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590 Current Pharmaceutical Design, 2016, 22, 590-594
Psychopharmacology of Attention-Deficit Hyperactivity Disorder: Effects and Side Effects
Javad Golmirzaei
1, Hamidreza Mahboobi
2,3*, Maryam Yazdanparast
2, Gohar Mushtaq
4, Mohammad A.
Kamal
5,6and Enayatollah Hamzei
71
Shahid Beheshti University of Medical Sciences, Tehran, Iran;
2Infectious and Tropical Diseases Research Cen- ter, Hormozgan University of Medical Sciences, Bandar Abbas, Iran;
3Payam Noor University (PNU), Tehran, Iran;
4Department of Biochemistry, College of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
5
King Fahd Medical Research Centre, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia;
6
Enzymoics, 7Peterlee Pl, Hebersham, NSW 2770, Australia;
7Hormozgan University of Medical Sciences, Bandar Abbas, Iran
Abstract: Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children which manifests with hyperactivity, impulsivity, and/or inattention. Several drugs are used in treatment of ADHD. Stimu- lants, atomoxetine, anti-depressants, and bupropion are common medications used in the treatment of ADHD.
Stimulants are widely used as the first line treatment in children with ADHD. Their mechanism of action is the re-
lease of dopamine and norepinephrine in central nervous system. Methylphenidate is the most common stimulant used for the treatment of ADHD. Methylphenidate significantly reduces ADHD symptoms in children both at home and school and improves their social skills.
Methylphenidate is safe in healthy children and has shown to have no cardiac side effects in these patients. Other medications include:
Atomoxetine, Amphetamines, Clonidine, Melatonin, and anti-depressants. Effects, side effects, and mechanism of action these drugs have been discussed in this paper.
Keywords: Attention-deficit hyperactivity disorder, Methylphenidate, Atomoxetine, Amphetamines.
INTRODUCTION
Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children which manifests with hyperactivity, impulsivity, and/or inattention [1]. ADHD is associated with de- cline in the cognitive, behavioral, social, and academic functions of the affected patients. ADHD patients may experience some learning difficulties which may be due to Dopamine function in the hippo- campus [2]. Although the symptoms of ADHD decrease with age, sometimes the symptoms can be seen in adults. Patients can retain their function by receiving suitable treatment. Pharmacological treatments have shown to be effective in improving the symptoms in ADHD patients. Moreover, some supplements are suggested to play an effective role in treatment of ADHD. Psychotherapy is also recommended in combination with pharmacological treatment in ADHD patients.
EPIDEMIOLOGY OF ADHD
Prevalence of ADHD is different among study reports. The prevalence of ADHD decreases with age, but it is still a common psychiatric disorder among adults and is known as adult ADHD.
One study in United Kingdom has reported the prevalence of 1.4 percent for ADHD [3]. Some studies suggested gender differences in response to ADHD treatment in ADHD patients [4].
In some countries the estimated rate of ADHD in children and adults seems to be higher than other studies worldwide. For exam- ple available studies in Iran show higher rates of ADHD in students in comparison to other countries [5]. In adult ADHD, it seems that gender, age, birth order, and socioeconomic status are not associ- ated with ADHD symptoms [5].
*Address correspondence to this author at the Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran;
E-mails: [email protected]; [email protected]
Several factors are shown to be the risk factors for ADHD.
ADHD is associated with depression in children and also parental depression [6, 7]. Other risk factors include low parental education, prenatal smoking, prenatal illicit drug use, and socioeconomic status (8]. Also, some genetic factors may be important in ADHD [9]. Anxiety disorder and oppositional disorder are among the most common ADHD co-morbidities [10].
DIAGNOSIS
Several screening tools are available for ADHD screening. The most common tools are ADHD Self-Report Scale V 1.1 and Con- ners' Adult ADHD Rating Scale-Self-Report. Several studies have shown the accuracy of these screening tools in ADHD patients [11- 14]. But these screening tools cannot replace the interview of the psychiatrists [15, 16], and these instruments cannot be used alone for diagnosis of ADHD [17], and their clinical application is limited [18]. Also, some studies suggested that they are not suitable for prediction of academic performance of the ADHD patients [19].
Due the cultural differences in the prevalence of ADHD which are not explainable by confounding factors, it seems that instruments for screening of ADHD should be prepared for each culture to in- crease the accuracy of these screening tools [20].
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria are used for diagnosis of ADHD in chil- dren and adults. There are some difficulties for diagnosis of adult ADHD and the features of the disease are less prominent in adult patients. ADHD diagnosis needs interview with the patient and parents. In adults, previous history of hyperactivity, inattention and impulsivity may be useful [21].
TREATMENT
Several drugs are used in treatment of ADHD. Stimulants, Atomoxetine, anti-depressants, and Bupropion are common medi- cations used in treatment of ADHD. The effects, side effects, and characteristics of each treatment are summarized to Table 1.
Hamidreza Mahboobi
1873-4286/16 $58.00+.00 © 2016 Bentham Science Publishers
Some non-pharmacological treatments are shown to be useful in treatment of ADHD. For example, neuro-feedback is shown to be associated with significant academic performance improvements in ADHD patients [22]. However, it seems that non-pharmacologic treatments should be used in combination to pharmacologic treat- ments for better results.
Stimulants
Stimulants are widely used as the first line treatment in children with ADHD. Their mechanism of action is release of dopamine and norepinephrine in central nervous system. They increase the atten- tion and concentration through an increase in dopamine and norepi- nephrine concentrations in the brain stem, midbrain, and frontal cortex. Stimulants are shown to be useful for improving memory and cognitive function in ADHD patients [23, 24). Effects of stimu- lants seem to be long-term and these agents are well tolerated in ADHD patients [25, 26]. Short acting stimulants may have better results in comparison to long-acting stimulants [27]. Stimulants are not useful for reducing the risk of substance abuse in ADHD pa- tients [28].
Methylphenidate is the most common stimulant used for treat- ment of ADHD [29, 30]. Short-acting methylphenidate is preferred in comparison to long acting methylphenidate [31]. Methylpheni- date significantly reduces ADHD symptoms in children both at home and school and improves their social skills [32]. Methylphe- nidate significantly improves hyperactivity symptoms [33] and increases the children performance in patients with ADHD with or without comorbid learning disability [34], and increases the cogni- tive and school performance in ADHD children [35, 36].
Methylphenidate acts by increasing the activation of frontal lobes, basal ganglia, and cerebellum in ADHD children [37]. Some studies suggest that methylphenidate increases cell proliferation and differentiation in dentate gyrus via increase in brain-derived neu- rotrophic factor level [38]. Some genetic variations have been shown to be effective in response to treatment with methylpheni- date [39].
In ADHD children, treatment with prolonged release methyl- phenidate changes the daily fluctuations in serotonin and melatonin concentration levels. This treatment improves the depression symp-
toms in these patients which is not related to the increase in morn- ing serotonin level [40]. Also in adults with ADHD methylpheni- date is useful for smoking reduction and quit attempts by prevent- ing weight gain [41].
Methylphenidate is safe in healthy children and has shown to have no cardiac side effects in these patients [42] and improves heart rate variability in children with ADHD [43, 44]. Stimulants seem to have no acute effects on the interaction between teenagers and their parents [45]. Sleep disorders are common side effect of methylphenidate [46].
Atomoxetine
Another type of available treatment for ADHD which is a selec- tive norepinephrine inhibitor is Atomoxetine [47]. Several studies have shown the effectiveness of atomoxetine in treatment of ADHD [48-52]. Atomoxetine can be used as an alternative for methylphe- nidate for treatment of ADHD, but usage of Atomoxetine is limited for its side effects including irritability, nausea, decreased appetite, and fatigue [48].
Amphetamines
Amphetamines are other medications used in treatment of ADHD. Their usefulness in treatment of the symptoms of ADHD is shown in several studies [53, 54]. Their use in adults is also benefi- cial [55, 56]. Even some researchers reported higher efficacy for amphetamines in comparison to methylphenidate products [57].
Side effects include: decreased appetite, nausea, abdominal pain, irritability, and insomnia [58].
Clonidine
Clonidine is another medication used for treatment of ADHD, but studies about its effectiveness are not enough and its use should be limited to combination therapy with other first line treatments of ADHD [59-61]. It has been shown that in adolescents and children with partial response to stimulants, adding clonidine extended- release tablets can significantly reduce ADHD symptoms in these patients [60]. Also, as an alternative treatment, clonidine is shown to be a safe and effective treatment for reducing hyperactivity and impulsivity symptoms in ADHD patients [61].
Table 1. Medications used for treatment of attention-deficit hyperactivity disorder (ADHD).
Medications used for treatment of ADHD
Methylphenidate • First line treatment of ADHD
• Significantly improves hyperactivity symptoms
• Increases the cognitive and school performance
• Methylphenidate is safe in healthy children
Atomoxetine • Selective norepinephrine inhibitor
• Alternative for methylphenidate for treatment of ADHD
• Side effects include: irritability, nausea, decreased appetite, and fatigue
Amphetamines • Some researchers reported higher efficacy for amphetamines in comparison to methylphenidate
• Side effects include: decreased appetite, nausea, abdominal pain, irritability, and insomnia Clonidine • Combination therapy with other first line treatments of ADHD
Melatonin • Combination with methylphenidate in order to increase sleeping time and decrease the adverse ef- fects of stimulant on sleep pattern and for improving height and weight growth in children Anti-depressants • Combination therapy with first line treatment
Bupropion • Its use is limited to situations that first line treatments for ADHD are contraindicated
Melatonin
Melatonin can be used in combination with methylphenidate in order to increase sleeping time and decrease the adverse effects of stimulant on sleep pattern and for improving height and weight growth in children [62-64]. Melatonin is recommended by some authors for treatment of insomnia in ADHD patients which may be effective in improving their daily function [62]. In children with ADHD, combination therapy of melatonin and stimulants is associ- ated with increased duration of sleep, and improved height and weight which may be through increased growth hormone release [63]. Some researchers confirmed long-term safety of melatonin in the treatment of ADHD [64].
Anti-Depressants
Although antidepressants may have benefits as combination therapy with first line treatment in ADHD, but their use is limited because of inadequate evidences for their efficacy and concerns about their safety [65, 66]. Venlafaxine has been shown to be effec- tive and safe in short-term treatment of ADHD in children and ado- lescents, but its long-term efficacy and safety remains unclear and more randomized clinical trials are needed in this regard [65].
Bupropion
Bupropion is shown to be effective in treatment of ADHD, but its use is limited to situations that first line treatments for ADHD are contraindicated [27, 67]. Results of an open trial have shown that sustained-release bupropion is associated with reduction of ADHD symptoms in adults with ADHD and substance use disorder [67].
CONCLUSION
In summary, methylphenidate is the drug of choice in the treat- ment of ADHD in children. Other medications used for treatment of ADHD in children are less effective and their use is limited to situa- tions where the patients have contraindications for using methyl- phenidate or when the physician decides to add combination ther- apy to methylphenidate.
Although current studies have shown that methylphenidate is the first line treatment in adult ADHD, its effectiveness is lower in comparison to its effects on children. Moreover, some cardiac side effects have limited its use in adults. Bupropion seems to be an effective alternative in patients with contraindications for methyl- phenidate.
Supplementary treatments, micronutrients, and non-pharma- cological treatments seem to be effective in treatment of ADHD.
However, their use is limited to combination therapy with first line medications of ADHD and their single use is not adequate for treatment of ADHD symptoms.
ADHD = Attention-deficit hyperactivity disorder
CONFLICT OF INTEREST
The authors confirm that this article content has no conflict of interest.
AKNOWLEDGEMENTS
The authors from Hormozgan University of Medical Sciences want to thank their directors for help and support. GM and MAK acknowledge [Department of Biochemistry, College of Science and KFMRC respectively], KAU, KSA.
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