The Philippine College of The Philippine College of PsychopharmacologyPsychopharmacology

20082008

Anxiety DisordersAnxiety Disorders(Focus on Panic Disorder)(Focus on Panic Disorder)

TEACHING MODULE FOR TEACHING MODULE FOR THE PRIMARY CARE THE PRIMARY CARE

PHYSICIANSPHYSICIANS

ObjectivesObjectives

At the end of this module, the primary At the end of this module, the primary care physician is expected to:care physician is expected to:

1. understand the nature of anxiety 1. understand the nature of anxiety disordersdisorders

2. diagnose the main anxiety disorder 2. diagnose the main anxiety disorder (Panic D)(Panic D)

3. treat panic disorder with the appropriate 3. treat panic disorder with the appropriate drugs drugs quickly, effectively, and safelyquickly, effectively, and safely

Basic Facts on Anxiety Basic Facts on Anxiety DisordersDisorders

Prevalence rates of 5-15% in adultsPrevalence rates of 5-15% in adults Can be quite debilitating ; affects Can be quite debilitating ; affects

quality of lifequality of life Frequently overlap with depression Frequently overlap with depression

(60%)(60%) When diagnosed properly, easy to When diagnosed properly, easy to

treattreat Most often seen first by non-Most often seen first by non-

psychiatristspsychiatrists

Who see anxious patients Who see anxious patients first?first?

1. Internists – 40%1. Internists – 40% 2. Family Physicians – 25%2. Family Physicians – 25% 3. OB-Gyne/EENT – 20%3. OB-Gyne/EENT – 20% 4. Psychiatrists – 10%4. Psychiatrists – 10% 5. Others – 5%5. Others – 5%

Anxious Patient: Usual Anxious Patient: Usual ProfileProfile

Young (20s – 30s)Young (20s – 30s) More women affectedMore women affected Natural worrier (from childhood)Natural worrier (from childhood) Strict, with high standards Strict, with high standards Inadequate outletsInadequate outlets

The Many ‘Faces’ of AnxietyThe Many ‘Faces’ of Anxiety

MSK – back/headache, spasms, fatigueMSK – back/headache, spasms, fatigue CVS – palpitations, chest painCVS – palpitations, chest pain RESP _ dyspnea, hyperventilationRESP _ dyspnea, hyperventilation GIT – lump in the throat, GIT – lump in the throat,

nausea/vomiting, nausea/vomiting, “butterflies”“butterflies”

GUT – frequent micturition, premature GUT – frequent micturition, premature ejaculation, impotence ejaculation, impotence

CNS – dizziness, tremors, numbness, CNS – dizziness, tremors, numbness, ‘pins ‘pins and needles’ and needles’

Try to rule out…Try to rule out…

Hyperthyroidism – THyperthyroidism – T33, T, T44, TSH, TSH Hypoglycaemia – RBS, FBSHypoglycaemia – RBS, FBS Complex partial seizure (TLE) – EEGComplex partial seizure (TLE) – EEG Mitral valve prolapse – 2D-ECHO; may co-existMitral valve prolapse – 2D-ECHO; may co-exist Illegal drugs, e.g. methamphetamines – urine Illegal drugs, e.g. methamphetamines – urine

testtest

Avoid too much work-up; may reinforce anxietyAvoid too much work-up; may reinforce anxiety If patients insist on more tests, convince If patients insist on more tests, convince

otherwise otherwise

Role of GeneticsRole of Genetics

Family studies:Family studies:

20% morbidity risk in relatives 20% morbidity risk in relatives compared to 2% in controlscompared to 2% in controls

Twin studies:Twin studies:

45% morbidity in identical versus 45% morbidity in identical versus 15% in non-identical twins15% in non-identical twins

Biological Abnormalities Biological Abnormalities

Functional imbalance in the followingFunctional imbalance in the following::

1. Autonomic nervous system – increased 1. Autonomic nervous system – increased sensitivity of the sympathetic system due sensitivity of the sympathetic system due to cumulative effects of life stressesto cumulative effects of life stresses

Other areas in the brain also affected , e.g. Other areas in the brain also affected , e.g. locus ceruleus (site of greatest number of locus ceruleus (site of greatest number of noradrenergic neurons)noradrenergic neurons)

Biological AbnormalitiesBiological Abnormalities

2. Locus ceruleus – abnormal 2. Locus ceruleus – abnormal increased sensitivity of increased sensitivity of noradrenergic neuronsnoradrenergic neurons

3. BZ/ GABA complex – decreased 3. BZ/ GABA complex – decreased sensitivity of BZ receptors and sensitivity of BZ receptors and decreased inhibition of GABA decreased inhibition of GABA

Panic Attack: Working Panic Attack: Working HypothesisHypothesis

Genetic vulnerabilities Genetic vulnerabilities → →

cumulative effects of life stresses cumulative effects of life stresses →→

increased activity of the SNS increased activity of the SNS → →

activation of locus ceruleus activation of locus ceruleus →→

decreased sensitivity of Bz receptors decreased sensitivity of Bz receptors → → decreased inhibition of GABA decreased inhibition of GABA → →

panic attackspanic attacks

Main Features of Anxiety Main Features of Anxiety Disorders Disorders

1. GAD - pervasive 1. GAD - pervasive worriesworries

2. 2. Panic Disorder - feeling of Panic Disorder - feeling of doomdoom

3. Phobias - morbid fear3. Phobias - morbid fear

4. OCD – repetitive rituals4. OCD – repetitive rituals

5. PTSD – recurrent 5. PTSD – recurrent flashbacksflashbacks

6. Others (drugs/6. Others (drugs/

medical cases) - feeling restlessmedical cases) - feeling restless

Panic DisorderPanic Disorder

Lifetime prevalence- 1-3%Lifetime prevalence- 1-3% More in women – 2-4xMore in women – 2-4x Co-morbid with depression – 60%Co-morbid with depression – 60% With or without agoraphobiaWith or without agoraphobia Tendency to become chronic (15%)Tendency to become chronic (15%) Main feature – panic attackMain feature – panic attack

PANIC ATTACKPANIC ATTACK

Main Characteristics:Main Characteristics: 1. Sudden, unexpected (“out of the 1. Sudden, unexpected (“out of the

blue”)blue”)

2. Feeling of “impending doom”2. Feeling of “impending doom”

3. Increasing and decreasing 3. Increasing and decreasing intensity intensity from start to finish from start to finish ( 30-60 minutes)( 30-60 minutes)

4. Several attacks in one month4. Several attacks in one month

5. Multi-system involvement 5. Multi-system involvement

Top Five Symptoms of PD Top Five Symptoms of PD (Noyes)(Noyes)

Fearfulness or worry - 96%Fearfulness or worry - 96% Nervousness - 95%Nervousness - 95% Palpitations - 93%Palpitations - 93% Muscle aches - 89%Muscle aches - 89% Trembling - 89%Trembling - 89%

Psychopharmacology of Panic Psychopharmacology of Panic DisorderDisorder

AntidepressantsAntidepressants 1. Tricyclics (TCAs)1. Tricyclics (TCAs)

2. Selective serotonin reuptake inhibitors 2. Selective serotonin reuptake inhibitors (SSRIs)(SSRIs)

3. Dual antidepressants (SNRIs, NaSSA)3. Dual antidepressants (SNRIs, NaSSA) AnxiolyticsAnxiolytics 1. Benzodiazepines (alprazolam, clonazepam)1. Benzodiazepines (alprazolam, clonazepam)

ANTIDEPRESSANTS 1ANTIDEPRESSANTS 1

Tricyclics: hardly a choice nowTricyclics: hardly a choice now

1. Effective (delayed by 1-2 weeks)1. Effective (delayed by 1-2 weeks)

2. Plenty of side-effects (almost 2. Plenty of side-effects (almost immediate)immediate)

3. Unsafe in overdose (arrhythmia)3. Unsafe in overdose (arrhythmia)

4. Inexpensive4. Inexpensive

5. No abuse potential 5. No abuse potential

6. Dose: 3x/day (e.g. Trimipramine 25 6. Dose: 3x/day (e.g. Trimipramine 25 mg)mg)

ANTIDEPRESSANTS 2ANTIDEPRESSANTS 2

SSRIs: drugs of choiceSSRIs: drugs of choice

1. Effective (delayed by 1-2 weeks)1. Effective (delayed by 1-2 weeks) 2. Side-effects mainly GIT (serotonin-2. Side-effects mainly GIT (serotonin-

based)based) 3. Safe in overdose3. Safe in overdose 4. Expensive (but generics now available)4. Expensive (but generics now available) 5. No abuse potential5. No abuse potential 6. Single dose (e.g. Sertraline 50 mg/day)6. Single dose (e.g. Sertraline 50 mg/day)

ANTIDEPRESSANTS 3ANTIDEPRESSANTS 3

SNRI/NaSSA: first choice for GADSNRI/NaSSA: first choice for GAD

1. Effective – (delayed also; NaSSA a tad 1. Effective – (delayed also; NaSSA a tad early?)early?)

2. Side-effects – mainly noradrenergic-based2. Side-effects – mainly noradrenergic-based

3. Safe in overdose3. Safe in overdose

4. Most expensive; one generic available4. Most expensive; one generic available

5. No abuse potential5. No abuse potential

6. Single dose (Duloxetine 60mg; 6. Single dose (Duloxetine 60mg; Mirtazapine 30mg)Mirtazapine 30mg)

ANXIOLYTICSANXIOLYTICS

Benzodiazepines: second choiceBenzodiazepines: second choice

1. Rapid onset ; excellent for acute attacks 1. Rapid onset ; excellent for acute attacks

2. Side-effects mainly drowsiness, 2. Side-effects mainly drowsiness, weaknessweakness

3. Tricky in overdose ; deadly with alcohol3. Tricky in overdose ; deadly with alcohol

4. Inexpensive ; generics available4. Inexpensive ; generics available

5. With abuse potential 5. With abuse potential

6. Dose: 1-2x/day (e.g. Alprazolam 500 mcg 6. Dose: 1-2x/day (e.g. Alprazolam 500 mcg -1 mg)-1 mg)

Practical Psychiatry 101Practical Psychiatry 101

Panic attacks are acute, intense, Panic attacks are acute, intense, prolongedprolonged

Quick symptom control crucialQuick symptom control crucial Drugs of choice are antidepressants Drugs of choice are antidepressants

( NOT benzodiazepines); slow in onset ( NOT benzodiazepines); slow in onset but no potential for abusebut no potential for abuse

Second choice is a benzodiazepine Second choice is a benzodiazepine like alprazolam, quick in onset but like alprazolam, quick in onset but with potential for abusewith potential for abuse

Practical Psychiatry 101Practical Psychiatry 101

What is needed is an approach that What is needed is an approach that would quickly control panic attacks would quickly control panic attacks without exposing patients to without exposing patients to dependence/abusedependence/abuse

Dependence usually takes weeks or Dependence usually takes weeks or months of continuous drug use, at months of continuous drug use, at higher than recommended doseshigher than recommended doses

So, what to do?So, what to do?

Practical Psychiatry 101Practical Psychiatry 101 Recommendations:Recommendations:

1.1. Give an SSRI (e.g. Sertraline 50 mg hs) Give an SSRI (e.g. Sertraline 50 mg hs) AND a benzodiazepine (e.g. Alprazolam AND a benzodiazepine (e.g. Alprazolam 500 mcg – 1.0 mg 2x a day) for 10 to 14 500 mcg – 1.0 mg 2x a day) for 10 to 14 daysdays

Rationale: Sertraline takes a while to take Rationale: Sertraline takes a while to take effect whilst alprazolam acts very quickly to effect whilst alprazolam acts very quickly to control the attacks. Patient is relieved of control the attacks. Patient is relieved of his panic symptoms in a day or two.his panic symptoms in a day or two.

Practical Psychiatry 101Practical Psychiatry 101

Recommendations:Recommendations:

2. After 10-14 days, gradually reduce 2. After 10-14 days, gradually reduce Altrox by 0.5 mg/week and totally stop it Altrox by 0.5 mg/week and totally stop it within two - three weeks. Keep Serenata at within two - three weeks. Keep Serenata at same dose as maintenancesame dose as maintenance

Rationale: At two weeks, the level of Rationale: At two weeks, the level of Sertraline is already peaking and can now Sertraline is already peaking and can now stand on its own; stopping alprazolam at stand on its own; stopping alprazolam at this time would avoid dependence or abuse this time would avoid dependence or abuse

Practical Psychiatry 101Practical Psychiatry 101

Recommendations:Recommendations:

3. Don’t give a benzodiazepine as the 3. Don’t give a benzodiazepine as the sole drug, either in acute phase or sole drug, either in acute phase or maintenance period (easier said than maintenance period (easier said than done)done)

Rationale: It would be hard to Rationale: It would be hard to discontinue and the danger of discontinue and the danger of dependence would be real (‘iatrogenic dependence would be real (‘iatrogenic dependence’)dependence’)

ALPRAZOLAMALPRAZOLAM

Very effective, especially in acute Very effective, especially in acute attacksattacks

Not too sedating (unlike clonazepam)Not too sedating (unlike clonazepam) Generic bioequivalent available Generic bioequivalent available

(Altrox)(Altrox) Dose range: 1-2 mg/day for acute Dose range: 1-2 mg/day for acute

attacksattacks Potential for abuse negligible when Potential for abuse negligible when

used wellused well

SUMMARYSUMMARY

Anxiety disorders are very common Anxiety disorders are very common and can be debilitating in their effectsand can be debilitating in their effects

Vague, multiple, repetitive, Vague, multiple, repetitive, nonphysiologic physical complaints nonphysiologic physical complaints suggest an anxiety disordersuggest an anxiety disorder

Panic attacks need to be controlled Panic attacks need to be controlled

quickly, effectively, and safelyquickly, effectively, and safely

SUMMARYSUMMARY

An initial combination of an An initial combination of an antidepressant and an anxiolytic is antidepressant and an anxiolytic is recommendedrecommended

After 10-14 days, (maximum of 30 After 10-14 days, (maximum of 30 days) antidepressant is continued days) antidepressant is continued whilst anxiolytic is discontinuedwhilst anxiolytic is discontinued

Giving anxiolytic as sole drug is not Giving anxiolytic as sole drug is not recommended because of recommended because of dependence problemsdependence problems

THANK YOU VERY MUCH THANK YOU VERY MUCH INDEED INDEED

No more worries, I hopeNo more worries, I hope