“Mr King” is a 50-year-old African-American male with a history of severe, recurrent major depressive disorder (MDD) without psychotic features. He has had partial or non-response, or tolerability issues with multiple classes of medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, lithium, and second-generation antipsychotics. He presents to the outpatient clinic to discuss a trial of ketamine. He asks whether there are any differences in efficacy between intravenous and intranasal routes of administration. As his psychiatrist, how would you respond?

There is evidence for efficacy of the N-methyl-D-aspartate receptor antagonist ketamine in the treatment of depression. Ketamine produces rapid antidepressant effects, within minutes to hours, that are most pronounced 24 to 48 hours after administration.

 Ketamine has 2 primary routes of administration: intravenous (IV) and intranasal (IN). The bioavailability for IV ketamine is 100% and 45% to 50% for IN.

In 2019, IN esketamine was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for MDD as well as acute suicidality. By contrast, IV ketamine is considered an off-label treatment for MDD.

A recent meta-analysis found that IV ketamine was superior to IN esketamine with regards to efficacy and dropout rates.

 However, a US study found evidence for superior cost-effectiveness of IN esketamine compared to IV ketamine from the patient perspective.

 Whether there are significant differences in the adverse effect profiles between IN esketamine and IV ketamine remains unclear. No previous studies have statistically compared the antidepressant effectiveness of IN and IV ketamine.

 performed a meta-analysis of randomized controlled trials in adults with MDD regarding the efficacy of a single dose of IN and IV ketamine to induce antidepressant response 24 hours after administration. They included randomized double-blind controlled trials of IV ketamine 0.5 ± 0.05 mg/kg body weight or IN esketamine 50 to 84 mg in patients aged 18-65 years with MDD. 

Studies were published in international peer-reviewed journals, included data on response rates, and assessed depression with either the Montgomery-Asberg Depression Rating Scale or the Hamilton Depression Rating Scale (HDRS). They excluded investigations of ketamine for disorders other than MDD, studies with non-saline placebos, studies without a control group, and case studies.

The authors searched PubMed, EBSCO, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Antidepressant response was defined as a 50% reduction in depression severity. Response rates for ketamine versus placebo were calculated as odds ratios (ORs). Individual studies were assessed for risk of bias. Data were analyzed using random effects meta-analysis. 

Potential publication bias was tested using rank correlation and regression tests for funnel plot asymmetry. Differences in efficacy between IV and IN ketamine were assessed by a z-test of the mean log ORs derived from the meta-analysis.

The authors screened 77 full-text articles for eligibility, and 11 studies met the study inclusion/exclusion criteria. The risk of bias was assessed as low for 7 and high for 1 of these studies. The 4 IN trials included 586 patients who received esketamine and 479 who received placebo. The 7 IV trials included 145 patients who received ketamine and 130 who received placebo. 

In the IV trials, the response rate at 24 hours was 42% for ketamine and 4.6% for placebo (OR=9.4, 95% CI 3.9-22.8), with no evidence of funnel plot asymmetry. In the IN trials, the response rate at 24 hours was 25% for esketamine and 16.5% for placebo (OR=3.3, 95% CI 1.2-9.0). Analysis of funnel plot asymmetry was limited due to the small number of studies. Despite the magnitude of the difference in the ORs for response to IV versus IN ketamine, this difference was not statistically significant (p=0.13).

The authors concluded that the odds of antidepressant response at 24 hours was 6 times greater for a single dose of ketamine versus placebo. There was not a statistically significant difference in the ORs for response to IV (9.4) and IN (3.3) ketamine. 

A strength of the meta-analysis was the stringent inclusion/exclusion criteria. A major limitation of the meta-analysis was the lack of statistical power to detect a difference between the routes of administration due to the small number of studies. Furthermore, the authors investigated the effect of a single dose of ketamine, so the present study does not inform on potential differential efficacy of multiple doses of ketamine.

A single dose of IN or IV ketamine is associated with a 6-fold increased odds of antidepressant response at 24 hours compared to placebo. Due to the small number of studies, data are inadequate to make definitive conclusions about the relative efficacy of IN versus IV routes of administration.

is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies

2. Zanos P, Moaddel R, Morris PJ, et al. 

Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms

 [published correction appears in Pharmacol Rev. 2018 Oct;70(4):879]. 

Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis

 [published correction appears in J Affect Disord. 2020 Nov 20;:]. 

Cost-effectiveness of esketamine nasal spray compared to intravenous ketamine for patients with treatment-resistant depression in the US utilizing clinical trial efficacy and real-world effectiveness estimates

5. Meiering MS, Weigner D, Gärtner M, et al. 

Does route of administration affect antidepressant efficacy of ketamine? a meta-analysis of double-blind randomized controlled trials comparing intravenous and intranasal administration

 [published online ahead of print, 2022 Nov 9]. 

Articles

Does route of administration affect antidepressant efficacy of ketamine? Researchers performed a meta-analysis of trials comparing intravenous and intranasal administration.

Meta-Analysis of Intravenous vs Intranasal Ketamine

Psychiatric issues continued to take center stage as the world stepped out of the depths of the COVID-19 pandemic. Was progress made, or did we stall? 

™ looked at some of the most pressing topics in psychiatry and mental health care as featured on our covers and asked leaders in the field to be the judge.

What is the most important issue in mental health? In an online 

™ poll, 30.7% of respondents felt that social determinants of mental health (SDOMH) were the top issue of 2022. Notably, SDOMH landed on the first cover of the year and were a focus of discussion during the 2022 American Psychiatric Association (APA) Annual Meeting in May. Have things changed?

, the Royal College of Psychiatrists [United Kingdom] has established a funded component to address the need for better education to address the impact of adverse [SDOMH], and in the US both the professional organizations for pediatrics and family medicine have advocated for urgent and concerted action,” Allan Tasman, MD; and Kenneth Thompson, MD, told 

™ in revisiting the subject. “These make it even more difficult to understand the hesitancy of the APA to do anything substantial on this issue.”

Tasman and Thompson shared that the APA eventually supported the formation of a SDOMH caucus, and the APA Assembly separately formed a SDOMH committee. However, the 2 doctors feel that these initiatives, although important, do not have enough meaningful financial support and must rely on the work of volunteer psychiatrists.

“Lack of attention to the role that adverse 

 play in the etiology and subsequent treatment of psychiatric disorders has led to insufficient change in our treatment outcomes in spite of multiple new medications and psychotherapies,” Tasman and Thompson said.

This topic is sure to remain of utmost importance to mental health care for years to come. Research suggests that addressing poverty, food security/nutrition, neighborhood/community impacts, trauma, and racism has significant positive benefits for children and adolescents

; this may be a good place upon which to build.

, psychedelics, the controversial treatment turning heads, took center stage. On the one hand, clinicians are eager for a promising new treatment. On the other, there is some skepticism about a treatment that has its roots in drugs of abuse. Thus, data are essential in determining psychedelics’ potential place in the psychopharmacological armamentarium.

™ also featured psychedelics among the many session topics at the 2022 Annual 

™ World CME Conference in August. Explained John J. Miller, MD, editor in chief of Psychiatric Times™ and cochair of the meeting, “We were honored to have 2 experts update us on the current status of [the pertinent] trials. 

, presented a detailed overview of psilocybin’s history and current research status. Corine de Boer, MD, PhD, provided a well-needed overview on MDMA [3,4-methylenedioxy-methamphetamine] and how it is being studied in patients with severe 

“Both psilocybin and MDMA are steadily moving forward in phase 2 and 3 FDA registration trials to determine their efficacy and safety for various treatments, especially for conditions with unmet needs such as treatment resistant depression and severe PTSD,” Miller added.

Most recently, a randomized, controlled, double-blind phase 2b study showed that a single 25-mg dose of psilocybin could improve symptoms in patients with treatment-resistant depression.

™ will continue to provide timely, accurate, and comprehensive updates as these 2 drugs move forward in the FDA approval process,” Miller said.

Amid the talk of increasing burnout, how do you care for yourself? Research shows that clinician reluctance to seek mental health care may begin as early as college and medical school, with 25% to 56% of medical students reporting depression and anxiety.

Fortunately, there are those taking a stand and fighting the stigma. In the March issue, Jake Goodman, MD, 

“One year ago, I posted about taking medication for my mental health to millions of people online. As a resident doctor, especially one who treats mental illness, this was extremely taboo. I hope my post was able to move the culture in a healthier and more compassionate direction.

“Today, I am still taking medication for my mental health. I still go to therapy for my mental health. I still have some bad days, but overall my mental health is in a really good place. Seeking treatment for depression was one of the best decisions I’ve ever made. Posting about it on social media, and letting others know that they are not alone, is one of my proudest moments. After that post, I received thousands of messages and comments from people around the world thanking me for making them feel seen and less alone.

“One year later, I’m still Dr Jake. I’m still a resident doctor who treats mental illness, and I still take medication for my mental health. By the way, I’m still proud of it.”

Much like Goodman, approximately 25% of practicing physicians in the US have depression.

 But an anonymous survey found less than half those who reported depressive symptoms sought treatment.

 By being open and honest not just with patients, but with colleagues as well, we can make strides to tamp down stigma in the mental health profession.

Like it or not, thanks to COVID-19, telehealth is here to stay, as we reported in the April issue.

“As a field, we have to now accept that new skill sets have to be developed: one skill set for seeing [patients] in person, and one for virtual. The art of psychiatry will have to evolve to include a distinction of who would benefit from which modality and how/when to switch modalities,” said 

™ Editorial Board Member Nidal Moukaddam, MD, PhD.

The highest rates of telehealth visits were among patients with Medicaid (29.3%) and Medicare (27.4%), Black individuals (26.8%), and those earning less than $25,000 a year (26.7%).

 But is telehealth actually helping underserved communities? Moukaddam has doubts.

“I worry this area may be a mixed bag of findings,” she said. “There [are] also data that indicate individuals with broadband connectivity disparities—only a data plan on their phone, no home internet—cannot fully benefit from virtual services because access is not guaranteed.”

On February 24, 2022, Russia invaded Ukraine, causing a worldwide ripple effect of mental health trauma as Ukrainians chose to seek refuge abroad or stay to defend their home. In September, the United Nations Human Rights Monitoring Mission reported that 14,059 civilians had been killed or injured since the invasion, although numbers are predicted to be much higher.

Peter Kowalski, MD, reported to us from the front lines for the 

. Here is the update he shared exclusively with 

“The horror waged by Russia against Ukraine continues. Ukraine pushed the Russians out of Kherson, the gateway to lands that Russia claims. The president of Ukraine asserted ‘this is the beginning of the end’ of the war. But this war is not over. Putin threatens nukes. Winter is here, and the brutal wind slices through the broken plain. Fuel and food are scarce. Refugees may need to leave their homes again.”

Although some volunteers have moved on, they have not forgotten what they saw in Ukraine. War grinds a people down. This should not be happening in the 21st century. Coordinated mental health care is mandatory after the bullets stop flying. As mental health professionals, we can lend expertise and assistance to help put a shattered country together again,” Kowalski said.

“The world continues to engage in multiple armed conflicts with dire consequences in places like Ukraine, Yemen, Syria, Burma, and the Middle East,” Omar Reda, MD, told 

™. “I refuse to preach despair, though; I remain full of hope and I am a strong believer that humans can hurt and also heal each other… We psychiatrists should strive to be the source of light and hope for everyone around us, starting with those we love, and not forgetting to nurse our own wounds in the process of healing others.”

Valeriia Palii, PhD, president of the National Psychological Association of Ukraine,

™: "Not only will we not break down, but we will also become stronger because the enemy shows its true face every time, destroying everything. People die in hospitals without electricity, schools cannot fully function because it is cold, we cannot cook for ourselves because we depend on resources. But we know that by capitulating, we will live even worse than now."

With young athletes admitting mental fatigue (or worse) during the 2022 Winter Olympics, in Beijing, China, all eyes turned to the field of 

In June, new research indicated the type of sport may affect a child’s mental state. The more intense the sport, the bigger the mental health impact. Hoffmann et al published results on the association between sports participation and mental health difficulties among US youth.

 Although they found that those who participated in team sports had fewer mental health problems than those who did not participate, youth involved with individual sports were more likely to have mental health problems such as increased anxiety, depression, withdrawal, social problems, and attentional problems.

“Unlike in team sports, an athlete who competes in individual sport is constantly faced with the realization that they are solely responsible for success or failure. This can take a toll on one’s mental health, particularly at a young age if one has not yet developed the coping skills to deal with this type of pressure or if one is not receiving the necessary support from others to manage the situation,” Matt D. Hoffmann, PhD, told 

Fortunately, the pleas for help have not gone entirely unanswered. Large athletic groups may be taking the first steps to combat this issue. In October, USA Gymnastics unveiled a new program that expands mental health coverage for athletes and coaches alike. Eight annual mental health provider visits will be covered for eligible national team members, and eligible coaches will be covered for 4 visits. Although the previous program provided mental health services during events such as training camps or meets, the new model will reimburse athletes/coaches up to $125 per visit when they return home.

Three digits had the mental health care community talking this year: 

. The new toll-free dialing code, which routes callers to the National Suicide Prevention Lifeline (now known as the 988 Suicide & Crisis Lifeline) has been active since July. Although there was a lot of trepidation at its rollout, how has it worked so far?

According to data from the US Department of Health and Human Services, there was a 45% increase in overall usage volume and 152,000 more calls, chats, and texts answered compared with August 2021. Furthermore, the average answer speed across all contacts decreased from 2.5 minutes to 42 seconds.

 Despite these increases, data also indicate overall contacts are slowing slightly; phone calls fell by 7% the following month.

 Could this be due to a lack of awareness? Results of a recent survey of 2000 US adults found 56% reported they had heard “nothing at all” about 988.

Adding insult to injury, there have been a few viral social media posts warning not to call 988. Why? Posters listed potential police involvement, involuntary treatment in emergency departments/psychiatric hospitals, and the possible emotional and financial toll.

, at least 12 more school shootings have occurred in the US.

 The violence of school shooters persists, as has the media’s erroneous focus on “psychopathological” shooters.

“There is a common misperception that has been perpetuated by the mainstream media that mental illness is the primary, if not sole, factor in 

. It is a very simplistic way of looking at a complex problem,” Alan D. Blotcky, PhD, exclusively told 

™. “The truth is that mass shootings are a complicated, multifactorial problem that is not easily described or researched, much less understood by the citizenry. What is crystal clear is that very few mass shooters have a major mental illness, such as schizophrenia.”

Blotcky does believe, however, that shooters are more likely to have externalizing disorders (ie, antisocial personality, substance use, and other impulsive and aggressive disorders). According to a 2-stage study from 2021, 10.1% to 24.3% of students met criteria for an externalizing disorder.

 “In my opinion, the obsession with mental illness as the culprit in mass shootings is a way of avoiding the harsh reality that firearms are too plentiful and too easily obtained,” Blotcky added.

Perhaps the bigger discussion should fall on prevention, and some progress has been made. In June 2022, President Joe Biden signed into law the first major gun safety legislation passed in decades, which includes funding for school safety. California, New York, and other states also have passed new laws to regulate untraceable ghost guns and strengthen background checks.

 According to an early 2022 study, such legislation might reduce gun deaths, as states with weaker gun laws had higher rates of homicides, suicides, and accidental killings using a gun.

Overall, the experts seem to agree that psychiatry has made steps toward dealing with the issues in 2022, but more needs to be done. 

™ readers seem to agree, according to results of a recent online survey (

Top Critical Issues in Psychiatry According to a 

In addition, there are ongoing factors, such as prior authorization and managed care struggles, the debate over how to address incomplete recovery and residual symptoms, and the need for additional resources and clinicians.

We want to hear from you! Was progress made in psychiatry in 2022? What story was most impactful to you?
What are some lingering issues you want to see addressed? Write to us at 

The key social determinants of mental health: their effects among children globally and strategies to address them: a narrative review.

2. Kuntz L. A single dose of psilocybin for treatment-resistant depression. 

https://www.psychiatrictimes.com/view/a-single-dose-of-psilocybin-for-treatment-resistant-depression

A conceptual model of medical student well-being: promoting resilience and preventing burnout.

Professional stigma of mental health issues: physicians are both the cause and solution.

5. Karimi M, Lee EC, Couture SJ, et al. National survey trends in telehealth use in 2021: disparities in utilization and audio vs. video services. Assistant Secretary for Planning and Evaluation; Office of Health Policy. February 1, 2022. Accessed November 8, 2022. 

https://aspe.hhs.gov/sites/default/files/documents/4e1853c0b4885112b2994680a58af9ed/telehealth-hps-ib.pdf

6. Ukraine: more than 14,000 casualties to date but ‘actual numbers are likely considerably higher.’ United Nations. September 9, 2022. Accessed November 8, 2022. 

https://news.un.org/en/story/2022/09/1126391

7. Hoffmann MD, Barnes JD, Tremblay MS, Guerrero MD. 

Associations between organized sport participation and mental health difficulties: data from over 11,000 US children and adolescents.

8. USA Gymnastics expands mental health services for athletes. AP News. October 10, 2022. Accessed November 8, 2022. 

https://apnews.com/article/sports-health-mental-gymnastics-57baecee03219f54c3726e91866cb30c

9. HHS Secretary: 988 transition moves us closer to better serving the crisis care needs of people across America. Substance Abuse and Mental Health Services Administration. September 9, 2022. Accessed November 8, 2022. 

https://www.samhsa.gov/newsroom/press-announcements/20220909/hhs-secretary-988-transition-moves-closer-to-better-serving-crisis-care-needs

10. 988 Lifeline performance metrics. Substance Abuse and Mental Health Services Administration. Updated October 31, 2022. Accessed November 8, 2022. 

https://www.samhsa.gov/find-help/988/performance-metrics

11. Lopes L, Kirzinger A, Sparks G, et al. KFF/CNN Mental Health in America Survey. KFF. October 5, 2022. Accessed November 8, 2022. 

https://www.kff.org/report-section/kff-cnn-mental-health-in-america-survey-findings/

12. Social media posts warn people not to call 988. Here’s what you need to know. NPR. August 25, 2022. Accessed November 8, 2022. 

https://www.npr.org/sections/health-shots/2022/08/11/1116769071/social-media-posts-warn-people-not-to-call-988-heres-what-you-need-to-know

13. School shootings this year: how many and where. EducationWeek. Updated October 31, 2022. Accessed November 8, 2022. 

https://www.edweek.org/leadership/school-shootings-this-year-how-many-and-where/2022/01

14. Norrholm SD, Blotcky AD. Most mass shooters are terrorists, not mentally ill. 

https://www.psychiatrictimes.com/view/most-mass-shooters-are-terrorists-not-mentally-ill

15. Danielson ML, Bitsko RH, Holbrook JR, et al. 

Community-based prevalence of externalizing and internalizing disorders among school-aged children and adolescents in four geographically dispersed school districts in the United States. 

16. Tucker E. These are the gun control laws passed in 2022 so far. CNN. July 30, 2022. Accessed November 8, 2022. 

https://www.cnn.com/2022/07/30/us/gun-control-laws-2022/index.html

17. Gun safety policies save lives. Everytown. Updated January 19, 2022. Accessed November 8, 2022. 

Assessing 2022: What’s the Prognosis in Psychiatry?

Let’s wrap things up by talking about insomnia in general and treatment. So far we’ve talked about the fact that insomnia is so prevalent in the general population—in our practices, in primary care, and in psychiatry. It’s often comorbid. Patients don’t ask about it. There are a lot of treatment options that we have, both medicinally and nonmedicinally. As far as medications, there are a lot of approved medications for insomnia. Leslie, what advice do you have for clinicians as far as improving the awareness of their patients with insomnia and sleep disorders? What to do about them?

We need to have a conversation with our patients routinely about their sleep, and we need to set aside enough time to discuss that. The last thing we want is someone to say, as they’re opening the doorknob on the way out, “By the way, I’m having trouble sleeping.” Then you’ll have to make another appointment to discuss this further with them if you have a waiting room full of patients. Because you do need to spend that time. It often gets ignored.

I’m going to tell you about a study done in Norway. I have this in front of me. It’s remarkable: 42000 patients participated in this study looking at their medical records. Forty percent of these patients experienced a sleep disturbance. Twenty-two percent reported insomnia as a problem to their caregivers. This was diagnosed in the medical record only 0.08% of the time, which is staggering. This is among mental health care centers where we spend a lot of time on these issues. It doesn’t get the attention it deserves. So No. 1, let’s ask about sleep, and let’s do something about it. Because the spillover effect into all their other conditions and their daytime function is substantial.

In primary care, when patients come to us for their complete physicals, we always emphasize the need for regular exercise, good eating habits, keeping your weight down, and taking your medications properly. How often do we emphasize the need of proper sleep? Getting to bed at the same time every day, waking up at the same time, making sure your total sleep time is adequate, and seeking attention if there’s something wrong with your sleep. How often do we do that? In primary care, with my colleagues I talk to all the time, there certainly is a need to improve in that area.

Hopefully, this discussion has been helpful for all of you to learn about the effects of sleep, the prevalence of sleep, the comorbidities of sleep, and some treatment approaches that we have for our patients. It’s important to make sleep very important in our lives for our patients and to identify insomnia in their treatments. But we should also know that there are many medications available for sleep. The DORAs [dual orexin receptor antagonists] are the most common or novel ones targeting insomnia in a different way than benzodiazepines do. Thank you all for listening. Hopefully this has been helpful for your needs in treating your patients with insomnia. Thank you, Leslie, for being with us.

Thank you, Paul. It’s always a pleasure working with you.

Videos

Drs Paul Doghramji and Leslie Citrome share approaches to communicate with patients and increase awareness of insomnia disorder

Increasing Awareness of Insomnia

So far, Leslie, you’ve talked about the study 1 and study 2 with data at 1 month and 3 months with daridorexant 10, 25, and 50 mg. You’ve said the 10 mg isn’t available. Has there been any duration increase of more than 3 months according to clinical trials?

Absolutely. When clinical trials are done, they’re usually placebo controlled. They’re done for a relatively short period of time, and then ordinarily there’s an extension study. There was a 40-week extension study giving us data up to a year. In that extension study, people continued to receive daridorexant. Those who were originally on placebo had an opportunity to be re-randomized to also receive daridorexant. That’s how you get people to agree to be in these longer-term extension studies. All the benefits that were observed in the first 3 months persisted through the 40-week extension study. We have data demonstrating that continuation in subjective total sleep time remaining improved, and the existent sleeping domain remaining improved as well.

They maintained all this over time, and there did not seem to be a deterioration of the medications’ benefit through the night and during the day. But these are observational, correct?

Clearly there was no loss of effect of daridorexant. This would be something of keen interest when looking at a hypnotic because in the past we’ve been burned by this. In the past with benzodiazepines and Z-drugs, we’ve seen a falloff of the clinical efficacy of the older hypnotics. This wasn’t observed with DORAs [dual orexin receptor antagonists], including daridorexant.

Let’s bring suvorexant and lemborexant back into the picture. Let’s talk about their long-term data and their risk of treatment discontinuation. Do we have any information there?

Yes. Overall, the DORAs are well tolerated. The rates of discontinuation due to adverse events are pretty close to what was seen with placebo or lower than what was seen with placebo. That’s very encouraging. There may be some dose-related issues with agents depending on their characteristics, so the dosing is different for suvorexant-lemborexant and daridorexant.

Leslie Citrome, MD, MPH, comments on long-term data for daridorexant, suvorexant, and lemborexant.

Long-Term Data on Daridorexant, Suvorexant, and Lemborexant

“Psychiatry is conventionally defined as a medical specialty concerned with the diagnosis and treatment of mental diseases. I submit that this definition, which is still widely accepted, places psychiatry in the company of alchemy and astrology and commits it to the category of pseudoscience. The reason for this is that there is no such thing as ‘mental illness.’”

Mental Illness Versus Real Medical Illness

Mental illness is a tough sell. All of us have patients who do not truly believe they have a medical illness, but insist they are ‘feeling sorry for themselves,’ and ‘just need to toughen up.’ 

 are even more blunt: They portray mental illnesses as DSM-defined cultural creations which are at best hopeful guesses, and at worst, pseudo-medical entities. Take, for instance, a recent article in 

 which contrasts the alienating medical pronouncements of psychiatric physicians with the ‘contrasting narratives’ of deeper self-understanding. (Evidently, according to 

 psychiatrists are not very interested in self-understanding.) Even some psychiatrists, such as former National Institute of Mental Health (NIMH) director Thomas Insel, MD, have contrasted objective modern medicine with the subjective and unscientific nature of psychiatric diagnosis, comparing psychiatrists with premodern physicians who made unhelpful diagnoses based on the “nature of chest pain and quality of fever.”

On the one hand, critics portray “real doctors” who diagnose medically defined illnesses with objective testing; on the other hand, psychiatrists are portrayed as would-be imitation doctors who insist that their arbitrary categories are biologically real.

 “Real” doctors treat real diseases with targeted and scientifically-proven cures, while psychiatrists “throw medications” at confused and victimized patients. “Real” doctors can cure real medical illnesses, while psychiatrists poison patients with 

 that provoke terrible adverse effects and provide questionable benefits.

These particular critiques of psychiatry are the products of ignorance and bias, for they carry the distorting weight of hidden assumptions that are profoundly misleading. What assumptions? Critics of all stripes routinely act as if true medical illnesses are easily definable, precisely diagnosable, and regularly curable. But these assumptions apply, at most, to 1 subtype of medical illness—acute illness.

Their assumptions completely fail as accurate descriptions of the other main type of medical illness—chronic illness. By confusing the two, would-be reformers of psychiatry confuse themselves and mislead the public, discouraging our patients and undermining efforts to help them. It is our job, as psychiatrists, to untangle these misunderstandings.

Critics mistakenly compare psychiatric illness to acute illness, with predictably misleading results. Acute illnesses, by definition, begin and end rapidly. Common examples are influenza, appendicitis, and cholecystitis. Acute illnesses often have well defined causes, such as an infective agent, injury, or internal bodily obstruction. People get sick from a virus, suffer a heart attack from a clotted coronary artery, or fracture bones in an accident. Diagnosis tends to be more definite than for chronic illnesses, with X-rays or lab work that can rapidly confirm the doctor’s suspicions. Treatments tend to be correspondingly definitive, such as 

, cardiac catheterization, or surgical correction. By contrast, psychiatric illnesses do not appear to be as neatly defined or effectively treated.

But psychiatric illnesses are overwhelmingly chronic, and chronic illnesses tend to be different in all of these ways. Chronic illnesses commonly have fuzzy boundaries and lack definitive cures. Yet chronic illnesses also constitute our most important public health problems today. Understanding them is critical to understanding just how real, devastating, and treatable mental illness is. So what does the public need to know about chronic medical illness?

Critics blame psychiatrists for manufacturing an epidemic of mental illness, citing surveys which find up to 50% lifetime occurrence.

 They wrongly assume that no medical illness can be so common. On the contrary, chronic illnesses are extraordinarily common: Up to 90% of people will develop hypertension during the lifetime, 40% will get 

, and 40% will have knee arthritis severe enough to manifest on X-rays. Chronic illnesses are so common that the majority of Americans suffer from at least 1—60% of us in total. So if 50% of all people in our country suffer from mental illness at some time of life, it would be entirely typical for this type of medical problem.

Chronic illnesses lack precise diagnostic boundaries

. Critics charge that psychiatric diagnosis lacks clear and objective boundaries, leading psychiatrists to confuse normal grief with 

. Yet most chronic illnesses have fuzzy boundaries which are difficult to distinguish from the extremes of normal. At what point, for instance, does hypertension begin? Does a diastolic blood pressure of 81 constitute an illness, where a blood pressure of 80 is entirely normal? Does a hemoglobin A1C level of 6.5 indicate diabetes, while 6.4 indicates only prediabetes? Where is the line between osteoarthritis and normal aging of joints, and how do we know exactly when osteoporosis or atherosclerotic cardiovascular disease begins? And yet all of these are well-defined biological illnesses with devastating consequences. The same is true for major mental illnesses.

Chronic illnesses are complex entities that have multiple causes. 

Critics have long held that social and psychological factors in mental illness undermine the notion of its biological reality. Yet the rest of medicine is currently waking up to the biopsychosocial nature of chronic illnesses, known as the social determinants of health. So it is rapidly becoming obvious that, while type II diabetes is a biological illness, its onset and course are profoundly influenced by personal health habits (psychology) and even more by social circumstances related to food availability, 

, and culture. The same can be said of heart disease, where psychology (eg, the ‘type A’ personality) and social factors (eg, tobacco use and physical activity) are overwhelmingly important in the genesis and treatment of the disorder.

 The fact that mental illness results from an interaction of human biology with psychological and social factors is simply another example of the nature of chronic illness.

Chronic illnesses are disabling and life shortening. 

By definition, chronic illnesses do not rapidly kill people. Yet illnesses like emphysema and diabetes take years off the lifespan and progressively impair functioning over time. The same is true of mental illness, which shortens the lifespan by an average of 10 years, and causes more years spent in disability than any other category of medical illness.

 By contrast, critics assert that it is psychiatrists who are hurting patients, by diagnosing them with stigmatizing labels and treating them with toxic medications.

Critics take psychiatry to task by noting high and implausible levels of comorbidity among psychiatric illnesses.

 and anxiety disorder occur together more often than they do separately,

 while half of those with a substance use disorder also have another mental disorder.

 And yet it is commonplace to find hypercholesterolemia, hypertension, diabetes, and heart disease together, and easy to show that 1 such illness tends to accompany other serious chronic illnesses. For instance, over half of those with diabetes will also experience cardiovascular disease.

 More than this, major mental illnesses have been found to substantially increase the risk of other major chronic illnesses: Individuals with severe mental illness are 2 to 3 times more likely to die of cardiovascular disease, and more likely to die of diabetes and 

 In this context, the high levels of comorbidity among psychiatric disorders do not appear particularly suspicious.

Chronic illnesses are treatable, but typically not curable. 

Do we have a cure for cardiovascular disease? Do we have a cure for type II diabetes? Can we eliminate osteoarthritis or osteoporosis? We have cures for none of these diseases, and yet no one despairs of getting treatment for them. In the same way, critics who emphasize our lack of definitive cures for major mental illness have overlooked the fact that we have scientifically validated biopsychosocial treatments for all of them. In fact, a meta-analysis by Leucht et al showed that psychiatric medications alone are as effective as the medications used in primary care for the most common conditions treated by each specialty.

Mental illness is medically real, and we can demonstrate this by the same standards that apply to chronic medical illnesses. It is time for critics of psychiatry to step out of the dream world of idealized modern medicine and into the realities of life with chronic medical illness. We will all be a lot better off when they do.

 is a psychiatrist and director of training for the general psychiatry residency at Tufts Medical Center in Boston. He frequently speaks as an advocate for mental health and is author of Science Over Stigma: Education and Advocacy for Mental Health, published by the American Psychiatric Association. He can be reached at 

The author wishes to thank Ronald W. Pies, MD, for his review and comments on an earlier draft of this article.

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Excess mortality in persons with severe mental disorders: a multilevel intervention framework and priorities for clinical practice, policy and research agendas.

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