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Beyond Benzos:
Tips for Managing Anxiety
Diane C. Reis, MD, MPH
IU Health Arnett
[email protected]
8/12/2017
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Disclosures
No financial conflicts of interest to report.
Objectives
• Identify and utilize non-benzodiazepine shortacting anxiolytics in a clinical setting.
• Select and utilize longer acting anxiolytics in a
clinical setting.
• Identify and apply appropriate uses for
benzodiazepines.
• Taper and discontinue benzodiazepines in a
safe and tolerable manner.
Anxiety
• Sort of the psychological equivalent of pain
• Disorders we are considering in this discussion:
– Generalized Anxiety Disorder
– Panic Disorder
– Social Anxiety Disorder
– Performance/situational anxiety
– Unspecified Anxiety Disorder
• Not included: OCD (has been broken out from
anxiety disorders in DSM V), PTSD
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Dx: Generalized Anxiety Disorder
• Excessive worry most of the time for at least 6
months about a variety of topics/problems
• Worry is challenging to control
• 3+ of the following physical or cognitive sx:
– Edginess/restlessness
– Tiring easily/fatigue
– Impaired concentration
– Irritability
– Muscle aches/soreness (and often others…)
– Poor sleep
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Dx: Generalized Anxiety Disorder
• Symptoms
cause
impairment
in function
• Symptoms
not better
explained by
another
physical or
mental
disorder or
substance
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Dx: Panic Disorder
• Spontaneous and unexpected occurrence of
panic attacks (at least 4 of 13 possible sx, rapid
onset, peak within 10 minutes)
• At least one month of persistent worry about
another attack or consequences of the attack
OR maladaptive behaviors related to the attack
• Not better explained by another disorder or
substance
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Dx: Social Anxiety Disorder
• Fear/anxiety in specific social settings in which
a person feels observed or scrutinized
• Fear that anxiety will show and lead to rejection
• Social interactions avoided or tolerated only
with pain/distress
• Sx disproportionate to situation
• 6+ months duration & impairment
• Not better explained by another disorder or
substance
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Performance Anxiety
• Subset of social anxiety disorder (specifier
added to indicate this)
• Generally related to specific situations such as
public speaking or similar performances
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Dx: Unspecified Anxiety Disorder
• Anxiety symptoms that are clearly out of the
ordinary and impairing but don’t meet criteria
for a more specific anxiety disorder
• Not due to another disorder or substance
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Please remember:
• These disorders are chronic – 3 days of anxiety
is not a disorder!
• First line treatment for anxiety disorders should
include therapy (CBT does particularly well for
these) and behavioral interventions (exercise,
sleep hygiene, limit/eliminate caffeine)
• Psychopharm interventions have significant
overlap across these disorders
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First steps in treatment
• SSRIs
– Can cause a few days of initial worsening of
anxiety; start low (half of minimum effective
dose)
– Take 3-6 weeks to see effect and it is unusual
for a person to describe a sudden, strong effect
– Takes up to 12 weeks to see the full effect of a
given dose (patience, grasshopper)
– Please note that paroxetine has multiple
negatives studies in age <25, would avoid in this
group
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First steps in treatment
• SSRIs
– My practice: try at least two before switching
class
– Selection based on metabolic interactions, drug
half-life, side effects
• Side note on bupropion: I see this used for
anxiety; it is mildly stimulating and has poor
evidence for use in anxiety, also if you’re using
the SR formulation for anything, make sure
you’re dosing AM and early PM (not HS!!!)
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Second line options
• SNRIs
– For some, the addition of the noradrenergic
effect has a notable difference
– Venafaxine note: minimal NE activity at doses
below 150 daily of the XR formulation
– Monitor BP, particularly if this has been a
problem in the past
– Can be difficult to discontinue, taper slowly and,
if needed, give the patient a brief (3-7 day)
course of fluoxetine to smooth the end of the
taper
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Second line options
• Mirtazapine
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– The good: sedating in most people and some
earlier anxiolysis due to activity alpha2 and
histamine receptors
– The bad: increased appetite causing weight gain
(though sometimes that’s a good thing)
– Can be used first line if you have a patient who’s
not sleeping or eating and you’re concerned
about weight loss
– Can be used to augment SSRIs/SNRIs
– Note: after 15 mg a day, sedation does not
increase
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Other longer-term treatments
• TCAs
– Differing balances of serotonergic and
noradrenergic activity
– Anti-cholinergic, beware of use in elderly, and be
aware of the related side effects
– Usually at least somewhat sedating
– HIGH LETHALITY IN OVERDOSE
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Shorter-acting anxiolytics
• Buspirone
– Generally takes at least a week for effect and up
to a month for full effect
– Dosed BID-TID
– More effective at higher doses (30-60 mg/day)
– Sometimes used PRN, very limited evidence
(active placebo???)
– Strongest evidence as augmentation strategy,
not as monotherapy
– Usually safe and well tolerated with very low
potential for abuse
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Shorter-acting anxiolytics
• Hydroxyzine
– Dosed BID-TID, generally 25-50 mg/dose
– Most sedating in the first 3 days
– Best evidence is for use as a scheduled agent
– Anti-cholinergic, avoid in elderly, consider if
other anti-cholinergics present and overall
burden (area of evolving research)
– No withdrawal, generally easy to discontinue
– Anxiolysis is fairly rapid though related to
sedation
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Shorter-acting anxiolytics
• Beta blockers
– Propranolol, metoprolol, atenolol most
commonly used
– Low doses (propranolol 10 g, metoprolol 12.525 mg, atenolol 25 mg)
– Strongest evidence for PRN use for
performance-type situations: speeches, tests,
musical performances
– I use this at times for social anxiety as well
– Take 30-60 minutes prior to event
– Warn for sx of low BP, do trial dose at home
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Shorter-acting anxiolytics
• Clonidine
– Used off-label, limited clinical studies
– Some evidence for managing irritability or mood
instability in borderline personality disorder
– Start 0.1 mg BID, I will often dose 0.1 mg BID
scheduled plus 0.1 mg daily PRN (3 total doses)
– Little or no abuse potential, fairly rapid effect
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Shorter-acting anxiolytics
• Gabapentin
– Usually used at lower doses (100-300 mg/dose)
either scheduled or PRN up to TID
– Off-label use, mimimal evidence base but ample
anecdotal suggestion that this has some
anxiolytic effect
– Compared to benzos, quite limited abuse
potential
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Benzodiazepines
• Effective in the short term
• Fail to separate from placebo after about 2
weeks of regular use
• Physiologic dependence and addiction
• Interaction with opiates
• Cognitive, motor, judgment effects
• Disinhibition and intoxication
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Benzodiazepines in practice
• Consider duration of action and potential for
withdrawal/discontinuation symptoms
• Consider site of metabolism (hepatic vs renal)
• Don’t start unless there’s a plan to stop!
• Avoid as a first line agent – remember most
anxiety disorders present in the chronic phase
(“it’s a marathon, not a sprint”)
• Know your own max doses and be willing to
stick to them
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Commonly used benzos
• Alprazolam (Xanax): effect 3-5 hrs, euphoria early in
dose, abrupt discontinuation effect, highest abuse
potential, ugly withdrawal
• Lorazepam (Ativan): effect 5-8 hrs, renally
metabolized, used as comparator for BZD
equivalencies
• Diazepam (Valium): effect 6-8 hrs plus active
metabolites, stored in fat and can have
unpredictable release
• Clonazepam (Klonipin): effect 7-10 hours,
“smoother” activity, generally 1:1 equivalence with
alprazolam, usually my first choice
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A small rant on Xanax…
• The “ideal” Xanax patient: severe anxiety/panic
that emerges in rare circumstances (e.g. bad
turbulence while flying) and resolves in a
predictable period of time, otherwise good
coping skills and function, probably uses this
less than once a month
• 2 mg “bars” have high street value
• Once people have tried this, it’s really hard to
get them to use something else (nothing else
gets you high the same way!)
• Interferes with therapy!
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My “max” doses
• Alprazolam: I don’t start this and I push my
patients to switch to a longer-acting agent
• Lorazepam: 1-2 mg TID
• Diazepam: 10 mg TID
• Clonazepam 1 mg TID
• Note: I do inherit patients on higher doses, next
steps are very case-dependent
• Note: I do not start regimens with multiple
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So what about chronic users?
Stable
Unstable
Motivated
Unmotivated
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Stable & motivated to taper
• Continue treatment with long-term anxiolytic
and/or therapy if applicable
• If needed, convert to longer-acting agent
• Taper total daily dose by 10-20% at a time,
decreasing no more frequently than q1-2 weeks
and ideally q1-2 months
• May need to slow even further at the end of the
taper
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Stable but not motivated to taper
• Explore concerns about tapering – bad
experiences in the past? Concerned that “this is
the only thing that keeps me together”?
• Psychoeducation: what is perceived as anxiety
may be benzo withdrawal, little evidence for
efficacy with long-term use, risk for interactions,
future potential problems, cognitive sfx
• Discuss expectations (“I know that this time of
year is stressful but when I see you in March,
expect that we will begin to very gently taper.”)
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Not stable but motivated to taper
• Consider increasing other treatment or support
– add therapy or increase frequency, plan
behavioral interventions, enlist family/friends,
substitute a non-benzo anxiolytic
• Err on the side of smaller dose changes that
are done less frequently and be willing to adjust
to life circumstances
• Reinforce positive changes that you are
observing
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Not stable or motivated to taper
• Establish clear treatment goals – what does
“better” look like?
• Create clear expectations, consider a signed
contract
• There are patients who will remain on high
doses of benzos – pick your battles
• Communication with other treating doctors is
key
• Motivational interviewing techniques
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Example 1
Mr. X is taking 2 mg of Xanax three times a day for
his GAD but is doing pretty well and wants to wean off
of this. He has been on this dose for 3 years.
1) Convert to a longer-acting agent (2 mg TID Xanax
= 2 mg TID clonazepam)
2) Decrease total daily dose by 10-20% (e.g. 1.5 mg
AM and HS, 2 mg PM or 2 mg AM and HS, 1 mg
PM)
3) Continue to decrease by 1 mg a month until he is
taking 1 mg TID, then decrease by 0.5 mg a
month.
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Sample Schedule
Month
AM Dose
PM Dose
HS Dose
0
2 mg
2 mg
2 mg
1
2 mg
1 mg
2 mg
2
1 mg
1 mg
2 mg
3
1 mg
1 mg
1 mg
4
1 mg
0.5 mg
1 mg
5
0.5 mg
0.5 mg
1 mg
6
0.5 mg
0.5 mg
0.5 mg
7
0.5 mg
0.25 mg
0.5 mg
8
0.5 mg
x
0.5 mg
9
0.25 mg
x
0.5 mg
10
0.25 mg
x
0.25 mg
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Example 1
Mr. X is taking 2 mg of Xanax three times a day
for his GAD but is doing pretty well and wants
to wean off of this. He has been on this dose
for 3 years.
• Consider adding regular exercise, meditation,
scheduled enjoyable activities
• Consider enlisting a friend or family member to
act as a “cheerleader”
• If symptoms begin to worsen, consider use of a
non-BZD anxiolytic
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