Andrej Kastelic

1


Differential diagnosis and comorbidity in
patients with ADHD

• Andrej Kastelic
• Global Addiction Association President
• EUROPAD General Secretary
• SEEA net President
• Center for Treatment of Drug Addiction
• University Psychiatric Clinic Ljubljana
• Ljubljana, Slovenia
• E-mail andrej.kastelic_at_psih-klinika.si

Global Addiction 2015
2
ATTENTION DEFICIT HYPERACTIVITY DISORDER
Michael Phelps
Jamie Oliver
Justin Timberlake
Paris Hilton
3
Heritability in the Range of Schizophrenia and
Height
1. Hudziak JJ, et al. Am Acad of Child and
Adolesc Psychiatry 200039(4)469-476. 2. Faraone
SV, et al. Biol Psychiatry 199844951-958.
4
Symptoms

• Core symptoms
• inatention
• impulsivness
• over-activity

INATENTION
IMPULSIVNESS
OVER-ACTIVITY
5

• In children ADHD is 3-5 times more comon in boys
  than girls. In adults it is more closer to
  even,incresing in women and decreasing in men.
• The prevalence of ADHD in adults declines with
  age. Partly due to age related the client in the
  symptoms, tough some patients with ADHD in
  childhood meet fewer criteria as adults but have
  persistent symptoms - ADHD in partial remission
  under DSM 5.
• Over - activity in adulthood declines more than
  attention deficit. There is more anxiety,
  attention deficit, presents more as inability to
  fulfill the tasks. Problems with employment,
  finances, interpersonal relationships including
  workplace, partnerships, divorces and specially
  as comorbidity of psychiatric disorders
  (depression, anxiety, substance abuse, including
  smoking).

Volkow N.D, Swanson J.M. Adult Attention
Deficit-Hyperactivity Disorder. New Enlg J Med
2013 369 1935-44.
6
(No Transcript)
7
Long term outcome without treatment
Shaw et al. BMC Medicine 2012, 1099, available
at http//www.biomedcentral.com/1741-7015/10/99
8
Increased Risk of Traffic Violations and
Accidents

• Findings from driving records obtained from the
  state department of motor vehicles

1. Barkley et al. Pediatrics 199698108995.

9
Increased Risk for Employment Problems

• Individuals with ADHD are 3 times more likely to
  be fired from a job than individuals without ADHD
• ADHD patients change their jobs at a rate of 23
  times within a 10-year period
• ADHD patients have lower work performance ratings
  than employees without ADHD

1. Barkley. J Clin Psychiatry 2002631015.

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Other Consequences of ADHD

• Outcomes of ADHD on Major Life Activities

plt0.001 plt0.01

Patients ()

1. Barkley et al. J Am Acad Child Adolesc Psych
   200645192202.

11
Why Should Adult Mental Health Services be
Interested in ADHD?

• ADHD is a common behavioural disorder associated
  with significant adult psychopathology, social
  and academic impairments and the risk for
  negative longterm outcomes1,2
• ADHD symptoms persist into adult life and cause
  significant clinical impairments1
• The main clinical issue is recognition of the
  disorder in adults and quantifying the load on
  adult psychopathology1
• ADHD is a treatable condition1

1. Asherson et al. Br J Psychiatry 200719045.
2. Antshel et al. BMC Med 2011972.

12
Treatment outcome
Shaw et al. BMC Medicine 2012, 1099, available
at http//www.biomedcentral.com/1741-7015/10/99
13
Key Principles

• ADHD in adults is no more difficult to diagnose
  and treat than other common mental health
  disorders1
• ADHD in adults is a symptomatic disorder (not
  just about behaviour)1,2
• ADHD in adults is often misdiagnosed for other
  common adult mental health disorders1,2
• ADHD in adults is in most cases treatable1

1. Asherson. 1st European Network Adult ADHD
   Conference. London, 2011.
2. Kooij et al. BMC Psychiatry 20101067.

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Assesment

• Psychiatric History
• Somatic histroy
• Screening for most common comorbid disorders
• Screening for special and general learning
  difficulties
• Family history
• Substance abuse
• Forensic history

1. Asherson. 1st European Network Adult ADHD
   Conference. London, 2011.

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Comorbid disorders

• Symptoms, syndromes or disorders?
• 1. Symptoms of ADHD
• 2. Overlapping neurodevelopmental disorders
• 3. ADHD as a risk factor for the development of
  co-occurring conditions later in life

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simptom otroci odrasli
nepozornost Odkrenljivost Ne morejo dokoncati dela Kot da ne slišijo, ko se jim govori Neorganiziranost Slabo razporejajo s casom Se izgubljajo v razgovoru, ker ne morejo slediti, saj se okoli njih dogaja toliko drugega Pozabljivost
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Symptoms of ADHD

• Anxiety1
• Ceaseless thoughts, avoidance behaviour
• Depression1
• Unstable mood, impatience, irritability, initial
  insomnia, low self-esteem
• Personality disorder1
• Antisocial, borderline, emotionally unstable,
  poor social interactions, impulsive, adulthood
  instability trait-like quality
• Hypomania, bipolar ll disorder, cyclothymia2
• Differentiated by grandiosity, clear focus of
  thoughts, episodic, reduced need for sleep,
  psychosis

1. Asherson. 1st European Network Adult ADHD
   Conference. London, 2011.
2. Babcock and Ornstein. Postgraduate Medicine.
   2009121(3)73-82.

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Overlapping Neurodevelopmental Disorders

• Dyslexia (overlapping genetic risk factors)1
• Specific and general learning difficulties
  (overlapping genetic risk factors, inattention)1
• Pervasive developmental disorder1
• Dyspraxia1
• Tic disorders/Tourette's disorder1
• Speech problems2
• Autism spectrum disorder1

1. Kooij et al. BMC Psychiatry 20101067
2. Tannock et al J Abnl Child Psychol, 2000
   28(3)237252

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ADHD and Physical Disorders

• Epilepsy
• Higher incidence of symptoms of ADHD in children
  with epilepsy
• Higher incidence of epilepsy among children with
  ADHD
• Appears to be more severe than in those without
  ADHD
• Brain Injury
• Risk of physical injuries because of ADHD
  symptoms
• Brain injuries (particularly to the frontal
  lobes) can produce secondary ADHD
• Children/adolescents with a moderate/severe brain
  injury have a 20 chance of developing secondary
  ADHD
• Others
• Obesity

1. CADDRA. Canadian ADHD Practice Guidelines. 3rd
   Edn. CADDRA Toronto ON 2011.

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ADHD and Physical Disorders

• Thyroid disorders
• Hypothyroidism may exhibit inattentive symptoms
• Hyperthyroidism may exhibit hyperactivity and
  inattention, act impulsively
• Iron deficiency anaemia
• Inattention
• Slowed cognitive processes

1. Young. ADHD Grown Up A Guide to Adolescent and
   Adult ADHD. London WW Norton 2007.

21
ADHD as a Risk Factor for Development of
Co-occurring Conditions Later in Life
Risk Model

• Antisocial behavior
• Addiction
• Depression/low self-esteem
• Anxiety

Adult with ADHD

• Environmental and genetic risks
• (maltreatment / COMT genotype)

Catechol-O-methyl transferase

1. Asherson. 1st European Network Adult ADHD
   Conference. London, 2011.

22

• ADHD in population with substance abuse disorders
  and and incarterated population is about 25 -
  significantly higher than in general population.

Philipsen A, Heslinger B, tebartz van Elst.
Attention Deficit Hyperactivity Disorder in
Adulthood Diagnosis, Etiology and Therapy. Dtsch
Arztebl Int 2008 105(17) 311-7
23
Medication for ADHD and criminality
Observational Swedish data base analysis

• Rate of Crime Over 4 Years in Swedish ADHD
  Subjects Aged gt15 years (N25,656)

Subjects committing crime Male ADHD Subjects Female ADHD subjects
ADHD 36.6 15.4
General population 8.9 2.2
2. Hazard Ratio for Conviction for Any Crime
During ADHD Medication (20062009) vs.
Non-Medication Periods
Treatment Men (N16,087) Hazard Ratio (95CI) Women (N9,569) Hazard Ratio (95CI)
All medications 0.68 (0.630.73) 0.59 (0.500.70)
Stimulants 0.66 (0.610.71) N/A
Atomoxetine 0.76 (0.630.91) N/A
Crimes occurred less often during medication
periods (men 32 reduction, women 41 reduction)
however, the observational nature of the data
cannot confirm a causal relationship with ADHD
medication and other factors co-occuring with
medication may play a role
Lichtenstein et al. N Engl J Med.
20123672006-14.
24

• High comorbidity of mental health disorders
  (80)
• depression (40-60),
• anxiety (20-60)
• substance abuse disorders (50-60).

Philipsen A, Heslinger B, tebartz van Elst.
Attention Deficit Hyperactivity Disorder in
Adulthood Diagnosis, Etiology and Therapy. Dtsch
Arztebl Int 2008 105(17) 311-7
25
Potential Traps

• ADHD symptoms
• May not be apparent in the clinical setting
  (sensitivity to novelty and stimulation)
• Differentiating ADHD
• Symptoms are trait-like and non-episodic
• Differentiating ADHD
• Mood instability is extremely common
• Age of onset
• Clear history of impairment

For the inexperienced ADHD diagnostician

1. Asherson. 1st European Network Adult ADHD
   Conference. London, 2011.

26
Do Not Dismiss ADHD1,2

• If clinician does not observe hyperactivity
• If there is no family history
• If patient dismisses symptoms reported by family
• If patient is well-educated or in a prestigious
  job
• If patient has had academic success in elementary
  school
• If ADHD symptoms in childhood lessened with
  adulthood
• If childhood symptoms are not remembered or denied

1. The DIVA Foundation. DIVA 2.0 2013. Available at
   http//www.divacenter.eu/DIVA.aspx?id461
2. Weiss et al. J Psychiatr Pract 2002899111.

27
Troubles to diagnose ADHD

• Change of the symptoms
• Overlooking the symptoms
• Comorbidities
• Heterogeneity of symptoms

1. Adler. CNS Spectr 20081345.

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• DD
• Depression specially with cognitive disfunction
  but no continuity of
• symptoms.
• Borderline personality disorder high overlaping
  the symptoms
• Impulsivity and emotional instability
• Anxiety offten followed by autoagressive/self-harm
  ing behaviour, suicidal ideation or PTSD.

Philipsen A, Heslinger B, tebartz van Elst.
Attention Deficit Hyperactivity Disorder in
Adulthood Diagnosis, Etiology and Therapy. Dtsch
Arztebl Int 2008 105(17) 311-7
29
ADHD and Depressive Mood Symptoms
ADHD Mood Disorder
Chronic mood instability Mood instability only during episode
No anhedonia, no appetite disturbances Neurovegetative symptoms present
Usually responds to control of symptoms and improvement in level of function Episodes of depression, requiring separate treatment of depression

1. Amons. J Affective Disord 2006912515.
2. Kooij et al. J Attention Disord 2012163S19S.

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ADHD and Bipolar Disorder
ADHD Bipolar Disorder
Early childhood onset1 Adolescent or adult onset1
Trait-like, no change from pre-morbid state1 Episodic course, change from pre-morbid state1
Excitable, but not grandiose/elated Grandiose/elated2
Reports being unable to function1 Reports high level function1
Chronic low self-esteem2 Episodes of depression1
Usually possesses insight, complains of changeable moods Trend to lack of insight1
Difficulty sleeping2 Reduced need for sleep2
Complains of being unable to concentrate/focus1 Subjective sense of sharpened mental abilities1
Restless (fidgety, difficult being still)1 Overactivity, often linked to unrealistic ideas/plans1

1. APA. DSM-IV-TR. APA 2000.
2. Kooij et al. J Att Dis 2012163S19S.

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Evaluation and Treatment of Patients with Mood
Instability

• Mood instability can be a core feature of ADHD
  syndrome1
• In the presence of (chronic) mood instability or
  depressive mood2
• Prompt for ADHD screening
• Evaluate presence of mood disorder (major
  depressive, hypomanic, or mixed episode)
• Management
• Mood instability as part of ADHD responds well to
  ADHD treatment3-4
• If ADHD and mood are comorbid, both should be
  addressed, but the order may depend upon the
  severity and type of comorbidity.5 For example
• First treat the severe mood episode, then review
  diagnosis and the need for treatment of ADHD
• With milder depressive symptoms or personality
  disorders, first treat ADHD

1. Skirrow et al. Expert Rev Neurother
   20099489?503.
2. McIntosh et al. Neuropsych Dis Treat
   20095137?50.
3. Reimherr et al. Biol Psych 200558125?31.

1. Rösler et al. World J Biol Psychiatry 201011709
   18.
2. Kooij et al. BMC Psychiatry. 20101067.

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ADHD and Anxiety
ADHD Anxiety Disorder
Ceaseless mental activity1 Anxious worrying (might look like obsessive thought processes OCD)2
Motor restlessness1 Nervous tension2
Family history of ADHD2 Family history of anxietydepression2
Avoids frustrating situations Shopping, social situations, queueing, travelling Phobic avoidance2
Easily feeling overwhelmed3 Easily becoming anxious2
Forgetfulness2 Hypervigilant
No somatic symptoms1 Somatic symptoms1
Improved by stimulants4 Exacerbated by stimulants4

1. Kooij et al. J Att Dis 2012163S19S.
2. APA. DSM-IV-TR. APA 2000
3. Reimherr et al Biol Psychiatry 200558125131.
4. Ritalin SPC

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ADHD and Personality Disorder
ADHD Borderline Personality Disorder
Childhood/adolescent onset1 Early adult/adolescent onset1
Defined by impairment2 Defined by impairment2
Chronic-like trait1 Chronic-like trait1
Pervasive across situations1 Pervasive across situations2
Affective lability (can be severe)4 Affective lability3
Impulsive3 Impulsive3
Inattention3 Frantic efforts to avoid real or imagined abandonment4
Recurrent suicidal behaviour4

1. APA. DSM-IV-TR. APA 2000.
2. Miller et al. J Clin Psychiatr 200869147784.
3. Distel et al. Am J Med Genet 201115681725.
4. Kooij et al. J Att Dis 201216(5S)3S19S.

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Conclusions

• ADHD is a neurobiological condition characterised
  by persistent patterns of inattention and/or
  hyperactivity, impulsiveness, and impairment in
  executive functioning
• ADHD symptoms persist into adult life and cause
  significant clinical, social, economic,
  psychological, and functional impairment
• ADHD in adults is often associated with a number
  of comorbidities
• Diagnosis of ADHD in adults is a multifaceted
  process
• Clinicians should carefully consider
  comorbidities and medical rule-outs
• ADHD in adults is a treatable condition

36


ADHD, SUBSTANCE USE DISORDERS AND TREATMENT

• Andrej Kastelic
• Global Addiction Association President
• EUROPAD General Secretary
• SEEA net President
• Center for Treatment of Drug Addiction
• University Psychiatric Clinic Ljubljana
• Ljubljana, Slovenia
• E-mail andrej.kastelic_at_psih-klinika.si

Global Addiction 2015
37

Curr Opin Psychiatry. 2011 Jul24(4)280-5. doi
10.1097/YCO.0b013e328345c956.The intersection of
attention-deficit/hyperactivity disorder and
substance abuse.Wilens TE, Morrison NR.
38
ADHD as a Risk Factor for Development of
Co-occurring Conditions Later in Life
Risk Model

• Antisocial behavior
• Addiction
• Depression/low self-esteem
• Anxiety

Adult with ADHD

• Environmental and genetic risks
• (maltreatment / COMT genotype)

Catechol-O-methyl transferase

1. Asherson. 1st European Network Adult ADHD
   Conference. London, 2011.

39

• Substance abuse disorders (SUD) are the most
  common co-morbidity disorder.
• Nicotine dependence in Germany is 27 , about 40
  in the USA (1).
• Second most common disorder is the harmful use of
  alcohol.
• In general, patients with ADHD are twice as much
  at risk of development of drug dependence (2).
  Co-morbidity of drug dependence is between 45 and
  70 (22-24) and one third of those addicted to
  alcohol has ADHD. (3,4).15-25 of adults with
  SUD fulfill criteria for ADHD.The most common
  illicit drug is cannabis 21 . Cocaine - 11-35
  (5,6).
• SUD with ADHD patients start earlier, course of
  the disease is more serious and the prognosis is
  worse.

1. Philipsen A, Heslinger B, tebartz van Elst.
   Attention Deficit Hyperactivity Disorder in
   Adulthood Diagnosis, Etiology and Therapy. Dtsch
   Arztebl Int 2008 105(17) 311-7
2. Huss M. Abschlussbericht and des
   Bundesministerium fur Gesundheit und Soziale
   Sicherung (BMGS). Bonn 2004.

40
simptom otroci odrasli
nepozornost Odkrenljivost Ne morejo dokoncati dela Kot da ne slišijo, ko se jim govori Neorganiziranost Slabo razporejajo s casom Se izgubljajo v razgovoru, ker ne morejo slediti, saj se okoli njih dogaja toliko drugega Pozabljivost
41
Increased Lifetime Substance Abuse

• Lifetime history of psychoactive substance use
  disorder

60
55
50
p0.001
40
27
30
20
10
0
Control (n262)
ADHD (n239)

1. Biederman et al. Biol Psychiatry 19984426973.

42

• ADHD and SUD share common neurobiological
  mechanisms and treatment of ADHD decreases
  craving and relapse rate.

Frodl T. Comorbidity of ADHD and substance
disorder (SUD) a neuroimaging perspective. J
Atten Disord. 2010 Sep 14(2) 109-20.
43
Brain Networks Implicated in ADHD

1. Liston et al. Biol Psychiatry 201169116877.

44
ADDICTION INVOLVES MULTIPLE BRAIN CIRCUITS AND
TREATMENTS SHOULD REFLECT THIS
http//archives.drugabuse.gov/NIDA_Notes/NNVol13N5
/Tearoff.html
45
ADHD and Substance Misuse

• Reason for the relationship
• High stimulus seeking behaviour
• Inherent component of ADHD (e.g. novelty seeking)
• Shared genetic risk
• Impaired social/academic/work function
• Secondary consequence of psychosocial impairments
• Relief from symptoms
• Self-treatment of symptoms (e.g. cannabis,
  alcohol, cocaine)

1. Arias et al. Addictive Behaviors
   200833(9)1199207.
2. Asherson. 1st European Network Adult ADHD
   Conference. London, 2011.

46

• 75 patients with ADHD in childhood have ADHD
  in adolescence and 50 in adulthood (1).
• 66 children with ADHD have in adulthood at
  least clnical significant symptom of mental
  health disorders (2).
• 25-50 adolescents with SUD have ADHD. 40-50
  those smoking marihuana have ADHD.
• Adults with ADHD and SUD have more serious
  symptoms of those disordes and have started using
  PAS when they were younger (3).

• Timoty E, Wilens M.D, R.Morrison N. The
  Intersection of Attention-deficit/Hyperactivity
  Disorder and Substance Abuse. Curr Opin
  Psychiatry. 2011 July 24(4) 208-285
• Kolar et.al. Treatment of adults with ADHD.
  Neuropsychiatric Disease and Treatment 2008
  4(2) 389-403
• Wilens T, R Morrison N. Substance-use disorders
  in adolescents and adults with ADHD focus on
  treatment. Neuropsychiatry (London). August 2012
  2(4) 301-312

47

• Understanding reasons for using PAS is important
  for treating these patients.

Wilson JJ, Levin FR. Attention deficit
hyperactivity disorder (ADHD) and substance use
disorders. Curr Psychiatry Rep. 2001 December
3(6) 497-506.
48

• Children with ADHD and comorbid conduct or
  bipolar disorder have the worst prognosis for SUD
  (1).
• Those without these disorders have a moderate
  risk (2).
• There is not much research about the role of ADHD
  and comorbid SUD in women (3).

1. Brook DW, Brook JS, Zhang C, Koppel J.
   Association between attention-deficit/hyoeractivit
   y disorder in adolescence and substance use
   disorder in adulthood. Arch Pediatr Adolesc Med.
   2010 Oct 164(10) 930-4.
2. Wilens TE. Attention-deficit/hyperactivity
   disorder and the substance use disorders the
   nature of the relationship, subtypes at risk, and
   treatment issues. Psychiatr Clin North Am. 2004
   Jun 27(2) 283-301.
3. Lynskey MT, Hall W. Attention deficit
   hyperactivity disorder and substance use
   disorder Is there a causal link? Addiction. 2001
   Jun 96(6) 815-22.

49

• In many patients with SUD ADHD was not recognized
  or diagnosed. In the group of patients with SUD
  54 had symptoms of ADHD in childhood and it was
  related to the earlier use of alcohol and other
  PAS (1).Because ADHD symptoms express earlier as
  SUD there is a small possibility that the SUD
  cause ADHD (2).ADHD is a significant risk factor
  for starting smoking before 15 years and when
  associated behavioral disorders or mood disorders
  are particularly risky. Early exposure to
  nicotine may make the brain more susceptible to
  subsequent behavioral and emotional disorders and
  PAS abuse.
• Hypothesis of selfmedication is of course linked
  to the fact that ADHD often associated with a
  loss of motivation, failure as are important
  factors for the abuse of drugs (2).

1. Ohlmeier et.al. Alcohol and drug dependence in
   adults with attention-deficit/hyperactivity
   disorder Data from Germany. Eur J Psychiat 2011.
   Vol 25. N3 150-163.
2. Timoty E, Wilens M.D, R.Morrison N. The
   Intersection of Attention-deficit/Hyperactivity
   Disorder and Substance Abuse. Curr Opin
   Psychiatry. 2011 July 24(4) 208-285

50

• As ADHD is recognized ahead of PAS abuse it can
  be successfully treated and so the possibility of
  the development of SUD and also ADHD in adulthood
  may be reduced (1).
• Persons who abuse drugs are more often
  hospitalized and have worse outcomes in ADHD in
  this population (2).
• Wilens et.al have demonstrated significant
  reduction in ADHD symptoms in adults with
  alcohol dependence but no effect on alcohol
  consumption (3).

1. Wilson JJ, Levin FR. Attention deficit
hyperactivity disorder (ADHD) and substance use
disorders. Curr Psychiatry Rep. 2001 December
3(6) 497-506. 2. Thurstone C et.al. J Am Acat
Child Adolesc Psychiatry 2010, 49573-582 3.
Wilens et.al. Drug Alcohol Depend 2008, 96
145-154
51
Atomoxetine in adult patients with ADHD and
co-morbid alcohol abuse treated for 12 weeks
LYBY
ADHD Investigator Symptom Rating Scale (AISRS)
Randomised (n147)
40.6 40.1
19.0 18.7
21.7 21.4
0
-2
Placebo (n75)
-4
Atomoxetine (n72)
-6
-8
p0.013
p0.009
Changes from Baseline
-10
-12
-14
Effect Size 0.48
p0.007
-16
-18
Hyperactive/ Impulsive Subscale
Inattentive Subscale
Total Score
Wilens et al. Drug Alcohol Depend 200896145-54.
52
Atomoxetine efficacy in adult ADHD and co-morbid
alcohol use disorders alcohol use

• No worsening of alcohol abuse in patients treated
  with atomoxetine

• This post-hoc analysis demonstrated robust
  effects of atomoxetine for reducing ADHD symptoms
  in adult ADHD patients with comorbid alcohol-use
  disorder and suggests a positive effect on
  reducing cumulative heavy drinking events over
  time

Randomised (n147)
p0.0230
Wilens et al. Drug Alcohol Depend 200896145-54.
53

• Because of high incidence of ADHD in SUD
  population we should always have in mind the
  possibility of ADHD.
• Correlates with worse quality of life(1).
• All patients with SUD should be screened for
  ADHD as soon as their PAS use is stabilisied
  (2).

1. Fatseas M, Debrabant R, Auriacombe M. The
diagnostic accuracy of attention-deficit/hyperacti
vity disorder in adults with substance use
disorders. Curr Opin Psychiatry. 2012 May 25(3)
219-25. 2. Matthys F, Joostens P, Van den Brink
W, Sabbe B. Summary of the practice guideline for
the diagnosis and treatment of ADHD in
adolescents and adults with addictions. Ned
Tijdschr Geneeskd. 2013 157(24) A 6025.
54

• Stabilisation of PAS use is priority though the
  treatment should be integrative and complex
  including pharmacotherapy starting with less
  adictive medications like atomoxetin or
  bupropion and if these are not affective start
  using stimulants.

• Wilens TE. Impact of ADHD and its treatment on
  substance abuse in adults. J Clin Psychiatry.
  2004 65
• Suppl 3 38-45.

55
Methylphenidate Increase Dopamine Levels in Rat
Nucleus Accumbens and Striatum
Dopamine Concentrationas of Baseline



Time (hours)
Methylphenidate 3 mg/kg i.p

• plt.05, overall concentration during 4-hour time
  period vs. baseline

• Bymaster et al. Neuropsychopharmacology
  200227(5)699-711.

56
Atomoxetine Does Not Increase Dopamine Levels in
Rat Nucleus Accumbens and Striatum

Dopamine Concentrationas of Baseline
Time (hours)
Atomoxetine 3 mg/kg i.p for PFC and nA 10 mg/kg
i.p for striatum

• plt.05, overall concentration during 4-hours
  time period vs. baseline

• Bymaster et al. Neuropsychopharmacology
  200227(5)699-711.

57
Proposed Effects of Atomoxetine in Brain Regional
Catecholamine Neurotransmissiona
Regions potentially affected by atomoxetines
action on the NE transporter

• aBased on rat studies

• Bymaster et al. Neuropsychopharmacology
  200227(5)699-711.

58

• Early beginning of treatment of ADHD delays the
  start of drug abuse. But the treatment should not
  be was interrupted prematurely in adolescence
  (1).An extensive meta-analysis has clearly shown
  that if treatment with stimulants begun in
  childhood is less possibility of 27 of stimulant
  abuse in adulthood (Wilens et al 2003).
• If the treatment is started only in adolescence,
  the possibility of SUD is increased to 44
  (Collins et al. 2008).
• It was also shown that abuse of stimulants in
  connection with the development of antisocial
  personality disorder.

• Bejerot S, Ryden EM, Arlinde CM. Two-year outcome
  of treatment with central stimulant medication in
  adult attention-deficit/hyperactivity disorder a
  prospective study. J Clin Psychiatry. 2010 Dec
  71(12) 1590-7.

59

• There is a constant concern about the abuse and
  misuse of the stimulant prescribed to treat ADHD.
  The vast majority of patients use medicament for
  the treatment of ADHD properly.
• But a significant proportion reports pressures to
  approve or sold medicines that have been
  prescribed to them (1,2).

1. McCabe SE, Knight JR, Teter CJ, Wechser H.
   Non-medical use of perscription stimulants among
   US college students prevalence and correlates
   from a national survey. Addiction. 2005 99(1)
   96-106.
2. Teter CJ. McCabe SE, LaGrange K, Cranford JA,
   Boyd CJ. Illicit use of specific perscription
   stimulants among college students prevalence,
   motives, and routes of administration.
   Pharmacotherapy. 2006 26(10) 1501-1510.

60

• Around 5 of students abuse stimulants for help
  with the study. More for improve cognitive
  functions than to achieve euphoria (1).The
  effect of 20 mg MPH on long-term memory and
  understanding of the information did not differ
  from placebo effect. Amphetamine does not affect
  short-term memory, long term memory improves, but
  only when new knowledge already is there. The
  reason that some students abuse them is to
  increase in the concentration (58 ), attention
  (43 ) and feel euphoria (43 ).

• Wilens TE, Adler LA, Adamson J, et. al. Misuse
  and diversion of stimulants perscribed for ADHD
  a systematic review of the literature. J Am Acad
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