnia/sedation usually subsides after 2-3 weeks of continued treatment
Transient jitteriness expected in first 1-2 w of starting
summary slide: what are the long term AE of pharmacotherapy?
- sexual dysfunction and weight gain common with anti-dep
the common reasons why pt discontinue; thus must counsel them on this and say that this AE are reversible
which are 2d6 inhibitors
fluoxetine, paroxetine, bupropion, duloxetine
which are 1a2 and 2c19 and 3a4 inhibitors
fluvoxamine
propanolol to be avoided in patients w?
asthma
which adjunct BZDs have no major active metabolites?
Alprazolam, Lorazepam
what is the duration of action of the adjunct BZDs?
short: alprazolam, lorazepam
long: clonazepam, diazepam
what drugs are not recommended for anxiety treatment?
- Kava (risk of hepatotoxicity)
- Chamomile (avoid in pregnancy)
- Valerian (increase GABA)
why do we usually Avoid TCAs in anxiety; why TCAs is not first line
TCAs can increase NE –> make people more anxious
Thus second line venlafaxine and clomipramine; 1st line SSRI
avoid TCA in patients with uncontrolled HTN
doses for alprazolam
0.5mg (approx oral dose equivalence); PO 0.25-0.5mg BD-TDS
dose for clonazepam
PO 0.5mg BD
dose for diazepam
10mg (approx oral dose equivalence); PO 2-10mg BD-QDS
dose for lorazepam
1mg (approx oral dose equivalence); PO 1-3mg/day (in 2-3 divided doses)
max 6-8mg/day
