Treatment Modalities for Attention-Deficit Hyperactivity Disorder - Research Paper Example

? A Risk-Benefit Analysis of Modern Treatment Modalities for Attention-Deficit Hyperactivity Disorder. INTRODUCTION Attention-deficit/hyperactivity disorder is a chronic neurological condition that becomes apparent in childhood, before the age of seven, but often continues into adulthood. It is characterized by persistent restless energy and an inability to quietly concentrate of intellectual tasks such as schoolwork; Which provides the primary impetus for the pharmaceutical investments towards treating it. While there is no single course of treatment that can be shown to 'cure it'. The symptoms can be improved with proper application of drug therapy, with favorable odds that the child will grow up to be a normal adult. The condition was once referred to simply as Attention-deficit disorder, but this does not encompass the hyperactivity element, and so modern practitioners prefer the full description of ADHD. The most common symptoms are described below: 1.)Difficulty sustaining attention to details 2.) Prone to careless mistakes 3.) Avoids tasks that require sustained mental effort 4.) Tendency to forget instructions even when addressed directly 5.) Difficulty with organizing activities 6.) Frequently misplaces personal articles. (psychiatryonline.com 2010) The hyperactive component includes restless energy, squirming/fidgeting, and an inability to focus quietly on tasks. 2 The condition manifests differently based on gender: Boys tend to act out in physical ways through distracting games or fidgeting, and are less compliant with authority figures. Girls tend to daydream with quiet inattentiveness. (Rucklidge, 2010) A wide variety of psychoactive pharmaceuticals are in the hands of medical and psychiatric practitioners, which some degree of overlap in functionality and efficacy. This article will endeavor to summarize the most popular treatment options; describing their essential modes of activity and comparing them with similar options. To the extent it is possible, the most effective ADHD medication will be determined. TREATMENTS Adderal A brand-name, amphetamine-salt based psycho stimulant for the treatment of attention-deficit hyperactivity disorder as well as narcolepsy. It appears to function by increasing levels of dopamine and norepinephrine in the brain, by preventing brain cells from taking up these neurotransmitters. (Health and Life, Adderal 2011). Available in both extended release (XR) and instant release forms. (IR) Like many stimulants, Adderall can directly effect the mesolimbic reward pathway in the brain; leading to a high potential for addition. (Schilling, 2003) Contraindications: MAOI's - do not administer for at least two weeks after last dose. SSRIs (selective serotonin re uptake inhibitors), NRIs (norepinephrine re uptake inhibitors, e.g., atomoxetine, etc.) SNRIs (selective serotonin-norepinephrine re uptake inhibitors), Tricyclics and related compounds, CYP2D6 (liver enzyme) inhibitors, including methadone. 3 Evidence exists that Adderal can significantly reduce symptoms of ADHD, and depending the dosage, symptoms can be alleviated sufficiently for improvement throughout the work/school day. Low doses of Adderal appear to have long periods of efficacy, according to some studies for a longer duration than Ritalin/Methylphenidate. (Health and Life, Adderal 2011) In the long term, effects include increased focus and motivation (reduction of ADHD symptoms) The areas of the brain that control these areas have been shown to actually increase in size. But a Free-Radical buildup in the brain may necessitate the use of anti-oxidants. The drug may also be described as 'diet pills' due to an appetite-suppressant function, which can lead to weight-loss. The drug has been shown to maintain efficacy for several years even with a consistent dose every day. In the majority of patients, the potency does not appreciably diminish.(Health and Life, Adderal 2011) Side effects can include increased blood pressure, with the accompanying risk of stroke, sudden death, and heart attack, but so does Methylphenidate/Ritalin In addition, it can exacerbate risk factors in patients with a history of seizures. (Adderal XR, 2009) Adderall appears stronger than Ritalin on a per-molecule basis, which allows the patient to take less of it. Numerous studies show that Adderall is slightly more effective at controlling ADHD symptoms, however in many studies these differences were so marginal that they were not statistical significant, however - these marginal benefits occurred across many different studies; enough that the number of slightly beneficial outcomes convinces some researchers that the differences are significant. Staff Clinicians at SUNY Buffalo were found to prefer it 3 to 1 over Ritalin/Methylphenidate. (Health and Life, Adderal 2011) Lisdexamphetamine Lisdexamphetamine, marketed under the brand name Vynanse is a newer ADHD treatment. It is among the amphetamine chemical classes, and functions as a stimulant. Vynanse/Lisdexamphetamine is a 4 prodrug, an inactive delivery agent that converts to an active form when it metabolizes inside the body later on. This measure is intended to limit the potential for abuse; the pill will only convert to the active form of the drug through oral ingestion into the gastrointestinal tract. This renders the drug inactive if it is injected intravenously. The pill itself delivers a pure isomer of the active compound, unlike Adderall, in which 25% of the ingredients have a different stereochemistry. But Vynanse is a pure formulation. (Health and Life, Vynanse vs. Adderall, 2011) Contraindications: Patients with a history of drug abuse, MAOIs, cardiovascular disease, Tourette's Syndrome, moderate to severe hypertension, hypersensitivity or idiosyncratic reaction to sympathomimetic amines, glaucoma, Advanced arteriosclerosis, cardiomyopathy, or heart rhythm abnormalities. (Drugs.com Vynanse, 2011) But Lisdexamphetamine is a powerful stimulant, and in additional to the addiction risk, other side effects include sudden death, stoke, and myocardial infarction can occur. (Heart Attacks) Generally, adults with heart abnormalities should not be treated with stimulants. Gastrointestinal distress has also been observed. Psychological side effects are also possible, and patients at risk for psychotic disorders should in general avoid stimulants. Studies of weight-loss in child patients as well as adolescents has indicated that Vynanse treatment for seven days per week for a period of one year results in a slowed growth rate. After close evaluation with a physician, treatment may be interrupted on this basis. (Drugs.com Vynanse, 2011) Methylphenidate First patented in 1954, it has become accepted worldwide as a treatment for ADD. psychostimulant for the central nervous system. Also known under the brand names of Concerta, Metadate, Methylin,Ritalin. Used for control over nerves that contribute to hyperactivity and control of impulses. 5 It is used primarily to treat ADD, ADHD; and it can be used to treat narcolepsy. (Drugs.com, 2010) It can also be used for the treatment of fatigue experienced by cancer patients due to chemotherapy treatments. Transdermal patches are available as delivery methods, similar to what is used for Hormone Replacement Therapy. Contraindications: MAOIs, (monamine oxidase inhibitors) such as furazolidone. tricyclic antidepressants, severe arrhythmia, hypertension or liver damage, (PSVT), Paroxysmal Supraventricular Tachycardia, and patients with a history of drug-seeking behavior. There is some evidence that Methylphenidate can alleviate ADHD symptoms in the short term, but the literature contains criticisms that the effect may be unreliable. There are large numbers of lower-quality studies of its effectiveness; many of which are conducted without the use of a placebo. There are few studies referencing a placebo in the long-term, beyond 4 weeks. Thus methylphenidate's effectiveness in terms of a permanent treatment modality are disputable. (Schachter et al 2001) In the short term, symptoms may be alleviated, but over the course of a child's academic career its ability to positively affect performance is not conclusively supported. (Swanson) And when it ADD is diagnosed, and Methylphenidate is prescribed considerable variance can exist between individual children, ranging from between 5-60 milligrams. (Kidd, 2000) Long-term side effects are less clear, but there are some indications that late in life, drug addiction, schizophrenia, and psychotic delusions, including visual and aural hallucinations. At present knowledge, the onset of Methylphenidate psychosis appears unpredictable. There is evidence that the psychosis is reversible if drug therapy is ended. (Kimko et al. 1999) 6 Bupropion Bupropion is a non-cyclic antidepressants and is often used as a non-smoking aid. But like many other drugs discussed, it acts as a norepinephrine (and also dopamine) re-uptake inhibitor. It belongs to the aminoketone chemical family, and acts to tie-up binding sites where nicotine would otherwise take effect. (Cantwell, 1998) While marketed initially as an antidepressants, its usefulness as an anti-smoking aid was discovered later, though it has been the fourth most prescribed antidepressant among retailers in the United States. In addition to its role in the treatment of ADHD, it is also effective in the treatment of depression, anxiety, sexual dysfunction, and obesity. Contraindications: MAOIs, Epilepsy, seizures, alcohol or benzodiazepine withdrawal, bulimia, anorexia, active brain tumors, severe kidney disease, Tourette syndrome, or hypertension. While not officially approved for the treatment of ADHD, Bupropion has been found effective in the case of adult ADHD. Positive case studies and uncontrolled clinical studies including children have been conducted, but the findings proved inconclusive. Teachers in the classroom reported decreases in hyperactivity and aggression, but neither clinicians or parents could distinguish the effects of Bupropion from that of a placebo. (Cantwell, 1998) Bupropion appears to be considerably weaker than the stimulant-class in general, and should these fail, behavioral therapy may prove a more viable option. According to the Texas Department of State Health, It may be useful if pharmaceutical treatments are still desirable after trying two different stimulants, and Strattera. (Pliszka, et al. 2006) Side effects include a risk for seizures, as well as clinical depression possibly leading to suicidal tendencies. Also a less than 1% tendency for hypertension. It was initially taken off the market for lowering the Seizure Threshold, making them more likely to occur. Most antidepressants yield a seizure risk never greater than 0.6% for the general population, Bupropion can yield up to a 2% risk at a 7 dosage of 600 milligrams. (Pisani et al. 2002) The suicidal tendencies are less likely if prescribed as an anti-smoking aid. Atomoxetine A non-stimulant drug approved for the treatment of ADHD. Marketed under the brand name Strattera. In a broad sense, it is a hydrochloric acid salt, and it functions as a norepinephrine re-uptake inhibitor. While approved for children and adults, its effects have not been studied in children under the age of six. The drug must be taken for a least a week before the effects can be felt - but some patients that may not respond to stimulants may respond to Aromexetine. Moreover, once the drug does take effect in the system, coverage of symptoms can remain for 24 hours with proper dosage. Contraindications: , Monoamine Oxidase Inhibitors (MAOI), Albuterol, Narrow Angle Glaucoma There are advantages in the use of Strattera/Atomoxetine for psychiatric patients for whom amphetamine stimulants are contraindicated. The likelihood of substance abuse is diminished. (Prasad, 2008) This is especially noteworthy in patients with a history of addiction. Strattera/Atomoxetine is not listed as a controlled substance. (Prasad, 2008) Twice-daily doses are effective in the short-term moderation of ADHD in children in several, thorough, placebo-based trials. Some subjects could experience benefits well into the evening with a single dose. (Garnock et al, 2009) Side effects can include changes in appetite, headaches, dry mouth, digestive problems (nausea, constipation), sexual problems, weight changes, obsessive behavior, fatigue, urinary retention, and in very rare cases, heart rate irregularities. on the issue of school performance, it is important to note that teenagers can experience mild depression, psychosis, mood disorders, and some cases suicidal tendencies. There was a traceable case of severe liver damage. (Health and Life, Strattera Side Effects, 2011) 8 But as noted, with the delay period needed before effects are felt, Strattera does not produce the same fast-acting benefits as Ritalin. And it is relatively expensive. There are patent issues that have delayed ts direct manufacture in the United States. When effects are felt, the results - while not as dramatic are better than a placebo. On the AISR scale to determine the severity of symptoms - in this case related to ADHD, Improvements were listed on 4.4 questions, out of 54 total, when compared to the placebo. Modest, but still an improvement. (Health and Life, Strattera Side Effects, 2011) SUMMARY & CONCLUSION The choice of treatment for Attention-Deficit Hyperactivity Disorder is a weighty decision in which multiple strategies may prove wisest. An agent that proves useful for one patient may not be either effective or safe for another. The contraindicating medical and psychological factors must be weighed carefully, and a risk/benefit analysis should be mediated between the parents and physician in regards to medical potentialities that currently exist, and whether and in what way a particular treatment may lead to adverse events. Studies show Vynanse to be effective, but if a child feels self-conscious over his or her height, then the growth-stunting effects may prove undesirable, for instance. In such instances, the most prudent course may not be to pick the 'best' treatment, but to adopt a strategy that incorporates a diversity of drug-options over time; especially if evidence of drug-seeking dependency becomes apparent. Nonetheless, an attempt will be made to generalize the most effective treatment option as applicable to the greatest number of healthy students in an abstract sense. Adderal provides evidence of effectiveness relatively quickly, and it appears to have reliable benefits for extended use, up to several years ultimately. Compared to Ritalin, it is stronger, and a this allows a physician to prescribe less of the drug for effective treatment. It is not entirely conclusive 9 whether it is truly more effective than Ritalin in every case, but there are many small studies that show enough marginal advantages such that clinicians must seriously consider it in most cases. Weight-Loss as an appetite suppressant is also a possibility, and may be seen as an advantage - but this feature could also encourage abuse if weight-loss is desired. The critical questions become, whether the risk of strokes/sudden death is acceptable? But Ritalin carries a similar risk. Treatment strategies requiring more than one drug are likely inadvisable if Adderal is among them; many of its contraindications would argue against most combination drug therapies. Ritalin has been shown to produce marginal, short-term benefits in concentration and a reduction of ADHD symptoms, but it is questionable whether it is truly effective in the long term. After a month of treatment, the child's condition should be closely evaluated with involvement from teachers and physicians, when it might prove beneficial to use a different drug; with scanty evidence of Ritalin's reliable effectiveness after four weeks. Plus, there are real side-effects that should be avoided in patients with diagnosable psychiatric disorders. If cost is less of a factor, Strattera has advantages for some patients. Patent issues may make it more difficult to acquire for the immediate future. But it would prove useful as a back-up, in cases where stimulants were contraindicated, which can be the case with certain heart arrhythmias or physical abnormalities. Many patients with a tendency for psychotic disorders may be advised to avoid stimulants. With that in mind, Strattera must be seen as a long-term strategy rather than a quick-fix. Though it is difficult to abuse - the build-up period before it can shown to have noticeable effects may be off-putting to some. Furthermore, it may take up to two months before a valid judgment can be made concerning its effectiveness in an individual case. Strattera is believed to be somewhat less potent than some of the stimulants, but a point in its favor is the different risk factors for its side effects. The risk to the heart appears minimal, which may be worth considering for patients with cardiac illnesses. 10 But suicidal thoughts have been reported, as well as a case of severe liver damage. In the case of Vynance, it too is a stimulant, and while it appears essentially effective, there are heart risks, and psychotic dangers associated with it, and other stimulants. While the side-effects are potentially off-putting, the fact that the pill itself is designed to be prodrug makes it more difficult to abuse for drug seekers. It would appear to be a valid option in cases where a stimulant is desired, but where concern of addiction exists. Bupropion is perhaps a last-ditch choice. Some studies show an effectiveness in treating adult ADHD, but if the objective is increased classroom performance, the benefits to school-age children appear to be negligible. Indeed, behavioral treatment is advised as an alternative before Bupropion. Plus, the side effects are severe, and noteworthy. The risk of seizure may not be outweighed by the small benefit it may provide for increasing focus and concentration. Also worth mentioning is that it is not officially approved for the use in treating ADHD. The inconclusive results make it seem an unattractive choice. Its most practical use seems to be in overcoming nicotine addiction. Ultimately, Adderal has the likelihood of being the best option for the widest range of patients; it is more potent, reliable, and can be effective for the long term. But alternatives should still be made available in cases of pre-existing vulnerabilities to the conditions Adderal can exacerbate. The other stimulants appear useful primarily as a means to avoid contraindications of Adderal. Even though Adderal has the support of many clinicians, there may be disagreement as to its ultimate superiority. But for the purpose of classroom performance, there is reason to classify it as the first-choice unless other factors intervene. REFERENCES Adderall XR prescribing information". Shire US. March 2009. http://www.adderallxr.com/pdf/AXR_FPI.pdf. Retrieved 2009-06-23. Attention-deficit/hyperactivity disorder. In: Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR. 4th ed. Arlington, Va.: American Psychiatric Association; 2000. http://www.psychiatryonline.com. 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