Ketamine vs ECT for Depression: First Head-to-Head Results

 Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than IV ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a "valuable" option for treating severe depression, particularly in younger patients, investigators note.

The high rate of remission for ketamine infusion "indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine," principal investigator Pouya Movahed Rad, MD, PhD (Pharmacology), senior consultant and researcher in psychiatry, Lund University, Sweden, told Medscape Medical News.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.

Primary Focus on Remission

The parallel, open-label, non-inferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery–Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (age 51-85 years) compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger vs older patients (61% vs 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).

Let the Patient Decide

As expected, ECT and ketamine had distinct side effect profiles. Prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

"Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable," Movahed Rad said.

The investigators note that participating study sites all had long-time experience with ECT but no experience administering ketamine.

"Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group," they write.

If both ECT and ketamine are available, "the patient's preference should, of course, be taken into account when choosing treatment," said Movahed Rad.

"Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa," he added.

A Good Alternative

Commenting on the findings for Medscape Medical News, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Canada, said the data confirm ECT is highly effective for treatment-resistant depression and show that "newcomer" IV ketamine also performs "exceptionally well."

"This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population," added McIntyre, who was not involved in the research.

McIntyre added that this "rigorous, well-designed study addresses a critical question" about the comparative efficacy of ECT and IV ketamine. It also makes "quite a strong statement about the efficacy of ketamine in younger people."

He cautioned, however, that this study represents the "first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we'll look forward to seeing the results."

The fact that 15% to 20% of the study patients had psychotic depression is also noteworthy, said McIntyre.

"We've been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients," he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

"I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say, 'Thanks but no thanks.' That's a problem because ECT is so effective.

The study was funded by the Swedish Research Council, The Crafoord Foundation, Skåne Regional Council, The Königska Foundation, Lions forsknings foundation Skåne, and the OM Perssons donation foundation. Movhed Rad has received lecturer honoraria from Lundbeck. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. McIntyre is also CEO of AltMed.

Int J Neuropsychopharmacol. Published online December 4, 2021. Full text

https://www.medscape.com/viewarticle/967472

High Drug Prices on State Legislatures' Radars in 2022

 Curbing high prescription drug prices is one of the healthcare priorities that state legislatures will be pursuing in 2022, experts said Friday at a briefing sponsored by the Alliance for Health Policy and Arnold Ventures.

Prescription drug spending has been a high priority for the last 6 years, according to Maureen Hensley-Quinn, MPA, senior program director of coverage, cost, and value at the National Academy for State Health Policy. Her organization brought state officials together in 2016 "and asked, 'What is keeping you up at night?' and it was prescription drug costs," she said. "It came on the heels of the hep C cure, which was amazing and groundbreaking, but incredibly expensive -- at a million dollars for a treatment cycle, it was taking over Medicaid budgets."

"State budgets were truly being dominated in a way that they were not anticipating by this drug, and state officials across Medicaid, employee health plans, and others did not want to be in a position to say, 'No, we can't provide you this life-saving, life-changing prescription drug,'" said Hensley-Quinn. "And so I believe that was an initial catalyst." Laws regulating prescription drug prices have been enacted in all 50 states, and since 2017, 49 states have enacted more than 200 such laws, she said.

State efforts to contain prescription drug costs have taken a variety of forms, said Colleen Becker, MPP, senior policy specialist at the National Conference of State Legislatures. "Many legislators have focused on reducing consumers' out-of-pocket costs, and one of the most prominent examples of that is insulin," she said. "The most common state action is limiting copays for insulin, and 19 states currently have laws which limit that amount and [limits] range anywhere from $25 to about $100 for a 30-day supply." In addition, "there's also been momentum around access to supplies such as continuous glucose monitors; some states have even developed a state-run patient assistance program," said Becker.

Another area of consumer action has been laws regarding copay accumulators -- this is when insurers bar patients from using drugmakers' copay coupons to help offset their plan's drug copays and deductibles. "Currently, 12 states and Puerto Rico have a requirement that any payment or discount made on behalf of the patient must be applied to a patient's annual out-of-pocket cost-sharing requirements," Becker said. States also have been looking at drug importation as a possible way to cut costs for patients. However, "even though eight states have importation laws, the state must first get their importation plan approved by the federal government," and none has thus far, she said.

Pharmacy benefit managers (PBMs) also have come under state scrutiny. "Last year, we tracked about 247 bills related to PBM reform, and that's about a third of total proposed prescription drug legislation," Becker noted, adding that about half of those bills were enacted. "This is very much an area where we've seen bipartisan support ... A common approach is requiring PBMs to register or obtain licensure to do business in the state."

Prohibiting PBMs from enforcing "gag clauses," which limit a pharmacist's ability to inform a patient if it would be cheaper to pay out-of-pocket for a drug rather than use their insurance, is another popular approach -- "over 30 states have this type of legislation implemented, and we're seeing it already proposed for 2022," she added, noting that there is also a federal prohibition against gag clauses. From a purchaser standpoint, some states are using "reverse auctions," in which PBMs compete to contract with the state's employee benefit plan, and the PBM with the lowest-priced offer wins.

Prescription drug affordability boards are another strategy being pursued by the states, according to Becker. "Some folks are seeing these boards as having the potential of helping policymakers drill down on costs and really helping to find viable solutions. Eight states have pursued this approach, and so far we're tracking three [more] states for 2022."

Although prescription drug prices are a big focus of state legislators' attention, "by far the largest proportion of U.S. healthcare spend is on hospitals, health systems, and high-cost providers," said Hensley-Quinn. State legislators are seeking to address those prices in a variety of ways; for example, "there are a growing number of states seeking the collection of detailed hospital price cost and financial data to inform their policy approaches," and states are also "seeking authority to mitigate further consolidation or enforce anti-competitive contracting [bans] among hospitals, health systems, and health plans," she said.

States are also starting to plan for the end of the COVID-19 pandemic, said Stephanie Anthony, JD, MPH, senior advisor at Manatt Health, a professional services firm. She noted that the public health emergency declared by President Biden is currently set to end on April 15, although it may be extended. The Families First Coronavirus Relief Act requires states to extend Medicaid eligibility through the public health emergency, so "many states are starting to think about that and determine their approaches for restarting eligibility determination," Anthony said.

https://www.medpagetoday.com/publichealthpolicy/generalprofessionalissues/96924

Murphy: Time for New Jersey to 'learn how to live' with COVID

 Gov. Phil Murphy (D-N.J.) said on Sunday that his state will need to "learn how to live" with the COVID-19 pandemic.

"We're not going to manage this to zero. We have to learn how to live with this," Murphy said of the pandemic on NBC's "Meet the Press." 

"You got to preempt this clearly, and we're now getting caught up as a country," he added, noting that COVID-19 cases are coming down in New Jersey and New York, which were “hit earliest by all of these waves.” 

Arkansas Gov. Asa Hutchinson (R) also voiced a similar sentiment during an appearance on "Meet the Press." 

"I do believe that we need to move from a pandemic status and mode of operation to more endemic," he said. "I think we need to move out of the panic mode. I think we need to handle this and make sure that we continue with our normal lives," Hutchinson added, noting that COVID-19 cases in Arkansas peaked last week. 

The governors’ remarks come as the White House said last week that roughly 60 million U.S. households had ordered free at-home COVID-19 tests from the Biden administration since the website used to order the tests launched.

Meanwhile, a Kaiser Family Foundation poll published last week found that 75 percent of Americans said they were tired of the pandemic.

Divided by party lines, 74 percent of Democrats, 72 percent of Republicans and 80 percent of independents said they were tired of the COVID-19, and over 70 percent of each group said they were frustrated by the pandemic as well. 

https://thehill.com/homenews/sunday-talk-shows/591996-murphy-says-time-for-state-to-learn-how-to-live-with-covid-19

Doctors were complicit in Holocaust atrocities. Current and future health care workers need to know

 The liberation of the concentration camp at Auschwitz on Jan. 27, 1945, revealed many horrors. Among them were the atrocities perpetrated by doctors who took ethics very seriously, albeit with an unusual code of ethics with the State as the “patient.”

When SS physician Fritz Klein was asked by a prisoner-physician how he reconciled his actions in concentration camps with his ethical obligations as a physician, he answered, “Out of respect for human life, I would remove a purulent appendix from a diseased body. The Jews are the purulent appendix in the body of Europe.”

These weren’t just a few “bad apples,” however, who knowingly harmed thousands of people in Auschwitz and other death camps. To understand what happened, and how it happened, it’s important to look at the entire tree from which the apples came:  medicine, public health, and biomedical research in Nazi Germany involving doctors, nurses, midwives, and many others, and encompassing disciplines such as psychiatry, neurology, neuropathology, anatomy and physiology, infectious diseases, surgery, genetics and twin research, and beyond.

Physicians voluntarily joined the Nazi party and, without any pressure, took part in forced sterilization in hospitals between 1933 and 1939, in forced human experiments at Auschwitz and other camps, and in programs to kill individuals diagnosed as “unworthy of life,” including people with mental illness and developmental disabilities. These programs were implemented in collaboration with nurses and midwives.

Some of the physicians and technical staff of the Aktion T4 forced “euthanasia” program then willingly lent their murderous technical expertise to the establishment of gas chambers in the extermination camps.

Medical and other scientists used their unfettered access to people in concentration camps to study things like the physiological impact of high altitude, freezing temperatures, and drinking seawater, of typhus and infectious jaundice, and to develop practical means of sterilization, maiming, and killing thousands of their “subjects” with extreme cruelty.

Although Josef Mengele, also known as the Angel of Death, was the best known of these morally corrupt physicians, he was certainly not alone. Many of them continued in their academic and clinical work after the war, in Germany and abroad; some were invited to come to the United States to continue their research. They did so supported by a pervasive silence about this history.

This gruesome episode in world history and human life continues to raise a deeply disturbing question: How could healers have become complicit in mass murder?

We believe that all health care workers, from doctors and nurses and midwives to radiation technologists, respiratory therapists, and others need to know this history and systematically reflect on its meaning in light of current health and other societal crises now underway: disparities in the Covid-19 pandemic fed by racism; political divisions and right-wing extremism that pose an immediate threat to democracies around the world; the new rising tide of antisemitism; the existence and continued risk of mass atrocities around the globe which create significant public and mental health issues; and more.

Health care practitioners need to be aware that the vulnerabilities and temptations in their profession that existed in Nazi Germany are still present today. At the same time, they should be aware of the health professionals in ghettos and camps who exhibited moral courage and resistance under oppression. These can serve as inspiration in health systems with their rapidly evolving technologies and economic pressures. They may also serve as inspiration for fundamental health care systems changes based on the recognition of the shared humanity of health professionals and patients.

Reflecting on this dark history of medicine and the Holocaust, as well as on examples of moral courage, can support the orientation of health care workers’ moral compasses. Health care trainees and professionals face “echoes” of this history when confronted with ubiquitous ethical dilemmas in medicine. As one health care trainee wrote upon learning this history, “Realizing our connection with the past is crucial…It is especially important not to dismiss the physicians who were compliant with the Holocaust as simply evil monsters. We all have the potential to do good or to do bad, and we have to be critically aware of this.” History can inform.

Learning the history of medicine during the Holocaust should become part of the toolkit of health care professionals as a guide to ethical vigilance and needs to be included in curricula. When the doctor in the white coat or the nurse in blue scrubs approaches you in your hospital bed, it is not enough that they bring a stethoscope, technical skills, and knowledge. They must bring humanity, moral character, and agency.

Every health care organization must be structured around a culture of moral leadership with adherence to core values that acknowledge universal human rights, including the right to health; the fight against social inequalities and racism that affect access to health care and education; and maintaining high professional and ethical standards in caring for patients and conducting biomedical research. Understanding the role medicine played during the Nazi period and especially in the Holocaust can inform these core values.

Trust in medicine is a precious and fragile resource that we simply cannot afford to lose, as the pandemic has cruelly shown us. When 8-year-old Irene Izme was liberated from Auschwitz, she said, “I hate doctors.” She had been deported to the camp as Renate Guttmann with her twin brother, René, and they were selected by Mengele for his inhumane and unethical research on twins. She never trusted another physician in her life.

Her story, and the stories of countless other people harmed or killed by unethical medical professionals, must not be forgotten, and instead must serve as a moral compass. We need to work for trust by learning from what all humans, including doctors, are capable of, and being aware of how this history still informs the trust that is so critical to the doctor-patient relationship today. Studying this history can help us remember and furthermore be inspired in our society to renew our dedication to truth and humanity in science in the decisions we make and the actions we take.

Hedy S. Wald is a clinical professor of family medicine at Alpert Medical School of Brown University in Providence, Rhode Island. Herwig Czech is a professor of history of medicine at the Medical University of Vienna, Austria. Shmuel P. Reis is a professor of medical education at Hebrew University/Hadassah Faculty of Medicine in Jerusalem. The authors are members of The Lancet Commission on Medicine and the Holocaust. They thank Sabine Hildebrandt, associate professor of pediatrics at Boston Children’s Hospital and Harvard Medical School, and Volker Roelcke, professor of the history of medicine at Giessen University in Germany, for their significant contributions to the essay.

https://www.statnews.com/2022/01/27/doctors-complicit-holocaust-atrocities/

Early data indicate vaccines still protect against Omicron’s sister variant, BA.2

 New data show that vaccines still protect against a spinoff of the Omicron variant, a welcome sign as the world keeps a close eye on the latest coronavirus iteration.

BA.2, as the sublineage is known, is part of the broader Omicron umbrella. Scientists are paying more attention to it as it begins to eat into the dominance of the more common Omicron strain, which is technically called BA.1.

BA.1 is what has driven massive spikes in cases around the world, but in countries including India, the Philippines, South Africa, and several countries in Europe, BA.2 has been picking up proportional steam and demonstrating a growth advantage over BA.1. The two lineages share many mutations, but have their own individual genetic twists as well.

As with any emerging variant, there are more questions than answers about BA.2’s transmissibility, severity, and ability to erode the immunity built by vaccination or prior infection. As the World Health Organization put it last week, “drivers of transmission and other properties of BA.2 are under investigation but remain unclear to date.” 

But data this week from the U.K. Health Security Agency — which has done some of the leading work on new variants — offered a piece of reassuring news: There does not seem to be any loss of vaccine effectiveness against BA.2 compared to BA.1.

Vaccines already took a decent hit in the face of BA.1, particularly in their ability to prevent infection entirely, which is why so many immunized people have had breakthrough infections in recent weeks. But crucially, the vaccines’ protection against severe disease with Omicron has broadly stood up, and booster doses have helped shore up much of the protection that was lost.

This week, the U.K. agency estimated that, for people at least two weeks out from their booster shot, vaccine effectiveness against symptomatic disease was 63% against BA.1, versus 70% for BA.2. While that might suggest that BA.2 is less of a threat to vaccine protection than its Omicron sister, the full estimate ranges overlapped.

That helps answer one question about BA.2, but there remains another pressing one: what the spinoff’s snowballing means epidemiologically. The fact that it’s demonstrating a growth advantage in multiple countries suggests BA.2 might be able to outcompete BA.1 generally, though if that happens, it could be more of a slow ascendance than a lightning-quick grab of dominance. (When scientists in South Africa first identified what quickly became known as Omicron, they spelled out that there were already several lineages, including BA.2.)

Jacob Lemieux, an infectious diseases physician at Massachusetts General Hospital who is helping lead a state program studying variants, said that in some countries, BA.2 is displacing BA.1, but that, “what we don’t know, and still have almost no information on, is what impact this will have on case counts, on hospitalizations, on death.”

Variants can behave differently in different places, depending on the levels and types of immunity people have there and what else is spreading. Different variants can co-circulate. And the composition of infections can change — with an emerging strain coming to take the lead in a given place — even as the total number of cases declines or stays flat. Put another way, even if BA.2 becomes dominant, it doesn’t have to cause another spike. 

One factor that will help determine that is cross-protection: essentially, how well are the millions of people who’ve now been infected with BA.1 protected against infection from BA.2? Some variants offer better cross-protection against other forms of the virus than others. It appears that people who’ve been vaccinated and infected with Omicron have strong protection against Delta, for example.

Another possibility is that BA.2 — if it is more transmissible in our current landscape than BA.1 — could cause another uptick in cases, but whatever spike occurs could be broadly limited to infections because of the high levels of population immunity. That is, the link between cases and subsequent hospitalizations and deaths could become even more decoupled than it already is.

This week, for example, Danish authorities announced that they were ending most pandemic restrictions starting next week, because even with a high infection tally, there were few resulting hospitalizations.

https://www.statnews.com/2022/01/28/early-data-indicate-vaccines-still-protect-against-omicrons-sister-variant-ba-2/

Omicron slows UK growth to weakest since April

 

British businesses grew at the slowest pace since April 2021 during the past three months, after demand for face-to-face services slumped due to the Omicron variant of coronavirus, the Confederation of British Industry said on Sunday.

Britain's economy only recovered to its pre-pandemic size in November, before being hit by the highly infectious Omicron variant which led to government advice to work from home and restrictions on hospitality in Scotland and Wales.

"Consumer services have borne the brunt of 'Plan B' restrictions and general Omicron caution, with activity here shrinking sharply," CBI economist Alpesh Paleja said.

The CBI's monthly growth index - which is based on quarterly growth rates from its previously published surveys of manufacturers, retailers and other services businesses - fell to +12 in January from +21 in December.

That was the lowest reading since April's, which covered a three-month period when pubs, restaurants and non-essential retailers were largely closed due to a previous COVID wave.

COVID-19 cases in Britain have fallen sharply since a peak in early January, and most economists think output will soon recover.

But there are headwinds for many businesses from sharply rising inflation, which hit its highest in nearly 30 years in December and is forecast to exceed 6% in April when regulated household energy bills rise.

"Consumer-facing firms will also have to contend with a deepening squeeze on household budgets," Paleja said.

The Bank of England is expected to raise interest rates on Thursday to 0.5% from 0.25%, the second increase in less than two months.

The CBI survey was based on responses from 477 firms between Dec. 20 and Jan. 17.

https://www.marketscreener.com/news/latest/Omicron-slows-UK-growth-to-weakest-since-April-CBI--37690173/

Thousands stage peaceful protest in Ottawa against Canada's vaccine mandates

 

Thousands held a loud but peaceful protest in Canada's capital Ottawa on Saturday against Prime Minister Justin Trudeau's COVID-19 vaccine mandates, on the streets and snow-covered lawn in front of parliament.

The so-called "Freedom Convoy" started out as a rally of truckers against a vaccine requirement for cross-border drivers, but turned into a demonstration against government overreach during the pandemic with a strong anti-vaccination streak.

"I'm not able to work no more because I can't cross the border," said Csava Vizi, a trucker from Windsor who noted he was the family's sole breadwinner.

"I refuse the vaccine," he said, calling it dangerous. He spoke from inside his truck in front of parliament.

"It's not just about the vaccines. It's about stopping the public health mandates altogether," said Daniel Bazinet, owner of Valley Flatbed & Transportation in Nova Scotia on the Atlantic coast. Bazinet is unvaccinated, but operates domestically and so is not affected by the cross-border mandate.

"Myself and a lot of other people are here because we're just sick of the vaccine mandates and the lockdowns," said Brendon from Ottawa, who declined to give his last name. He was carrying a sign reading: "Justin Trudeau makes me ashamed to be a Canadian".

The rally started early and built through the afternoon. Some handed out bag lunches to the truckers, who convoyed to Ottawa from the east and west coasts and places in between.

Few wore masks, but many were in balaclavas as the temperature with windchill was minus 21 Celsius (minus 6 Fahrenheit). A downtown mall closed because demonstrators refused to wear masks inside, CTV reported.

The violent rhetoric used by some of the promoters on social media in the run-up to the protest had worried police, who were out in force, but mostly the protest felt like a very cold street party, punctuated by blaring truck horns.

Due to security concerns, Trudeau and his family left their downtown Ottawa home due to security concerns, the CBC reported. His office said it does not comment on security matters.

Earlier this week Trudeau said the convoy represented a "small fringe minority" who do not represent the views of Canadians. About 90% of Canada's cross-border truckers and 77% of the population have had two COVID vaccination shots.

Trudeau announced a vaccine mandate for federal workers on the eve of the October election, then last month Canada and the United States imposed one for cross-border truckers.

Conservative leader Erin O'Toole opposes vaccine mandates and expressed support for the protest after holding talks with some of the truckers on Friday.

"I support their right to be heard, and I call on Justin Trudeau to meet with these hard-working Canadians to hear their concerns," O'Toole said after the meeting.

The Canadian Trucking Alliance, which represents some 4,500 carriers, owner-operators and industry suppliers, has opposed the demonstration.

"We ask the Canadian public to be aware that many of the people you see and hear in media reports do not have a connection to the trucking industry," the CTA said on Saturday.

The CTA urged the truckers who participated to do so peacefully and then leave Ottawa. The protest organizers had said they would stay in Ottawa until the government abandons the mandates. Downtown streets could be clogged for days.

"If I have to stay here two months, I'm going be here," said Vizi.

https://www.marketscreener.com/news/latest/Thousands-stage-peaceful-protest-in-Ottawa-against-Canada-s-vaccine-mandates--37678381/