Holistic approach in management of ADHD

Transcription

1 Holistic approach in management of ADHD

2 Outline Historic timeline Prevalence ADHD development Treatment modalities Current guidelines for management

3 ADHD Historical Timeline Described in 19 th century literature 1902 ADHD Syndrome first described 1918 Possible manifestation of Von Economo s Encephalitis in children 1930 Minimal Brain Damage 1960 Minimal Brain Dysfunction 1968 Hyperkinetic Reaction (DSM-II) 1980 ADD ± hyperactivity (DSM-III) 1987 ADHD (DSM-IIIR) 1994 Attention Deficit/Hyperactivity Disorder (DSM-IV)

4 Worldwide Prevalence of ADHD Is 3% to 7% Studies of ADHD prevalence United States (Shaffer et al 1996) Tennessee (Wolraich et al 1996) Mannheim, Germany (Esser et al 1990) London, England (Esser et al 1990) Germany (Baumgaertel et al 1995) Iowa (Lindgren et al 1990) Pittsburgh, Pa (Costello et al 1988) US inner city (Newcorn et al 1989) Ontario (Szatmari et al 1989) New Zealand (Anderson et al 1997) Prevalence of ADHD 0 (%) in school-age 5 children oldman, et al. JAMA.1998;279:

5 Potential Areas of Impairment Academic limitations Occupational/ vocational Relationships Legal difficulties ADHD Low self esteem Motor vehicle accidents Injuries Smoking and substance abuse

6 Developmental impact of ADHD Behavior disturbance Academic problems, difficulty with social interactions, self esteem issues, legal issues, drugs injuries/accident, risky sexual behaviors Occupational failure, relationship problems, self esteem issues, legal issues, drugs, injuries/ accident, risky sexual behaviors Preschool School age Adolescent College-age Adult Behavior disturbance, academic problems, difficulty with social interactions, self esteem issues Academic problems, occupational difficulties, relationship problems, self esteem issues, legal issues, drugs, injuries/accident, risky sexual behaviors

7 ADHD treatments Both pharmacological and non-pharmacological treatments for ADHD for children Treatment for children with ADHD includes parent and teacher training in effective behavior-management techniques aimed at reducing the problem behaviors associated with ADHD

8 ADHD Pharmacotherapies Approved by FDA Not Approved by FDA Stimulants Methylphenidate Antidepressants Tricyclics Amphetamine Bupropion Dextroamphetamine Antihypertensives Clonidine Lisdexamfetamine Guanfacine Nonstimulant Atomoxetine Miscellaneous Combine Pharmacotherapy Modafinil/Venafaxine

9 Pharmacotherapy in ADHD Optimal management of ADHD aims to minimise core symptoms of the disorder and associated impairments 1 Functional improvement should be the key goal of management 2 Clinical guidelines recommend methylphenidate (MPH) as a first-line pharmacological treatment for ADHD 3,4 Pharmacotherapy for patients with ADHD should form part of a comprehensive treatment plan that includes psychological, behavioural and educational advice and interventions 3 1. Remschmidt et al. Eur Child Adolesc Psychiatry 2005;14: ; 2. Weiss et al. J Clin Psychiatry 2006;67(suppl 8):38-45; 3. NICE (UK) National Clinical Practice Guideline Number 72; CADDRA. Canadian ADHD Practice Guidelines Third edition

10 Why extended release MPH? IR MPH Rapid, Saturating & short-acting OROS MPH Slow-acting, Incomplete target saturation, Long acting Highs/Euphoria, Need for reinforcement Compulsive use Therapeutic action without Highs Firing pattern of DA would be tonic & regular Lesser abuse potential

11 IR MPH formulations are associated with some limitations Short duration of effect 1 Immediate-release methylphenidate: bid/tid dosing Peak/trough fluctuations throughout day Rebound/End of dose effects Requires in-school and after-school dosing Compliance issues 1 Controlled substances often required to be kept in school office and may have special requirements for administration in school Compromised privacy: children with ADHD often report experience of stigma as a direct result of taking tablets 2 1. Pelham et al. Pediatrics 2001;107(6):E105; 2. NICE (UK) National Clinical Practice Guideline Number 72;2009

12 1. Banaschewski et al. Eur Child Adolesc Psychiatry 2006;8: ; 2. NICE (UK) National Clinical Practice Guideline Number 72; CADDRA Canadian ADHD Practice Guidelines Third edition Guideline recommendations for long-acting stimulants Long-acting formulations offer the possibility of addressing limitations of IR-MPH Potential benefit of long-acting drug formulations for the treatment of ADHD 1,2 : Pharmacokinetic profiles Improving adherence Reduced stigma (because a child or young person does not need to take medication at school) Reduced problems schools have in storing and administering controlled drugs Guideline recommendations 1 : Long-acting preparations should be available and used Long-acting formulation should be used first-line in the pharmacological treatment of uncomplicated ADHD 3 Individual clinical choice is needed

13 Osmotic-release oral system methylphenidate (OROS-MPH) has a unique, long-acting, formulation 1. CONCERTA Summary of Product Characteristics; 2. Swanson et al. Arch Gen Psychiatry 2003;60(2):

14 Concentration (ng/ml) Pharmacokinetic profile of OROS MPH IR-MPH 10 mg tid (n=15) OROS-MPH 36 mg qd (n=15) Time (h) OROS-MPH provides 1 : Immediate release followed by extended release of MPH 2 Minimized fluctuations in peak and trough plasma concentrations compared to MPH tds 2 Ascending pharmacokinetic profile to overcome acute tolerance 1 MPH delivery unaffected by food 3 OROS-MPH or IR MPH IR-MPH IR-MPH 1. Swanson et al. Arch Gen Psychiatry 2003;60:204-11; 2. Modi et al. J Clin Pharmacol. 2000;40: ; 3. Modi et al. Biopharm Drug Dispos. 2000;21:23-31

15 OROS-MPH treatment provides full active day coverage in children with ADHD Beneficial effects on attention and behaviour occur rapidly (~1.5hours after dosing) and are sustained over a complete 12-hour period 1 Time Additional benefits were observed for other measures with OROS-MPH 1 Time SKAMP=Swanson, Kotkin, Agler, M-Flynn, and Pelham; Means (+ standard error) for SKAMP-attention and SKAMP-deportment measures from the laboratory sessions. Pelhman et al. Pediatrics 2001;107(6):E105

16 Clinical data in children and adolescents: Overview Randomised, double-blind, controlled trials showed OROS-MPH to be effective in treating the symptoms of ADHD in children and adolescents 1-3 Long-term studies showed treatment effectiveness is maintained for up to 2 years with OROS-MPH 4-6 Open-label data showed OROS-MPH provided greater symptom control, compared with IR-MPH 7 Short-term, double-blind, randomised, controlled trials demonstrated the superiority of OROS-MPH, compared with atomoxetine 8,9 Observational studies show the benefits of switching to OROS-MPH from other treatments 10,11 1. Swanson et al. Pediatr Res. 2000;47:34; 2. Pelham et al. Pediatrics 2001; 107: E105; 3. Wolraich et al. Pediatrics 2001;108: ; 4. Wilens et al. J Am Acad Child Adolsec Psychiatry 2003;42: ; 5. Wilens et al. J Am Acad Child Adolesc Psychiatry 2005;44(10): ; 6. Hoare et al. Eur Child Adolesc Psychiatry 2005;14(6):305-9; 7. Steele et al. Can J Clin Pharmacol. 2006;13:e50-e62; 8. Newcorn et al. Am J Psychiatry 2008;165:721-30; 9. Kemner et al. Advances in Therapy 2005;22(5): ; 10. Wolff et al. Curr Med Res Opin. 2011;27 Suppl 2: 35-44; 11. Niederkirchner et al. Expert Rev Neurother. 2011;11(4):

17 ADHD Pharmacotherapy Responsiveness Methylphenidate Amphetamine Pemoline Tricyclic antidepressants Bupropion MAOI Clonidine/ Guanfacine % Responders Wilens TE, Spencer TJ. Presented at Massachusetts General Hospital s Child and Adolescent Psychopharmacology Meeting, March 10-12, 2000, Boston, MA

18 Non-pharmacological interventions for the treatment of ADHD 1,5-7 Lifestyle & Diet Behavioral Therapy Psycho-education

19 Psychoeducation in ADHD Psychoeducation is a novel treatment paradigm, which includes information about the illness and its treatment, skills development, and patient empowerment errin M, Taylor E. Future Neurology 2011; 6;

20 ontoya et al, Eur Psychiatry 2011; 26:

21 Potential benefits of Psychoeducation!! Improvement in consumer satisfaction levels An enhancement of adherence to medical regimens Improvement in positive functioning outcomes Reduction of the number of parent-child issues and conflicts Reduction of externalizing behavior J Am Acad Child Adolesc Psychiatry 1993;32(1):182 9 Can J Psychiatry 1999;44(10): J Learn Disabil 2002;35(6):546 62

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24 Does combined drug therapy and behavior therapy benefit Multimodal Treatment Study of Children with ADHD (MTA).

25 The multimodal treatment study of children with ADHD (MTA) NIMH funded multisite study in the late 90s 14-month clinical trial of treatment strategies 579 children with ADHD Subjects randomized to 1 of 4 treatment conditions Medication management Behavior management Medication management and behavior management Community-based treatment MTA Cooperative Group. Arch Gen Psych. 1999;56:

26 Improvement at 14 months (%) Long-term Outcomes of Therapies for ADHD in the MTA Study % Hyperactive Impulsive Symptoms (Teacher Reports) Medication management 60% 45% Combination Behavioral therapy treatment (medication + behavior therapy) 36% Community-based treatment

27 Conclusion of MTA study Drug therapy was superior to behavioral therapy in managing ADHD symptoms/manifestations and a combination of the 2 did have a marginal additive effect. Behavioral therapy was useful, but the effect was not as robust as for drug therapy Behavioral therapy is useful for ADHD patients with mild symptoms and minimal impairment or when parents prefer it over drug therapy

28 Guidelines on ADHD 56

29 AAP Guidelines on ADHD For elementary school aged children (6 11 years of age): Pharmacotherapy + Behavior Therapy The evidence is particularly strong for stimulant medications and sufficient but less strong for Atomoxetine For adolescents (12 18 years of age): - Should prescribe US-FDA approved medications for ADHD with the assent of the adolescent - May prescribe behavior therapy as treatment for ADHD. - Preferably both ADHD needs to be identified as a chronic condition and followup care and management for atleast 2 years needs to be given

30 CADDRA Guidelines on ADHD Methylphenida te ER is first line Treatment for uncomplicated ADHD Atomoxetine is second line agent in ADHD IiImmediate release preparations are second line agents in ADHD CADDRA: Canadian ADHD Resource Alliance

31 NICE Guidelines on ADHD When a decision has been made to treat children or young people with ADHD with drugs, healthcare professionals should consider: Methylpheni date for ADHD with comorbid conduct disorder Methylpheni date for ADHD without significant comorbidity Methylpheni date or Atomoxetine when tics, Tourette's syndrome, anxiety disorder, stimulant misuse or risk of stimulant diversion are present NICE : National Institute for health and Clinical Excellence

32 Atomoxetine if methylphenidate has been tried and has been ineffective at the maximum tolerated dose, or the child or young person is intolerant to low or moderate doses of methylphenidate.

33 NICE Guidelines on ADHD When prescribing methylphenidate for the treatment of children or young people, modified-release preparations should be considered for the following reasons: Convenience Improving adherence Reducing stigma Pharmacoki netic profiles.

34 Conclusion Stimulants remain the first choice of therapy in management of ADHD Long acting formulation is desirable for overall development of child of ADHD Better outcomes can be encouraged with behavioral therapy along with medications

35 Myths and facts in management of ADHD

36 Evidence for an association between drugs used to treat ADHD and loss of appetite/ growth delay Appetite reduction was found in 24% of individuals treated with MPH-IR, 18% of those assigned to OROS methylphenidate, and 4% of individuals in the placebo condition Appetite reduction following treatment initiation with an ADHD drug often attenuates with time Samuele et al.

37 EAGG recommendations to manage loss of appetite Giving medication after meals, rather than before. Encouraging the use of high-calorific snacks and late evening meals Concept of Drug Holiday European ADHD Guidelines Group- EAGG

38 Is it important to give Drug Holiday?

39 Drug holiday concept Both parents and practitioners propose drug holiday In one survey, 24% of patients in a psychiatric environment and 17% in a primary care setting took drug holidays Patients initiated drug holidays 57% of the time Some studies support for drug holidays in reducing insomnia and appetite suppression without a significant increase in symptoms while other studies show no benefit Because there is no clear guidelines on whether to use drug holidays, the decision to implement is typically based on the degree of dysfunction associated with ADHD symptoms Manos M. Medscape J Med. 2008; 10(1): 5.

40 Need for Drug Holiday EAGG guidelines on Drug Holiday Drug holidays may be useful in managing loss of appetite. Further evidence is needed on the efficacy of drug holidays in reducing AEs, including appetite reduction and growth retardation. The risk-benefit balance of drug holidays during weekend must be taken into account and better investigated To date, only one randomized trial showed a trend (p = 0.08) for an association between drug holidays on the weekend and less interference on appetite (Martins et al., 2004) Evidence on the beneficial effects on appetite of stopping medication during longer drug holidays to allow for catch-up growth is mixed (Faraone et al., 2008)

41 J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 45:5, MAY 2006 The effects of prolonged OROS MPH therapy on growth were clinically insignificant and limited to slight decreases in weight during the first months of therapy Drug holidays did not reduce any impact on growth and are thus of questionable utility for limiting potential effects of treatment on growth. J.

42 NICE Guideline for drug holiday NICE Guidelines available at Accessed on 22 nd september 2016

43 How long should the treatment be continued?

44 Continue as long as the treatment is clinically effective NICE Guidelines available at Accessed on 22 nd september 2016

45 Treatment strategies should focus on Adherence NICE Guidelines available at Accessed on 22 nd september 2016

46 Continuity of methylphenidate treatment for ADHD OBJECTIVE: To compare the continuity of MPH therapy among youth treated for ADHD with IR or ER MPH RESULTS: Patients initiating ER-MPH treatment had a significantly longer duration of treatment (ER- MPH, days vs IR-MPH, days ER-MPH treatment initiation was associated with an average 37% longer duration of treatment than IR-MPH treatment. Among ER-MPH, OROS MPH was associated with significantly longer mean duration days than treatment initiation with SR-MPH113.0 days or long acting MPH days CONCLUSIONS: Extended-release MPH formulations were associated with greater continuity of MPH treatment than IR formulations in the study population. Marcus Et al. Arch Pediatr Adolesc Med Jun;159(6):572-8.

47 Summary ADHD is one of the most common neurobehavioral disorders of childhood. Should be diagnosed and treated for overall development of child Stimulants remain the first choice of therapy Long duration therapy have shown better adherence, quality of life and improved pharmacokinetic profile No clear guidelines are present on whether to use drug holidays, so it will be based on the clinician and caregivers comfort Continuity of treatment is essential for the preventing the transition of symptoms from childhood to adolescent to adulthood