John I. Bailey, Jr., MD

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John I. Bailey, Jr., MD Mobile, Alabama 251 342-6443 ADHD and Related Conditions in Children & Adults www.calofmobile.com adddoc@bellsouth.net

WHY I LEFT FAMILY PRACTICE FOR PSYCHIATRY Your insurance company is refusing to pay your medical bills. They say you were already an idiot before you decided to roller-blade down the interstate.

DISCLOSURE Paid participant: Real-world Adderall Studies, 1990 s Adderall IR Paid participant: LADD-CAT Study, 2001 Adderall XR Paid speaker: Tris Pharma, 2016 -> Otherwise, since 2001, I have had no financial involvement with any entity involved with ADHD some travel expenses for ADHD conferences at which I spoke gratis.

PSYCHIATRIC TREATMENT

ADHD MEDICATIONS How to Use Your Brain All Day

TREATMENT SUCCESS -- Bailey s 1 st Law of Medication -- SUCCESS IN LIFE WITH ADHD IS PROPORTIONAL TO THE PERCENTAGE OF LIFE TREATED WELL

TREATMENT SUCCESS -- Bailey s 2nd Law of Medication -- LIFE S HARDER IF THE MEDICINE ISN T RIGHT

TREATMENT SUCCESS -- Bailey s 2nd Law of Medication -- LIFE S HARDER IF THE MEDICINE ISN T RIGHT Drug Delivery System Dose Frequency Timing

SLIM OUTLINE Available medications Non-stimulants & stimulants What s officially OK & what s not What works - what doesn t Forms & delivery systems Dosages Durations of action Engineering continuous action

CAVEATS and all that stuff What I say isn t all you need to know nor gospel. Information presented is for general medical education. It is not intended to establish a standard of care or to bear upon any specific patient. I am not endorsing or condemning any product. I may use brand names at times because of audience familiarity, not recommendation. Any drug may be the best drug for any 1 patient.

CAVEATS and all that stuff Ages, dosages, frequencies, durations, indications, etc. discussed will not all conform to FDA s or manufacturer s product information. Not every statement or treatment possibility mentioned has received ideal scientific study. Some have received none. Some is fact, some is observation, some is opinion. Don t rely on or do anything treatment-related in this presentation unless your doctor agrees with it. Follow label directions, cautions, & all drug laws. Your mileage may vary.

PSYCHIATRIC APOTHECARY DIAGNOSIS AVAILABLE MEDS Depression 25 + 0000000000000000000000000 Anxiety 18 + 000000000000000000 Sleep 17 + 00000000000000000 Cyclic Moods 11 + 00000000000 ADHD 6 000000

ADHD APOTHECARY NON - STIMULANTS STIMULANTS Adrenalin Inhibitors Selective D/N RI Miscellaneous True amphetamines Near-amphetamine clonidine guanfacine atomoxetine (none are indicated) amphetamine methamphetamine methylphenidate

ADHD MEDS NOT INDICATED FOR ADHD Off-Label Usage with Minimal Evaluation Antinarcoleptics Provigil, Nuvigil Appetite Suppressants Adipex-P (phentermine), Tenuate, Bontril, Didrex Antiparkinsonians Symmetrel (amantadine), Requip (ropinirole) MAOI s Parnate, Nardil, Marplan, Emsam (selegiline patch) Antidepressants Wellbutrin, Effexor, Cymbalta, tricyclics

WHY ANTIDEPRESSANTS? DEPRESSION Mimics ADHD Memory Concentration Focus Motivation Interest TWICE AS HARD -- -- HALF AS FAR --ADDA Conference Theme, 1996

HERBALS NUTRACEUTICALS NOOTROPICS HOMEOPATHIC MEDS DIETARY SUPPLEMENTS No rigid, placebo-controlled, scientific study has ever shown a useful and statistically valid benefit from any such agent.*

WHAT IS A DRUG?

DRUG A substance which, when administered to a rat, produces a doctoral dissertation.

ADHD MEDICATION FIELD

ADHD MEDICATION FIELD Left Field amantadine phentermine modafinil Center Field amphetamine methylphenidate Right Field guanfacine clonidine Stay on the Bus methamphetamine MAOI s tricyclic anti-d s Dugout atomoxetine buproprion venlafaxine

APPROVED ADHD FIELD Left Field amantadine phentermine modafinil Center Field AMPHETAMINE METHYLPHENIDATE Right Field GUANFACINE CLONIDINE Stay on the Bus METHAMPHETAMINE MAOI s tricyclic anti-d s Dugout ATOMOXETINE buproprion venlafaxine

ADHD STIMULANT FIELD Left Field amantadine phentermine modafinil Center Field AMPHETAMINE METHYLPHENIDATE Right Field GUANFACINE CLONIDINE Stay on the Bus METHAMPHETAMINE MAOI s tricyclic anti-d s Dugout ATOMOXETINE buproprion venlafaxine

ADHD STIMULANT FIELD Left Field amantadine phentermine modafinil Center Field AMPHETAMINE METHYLPHENIDATE Right Field GUANFACINE CLONIDINE Stay on the Bus METHAMPHETAMINE MAOI s tricyclic anti-d s Dugout ATOMOXETINE buproprion venlafaxine

STRATTERA Atomoxetine Failed Antidepressant Non-Stimulant Better P.R. In drug-misuse patients? Non-Controlled Can be called in Can be refilled OK: 6 YO - Adults Doses missable Effect rolls over Main engine vs helper-engine Booster?

STRATTERA Atomoxetine Frequent Side Effects... GI upset common - 20% - nausea, vomiting, pain Poor appetite common Sleepiness frequent Headache Urinary flow problems Other Issues... Black-box warning - suicide discussion required Blows up bipolar & cyclothymia - especially teens? Liver damage occasional

STRATTERA Atomoxetine Nuisances Rarer success than stimulants - 75% vs 95% Slow onset - 1 month -- after target dose Concerns Unpredictable metabolism Dosage & frequency vary Drug interactions CV cautions suggested -- as with stimulants 2 Achilles Heels!! Vague, indistinct effect Harm from missed doses not noticed Initial reassurance... ---> stealthy fadeaway Frequently works for 4-6 months - only!!

ALPHA-2 AGONISTS INHIBITORS Clonidine - Guanfacine Inhibit norepinephrine signaling in brain Reduces overactivation Best ---- ADHD w/ Oppositionality, Agitation, Anger, & Aggression Good ---- Impulsivity & Distractibility Fair ---- Physical Hyperactivity Poor ---- Inattention & Focus Helpful with tics Virgin or stimulant-augmented (disputed) De-fuser

ALPHA-2 AGONISTS DE-FUSING CANDIDATE

CLONIDINE OLD ADULT ANTIHYPERTENSIVE - Catapres Short-acting tabs not indicated for ADHD Not practical 4 doses/day - ADHD rebound 3 X a day if dose late Daytime sleepiness Kapvay - time-release No adult or long-term studies Tic treatment consideration BEST FOR HYPERACTIVITY - IMPULSIVITY Good inhibitor Poor attention magnifier BEST USES: Tabs as sleep agent (not indicated) Add to stimulants

GUANFACINE Old adult antihypertensive drug - Tenex Better for ADHD than for HBP Most US use is ADHD Inherent 8-12 hour duration Economical - generic long and short work well Useful addition to stimulants First-line / safest agent for tics (disputed) Suppresses night ADHD awakenings Intuniv - 12-24 hour duration More magical than generic guanfacine Most prefer to generic Best for Irritability, Anger, S.T.O. (Status Ticked Off) He s nicer!

GUANFACINE DEFICIENCY

STIMULANTS

STIMULANT DRUG One which causes a temporary arousal of central nervous system activity, resulting in increases in: Alertness Wakefulness Consciousness Awareness Stimulus recognition Sense of well-being Mood Energy Interest Motivation

STIMULANT DURATIONS -- VIP! 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Rit. Tabs? Focalin Tabs Dex Tabs Adderall Tabs? Dextroamphetamine ER F-XR R-LA M-CD Aptensio XR Adderall XR? Concerta? Vyvanse Dyanavel XR Mydayis?? 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9

DISPENSING or CONCENTRATION CURVES VS EFFECTIVENESS CURVES

CONCENTRATION EFFECTIVENESS

T M GENERAL EFFECTIVENESS CURVE E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

T M GENERAL EFFECTIVENESS CURVE E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 Rapid Onset

T M GENERAL EFFECTIVENESS CURVE E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 Slow Onset

SOAPBOX MODE T M E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

NOT LONG ENOUGH E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

SO GIVE MORE? T M E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

PLAN B - ALL TOO COMMON E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

ALL TOO COMMON

PLAN B - MIDDAY GAP E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

GAP CURE? - FAIL! E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

GAP CURE? - FAIL! E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

GAP CURE... but... E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

GAP CURE... better, but... E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

GAP CURE... betterer, but... E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

NEW PROBLEM... E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

METHYLPHENIDATE

METHYLPHENIDATE - The Early Years 1955 Ritalin 1982 Ritalin SR discontinued 1999 Metadate ER 2000 Concerta 2001 Metadate CD 2001 Focalin 2002 Ritalin LA 2002 Methylin IR liquid & chewable tabs 2005 Focalin XR 2006 Daytrana patch

METHYLPHENIDATE - The Recent Years 2012 Quillivant XR liq 2015 Aptensio XR cap 2015 QuilliChew ER tab 2017 Cotempla XR-ODT orally dissolving

METHYLPHENIDATE IR 10 mg 10 MG E 0 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 INEFFECTIVE

METHYLPHENIDATE IR 10 mg 10 MG 10 MG E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 INEFFECTIV E INEFFECTIVE

METHYLPHENIDATE IR 10 mg E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

TEXAS LIMOUSINE

METHYLPHENIDATE IR 10 mg E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

GENERAL LONG-ACTING CURVE E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

METHYLPHENIDATE IR Useful for Short Treatment Periods E FAST CRANK 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

METHYLPHENIDATE IR Useful for Short Treatment Periods E FAST CRANK PM ADD-ON 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

DELIVERY SYSTEMS

IMMEDIATE - RELEASE DELIVERY SYSTEM

EXTENDED - RELEASE DELIVERY SYSTEM

Metadate CD Delivery System 30% - Rapid Release (IR) 70% - Continuous Release (ER) 30% of dose rapidly released 70% of dose continuously released Core Methylphenidate HCI Protective Coating Core Methylphenidate HCI Protective Coatings Release-control Membrane Beads shown are not actual sizes Metadate is a registered trademark of Celltech Pharma, Ltd.

2-PHASE SYSTEM - 1X 5-7 Hours +/- E 3.5 H 3.5 H 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

2-PHASE SYSTEM - 2X E 3.5 H 3.5 H 3.5 H 3.5 H 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

CONCERTA - Delivery System Janssen Pharmaceuticals, Inc.

CONCERTA E Range: 6-12 Hours Average: 8 Hours 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

CONCERTA - BAD LUCK E 6-7+ Hours 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

CONCERTA 2X TM E 36 MG 36 MG 1 st 2 nd 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

BUMPY DAY

CONCERTA 2X TM E 36 MG 1 st 2 nd 18 or 27 MG 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

CONCERTA + MPD-IR BOOST E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

CONCERTA + MPD-IR - PM 2X E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

MID-RANGE + SHORT 10-11 Hours +/- E 6-7 Hours 4 Hours 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

2-PHASE SYSTEM - 2X E 3.5 H 3.5 H 3.5 H 3.5 H 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

LONG-ACTING PRODUCT E????? 8-10 - 12 Hours? 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

DAYTRANA PATCH Ritalin Patch 4 patch sizes - $13/patch/day Not adult indicated Hold to hip x 30 seconds Slow to crank - 2 hours Only ADHD Rx must remember to start and stop! Must remember to remove at 9 hrs Then remains 3 hours - problem for sleep-sensitive patients Beware: Waistbands, water, contact sports, application difficulties, impatience, heat, forgetfulness, skin irritation Irritated skin absorbs more* Contact sensitization is rare, but: be aware that if it happens, it may preclude oral MPD treatment -- for life.

AMPHETAMINES

AMPHETAMINES - The Early Years 1887 - Amphetamine synthesized in Germany 1893 - Methamphetamine synthesized 1932 - Benzedrex OTC amphetamine inhaler till 1959 1935 - Methamphetamine study #1 1937 - Benzedrine for headaches - Chas. Bradley, MD* 1937 - Dexedrine marketed by SKF fatigue, etc 1940 - Dextroamphetamine in WWII go pills 1942 - Benzedrine ADHD study #1 published Bradley 1950 Marketing explosion not for ADHD

AMPHETAMINES The Later Years 1960 - Obetrol - dex + meth 1976 - Dexedrine Spansules - 1 st E-R ADHD Rx 1994 - Obetrol - meth removed, reformulated as MSA 1996 - Adderall - Obetrol renamed. approved for ADHD 2001 - Adderall XR - 1st good ER system 2007 - Vyvanse - very long acting, approved for ADHD

AMPHETAMINES The Recent Years 2013 - ProCentra - dex IR liquid 2015 - Vyvanse - new approval for Binge Eating Disorder 2015 - Evekeo - the return of Benzedrine 2015 - Zenzedi - dex tabs 2015 - Dyanavel XR - dex time-release liquid 2016 - Adzenys XR-ODT - orally dissolving tablet 2017 - Mydayis - 3-phase capsule

DEXTROAMPHETAMINE Dextroamphetamine Tabs - 2.5-30 mg Dextroamphetamine ER - 5, 10, 15 mg Extended Release 5.5 Hours Tabs 4 Hours E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

ADD-ER-ALL TABS 1X E 3.5-4 Hours 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

ADDERALL TABS 3X TM E 20 MG 20 MG 20 MG 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

ADDERALL XR 1X 6-10 Hours +/- E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

ADDERALL XR 2X 12-16 Hours +/- E 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

COMMON STIMULANT DOSING & DURATION INCREASING THE DOSE OF MOST STIMULANTS INCREASES THE CONCENTRATION -- NOT THE DURATION

MPD ER 20 mg 1X E 5-7 Hours +/- 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

MPD ER 40 mg 1X TM E 6-8 Hours +/- 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

MPD ER 20 mg 2X E 5-7 Hours +/- 5-7 Hours +/- 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

VYVANSE 30 mg E 9-10 Hours ---> 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

VYVANSE 40 mg E 10-12 Hours -----> 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

VYVANSE 50 mg E 12-14 Hours -------> 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

VYVANSE 60 mg TM E 12-14 Hours -------> 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10

STIMULANT DOSING PRACTICAL BUT NONSTANDARD PROCESS FOR STIMULANT DOSING This must be done with thoughtful discussion and physician direction. The patient doesn t know what normal is! Go up carefully until it doesn t feel right Drop down one notch That s frequently the best dose If then it s not good enough, change the drug! Even if it seems fine, it s OK to try a change!

STIMULANT DOSING Insufficient dosages and durations of dosing mislead everyone involved - teachers, spouses, bosses, doctors - and the patient - to think maximum potential has been reached!

ADHD MEDS I take my pill, but my life doesn t seem to be getting any better.

TREATMENT SUCCESS Bailey s 1 st Law: SUCCESS IS PROPORTIONAL TO THE PERCENTAGE OF LIFE TREATED WELL

TREATMENT SUCCESS Bailey s 1 st Law: SUCCESS IS PROPORTIONAL TO THE PERCENTAGE OF LIFE TREATED WELL Treat 7 days a week Treat from arising Treat as close to bedtime as practical Treat weekends, holidays, breaks, & summers Drug holidays hurt you, not help you Keep level constant through the day Use long-acting meds whenever possible Combine products and even different drugs if needed

- ADHD MEDS - Use Your Brain All Day

- YOU MAY REJOICE -

John I. Bailey, Jr., MD Mobile, Alabama 251 342-6443 ADHD and Related Conditions in Children & Adults www.calofmobile.com adddoc@bellsouth.net