Attention-deficit/hyperactivity disorder (ADHD) is a fairly common disorder characterized by inattention, impulsivity and/or hyperactivity. It is estimated to affect 5-15% of school-aged children. There are three major subtypes: predominantly inattentive (pI), predominantly hyperactive-impulsive (pHI) and combined (C). The predominantly inattentive subtype is sometimes just called attention-deficit disorder (ADD). ADHD is usually treated with medications along with behavioural and education interventions. It is believed to be caused by reduced dopamine and noradrenergic activity in the prefrontal cortex (PFC), along with other brain abnormalities.
For psychiatric disorders there are two major diagnostic manuals: the DSM-5 and ICD-10. ADHD is a term used in the DSM-5, but not the ICD-10. The ICD-10 instead describes a condition called hyperkinetic disorder which is believed to be a more severe form of the disorder with combined features and affects significantly fewer children.:26
Signs and symptomsEdit
Either one of two features (or both features) are required: inattentive and/or hyperactivity/impulsive features. Inattentive features must persist for at least 6 months, must adversely affect education or work activities and include at least six of the following features:
- Fails to give adequately close attention to details, or makes careless mistakes.
- Has a short attention span (e.g., making it difficult to remain focused in class)
- Being often seems distracted when spoken to directly, without an obvious cause.
- Being often does not follow through on instructions and fails to complete tasks. For example they might forget to complete an assignment.
- Disorganized work; leading to failing to meet deadlines, poor time management, keeping things in order, etc.
- Avoids, dislikes or is reluctant to perform tasks that require sustained attention, like paperwork, reading long pages, school work or homework, etc.
- Looses things required for day-to-day talks like glasses, mobile phones, paperwork, wallets, etc.
- Easily distracted
- Being often forgetful in daily activities like paying bills, doing chores, etc.
Hyperactive and impulsive features which includes (at least six of these features are required):
- Excessive talking
- Completes people's sentences or interrupts people while talking.
- Restlessness manifesting, in children, as running around, or climbing inappropriately; in adolescents and adults it may be limited to feeling restless.
- Leaving one's seat even when it is inappropriate
- Unable to perform leisure activities quietly.
- Being constantly, "On the go"
- Being unable to wait in line
- Often invades or interrupts others; for example they may butt into conversations, force themselves into games others are playing, they may start using an item without the owner's permission, etc.
- Family history of ADHD
- Maternal (that is by the biological mother) smoking, alcohol consumption or the use of heroin during pregnancy
- Exposure to lead and other poisonous chemicals
- Fetal oxygen deprivation during pregnancy
- Very low birth weight
- Zinc deficiency
There are three major treatments: psychosocial interventions (like the talking approach, which can also involve the affected person's family or school interventions to help the affected person do well at school), dietary changes and medications. Psychosocial interventions are usually preferred in mild-moderate cases or in younger patients (that is children and adolescents). Medications are usually only used in severe cases, or where the affected person has a moderate case and refuses to/cannot participate in psychosocial inventions or where these interventions have been trialled and failed.
Medications include stimulants, atomoxetine, antidepressants (although these agents are all off-label), alpha-2 adrenoceptor agonists and assorted others. All have advantages and disadvantages, sadly 30% of patients will fail to respond to stimulants.
Stimulants are generally regarded as the most effective drug treatments for ADHD, they include: dexamfetamine (dexamphetamine or dextroamphetamine; brand names: Dexedrine, Dextrostat and generics), dexmethylphenidate (brand name: Focalin), lisdexamfetamine (brand name: Elvanse, Vyvanse), metamfetamine (brand name: Desoxyn; only available in the U.S.A.; it is the most addictive of stimulants used in the treatment of ADHD), methylphenidate (brand names: Concerta, Equasym, Medikinet, Ritalin) and mixed amfetamine salts (brand name: Adderall). They are all characterized by a rapid onset of action (within an hour usually), potential for abuse and addiction, similar side effect profiles, that often include:
- Weight loss/growth stunting
- Stomach pains
- Dry mouth
- Heart attacks
- Blood pressure changes[note 1]
- Changes in sex drive
a comedown period may occur, with symptoms of fatigue and depression.
Amfetamines (everyone one of these have 'amfetamine' in their names) work by activating the TAAR1, hence inhibiting the noradrenaline and dopamine reuptake pumps, whilst simultaneously inhibiting VMAT2 hence directly inducing the release of these neurotransmitters into the synapse. Methylphenidate and its d-isomer (dexmethylphenidate) work by inhibiting the reuptake of noradrenaline and dopamine.:235
Atomoxetine (brand name: Strattera) works by serving as a noradrenaline reuptake inhibitor (NRI). The noradrenaline transporter is also present in areas of the brain (namely the prefrontal cortex) where the dopamine transporter is absent, despite the presence of the neurotransmitter dopamine, and it serves as the transporter for dopamine in these brain regions. Hence NRIs also increase dopamine concentrations in the PFC, without increasing dopamine concentrations in the reward centres of the brain, hence does not cause addiction or euphoria. Despite this it is plagued by a delayed onset of action of a few weeks, usually.
Alpha-2 adrenoceptor agonists include clonidine (brand name: Catapres, Dixarit, Duraclon, Jenloga, Kapvay) and guanfacine (only available in the U.S.A., now; brand name: Intuniv, Tenex). They are very sedating (less of a problem with guanfacine) and often cause low blood pressure during early treatment (in fact they are both approved to treat hypertension), depression can also be a problem with them. With repeated treatment these side effects tend to subside but the delayed onset of action means they must be taken repeatedly for weeks and this can be problematic. See in Australia and the U.K. only immediate release formulations of clonidine, and as clonidine does not last in the body for very long this necessitates twice or three times daily dosing, which means that it can cause sedation during the rest of the day. In the U.S.A., an extended release formulation is available allowing once daily dosing.:275-280 They can be either used alone or in combination with stimulants; the combination has been associated with sudden death,Cite error: Closing </ref> missing for <ref> tag. despite this the combination has been found to more effective than either drug alone, however. Guanfacine extended relase formulations have been found to be more effective than atomoxetine in a recent meta-analysis.
Antidepressants used in the treatment of ADHD includes bupropion, desipramine, imipramine, nortriptyline and venlafaxine. Bupropion is the most commonly used, although the evidence only supports its use in adults; desipramine' is a tricyclic that's use is supported in children and adolescents but it is rarely used due to side effects and its toxicity in cases of overdose, it is only available in a handful of countries, with the only notable example being the U.S.A.; imipramine is a tricyclic that is more sedating than desipramine, it can be used and is more widely available; nortriptyline is the least sedating tricyclic; venlafaxine's use is supported solely by small studies, hence its clinical use is generally advised against except in desperate circumstances. Desipramine and nortripyline are tricyclic noradrenaline reuptake inhibitors; imipramine is a serotonin-noradrenaline reuptake inhibitor; venlafaxine is a serotonin-noradrenaline reuptake inhibitor; bupropion is a noradrenaline-dopamine reuptake inhibitor.
Dietary changes include consuming fish oils, which have been found to produce modest, yet significant improvements in ADHD symptoms, and removing certain artificial colours and flavours in those with insensitivities to these substances (which tends to produce fairly robust improvements in symptoms).
Untreated ADHD is associated with an increased risk of overweight/obesity, substance abuse problems, criminal behaviour and antisocial personality disorder in adulthood.:25-28 Treatment, especially with medications, is believed to reduce the risk of these complications.
ADHD is believed to affect between 5-15% of school aged children; the predominantly inattentive form of the disorder affects both genders equally, whereas the predominantly hyperactive/impulsive subtype affects males far more commonly than females. It is significantly more common in children than adults, most cases present before the age of 7; with age the rate of ADHD declines and many people that fulfilled the diagnostic criteria for the condition as children do not as adults.:26-27
- MedlinePlus entry
- Medscape Reference entry
- Merck Manual Professional Edition. Written for healthcare professionals in American English.
- Merck Manual Home Edition. Written for lay people in American English.
- NCBI Bookshelf provides free book resources on this topic.
- PubMed provides review articles from the past five years (limit to free review articles or to systematic reviews)
- The TRIP database provides clinical publications about evidence-based medicine.
- ↑ Usually increases but decreases also reported
- ↑ Del Campo, N; Chamberlain, SR; Sahakian, BJ; Robbins, TW (June 2011). "The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder.". Biological Psychiatry 69 (12): e145–57. PMID 21550021. doi:10.1016/j.biopsych.2011.02.036.
- ↑ "ICD-10 Version: 2010". International Classification of Diseases 10th Revision. Geneva, Switzerland. 2010. Retrieved 3 September 2014.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 National Collaborating Centre for Mental Health (2009). Attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people, and adults (PDF). Leicester, UK: British Psychological Society/The Royal College of Psychiatrists. ISBN 978-1-85433-471-8.
- ↑ American Psychiatric Association (18 May 2013). "Neurodevelopmental Disorders". Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. United States: PsychiatryOnline. ISBN 978-0-89042-554-1. doi:10.1176/appi.books.9780890425596.514988. Retrieved 2 September 2014.
- ↑ 5.0 5.1 Feldman, HM; Reiff, MI (February 2014). "Clinical practice. Attention deficit-hyperactivity disorder in children and adolescents.". The New England Journal of Medicine 370 (9): 838–46. PMID 24571756. doi:10.1056/NEJMcp1307215.
- ↑ "Attention deficit hyperactivity disorder: Diagnosis and management of ADHD in children, young people and adults". NICE clinical guideline 72. National Institute for Health and Clinical Excellence. March 2013. Retrieved 2 September 2014.
- ↑ Heal, DJ; Smith, SL; Gosden, J; Nutt, DJ (June 2013). "Amphetamine, past and present--a pharmacological and clinical perspective.". Journal of Psychopharmacology 27 (6): 479–96. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642.
- ↑ Sotnikova, TD; Caron, MG; Gainetdinov, RR; Grandy, DK (August 2009). "Trace amine-associated receptors as emerging therapeutic targets.". Molecular pharmacology 76 (2): 229–35. doi:10.1124/mol.109.055970. PMC 2713119. PMID 19389919.
- ↑ 9.0 9.1 Wilens, TE; Spencer, TJ (September 2010). "Understanding attention-deficit/hyperactivity disorder from childhood to adulthood.". Postgraduate Medicine 122 (5): 97–109. PMC 3724232. PMID 20861593. doi:10.3810/pgm.2010.09.2206.
- ↑ Sallee, F; Connor, DF; Newcorn, JH (June 2013). "A review of the rationale and clinical utilization of α2-adrenoceptor agonists for the treatment of attention-deficit/hyperactivity and related disorders.". Journal of Child and Adolescent Psychopharmacology 23 (5): 308–19. PMID 23782125. doi:10.1089/cap.2013.0028.
- ↑ Soreff, S (4 February 2014). Dunayevich, E; Darko, DF; Talavera, F; Harsch, HH, ed. "Attention Deficit Hyperactivity Disorder Treatment & Management". United States of America. Retrieved 20 September 2014.
- ↑ Sikirica, V; Findling, RL; Signorovitch, J; Erder, MH; Dammerman, R; Hodgkins, P; Lu, M; Xie, J; Wu, EQ (November 2013). "Comparative efficacy of guanfacine extended release versus atomoxetine for the treatment of attention-deficit/hyperactivity disorder in children and adolescents: applying matching-adjusted indirect comparison methodology.". CNS Drugs 27 (11): 943–53. PMC 3824845. PMID 23975660. doi:10.1007/s40263-013-0102-x.
- ↑ Greydanus, DE; Sloane, MA; Rappley, MD (October 2002). "Psychopharmacology of ADHD in adolescents.". Adolescent Medicine 13 (3): 599–624. PMID 12270803.
- ↑ Himpel, S; Banaschewski, T; Heise, CA; Rothenberger, A (March 2005). "The safety of non-stimulant agents for the treatment of attention-deficit hyperactivity disorder.". Expert Opinion on Drug Safety 4 (2): 311–21. PMID 15794722. doi:10.1517/14740318.104.22.1681.
- ↑ 15.0 15.1 Wilens, TE; Spencer, TJ (September 2010). "Understanding attention-deficit/hyperactivity disorder from childhood to adulthood.". Postgraduate Medicine 122 (5): 97–109. PMC 3724232. PMID 20861593. doi:10.3810/pgm.2010.09.2206.
- ↑ Ghanizadeh, A (July 2013). "A systematic review of the efficacy and safety of desipramine for treating ADHD.". Current Drug Safety 8 (3): 169–74. PMID 23914752. doi:10.2174/15748863113089990029.
- ↑ Ghanizadeh, A; Freeman, RD; Berk, M (March 2013). "Efficacy and adverse effects of venlafaxine in children and adolescents with ADHD: a systematic review of non-controlled and controlled trials.". Reviews on Recent Clinical Trials 8 (1): 2–8. PMID 23157376. doi:10.2174/1574887111308010002.
- ↑ Sonuga-Barke, EJ; Brandeis, D; Cortese, S; Daley, D; Ferrin, M; Holtmann, M; Stevenson, J; Danckaerts, M; van der Oord, S; Döpfner, M; Dittmann, RW; Simonoff, E; Zuddas, A; Banaschewski, T; Buitelaar, J; Coghill, D; Hollis, C; Konofal, E; Lecendreux, M; Wong, IC; Sergeant, J; European ADHD Guidelines Group (March 2013). "Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments.". The American Journal of Psychiatry 170 (3): 275–89. PMID 23360949. doi:10.1176/appi.ajp.2012.12070991.
- ↑ Royal Australasian College of Physicians (2009). "Australian Guidelines on Attention Deficit Hyperactivity Disorder (ADHD)" (PDF). National Health and Medical Research Council. Royal Australasian College of Physicians. Retrieved 20 September 2014.
- ↑ Faraone, SV; Wilens, TE (2007). "Effect of stimulant medications for attention-deficit/hyperactivity disorder on later substance use and the potential for stimulant misuse, abuse, and diversion.". The Journal of Clinical Psychiatry. 68 Suppl 11: 15–22. PMID 18307377.
- ↑ Harstad, E; Levy, S; Committee on Substance, Abuse (July 2014). "Attention-deficit/hyperactivity disorder and substance abuse.". Pediatrics 134 (1): e293–301. PMID 24982106. doi:10.1542/peds.2014-0992.
- ↑ Sulkes, SB, ed. (October 2013). "Attention-Deficit/Hyperactivity Disorder (ADHD, ADD)". Merck Manual Professional Edition. Merck Sharp & Dohme Corp. Retrieved 19 September 2014.