Dual studies highlight Ketamine’s potential to treat anxiety and addiction

Two new studies suggest the psychiatric benefits of ketamine treatment may extend beyond just the targeting of depression. The research demonstrates ketamine may be helpful in targeting both anxiety- and substance abuse-related depression.

Although ketamine is a relatively old drug, originally developed in the 1950s as an anesthetic, over the last decade a growing body of research has affirmed its unique, and rapid, antidepressant effects. The anecdotal effects of the drug on depression have raced ahead of scientific research so quickly that ketamine clinics have popped up all across the United States, where the drug can be administered for up to US$1,000 a dose.

Much is still unknown about how efficacious ketamine actually is for depression. We don’t know ideal dosages, how long the treatments last, or how safe long-term usage is. Two newly published studies are adding to our knowledge about ketamine’s psychiatric uses, adding weight to the drug’s burgeoning new potential.

The first study, led by a team from Massachusetts General Hospital and Harvard Medical School, set out to study how effective ketamine is at treating patients with anxiety-based treatment-resistant depression. This is an important question to resolve, as many traditional antidepressants do not consistently improve anxiety-based symptoms in cases of major depression.

The study took 99 subjects with treatment-resistant depression, half of whom suffered from high anxiety and half of whom displayed no anxious symptoms. The study randomly administered subjects either one of four different intravenous ketamine doses, or midazolam, a general sedative that could serve as a control.

As well as demonstrating ketamine’s novel antidepressant qualities, the study revealed the drug worked equally well in both anxious and non-anxious subjects. This suggests that ketamine’s antidepressant effects are uniquely effective across different types of treatment-resistant depression, something that cannot be said for many major antidepressant drugs.

“In contrast to reports from monoaminergic antidepressants, our data suggest that patients with anxious depression respond equally as well to ketamine compared to those with non-anxious depression,” write the researchers in the published study.

The second new study comes from a team at Yale University School of Medicine. This research investigated whether ketamine could be effective in treating addiction-related depression when administered in tandem with naltrexone.

A study in 2018 offered a small but significant finding, revealing that ketamine was ineffective in treating depression when administered alongside naltrexone. These results were important because they suggested that part of ketamine’s antidepressant effects may be related to the activation of opioid receptors, which would mean long-term ketamine use may potentially result in problems with addiction, something that many researchers have long argued against.

Naltrexone, an opioid receptor blocker, is often administered effectively to combat serious substance abuse problems, so if it rendered ketamine ineffective then that would cast doubt on much research into how ketamine actually works to reduce symptoms of depression. The new Yale research was small, with a sample of only five patients, but its results strongly suggest ketamine and naltrexone do not cancel each other out.

All five subjects suffering from alcohol use disorder and depression displayed significant depressive relief from ketamine dosages despite long-term naltrexone consumption. Senior author on the study, John Krystal, says although larger studies still need to be completed the research does suggest ketamine and naltrexone may be a complimentary combination that helps treat substance abuse and its related depression.

“[The results] raise the possibility that for people who have depression complicated by substance abuse disorders, the combination of ketamine and naltrexone may be a strategy to explore in the effort to optimally treat both conditions,” says Krystal.

Although this new study only consisted of five subjects, the prior research linking ketamine to the opioid system was generated from just 12 subjects. So we are still in uncharted territory regarding ketamine’s mechanistic effects of the brain. But the Yale research should assuage some fears that ketamine may be, “merely another opioid in a novel form.”

The ketamine anxiety study was published in the journal Depress Anxiety.

The ketamine naltrexone study was published in the journal JAMA Psychiatry.

Source: Yale News

Intranasal ketamine as effective as fentanyl at relieving acute pain in kids

Intranasal ketamine is noninferior to intranasal fentanyl at relieving pain in children with acute extremity injuries, a new study found.

“We were happy to discover similar results to the two other prior pediatric trials and pleasantly surprised to see how similar the rates of rescue analgesia were to those studies,” Dr. Theresa M. Frey of Cincinnati Children’s Hospital Medical Center told Reuters Health by email.

Opioids are commonly used to treat children presenting with severe pain due to traumatic injuries, but concerns regarding adverse effects and the ongoing opioid epidemic have led clinicians to seek non-opioid alternatives, such as ketamine.

Dr. Frey and colleagues in the PRIME randomized noninferiority study compared intranasal ketamine (1.5 mg/kg) to intranasal fentanyl (2 mcg/kg) for pain reduction in children with acute extremity injuries.

The 43 children randomized to ketamine and 42 children randomized to fentanyl experienced similar significant pain reduction at 15, 30, and 60 minutes, and ketamine was noninferior to fentanyl regarding the primary outcome of pain reduction 30 minutes after study medication administration.

Highest achieved sedation scores did not differ significantly between the groups, and neither group experienced a University of Michigan Sedation Scale score higher than 2, the researchers report in JAMA Pediatrics, online December 28, 2018.

More children in the ketamine group (77%) than in the fentanyl group (31%) experienced at least one adverse event, but all such events were minor and transient.

“I would like to highlight that we did not find significantly more adverse events despite higher doses of both medications, and the only significant difference in adverse events between groups was at the 15-minute assessment during which ketamine patients experienced more drowsiness,” Dr. Frey said. “I would argue that a parent may welcome this drowsiness after observing their child suffering from such significant pain prior to medication.”

The need for rescue analgesia at 15, 30, and 60 minutes did not differ significantly between the groups.

“We know opioids can lead to a decrease in blood pressure, so for patients presenting in shock or impending shock due to infection, hemorrhage, etc, clinicians may not give any analgesia and their patients are left in pain,” Dr. Frey said. “My hope is that physicians at least consider ketamine, especially for these types of patients.”

“Additionally,” she said, “I hope that physicians consider ketamine for pain in the emergency setting if they are anticipating that their patients will need ketamine procedural sedation during their emergency department (ED) stay, as we know there is increased risk when opioids are administered prior to the sedation.”

Dr. Sergey M. Motov from Maimonides Medical Center, in Brooklyn, NY, who recently found intranasal ketamine (1 mg/kg) to be inferior to intranasal fentanyl (1.5 mcg/kg) in children with moderate to severe pain, told Reuters Health by email, “In the situations when opioids are contraindicated or may worsen patients’ condition, low-dose ketamine administered intravenously or intranasally is a viable and effective analgesic alternative for short-term analgesia in the ED. However, ketamine use is associated with high rates of minor and transient but bothersome adverse effects.”

“Patient coaching prior to administration of low-dose ketamine with respect to development of psycho-perceptual adverse effects (mainly feelings of unreality) will greatly improve patients’ experience with this medication,” said Dr. Motov, who was not involved in the new work.

Dr. Marcus Nemeth of the University Hospital Goettingen in Germany recently reported that intranasal fentanyl, ketamine, midazolam, or combinations thereof provided effective analgesia in pediatric emergency care. He told Reuters Health by email, “Ketamine as a widely available analgesic can be used effectively and equivalently with respect to pain reduction, when opioids are not readily available or contraindicated. Physicians should take ketamine as a good treatment option for moderate to severe traumatic pain into account.”

Dr. Nemeth, who also was not involved in the study, added, “I would favor fentanyl/sufentanil for a child that ‘only’ needs analgesia, ie, a child which is non-agitated with no need for any desired sedating effect.”

—Will Boggs, MD

Original article: https://www.mdlinx.com/practice-management/top-medical-news/article/2019/01/07/7552666

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