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Anxiety Treatment
Good News !
E. Jane Garland MD, FRCPC
Clinical Professor, UBC
Head, Mood & Anxiety Disorders Clinic,
BC’s Children’s Hospital
Key challenges in anxiety Rx
• Anxiety is “normal”
• Disorders are prevalent (10-15%)
• Disorders are chronic & recurrent
• The good news! Medication effect size
greater in anxiety than in depression
• Functional improvement is greater with
CBT but it is hard to “take”
Case Example
• 10 year old boy
• Anxious parents; shy child, past excessive
separation anxiety; allergies, food
sensitivities, intermittent asthma
• c/o stomach aches sending him home
from school, also gets SOB when upset
• Mom having to take time off work to pick
him up and stay home with him
Symptoms
• Chronic bedtime resistance and initial insomnia;
some cosleeping
• c/o stomach aches in am, rarely vomits
(retching?)
• being sent home from school almost daily since
Sept with c/o stomachaches and/or breathing
problems
• Fussy about food, smells, textures;
perfectionistic about work, checks locks x2
• worries about “everything”
Where to begin?
• Assessment issues
• Treatment issues
The questionable outcome: the
“treated” anxiety disorder
• Children referred to clinic on good doses of
SSRI’s, chronically
• Hx of Panic, Sep Anx, GAD or social phobia
• Essentially free of anxiety symptoms now
• But don’t attend school, don’t function in
community, have no anxiety tolerance
• Unmotivated to move forward because they
are “comfortable” and intolerant of any
“discomfort” such as going out of the house
-- & especially intolerant of CBT!
Functional Outcomes
• Adult data suggests that for panic
disorder, although medication reduces
symptoms more rapidly, functional outcome
is superior for CBT, 2 years later
• Competing goals?
The “goal” of medication is to take
symptoms away
The goal of CBT is to learn to tolerate and
cope with symptoms
• Be sure that medication is prescribed and
evaluated with functional outcomes in mind
What is the Goal of
Treatment?
• Elimination of anxiety symptoms?
• Or Reduction of symptoms to match coping
level, with resultant ability to function
• Then: Reduction of medication with upwards
titration of skills
• Risks of accepting the goal of eliminating anxiety?
• 1. Failure to achieve goal
• 2. If achieve elimination of anxiety
a) they don’t developing coping skills
b) amotivational side effects
Solutions?
• Always use the psychoeducational model
- “Anxiety is natural and self-protective”
- “However, those with sensitive body alarm
systems AND a talent for creative worrying
develop excessive anxiety and avoidance”
- Need coping skills lifelong
- Medication can reduce alarm sensitivity and
reduce intensity of catastrophic worrying
- Taper medication very slowly
Role of Medications
in this Model
• Reset “panic alarm” (goes off less easily)
• Calm physiological sensations (turn down
the volume on the alarm)
• Reduce intensity of cognitive worry
• Regulate serotonergic, noradrenergic, gabaergic, glutamatergic systems etc.
Take Home Message #1: SSRIs
Effective in Anxiety Disorders
• OCD: sufficient evidence for labelling in US
(sertraline, fluoxetine, fluvoxamine) (2 DBPC
trial each with endpoint 25-40% decrease in YBOCS
with about 50% responding)
• GAD/Mixed anxiety disorders: One +ve DBPC
trial for each of the above
• Social phobia (Parox); selective mutism (Fluox)
• Placebo effect lower in anxiety disorders
• In 1997 Emslie MDD fluoxetine study if control for
anxiety, no effect for depression (CDER 2001)
Other medications
• Buspirone
– limited
older research but maybe effective, fewer
behavioral SE; may avoid activation in bipolars
• Benzodiazepines
• – clonazepam: one RCT in adolescent panic, irritability
is a limiting side effect;
- alprazolam – limited data in school refusal
• Trazodone – low dose, adjunctive for sleep
• SNRI – not effective in 2 good GAD trials
Walkup at al NEJM 2001:
Fluvoxamine & Anxiety
• Placebo-controlled trial total N=128
• Mixed Current Anxiety Dx (51-69% for each)
GAD, Sep Anx , Soc Phobia
• Relatively low comorbidity: about 15% current
or past ADHD; 5-6% current or past ODD; 5%
past MDD
• Mean medication dose 2.9 mg/kg; mean last
dose 4.0 mg/kg fluvoxamine
• (RUPP at NIMH)
Walkup et al NEJM 344: 1279-1285, 2001
Mean scores on PARS (<10=mild)
Figure 3. Cumulative Response Rates on the CGI-Improvement
76% (48/63) of fluvoxamine had a response;
29% (19/65) of placebo (p<.001)
Rynn et al – AJP Dec 2001
• Placebo controlled trial of sertraline, 25 mg
first week, 50 mg weeks 2-9
• Ages 5-17; total 22 patients
• Primary Diagnosis GAD, Ham-Anxiety Score >
16, no comorbid non-anxietyAxis I
• No other Rx offered but able to continue
usual psychoRx if stable for 3 mos
• Huge effect size in small study*
PC Trial of Sertraline in GAD
Rynn et al Am J Psych (p<0.001)
Additional findings
• Fluoxetine mixed anxiety study (Birmaher et
al 2003, JAACAP) 61% responded to
fluoxetine 20 mg and 35% to placebo
• Extension of RUPP fluvoxamine study (Walkup
at al JCAP 2002) found gains maintained, also
did well if switched to fluoxetine from
placebo
“Psychiatric” effects of SSRIs
10-25% rate in children
• “emotional lability”
• Aggression/hostility
• Agitation/akathisia/activation
• Suicidal ideation & self-harm
• Disinhibition
• Motor hyperactivity (Fluvoxamine
anxiety trial 27% vs 10% placebo)
• Later: sexual, amotivational
Side effects to mention to
family (plus give handout*)
• Behavioral activation
• Disinhibition
• Increased motor activity/tics
• Obsessive suicidal thoughts
Be aware of:
• Sexual side effects
• Amotivational syndrome (later)
*our handout mentioned behavioral, suicidal and bleeding side
effects several years before labelling
Dosing SSRIs in Anxiety
• Start low in kids (lower and slower in anxiety)
• Titrate with patient/family – phone
• Slower titration reduces psychiatric adverse
effects especially disinhibition
• Slow titration for adaptation in social phobia
• Low doses may work eg 50 mg Ser in GAD
• Higher doses in OCD (eg 200 fluvoxamine)
• If no response at all by 6 wk to 20 mg fluxetine or
equivalent, increase to 30 mg then, if partial
response, can increase to 40 mg
• If no response at 8 wk (10 weeks OCD) switch?
• Target dose 20-40 mg (100-200 mg Ser/Fluv) or
lowest effective
The family returns…
• 2 weeks later:
Good News – less intensity of worry,
fewer complaints of stomach
aches
• BUT – a week after started,
seems excitable, overactive, not
sitting still, giddy at times, teacher
has sent home a note that the
child is very restless……
What could be going on?
How would you assess?
Differential Diagnosis of
“Activated” side effects
• Simple stimulation (caffeine-like): very brief,
settles with low dose, time
• Behavioral activation: increased motor
activity, more giddy, few hours after meds
(watch dose, often settles with time)
• Hypomania/Mania – dramatic, hyperarousal,
sleep disturbance, family history, persistent,
extreme
• Movement disorders: akathisia (often
persists), choreiform (often settles)
How long to continue?
• The child is improving on lowered dose
Tips on discontinuing medication
(after 6 months to a year, try it!)
• Careful preparation is essential
• Remind them that their body alarm system
is sensitive so we’ll go very slowly
– but this is an opportunity to practice
skills
• Remind them that discontinuation effects
(dizzy, nausea, funny pains and shooting
sensations, sleep disturbance) will pass
• Slow titration downward (eg 5-10 mg/month)
• Open & empty out capsules, split pills
• Accompany with “booster” CBT training
The Promise of Medications
• Prevent psychosocial impairments
• Prevent the personality “shaping” which
anxiety achieves
• Improved academic output
• Prevent secondary depression
• Positive impact on family dynamics
• Available when CBT is not
Challenges in
Prescribing
• Anxiety disorders are common (up to 10%
of kids), chronic and recurrent
• Thresholds for treatment?
• Behavioral adverse effects especially in
younger kids; sexual side effects in teens
• Trouble discontinuing (sensitive to
discontinuation effects: anxiety
sensitivity)
Ideal Approach
• See medication as one of many “Tools”
• Always combine medications with coping
strategies which increase self-efficacy
• “Prescribe” behavioral and coping
strategies (including exercise, sleep
hygiene, exposure practice) as “medically
necessary” too: write them on a
prescription pad
Detecting clinical trends:
Guess what we are using?
• Quetiapine for anxiety & sleep (low dose)
• (olanzepine less so due to weight gain)
• Risperidone in OCD or anxiety/Tourette’s
• Valproate in anxiety with rages, mood
instability
• * Lamotrigine in adolescents with OCD, panic,
mood instability (watch for this class)
• Anything else?