Prevalence of Anxiety Disorders by Rabia06

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									                     Prevalence of Anxiety Disorders
                              27
                              24
    Lifetime Prevalence (%)




                              21
                              18
                              15
                              12
                              9
                              6
                              3
                              0
                                   Any Anxiety    Social    PTSD   Generalized    Panic
                                    Disorder     Anxiety            Anxiety      Disorder
                                                 Disorder           Disorder

Kessler et al. Arch Gen Psychiatry. 1995;52:1048.
Kessler et al. Arch Gen Psychiatry. 1994;51:8.
  Outcome of Panic Disorder at
     Long-Term Follow-up

    Persistence of      Rate (%) Range (%)

Panic attacks             46            17-70

Phobic avoidance          69            36-82

Functional impairment     50            39-67

                               Roy-Byrne & Cowley, 1995
     Pharmacopoeia for Anxiety
            Disorders
Antidepressants
   Serotonin Selective Reuptake Inhibitors (SSRIs)
   Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
   Atypical Antidepressants
   Tricyclic Antidepressants (TCAs)
   Monoamine Oxidase Inhibitors (MAOIs)

Benzodiazepines

Other Agents
   Azaspirones
   Beta blockers
   Anticonvulsants
   Other strategies
Serotonin Selective Reuptake Inhibitors
 • Fluoxetine (Prozac), 20-80 mg/d
    – Initiate with 5-10 mg/d
 • Sertraline (Zoloft), 50-200 mg/d
    – Initiate with 25-50 mg/d
 • Paroxetine (Paxil), 20-50 mg/d
    – Initiate with 10mg/d
 • Fluvoxamine (Luvox), 50-300 mg/d
    – Initiate with 25 mg/d
 • Citalopram (Celexa)
   - Initiate with 10-20 mg/d
 • Start low to minimize anxiety
   Adjunctive BZD, beta blocker
    Serotonin Selective Reuptake
          Inhibitors (cont)
• Typical SSRI side effects:
  – GI distress, jitteriness, headaches, sleep
    disturbance, sexual disturbance
• Clomipramine (Anafranil), 25-250 mg/d
  – Initiate with 25 mg/d
• Efficacy: PDAG, PTSD, SP, OCD, GAD
           Sertraline In Comorbid PTSD
                  And Alcoholism
                                            Pre-treatment
                                            Post-treatment

           60                                                              140



           40
 IES                                                                       70 Standard
score                                                                        drinks/week
           20


             0                                                             0
                                 IES                         Alcohol use


   Brady et al. J Clin Psychiatry. 1995;56:502.
Discontinuation of Treatment for
      Anxiety Disorders
• Withdrawal/rebound more common with Bzd than
  other anxiolytic treatment
• Relapse: a significant problem across treatments.
  Many patients require maintenance therapy
• Bzd abuse is rare in non-predisposed individuals
• Clinical decision: balance comfort/compliance/
  comorbidity during maintenance treatment with
  discontinuation-associated difficulties
        Strategies for Anxiolytic
            Discontinuation
•   Slow taper
•   Switch to longer-acting agent for taper
•   Cognitive-Behavioral therapy
•   Adjunctive
    – Antidepressant
    – Anticonvulsant
    – ?clonidine, ?beta blockers, ? buspirone
     Serotonin-Norepinephrine
        Reuptake Inhibitor
• Venlafaxine-XR (Effexor-XR) 75-300 mg/d
  – Initiate with 37.5 mg/d
• Indicated for GAD; effective for panic
  disorder, social phobia, PTSD, OCD
• Typical side effects
  – GI distress, jitteriness, headaches, sexual
    disturbance
       Atypical Antidepressants

• Nefazadone (300-500 mg/d)
  – 5-HT reuptake inhibitor
  – 5-HT2 antagonist
  – Initiate with 50 mg bid
• Mirtazapine
  – Limited experience to date in anxiety disorders
Atypical Antidepressants (cont.)
• Bupropion
  – Based on limited data, considered less effective
    for panic and other anxiety disorders, but
    reports suggestive of efficacy for
     • panic disorder
     • social anxiety disorder
     • PTSD
• Trazodone
  – Based on limited data, considered less effective
    for panic and other anxiety disorders
          Tricyclic Antidepressants
•   Imipramine (Tofranil)
•   Nortriptyline (Pamelor)
•   Desipramine (Norpramin)
•   Amitriptyline (Elavil)
•   Doxepin (Sinequan)

• Effective in anxiety with or without comorbid depression
• Recommended dosage 2.25 mg/kg/d Imipramine or its
  equivalent for panic
• Initial anxiety worsening (Initiate with “test” dose, e.g.
  10 mg/d IMI)
 Tricyclic Antidepressants (cont)
• Typical TCA side effects
   – anticholinergic effects (dry mouth, blurred
     vision, constipation)
   – orthostatic hypotension
   – cardiac conduction disturbance
   – weight gain
   – sexual dysfunction
• Lethal in overdose
• Weight gain and sedation often become
  increasingly problematic over time
• Efficacy: PDAG, GAD, PTSD
    Monoamine Oxidase Inhibitors
•   Phenelzine (Nardil) 45-90 mg/d
•   Tranylcypromine (Parnate) 30-60 mg/d
•   Isocarboxacid (Marplan) 10-30 mg/d
•   Initial worsening of anxiety is unusual
•   Side effects: light-headedness, neurological
    symptoms, weight gain, sexual dysfunction,
    edema
•   Dietary restrictions/Hypertensive crisis; “cheese
    reaction”
•   Risk of lethal overdose and toxicity
•   Generally reserved for refractory cases
•   Efficacy: PDAG, SP, OCD, PTSD
           Benzodiazepines
• Potency was considered critical determinant
  of anti-panic efficacy
  – Alprazolam (Xanax)
  – Clonazepam (Klonopin)
  – +/- Lorazepam (Ativan)
• But comparable doses of diazepam as
  effective as alprazolam
• All benzodiazepines effective for
  generalized anxiety
         Potential Benefits of
        Benzodiazepine Therapy

•   Effective
•   Short latency of therapeutic onset
•   Well tolerated
•   Rapid dose adjustment feasible
•   Can be used “prn” for situational anxiety
        Potential Drawbacks of
        Benzodiazepine Therapy

•   Initial sedation
•   Discontinuation difficulties
•   Potential for abuse in substance abusers
•   Not effective for comorbid depression
                       Alprazolam

•Effective as AD in panic
•Advantages: rapid onset of effect, lacks typical AD side effects
•Disadvantages: short duration of effect (i.e., multiple dosing,
interdose rebound), discontinuation syndromes, early relapse,
abuse potential, disinhibition
•Dosing: anticipate initial sedation (tachyphylaxis usually
develops).
•Range: 2-10 mg/d (4-6 mg/d usual) (QID dosing)
                        Clonazepam
• Labeled as anticonvulsant
• As effective as alprazolam for panic; issue of potency for anti-
  panic efficacy
• Advantages: Pharmacokinetic: longer duration of effect results
  in less frequent dosing, interdose symptoms, early relapse, or
  acute withdrawal symptoms. Slower onset of effect diminishes
  abuse potential
• Disadvantages: Depression not more frequent than with other
  Bzd”s; disinhibition, headaches
• Dosing: anticipate initial sedation (initiate at 0.25-0.5 mg qhs)
• Range: 1-5 mg/d (BID dosing)
    Combining Antidepressants
      with Benzodiazepines
• Provides rapid anxiolysis during
  antidepressant lag
• Decreases early anxiety associated with
  initiation of antidepressant
• Treats residual anxiety wtih antidepressant
  treatment
• Prevents and treats depression on
  benzodiazepines
                             End-Point (LVCF) Analysis of Panic Disorder Severity
                                         Scale Scores for Each Group

                      2.5
                                                                                                   Paroxetine + Placebo
                                     †                                                             Paroxetine + Clonazepam
                                     *
                                                                                                   Paroxetine + Clonazepame w/taper
                       2
                                              *
Average PDSS scores




                      1.5                                      *
                                                                        *


                       1


                      0.5
                                                                             Clonazepam Taper
                                                                                  Phase
                       0
                            Week   Week     Week     Week    Week     Week     Week    Week     Week   Week    Week       Week
                             00     01       02       03      04       05       06      07       08     09      10         12


                            * Together the Clonazepam groups differ from the Placebo group at p< .05
                            † Clonazepam groups differ from each other at p<.05
                                                                                                                    Pollack, et al 2001
                 Buspirone
• Non-benzodiazepine anxiolytic
• Non-sedating, muscle relaxant, anticonvulsant
• Effects on serotonin and dopamine receptors
• Indicated for GAD; weak antidepressant
  effects
• Useful as SSRI augmentation for panic, social
  phobia, depression, sexual dysfunction
• Dosing: 30-60 mg/d
             Beta Blockers
• Decrease autonomic arousal
• May be useful as adjunct for somatic
  symptoms of panic and GAD but not as
  primary treatment
• Useful for non-generalized social phobia,
  performance anxiety subtype
• Propranolol 10-60 mg/d; Atenolol 50-150
  mg/d
           Anticonvulsants
• Valproate and gabapentin effective for non-
  ictal panic
• Gabapentin effective for social phobia
• Gabapentin (600-5400 mg/d) used as
  alternative to benzodiazepine
• Valproate, Carbamazepine, Gabapentin,
  Topiramate and Lamotrigine for PTSD
Strategies for Refractory Anxiety
             Disorder
•   Maximize dose
•   Combine antidepressant and benzodiazepine
•   Administer cognitive-behavioral therapy
•   Attend to psychosocial issues




                                .
         Strategies for Refractory Anxiety
                     Disorders
• Augmentation                 • Combined SSRI/TCA
  – Anticonvulsants            • Alternative
       • Gabapentin              antidepressant
       • Valproate               – Clomipramine
       • Topiramate              – MAOI
  –   Beta blocker          • Other
  –   Buspirone               – Inositol
  –   Clonidine/Guanfacine    – Kava-kava
  –   Pindolol                – Atypical neuroleptics
  –   Dopaminergic agonists
      (e.g., Ropinirole) for
      social phobia
  – Cyproheptadine
   Cognitive-Behavioral Therapy
      for Anxiety Disorders
• CBT useful alone or in combination with
  medication for
   – Refractory symptoms
   – Persistent cognitive factors, behavioral patterns and
     anxiety sensitivity
   – Comorbid conditions
   – Early intervention for PTSD prophylaxis
• CBT may be provided by therapist or self-
  administered (TherapyWorks manuals 800-228-
  0752///http://www.psychcorp.com)
• CBT may facilitate medication discontinuation
                                             .
                Continuation Phase Outcome with
              Sertraline Treatment of PTSD Based on
                  Acute Phase Response Category
      Acute Phase                                      Continuation Phase
    Responder Status                                    Responder Status




                                                  Sustained
                                                  Response                        92%
    Acute Phase
    Responders                  8%                Lost response




                                Converted to responder 54%
   Acute Phase
Non-responders                                                46%
                          Continued non-response



                     0%               20%              40%          60%     80%   100%


   Responder = > 30% decrease CAPS and CGI-S = 1 or 2
   Londborg et al. J Clin Psychiatry, in press.
            Long-Term Treatment Of
                    GAD
 • Need to treat long-term
 • Full relapse in approximately 25% of
   patients 1 month after stopping treatment
 • 60%-80% relapse within 1st year after
   stopping treatment
Hales et al. J Clin Psychiatry. 1997;58(suppl 3):76.
Rickels et al. J Clin Psychopharmacol. 1990;10(3 suppl):101S.
        Effect Of Venlafaxine On Total
                HAM-A Scores
                  0
                                                                                          Placebo (N=123)
                 -2                                                                       Venlafaxine XR (N=115)
                 -4
                 -6
 Change In -8
Mean HAM-A
Total Score -10
               -12
               -14
               -16
               -18
                        0      2     4       6     8     10     12     14     16     18     20     22    24     26     28
                                                         Week Of Treatment

    P<.001 for venlafaxine XR vs placebo for all study weeks except week 1 (.003), week 4 (.002), and week 20 (.007)
    Venlafaxine XR doses: 75 to 225 mg/d.
    Gelenberg et al. JAMA. 2000;283:3082.
   Paroxetine Long-Term GAD Treatment
               % Remission
                          Phase I: Single-Blind                 Phase II: Double-Blind
                                                            Placebo (N=274)
           80            Paroxetine 20-50 mg
                                                            Paroxetine (N=285)        *    *
                         (N=599 responders)                                      *
           70                                                          *
                                      Randomization              *
           60
                                                            *
Patients
  (%)    50

           40

           30

           20

           10

            0
                     1       2       3    4     6      8   12   16    20    24       28   32
  * P<.01 vs placebo.                                 Week
    Remission = HAM-A 7; LOCF dataset.
    GlaxoSmithKline data on file, 2001.
Discontinuation of Treatment for
      Anxiety Disorders
• Withdrawal/rebound more common with Bzd than
  other anxiolytic treatment
• Relapse: a significant problem across treatments.
  Many patients require maintenance therapy
• Bzd abuse is rare in non-predisposed individuals
• Clinical decision: balance comfort/compliance/
  comorbidity during maintenance treatment with
  discontinuation-associated difficulties
        Strategies for Anxiolytic
            Discontinuation
•   Slow taper
•   Switch to longer-acting agent for taper
•   Cognitive-Behavioral therapy
•   Adjunctive
    – Antidepressant
    – Anticonvulsant
    – ?clonidine, ?beta blockers, ? buspirone

								
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