Aripiprazole for the treatment of methamphetamine dependence.
Received Sep 2; Accepted Dec 8.
Abstract Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type.
A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist aripiprazoleGABAergic agents gabapentin and serotonergic agents SSRI, ondansetron, mirtazapine.
Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise.
Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.
While the prevalence of methamphetamine use in the general population is low, rates in some social groups in Aripiprazole for the treatment of methamphetamine dependence essay age groups are significantly higher [ 12 ]. Methamphetamine is available in different forms such as a pure crystalline hydrochloride salt or as formulated tablets.
Routes of administration are intranasal sniffing, pulmonary inhalation, injection and oral ingestion [ 3 ]. The effects of methamphetamine use include euphoria and many of the same stimulant effects seen with cocaine, but these effects may last much longer [ 3 ]. Methamphetamine exerts multiple effects in the central nervous system and acts as a highly potent releaser of monoamines by increasing cytoplasmic concentrations of dopamine and serotonin and also norepinephrine, adrenaline and histamine [ 4 ] i by blocking the activity of the intracellular vesicular monoamine transporter 2 VMAT2 [ 56 ], ii by decreasing the expression of the dopamine transporter DAT at the cell surface [ 7 ] and iii by inhibiting the activity of monoamine oxidase and increasing the activity and the expression of tyrosine hydroxylase [ 8 ].
Brain imaging studies of methamphetamine dependent patients have demonstrated brain structural abnormalities severe grey-matter deficits in the cingulate, limbic and paralimbic cortices, smaller hippocampal volumes, significant white-matter hypertrophy, medial temporal lobe damage and striatal enlargement [ 910 ] and neurochemical and metabolite changes particularly prominent in the ventral striatum [ 1112 ].
Prolonged use leads to down-regulation of dopamine D2-receptors and uptake sites [ 13 ]. A state of hypodopaminergic activity is reported as in other addictions [ 1415 ]. There is also evidence for disturbances of mood and anxiety and regional cerebral metabolic abnormalities in recently abstinent methamphetamine dependent patients [ 16 ].
Methamphetamine dependence is a serious worldwide public health problem with major medical [ 17 — 21 ], psychiatric [ 22 — 25 ], cognitive [ 26 — 29 ], socioeconomic and legal consequences [ 18 ].
Currently, there is no pharmacological therapy with established efficacy for the treatment of this addictive disorder, nor is there any medication approved by the regulatory authorities for such treatment [ 30 ]. Recent reviews on pharmacotherapy for methamphetamine dependence have been published [ 30 — 34 ], but this is a quickly evolving area with preclinical findings and clinical trials reported frequently.
Although there is not much substantial evidence in terms of proof of concept studies and randomized clinical trials, this review will bring to light some of the newer pharmacological targets.
We will focus on agents affecting the biogenic amine transporters mentioned above and other neurotransmitter systems acetylcholine, GABA, endogenous opioids, endocannabinoids. We will also discuss pharmacological candidates in the pipeline such as immunotherapies vaccine, anti-methamphetamine monoclonal antibodies and other approaches based on preclinical data.
We will not discuss the management of acute methamphetamine intoxication or the treatment of methamphetamine dependence in patients with comorbid psychiatric disorders.
References in empirical articles and narrative and meta-analytic reviews were used for further potential sources of articles. Tables are included to summarize the salient details of some studies.
The tables include clinical trials for those medications that appear to have shown the greatest promise at the time of this review e.
Human laboratory studies are not included in the tables, nor are studies involving compounds that have not yielded positive results e. The precise neurobiological mechanism of action of this medication is complex and includes dopaminergic and glutamatergic effects [ 39 ].
A recent brain imaging study showed that modafinil binds to the DAT, and thus shares some properties with methylphenidate [ 40 ]. Clinical studies suggest that modafinil may be effective in treating cocaine dependence [ 41 — 43 ], and might also be effective for methamphetamine dependence.
Modafinil stimulant-like activity has been proposed as a potential treatment to decrease the symptoms of cocaine withdrawal [ 43 ].
No evidence of significant abuse liability has been reported [ 44 ]. Modafinil may be a cognitive enhancer [ 50 ] in methamphetamine-dependent patients [ 51 ] and may therefore have the potential to improve the response to behavioural therapies.
Because of its weak stimulant properties, modafinil has been cited as a putative treatment to decrease stimulant drug seeking and craving. The findings of an open-label study of modafinil to treat methamphetamine withdrawal symptoms in an inpatient setting [ 53 ] indicated possible amelioration of these symptoms.
Primary outcome measures were self-reported use of drugs per week plus urine toxicology assays. There were no differences in treatment retention, medication adherence, methamphetamine abstinence, craving or severity of dependence.
Of possible clinical significance, there was a statistically significant reduction in systolic blood pressure in the modafinil group [ 54 ]. Modafinil therefore may have some beneficial effects in methamphetamine-dependent patients, although there is no clear evidence of its efficacy in reducing methamphetamine use.Addiction Drug Treatment Word count – date – 17/8/ Description: Addiction drug treatment is a treatment for the person who is having chronic or periodic dependence on the drug by repeated consumption of it.
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In summary, we found no evidence that aripiprazole is more effective than placebo at reducing methamphetamine use among actively-using, dependent adults. Future efforts to identify pharmacologic treatments for methamphetamine dependence may need to consider agents modifying multiple neurobiologic pathways concurrently.
Aripiprazole for the treatment of methamphetamine dependence Essay Sample Methamphetamines (Meth) cause a wide array of problems with its users, a lot of which are permanent. Meth’s affects range from neurological issues, alertness, paranoia, and aggression. Methamphetamine (METH) use and dependence is a serious public health concern with implications across multiple areas from societal impact to burden on psychiatric and medical resources.
An estimated 8% of admissions to substance abuse treatment programs are related to stimulants with METH/amphetamine abuse.
Aripiprazole for the treatment of methamphetamine dependence Essay Sample Methamphetamines (Meth) cause a wide array of problems with its users, a lot of which are permanent.
Meth’s affects range from neurological issues, .