Compared with placebo, 50 mg lisdexamfetamine significantly increased the peak systolic blood pressure when administered both orally and intravenously and diastolic blood pressure when given orally (Figure 6). What is also evident from the data in Figure 6 is that the magnitude of increases in systolic and diastolic blood pressures was not statistically different after oral or intravenous administration of lisdexamfetamine. Once again, the reproducible pharmacokinetics of its active metabolite, d-amphetamine, are probably due to the rate-limited, enzymatic cleavage of the precursor molecule that occurs primarily in red blood cells (Ermer et al., 2010). Biederman et al. (2007a) published results from the only clinical trial where the efficacy and safety of lisdexamfetamine in ADHD was compared directly against another clinically proven drug, MES-amphetamine XR. Following a 3-week, open-label run-in period where the dose of MES-amphetamine XR was optimised to 10, 20 or 30 mg once a day, subjects were then randomised into a 3-way double-blind, placebo-controlled crossover trial. They received their optimal dose of MES-amphetamine XR, an equivalent dose of lisdexamfetamine in terms of d-amphetamine base, or placebo.
Amphetamine-related emergency visits to sentinel hospitals
These differences in the PK and PD characteristics of IR d-amphetamine and lisdexamfetamine observed in humans by Jasinski and Krishnan (2009b) are very similar to the results from the rat PK/PD study that are described earlier in this review (Jackson et al., 2011; Rowley et al., 2011). Several currently marketed amphetamine formulations contain both enantiomers, including those marketed under the brand names Adderall, Adderall XR, Mydayis,note 1 Adzenys ER, Adzenys XR-ODT, Dyanavel XR, Evekeo, and Evekeo ODT. A prodrug form of dextroamphetamine, lisdexamfetamine, is also available and is marketed under the brand name Vyvanse. Appropriate studies have not been performed on the relationship of age to the effects of amphetamine tablets in children with obesity who are younger than 12 years of age, in children with narcolepsy who are younger than 6 years of age, and in children with ADHD who are younger than 3 years of age. Amphetamine is a medication used in the management and treatment of ADHD and narcolepsy. This activity reviews the indications, action, and contraindications for amphetamine as an agent in treating ADHD and narcolepsy.
Dextroamphetamine
On the other hand, the innovations in formulation technology and drug delivery systems have made significant strides forward in improving the clinical management of ADHD. All of the stimulants have biological half-lives that require at least twice-daily dosing to deliver efficacy over 12–14 h. ADHD is characterised by inattention, distractibility, working memory deficits and impulsivity, and as such, subjects with this disorder are particularly unsuited to compliance with rigid dosing schedules. Administering a once-daily stimulant medication to a child or adolescent first thing in the morning under parental supervision relieves him/her of the requirement to take additional medication outside of the home, and it also eliminates the need for the patient to take additional medication within strict time-windows. One of the additional benefits of these new formulations is their tamper deterrence, making it difficult for abusers to extract amphetamine for self-administration by hazardous routes, such as smoking, ‘snorting’ or intravenous injection.
Treatment Options
Therefore, optimising therapeutic efficacy whilst simultaneously maintaining side effects at an acceptable level is a difficult balance requiring careful dose titration in the patient. Volkow and colleagues have performed an enormous body of research using PET and other brain imaging techniques to explore the relationship between DAT occupancy, synaptic dopamine concentration and dopamine D2 receptor occupancy for psychostimulant drugs of abuse. These researchers have also demonstrated that the rate of DAT occupancy by drugs such as cocaine and methylphenidate is critical to their ability to produce ‘highs’ in human subjects (Volkow and Swanson, 2003; Volkow et al., 1996a,b, 1997, 1999a,b).
- This medicine may cause Raynaud’s phenomenon, which is a problem with blood circulation in the fingers or toes.
- The use of stimulants such as amphetamines and methylphenidate were shown to be effective and well-tolerated when taken over several years.
- Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- On the other hand, the innovations in formulation technology and drug delivery systems have made significant strides forward in improving the clinical management of ADHD.
- Furthermore, switching to the intravenous route for lisdexamfetamine appeared to have relatively little influence on the abuse potential of the prodrug.
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As shown in Table 4, the average maximum scores on the DQRS and Drug Rating Questionnaire – Observer (DRQO) scales for ‘Liking’, ‘Feel drug effect’, and ‘Disliking’ reveal that the subjective effects of lisdexamfetamine (50 mg) were not significantly different when the prodrug was administered orally or intravenously. This result shows that the subjective effects of lisdexamfetamine were not enhanced when the drug was given intravenously. Blood pressure measurements are useful objective measures of the PD effects of sympathomimetic drugs.
Reinforcement disorders
Another factor was the use of d-amphetamine as an antidepressant in the 1950s before the discovery of the tricyclic monoamine reuptake inhibitors. There were cases of misuse by patients, and also a significant degree of diversion of the prescribed drug into youth misuse and/or abuse that may also have contributed to wariness by prescribers regarding its clinical use. In later years, local outbreaks of d-amphetamine abuse have occurred in various parts of the UK, often using locally synthesised d-amphetamine; again, this will have made doctors shy away from prescribing d-amphetamine lest it contributes to its misuse. In the USA, d-amphetamine-containing medications, especially MES-amphetamine, have been very widely used as treatments for ADHD.
If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines. From sinus infections and high blood pressure to preventive screening, we’re here for you. If you have questions about whether or not a shortage might affect you, ask your provider or a pharmacist. They may also be able to offer suggestions on how to avoid running out of your medications. It’s similar to how your hands have the same structure but are mirror images of each other. The Recovery Village Baptist Health specializes in compassionate, evidence-based care tailored to your needs.
Both isomers of amphetamine dose-dependently increased the extracellular concentrations of noradrenaline in the prefrontal cortex (PFC) and dopamine in the striatum. When comparing the effects of drugs on the efflux of catecholamines in the PFC it is important to take into account the highly unusual neuroanatomy of this brain region. The density of DAT sites on PFC dopaminergic neurones is very low (Hitri et al., 1991), and as a consequence, most dopamine that is released is sequestered via NET into noradrenergic neurones (Mazei et al., 2002; Morón et al., 2002; Stahl, 2003).
- Amphetamines are a type of stimulant drug that makes your nervous system more active.
- However, it is possible that the actions of amphetamine to increase serotonergic drive may have a beneficial effect on anxiety or depression that is often comorbid with ADHD.
- Treatment programs use behavior change techniques through counseling (talk therapy).
- There has been little research conducted in humans on this kinetic course using brain imaging, but it seems likely that the same rules apply.
- We have used dual-probe intracerebral microdialysis to explore the in vivo effects of d- and l-amphetamine in the spontaneously hypertensive rat (SHR), which has been proposed as a rodent model of ADHD (Heal et al., 2008; Sagvolden, 2000; Sagvolden et al., 2005, 2009; see review by Wickens et al., 2011).
Some of the common short-term effects of amphetamine include nervousness, insomnia, headaches, increased blood pressure and heart rate, and loss of appetite. Other symptoms may include increased anxiety, irritability, negative affect and worsening motor tics. Side effects due to the action of amphetamines on the digestive system may include vomiting, nausea and abdominal cramps. High doses of amphetamines can also induce symptoms of psychosis and agitation in some (but not all) healthy individuals, that are similar to schizophrenia. Such drug-induced psychosis often involves paranoid delusions, hallucinations, violent behavior and occasionally disorganized speech.
These findings strengthen the view that the unusual mechanism for metabolic conversion of lisdexamfetamine to d-amphetamine has important implications for its liability for recreational abuse. The subjective effects of a 50 mg dose of lisdexamfetamine were identical in magnitude when the prodrug was administered orally or Amphetamine Drug Profile by intravenous injection, demonstrating that intravenous injection did not enhance the pharmacological potency of lisdexamfetamine in the CNS. The increases in systolic and diastolic blood pressures after oral or by intravenous administration of lisdexamfetamine were also identical, confirming by objective and quantifiable physiological measures that the intravenous injection route did not enhance its pharmacological potency.
Amphetamine has occasional therapeutic use in the treatment of narcolepsy and attention deficit hyperactivity disorder (ADHD). Amphetamine belongs to a family of stimulants that share similar chemical and biological properties, referred to as amphetamine-type substances. Besides amphetamine and methamphetamine, this family also includes other stimulant substances such as methylphenidate, methylenedioxymethamphetamine, ephedrine and pseudoephedrine.
Methylphenidate is sold under the brand names of Ritalin and Concerta, and is another commonly used stimulant for the treatment of ADHD. Methylphenidate is not an amphetamine but belongs to the amphetamine-type substance family. Ritalin has a similar mode of action and side effect profile as Adderall but it has a shorter half-life. Amphetamine exists in two chemically identical, or isomeric, forms that are mirror images of each other. These two forms (referred to as enantiomers) are non-superimposable and only differ in spatial configuration. The two mirror-image isomers are referred to as the dextro and levo forms of the compound.
It is believed that amphetamine was first manufactured in the 1880s by the German chemist Leuckart, although evidence for this is lacking. It appears that, as in the case of methamphetamine, systematic studies of its chemistry did not come about until the early twentieth century. Amphetamine has some limited therapeutic use, but most is manufactured in clandestine laboratories in Europe.
On the primary and secondary efficacy variables of behaviour, attention and problem solving, lisdexamfetamine delivered equivalent or better efficacy than MES-amphetamine XR with both drugs being maximally effective at 2 h post-dose (Biederman et al., 2007a). However, on the problem-solving endpoints, it was also evident that lisdexamfetamine maintained its maximum effect for at least 12 h, whereas the effect of MES-amphetamine XR showed a clear decline after 6–8 h (Biederman et al., 2007a). A post-hoc analysis of the data also showed that the sex and age of the subjects had no significant influence on the efficacy of lisdexamfetamine (Wigal et al., 2010b). Translocation of monoamines from the cytosolic pool into the storage pool is performed by a similar active transporter system, the vesicular monoamine transporter 2 (VMAT2) (Fei et al., 2008; Fleckenstein et al., 2009; Ramamoorthy et al., 2011). Since amphetamine competes with the endogenous monoamines for transport into the nerve terminals via NET, DAT or SERT, the higher the concentration of amphetamine present in the synapse, the greater the number of amphetamine molecules transported relative to every molecule of monoamine (see Figure 3). Once inside the presynaptic terminal, amphetamine displaces monoamines from the cytosolic pool.