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Concerns about side effects and long term effectiveness

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Some parents and professionals have raised questions about the side effects of drugs and their long term use.[1] Studies have shown that stimulants offer no benefits over behavioral management for periods over 3 years.[2][3] Other side effects of concern include addiction, growth retardation, suicidal thoughts and effects on the heart. This has led to interest in non-drug treatments such as omega 3 oils which can help symptoms of ADHD.[4] On February 9, 2006, the U.S. Food and Drug Administration voted to recommend a "black-box" warning describing the cardiovascular risks of stimulant drugs used to treat ADHD.[5]

A 2008 review found that the use of stimulants improved teachers' and parents' ratings of behavior; however, it did not improve academic achievement.[3] Stimulants neither increased nor decreased rates of delinquency or substance abuse at 3 years.[3] Intensive treatment for 14 months has no effect on long term outcomes 8 years later.[6] No significant differences between the various drugs in terms of efficacy or side effects have been found.[7][8] A meta analysis of clinical trials found that about 70% of children improve after being treated with stimulants in the short term but found that this conclusion may be be biased due to the high number of low quality clinical trials in the literature. There have been no randomised placebo controlled clinical trials investigating the long term effectiveness of methylphenidate (Ritalin) beyond 4 weeks. Thus the long term effectiveness of methylphenidate has not been scientifically demonstrated. Serious concerns of publication bias regarding the use of methylphenidate for ADHD has also been noted.[9]

Animal research on the neurotoxicity of amphetamines has found contradictatory results. For example in rats doses of amphetamines equivalent to those used therapeutically to treat ADHD were suggestive of benefits to the dopamine system, whereas in primates therapeutic equivalent doses were found to cause neurotoxicity.[10]

Long term effects

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Methylphenidate, an amphetamine derivative and potent central nervous system stimulant,[11][12] can also lead to a psychosis from chronic use. Although the safety profile of short-term methylphenidate therapy in clinical trials has been well established, repeated use of psychostimulants such as methylphenidate is less clear. Long term effects of methylphenidate, such as drug addiction, withdrawal reactions and psychosis, have received very little research attention and thus are largely unknown.[13] Knowledge of the effects of chronic use of methylphenidate is poorly understood with regard to persisting behavioral and neuroadaptational effects.[14] Stimulants can cause delayed growth in children for up to 3 years. Animal studies have led to concerns of the safety of long term use of stimulants in the developing brain of humans.[15] A study has shown persisting molecular changes to the dopamine system, specifically the reward system, when methylphenidate is given to adolescent rats.[16] Whether long term stimulants cause similar changes in the brain of children leading to increased substance abuse is unclear.[17] There is limited data regarding long term use of stimulants which suggests that there may be modest benefits in correctly diagnosed children with ADHD but there are also overall modest risks.[18] Effects resulting from long term use of methylphenidate most likely result from changes induced in the dopamine system.[19] Methylphenidate has an incidence 0.1 % of psychosis in short term clinical trials.[20] A small study of just under 100 children which assessed long term outcome of stimulant use found that 6% of the children became psychotic after months or years of stimulant therapy. Typically psychosis abates soon after stopping stimulant therapy. As the study size was small and was not standardised, larger studies have been recommended.[21] The long term effects on the developing brain and on mental health disorders in later life of chronic use of methylphenidate is unknown. Despite this, between 0.51% to 1.23% of children between the ages of 2 and 6 years take stimulants in the USA. Stimulants drugs are not approved for this age group.[22][23]

Concerns have been raised that long-term therapy might cause drug dependence, paranoia, schizophrenia and behavioral sensitization, similar to other stimulants.[24] Psychotic symptoms from methylphenidate can include hearing voices, visual hallucinations, urges to harm oneself, severe anxiety, euphoria, grandiosity, paranoid delusions, confusion, increased aggression and irritability. It is unpredictable in whom methylphenidate psychosis will occur. Family history of mental illness does not predict the incidence of stimulant toxicosis in ADHD children. High rates of childhood stimulant use have been noted in patients with a diagnosis of schizophrenia and bipolar disorder independent of ADHD. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder in children who are vulnerable to psychotic disorders.[25][26][27]

Studies investigating whether stimulant medication can lead to drug abuse later in life found that despite the higher rate of substance abuse among ADHD patients as a whole, stimulant medication use in childhood did not affect, or lowered, the risk for substance of abuse in adulthood compared to unmedicated individuals with ADHD.[28]

Young ADHD patients taking stimulant medication may have a reduced rate of height and weight gain during adolescence, but stimulant medication has little effect on the ultimate weight and height of the medicated patient.[29] It is unclear whether the delay in growth is due to stimulant medication or ADHD itself; ethical problems in giving stimulant medication to children without ADHD as experimental controls makes such studies problematic.[30] Some patients will take a period of time off of medication, called a "drug holiday," in hopes of allowing the normal rate of height and weight attainment to resume.[30] Stimulant medication may also inhibit cartilage growth, liver development and central nervous system growth factors.[30] Periodic CBC, differential, and platelet counts are recommended during prolonged use of methylphenidate.[31]

old stuff break

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old stuff break

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Long term effects

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Much research about the effects of stimulants used to treat ADHD has been focused on methylphenidate, a potent central nervous system stimulant.[32] Although the safety profile of short-term methylphenidate therapy in clinical trials has been well established,[33] the long term effects of methylphenidate have not been studied as thoroughly.[34]

Methylphenidate psychosis may be a concern for children on long term methylphenidate.[35] There has been very little research into the rates of psychosis or mania induced by therapeutic doses methylphenidate, but an aggregation of results from various studies tentatively estimates these symptoms will occur in approximately 0.25% of children taking therapeutic doses of methyphenidate.[36] Another study found methylphenidate has an incidence 0.1 % of psychosis in short term clinical trials.[20] For the majority of cases, the psychotic-like or mania-like symptoms resolved after methylphenidate treatment was discontinued.[37] The same study found that methylphenidate psychosis is unpredictable and family history of mental illness does not predict the incidence of stimulant induced psychotic or mania-like symptoms in ADHD children.[36]

Concerns have been raised that long-term therapy might cause drug dependence, paranoia, schizophrenia and behavioral sensitisation. [38] Studies investigating whether stimulant medication can lead to drug abuse later in life found that despite the higher rate of substance abuse among ADHD patients as a whole, stimulant medication use in childhood did not affect or lowered the risk for substance of abuse in adulthood compared to unmedicated individuals. [39]


High rates of childhood stimulant use is found in patients with a diagnosis of schizophrenia and bipolar disorder independent of ADHD. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder.[40][41][42]

Addiction, Abuse Potential, and Withdrawal

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Long term effects of methylphenidate such as drug addiction, withdrawal reactions and psychosis


Cardiovascular and blood pressure

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Sources to look at

  1. Does Childhood Treatment of ADHD With Stimulant Medication Affect Substance Abuse in Adulthood?
  2. Guideline ADHD, Substance Use Disorders, and Psychostimulant Treatment: Current Literature and Treatment
  3. Pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) decreases the risk for substance abuse: Findings from a longitudinal follow-up of youths with and without ADHD
  4. Variables That Affect the Clinical Use and Abuse of Methylphenidate in the Treatment of ADHD
  5. ADHD and Addiction
  6. Evolution of the treatment of attention-deficit/hyperactivity disorder in children: a review.
  7. Development of 5-HT transporter density and long-term effects of methylphenidate in an animal model of ADHD.
  8. Safety of therapeutic methylphenidate in adults: a systematic review of the evidence.
  9. Psychotic side effects of psychostimulants: a 5-year review.
  10. Methylphenidate does not increase ethanol consumption in a rat model for attention-deficit hyperactivity disorder-the spontaneously hypertensive rat.

When changes get made stuff to talk about

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One publication suggests a rate of psychosis of 6% in children on long term methylphenidate.[43] As the study is retrospective, assessments are not fully standardized, nor is the follow-up consistent.

References

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  1. ^ Lakhan SE, Hagger-Johnson GE (2007). "The impact of prescribed psychotropics on youth". Clin Pract Epidemol Ment Health. 3: 21. doi:10.1186/1745-0179-3-21. PMC 2100041. PMID 17949504.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  2. ^ Jensen, PETER S. (2007). "3-Year Follow-up of the NIMH MTA Study". J Am Acad Child Adolesc Psychiatry. 46 (8): 989–1002. doi:10.1097/CHI.0b013e3180686d48. PMID 17667478.
  3. ^ a b c "What is the evidence for using CNS stimulants to treat ADHD in children?". March - May 2008. Retrieved 2008-09-10. {{cite web}}: Check date values in: |date= (help)
  4. ^ Matsudaira T (2007). "Attention deficit disorders--drugs or nutrition?". Nutr Health. 19 (1–2): 57–60. doi:10.1177/026010600701900206. PMID 18309764.
  5. ^ Nissen SE (April 2006). "ADHD drugs and cardiovascular risk". N. Engl. J. Med. 354 (14): 1445–8. doi:10.1056/NEJMp068049. PMID 16549404.{{cite journal}}: CS1 maint: date and year (link)
  6. ^ Molina BS, Hinshaw SP, Swanson JM; et al. (March 2009). "MTA at 8 Years: Prospective Follow-up of Children Treated for Combined-Type ADHD in a Multisite Study". J Am Acad Child Adolesc Psychiatry. 48 (5): 484–500. doi:10.1097/CHI.0b013e31819c23d0. PMC 3063150. PMID 19318991. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  7. ^ King S, Griffin S, Hodges Z; et al. (July 2006). "A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents". Health Technol Assess. 10 (23): iii–iv, xiii–146. doi:10.3310/hta10230. PMID 16796929. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  8. ^ Brown RT, Amler RW, Freeman WS; et al. (June 2005). "Treatment of attention-deficit/hyperactivity disorder: overview of the evidence". Pediatrics. 115 (6): e749–57. doi:10.1542/peds.2004-2560. PMID 15930203. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  9. ^ Schachter HM, Pham B, King J, Langford S, Moher D (November 2001). "How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis". CMAJ. 165 (11): 1475–88. PMC 81663. PMID 11762571. Retrieved 2009-05-02.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  10. ^ Advokat C (July 2007). "Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD". J Atten Disord. 11 (1): 8–16. doi:10.1177/1087054706295605. PMID 17606768.{{cite journal}}: CS1 maint: date and year (link)
  11. ^ Auriel E, Hausdorff JM, Giladi N (October 2008). "Methylphenidate for the Treatment of Parkinson Disease and Other Neurological Disorders". Clin Neuropharmacol. 32 (2): 75–81. doi:10.1097/WNF.0B013E318170576C. PMID 18978488.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  12. ^ Abramowicz MJ, Van Haecke P, Demedts M, Delcroix M (September 2003). "Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation". Eur. Respir. J. 22 (3): 560–2. doi:10.1183/09031936.03.00095303. PMID 14516151.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  13. ^ Ashton H, Gallagher P, Moore B (September 2006). "The adult psychiatrist's dilemma: psychostimulant use in attention deficit/hyperactivity disorder". J. Psychopharmacol. (Oxford). 20 (5): 602–10. doi:10.1177/0269881106061710. PMID 16478756.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  14. ^ Kuczenski R, Segal DS (June 2005). "Stimulant actions in rodents: implications for attention-deficit/hyperactivity disorder treatment and potential substance abuse". Biol. Psychiatry. 57 (11): 1391–6. doi:10.1016/j.biopsych.2004.12.036. PMID 15950013.{{cite journal}}: CS1 maint: date and year (link)
  15. ^ Hoza B, Kaiser NM, Hurt E (December 2007). "Multimodal treatments for childhood attention-deficit/hyperactivity disorder: interpreting outcomes in the context of study designs". Clin Child Fam Psychol Rev. 10 (4): 318–34. doi:10.1007/s10567-007-0025-5. PMID 17710545.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  16. ^ Carlezon WA, Konradi C (2004). "Understanding the neurobiological consequences of early exposure to psychotropic drugs: linking behavior with molecules". Neuropharmacology. 47 (Suppl 1): 47–60. doi:10.1016/j.neuropharm.2004.06.021. PMC 4204484. PMID 15464125.
  17. ^ Fone KC, Nutt DJ (February 2005). "Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder". Curr Opin Pharmacol. 5 (1): 87–93. doi:10.1016/j.coph.2004.10.001. PMID 15661631.{{cite journal}}: CS1 maint: date and year (link)
  18. ^ Kociancic T, Reed MD, Findling RL (March 2004). "Evaluation of risks associated with short- and long-term psychostimulant therapy for treatment of ADHD in children". Expert Opin Drug Saf. 3 (2): 93–100. doi:10.1517/eods.3.2.93.27337. PMID 15006715.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  19. ^ Viggiano D, Vallone D, Sadile A (2004). "Dysfunctions in dopamine systems and ADHD: evidence from animals and modeling" (PDF). Neural Plast. 11 (1–2): 97–114. doi:10.1155/NP.2004.97. PMC 2565441. PMID 15303308.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ a b "Ritalin & Ritalin-SR Prescribing Information" (PDF). Novartis. April 2007.{{cite web}}: CS1 maint: date and year (link)
  21. ^ Cherland E, Fitzpatrick R (October 1999). "Psychotic side effects of psychostimulants: a 5-year review" (PDF). Can J Psychiatry. 44 (8): 811–3. doi:10.1177/070674379904400810. PMID 10566114.{{cite journal}}: CS1 maint: date and year (link)
  22. ^ Kimko HC, Cross JT, Abernethy DR (December 1999). "Pharmacokinetics and clinical effectiveness of methylphenidate". Clin Pharmacokinet. 37 (6): 457–70. doi:10.2165/00003088-199937060-00002. PMID 10628897.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  23. ^ Vitiello B (October 2001). "Psychopharmacology for young children: clinical needs and research opportunities". Pediatrics. 108 (4): 983–9. doi:10.1542/peds.108.4.983. PMID 11581454.{{cite journal}}: CS1 maint: date and year (link)
  24. ^ Dafny, N.; Yang, P. B. (15). "The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: A review of its locomotor effects". Brain Research Bulletin. 68 (6): 393–405. doi:10.1016/j.brainresbull.2005.10.005. PMID 16459193. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
  25. ^ Ross RG (July 2006). "Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder". Am J Psychiatry. 163 (7): 1149–52. doi:10.1176/appi.ajp.163.7.1149. PMID 16816217.{{cite journal}}: CS1 maint: date and year (link)
  26. ^ DelBello MP, Soutullo CA, Hendricks W, Niemeier RT, McElroy SL, Strakowski SM (April 2001). "Prior stimulant treatment in adolescents with bipolar disorder: association with age at onset". Bipolar Disord. 3 (2): 53–7. doi:10.1034/j.1399-5618.2001.030201.x. PMID 11333062.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  27. ^ Soutullo CA, DelBello MP, Ochsner JE; et al. (August 2002). "Severity of bipolarity in hospitalized manic adolescents with history of stimulant or antidepressant treatment". J Affect Disord. 70 (3): 323–7. doi:10.1016/s0165-0327(01)00336-6. PMID 12128245. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  28. ^ Scott H. Kollins (1a). "Guideline ADHD, Substance Use Disorders, and Psychostimulant Treatment: Current Literature and Treatment". Journal of Attention Disorders. 12 (2): 115–125. doi:10.1177/1087054707311654. PMID 18192623. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
  29. ^ Faraone SV; Biederman J; Morley CP; Spencer TJ (September 2008). "Effect of stimulants on height and weight: a review of the literature". J Am Acad Child Adolesc Psychiatry. 47 (9): 977–80. doi:10.1097/CHI.ObO13e31817eOea7. PMID 18580502.{{cite journal}}: CS1 maint: date and year (link)
  30. ^ a b c Joshi SV (February 2002). "ADHD, growth deficits, and relationships to psychostimulant use". Pediatr Rev. 23 (2): 67–8, discussion 67–8. doi:10.1542/pir.23-2-67. PMID 11826259.{{cite journal}}: CS1 maint: date and year (link)
  31. ^ Cite error: The named reference pmid11056411 was invoked but never defined (see the help page).
  32. ^ Auriel E, Hausdorff JM, Giladi N (October 2008). "Methylphenidate for the Treatment of Parkinson Disease and Other Neurological Disorders". Clin Neuropharmacol. 32 (2): 75–81. doi:10.1097/WNF.0B013E318170576C. PMID 18978488.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  33. ^ "NIMH · ADHD · The Treatment of ADHD".
  34. ^ Ashton H, Gallagher P, Moore B (September 2006). "The adult psychiatrist's dilemma: psychostimulant use in attention deficit/hyperactivity disorder". J. Psychopharmacol. (Oxford). 20 (5): 602–10. doi:10.1177/0269881106061710. PMID 16478756.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  35. ^ Cherland E, Fitzpatrick R (October 1999). "Psychotic side effects of psychostimulants: a 5-year review". Can J Psychiatry. 44 (8): 811–3. doi:10.1177/070674379904400810. PMID 10566114.{{cite journal}}: CS1 maint: date and year (link)
  36. ^ a b Ross RG (July 2006). "Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder". Am J Psychiatry. 163 (7): 1149–52. doi:10.1176/appi.ajp.163.7.1149. PMID 16816217.{{cite journal}}: CS1 maint: date and year (link)
  37. ^ Cherland E, Fitzpatrick R (October 1999). "Psychotic side effects of psychostimulants: a 5-year review". Can J Psychiatry. 44 (8): 811–3. doi:10.1177/070674379904400810. PMID 10566114.{{cite journal}}: CS1 maint: date and year (link) 55 out of 60 cases or 92%. The remaining five patients whose psychotic-like or mania-like symptoms persisted were later rediagnosed as having either bipolar disorder or schizophrenia.
  38. ^ Dafny, N.; Yang, P. B. (15). "The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: A review of its locomotor effects". Brain Research Bulletin. 68 (6): 393–405. doi:10.1016/j.brainresbull.2005.10.005. PMID 16459193. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
  39. ^ Scott H. Kollins (1a). "GuidelineADHD, Substance Use Disorders, and Psychostimulant Treatment: Current Literature and Treatment". Journal of Attention Disorders. 12 (2): 115–125. doi:10.1177/1087054707311654. PMID 18192623. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
  40. ^ Ross RG (July 2006). "Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder". Am J Psychiatry. 163 (7): 1149–52. doi:10.1176/appi.ajp.163.7.1149. PMID 16816217.{{cite journal}}: CS1 maint: date and year (link)
  41. ^ DelBello MP, Soutullo CA, Hendricks W, Niemeier RT, McElroy SL, Strakowski SM (April 2001). "Prior stimulant treatment in adolescents with bipolar disorder: association with age at onset". Bipolar Disord. 3 (2): 53–7. doi:10.1034/j.1399-5618.2001.030201.x. PMID 11333062.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  42. ^ Soutullo CA, DelBello MP, Ochsner JE; et al. (August 2002). "Severity of bipolarity in hospitalized manic adolescents with history of stimulant or antidepressant treatment". J Affect Disord. 70 (3): 323–7. doi:10.1016/s0165-0327(01)00336-6. PMID 12128245. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  43. ^ Cherland E, Fitzpatrick R (October 1999). "Psychotic side effects of psychostimulants: a 5-year review". Can J Psychiatry. 44 (8): 811–3. doi:10.1177/070674379904400810. PMID 10566114.{{cite journal}}: CS1 maint: date and year (link)
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