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Zizzer Zazzer Zuzz 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?