Generalized Anxiety Disorder 2 Flashcards
Non-Pharm
Therapies
- Education about disorder(s)
- Psychotherapy à effective 1st line option
- Group or Individual are both efficacious
- Exposure-based/other cognitive behavioural therapy
(CBT) protocols - Self-help books, internet/phone-based therapy
- Virtual reality for exposure therapy
- Mindfulness-based cognitive therapy (MBCT)
- Often see once weekly therapy x 12-20 weeks
- Lots of variation in studies
- Evidence shows that long-term psychotherapy sessions have a benefit years later
- continuous therapy can help maintain control (in GAD)
once weekly therapy for three months +
Non-Pharm
Therapies
- Some evidence for the following, but not first line
- rTMS (monotx or adjunct to SSRI)
- Herbal products
- Resistance or aerobic exercise, yoga
- Acupuncture
Bright light therapy did NOT show any benefit in studies
resistance or aerobic exercise does have some benefit, but it’s not enough to recognize as a first-line therapy as does yoga. I don’t think acupuncture had very good evidence, but there was some for it. Bright light therapy did not show any benefit in anxiety disorders.
Psychotherapy
vs.
Pharmacotherapy
- Psychotherapy and pharmacotherapy generally
demonstrate about equivalent efficacy for the
treatment of most anxiety and related disorders - Results with combination therapy vary for different
anxiety disorders
Therefore, current evidence does NOT support routine
combination of psychotherapy + pharmacotherapy as
initial treatment!
However… - If either option provides limited response as
monotherapy initially, a switch to the other option or
combination therapy is appropriate to recommend
So usually with anxiety, you actually pick one or the other first-line. You pick psychotherapy or you pick pharmacotherapy and you give one of them a try as monotherapy, it is not recommended. Actually, there’s no evidence that supports the use of combination therapy, of psychotherapy and pharmacology. Pick one or the other initally
Pharmacotherapy
* The choice of medication should take into
consideration the:
- evidence of its efficacy for the specific anxiety/related
disorder - safety/tolerability
- comorbid conditions
- previous experience with potential therapy options
Pharmacotherapy
for GAD
Strength of Evidence
SSRIs
SNRIs
TCAs
Anxiolytics
Benzos
Atypical antipsychotics
Anticonvulstants
Other tx
escitalopram, paroxetine, sertraline have level one evidence, but citalopram, fluoxetine, paroxetine CR have level 3
when we’re considering SNRIs, we can use duloxetine or venlafaxine
TCAs tend to be 2nd line
Vortioxetine has good evidence but is newer drug
Bupropion, trazodone, mirtazapine can be utilized as well. Just keep that in mind, but they’re not first-line recommendations
for anticonvulsants, pregabalin is actually a first-line therapy.
benzodiazepines are a second line option for anxiety disorders, specifically generalized anxiety disorder as well. They’re really effective, but they have a lot of concerns
buspirone is an older medication, is very soft, very commonly used anxiety. It has been used for a long time and anxiety, but it is once again a second or third line option as this hydroxyzine.
Hydroxyzine is actually an anti histamine. It’s a very potent anti histamine, but it has anxiolytic properties to it that worked really well for different people.
Pharmacotherapy
for GAD
Recommendations
First line therapy
SSRI / SNRI / Pregabalin
first line: dulox, escit, parox, pregab, sert, venlafax
2nd line: alprazolam, bromazepam, bupropion XL, buspirone, diazepam, hydroxyzine, imipramine, loraz, quet, vortioxetine
within 2nd line, benzos would be considered first in most cases`
first-line is SSRIs, SNRIs pregabalin. Recognized with SSRIs, there are specific ones that are preferred.
You will see gabapentin often - it’s not based on guidelines but often similar to pregab
2nd line: benzodiazepines (end in paim or lam), bupropion, your buspirone, hydroxyzine, imipramine, quet, vortio\
Benzos are effective - considered 1st for 2nd line tx
Anxiolytics
Benzodiazepine
PD/PK
- Bind non-selectively to various subtypes of
GABAA receptor complexes - α1 subunit binding = sedation, ataxia, and amnesia
- α2 and/or α3 subunits binding = anxiolytic activity
- The major pathway of metabolism is Phase I
- hepatic microsomal oxidation, demethylation
- Phase II metabolism produces more polar byproducts, allowing for easier renal excretion.
- conjugation
- Phase I metabolism (e.g., oxidation) can be
compromised by disease states, age, or CYP inhibitors - Drugs that only undergo Phase II metabolism are not
affected to the same degree - lorazepam, oxazepam, temazepam à consider in older?
they bind non selectively to various subtypes of gaba a receptor complexes.
when they bind a gaba, a complexes associated with chloride influx into a cell or a flux, = depressant
So A1 subunits can cause side effects. So we often see sedation, Ataraxia, amnesia related to A1 sub-unit binding, A2 and A3 are more related to anxiolytic activity.
benzos are non-selective in their binding. So we bind all three of these subunits
if something is metabolized by a phase one reaction and our metabolism of phase one is impaired and age, we’re gonna get a buildup of it in the body, which can be dangerous
the ones that only undergo phase two, are not affected to the same degree in these people that have a decrease or compromised phase one reaction because they’re primarily metabolized by phase two. people have older age can benefit from a benzodiazepine that’s targeted to phase two metabolism more than phase one,
Anxiolytics
Benzodiazepines
PD/PK + Older Age
see slide for explainations
- Shorter t1/2:
- Inter-dose withdrawal (worse withdrawal)
- anterograde amnesia
- Increased abuse potential (faster onset)
- Longer t1/2:
- hangover effect
- Concern in Older Age:
- BEERS Criteria – Benzodiazepines1
- Older adults have incr. sensitivity to and decr.
metabolism of BZDs - Reduced mobility, ADL disability, hip fracture, falls, motor
vehicle collisions, cognitive impairment, addiction,
tolerance, dependence - Reserve for severe GAD in the older population
which are long acting, short acting benzos
KNOW: long acting: chlordiazepoxide, diazepam
Short acting: midazolam, triazolam
Everyhting else is intermediate
Anxiolytics
Benzodiazepines
Side Effects +
Precautions
- The most common side effects associated with
benzodiazepines (BZDs) include: - sedation, fatigue: These 2 are more related to short acting, but you can see them in longer acting
- ataxia, weakness, slurred speech
- memory impairment, cognitive impairment
- Benzodiazepines are associated with:
- dependence (caution in SUD), tolerance
- withdrawal reactions
- rebound anxiety between doses
Greater risk (of associated effects) with short and
intermediate-acting benzodiazepines compared to
long-acting agents
2nd Line / Short-Term Use
- Level one evidence, but 2nd line
due to SEs, depend., withdrawal
Anxiolytics
Benzodiazepines
Discontinuing Therapy
- Rebound:
- Occurs hours to days after drug discontinuation
- Anxiety is similar, but more intense than reported originally
- Dependence/Tolerance
- Tolerance to the hypnotic and sedative effects develops rapidly
- In contrast, even after prolonged use, clinically significant
tolerance to the anxiolytic effect does not usually occur - Withdrawal:
- Occurs in 1-2 days (with SA agent) to 5-10 days (with LA agent)
following drug discontinuation - Common symptoms: insomnia, agitation, anxiety, perceptual
changes, dysphoria, headache, muscle aches, twitches, tremors,
loss of appetite, diaphoresis, tachycardia, and GI distress. - Catatonia and depression have also been reported. Severe reactions can
occur such as grand mal or petit mal seizures, delirium,
depersonalization, psychotic states, and coma
Coming off of a benzodiazepine is very risky and you will notice very poor benzodiazepine tapering
Benzodiazepine Discontinuation
- In patients on prolonged benzodiazepine therapy, dosage should be gradually
decreased over about 6–12 weeks - WHEN?
- history of short duration/high dose/SA or IA OR long duration of therapy
- HOW? à varies depending on resource and clinical situation
- Decrease by 10-20% of current dose Q3-7D
- For patients taking a short-acting agent, substitution with a longer-acting
benzodiazepine may provide a gradual decrease in drug concentration and
reduce the possibility of withdrawal symptoms - First 50% of decrease can be more rapid than last 50%
buspirone
- Largely unknown pharmacology:
- central D2 agonist/antagonist, 5-HT1A partial agonist
- metabolite can increase NE release
- Effectiveness largely limited to GAD
- Limited effectiveness in clinical practice (2nd line)
- SEs: dizziness, light-headedness, headache, nausea,
sweating, nervousness - Generally well-tolerated, causes little sedation
- CYP 3A4 substrate
- metabolite is a 2D6 substrate
- Usual therapeutic dose = 20-30 mg/day div. doses (TID-QID) –
- May take 2-4 weeks to see an effect
- Not effective when used on a PRN basis
Hydroxyzine
- Antihistamine
- competes with histamine for H1-receptor
- ceterizine is an active metabolite (hepatic metabolism)
- activity at muscarinic, serotonergic, and dopaminergic
receptors in the brain may produce anxiolytic effects - 25 – 100 mg QID (when used for anxiety)
- evidence for efficacy in reducing symptoms vs. placebo
- Based on poor quality evidence, may be comparable to BZDs
and buspirone - Significant risk of adverse effects à sedating, dizziness
- QTc prolongation
Treatment
Considerations
- Medication should be initiated at low doses and
titrated to the recommended dosage range at 1–2
week intervals - Pharmacological treatment is often associated with
a delay of about 2 - 8 weeks in onset of symptom
relief, with full response taking up to 12 weeks or
more - Optimal goal is full remission and return to
premorbid level of functioning - Remission = loss of dx status, pre-specified score on scale, or no
functional impairment - Response is often defined as a 25-50% reduction of
symptoms on an appropriate scale
Notice how anxiety disorders
have a less “rigid” definition for
“remission”, “response”, etc
They’re “guideline definitions”
