User:Sifaka/Attention-deficit hyperactivity disorder: controversies

Concerns about side effects and long term effectiveness
Some parents and professionals have raised questions about the side effects of drugs and their long term use. Studies have shown that stimulants offer no benefits over behavioral management for periods over 3 years. 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. 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.

A 2008 review found that the use of stimulants improved teachers' and parents' ratings of behavior; however, it did not improve academic achievement. Stimulants neither increased nor decreased rates of delinquency or substance abuse at 3 years. Intensive treatment for 14 months has no effect on long term outcomes 8 years later. No significant differences between the various drugs in terms of efficacy or side effects have been found. 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.

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.

Long term effects
Methylphenidate, an amphetamine derivative and potent central nervous system stimulant, 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. Knowledge of the effects of chronic use of methylphenidate is poorly understood with regard to persisting behavioral and neuroadaptational effects. 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. A study has shown persisting molecular changes to the dopamine system, specifically the reward system, when methylphenidate is given to adolescent rats. Whether long term stimulants cause similar changes in the brain of children leading to increased substance abuse is unclear. 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. Effects resulting from long term use of methylphenidate most likely result from changes induced in the dopamine system. Methylphenidate has an incidence 0.1 % of psychosis in short term clinical trials. 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. 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.

Concerns have been raised that long-term therapy might cause drug dependence, paranoia, schizophrenia and behavioral sensitization, similar to other stimulants. 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.

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. 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. 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. 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. Stimulant medication may also inhibit cartilage growth, liver development and central nervous system growth factors. Periodic CBC, differential, and platelet counts are recommended during prolonged use of methylphenidate.

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

Methylphenidate psychosis may be a concern for children on long term methylphenidate. 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. Another study found methylphenidate has an incidence 0.1 % of psychosis in short term clinical trials. For the majority of cases, the psychotic-like or mania-like symptoms resolved after methylphenidate treatment was discontinued. 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.

Concerns have been raised that long-term therapy might cause drug dependence, paranoia, schizophrenia and behavioral sensitisation. 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.

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.

Addiction, Abuse Potential, and Withdrawal
Long term effects of methylphenidate such as drug addiction, withdrawal reactions and psychosis

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