Effectiveness of Medications:

One of the world’s first long term studies reveals that using stimulants, amphetamine based drugs like dexamphetamine and Ritalin, increased the chances of an ADHD diagnosed child failing to reach an age appropriate educational standard by a massive 950%. 

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Another sudden death in a child treated with desipramine., Riddle MA, Geller B, Ryan N.
J Am Acad Child Adolescent Psychiatry 1993 Jul;32(4):792-7.

This article reports on another case of sudden death in a child taking the tricyclic antidepressant drug desipramine. The mechanism proposed for the sudden death implies the triggering of fatal cardiac arrhythmia by the drug.

Case study: two additional sudden deaths with tricyclic antidepressants., Varley CK, McClellan J.
J Am Acad Child Adolescent Psychiatry 1997 Mar;36(3):390-4.

This article reports on the cases of 2 children who experienced sudden death while on treatment with the tricyclic antidepressant desipramine. This brings to 7 the number of deaths reported in the literature associated with use of this drug in children.

Effect of tricyclic antidepressants on switching to mania and on the onset of bipolarity in depressed 6- to 12-year-olds., Geller B, Fox LW, Fletcher M.
J Am Acad Child Adolescent Psychiatry 1993 Jan;32(1):43-50.

This article emphasizes that children treated for depression with tricyclic antidepressants are at high risk of developing mania. The authors found high rates of mania and bipolar disorder (cyclic alternation of states of mania and depression) in 6- to 12-year old children with depression treated with tricyclic antidepressants. Mania occurred only in depressed children who were currently taking, or had taken in the past, this class of drugs.

Clonidine overdose in childhood: implications of increased prescribing., Kappagoda C, Schell DN, Hanson RM, Hutchins P., J Paediatr Child Health 1998 Dec;34(6):508-12.

This study reports on the case of 16 children admitted to the emergency department of a pediatric hospital for clonidine overdose during the period 1990-1997. Fourteen of them were taking clonidine for attention deficit disorder. Of all the cases, only 1 occurred before 1994, indicating a 15-fold increase of this complication in the period 1994-1997, compared to 1990-1993. Symptoms of toxicity included low heart rate in 88% of the children and depressed level of consciousness in 75% of them. Clonidine overdose is being increasingly recognized as clinical entity due to increased prescription of the drug in children diagnosed with attention deficit disorder.

Clonidine poisoning--an emerging problem: epidemiology, clinical features, management and preventative strategies., Erickson SJ, Duncan A., J Paediatr Child Health 1998 Jun;34(3):280-2.
This article reports on the case of 14 children with clonidine overdose reported between 1985 and 1995. Of all the cases, 8 occurred in the last two years, in children who received the drug for attention-deficit disorder. The most common signs of toxicity were depressed consciousness in 71% of cases, and slowness of the heart beat in 50% of cases. The authors conclude that the increased incidence of clonidine toxicity in the last years is consistent with the increased prescription of this drug for childhood behavioral disorders.

Clonidine poisoning in young children. , Wiley JF 2d, Wiley CC, Torrey SB, Henretig FM.
J Pediatrics 1990 Apr;116(4):654-8.

In this article, the case of 47 children hospitalized for clonidine overdose is presented.
Signs of toxicity included slowness of heart rate in 25 children, and cessation of breathing or depressed respiration in 18. Six children required endotracheal intubation and mechanical ventilation. Naloxone was ineffective in reverting clonidine poisoning.

Case study: accidental clonidine patch overdose in attention-deficit/hyperactivity disorder patients.
Broderick-Cantwell JJ., J Am Acad Child Adolescent Psychiatry 1999 Jan;38(1):95-8.
This article reports on the case of two children treated for attention-deficit disorder who experienced clonidine poisoning from a transdermal patch.

Case study: adverse response to clonidine., Cantwell DP, Swanson J, Connor DF.
J Am Acad Child Adolescent Psychiatry 1997 Apr;36(4):539-44.

This article reports on the case of 4 children who experienced adverse effects during clonidine treatment.

Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder
A systematic chart review of 62 cases., Prince JB, Wilens TE, Biederman J, Spencer TJ, Wozniak JR.
J Am Acad Child Adolescent Psychiatry 1996 May;35(5):599-605.

The results of this study show that treatment with clonidine in children with attention-deficit disorder is associated with a high rate of adverse effects. Clonidine is prescribed to relieve sleep disturbances secondary to treatment with stimulants or pre-existing to treatment. The study, conducted 64 children and adolescents with attention-deficit disorder, show that while 85% of children reported improvements in sleep disturbances (sedation, lethargy and drowsiness are the most common adverse effects of treatment with clonidine, a drug that has received approval only for the management of high blood pressure), 30% of them experienced other unwanted adverse effects.

Guanfacine, but not clonidine, improves planning and working memory performance in humans.
Jakala P, et al., Neuropsychopharmacology 1999 May;20(5):460-70.

The results of this double blind, placebo-controlled study, indicate that clonidine disrupts planning and working memory performances in a dose-dependent manner.

Clonidine, but not guanfacine, impairs choice reaction time performance in young healthy volunteers.
Jakala P, Riekkinen M, Sirvio J, Koivisto E, Riekkinen P Jr.
Neuropsychopharmacology 1999 Oct;21(4):495-502.

This double blind, placebo controlled study evaluated the impact of clonidine on motor and cognitive performances in healthy young individuals. While the drug did not affect performances at the easy levels of an attentional test, at the most difficult level individuals who took clonidine made an increased number of mistakes and exhibited increased reaction time, compared to those who took placebo. This study indicates that clonidine significantly impair performances that require complex processing in young, healthy individuals, while leaving intact those that require more automatic functioning.

Contrasting effects of clonidine and diazepam on tests of working memory and planning.
Coull JT, Middleton HC, Robbins TW, Sahakian BJ.
Psychopharmacology (Berl) 1995 Aug;120(3):311-21.

The results of this double blind, placebo-controlled study conducted on healthy young volunteers show that clonidine impairs memory in a dose-dependent way, and therefore negatively affect cognitive function in this age group.

Differences in psychic performance with guanfacine and clonidine in normotensive subjects.
Kugler J, Seus R, Krauskopf R, Brecht HM, Raschig A.
Br J Clin Pharmacol 1980;10 Suppl 1:71S-80S.

This study evaluated the effects of the alpha 2-agonists clonidine and guanfacine on 24 healthy young volunteers. Individuals taking clonidine had significantly more depressed central nervous system function, as shown by reduced information processing and increased latency of reaction, than those taking guanfacine. The increased suppression of mental activity in individuals taking clonidine versus those taking guanfacine was also demonstrated at EEG evaluation.

Electroencephalographic and psychometric assessment of the CNS effects of single doses of guanfacine hydrochloride (Estulic) and clonidine (Catapres).
Yamadera H, Ferber G, Matejcek M, Pokorny R.
Neuropsychobiology 1985;14(2):97-107.

The results of this study, conducted on 10 young and healthy volunteers, show that intake of clonidine is associated with significant depression of the central nervous system, as shown by EEG changes, and induction of feelings of decreased alertness, extroversion, concentration and mood paralleling the electroencephalographic findings.

Sources of poisoning exposures in children during 1990-1995. An analysis of the National Poison Information Centre files., Kotwica M. et al.
Int J Occup Med Environ Health, 10(2):177-86 1997.

This study evaluated the cause of acute poisoning in Polish children up to 14 years of age, and showed that 96% of intoxications were accidental, and 44% were due to drugs. Twenty-five percent of drug-poisonings were caused by sedatives and psychotropic drugs.

National trends in the prevalence of attention-deficit/hyperactivity disorder and the prescribing of methylphenidate among school-age children: 1990-1995.
Robison LM, et al., Clin Pediatr (Phila) 1999 Apr;38(4):209-17.

The results of this study show that the number of office visits in which a child was diagnosed with attention-deficit/hyperactivity disorder increased from 947,208 in 1990, to 2,357,833 in 1995. Concurrently, the number of children prescribed stimulant therapy increased by threefold.

Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents.
Council on Scientific Affairs, American Medical Association.
Goldman LS, et al., JAMA 1998 Apr 8;279(14):1100-7.

The results of this study show that in the U.S., 3% to 6% of school-aged children are diagnosed with attention-deficit/hyperactivity disorder, and approximately 3% of all children are treated for this condition. Definition criteria have expanded so that more children, especially girls, are now included in the diagnosis, and are being treated for longer periods of time. Treatment has been proven to offer only short-term amelioration of symptoms and academic performances, and the disorder, in spite of drug therapy, seems to continue into adolescence and adulthood.

Increased methylphenidate usage for attention deficit disorder in the 1990s.
Safer DJ. et al., Pediatrics 1996 Dec;98(6 Pt 1):1084-8.

The results of this study show that in 1995, approximately 2.8% of U.S. youths (1.5 million of children and adolescents) were being treated with methylphenidate (Ritalin) for attention deficit disorder.

Ethical and pragmatic issues in the use of psychotropic agents in young children.
Jensen PS., Can J Psychiatry, 43(6):585-8 1998 Aug.

This article cautions against use of psychotropic drugs in young children with mental health problems or mental retardation, since, despite the high rate of prescribing, no adequate testing for safety and efficacy has been performed yet in this category of patients.

The use of psychotropic medication in preschoolers: indications, safety, and efficacy.
Greenhill LL., Can J Psychiatry, 43(6):576-81 1998 Aug.

This article emphasizes that in spite of the high rates of prescribing of psychotropic drugs to children younger than 6 years, the use of this class of drugs for psychiatric disorders other than attention deficit disorder in preschool children has not been approved by the Food and Drug Administration.

Methylphenidate slows right hemisphere processing in children with attention-deficit/hyperactivity disorder., Campbell L. et al., J Child Adolescent Psychopharmacology 1996 Winter;6(4):229-39.

The results of this study, conducted on a group of children diagnosed with attention-deficit/hyperactivity disorder, show that those treated with methylphenidate (Ritalin) have slower reaction times to tasks involving the right hemisphere, compared to those receiving placebo.

Emergence of self-destructive phenomena in children and adolescents during Fluoxetine treatment.
King RA; et al., J Am Acad Child Adolescent Psychiatry, 30(2):179-86 1991 Mar.

The results of this study, conducted on a cohort of 42 children with obsessive-compulsive disorder, show that after initiation of treatment with the selective serotonin reuptake inhibitor Fluoxetine, 6 of them (14%) developed or experienced worsening of self-destructive ideation or behavior, of such intensity to require the hospitalization in 4 cases.

Estimation of the association between desipramine and the risk for sudden death in 5- to 14-year-old children., Biederman J. et al., J Clin Psychiatry, 56(3):87-93 1995 Mar.

This article reports on the cases of 4 sudden deaths in children treated with the tricyclic antidepressant desipramine. The authors highlight the importance of carefully evaluating the risks and benefits of treatment before using this drug in children.

Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms.
Swanson JR. et al.
J Forensic Sci, 42(2):335-9 1997 Mar.

This article reports on the case of 2 sudden deaths in a 7-year old boy and a 21-year old woman, on chronic treatment with the antidepressant imipramine. Concurrent use of phenothiazines and/or genetic predisposition may have contributed to antidepressant-related fatal toxicity.

Cardiovascular effects of tricyclic antidepressants in childhood asthma: a case series and review.
Wamboldt MZ, et al.
J Child Adolescent Psychopharmacology 1997 Spring;7(1):45-64.

The results of this study, conducted on a cohort of 40 children and adolescents with asthma, for which each was receiving an average of 5 drugs, show that concurrent use of antidepressants caused significant cardiovascular effects such as tachycardia, increased blood pressure, and postural hypotension in 5 of them (12.5%), and hypomanic symptoms necessitating discontinuation of therapy in 2 of them. The high prevalence of asthma symptoms and treatment in children and adolescents, coupled with the widespread use of psychotropic drugs, makes the occurrence of adverse cardiovascular effects from combined treatment a serious concern.

Cardiovascular effects of therapeutic doses of tricyclic antidepressants in children and adolescents.
Wilens TE, et al.
J Am Acad Child Adolescent Psychiatry 1996 Nov;35(11):1491-501.

This study reviewed available literature on the effects of tricyclic antidepressants on the cardiovascular system after several reports of cases of sudden death in children and adolescents on treatment with these drugs. Indeed, analysis of 24 studies conducted on 730 children, documented electrocardiographic changes and abnormalities, increased diastolic and systolic blood pressure, and increased heart rate during exposure to this class of drugs.

Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study.
Rowe KS, Rowe KJ.
J Pediatr 1994 Nov;125(5 Pt 1):691-8.

The results of this study show that intake of tartrazine (synthetic food coloring) is associated with behavioral changes typical of attention-deficit disorder (ADD) in a significant number of children. The study was conducted on 200 children referred for suspected attention-deficit disorder to a children's hospital. They were started on a 6-week period of synthetic food coloring-free diet. One hundred-fifty mothers reported that their children's behavior improved with diet, and worsened when synthetic food coloring was re-introduced. In addition, the researchers conducted a three-week long, double- blind, placebo-controlled trial, to test the behavioral responses of children with ADD and controls, to escalating doses of tartrazine or placebo. Twenty-two of 34 children with suspected ADD and 2 of 20 controls were found to have clear reactions to tartrazine, manifested by restlessness, irritability, and sleep disturbances. All doses produced behavioral responses, and the response was prolonged in children who received higher doses. These results indicate that intake of synthetic food coloring induces behavioral disturbances typical of attention deficit disorder in a significantly high number of children diagnosed with this condition. The symptoms are reproducible, and the responses are dose-related. Based on these results, it seems consequential that dietary approaches entailing removal of artificial food coloring be attempted in every child with suspected ADD, before any other form of treatment is pursued.

Does oligoantigenic diet influence hyperactive/conduct-disordered children--a controlled trial.
Schmidt MH, et al.
Eur Child Adolescent Psychiatry 1997 Jun;6(2):88-95.

This double-blind, placebo-controlled, crossover study, evaluated the impact of an oligoantigenic diet in 49 children with attention-deficit hyperactive disorder, and compared the effects of diet with those obtained by treatment with Ritalin. Twenty-four percent of children responded to diet, and 44% responded to Ritalin. Both treatments yielded the same amount of positive changes. This study indicates that the benefits of a dietary treatment equal those of a regimen based on psychotropic drugs in 1 out of 4 children diagnosed with hyperactive/disruptive disorder. In addition, these results indicate that psychotropic drugs improve behavior in less than half of treated children. The authors conclude that a dietary approach cannot be neglected as potentially effective treatment for this condition.

Synthetic food colourings and 'hyperactivity': a double-blind crossover study.
Rowe KS.
Aust Paediatr J 1988 Apr;24(2):143-7.

The results of this study show that artificial food colors induce behavioral changes typical of attention-deficit hyperactive disorder (ADHD) in susceptible children. Fifty-five children with suspected ADHD were put on the Feingold diet for a 6-week period. Approximately three-quarters of them exhibited significant behavior improvements, which lasted for 3-6 months after discontinuation of the diet. In 14 of these children hyperactive symptoms seemed to be triggered by artificial food coloring.

Effect of artificial food colors on childhood behavior.
Pollock I, Warner JO.
Arch Dis Child 1990 Jan;65(1):74-7.

The results of this study show that artificial food coloring adversely affect behavior in susceptible children. The double-blind, placebo-controlled study was conducted on 19 of 39 children who had been reported by their parents to react to these food additives. Artificial food colors adversely affected behavior in all children.

Effects of a few food diet in attention deficit disorder.
Carter CM, et al.
Arch Dis Child 1993 Nov;69(5):564-8.

The results of this study indicate that diet is an effective treatment in some children with attention-deficit hyperactive disorder. The study was conducted on 78 children who were started on a food elimination diet for hyperactivity disorder. Behavior improved in 59 (75%) of them. In 19 of the diet-responsive children, specific foods or additives were identified that triggered an adverse response. A double-blind placebo-controlled crossover trial, showed that exposure to reactive substances was significantly associated with hyperactive behavior and with impaired psychological test performance, highlighting that diet is a common cause of hyperactive disorder in children.

Foods and additives are common causes of the attention deficit hyperactive disorder in children.
Boris M, Mandel FS.
Ann Allergy 1994 May;72(5):462-8.

The results of this study indicate that diet is a frequent cause of attention-deficit hyperactive disorder (ADHD) in children. Twenty-six children diagnosed with ADHD underwent a food elimination diet. Improved behavior was observed in 19 (73%) of them. All children reacted adversely when re-challenged with specific foods, dyes, and/or preservatives. A double-blind, placebo controlled food challenge confirmed significant behavior improvement in children randomized to receive placebo, compared to those who received the reactive food or food additive. According to the authors' own conclusions, diet may have an important causative role in the majority of children diagnosed with ADHD.

The role of diet and behavior in childhood.
Breakey J.
J Paediatr Child Health 1997 Jun;33(3):190-4.

This article reviewed the results of the most important research published in 1985-1995, on the relationship between diet and behavior in children. Particular emphasis was placed on double-blind, placebo controlled studies. A definite connection between diet and behavior was found in some children. A wide range of foods and foods additives were found to adversely affect behavior, and the symptoms triggered were typical of those of attention-deficit disorder, attention-deficit hyperactive disorder, sleep disturbances and mood swings.

Relative effects of drugs and diet on hyperactive behaviors: an experimental study.
Williams JI, Cram DM, Tausig FT, Webster E.
Pediatrics 1978 Jun;61(6):811-7.

The results of this study show that food additives adversely affect behavior in a significant number of children. Of 26 children with hyperactivity disorder who were challenged with synthetic food colorings, 7 were no longer hyperactive when the food additives were removed. According to the authors, these results are in support of Feingold's hypothesis that additives present in foods trigger hyperactive behavior in susceptible children.