Tag: suicide prevention

02/22/22

Risks of Ketamine for Suicide Prevention

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As 2021 drew to a close, there was another study published online that evaluated ketamine’s value in mental health therapy. As other research has shown, this metanalysis found that ketamine could quickly relieve depression and thoughts of suicide. But the rapid response was usually short-lived. While there was some evidence it helped with other disorders, the evidence base was of a small number of primarily non randomized trials with short follow-up periods, which require confirmation and extension.

The study, “Ketamine for the treatment of mental health and substance use disorders,” was published in the British Journal of Psychiatry Open. The write up of the study in Medical News Today, “What 83 studies say about ketamine and mental health,” was generally positive. However, one of the study’s co-authors thought it was best administered in a clinical environment. In such a setting, people can be provided with “preparation and psychological support during and after the ketamine infusions” which can reduce the risk of adverse events. This is a methodology that follows similar attention to the “set and setting” in psychedelic drug research.

Commenting on the study, Alan Schatzberg, a professor of psychiatry and behavioral sciences at Stanford, thought the research to date was not enough to determine whether ketamine was effective enough to be worth it. He said, “I haven’t seen enough real data to say that we [have] got a huge winner here.” One of his concerns was that he thought ketamine worked through an opioid mechanism, acting significantly with mu opioid receptors. In certain forms and situations “it’s highly addictive.” Opioid drugs had been used to treat depression until the mid-1950s, but were largely abandoned because of concern about abuse.

Schatzberg was the senior author of a 2018 study in The American Journal of Psychiatry that showed how ketamine activates the opioid system. The study was created after the authors saw research that suggested drugs that only worked on the brain’s glutamate system weren’t very effective antidepressants.

Speaking to NPR about the study, Schatzberg said: “We think ketamine is acting as an opioid. . . That is why you’re getting these rapid effects.” The researchers commented their findings challenged the current understanding of ketamine’s mechanisms of action and its antidepressant properties.

They designed their study to investigate whether ketamine activates mu opioid receptors. This meant they treated patients with depression in two ways. First, depressed patients were given an infusion of ketamine alone. Second, depressed patients were given naltrexone, which blocks the effects of opioid drugs, before they received their infusion of ketamine. This was not a blinded study for ketamine; it is essentially impossible to design a double-blinded study with drugs like ketamine that have dissociative side effects.

An analysis of a dozen patients who got both treatments showed a dramatic difference. Seven of the 12 saw their depression symptoms decrease by at least 50 percent a day after they got ketamine alone. But when they got naltrexone first, there was “virtually no effect.”

Dr.  Schatzberg gave a talk on “Clinical Use of Ketamine in Suicide Prevention” for McLean Hospital and discussed the above research. In the slide below, taken from his talk, you see a clear antidepressant effect with the ketamine plus placebo group (K+P). When the same patients get naltrexone first (K+N), there is no evidence of a ketamine effect. The “B” graph shows the dissociative effect of ketamine was not blocked in the ketamine and naltrexone group, while the antidepressant effect was.

The anti-suicide effects of ketamine were also blocked by naltrexone, as shown in the graph below, taken again from Dr. Schatzberg’s McLean talk. This led the researchers to conclude, “the antidepressant effect of the ketamine is being mediated in some way through mu opioid receptors.”

Schatzberg noted how there have been five reports since 2018, three of which have been published, all of which show that mu opioid antagonists block ketamine’s behavioral effects. “We can show that ketamine works through an opioid effect.” He then asked, if this effect could be harnessed. In further research, Schatzberg and others looked at buprenorphine, which is a partial mu opioid agonist. At high doses (16-24 mg per day) it has an antagonist effect, blocking typical opioid effects. But very low doses, under 2 mg, have been used to treat refractory depression.

There was a 1995 study by Bodkin and Cole that investigated the potential for low doses (less than 2.0 mg per day) of buprenorphine to treat refractory depression. Its findings suggested a potential role for buprenorphine in treating depression. There was also a 2016 Israeli study by Yovell et al that looked at whether ultra-low doses of buprenorphine (.2 mg-.8 mg) could treat severe suicidal ideation.

At two weeks, Yovell et al had a dramatic reduction in suicidal ideation as assessed by the Beck Suicide Ideation Scale. This was true at the end of two weeks and at the end of four weeks. At the end of week 4, the buprenorphine was discontinued, reportedly without withdrawal symptoms at a one-week follow-up appointment. “It is possible that in this opioid-naïve population, the short duration and low dosages protected against dependence.” See the graph below taken from the Yovell et al study.

Notice that the dramatic reduction in suicidal ideation was not evident until after one week of ultra-low dose buprenorphine. Contrasting this to the rapid, within one day, antidepressant response noted above, raised a research question Schatzberg and other are currently investigating. Can you get a more immediate anti-suicide effect if you first pre-treat buprenorphine patients with ketamine?

Schatzberg and a team of researchers are looking at 60 patients with major depression and active suicidal behavior. They are repeating the Israeli experiment, but adding it after a ketamine infusion. All patients receive an open label, intravenous infusion of ketamine. Two days later, patients are randomized to receive ultra-low dose buprenorphine or placebo for 4 weeks. This research is ongoing; no results were discussed or presented in Schatzberg’s talk.

Given the previous research, it seems likely these researchers will demonstrate a rapid antidepressive reduction in active suicidal behavior. Combining ketamine and buprenorphine as Schatzberg does in this experiment will simultaneously engage two systems that seem to mediate depression and suicidal ideation—the endogenous opioid system and the glutamatergic system. However, we need to keep in mind that both of the drugs in Schatzberg’s experiment, ketamine and buprenorphine, are classified as Schedule III Controlled Substances.

The Yovell et al study suggested that ultra-low doses of buprenorphine were successfully discontinued without withdrawal. But wasn’t that after a single treatment? Studies of ketamine’s rapid antidepressant effects indicate the changes are temporary and require repeated therapeutic interventions in order to maintain an improvement in mood. In time, could tolerance and withdrawal become evident with ultra-low dose buprenorphine as it has already been shown with ketamine?

Considering the ultimate risk of suicidal ideation leading to completed suicide, it would seem to be an acceptable risk-benefit ratio as a therapeutic intervention for suicidality. But as an ongoing, repeated cycle to treat major depression, the ketamine-buprenorphine combination does not appear to be an acceptable risk to me. In time, the patient could add physical dependency concerns with ketamine and buprenorphine to his ongoing struggle against depression.

I look forward to the completion of Schatberg’s study and hope the publication of the results will address this concern. For more information on ketamine, see this review of research by The Mental Elf and other articles on this website: “Ketamine to the Rescue?”, “In Search of a Disorder for Ketamine,” and “Is Ketamine Really Safe & Non-Toxic?”

05/18/21

Support and Defend Against Suicide

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There has been an alarming increase in the number of veterans who commit suicide each year. The latest statistics in the 2020 National Veteran Suicide Prevention Annual Report indicated that the number of veteran suicide deaths per year in 2018 was 6,435, an increase 379 per year since 2005. Age- and sex-adjusted suicide rates for the U.S. adult population was 18.3 per 100,000 in 2018. For veterans, their age- and sex-adjusted rates were 27.5 per 100,000 in 2018. “Over the period 2005-2018, age- and sex-adjusted suicide rates rose faster among Veterans than among non-Veteran U.S. adults.”

Veterans between the ages of 18 and 34 had the highest suicide rate in 2018, 45.9 per 100,000, while veterans 75 and older had the lowest suicide rate in 2018, 27.4 per 100,000. The absolute number of suicides was highest among veterans 55-74 years old, accounting for 40% of all veteran deaths by suicide in 2018. There were clear sex differences with Veterans, where the age-adjusted suicide rate among women was 15.9 per 100,000 and 39.6 per 100,000 among men. Suicide rates rose faster among men than among women both for veteran and non-veteran populations. See the following graphs from the 2020 National Veteran Suicide Prevention Annual Report.

Compared to the steep rise of suicides among U.S. adults, these increases may not seem so alarming. The suicide rate for U.S. adults has increased 47.1% since 2005. The number of American adults who died by suicide in 2018 was 46,510, and 31,610 in 2005. This compares with a 6.3% increase among veterans during the same time period. The number of suicide deaths among veterans in 2018 was 6,435; and in 2005 the number of veteran suicides was 6,056. See the following graph.

Yet an analysis of the data from the 2019 National Veteran Suicide Prevention Annual Report by Robert Whitaker suggested a somwhat disturbing factor hiding in the statistics. In “Screening + Drug Treatment = Increase in Veteran Suicides,” Whitaker noted the increase in suicide among Veterans was at least partly driven by the VA’s suicide prevention efforts. The VA’s screening protocols resulted in a greater number of veterans coming into psychiatric care, where treatment with psychiatric drugs is regularly prescribed. “Suicide rates have increased in lockstep with the increased exposure among veterans to such medications.”

Suicide prevention efforts began in the U.S. in the late 1980s, when The American Foundation for Suicide Prevention and other organizations like the American Psychiatric Association and the National Alliance on Mental Illness drew attention to suicide as an “unrecognized public health” problem. Individuals with mood disorders who were “untreated” were said to be at particularly high risk of suicide. “The Foundation pushed screening programs as a way to get more people into treatment. Its advisory board and presidents touted antidepressants as ’anti-suicide’ pills.”

The American Psychiatric Association, the National Alliance on Mental Illness, and the pharmaceutical companies that sold antidepressants all helped promote this message to the public. In 1997, their efforts prompted both houses of Congress to declare suicide a “national problem.” Two years later, U.S. Surgeon General David Satcher issued a “Call to Action to Prevent Suicide,” and the U.S. Department of Health and Human Services formed a task force, composed of individuals and organizations from the private and public sectors, to develop a “National Strategy for Suicide Prevention.” The task force published its recommendations in 2001, which doubled-down on the “public health” approach that had been promoted by the American Foundation for Suicide Prevention.

Government agencies launched suicide prevention efforts. Crisis call centers were created; depression screening programs were introduced. Checklists like the CDC Depression checklist and the Patient Health Questionnaire (PHQ-9) were developed. Medical professionals were trained to recognize the “warning signs” for suicide. “The goal was to get more people struggling with mood disorders into treatment, with antidepressants recommended as a first-line therapy.”

The prescribing rates for antidepressants have steadily increased since 2000. And the age-adjusted suicide rate has also increased from 10.4 per 100,000 in 2000 to 14.0 per 100,000 in 2017. The CDC reported past month use of antidepressants increased from 7.7% in 1999-2002, to 12.7% in 2011-2014. The age-adjusted suicide rate for Americans rose from 10.4 per 100,000 in 2000 to 14.0 per 100,000 in 2017. Whitaker’s data on suicide rates was only age-adjusted, not age- and sex-adjusted suicide rates, so his statistics will not be an exact match with those reported above in the National Veteran Suicide Prevention Annual Reports. See the following graph from the Whitaker article.

The failure of this approach to suicide prevention, which emphasizes getting people into treatment, is not a uniquely American phenomenon. In the 1990s, the World Health Organization urged countries around the world to develop national mental health policies and to improve their mental health services, which included providing their citizens with better access to psychiatric medications. The belief was that this would lead to better mental health outcomes, which would become visible in the form of reduced suicide rates.

Researchers from the UK, Denmark and Australia have now conducted three studies of whether such efforts have affected suicide rates, and all came to the same conclusion: improved access to psychiatric services and psychiatric drugs was associated with an increase in national suicide rates.

Soon after Prozac came to market in the late 1980s a significant number of patients taking Prozac began having suicidal thought (See “Antidepressant Fall from Grace, Part 1”). There were numerous case reports of people taking the drug who committed suicide. At this point, there is clear evidence that SSRI and SNRI antidepressants can prompt suicidal impulses and acts in some users. In 2003, David Healy and a team of researchers conducted a metanalysis of all random controlled trials (RCTs) of SSRIs and found that suicide attempts were 2.28 times more likely with an SSRI than a placebo.

Like the federal government, the VA sees suicide as a “public health” issue. In 2006 it appointed a National Suicide Prevention Coordinator. The next year it established a toll-free Veterans Crisis line. It has steadily increased resources devoted to this issue, even spending almost $20 million for Make the Connection to market the VHA’s services to veterans. The VA introduced mandatory screening for all veterans. This screening is a regular feature of VHA care, with screening of some sort as part of every patient appointment.

The VA’s clinical guidelines for treating depression and PTSD, the two most commonly diagnosed psychiatric disorders, recommend SSRI and SNRI antidepressants as first-line therapies. A 2015 report by the General Accounting Office (GAO) said 94% of all VHA patients diagnosed with depression from 2009 to 2013 were prescribed an antidepressant. “Studies of VHA patients with PTSD have reported that about 80% are prescribed a psychiatric medication, with antidepressants the drug class of choice.” Polypharmacy, taking multiple medications, is common with 35% of those diagnosed with depression taking two classes of psychiatric drugs and 15% taking three classes of drugs. Those diagnosed with PTSD had an even more pronounced polypharmacy, with 36% taking two classes of psychiatric drugs and 25% taking three or more classes.

In the 2016 report, Suicide Among Veterans and Other Americans, the VA divided patients into four subgroups: 1) undiagnosed and untreated (for a mental health or substance use disorder); 2) undiagnosed and treated (with either a psychiatric drug or non-pharmacologic treatment); 3) diagnosed and untreated; and 4) diagnosed and treated. Given the regular screening for mental health disorders, undiagnosed patients apparently did not show symptoms of depression, PTSD or any other psychiatric disorder that would have generated a diagnosis during the screening process. These patients should be at low risk of suicide and theoretically, any treatment should further reduce this risk.

The “diagnosed” patients should be at a higher risk of suicide. Suicide prevention efforts focus on getting these patients into treatment, with antidepressants seen as a first-line therapy than can lower the risk of suicide. Thus, if suicide prevention efforts are helpful, the suicide rate for the diagnosed patients who are treated should be lower than for diagnosed patients who, for whatever reason, shun treatment. The 2019 GAO report found that 18% of diagnosed patients did not get treatment.

The results were as follows. Those without a diagnosis who received MH treatment were more likely to die by suicide than those without a diagnosis who did not receive treatment. “In 2014, those who got treatment died at twice the rate of the ‘untreated’ group.”

Those with a mental health or substance use diagnosis who received mental health treatment were also about twice as likely to die by suicide than those who were diagnosed but did not receive mental health treatment. “The difference in suicide rates for the treated and untreated groups is consistent over time, year after year.” The suicide rates for those diagnosed with a mental health or substance use diagnosis have remained stable since 2005. They have hovered around 70 per 100,000 population. “The reason that the suicide rates for VHA patients have been rising is that the VA’s suicide prevention efforts—the outreach campaigns and the mandatory screening—have led to a steady increase in the number of veterans diagnosed and treated for those disorders.”

The data for the four subgroups suggested an increased the risk of suicide with the diagnosed and treated group having the greatest risk:

  • Undiagnosed/untreated: 24.8 per 100,000
  • Diagnosed/untreated:  34.4 per 100,000
  • Undiagnosed/treated: 47.6 per 100,000
  • Diagnosed/treated: 68.2 per 100,000

This finding runs directly counter to the variable suicide rates that would be expected if the “treatment” were effective. Yet it is consistent with RCT data showing antidepressants double the risk of suicide compared to placebo. Since the VA launched its suicide prevention efforts in 2006, there have been more than 70,000 suicides. “That is a number greater than the total of all combat deaths since 9/11.”

When you join the military, you take an oath to “support and defend” the Constitution against all enemies, foreign or domestic. Fulfilling that oath means you risk being killed in combat. But it doesn’t mean you have to be willing to risk committing suicide from taking psychiatric medications.

08/20/14

Suicide is NOT Painless

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Recently we all heard of the successful suicide of Robin Williams. The media aftermath has stirred up a shit-storm of debate and controversy. I asked someone who lost a loved one to a completed suicide how they reacted to the news. The person’s hope was that since Robin Williams was a celebrity, that a constructive dialogue would occur and help someone else decide not to try suicide. So I want to introduce you to some suicide statistics that relate directly to the tragic loss of Robin Williams. And perhaps start us thinking about how we can help prevent other people from trying to end their life.

The Center for Disease Control and Prevention (CDC) maintains a wealth of statistics on suicide at “National Suicide Statistics at a Glance.”  Among the trends in suicide rates for males between the age of 45 and 64, suicide by firearms were most common, 15.52 per 100,000 in 2009. Suicide by suffocation was second. “Suffocation suicide rates among males aged 45 to 64 years have increased 103.5% since 2001 from 2.91 to 5.92 suicides per 100,000 in 2009.”

“From 1991 to 2009 the suicide rates were consistently higher among males 65 years and older compared to the younger age groups.” But they were decreasing, from 40.12 per 100,00 in 1991 to 29.09 in 2009. HOWEVER, the rates of males between 25 and 64 increased from 21.27 per 100,000 in 2000, to 25.37 per 100,000 in 2009.

I then looked at the latest census figures available on the US census website for males between the ages of 25 and 64 to estimate the number of males these suicide statistics would reflect. Roughly 2,000 men like Robin Williams between the ages of 25 and 64 successfully completed suicide—480 who did so by suffocation—in 2009, the last year statistics were available. So there were 479 other families who suffered the pain of a completed suicide, as does the family of Robin Williams.

What can you do to help prevent more suicides? Look at the website for the National Strategy for Suicide Prevention  (NSSP) for information. The NSSP has a number of goals and objectives to facilitate suicide prevention:

  • Foster positive public dialogue; counter shame, prejudice, and silence; and build public support for suicide prevention;
  • Address the needs of vulnerable groups, be tailored to the cultural and situational contexts in which they are offered, and seek to eliminate disparities;
  • Be coordinated and integrated with existing efforts addressing health and behavioral health and ensure continuity of care;
  • Promote changes in systems, policies, and environments that will support and facilitate the prevention of suicide and related problems;
  • Bring together public health and behavioral health;
  • Promote efforts to reduce access to lethal means among individuals with identified suicide risks;
  • Apply the most up-to-date knowledge base for suicide prevention.

From the revised NSSP, the Action Alliance selected four priorities in suicide prevention that, if accomplished, they hope will help the group reach its goal of saving 20,000 lives in the next five years. These priorities are:

  1. Integrate suicide prevention into health care reform and encourage the adoption of similar measures in the private sector.
  2. Transform health care systems to significantly reduce suicide.
  3. Change the public conversation around suicide and suicide prevention.
  4. Increase the quality, timeliness, and usefulness of surveillance data regarding suicidal behaviors.

One agency I worked for required counselors to complete the background paperwork and have the necessary forms signed during the initial session with a new client NO MATTER WHAT. In a way that was understandable, because if the person never returned and you didn’t have the right forms signed, the agency wouldn’t get paid for the time you spent with the individual. But it made it difficult for the counselor if someone was in crisis, or needed some encouragement. One time I broke that rule and inadvertently helped prevent a suicide.

The more information and forms I completed, the greater was my impression that the woman was discouraged and hopeless. So I stopped the paper pushing and really talked with her about her problems. She had struggled off and on with drug use for over twenty years and didn’t have much hope at that moment that she could stop and get her life together. Her last relapse had led to the breakup of a long-term relationship. We talked and I was able to help her see she could re-establish abstinence; maybe even reconcile the relationship. There was some hope.

When she returned for the second appointment we completed the required paperwork that I didn’t do during the first session. And then she told me she had decided before our first counseling session that if she felt as hopeless after the session as she did before it, she had intended to kill herself. People will sometimes say that they intended to kill themselves, but not really have more than the idea of suicide. But she has a prior history of attempts; and she had a plan that would have been successful if she attempted it.

We have a responsibility to be with one another, to make space for one another, to be kind to one another… and hopefully through doing so, we make life that much more bearable. We do our best suicide prevention by letting go of the goal of suicide prevention, and, instead, creating alternatives.

I think this quote’s essay is headed in the right direction for suicide prevention. Maybe the best technique is to simply be committed to letting people know that you care enough about them to enter their darkness and help them move out into some light.