How To Increase Vyvanse Euphoria
Innov Clin Neurosci. 2022 Jan; 8(ane): 47–53.
Published online 2022 Jan.
The Dopamine Dilemma—Part II
Could Stimulants Cause Tolerance, Dependence, and Paradoxical Decompensation?
Jason Yanofski
Dr. Yanofski is a forensic and clinical psychiatrist at the Minor Traumatic Brain Injury (MTBI) Dispensary at Us Army Garrison, Bamberg, Germany; Dr. Yanofski was working at the San Quentin State Prison, San Quentin, California, during preparation of this manuscript. Dr. Yanofski trained at Johns Hopkins University in Baltimore, Maryland; University of Texas Southwestern in Dallas, Texas; and Yale University in New Haven, Connecticut.
Abstract
In this commentary, the writer calls to attention that stimulants are ordinarily prescribed to children for years without seeming regard to the lack of studies on efficacy and safety during long-term utilize. The writer examines evidence for stimulants losing efficacy over time and provides multiple possible mechanisms. The potential for paradoxical decompensation, an iatrogenic worsening of symptoms over time, is considered and discussed. Recommendations for detecting and responding to possible stimulant tolerance and dependence are provided.
Keywords: Stimulants, dopamine, children, ADHD, psychopharmacology, tolerance, dependence
Introduction
Attention deficit hyperactivity disorder (ADHD) is the nearly-studied and most-diagnosed psychiatric status in children. 1 National guidelines report that the first-line treatment for ADHD is a stimulant medication, ii and stimulants have been shown to have a brusque-term success rate as high as 68 to fourscore per centum. 2
Prescriptions for stimulants have increased dramatically over the concluding two decades. There was a iv-fold increase in the use of stimulants in children from 1987 to 1996, 3 and more contempo examination showed that this increment remains stable. 4 More than half of pediatric outpatient appointments where a psychiatric medication is prescribed include a prescription for a stimulant. five
The loftier per centum of children being treated with stimulants suggests that about psychiatrists believe the benefits of stimulants outweigh the risk of any potential side effects. In fact, information technology is not uncommon for children to be prescribed stimulants continuously for a course of years. However, while the therapeutic effects of stimulants tin can be seen within minutes, concerns take been expressed that long-term studies on the safety and efficacy of these medications are lacking, 7 specially in light of the fact that children may exist more vulnerable than adults to psychiatric medication side effects. 6,10
In this commentary, I will review the data available on the efficacy of long-term stimulant use. I will so discuss the possible mechanisms for loss of efficacy. I advise that an examination of stimulant tolerance and its potential ramifications is of import and should be considered in clinical exercise.
Addiction, Tolerance, and Dependence
It is helpful to brainstorm by defining the relevant terms. Addiction is a complicated biological and psychological phenomenon in which difficulty abstaining from substances leads to problems performance inside multiple life areas. Tolerance to a medication is present when the response to the same dose of a drug decreases with repeated utilize over fourth dimension, such that larger doses of the medication become necessary to reach the same level of response. 12
Dependence on a medication is present when chronic utilize of a medication has caused the brain to adapt in such a manner that the medication is at present necessary in order to function at a level that was previously reachable without any medication. Furthermore, when the medication is removed, withdrawal symptoms appear, often leading to addiction. xiii
Generally, higher doses of medications and longer durations of use put patients at increased take chances of developing dependence and tolerance. However, during periods of forbearance from the medication, these phenomena are reversible. Most psychopharmacological agents have the potential to crusade at least some tolerance, dependence, and addiction, even medications considered safety for long-term use, such as antidepressants. 14
Mechanisms of addiction vary, depending on the substance, but they share a common endpoint: feelings of reward and reinforcement due to dopamine (DA) release within the brain's "advantage arrangement." 15,16 The reward system is a product of the mesolimbic DA pathway, which connects the ventral tegmental area of the midbrain to the limbic system and involves the nucleus accumbens, amygdala, hippocampus, and medial prefrontal cortex. 17
Complex DA Theory includes explanations of DA regulation at the level of the pre- and postsynaptic DA receptors. Both of these receptor types have been associated with of import negative feedback mechanisms of DA regulation, especially at D1 and D2. 24,28–32 When the brain becomes overstimulated by hyperdopaminergic states, it uses regulatory mechanisms as counter-interim defenses. More specifically, presynaptic DA receptors respond to hyperdopaminergic states by decreasing their rate of farther DA release into the synapse. 29 Additionally, postsynaptic receptors respond by downregulating themselves, decreasing the bounden of DA already in the synapse, desensitizing the brain to DA, and leading to tolerance and habit. 24,30
The about addicting substances known are heroine, cocaine, tobacco, barbituates, alcohol, benzodiazepines, amphetamine, cannabis, lysergic acid diethylamide (LSD), and iii,iv-methylenedioxymethamphetamin (i.eastward., ecstacy), respectively. 18 While cocaine and amphetamine have direct effects on DA receptors, the remaining substances activate DA transmission indirectly, by way of secondary messengers. xiii,fifteen,xvi,19–24 For example, chronic nicotine use causes euphoria, relaxation, and eventual addiction as a result of bounden to acetylcholine receptors, which indirectly causes DA release inside the reward organization. 16,24
Paradoxical Decompensation
When a substance causes physical dependence, removal of the substance often leads to withdrawal symptoms. If a medication causes dependence over time, removal of the medication may unmask worsened symptoms. The phenomenon of long-term use of a medication causing a worsened baseline of the condition it was treating will be referred to as paradoxical decompensation.
Clear examples of paradoxical decompensation are hard to find in the literature, just they exist, often with their ain terminology. Restless legs syndrome (RLS) has been linked with ADHD, and is treated with similar medications (due east.one thousand., dopamine agonists). 46 While these medications care for RLS symptoms initially, within a matter of days, they cause a worsening of symptoms in upwards to 82 percentage of patients, referred to every bit augmentation. This is reflected by higher intensity of symptoms and by symptoms starting before in the evening. 47
Benzodiazepines are highly constructive at apace reducing anxiety. 48,49 Nonetheless, similar to stimulant use, it is mutual for patients using benzodiazepines to require an increased dose or use of multiple agents when the medication was initially effective but then lost efficacy over time. 50–52
The same phenomenon has been recognized with long-term use of antidepressants and has been referred to as the oppositional model of tolerance. There is evidence that long-term use of antidepressants can result in more depressive episodes and worse outcomes over time. This oppositional model suggests that chronic use of antidepressants "recruit processes that oppose the initial astute upshot of a drug," and when the drug is removed, "these processes may operate unopposed, at least for some time and increase vulnerability to relapse." fourteen
Recognition of paradoxical decompensation acquired by caffeine is especially relevant to stimulant use, considering of the shared ability to increase alacrity and motivation. People who regularly utilise caffeine, an adenosine antagonist, suit to the frequent presence of information technology by up-regulating the number of adenosine receptors. This mechanism of tolerance and dependence seen with coffee has been referred to as tolerance adaptation. 53
Stimulants and Addiction: Basic Science
While most substances that lead to addiction increase DA release by indirect pathways, stimulants human activity directly on presynaptic DA receptors themselves, leading to release of DA in storage vesicles. The two types of prescribed stimulants, methylphenidate and amphetamine, have slightly dissimilar mechanisms of activeness. Methylphenidate inhibits the reuptake of dopamine. 37,38 Amphetamine has the additional part of entering the presynaptic neuron and forcing boosted vesicular DA into the synapse. Stimulants are thought to accept their therapeutic effects more often than not through D1, only they have been shown to also accept significant action at D2. 38,39
In theory, by manipulating DA directly, stimulants should exist especially conducive to activating DA regulatory mechanisms (e.g., reduction of presynaptic release and postsynaptic receptor downregulation). DA receptor changes have been found to correlate both with observed and reported signs of tolerance to both DA agonists (e.g., stimulants) and antagonists (east.1000., antipsychotics) every bit a result changes in D2 receptor density. 31,32 For case, "supersensitive" DA receptors have been demonstrated with chronic antipsychotic use 31 and correlate with observed medication tolerance. 32 1 study showed that repeating the same dose of stimulant, immediately after therapeutic effects were lost, produced only half the efficacy of the initial dose. 44 This suggests that tolerance to stimulants occurs at some degree even inside several hours.
Additionally, the pre- and postsynaptic DA regulatory mechanisms associated with stimulants lead non only to tolerance of the stimulants, but to the brain's endogenous DA, as well. 28–30 Since low dopamine is theorized to be the crusade of ADHD, decreasing the brain'southward sensitivity to DA is the reverse of what patients with ADHD need, and could theoretically atomic number 82 to paradoxical decompensation of the ADHD symptoms (Figures 1 and 2).
Stimulants and complex dopamine theory. Box 1 represents the brusk-term furnishings of a stimulant: an increased amount of DA in the synapse;Box 2 represents the long-term effects of a stimulant on the DA synapse. Over fourth dimension, high levels of synaptic DA initiate negative feedback mechanisms: post-synaptic receptors down-regulate and pre-synaptic DA release is decreased.
Paradoxical decompensation in a medicated patient. Solid line: symptom improvement over time (including furnishings of medication); Dotted line: underlying condition (symptom improvement if medication was not present at any given moment); 1=medication started, 2=dose increased, 3=dose increased once more, 4=medication discontinued
Clinical Examination of ADHD, Stimulants, and Tolerance
Though stimulants and cocaine share a similar mechanism, a longer half-life has been suggested as the reason that stimulant medications, when used accordingly, are less probable to cause addiction. 25 Abuse of stimulants is widespread, particularly abuse of stimulants with a short fourth dimension of onset. Studies take shown stimulant abuse to be as prevalent as eight to 14 percent in certain populations, and the most common reasons for stimulant corruption include increasing concentration/alacrity and getting "high." Amphetamine, the stimulant closest to cocaine, is called three times more often than methylphenidate. Non surprisingly, snorting stimulants, which increases the speed that the chemical reaches the encephalon, is a popular route of corruption. 26,27
Stimulants' power to cause tolerance is controversial, only the need for dose increases over time has been recognized in the literature by the American University of Kid and Adolescent Psychiatry (AACAP). Their treatment guidelines state that "nigh" children will "crave dose aligning upward as treatment progresses." 55 Additionally, the Multimodal Treatment Report of Children with ADHD (MTA), the largest ADHD treatment written report in being, establish that stimulants may take less efficacy over time. Their data supported the short-term efficacy of stimulants in ADHD, but recent follow-upwards afterwards several years showed that patients taking stimulant medications had the same level of symptoms every bit those who had never been medicated. 11
These findings do not necessarily suggest the presence of tolerance. The participants may take also been nonadherent, dosed inadequately, or misdiagnosed to begin with. Nonetheless, when a correctly diagnosed and dosed child'south ADHD symptoms respond to a stimulant for several weeks or months and then relapse, what is the nigh likely cause? Why might stimulants lose efficacy, requiring college doses over time?
The four chief proposed mechanisms for tolerance include the following:
-
Changes in pharmacokinetics. It has been shown that larger children take less exposure to the same dose of stimulant medications than smaller children. 66 This suggests that if a child grows and his stimulant dose is kept the same, it may lose efficacy.
-
Progression of disorder. The underlying illness may have worsened naturally and a higher dose of stimulant is required. 43 While the usual tendency is for symptoms to stay the same or improve over time, 45 it is possible for a kid to have a naturally worsening course.
-
Environmental changes. A kid could be placed in a new surround with more than attention demands, unmasking hidden symptoms and requiring a higher dose of stimulant.
-
Paradoxical decompensation. An alternative explanation is that the medication itself has worsened the ADHD 28,31,32 considering tolerance and dependence have acquired paradoxical decompensation (Figure 1). If this is the case, an increment in the dose may assist temporarily but atomic number 82 to worsened decompensation in the long term. There also may be a psychological component. Children who accept stimulants for several years may develop less natural coping mechanisms while medicated than children who were not treated. 54
Because long-term studies are lacking and the efficacy of stimulants over time is not known, it is unclear which of these mechanisms is most likely to cause loss of efficacy. The first 3 mechanisms warrant dose increases, while the fourth mechanism does not. Despite United States Nutrient and Drug Administration (FDA) warnings nearly risks of tolerance and dependence with long-term stimulant use, practice trends suggest that psychiatrists are non concerned near the possibility of paradoxical decompensation. 3–six In fact, AACAP practice parameters state that stimulant treatment should be continued, "equally long as symptoms remain present." 55
Is the general lack of business almost paradoxical decompensation justified? While the basic science research I describe is suggestive of the potential for this miracle, clinical research aimed specifically at examining the likelihood of stimulant tolerance is sparse. At that place has never been a study designed specifically to examine whether or not stimulants take the potential to worsen ADHD symptoms over fourth dimension. One review of 166 patients found that threescore pct of children developed dose-dependent tolerance to stimulants. 43 However, because of the lack of other research in this area, the verdict is nonetheless out.
Recognizing and Reacting to Stimulant Tolerance and Paradoxical Decompensation
While it is unclear whether paradoxical decompensation is a frequent miracle with stimulant use, at the very least, it should be recognized equally a possibility that may exist seen with some children.
If stimulants were to cause long-term worsening of underlying ADHD symptoms, and complete symptom relief was continuously sought subsequently, this could lead to a paradoxical decompensation bike (i.e., progressive symptom worsening over time and the advent of higher and higher dosages being needed to reach the same level of do good).
The potential long-term price of chasing symptom relief past way of multiple increases in dose size or frequency warrants farther study. If paradoxical decompensation is present, information technology may exist advisable to view the symptom relief received past stimulants as a "borrowed benefit." Much like borrowing money from a bank, these symptoms must be paid dorsum in the future. The payback upon stimulant discontinuation may be a subacute syndrome, during which the patient will function "attention-wise" beneath their baseline (due to downregulated postsynaptic DA receptors and decreased presynaptic DA release). 28–30 This subclinical withdrawal would decrease over time, merely may be present, to some degree, until the receptors are completely reversed back to their baseline gear up-bespeak.
If stimulant dependence exists with a patient, information technology may be difficult to recognize because, even though the medication may appear to have "pooped out," removing information technology may cause symptoms to worsen farther. This need for higher doses of stimulants would mask the possibility of stimulants causing dependence because stimulants are not classically considered to be addictive medications.
If paradoxical decompensation with stimulants is suspected, the appropriate cosmetic action would be a period of abstinence from the medication. These temporary detoxifications have has often been referred to as drug holidays. These breaks from treatment serve to "partially reverse the physiological adaptive effects that result from chronic pharmacological stimulation," and they consequence in resensitizing neurons." 59 These changes should help to both decrease the underlying ADHD symptoms over time and brand stimulant medications more than effective again if used in the future, essentially by reversing tolerance, dependence, and paradoxical decompensation.
Studies take shown that weekend drug holidays reduce stimulant side effects without causing significant symptom increases, likely because the medications were reduced during the days when less focus was required. sixty However, the exact elapsing and dosage of the preceding treatment needed for a drug holiday to be effective is unclear and needs farther research. Because paradoxical decompensation is minimized in the literature, stimulant drug holidays are not included in ADHD treatment guidelines.
Eliciting adherence with stimulant drug holidays may be difficult. A parent who frequently seeks increases in their child'southward stimulant dose over fourth dimension because they cannot tolerate whatsoever ADHD symptoms may be resistant to discontinue the medication for even a short menses. This scenario may represent a form of habit-by-proxy.
When drug holidays are found to be ineffective at reducing dependence and paradoxical decompensation, complete abstinence of the medication should be considered. Withdrawal furnishings from stimulant discontinuation do occur, but they are commonly not serious and tin be minimized by gradually tapering the dose. 61 Close psychological support for both the child and the parent are important at this time.
Nonstimulant medications, such every bit atomoxetine, clonidine, buproprion, modafinil, guanfacine extended release, and tricyclic antidepressants may be advisable treatments post-obit stimulant discontinuation. 62,63 Nonpharmacological approaches, including parent training, social skills training, and assessment for appropriate educational placement, are also likely to provide significant benefit. 64
Conclusion
Complex dopamine theory and clinical studies suggest that stimulant medications may have the potential to cause tolerance and dependence over time only the data are unclear. Only time volition tell what the "stimulant generation" volition teach us about ADHD treatment patterns over the recent decades.
Thoughtful physicians should appreciate the following guiding points:
-
Stimulants deed to directly increment dopamine activity in the encephalon, sharing a similar machinery of activeness with many addictive drugs of abuse.
-
Theory and bear witness suggest the possibility that even '"appropriate" use of stimulants may atomic number 82 to tolerance and dependence, simply to what degree, if whatsoever, these phenomena should be considered existent concerns is unclear.
-
A child'south pattern of requiring multiple stimulant dose increases over weeks, months, and years may suggest that he or she has been developing tolerance and dependence, but this is only i of multiple possible explanations.
-
Using stimulants for curt durations or with consistent drug holidays might subtract the risk of these phenomena.
-
If drug holidays are shown to exist ineffective at preventing escalating symptom intensity and the need to make frequent dose increases, the patient may demand to be gradually tapered off the stimulant with close psychological back up.
References
1. Nair J, Ehimare U, Beitman BD, et al. Clinical review: prove-based diagnosis and treatment of ADHD in children. Mo Med. 2006;103(6):617–621. [PubMed] [Google Scholar]
2. Rappley M. Attention deficit-hyperactivity disorder. N Engl J Med. 2005;352:2. [PubMed] [Google Scholar]
3. Olfson Yard, Gameroff M, Marcus S, Jensen P. National trends in the treatment of attention deficit hyperactivity disorder. Am J Psychiatry. 2003;160:1071–1077. [PubMed] [Google Scholar]
4. Zuvekas SH, Vitiello B, Norquist GS. Recent trends in stimulant medication use among U.s.a. children. Am J Psychiatry. 2006;163(4):579–585. [PubMed] [Google Scholar]
five. Goodwin R, Gould MS, Blanco C, Olfson M. Prescription of psychotropic medications to youths in office-base practice. Psychiatr Serv. 2001;52(8):1081–1087. [PubMed] [Google Scholar]
6. Zito JM, Safer DJ, dosReis S, et al. Trends in the prescribing of psychotropic medications to preschoolers. JAMA. 2000;23;283(eight):1025–1030. [PubMed] [Google Scholar]
seven. Zhang H, Du M, Zhuang South. Bear on of long-term handling of methylphenidate on height and weight of school age children with ADHD. Neuropediatrics. 2010;41(two):55–59. [PubMed] [Google Scholar]
8. Kraemer One thousand, Uekermann J, Wiltfang J, Kis B. Methylphenidate-induced psychosis in developed attention-arrears/hyperactivity disorder: report of three new cases and review of the literature. Clin Neuropharmacol. 2010;33(4):204–206. [PubMed] [Google Scholar]
9. Rösler K, Casas Grand, Konofal East, Buitelaar J. Attention deficit hyperactivity disorder in adults. World J Biol Psychiatry. 2010;eleven(5):684–698. [PubMed] [Google Scholar]
10. Ratzoni 1000, Gothelf D, Brand-Gothelf A, et al. Weight proceeds associated with olanzapine and risperidone in adolescent patients: a comparative prospective study. J Am Acad Kid Adolesc Psychiatry. 2002;41(3):337–343. [PubMed] [Google Scholar]
11. Jensen PS, Arnold LE, Swanson JM, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Kid Adolesc Psychiatry. 2007;46(eight):989–1002. [PubMed] [Google Scholar]
12. Adriaensen H, Vissers K, Noorduin H, Meert T. Opioid tolerance and dependence: an inevitable upshot of chronic handling? Acta Anaesthesiol Belg. 2003;54(1):37–47. [PubMed] [Google Scholar]
13. Kosten TR, George TP. The neurobiology of opioid dependence: implications for handling. Sci Pract Perspect. 2002;1:xiii–twenty. [PMC gratuitous article] [PubMed] [Google Scholar]
xiv. Fava GA, Offidani E. The mechanisms of tolerance in antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Aug 19; [PubMed] [Google Scholar]
xv. Pierce RC, Kumaresan 5. The mesolimbic dopamine system: the last common pathway for the reinforcing result of drugs of abuse? Neurosci Biobehav Rev. 2006;30(two):215–238. [PubMed] [Google Scholar]
16. Kenny P, Markou A. Nicotine cocky-administration acutely activates brain reward systems and induces a long-lasting increment in advantage sensitivity. Neuropsychopharmacology. 2006;31:1203–1211. [PubMed] [Google Scholar]
17. Ikemoto S. Encephalon reward circuitry beyond the mesolimbic dopamine organization: A neurobiological theory. Neurosci Biobehav Rev. 2010 Feb 10; [PMC free commodity] [PubMed] [Google Scholar]
xviii. Nutt D, King LA, Saulsbury W, Blakemore C. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet. 2007;369(9566):1047–1053. [PubMed] [Google Scholar]
19. Zhang D, Wang X, Xiang X, et al. The dopamine D(2) partial agonist and antagonist terguride decreases heroin self-administration on stock-still- and progressive-ratio schedules. Pharmacol Biochem Behav. 2010 Aug 9; [PubMed] [Google Scholar]
20. Yoshimoto Thou, McBride WJ, Lumeng Fifty, Li TK. Booze stimulates the release of dopamine and serotonin in the nucleus accumbens. Booze. 1992;9(1):17–22. [PubMed] [Google Scholar]
21. Keller HH, Schaffner R, Haefely W. Interaction of benzodiazepines with neuroleptics at central dopamine neurons. Naunyn Schmiedebergs Arch Pharmacol. 1976;294(ane):ane–vii. [PubMed] [Google Scholar]
22. Lavielle Southward, Tassin JP, Thierry AM, et al. Blockade past benzodiazepines of the selective high increase in dopamine turnover induced by stress in mesocortical dopaminergic neurons of the rat. Brain Res. 1979;168(iii):585–594. [PubMed] [Google Scholar]
23. Kitai ST, Sugimori One thousand, Kocsis JD. Excitatory nature of dopamine in the nigro-caudate pathway. Exp Brain Res. 1976;24(iv):351–363. [PubMed] [Google Scholar]
24. Fehr C, Yakushev I, Hohmann N, et al. Association of low striatal dopamine D2 receptor availability With Nicotine Dependence Similar to that seen with other drugs of abuse. Am J Psychiatry. 2008;165:507–514. [PubMed] [Google Scholar]
25. Volkow ND, Swanson JM. Variables that impact the clinical apply and abuse of methylphenidate in the treatment of ADHD. Am J Psychiatry. 2003;160(11):1909–1918. [PubMed] [Google Scholar]
26. Teter CJ, McCabe SE, LaGrange K, et al. Illicit use of specific prescription stimulants among higher students: prevalence, motives, and routes of administration. Pharmacotherapy. 2006;26(10):1501–1510. [PMC free article] [PubMed] [Google Scholar]
27. Bright GM. Abuse of medications employed for the treatment of ADHD: results from a large-scale community survey. Medscape J Med. 2008;ten(five):111. [PMC gratuitous article] [PubMed] [Google Scholar]
28. Yanofski J. The dopamine dilemma: using stimulants and antipsychotics concurrently. Psychiatry. 2010;seven(vi):18–23. (Edgemont) [PMC free article] [PubMed] [Google Scholar]
29. Grace AA. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience. 1991;41(1):1–24. [PubMed] [Google Scholar]
30. Braun AR, Laruelle M, Mouradian MM. Interactions betwixt D1 and D2 dopamine receptor family agonists and antagonists: the effects of chronic exposure on behavior and receptor binding in rats and their clinical implications. J Neural Transm. 1997;104(4-5):341–362. [PubMed] [Google Scholar]
31. Gianutsos G, Drawbaugh RB, Hynes Md, Lal H. Behavioral evidence for dopaminergic supersensitivity subsequently chronic haloperidol. Life Sci. 1974;14:887–898. [PubMed] [Google Scholar]
32. Samaha AN, Seeman P, Stewart J, et al. "Breakthrough" dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci. 2007;27(eleven):2979–2986. [PMC free article] [PubMed] [Google Scholar]
33. Breggin PR. Questioning the treatment for ADHD. Scientific discipline. 2001;291:595. [PubMed] [Google Scholar]
34. Furman LM. Attention-deficit hyperactivity disorder (ADHD): does new research support old concepts? J Child Neurol. 2008;23(7):775–784. [PubMed] [Google Scholar]
35. Adriani W, Boyer F, Gioiosa L, et al. Increased impulsive behavior and risk proneness post-obit lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens. Neuroscience. 2008;159(1):47–58. [PubMed] [Google Scholar]
36. Biederman J, Faraone SV, Monuteaux MC. Differential effect of environmental adversity by gender: Rutter's index of adversity in a grouping of boys and girls with and without ADHD. Am J Psychiatry. 2002;159(9):1556. [PubMed] [Google Scholar]
37. Solanto MV. Neuropsychopharmacological mechanisms of stimulant drug activeness in attention-arrears hyperactivity disorder: a review and integration. Behav Brain Res. 1998;94(1):127–152. [PubMed] [Google Scholar]
38. Volkow N, Wang One thousand, Fowler J, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry. 1998;155:1325–1331. [PubMed] [Google Scholar]
39. Botly LC, Burton CL, Rizos Z, Fletcher PJ. Characterization of methylphenidate self-adminstration and reinstatement in the rat. Psychopharmacology. 2008;199(1):55–66. (Berl) [PubMed] [Google Scholar]
40. Berridge CW, Devilbiss DM, Andrzejewski ME, et al. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive office. Biol Psychiatry. 2006;threescore(x):1111–1120. [PubMed] [Google Scholar]
41. Moore KE. The actions of amphetamine on neurotransmitters: a cursory review. Biol Psychiatry. 1977;12(iii):451–462. [PubMed] [Google Scholar]
42. Jones S, Kornblum JL, Kauer JA. Amphetamine blocks long-term synaptic depression in the ventral tegmental area. J Neurosci. 2000;20(15):5575–5580. [PMC gratuitous article] [PubMed] [Google Scholar]
43. Ross DC, Fischehoff J, Davenport B. Treatment of ADHD when tolerance to methylphenidate develops. Psychiatr Serv. 2002;53(1):102. [PubMed] [Google Scholar]
44. Swanson J, Gupta Due south, Guinta D, et al. Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children. Clin Pharmacol Ther. 1999;66:295–305. [PubMed] [Google Scholar]
45. Bálint S, Czobor P, Mészáros A, et al. Neuropsychological impairments in adult attention deficit hyperactivity disorder: a literature review. Psychiatr Hung. 2008;23(5):324–335. [PubMed] [Google Scholar]
46. Schimmelmann BG, Friedel S, Nguyen TT, et al. Exploring the genetic link between RLS and ADHD. J Psychiatr Res. 2009;43(10):941–945. [PubMed] [Google Scholar]
47. Garcia-Borreguero D. Augmentation: understanding a key feature of RLS. Sleep Med. 2004;v(1):v–6. [PubMed] [Google Scholar]
48. Hollister LE, Muller-Oerlinghausen B, Rickels Thousand, et al. Clinical uses of benzodiazepines. J Clin Psychopharmacol. 1993;13(Suppl 1):1S–169S. [PubMed] [Google Scholar]
49. Schweizer Eastward, Rickels Thousand, Weiss S, Zavodnick S. Maintenance drug handling of panic disorder. I: Results of a prospective, placebo-controlled comparison of alprazolam and imipramine. Arch Gen Psychiatry. 1993;50:51–60. [PubMed] [Google Scholar]
50. Morin CM, Belanger L, Bastien C, Vallieres A. Long-term issue after discontinuation of benzodiazepines for insomnia: a survival assay of relapse. Behav Res Ther. 2005;43:ane–14. [PubMed] [Google Scholar]
51. Poyares D, Guilleminault C, Ohayon C, Tufik S. Chronic benzodiazepine usage and withdrawal in insomnia patients. J Psychiatr Res. 2004;38:327–334. [PubMed] [Google Scholar]
52. Ashton H. Benzodiazepine withdrawal: effect in 50 patients. Br J Addict. 1987;83:665–671. [PubMed] [Google Scholar]
53. Holtzman SG, Mante S, Minneman KP. Part of adenosine receptors in caffeine tolerance. J Pharmacol Exp Ther. 1991;256(ane):62–68. [PubMed] [Google Scholar]
54. Adler LA. Clinical presentations of developed patients with ADHD. J Clin Psychiatry. 2004;65(Suppl three):8–11. [PubMed] [Google Scholar]
55. Pliszka Southward. AACAP Piece of work Group on Quality Issues. Practice parameter for the cess and treatment of children and adolescents with attention-arrears/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894–921. [PubMed] [Google Scholar]
56. Carlson GA, Kelly KL. Stimulant rebound: how common is information technology and what does it mean? J Kid Adolesc Psychopharmacol. 2003;thirteen(two):137–142. [PubMed] [Google Scholar]
57. Buitelaar J, Medori R. Treating attention-arrears/hyperactivity disorder beyond symptom control lone in children and adolescents: a review of the potential benefits of long-interim stimulants. Eur Child Adolesc Psychiatry. 2010;19(iv):325–340. [PMC free commodity] [PubMed] [Google Scholar]
58. Griffiths RR, Weerts EM. Benzodiazepine cocky-administration in humans and laboratory animals: implications for problems of long-term utilize and abuse. Psychopharmacology. 1997;134:1–37. [PubMed] [Google Scholar]
59. Howland RH. Medication holidays. J Psychosoc Nurs Ment Health Serv. 2009;47(9):fifteen–eighteen. [PubMed] [Google Scholar]
60. Martins S, Tramontina S, Polanczyk G, et al. Weekend holidays during methylphenidate utilize in ADHD children: A randomized clinical trial. J Kid Adolesc Psychopharmacol. 2004;14(ii):195–206. [PubMed] [Google Scholar]
61. Howland RH. Potential agin effects of discontinuing psychotropic drugs. J Psychosoc Nurs Ment Health Serv. 2010;48(9):11–14. [PubMed] [Google Scholar]
62. Pataki CS, Feinberg DT, McGough JJ. New drugs for the treatment of attending-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2004;nine(2):293–302. [PubMed] [Google Scholar]
63. Garnock-Jones KP, Keating GM. Spotlight on atomoxetine in attention-deficit hyperactivity disorder in children and adolescents. CNS Drugs. 20101;24(1):85–88. [PubMed] [Google Scholar]
64. Safren SA, Sprich S, Mimiaga MJ, et al. Cognitive behavioral therapy vs relaxation with educational support for medication- treated adults with ADHD and persistent symptoms: a randomized controlled trial. JAMA. 2010;304(eight):875–880. [PMC free article] [PubMed] [Google Scholar]
65. Ashton H, Gallagher P, Moore B. The adult psychiatrist's dilemma: psychostimulant employ in attention deficit/hyperactivity disorder. J Psychopharmacol. 2006;xx(5):602–610. [PubMed] [Google Scholar]
66. Wigal SB, Gupta Southward, Greenhill L, et al. Pharmacokinetics of methylphenidate in preschoolers with attending-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2007;17(2):153–164. [PubMed] [Google Scholar]
Articles from Innovations in Clinical Neuroscience are provided hither courtesy of Matrix Medical Communications
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036556/
0 Response to "How To Increase Vyvanse Euphoria"
Post a Comment