Attention deficit hyperactivity disorder management options are evidence-based practices with established treatment efficacy for ADHD.
The American Academy of Pediatrics (AAP) recommends different treatment paradigms depending on the age of the person being treated. For those aged 4–5, the AAP recommends evidence-based parent- and/or teacher-administered behavioral interventions as first-line treatment, with the addition of methylphenidate if there is continuing moderate-to-severe functional disturbances. For those aged 6–11, the use of medication in combination with behavioral therapy is recommended, with the evidence for stimulant medications being stronger than that for other classes. For adolescents aged 12–17, use of medication along with psychosocial interventions are recommended. [1] Clinical picture of ADHD can be corrected if rehabilitation interventions are started from the early preschool age, when the compensatory capabilities of the brain are great and a persistent pathological stereotype has not yet formed. If symptoms persist at a later age, as the child grows, defects in the development of higher brain functions and behavioral problems worsen, which subsequently lead to difficulties in schooling. [2]
There are a number of stimulant and non-stimulant medications indicated for the treatment of ADHD. The most commonly used stimulant medications include methylphenidate (Ritalin, Concerta), dexmethylphenidate (Focalin, Focalin XR), Serdexmethylphenidate/dexmethylphenidate (Azstarys), mixed amphetamine salts (Adderall, Mydayis), dextroamphetamine (Dexedrine, ProCentra), methamphetamine (Desoxyn), and lisdexamfetamine (Vyvanse). Non-stimulant medications with a specific indication for ADHD include atomoxetine (Strattera), viloxazine (Qelbree), guanfacine (Intuniv), and clonidine (Kapvay). Other medicines which may be prescribed off-label include bupropion (Wellbutrin), tricyclic antidepressants, SNRIs, or MAOIs. [3] [4] [5] The presence of comorbid (co-occurring) disorders can make finding the right treatment and diagnosis much more complicated, costly, and time-consuming. So it is recommended to assess and simultaneously treat any comorbid disorders. [6]
A variety of psychotherapeutic and behavior modification approaches to managing ADHD including psychotherapy and working memory training may be used. Improving the surrounding home and school environment with parent management training and classroom management can improve behavior and school performance of children with ADHD. [7] [8] Specialized ADHD coaches provide services and strategies to improve functioning, like time management or organizational suggestions. [9] Self-control training programs have been shown to have limited effectiveness.[ citation needed ]
There are a variety of psychotherapeutic approaches employed by psychologists and psychiatrists; the one used depends on the patient and the patient's symptoms. The approaches include psychotherapy, cognitive-behavior therapy, support groups, parent training, meditation, and social skills training. In a 2019 review the effectiveness of social skills training was evaluated in children aged 5 to 18 years. At the time there was little evidence to support or refute this type of training for the treatment of ADHD in this age group. [10]
Improving the surrounding home and school environment can improve the behavior of children with ADHD. [7] Parents of children with ADHD often show similar deficits themselves, and thus may not be able to sufficiently help the child with his or her difficulties. [11] Improving the parents' understanding of the child's behavior and teaching them strategies to improve functioning and communication and discourage unwanted behavior has measurable effect on the children with ADHD. [7] The different educational interventions for the parents are jointly called Parent Management Training. Techniques include operant conditioning: a consistent application of rewards for meeting goals and good behavior (positive reinforcement) and punishments such as time-outs or revocation of privileges for failing to meet goals or poor behavior. [7] Classroom management is similar to parent management training; educators learn about ADHD and techniques to improve behavior applied to a classroom setting. Strategies utilized include increased structuring of classroom activities, [12] daily feedback, and token economy. [7] In order for Token Economy to benefit students with ADHD, all staff must be consistent in rewarding the same behaviors. Additionally, establishing classroom routines will help to ensure that students with ADHD remain focused throughout the day. [13]
A 2013 paper published by two researchers from the University of Oslo concluded that working memory training provides short term improvements, but that there was limited evidence that these improvements were sustained or that they were generalized to improved verbal ability, mathematical skills, attention, or word decoding. [14] A 2014 paper published by a group of researchers from the University of Southampton presented the result of meta analysis study of 14 recently published randomized controlled trials (RCTs). The authors concluded that "more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms". [15]
Stimulants are the most commonly prescribed medications for ADHD. The stimulant medications indicated to treat ADHD are methylphenidate (Ritalin, Concerta), dexmethylphenidate (Focalin, Focalin XR), Serdexmethylphenidate/dexmethylphenidate (Azstarys), mixed amphetamine salts (Adderall, Mydayis), [16] dextroamphetamine (Dexedrine), lisdexamfetamine (Vyvanse), [17] and in rare cases methamphetamine (Desoxyn). [18] Controlled-release pharmaceuticals may allow once daily administration of medication in the morning. This is especially helpful for children who do not like taking their medication in the middle of the school day. Several controlled-release methods are used. [19] [20]
Stimulants used to treat ADHD raise the extracellular concentrations of the neurotransmitters dopamine and norepinephrine, which increases cellular communication between neurons that utilize these compounds. Stimulants increase the availability of synaptic dopamine, reduce the overactivity, impulsivity, and inattention characteristics of patients with ADHD, and improve associated behaviors, including on-task behavior, academic performance, and social functioning. [21]
The therapeutic benefits are due to noradrenergic effects at the locus coeruleus and the prefrontal cortex and dopaminergic effects at the ventral tegmental area, nucleus accumbens, and prefrontal cortex. [22] [23]
Stimulant medications are considered safe when used under medical supervision. [7] Nonetheless, there are concerns that the long term safety of these drugs has not been adequately documented, [24] [25] [26] [27] as well as social and ethical issues regarding their use and dispensation. The U.S. FDA has added black-box warnings to some ADHD medications, warning that abuse can lead to psychotic episodes, psychological dependence, and that severe depression may occur during withdrawal from abusive use. [28] Stimulants may be a little harder to be prescribed because they are controlled substances and can be abused easily, an example of this would be Adderall. Studies consistently show that most students report using stimulant medications, legally or illegally to improve academic performance, specifically to increase concentration, organization, and the ability to stay up longer and study. [29] The abuse of this drug has made prescribing it much more meticulous.
Stimulants are some of the most effective medications available for the treatment of ADHD. [30] Seven different formulations of stimulants have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD: four amphetamine-based formulations, two methylphenidate-based formulations, and dextromethamphetamine hydrochloride. Atomoxetine, viloxazine, guanfacine, and clonidine are the only non-controlled, non-stimulant FDA approved drugs for the treatment of ADHD.[ citation needed ]
Short-term clinical trials have shown medications to be effective for treating ADHD, but the trials usually use exclusion criteria, meaning knowledge of medications for ADHD is based on a small subset of the typical patients seen in clinical practice. [31] They have not been found to improve school performance and data is lacking on long-term effectiveness and the severity of side effects. Stimulants, however, may reduce the risk of unintentional injuries in children with ADHD. [32] [33]
This class of medicines is generally regarded as one unit; however, they affect the brain differently. [34] Some investigations are dedicated to finding the similarities of children who respond to a specific medicine. [34] The behavioral response to stimulants in children is similar regardless of whether they have ADHD or not. [35]
Stimulant medication is an effective treatment [36] for adult attention-deficit hyperactivity disorder [37] [38] although the response rate may be lower for adults than children. [39] Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants [40] although antidepressants have much lower treatment effect sizes than stimulant medication. [41]
Brand name | United States Adopted Name | (D:L) ratio | Dosage form | Marketing start date | Sources |
---|---|---|---|---|---|
Adderall | Mixed Salts of a Single-Entity Amphetamine Product | 3:1 (salts) | tablet | 1996 | [42] [43] |
Adderall XR | 3:1 (salts) | capsule | 2001 | [42] [43] | |
Mydayis | 3:1 (salts) | capsule | 2017 | [44] | |
Adzenys XR | amphetamine | 3:1 (base) | ODT | 2016 | [45] [46] |
Dyanavel XR | 3.2:1 (base) | suspension | 2015 | [47] [48] | |
Evekeo | amphetamine sulfate | 1:1 (salts) | tablet | 2012 | [49] [50] |
Dexedrine | dextroamphetamine sulfate | 1:0 (salts) | capsule | 1976 | [42] [43] |
ProCentra | 1:0 (salts) | liquid | 2010 | [43] | |
Zenzedi | 1:0 (salts) | tablet | 2013 | [43] | |
Vyvanse | lisdexamfetamine dimesylate | 1:0 (prodrug) | capsule | 2007 | [42] [51] |
tablet | |||||
Xelstrym | dextroamphetamine | 1:0 (base) | patch | 2022 | [52] |
Amphetamine is a chiral compound which is composed of two isomers: levoamphetamine and dextroamphetamine. Levoamphetamine and dextroamphetamine have the same chemical formula but are mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. This mirror difference is enough to produce a small difference in their pharmacological properties; levoamphetamine has a slightly longer half-life than dextroamphetamine, but dextroamphetamine is a more potent central nervous system stimulant. Although it is effective in reducing primary ADHD symptoms such as hyperactivity and inattention, multiple adverse side effects presented. Included in these were headaches, anxiety, nausea and insomnia. [53]
Five different amphetamine-based pharmaceuticals are currently used in ADHD treatment: racemic amphetamine, dextroamphetamine, lisdexamfetamine, and two mixed enantiomer products (Adderall and Dyanavel XR). [42] [47] [49] Lisdexamfetamine is an inactive prodrug of dextroamphetamine (i.e., lisdexamfetamine itself does not do anything in the body, but it metabolizes into dextroamphetamine). [42] Adderall is a proprietary mixture of (75%) dextroamphetamine and (25%) levoamphetamine salts, which results in very mild differences between their effects. [42] Dyanavel XR contains a similar mixture. [47] Adderall begins to work before dextroamphetamine because of levoamphetamine. [54] Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. Some children with ADHD and comorbid disorders respond well to levoamphetamine. [34] Amphetamines are modestly more effective than methylphenidate but also potentiate more side effects. [55] [56] [57]
The body metabolizes methamphetamine into amphetamine (in addition to less active metabolites). A quarter of methamphetamine will ultimately become amphetamine. [58] After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant. [59]
Brand name(s) | Generic name(s) [lower-alpha 1] | Duration | Dosage form |
---|---|---|---|
Ritalin | methylphenidate | 3–4 hours [64] | tablet |
Focalin (US) | dexmethylphenidate (US) [lower-alpha 2] | 3–4 hours [64] | tablet |
Aptensio XR (US); Biphentin (CA) | Currently unavailable | 12 hours [lower-alpha 3] | XR capsule |
Concerta (US/CA); Concerta XL (UK) | methylphenidate ER (US/CA); [lower-alpha 4] methylphenidate ER‑C (CA) [lower-alpha 5] | 12 hours [67] | OROS tablet |
Focalin XR (US) | dexmethylphenidate XR (US) [lower-alpha 6] | 12 hours [64] | XR capsule |
Quillivant XR (US) | Currently unavailable | 12 hours [67] | oral suspension |
Daytrana (US) | Currently unavailable | 11 hours [68] | transdermal patch |
Metadate CD (US); Equasym XL (UK) | methylphenidate ER (US) [lower-alpha 7] | 8–10 hours [67] | CD/XL capsule |
QuilliChew ER (US) | Currently unavailable | 8 hours [69] | chewable tablet |
Ritalin LA (US); Medikinet XL (UK) | methylphenidate ER (US) [lower-alpha 8] | 8 hours [67] | ER capsule |
Azstarys | serdexmethylphenidate /dexmethylphenidate | 13 hours [70] | ER capsule |
Ritalin SR (US/CA/UK); Rubifen SR (NZ) | Metadate ER (US); [lower-alpha 9] Methylin ER (US); [lower-alpha 10] methylphenidate SR (US/CA) [lower-alpha 11] | 5–8 hours [67] | CR tablet |
|
Like amphetamine, methylphenidate (MPH) is a chiral compound which is composed of two isomers: d-threo-methylphenidate (also known as dexmethylphenidate, d-methylphenidate, or d-MPH) and l-threo-methylphenidate (also known as l-methylphenidate or l-MPH). Both isomers have the same chemical formula but are mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. Unlike amphetamine, the difference in pharmacological properties between d-MPH and l-MPH is significant, as l-MPH is markedly inferior to d-MPH in its effects, which is due to a number of major differences between the isomers. [71] [72]
The effectiveness of methylphenidate is comparable to atomoxetine [73] [74] [75] [76] but modestly lower than amphetamines. [55] [56] [57]
There are two major medications derived from methylphenidate's isomers: a racemic mixture of half d-threo-methylphenidate and half l-threo-methylphenidate called methylphenidate (Ritalin, Concerta), and an enantiopure formulation containing just d-threo-methylphenidate called dexmethylphenidate (Focalin).[ citation needed ]
Atomoxetine, [77] viloxazine, guanfacine, and clonidine are drugs approved for the treatment of ADHD that have been classified as "non-stimulant".
Some medications used to treat ADHD are prescribed off-label, [90] outside the scope of their US government approved indications for various reasons. The U.S. FDA requires two clinical trials to prove a potential drug's safety and efficacy in treating ADHD. The drugs below have not been through these tests, so the efficacy is unproven (however these drugs have been licensed for other indications, so have been proven to be safe in those populations) and proper dosage and usage instructions are not as well characterized.[ citation needed ]
Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants (TCAs), SNRIs, SSRIs, or MAOIs. [4] [5] [3]
Atypical antipsychotic medications, which are approved for the treatment of certain behavioral disorders, are sometimes prescribed off-label as a combination therapy with stimulants for the treatment of comorbid (i.e., co-occurring diseases) ADHD and disruptive behavioral disorders. [101] [102] Canadian clinical practice guidelines only support the use of dopaminergic antipsychotics with selectivity for D2-type dopamine receptors, particularly risperidone, as a third-line treatment for both disorders following the failure of stimulant monotherapy and psychosocial interventions. [101] [103] Combined use of D2-type receptor antagonists and ADHD stimulants for the treatment of ADHD with comorbid behavioral disorders does not appear to have significantly worse adverse effects than ADHD stimulant or antipsychotic monotherapy. [101] [104] Research suggests, but has not yet confirmed, the treatment efficacy of antipsychotic and stimulant combination treatment for both disorders; [101] it is unclear if the combination therapy for both disorders is superior to stimulant or antipsychotic monotherapy. [101] There is no evidence to support the use of any subclass of antipsychotics for the treatment of the core symptoms of ADHD (i.e., inattention and hyperactivity) without comorbid behavioral disorders. [105]
Dopaminergic antipsychotics affect dopamine neurons by binding to postsynaptic dopamine receptors, where they function as receptor antagonists. [104] In contrast, ADHD stimulants are indirect agonists of postsynaptic dopamine receptors; [104] in other words, these stimulants increase levels of synaptic dopamine, which then binds to postsynaptic receptors. [104] Stimulants increase the concentration of synaptic dopamine by activating certain presynaptic receptors (i.e., TAAR1) or by blocking or altering the function of reuptake transporters (e.g., DAT, VMAT2) in the presynaptic neuron.[ citation needed ]
Generic Name (INN) | Brand Name(s) | TGA-indicated for ADHD? | MHRA-labelled for ADHD? | FDA-labelled for ADHD? | Pharmacological class [106] | Level of support | Efficacy and miscellany [lower-alpha 1] | ||
---|---|---|---|---|---|---|---|---|---|
Central nervous system stimulants | |||||||||
Classical | |||||||||
Amphetamine (racemic) | Evekeo [49] [50] | Not available | Not available | Children ≥3 years & adults | Monoamine reuptake inhibitor & releasing agent | Approved | Highly efficacious; modestly more than methylphenidate [111] [112] [113] [114] with rapid onset of action. 1:1 mix of d-amp & l-amp. | ||
Adderall [lower-alpha 2] | Adderall [115] | Not available | Not available | Children ≥3 years & adults | Monoamine reuptake inhibitor & releasing agent | Approved | Highly efficacious, [116] [117] therapeutic effects are usually seen within an hour of oral administration. 3:1 mix of d-amp and l-amp. | ||
Dexamfetamine | Dexedrine, Dexrostat | Children ≥3 years & adults | Children ≥6 years & adults | Children ≥3 years & adults | Monoamine reuptake inhibitor & releasing agent | Approved | Highly efficacious, [116] [117] therapeutic effects are usually seen within 1–1.5 hours of oral administration. | ||
Lisdexamfetamine | Vyvanse, Elvanse [118] | Children ≥6 years & adults | Children ≥6 years & adults | Children ≥6 years & adults | Monoamine reuptake inhibitor & releasing agent | Approved | Highly efficacious, [116] therapeutic effects are usually seen within 1–3 hours of oral administration. This is a prodrug formulation of d-amp. | ||
Methamphetamine | Desoxyn [119] | Not available | Not available | Children ≥6 years & adults | Monoamine reuptake inhibitor & releasing agent | Approved | Highly efficacious, therapeutic effects are usually seen within an hour of oral administration. | ||
Methylphenidate | Ritalin, Concerta [120] | Children ≥6 years & adults | Children ≥6 years & adults | Children ≥6 years & adults | NDRI | Approved | Highly efficacious, [117] comparable to atomoxetine [121] [122] [123] [124] but modestly lower than amphetamines. [125] [126] [127] Therapeutic effects are usually seen within 0.5–1.5 hours of oral administration (depending on formulation). | ||
Dexmethylphenidate | Focalin [128] | Not available | Not available | Children ≥6 years & adults | NDRI | Approved | Highly efficacious, [117] therapeutic effects are usually seen within 0.5–1.5 hours of oral administration (depending on formulation). No significant advantages over methylphenidate at equipotent dosages. | ||
Non-classical | |||||||||
Atomoxetine | Strattera [129] | Children ≥6 years & adults | Children ≥6 years & adults | Children ≥6 years & adults | NRI | Approved | Highly efficacious; comparable to methylphenidate in children and adolescents and equivalent in adults. [130] [131] [132] [133] It yields a slower onset of action (usually takes at least a couple weeks) but has a lower risk of abuse and dependence than stimulants. | ||
Modafinil | Provigil, Modavigil [134] | No | No | No | Dopamine reuptake inhibitor | Low | Rapid onset of action (several hours). Level of support enough to potentially gain approval for pediatric ADHD, however the FDA rejected approval due to concerns over serious skin reactions. [98] Poorly evaluated for adult ADHD as most published research trials focus on pediatric ADHD. [98] | ||
α2 adrenoceptor agonists | |||||||||
Clonidine | Catapres, Dixarit, Kapvay [135] | No | No | Children ≥6 years | α2 adrenoceptor agonist | Approved | Delayed onset of action (1 week). Insufficient data to judge its relative efficacy. Only the more sedating, immediate-release formulations are available in some countries, including Australia. [136] | ||
Guanfacine | Intuniv, Tenex [137] | Children 6 to 17 years | Children ≥6 years | Children ≥6 years | α2 adrenoceptor agonist | Approved | Delayed onset of action (1 week). May be slightly less efficacious than stimulant medications. [116] Not available in many countries. | ||
Antidepressants/Anxiolytics | |||||||||
Amitriptyline | Elavil, Endep [138] | No | No | No | Tricyclic | Low [139] | Delayed onset of action. | ||
Bupropion | Wellbutrin [140] | No | No | No | NDRI & nAChR antagonist | High [141] | Delayed onset of action. Is slightly-modestly less efficacious than methylphenidate and atomoxetine. [142] | ||
Buspirone | Buspar [143] | Not available | No | No | 5-HT1A partial agonist | Low [lower-alpha 3] | Delayed onset of action. Being a 5-HT1A receptor partial agonist may afford it the ability to increase dopamine release in the prefrontal cortex. [148] [149] | ||
Clomipramine | Anafranil | No | No | No | Tricyclic | Low [150] | Delayed onset of action. | ||
Desipramine | Norpramin [151] | Not available | No | No | Tricyclic | Moderate [152] | Delayed onset of action. | ||
Duloxetine | Cymbalta [153] | No | No | No | SNRI | Moderate [154] | Delayed onset of action. | ||
Imipramine | Tofranil [155] | No | No | No | Tricyclic | Low [156] | Delayed onset of action. | ||
Milnacipran | Savella, Ixel [157] | No | No | No | SNRI | Negligible [158] | Delayed onset of action. | ||
Moclobemide | Aurorix | No | No | Not available | Reversible MAO-A inhibitor | Low [159] | Delayed onset of action. | ||
Nortriptyline | Pamelor, Allegron [160] | No | No | No | Tricyclic | Low [lower-alpha 4] | Delayed onset of action. | ||
Reboxetine | Edronax | No | No | Not available | Norepinephrine reuptake inhibitor | Low [163] | Delayed onset of action. | ||
Selegiline | Emsam | No | No | No | Monoamine oxidase inhibitor | Low [164] | Delayed onset of action. | ||
Venlafaxine | Effexor [165] | No | No | No | SNRI | Moderate [166] | Delayed onset of action. | ||
Miscellaneous others | |||||||||
Amantadine | Endantadine, Symmetrel [167] | No | No | No | NMDA antagonist and dopamine agonist | Low [168] | ? | ||
Carbamazepine | Equetro, Tegretol [169] | No | No | No | Sodium channel blocker | Moderate [170] | Use in ADHD is generally considered clinically inadvisable. [171] | ||
Memantine | Namenda [172] | No | No | No | NMDA antagonist | Low [173] | ? | ||
Levels of support
| |||||||||
Notes |
Some parents and professionals have raised questions about the side effects of drugs and their long-term use. [90]
Outpatient treatment rates held steady in the U.S. from the late 1990s to early 2000s. Prior to this, outpatient treatment for ADHD in the U.S. grew from 0.9 children per 100 in 1987 to 3.4 per 100 in 1997. [174] A survey conducted by the Centers for Disease Control and Prevention in 2011–2012 found 11% of children between the ages of 4 and 17 were reported to have ever received a health care provider diagnosis of ADHD at some point (15% of boys and 7% of girls), [175] a 16% increase since 2007 and a 41% increase over the last decade. [176] The CDC notes that community samples suggest the incidence of ADHD in American children is higher than the five percent stated by the American Psychiatric Association in DSM-5, with 8.8% of U.S. children having a current diagnosis in the 2011 survey. [176] [177] However, only 6.1% of children in the 2011 survey were taking ADHD medication, suggesting as many as 17.5% of children with current ADHD were not receiving treatment. [176]
Parents of children with ADHD note that they usually display their symptoms at an early age. There have been few longitudinal studies on the long-term effects of stimulant use in children. [178] The use of stimulant medication has not been approved by the FDA for children under the age of six. [179] A growing trend is the diagnosis of younger children with ADHD. Prescriptions for children under the age of 5 rose nearly 50 percent from 2000 to 2003. [180] [181] Research on this issue has indicated that stimulant medication can help younger children with "severe ADHD symptoms" but typically at a lower dose than older children. It was also found that children at this age are more sensitive to side effects and should be closely monitored. [179] Evidence suggests that careful assessment and highly individualized behavioural interventions significantly improve both social and academic skills, [182] while medication only treats the symptoms of the disorder. "One of the primary reasons cited for the growing use of psychotropic interventions was that many physicians realize that psychological interventions are costly and difficult to sustain." [183]
Central nervous system stimulants such as lisdexamfetamine may be associated with occurrences of constipation, diarrhea, nausea, and stomach pain. [184]
There is some evidence of mild reductions in growth rate with prolonged stimulant treatment in children, but no causal relationship has been established and reductions do not appear to persist long-term. [185] Weight loss almost always corresponds with loss of appetite, which may result from the medication. Severe weight loss is very uncommon though. Loss of appetite is very temporary and typically comes back as daily effects of stimulants wear off. Nausea, dizziness, and headaches, other side effect, can also indirectly affect appetite and result in weight loss. [186]
There is concern that stimulants and atomoxetine, which increase the heart rate and blood pressure, might cause serious cardiovascular problems. [187] [188] Recent extremely large-scale studies by the FDA indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, myocardial infarction, and stroke) and the medical use of amphetamine, methylphenidate, or other ADHD stimulants. [189] [190] [191] [192]
Many of these drugs are associated with physical and psychological dependence. [193] [ page needed ] Sleep problems may occur. [194]
Methylphenidate can worsen psychosis in psychotic patients, and in very rare cases it has been associated with the emergence of new psychotic symptoms. [195] It should be used with extreme caution in patients with bipolar disorder due to the potential induction of mania or hypomania. [196] There have been very rare reports of suicidal ideation, but evidence does not support a link. [185] The long-term effects on mental health disorders in later life of chronic use of methylphenidate is unknown. [197]
A 2009 FDA review of 49 clinical trials found that approximately 1.5% of children in clinical trials of medications for ADHD had experienced signs or symptoms of psychosis or mania. Postmarketing reports were also analyzed, with nearly half of them involving children under the age of eleven. Approximately 90% of cases had no reported previous history of similar psychiatric events. Hallucinations involving snakes, worms or insects were the most commonly reported symptoms. [198]
Long-term methylphenidate or amphetamine exposure in some species is known to produce abnormal dopamine system development or nerve damage, [199] [200] but humans experience normal development and nerve growth. [201] [202] [203] Magnetic resonance imaging studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function of the right caudate nucleus. [201] [202] [203]
Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD. [204] [205] Controlled trials spanning two years have demonstrated continuous treatment effectiveness and safety. [205] [206] One review highlighted a nine-month randomized controlled trial of amphetamine in children that found an average increase of 4.5 IQ points and continued improvements in attention, disruptive behaviors, and hyperactivity. [206]
There is some evidence that ADHD itself may protect the brain against the natural aging process later in life, [207] perhaps by exercising the brain, and helping maintain volume. It is unknown how long term medication treatment effects the trajectory of brain volume decline in the aging ADHD brain. [207]
Tolerance to the therapeutic effects of stimulants can occur, [208] and rebound of symptoms may occur when the dose wears off. [209] Rebound effects are often the result of the stimulant dosage being too high or the individual not being able to tolerate stimulant medication. Signs that the stimulant dose is too high include irritability, feeling stimulated or blunting of affect and personality. [210]
Stimulant withdrawal or rebound reactions can occur and can be minimised in intensity via a gradual tapering off of medication over a period of weeks or months. [211] A small study of abrupt withdrawal of stimulants did suggest that withdrawal reactions are not typical, and may only occur in susceptible individuals. [212]
Concerns about chromosomal aberrations and possible cancer later in life was raised by a small-scale study on the use of methylphenidate, though a review by the Food and Drug Administration (FDA) found significant methodological problems with the study. [213] A follow-up study performed with improved methodology found no evidence that methylphenidate might cause cancer, stating "the concern regarding a potential increase in the risk of developing cancer later in life after long-term MPH treatment is not supported." [214]
The first reported evidence of stimulant medication used to treat children with concentration and hyperactivity problems came in 1937. [215] Charles Bradley in Providence, Rhode Island, reported that a group of children with behavioral problems improved after being treated with the stimulant Benzedrine. [215] [216] In 1954, the stimulant methylphenidate (Ritalin, which was first produced in 1944) became available; it remains one of the most widely prescribed medications for ADHD. Initially the drug was used to treat narcolepsy, chronic fatigue, depression, and to counter the sedating effects of other medications. The drug began to be used for ADHD in the 1960s and steadily rose in use. [215]
In 1975, pemoline (Cylert) was approved by the U.S. FDA for use in the treatment of ADHD. While an effective agent for managing the symptoms, the development of liver failure in 14 cases over the next 27 years would result in the manufacturer withdrawing this medication from the market. New delivery systems for medications were invented in 1999 that eliminated the need for multiple doses across the day or taking medication at school. These new systems include pellets of medication coated with various time-release substances to permit medications to dissolve hourly across an 8–12 hour period (Metadate CD, Adderall XR, Focalin XR) and an osmotic pump that extrudes a liquid methylphenidate sludge across an 8–12 hour period after ingestion (Concerta).[ citation needed ]
In 2003, atomoxetine (Strattera) received the first FDA approval for a nonstimulant drug to be used specifically for ADHD. [217] In 2007, lisdexamfetamine (Vyvanse) became the first prodrug [218] for ADHD to receive FDA approval. [219] In March 2019, a Purdue Pharma subsidiary received approval from the FDA for Adhansia XR, a methylphenidate medication to treat ADHD. [220]
Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment. [30] In terms of cost-effectiveness, management with medication has been shown to be the most cost-effective, followed by behavioral treatment, and combined treatment. [30] The individually most effective and cost-efficient way is with stimulant medication. Additionally, long-acting medications for ADHD, in comparison to short-acting varieties, generally seem to be cost-effective. [221] Comorbid (relating to two diseases that occur together, e.g. depression and ADHD) disorders makes finding the right treatment and diagnosis much more costly than when comorbid disorders are absent.[ citation needed ]
Most alternative therapies do not have enough supporting evidence to recommend them. [222] [223] Moreover, when only the best conducted studies are taken into account results tend to be similar to placebo. [223]
Neurofeedback (NF) or EEG biofeedback is a treatment strategy used for children, adolescents and adults with ADHD. [224] The human brain emits electrical energy which is measured with electrodes. Neurofeedback alerts the patient when beta waves are present. This theory believes that those with ADHD can train themselves to decrease ADHD symptoms.[ citation needed ]
No serious adverse side effects from neurofeedback have been reported. [225] Research into neurofeedback has been mostly limited and of low quality. [225] While there is some indication on the effectiveness of biofeedback it is not conclusive: several studies have yielded positive results, however the best designed ones have either shown reduced effects or non-existing ones.[ failed verification ] [225] [226] In general no effects have been found in the most blinded ADHD measures, which could be indicating that positive results are due to the placebo effect. [227]
Preliminary studies have supported the idea that playing video games is a form of neurofeedback, which helps those with ADHD self-regulate and improve learning. [228] [229] Memory, multitasking, fluid intelligence, and other cognitive talents may be improved by certain computer programmes and video games. [230] On the other hand, ADHD may experience great difficulty disengaging from the game, which may in turn negate any benefits gained from these activities, [231] and time management skills may be negatively impacted as well. [232]
Children who spend time outdoors in natural settings, such as parks, seem to display fewer symptoms of ADHD, which has been dubbed "Green Therapy". [233] But it may be due to reverse causation.[ clarification needed ]
There is insufficient evidence to support dietary changes in ADHD and thus they are not recommended by the American Academy of Pediatrics as of 2019. [234] Perhaps the best known of the dietary alternatives is the Feingold diet which involves removing salicylates, artificial colors and flavors, and certain synthetic preservatives from children's diets. [235] However, studies have shown little if any effect of the Feingold diet on the behavior of children with ADHD. [236]
Results of studies regarding the effect of eliminating artificial food coloring from the diet of children with ADHD have been very varied. It has been found that it might be effective in some children but as the published studies have been of low quality results can be more related to research problems such as publication bias. [237] The UK Food Standards Agency (FSA) has called for a ban on the use of six artificial food colorings [238] and the European Union (EU) has ruled that some food dyes must be labeled with the relevant E number as well as this warning: "may have an adverse effect on activity and attention in children." [239] Nevertheless, existing evidence neither refutes nor supports the association between ADHD and food colouring. [240]
Dietary supplements, self-medication, [241] and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. However a 2009 article in the Harvard Mental Health Letter states, "Although vitamin or mineral supplements [micronutrients] may help children diagnosed with particular deficiencies, there is no evidence that they are helpful for all children with ADHD. Furthermore, megadoses of vitamins, which can be toxic, must be avoided." [242] In the United States, no dietary supplement has been approved for the treatment for ADHD by the FDA. [243]
Some popular supplements used to manage ADHD symptoms:
Regular physical exercise, particularly aerobic exercise, is an effective add-on treatment for ADHD in children and adults, particularly when combined with stimulant medication (although the best intensity and type of aerobic exercise for improving symptoms are not currently known). [254] [255] [256] The long-term effects of regular aerobic exercise in ADHD individuals include better behavior and motor abilities, improved executive functions (including attention, inhibitory control, and planning, among other cognitive domains), faster information processing speed, and better memory. [254] [255] [256] Parent-teacher ratings of behavioral and socio-emotional outcomes in response to regular aerobic exercise include: better overall function, reduced ADHD symptoms, better self-esteem, reduced levels of anxiety and depression, fewer somatic complaints, better academic and classroom behavior, and improved social behavior. [254] Exercising while on stimulant medication augments the effect of stimulant medication on executive function. [254] It is believed that these short-term effects of exercise are mediated by an increased abundance of synaptic dopamine and norepinephrine in the brain. [254]
Because ADHD comorbidities are diverse and the rate of comorbidity is high, special care must dedicated to certain comorbidities. The FDA is not set up to address this issue, and does not approve medications for comorbidities, nonetheless certain such topics have been extensively researched.
Patients with Tourette syndrome who are referred to specialty clinics have a high rate of comorbid ADHD. Patients who have ADHD along with tics or tic disorders may also have problems with disruptive behaviors, overall functioning, and cognitive function, accounted for by the comorbid ADHD. [257]
The treatment of ADHD in the presence of tic disorders has long been a controversial topic. Past medical practice held that stimulants could not be used in the presence of tics, due to concern that their use might worsen tics; [258] however, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders. [259] [212] Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity. [260] A 2011 Cochrane Collaboration review concluded that most major ADHD medications were effective in children with tics, and that stimulants did not generally worsen tics outside of individual cases. [261] Methylphenidate, guanfacine, clonidine, and desipramine were associated with improvement of tic symptoms. [261] Controversy remains, and the PDR continues to carry a warning that stimulants should not be used in the presence of tic disorders, so physicians may be reluctant to use them. Others are comfortable using them and even advocate for a stimulant trial when ADHD co-occurs with tics, because the symptoms of ADHD can be more impairing than tics. [258] [262]
The stimulants are the first line of treatment for ADHD, with proven efficacy, but they do fail in up to 20% of cases, even in patients without tic disorders. [263] Current prescribed stimulant medications include: methylphenidate, dextroamphetamine, and mixed amphetamine salts (Adderall). Other medications can be used when stimulants are not an option. These include the alpha-2 agonists (clonidine and guanfacine), tricyclic antidepressants (desipramine and nortriptyline), and newer antidepressants (bupropion and venlafaxine). There have been case reports of tics worsening with bupropion. There is good empirical evidence for short-term safety and efficacy for the use of desipramine, bupropion and atomoxetine. [263]
Amphetamine is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu, and then as a drug in the late 1920s. It exists as two enantiomers: levoamphetamine and dextroamphetamine. Amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by executive dysfunction occasioning symptoms of inattention, hyperactivity, impulsivity and emotional dysregulation that are excessive and pervasive, impairing in multiple contexts, and otherwise age-inappropriate.
Stimulants are a class of drugs that increase the activity of the brain and the spinal cord. They are used for various purposes, such as enhancing alertness, attention, motivation, cognition, mood, and physical performance. Some of the most common stimulants are caffeine, nicotine, amphetamines, cocaine, and modafinil.
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is a central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD ; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2–4 hours. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamines.
Dextroamphetamine (INN:dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant.
Developmental disorders comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas. There are several ways of using this term. The most narrow concept is used in the category "Specific Disorders of Psychological Development" in the ICD-10. These disorders comprise developmental language disorder, learning disorders, motor disorders, and autism spectrum disorders. In broader definitions ADHD is included, and the term used is neurodevelopmental disorders. Yet others include antisocial behavior and schizophrenia that begins in childhood and continues through life. However, these two latter conditions are not as stable as the other developmental disorders, and there is not the same evidence of a shared genetic liability.
A paradoxical reaction is an effect of a chemical substance, such as a medical drug, that is opposite to what would usually be expected. An example of a paradoxical reaction is pain caused by a pain relief medication.
Atomoxetine, sold under the brand name Strattera, is a medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndrome. It may be used alone or along with psychostimulants. It is also used as a cognitive and executive functioning enhancer to improve self-motivation, persistence, attention, inhibition, and working memory. Use of atomoxetine is only recommended for those who are at least six years old. It is taken orally. Atomoxetine is a selective norepinephrine reuptake inhibitor and is believed to work by increasing norepinephrine and dopamine levels in the brain. The effectiveness of atomoxetine is comparable to the commonly prescribed stimulant medication methylphenidate.
Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio between dextroamphetamine and levoamphetamine, the two enantiomers of amphetamine. Both enantiomers are stimulants, but differ enough to give Adderall an effects profile distinct from those of racemic amphetamine or dextroamphetamine, which are marketed as Evekeo and Dexedrine/Zenzedi, respectively. Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used illicitly as an athletic performance enhancer, cognitive enhancer, appetite suppressant, and recreationally as a euphoriant. It is a central nervous system (CNS) stimulant of the phenethylamine class.
Nootropics, colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.
Reboxetine, sold under the brand name Edronax among others, is a drug of the norepinephrine reuptake inhibitor (NRI) class, marketed as an antidepressant by Pfizer for use in the treatment of major depression, although it has also been used off-label for panic disorder and attention deficit hyperactivity disorder (ADHD). It is approved for use in many countries worldwide, but has not been approved for use in the United States. Although its effectiveness as an antidepressant has been challenged in multiple published reports, its popularity has continued to increase.
Dexmethylphenidate, sold under the brand name Focalin among others, is a potent central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years. It is taken by mouth. The immediate release formulation lasts up to five hours while the extended release formulation lasts up to twelve hours. It is the more active enantiomer of methylphenidate.
Adult Attention Deficit Hyperactivity Disorder is the persistence of attention deficit hyperactivity disorder (ADHD) in adults. It is a neurodevelopmental disorder, meaning symptoms must have been present in childhood except for when ADHD occurs after a traumatic brain injury. Specifically, multiple symptoms must be present before the age of 12, according to DSM-5 diagnostic criteria. The cutoff age of 12 is a change from the previous requirement of symptom onset, which was before the age of 7 in the DSM-IV. This was done to add flexibility in the diagnosis of adults. ADHD was previously thought to be a childhood disorder that improved with age, but recent research has disproved this. Approximately two-thirds of childhood cases of ADHD continue into adulthood, with varying degrees of symptom severity that change over time, and continue to significantly affect individuals' daily functioning in multiple domains.
Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a selective norepinephrine reuptake inhibitor medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almost 30 years as an antidepressant for the treatment of depression before being discontinued and subsequently repurposed as a treatment for ADHD. Viloxazine is taken orally. It was used as an antidepressant in an immediate-release form and is used in ADHD in an extended-release form.
Cognitive disengagement syndrome (CDS) is an attention syndrome characterised by prominent dreaminess, mental fogginess, hypoactivity, sluggishness, slow reaction time, staring frequently, inconsistent alertness, and a slow working speed. To scientists in the field, it has reached the threshold of evidence and recognition as a distinct syndrome.
Guanfacine, sold under the brand name Tenex (immediate-release) and Intuniv (extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD, as well as being used for augmentation of other treatments, such as stimulants. Guanfacine is also used off-label to treat tic disorders, anxiety disorders, and post-traumatic stress disorder (PTSD).
Attention deficit hyperactivity disorder predominantly inattentive, is one of the three presentations of attention deficit hyperactivity disorder (ADHD). In 1987–1994, there were no subtypes and thus it was not distinguished from hyperactive ADHD in the Diagnostic and Statistical Manual (DSM-III-R).
Despite the scientifically well-established nature of attention deficit hyperactivity disorder (ADHD), its diagnosis, and its treatment, each of these has been controversial since the 1970s. The controversies involve clinicians, teachers, policymakers, parents, and the media. Positions range from the view that ADHD is within the normal range of behavior to the hypothesis that ADHD is a genetic condition. Other areas of controversy include the use of stimulant medications in children, the method of diagnosis, and the possibility of overdiagnosis. In 2009, the National Institute for Health and Care Excellence, while acknowledging the controversy, stated that the current treatments and methods of diagnosis are based on the dominant view of the academic literature.
Tourette syndrome is an inherited neurodevelopmental disorder that begins in childhood or adolescence, characterized by the presence of motor and phonic tics. The management of Tourette syndrome has the goal of managing symptoms to achieve optimum functioning, rather than eliminating symptoms; not all persons with Tourette's require treatment, and there is no cure or universally effective medication. Explanation and reassurance alone are often sufficient treatment; education is an important part of any treatment plan.
Lisdexamfetamine, most commonly sold under the brand name Vyvanse and Elvanse among others, is a stimulant medication that is used to treat attention deficit hyperactivity disorder (ADHD) in children and adults and for moderate-to-severe binge eating disorder in adults. Lisdexamfetamine is taken by mouth. Its effects generally begin within two hours and last for up to 14 hours. In the United Kingdom, it is usually less preferred to methylphenidate for the treatment of children.
ADZENYS XR-ODT (amphetamine extended-release orally disintegrating tablet) contains a 3 to 1 ratio of d- to l-amphetamine, a central nervous system stimulant.
Ritalin‑SR, methylphenidate SR, Methylin ER, and Metadate ER are the same formulation and have the same drug delivery system
An alternative to Ritalin‑SR from Novartis
Conclusion: When severe disruptive or aggressive behaviour occurs with ADHD, medications for ADHD should be used first. Other medications have major adverse effects and, with the exception of risperidone, very limited evidence to support their use.
Most importantly, antipsychotics are not approved for the treatment of symptoms of ADHD and limited, if any, evidence exists to suggest their utility for the core symptoms of inattention and hyperactivity. Although, aripiprazole and risperidone are approved for irritability and aggression associated with autistic disorder (age 5 or 6–17 years), and data exist for their utility in disruptive behavior disorders and aggression, antipsychotics should be the last resort for the treatment of impulsivity, oppositionality and aggression.
Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.
Beneficial chronic effects of cardio exercise were found on various functions as well, including executive functions, attention and behavior.
We may conclude that all different types of exercise ... attenuate the characteristic symptoms of ADHD and improve social behaviour, motor skills, strength and neuropsychological parameters without any undesirable side effects. Available reports do not reveal which type, intensity, duration and frequency of exercise is most effective
The findings from these studies provide some support for the notion that exercise has the potential to act as a protective factor for ADHD.