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Author Topic: Treatment of Methamphetamine withdrawal (in trauma patients)  (Read 3162 times)

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Treatment of Methamphetamine withdrawal (in trauma patients)
« on: September 12, 2023, 02:17:01 AM »

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note: This is an excerpt only

Treatment of Methamphetamine withdrawal in trauma patients

Few drugs have shown any clinical efficacy in managing methamphetamine-withdrawal and there is only a limited number of randomized trials available on this topic.

However, we identified clinical trials showing promising results for the acute medical management of methamphetamine-positive patients.

N-acetylcysteine (NAC), a drug used to treat acetaminophen overdose and IV contrast toxicity, has also been found to decrease methamphetamine cravings. In one controlled, double-blinded randomized study, patients receiving 1200 mg per day of oral NAC over a four-week period had decreased cravings for methamphetamine compared to placebo (P<0.001). This drug may prove useful in the acute setting.

Bupropion, a dopamine reuptake inhibitor used to treat depression and nicotine dependence, is thought to increase synaptic concentrations of dopamine. Chronic methamphetamine use results in low dopaminergic tone. One randomized, placebo-controlled trial of bupropion in methamphetamine dependence found that 150 mg BID of oral bupropion increased abstinence from methamphetamine in low to moderate users. Bupropion is fairly well-tolerated with limited side effects of insomnia, dry mouth, and nausea. In a study of 151 patients, bupropion has also been shown to produce nearly-statistically significant differences in methamphetamine abstinence when compared to a placebo (p=0.09), possibly leading to decreased recidivism in an outpatient setting.

Modafinil is a glutamate enhancer which produces many contradictory effects of stimulant withdrawal, such as increased energy, attention, wakefulness, and locomotion, while improving mood and reducing appetite. Patients dependent on cocaine who were treated with modafinil reported less use (p=0.03) when compared to a placebo group. Applying this to the use of methamphetamine, the drug may assist with the dysphoria characteristic of methamphetamine withdrawal. Modafinil may also decrease craving for methamphetamine while improving overall cognition and is currently being investigated in a number of clinical trials.

Dextroamphetamine has also shown some benefit in decreasing methamphetamine cravings and withdrawal symptoms. Researchers have used 60 mg of oral sustained-release dextroamphetamine over a period of 8 weeks to achieve these results. Dextroamphetamine may play a role in the recovery and rehabilitation of an injured patient through a mechanism similar to bupropion.

Gamma-vinyl GABA (GVG), an antiepileptic that prevents breakdown of GABA, has shown efficacy in sustaining abstinence from methamphetamine. In a study evaluating abstinence, 16 of 18 participants completing the 9-week study tested negative for methamphetamine and cocaine. GVG was started at 500 mg twice daily for days 1-3 and increased to 1.5 g once daily for days 4-7 and 2 g once daily for days 8-14. On day 15, subjects were placed on 3 g once daily for 4 weeks, and then tapered to zero over the next 3 weeks, for a total of 137 grams over the entire study. Although GVG is associated with changes in visual acuity, it was not observed in the study.

Antipsychotics have also been proposed to aid in withdrawal management. In one study, risperidone was administered at 3.6 mg/day and resulted in decreased methamphetamine use and significantly improved fine motor functioning after 30 days (p = 0.001). Antipsychotic medications can manage symptoms such as irritability, agitation, depression, increased sleeping, increased appetite, and muscle aches. Antipsychotics have been showed to resolve these symptoms within one week after discontinuation of stimulants such as methamphetamine. This lends support for antipsychotics having potential use in trauma patients with prolonged hospital stays.

Rivastigmine is an acetylcholinesterase inhibitor studied for use in methamphetamine-positive patients. Acetylcholine has been linked to the reinforcing and psychomotor activating effects of methamphetamine [10] thus, an acetylcholinesterase inhibitor may decrease such behaviors. Rivastigmine has reduced methamphetamine-associated increases in diastolic blood pressure and self-reported feelings of anxiety as well as the desire for more drugs.

Other agents have limited efficacy in managing methamphetamine-positive patients. Mirtazapine has been shown in one study to be well tolerated, although participants reported myalgia more frequently than those treated with modafinil. Of note, modafinil was noted to cause less sleep disturbance than mirtazapine. Another study of mirtazapine revealed that it may lessen anxiety and hyperarousal caused by methamphetamine withdrawal; however, other investigations have failed to duplicate these results. Imipramine has not shown any significant benefits in managing cocaine/methamphetamine-abusing patients].

Ondansetron, a 5-HT3 receptor antagonist and modulator of corticomesolimbic dopamine, functions through its low affinity for dopamine receptors and has shown potential benefit in outpatient settings. Some data in an animal-based investigation suggested that the combination of ondansetron with pergolide, ergoline-based dopamine receptor, may serve as a useful treatment for methamphetamine abuse by reducing relapse rates. Sertraline, a selective serotonin reuptake inhibitor has proven to be useful to an extent. When combined with contingency management, sertraline allowed more patients to abstain from methamphetamine when compared to patients treated with sertraline alone. Contingency management involves rewarding of good behavior and implementation of operant conditioning and reinforcement, which can be used to support drug abusers. However, in patients with symptoms of depression, sertraline did not have an improved outcome compared to placebo, and actually resulted in increased methamphetamine use and more frequent relapse (p<0.05).

Lobeline may be very useful for the treatment of stimulant abusers, including those of methamphetamine. It may interact and stimulate the vesicular monoamine transporter (VMAT), as well as the cell surface dopamine transporter (DAT), which are both action sites for methamphetamine. Lobeline has long been used to aid in smoking cessation and has a low abuse potential. A study showed that lobeline induced dopamine release in mammalian cells expressing dopamine transport proteins DAT and VMAT-2.  In methamphetamine users, dopamine release may reduce overall cravings.

Memantine, a non-competitive antagonist of the N-methyl-D-aspartate receptor (NMDA glutamate receptor), was used in a 2010 study with methamphetamine-intoxicated rats.

This study found that memantine inhibited methamphetamine-triggered behavior and reversed overall anxiety. Adverse effects of methamphetamine can be potentially treated with memantine in an attempt to prevent cognitive deficits.

Animal studies provide a plethora of information regarding certain drug treatments for methamphetamine withdrawal. For example, one study tested the usefulness of propofol in methamphetamine-intoxicated rats and found reduced cerebral oxidative stress and swelling and improved mitochondrial function].

Another study showed the protective role of melatonin on the blood brain barrier in methamphetamine-induced inflammatory responses.  More clinical trials will be necessary to investigate the potential of these drugs for the treatment of methamphetamine-withdrawal.

The PDF version is attached:
« Last Edit: September 12, 2023, 02:31:52 AM by Chip »
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