View Full Version : Safety of long term stimulants:


Kunga Dorji
05-27-15, 10:12 AM
We have had some discussion about the long term use of stimulant medication in ADHD and for a long while the evidence has been hard to clarify.


The latest science that has come to light suggests very strongly that far from being potentially harmful to the brain, stimulants in therapeutic doses are positively beneficial to brain function:
Much of this is summarised in the latest review of the Wikipedia entry on Dextroamphetamine- all heavily referenced from peer reviewed journals:

Long-term amphetamine exposure in some animal species is known to produce abnormal dopamine system (http://en.wikipedia.org/wiki/Dopamine_receptor) development or nerve damage,<sup id="cite_ref-pmid22392347_15-0" class="">[12] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-pmid22392347-15)</sup><sup id="cite_ref-AbuseAndAbnormalities_16-0" class="">[13] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-AbuseAndAbnormalities-16)</sup> but, in humans with ADHD, pharmaceutical amphetamines appear to improve brain development and nerve growth.<sup id="cite_ref-Neuroplasticity_1_17-0" class="">[14] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Neuroplasticity_1-17)</sup><sup id="cite_ref-Neuroplasticity_2_18-0" class="">[15] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Neuroplasticity_2-18)</sup>[16 (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Neuroplasticity_3-19)
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Reviews of [URL="http://en.wikipedia.org/wiki/Magnetic_resonance_imaging"]magnetic resonance imaging (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Neuroplasticity_3-19) (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus (http://en.wikipedia.org/wiki/Caudate_nucleus) of the basal ganglia (http://en.wikipedia.org/wiki/Basal_ganglia).<sup id="cite_ref-Neuroplasticity_1_17-1" class="">[14] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Neuroplasticity_1-17)</sup><sup id="cite_ref-Neuroplasticity_2_18-1" class="">[15] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Neuroplasticity_2-18)</sup><sup id="cite_ref-Neuroplasticity_3_19-1" class="">[16] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Neuroplasticity_3-19)</sup>

Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD.<sup id="cite_ref-Millichap_20-0" class="">[17] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Millichap-20)</sup><sup id="cite_ref-Long-term_2015_21-0" class="">[18] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Long-term_2015-21)</sup><sup id="cite_ref-Long-Term_Outcomes_Medications_22-0" class="">[19] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Long-Term_Outcomes_Medications-22)</sup> Controlled trials spanning two years have demonstrated treatment effectiveness and safety.<sup id="cite_ref-Millichap_20-1" class="">[17] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Millichap-20)</sup><sup id="cite_ref-Long-Term_Outcomes_Medications_22-1" class="">[19] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Long-Term_Outcomes_Medications-22)</sup> One review highlighted a nine-month randomized controlled trial (http://en.wikipedia.org/wiki/Randomized_controlled_trial) in children with ADHD that found an average increase of 4.5 IQ (http://en.wikipedia.org/wiki/Intelligence_quotient) points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.<sup id="cite_ref-Millichap_20-2" class="">[17] (http://en.wikipedia.org/wiki/Dextroamphetamine#cite_note-Millichap-20)</sup>


But wait -- there's more:

In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces unambiguous improvements in cognition, including working memory, episodic memory, and inhibitory control, in normal healthy adults;[33][34]






So it would appear that at therapeutic doses, as opposed to the doses used by Recreational users of Ice, that there is every reason to use stimulants in ADHD and no reason not to unless there are unaccceptable side effects:

from the wikipedia entry on methylphenidate (Ritalin)

Methylphenidate may protect neurons from the neurotoxic effects of Parkinson's disease (http://en.wikipedia.org/wiki/Parkinson%27s_disease) and methamphetamine (http://en.wikipedia.org/wiki/Methamphetamine) abuse.<sup id="cite_ref-neuroprotection_107-0" class="">[106] (http://en.wikipedia.org/wiki/Methylphenidate#cite_note-neuroprotection-107)</sup>


So- to paraphrase Dr John Ratey-- are stimulants at controlled doses actually better understood as bottle derived neurotrophic factor (BDNF/ "Miracle Gro for Brains"- again to paraphrase Ratey's discussion of brain derived neurotrophic factor.


Given that the cerebral activity pattern that is produced by stimulant medication is virtually identical to that produced by good meditation, maybe this question is not as flippant and overstated as it may seem?


Interesting? no??

Pilgrim
05-28-15, 09:25 AM
This might be a dumb question, but if there are certain areas of development with the neurons does this change the structure of the mind? Therefore the way it works

Greyhound1
05-28-15, 10:09 AM
Kunga,

Thank you for sharing that information! That sounds like great news for most of us here.

Kunga Dorji
05-28-15, 07:58 PM
This might be a dumb question, but if there are certain areas of development with the neurons does this change the structure of the mind? Therefore the way it works

The stimulants improve focus- so the set the scene for neuroplastic brain growth.

The growth depend on what you choose to attend to.

However the mind is not the brain-- and that is provable.

willow129
05-28-15, 09:53 PM
That is SO interesting. Well timed too!
Was just discussing with boyfriend the possibility/probability of being on this stuff long term and he was wondering about the affects longterm...

Kunga Dorji
05-31-15, 09:53 PM
But there is more:
This is what I have just extracted from Wikipedia:

I have posted this to our Doctor's peer review group:

<style type="text/css">P { margin-bottom: 0.21cm; }A:link { }</style> There has been concern about long term amphetamine use. While I personally believe that with comprehensive treatment we should be able to move past the need for lifelong stimulant therapy, there is good new evidence - largely from material published this year and these answer most of the criticisms voiced about treatment of ADHD by those opposed to the diagnosis and to the use of medications.
I apologise for the length of this next section-- but it answers most of the criticisms that we, ads prescribers, need to be concerned about


The key findings are that:
- real deficits in brain development occur in ADHD
- that stimulants help remedy those deficits

Refs:

Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5 (https://dx.doi.org /10.1007%2Fs00204-012-0815-5). PMID 22392347 (https://www.ncbi.nlm.nih.gov/pubmed/22392347). Berman S, O'Neill J, Fears S, Bartzokis G, London ED (October 2008). "Abuse of amphetamines and structural abnormalities in the brain" (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC2769923). Ann. N. Y. Acad. Sci. 1141: 195–220. doi:10.1196/annals.1441.031 (https://dx.doi.org/10.1196%2Fannals.1441.031). PMC 2769923 (https://www.ncbi.nlm.nih.gov /pmc/articles/PMC2769923). PMID 18991959 (https://www.ncbi.nlm.nih.gov/pubmed/18991959). Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277 (https://dx.doi.org /10.1001%2Fjamapsychiatry.2013.277).
PMID 23247506 (https://www.ncbi.nlm.nih.gov /pubmed/23247506).
Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies" (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC3801446). J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287 (https://dx.doi.org /10.4088%2FJCP.12r08287). PMC 3801446 (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC3801446). PMID 24107764 (https://www.ncbi.nlm.nih.gov/pubmed/24107764). Frodl T, Skokauskas N (February 2012). "Meta- analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.x (https://dx.doi.org /10.1111%2Fj.1600-0447.2011.01786.x).
PMID 22118249 (https://www.ncbi.nlm.nih.gov /pubmed/22118249).


- that stimulants may be useful in stroke or acute traumatic brain injury


-that stimulants at therapeutic doses can enhance cognition in any healthy adult: when used at low (therapeutic) doses, amphetamine produces unambiguous improvements in cognition, including working memory (http://en.wikipedia.org/wiki/Working_memory), episodic memory (http://en.wikipedia.org/wiki/Episodic_memory), and inhibitory control (http://en.wikipedia.org/wiki/Inhibitory_control_test), in normal healthy adults
Refs:

32. Dale E, Bang-Andersen B, Sánchez C (May 2015). "Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs". Biochem. Pharmacol. 95 (2): 81–97. doi:10.1016/j.bcp.2015.03.011 (https://dx.doi.org /10.1016%2Fj.bcp.2015.03.011). PMID 25813654 (https://www.ncbi.nlm.nih.gov/pubmed/25813654
and
Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex". Biol. Psychiatry 77 (11): 940–950. doi:10.1016/j.biopsych.2014.09.013 (https://dx.doi.org /10.1016%2Fj.biopsych.2014.09.013).
PMID 25499957 (https://www.ncbi.nlm.nih.gov /pubmed/25499957).



"The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. ... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacologic treatments for attention- deficit/hyperactivity disorder and other conditions associated with PFC dysregulation."




- that stimulants need to be taken at abuse doses to become addictive


According to another Cochrane Collaboration review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose."[97] This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.[97] Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams.[97] The review indicated that withdrawal symptoms are associated with the degree of dependence, suggesting that therapeutic use would result in far milder discontinuation symptoms.[97] Manufacturer prescribing information does not indicate the presence of withdrawal symptoms following discontinuation of amphetamine use after an extended period at therapeutic doses.[98][99][100]


refs

Adderall IR Prescribing Information" (http://www.accessdata.fda.gov/drugsatfda_docs /label/2007/011522s040lbl.pdf) (PDF). United States Food and Drug Administration. Barr Laboratories, Inc. March 2007. Retrieved 4 November 2013. "Dexedrine Medication Guide" (http://www.accessdata.fda.gov/drugsatfda_docs /label/2013/017078s046lbl.pdf) (PDF). United States Food and Drug Administration. Amedra Pharmaceuticals LLC. May 2013. Retrieved
4 November 2013.
"Adderall XR Prescribing Information" (http://www.accessdata.fda.gov/drugsatfda_docs /label/2013/021303s026lbl.pdf) (PDF). United States Food and Drug Administration. Shire US Inc. December 2013. Retrieved 30 December 2013.





-People with ADHD have an increased risk of substance abuse (http://en.wikipedia.org/wiki/Substance_abuse), and stimulant medications reduce this risk


Faraone SV, Wilens TE (2007). "Effect of stimulant medications for attention-deficit/hyperactivity disorder on later substance use and the potential for stimulant misuse, abuse, and diversion". J Clin Psychiatry. 68 Suppl 11: 15–22. doi:10.4088/jcp.1107e28 (https://dx.doi.org/10.4088%2Fjcp.1107e28). PMID 18307377 (https://www.ncbi.nlm.nih.gov/pubmed/18307377).
Wilens TE, Faraone SV, Biederman J, Gunawardene S (2003). "Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse? A Meta-analytic Review of the Literature". Pediatrics 111 (1): 179–85. doi:10.1542/peds.111.1.179 (https://dx.doi.org/10.1542%2Fpeds.111.1.179). PMID 12509574 (https://www.ncbi.nlm.nih.gov/pubmed/12509574).




- that methylphenidate at least may be neuroprotective in Parkinson's disease


Volz TJ (2008). "Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate"
(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286). Current Neuropharmacology 6 (4): 379–385. doi:10.2174/157015908787386041 (https://dx.doi.org/10.2174%2F157015908787386041). PMC 2701286 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286). PMID 19587858 (https://www.ncbi.nlm.nih.gov/pubmed/19587858).






Aggression and criminality

Two studies state that methylphenidate is indicated for the treatment of ADHD in adults with a history of aggressive and criminal behavior. A large clinical study conducted in Sweden found a significant reduction of the criminality rate in males (32%) and females (42%) as compared with the rate for the same patients while not receiving medication.[36] Some of these clinical outcomes have been confirmed in similar studies with children and adolescents.[37]



36. Lichtenstein P, Halldner L, Zetterqvist J, Sjölander A, Serlachius E, Fazel S, Långström N, Larsson H (2012). "Medication for Attention Deficit–Hyperactivity Disorder and Criminality" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664186). New England Journal of Medicine 367 (21): 2006–14. doi:10.1056/NEJMoa1203241 (https://dx.doi.org/10.1056%2FNEJMoa1203241).PMC 3664186 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664186). PMID 23171097 (https://www.ncbi.nlm.nih.gov/pubmed /23171097).


Pappadopulos E, Woolston S, Chait A, Perkins M, Connor DF, Jensen PS (2006). "Pharmacotherapy of aggression in children and adolescents: Efficacy and effect size" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277275). Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent 15 (1): 27–39.
PMC 2277275 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277275). PMID 18392193 (https://www.ncbi.nlm.nih.gov/pubmed /18392193).

Kunga Dorji
06-04-15, 12:04 AM
But there is more:
This is what I have just extracted from Wikipedia:

I have posted this to our Doctor's peer review group:

<style type="text/css">P { margin-bottom: 0.21cm; }A:link { }</style> There has been concern about long term amphetamine use. While I personally believe that with comprehensive treatment we should be able to move past the need for lifelong stimulant therapy, there is good new evidence - largely from material published this year and these answer most of the criticisms voiced about treatment of ADHD by those opposed to the diagnosis and to the use of medications.
I apologise for the length of this next section-- but it answers most of the criticisms that we, ads prescribers, need to be concerned about


The key findings are that:
- real deficits in brain development occur in ADHD
- that stimulants help remedy those deficits

Refs:

Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5 (https://dx.doi.org /10.1007%2Fs00204-012-0815-5). PMID 22392347 (https://www.ncbi.nlm.nih.gov/pubmed/22392347). Berman S, O'Neill J, Fears S, Bartzokis G, London ED (October 2008). "Abuse of amphetamines and structural abnormalities in the brain" (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC2769923). Ann. N. Y. Acad. Sci. 1141: 195–220. doi:10.1196/annals.1441.031 (https://dx.doi.org/10.1196%2Fannals.1441.031). PMC 2769923 (https://www.ncbi.nlm.nih.gov /pmc/articles/PMC2769923). PMID 18991959 (https://www.ncbi.nlm.nih.gov/pubmed/18991959). Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277 (https://dx.doi.org /10.1001%2Fjamapsychiatry.2013.277).
PMID 23247506 (https://www.ncbi.nlm.nih.gov /pubmed/23247506).
Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies" (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC3801446). J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287 (https://dx.doi.org /10.4088%2FJCP.12r08287). PMC 3801446 (https://www.ncbi.nlm.nih.gov/pmc/articles /PMC3801446). PMID 24107764 (https://www.ncbi.nlm.nih.gov/pubmed/24107764). Frodl T, Skokauskas N (February 2012). "Meta- analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.x (https://dx.doi.org /10.1111%2Fj.1600-0447.2011.01786.x).
PMID 22118249 (https://www.ncbi.nlm.nih.gov /pubmed/22118249).


- that stimulants may be useful in stroke or acute traumatic brain injury


-that stimulants at therapeutic doses can enhance cognition in any healthy adult: when used at low (therapeutic) doses, amphetamine produces unambiguous improvements in cognition, including working memory (http://en.wikipedia.org/wiki/Working_memory), episodic memory (http://en.wikipedia.org/wiki/Episodic_memory), and inhibitory control (http://en.wikipedia.org/wiki/Inhibitory_control_test), in normal healthy adults
Refs:

32. Dale E, Bang-Andersen B, Sánchez C (May 2015). "Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs". Biochem. Pharmacol. 95 (2): 81–97. doi:10.1016/j.bcp.2015.03.011 (https://dx.doi.org /10.1016%2Fj.bcp.2015.03.011). PMID 25813654 (https://www.ncbi.nlm.nih.gov/pubmed/25813654
and
Spencer RC, Devilbiss DM, Berridge CW (June 2015). "The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex". Biol. Psychiatry 77 (11): 940–950. doi:10.1016/j.biopsych.2014.09.013 (https://dx.doi.org /10.1016%2Fj.biopsych.2014.09.013).
PMID 25499957 (https://www.ncbi.nlm.nih.gov /pubmed/25499957).

[color=#0000ff]



- that stimulants need to be taken at abuse doses to become addictive

[/size]
refs

Adderall IR Prescribing Information" (http://www.accessdata.fda.gov/drugsatfda_docs /label/2007/011522s040lbl.pdf) (PDF). United States Food and Drug Administration. Barr Laboratories, Inc. March 2007. Retrieved 4 November 2013. "Dexedrine Medication Guide" (http://www.accessdata.fda.gov/drugsatfda_docs /label/2013/017078s046lbl.pdf) (PDF). United States Food and Drug Administration. Amedra Pharmaceuticals LLC. May 2013. Retrieved
4 November 2013.
"Adderall XR Prescribing Information" (http://www.accessdata.fda.gov/drugsatfda_docs /label/2013/021303s026lbl.pdf) (PDF). United States Food and Drug Administration. Shire US Inc. December 2013. Retrieved 30 December 2013.





-People with ADHD have an increased risk of substance abuse (http://en.wikipedia.org/wiki/Substance_abuse), and stimulant medications reduce this risk


Faraone SV, Wilens TE (2007). "Effect of stimulant medications for attention-deficit/hyperactivity disorder on later substance use and the potential for stimulant misuse, abuse, and diversion". J Clin Psychiatry. 68 Suppl 11: 15–22. doi:10.4088/jcp.1107e28 (https://dx.doi.org/10.4088%2Fjcp.1107e28). PMID 18307377 (https://www.ncbi.nlm.nih.gov/pubmed/18307377).
Wilens TE, Faraone SV, Biederman J, Gunawardene S (2003). "Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse? A Meta-analytic Review of the Literature". Pediatrics 111 (1): 179–85. doi:10.1542/peds.111.1.179 (https://dx.doi.org/10.1542%2Fpeds.111.1.179). PMID 12509574 (https://www.ncbi.nlm.nih.gov/pubmed/12509574).




- that methylphenidate at least may be neuroprotective in Parkinson's disease


Volz TJ (2008). "Neuropharmacological Mechanisms Underlying the Neuroprotective Effects of Methylphenidate"
(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286). Current Neuropharmacology 6 (4): 379–385. doi:10.2174/157015908787386041 (https://dx.doi.org/10.2174%2F157015908787386041). PMC 2701286 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701286). PMID 19587858 (https://www.ncbi.nlm.nih.gov/pubmed/19587858).





Aggression and criminality

Two studies state that methylphenidate is indicated for the treatment of ADHD in adults with a history of aggressive and criminal behavior. A large clinical study conducted in Sweden found a significant reduction of the criminality rate in males (32%) and females (42%) as compared with the rate for the same patients while not receiving medication.[36] Some of these clinical outcomes have been confirmed in similar studies with children and adolescents.[37]



36. Lichtenstein P, Halldner L, Zetterqvist J, Sjölander A, Serlachius E, Fazel S, Långström N, Larsson H (2012). "Medication for Attention Deficit–Hyperactivity Disorder and Criminality" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664186). New England Journal of Medicine 367 (21): 2006–14. doi:10.1056/NEJMoa1203241 (https://dx.doi.org/10.1056%2FNEJMoa1203241).PMC 3664186 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664186). PMID 23171097 (https://www.ncbi.nlm.nih.gov/pubmed /23171097).


Pappadopulos E, Woolston S, Chait A, Perkins M, Connor DF, Jensen PS (2006). "Pharmacotherapy of aggression in children and adolescents: Efficacy and effect size" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277275). Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent 15 (1): 27–39.
PMC 2277275 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277275). PMID 18392193 (https://www.ncbi.nlm.nih.gov/pubmed /18392193).



So now there is enough to say that the burden of proof lies with the use of stimulants in ADHD, that this is rapidly becoming, provably, the scientific gold standard.