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Remembering Martin Luther King 

May his words and ideals continue to inspire... 

Remembering Martin Luther King Jr in 2022

The US Food and Drug Administration (FDA) has given Investigational New Drug (IND) clearance to Atai Life Sciences to conduct a clinical drug-drug interaction study of R-ketamine (PCN-101). Atai intends to initiate the study early this year through its platform company, Perception Neuroscience, as part of the clinical development program for R-ketamine.

PCN-101 is a single isomer of ketamine and pharmacologically a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It belongs to a new class of glutamate receptor modulators with the potential for rapid acting antidepressant activity and antisuicidal effects.

In nonclinical depression model studies in rodents, research suggests that R-ketamine could possess longer durability and a potentially more favorable safety and tolerability profile than S-ketamine. An open-label clinical study also demonstrated rapid, durable response and limited dissociative adverse effects in treatment-resistant depression (TRD) patients after a single intravenous dose.

“TRD represents a large percentage of people with severe, difficult to treat depression who have failed to sufficiently respond to at least 2 different antidepressant treatments,” said Terence Kelly, PhD, CEO of Perception Neuroscience. “We believe that PCN-101 has the potential to offer a differentiated therapeutic effect, in terms of both efficacy and ease of administration, for clinicians and patients, as a potentially rapid-acting antidepressant. We look forward to progressing its clinical development.”

This clinical DDI trial will advance alongside an existing phase 2a proof-of-concept trial in TRD, which was recently initiated in Europe.

 Furthermore, Atai will run a bioavailability study in 2022, designed to bridge the IV formulation to a subcutaneous formulation of PCN-101, supporting the potential for at-home self-administration.

“We see great promise in PCN-101 as a potentially rapid-acting anti-depressant with a more favorable safety and tolerability profile than S-ketamine, which could enable at-home use,” said Florian Brand, CEO and Co-Founder of Atai Life Sciences. “With today’s IND clearance, we are excited to continue assessing the therapeutic potential of PCN-101 in the US, where, like elsewhere in the world, many patients struggle with treatment-resistant depression and desperately need innovative therapeutic options.”

1. Atai Life Sciences announces FDA Investigational New Drug (IND) Clearance for PCN-101 R-ketamine program. News release. January 12, 2022. 

https://www.atai.life/2022/01/12/atai-life-sciences-announces-fda-investigational-new-drug-ind-clearance-for-pcn-101-r-ketamine-program

2. Perception Neuroscience initiates Phase 2a study of PCN-101 (R-ketamine) for treatment resistant depression. News release. September 14, 2021. Accessed January 12, 2022. 

https://ir.atai.life/news-releases/news-release-details/perception-neuroscience-initiates-phase-2a-study-pcn-101-r

The FDA has given Investigational New Drug clearance for a clinical drug-drug interaction study of R-ketamine (PCN-101). 

Investigational New Drug Clearance Given to R-Ketamine

There is a reason why so many holidays occur during the fall and winter months. For many, these light-filled festivities serve as a symbol of hope, something to look forward to when darkening days threaten to bring a bout of seasonal depression.

With time changes, shorter days, and inclement weather driving people indoors, seasonal depression affects about 5% of adults annually and can last up to 40% of the year.

 Interestingly, it is 4 times more common in women than men.

 (SAD), this recurrent major depressive disorder has a pattern of seasonal emergence and remission.

SAD is thought to be mainly caused by a lack of sunlight. More than 50% of the human population lives in the northern temperate zone between the Tropic of Cancer and the artic region to the north. As a result, SAD tends to peak from December through February, often coinciding with the time of the year when shorter days means 

Although the intention of the holidays is to bring us closer to friends and family, for many it is also a very stressful time. Taking on too many commitments, interactions with family, travel, and disrupted schedules can heap on the stress and make SAD symptoms even worse.

Part of the challenge with SAD is its seasonality, which can catch people off guard if they are not usually depressed. By teaching patients how to identify and address SAD, clinicians can give patients a valuable gift.

SAD was first identified in 1984 by Norman Rosenthal, MD, along with other colleagues. Upon moving from his home of South Africa to the United States, Rosenthal noticed he felt less productive and more lethargic during the winter months. Subsequent research noted that the further people lived from the equator, the higher the rates of SAD. In Florida, for example, only 1.5% of people studied experienced SAD, while it affected close to 10% in New Hampshire.

Symptoms of SAD most commonly include a persistently low mood and a lack (or perceived lack) of energy. People experiencing seasonal depression may feel more irritable than usual, cry easily or frequently, experience lethargy or tiredness, tend to be socially withdrawn or disengaged, and may experience difficulties concentrating. Those affected also tend to sleep more than usual, experience cravings for sugars and carbohydrates, report being less active, and 

Winter depression is the most common form of SAD, with symptoms emerging in the fall and persisting through the winter months. Its milder form is known as “

.” Less common is summer depression, which can occur in the spring and summer months. Symptoms during this time can include insomnia, loss of appetite and weight loss, and increased psychomotor activity, often resulting in agitation, restlessness, or anxiety.

In either form, cases can become severe and cause significant impairment of function. Like all types of depressive disorders, 

Lack of sunlight is the main culprit of SAD, but there are other causes. A series of cloudy days, spending time mostly indoors, and adjusting to the hiccup of time changes are just some of the situations that can cause SAD to proliferate.

The exact cause of SAD has not been confirmed, but scientific research indicates several causal factors.

Low serotonin activity in the brain is thought to be a cause of SAD. Low sunlight leads to higher levels of the serotonin transporter protein, which can lead to a decrease in serotonin activity in the brain. In the summer months, sunlight naturally keeps these protein levels low.

Lack of sunlight can also spur an overproduction of melatonin, a hormone created by the pineal gland that regulates the sleep-wake.

Decreased exposure to sunlight can increase melatonin levels, which can cause increased 

These disruptions in serotonin and melatonin levels can throw off a person’s circadian rhythm. People with seasonal depression tend to have greater difficulty adjusting their internal clocks to seasonal changes in day length, and this can affect their sleep, mood, and behavior.

 levels are also affected by light. Vitamin D is believed to affect serotonin levels, and a deficiency is related to clinically significant depressive symptoms.

 More accurately a hormone, Vitamin D is found in certain foods and is also produced by the skin when exposed to sunlight.

People living away from the equator in far northern and southern latitudes are more at risk for developing SAD. In northern countries, 2% to 9% of people experience SAD, with 15% to 20% experiencing the milder “winter blues.”

 Actual prevalence could be higher due to potential underdiagnosis or underreporting.

SAD is much more common in women, likely related to changes in estrogen levels.5 It also appears more frequently in those with a family history of depression as well as younger people. The onset of 

 Those engaged in shift work, such as health care workers or law enforcement agents, may be at a particularly high risk.

The prevalence of SAD, however, is not without its critics. One 2008 study pointed out that residents of Northern Norway live without the sun for 2 months during the winter, but do not “spontaneously complain” about depression during this time.

 Another study in 2016 examined US data from a cross-sectional survey by the Centers for Disease Control and Prevention.

 Authors said they were unable to find any significant increase in depression rates that could be attributed to a particular season.

 Despite this criticism, identifying cases of SAD is critical for helping people navigate the darkness of the fall and winter months.

SAD is classified in both the ICD-10 and the DSM-5. For a diagnosis to be made, a person must experience depression during a specific time each year for at least 2 years. Once SAD has been diagnosed, there are several promising treatments to help reverse its effects.

 Antidepressants remain a promising and viable treatment option for moderate to severe cases of seasonal depression.

 Although there are concerns about the side effects of these medications, there are several newer options available that have shown promise. Additionally, there are other nonmedication options available, such as neuromodulation, which are effective and may be better tolerated.

 can help significantly reduce the distress and impairment caused by symptoms of SAD. In cases of mild depression, it can be effective by itself or in combination with medications to treat moderate to severe depression. Most of the existing research evidence supports the use of cognitive behavioral therapy.

, including mindfulness-based stress reduction, positive psychotherapy, interpersonal psychotherapy, and brief problem-focused psychotherapies, can also be highly effective. These can empower a person to effectively manage or deflect away from unhelpful thoughts and emotions. It also can help them find successful ways to relax, preserve their ability to function, anticipate and prepare for potential emotional triggers, and see the light at the end of what might seem like a long, dark winter. Reemerging interest in complimentary modalities, including psychedelic psychotherapy, is also inviting greater research and focus.

 seeks to reverse the effects of diminished daylight by exposing a person to an artificial full-spectrum light. Light boxes are easily available, often without prescription, and usually recommended for use during morning hours.

 This is similar in composition to natural sunlight, but with ultraviolet light filtered out. Medical supervision is suggested to ensure the appropriate light intensity, as well as distance, duration, frequency, and timing. This will help avoid any unwanted effects, such as headaches, eyestrain, and, in rare cases, mania and suicidal thoughts. Light therapy is not recommended for people who take certain medications that may cause them to experience unusual sensitivity to light.

 Preliminary clinical studies suggest that people with seasonal depression have insufficient (mild or borderline low levels) or deficient (significantly low levels) vitamin D levels, which are usually caused by a combination of reduced intake through diet, low sunlight exposure due to lifestyle issues or availability during winter/fall months or those engaged in night shift work. Researchers have suggested that daily supplementation with moderate to high dose vitamin D may prevent symptoms of seasonal depression or improve ongoing symptoms.

 Although rare, there is a small risk of adverse effects or toxicity developing with very large doses of vitamin D, so clinicians should work closely with patients and their primary care providers.

 There are many actions people can do on their own to mitigate the effects of SAD. Finding ways to reduce stress, 

, and spending time outside can help shore up energy levels. Eating a diet that is high in protein, along with complex carbohydrates and vegetables, and avoiding fatty foods or simple carbs can also be beneficial. Traveling to sunny destinations has also been associated with helping with mood. 

 Complementary and alternative medicine options have gained popularity in recent decades due to increased awareness, research evidence, and a shift toward a more holistic approach to health care. Nutraceuticals, dietary and herbal supplements, 

 and meditation practices, yoga, acupuncture, and the traditional practices of Ayurvedic, Unani, or Chinese medicine may be useful. 

Although the concrete causes of SAD are still elusive, SAD is a clinical condition that affects millions of people each year.

Several mechanisms may play a role in its emergence, with lack of exposure to light during the fall and winter months being the most notable. Symptoms may vary, but they tend to share similarities with other types of depression.

Timely identification and treatment can be very helpful; lifestyle modulation and adjustments can go a long way. Due to the nature of the condition and risk of being underdiagnosed or undertreated, mental health clinicians should be on the lookout for SAD when assessing referred patients.

is a psychiatrist and Regional Medical Director for 

1. Traffanstedt MK, Mehta S, LoBello SG. 

Major depression with seasonal variation: is it a valid construct? 

2. Rosenthal NE. What is seasonal affective disorder? Accessed December 22, 2021. 

https://www.normanrosenthal.com/about/research/seasonal-affective-disorder/

Seasonal affective disorder: an overview of assessment and treatment approaches. 

4. Rosen LN, Targum SD, Terman M, et al. Prevalence of seasonal affective disorder at four latitudes. 

Estrogen could control photoperiodic adjustment in seasonal affective disorder. 

6. Seasonal affective disorder. American Psychiatric Association. October 2020. Accessed December 22, 2021. 

https://www.psychiatry.org/patients-families/depression/seasonal-affective-disorder

What is this thing called "SAD"? A critique of the concept of seasonal affective disorder. 

8. Turner VS. Study finds “seasonal affective disorder” doesn’t exist. 

March 15, 2016. Accessed December 22, 2021. 

https://www.scientificamerican.com/article/study-finds-seasonal-affective-disorder-doesn-t-exist/

9. Hansen BT, Sønderskov KM, Hageman I, et al. 

Daylight savings time transitions and the incidence rate of unipolar depressive episodes.

10. Daylight saving time 2021: when does the time change? Almanac. November 4, 2021. Accessed December 22, 2021. 

https://www.almanac.com/content/when-daylight-saving-time

National Center for Complementary and Integrative Health. 6 things to know about complementary health approaches for seasonal affective disorder. Accessed January 10, 2022. 

https://www.nccih.nih.gov/health/tips/things-to-know-about-complementary-health-approaches-for-seasonal-affective-disorder

Here’s how to help patients see the light when faced with the winter blues.

A Way Out of Seasonal Depression 

Our tradition of making New Year’s resolutions is a good one, as we start the new year with hopefulness for improvements and growth for ourselves, humanity, and our planet. Unfortunately, all too often, by spring the resolutions are forgotten, as we fall into our usual routines and well-established habits. In psychiatry, our hope is often for a new treatment and ideally a cure for one of the many chronic and disabling conditions that are at the very center of our profession.

This past year, I read several articles as well as a book declaring that progress in psychiatric research is stagnant. These “glass half empty” opinions went so far as to claim that we have made no significant progress since the 1950s, when chlorpromazine and imipramine transformed psychopharmacology and were paradigm changes for our treatments for disorders such as schizophrenia and major depression. These writings went on to opine that all the research and drug development of the past 50 years have contributed very little to improved outcomes for our patients, and that all subsequent pharmacological agents developed are simply “me too” additions.

Working at a community mental health center, we serve a population that often has chronic symptoms, many of whom continue to decline in function over years and decades. Despite this, I hope to convince you that the glass is actually half full.

Psychiatry shares the challenges of all the other medical professions: many of the disease states that we treat have complex and multifactorial etiologies. These range from genetic vulnerabilities to intrauterine events to perinatal complications to environmental insults to results of suboptimal lifestyle behaviors to random accidents. Additionally, there is the simple fact that the great majority of us will die prior to the age of 100.

Yet it is quite remarkable that the average life expectancy in the United States was 48 years in 1900 and had increased to 79 years by 2020.

 Many factors have contributed to this striking increase in longevity, including a dramatic decrease in infant and child mortality rates, vaccinations, antibiotics, improved health care on many fronts, access to good nutrition for many, and the numerous advances in science and technology. And, although the life expectancy statistics look promising, they do not factor in the many possible acute and chronic diseases that can affect quality of life and virtually every organ system, including the brain.

Medicine continues to make great strides in technology, drugs, and treatments to minimize the impact of these diseases on quality of life and, in some cases, to cure them. However, virtually every medical specialty has disease states that persevere and, rather than being cured, are managed. Additionally, multiple factors—some modifiable and others unchangeable—will converge to accelerate or delay disease progression. Although the completion of the sequencing of all 3 billion base pairs in the human genome in 2003 was predicted to result in significant advances in diagnosing and treating all diseases, for the most part those advances did not happen.

According to the Centers for Disease Control and Prevention, the most common cause of death in the United States in 2019 continued to be heart disease.

 Despite the heart being a very straightforward and extensively studied organ—basically a pump—diseases of the heart continue to result in significant morbidity and functional impairment for many individuals. Does this mean that cardiology has failed as a specialty and no progress has been made? Of course not.

The human brain, the most complex organ known in the universe as of today, has many secrets awaiting our discovery. Over the past 100 years, we have merely begun our journey toward understanding the brain, and I posit that we have made great strides in treating psychiatric disorders, despite the likelihood that cures for many of these disorders, as for the heart, are far off in the future.

As I begin my 31st year as a practicing psychiatrist, I would like to welcome 2022 with reflections and hope for where we currently are as well as where we are heading in psychiatry.

I look forward to the time when the term 

 disappears from our nosology. First named 

 in 1886 by German psychiatrist Heinrich Schüle, this descriptor was popularized in 1893 by Emil Kraepelin, MD, who famously divided psychotic disorders into 2 subtypes: (1) dementia praecox for what now is named schizophrenia and (2) manic depression, which we now call bipolar disorder. In 1908, Eugen Bleuler, MD, introduced the term 

, which translates from 2 Greek words as a split in the mind; this is the name that persists today.

A genetic vulnerability is well established, as well as effects from developmental challenges and environmental exposures. The savvy clinician will aggressively rule out many potential medical etiologies before settling on the diagnosis of schizophrenia, which will likely be a permanent label once etched into the patient’s medical record. A sampling of medical conditions that can mimic schizophrenia includes tertiary syphilis, seizure disorders, hyperthyroidism, Wilson disease, substance intoxication, medication toxicity, brain lesions, and anti-NMDA glutamate receptor autoimmune encephalitis, first reported in 2005.

It is thought-provoking that back in 1908 when Bleuler first described schizophrenia, most of these medical diagnoses had not been identified. Hence, these individuals would likely have received an incorrect diagnosis. A disturbing autobiography by a young 

 journalist who, in 2009, developed an abrupt onset of manic, psychotic, delusional, and paranoid symptoms and was deteriorating with no response to usual treatment, revealed that she eventually received a diagnosis of anti-NMDA glutamate receptor autoimmune encephalitis, the 217th person diagnosed with this condition. She recovered completely following treatment with steroids, plasmapheresis, and intravenous immunoglobulin.

What other as-yet undiscovered medical conditions are now lumped into the outdated diagnosis of schizophrenia? The half-full glass predicts that there are quite a few, but it may take years, decades, or even centuries to differentiate them.

More disturbing to me is our lack of treatments for the negative and cognitive symptoms of schizophrenia. We have no pharmacological treatments for these common symptoms, which are ultimately the cause of disability and progressive functional impairment of individuals with schizophrenia. Why do we focus on searching for pharmacological solutions to these core symptoms? What if cardiologists treated patients with heart disease with only pharmacology? Individuals with heart disease maximize their functional improvement when they aggressively participate in cardiac rehabilitation, dietary modification, smoking cessation, daily exercise, and quality management of other comorbidities, and have increased social support.

Drawing upon this analogy, a major step forward has been the growing implementation of first-episode psychosis (FEP) programs in psychiatric clinics across the country. In 2009, the National Institute of Mental Health funded a study to investigate the benefits of aggressive and comprehensive treatment of individuals in their first psychotic episode. The study, Recovery After an Initial Schizophrenia Episode (RAISE), demonstrated that comprehensive early intervention for FEP improves symptoms and functioning superior to the usual standard-of-care models using 4 pillars of treatment (

 We can call this half-full glass psychosis rehabilitation.

Finally, improved treatments with improved outcomes will happen as we further our understanding of the human brain, which will likely be a slow and arduous process. Our future treatment armamentarium for schizophrenia will likely include interventions about which we currently know nothing. As our learning progresses, our responsibility is to utilize all the tools that are available, and to give all patients full access to these treatments.

It is well established that one-third of patients being treated for a major depressive episode will ultimately fall into the category of treatment resistant.

 Currently, when a patient’s initial presenting depression score improves by 50% or more with treatment, we classify this as a “response.” For patients whose depression score improves by 75% or more, we classify them as “in remission.” For an individual who is severely depressed, a 50% improvement translates to continued significant depressive symptoms. Once a patient has completed and not responded to 2 adequate antidepressant trials of adequate dose and duration, the current consensus in psychiatry in the United States is that their depression is treatment resistant. This definition is arbitrary.

Depression is a complex emotional state, and the range of available treatments beyond pharmacology is immense.

 During my 30 years of practice, I have seen a steady decline in the use of nonpharmacological treatments, and a growing momentum that depression will improve once the right medication or combination of medications has been prescribed. The devolution toward this paradigm has been accelerated and supported by the policies of insurance companies reimbursing psychiatric providers for what they expect will be a 15- to 20-minute medication management visit. This is barely enough time to ask a few questions, continue or modify the medication regimen, order a lab or 2, review risks/benefits/adverse effects, and decide on follow-up. Oh, I almost forgot: This time theoretically also includes the extensive template-driven electronic medical record documentation. Realistically, there is no time to explore significant stressors or events, ask open-ended questions, or discuss nonpharmacological treatments that are viable and, at times, more appropriate options.

Our goal should always be full remission of depressive symptoms—as with the cardiologist, who ideally would treat heart disease back to an optimum cardiac output with no arrhythmias, normal blood pressure, and complete absence of any atherosclerotic plaques. However, just as many patients with cardiology issues continue to have significant heart disease even in the presence of optimal management, many patients with depression may have significant depressive symptoms once they are on an optimal medication regimen. In these settings, our goal is to maximize function and collaborate with the patient to educate them about and assist them in accessing all nonpharmacological treatments.

I treat a woman in her 40s who has had treatment-resistant depression for 9 years and has failed a long list of aggressive pharmacological trials. Recently, her daughter and only child informed her that she was pregnant and that my patient was going to be a grandmother. This news improved my patient’s chronic depressive symptoms significantly more than my 9 years of pharmacological trials. If our patients’ treatment-resistant depression coexists with significant psychosocial stressors, recent unpleasant major life changes, or a history of chronic abuse and trauma that began in childhood, rethinking the treatment plan to include a broader array of interventions than medications may provide substantial benefit, or at the very least affirm the patient’s residual symptoms in the context of their life experiences.

Much excitement followed the complete sequencing of the human genome in 2003. It was a remarkable accomplishment resulting from the convergence of scientific understanding, technological advances in sequencing DNA, generous funding, worldwide cooperation, and a heroic commitment by all the individuals who contributed to the Human Genome Project’s completion.

Initially, the hope was that this treasure trove of information containing the blueprint of the human organism would accelerate our research and treatment of many diseases. Although much has been learned, 18 years later there have been few actionable clinical advances. One shocking discovery early on was that only 2% of the entire human genome coded for proteins—the remaining 98% was initially referred to as “junk DNA.”

 Our limited understanding at the time was that the purpose of DNA was to preserve the information required to construct the many proteins necessary for human life. Since that time, the term 

, and it is likely that much of this DNA has functions that we are just beginning to understand.

We now know that a significant percentage of noncoding DNA is evolutionarily preserved just like essential proteins, which strongly suggests that these sequences play a necessary role in the preservation of our species. It is likely that our future understanding of noncoding DNA will contain novel approaches to treat the wide range of human disease and disorders. That glass keeps filling up with more water.

Epigenetics is a rapidly advancing field that nicely complements genetics and allows for the turning on and off of genes depending on developmental or environmental factors. Genetics and epigenetics are the embodiment of the beauty and necessity of nature and nurture in understanding the inherent plasticity of our genome. Epigenetic modification of the human genome is yet another fertile area that will likely greatly contribute to our understanding of the complex human disorders schizophrenia and major depression. For the interested reader, 2 articles I authored in 2021 issues of 

Epigenetics Collides with Pharmacogenomics

Our growing understanding of the circuits of the human brain provides yet another opportunity to appreciate that, rather than being a prewired organ at birth, which I was taught in the early 1980s, the brain has inherent neuroplasticity, allowing it to change to its environment. A drug-receptor interaction, a memory-activated neuron, or a meaningful psychotherapeutic insight may trigger a cascade of neurochemical processes that ultimately can result in elevated levels of brain-derived neurotrophic factor, which then directs a target protein such as the mammalian target of rapamycin to facilitate synaptogenesis. For drugs such as ketamine and esketamine, this process is one putative mechanism that may contribute to their rapidly acting antidepressant effect.

 Abdallah et al demonstrated that patients who responded to ketamine showed an increase in global brain connectivity in the caudate, insula, and lateral prefrontal cortex.

As the new year begins, taking a moment to reflect on where we have been, where we are, and where we are going is a useful exercise. In our young field of psychiatry, much has happened since Bleuler introduced the term 

 in 1908. Clinical psychiatry today is very different than the field I trained in during the late 1980s—with a potpourri of advances, frustrations, external intrusions, and setbacks. But alas, such is the history of science, medicine, and psychiatry. Our challenge is to keep that flame of hope and optimism burning brightly, and to continue our journey together toward greater understanding, increased global citizenship and cooperation, and a strong dose of humility.

 is medical director, Brain Health, Exeter, New Hampshire; Editor in Chief, 

; staff psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

Life expectancy (from birth) in the United States, from 1860 to 2020

. Statista. February 3, 2021. Accessed December 1, 2021.

. NCHS Data Brief No. 395. December 2020.

Evidence-based treatments for first episode psychosis: components of coordinated specialty care

. National Institute of Mental Health. April 14, 2014. Accessed December 1, 2021.

5. Kane JM, Robinson DG, Schooler NR, et al. 

Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE Early Treatment Program

6. Rush AJ, Trivedi MH, Wisniewski SR, et al. 

Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report

Antidepressants, part 1: 100 years and counting

Junk DNA: A Journey Through the Dark Matter of the Genome

Epigenetics collide with pharmacogenetics

Ketamine/esketamine: putative mechanisms of action

12. Abdallah CG, Averill LA, Collins KA, et al. 

Ketamine treatment and global brain connectivity in major depression

The glass is half full: reflections on where we are and hope for where we are heading in psychiatry.

Hope for the New Year

A new study found that a form of digital cognitive behavioral therapy (dCBT) may help prevent 

 in women for up to 6 months after they give birth.

The study, which was conducted by researchers at the University of California San Francisco (UCSF), tested the efficacy of Sleepio, a self-paced sleep app and form of dCBT, to determine whether treating insomnia would also help prevent depression in postpartum women.

 The study was a follow-up to a study by UCSF researchers in January 2020,

 which found that dCBT treatment helped reduce insomnia and symptoms of anxiety and depression in participants during pregnancy.

“We were curious to see whether the benefits of dCBT for insomnia would maintain after the birth of the child, especially given the demands of having a young infant,” said Jennifer Felder, PhD, lead author of the study; assistant professor of psychiatry; and core research faculty at the UCSF Osher Center for Integrative Health, in a press release. “We were particularly excited to see the benefits lasted to 6 months not just for insomnia, but for mental health more broadly.”

In the study, 105 out of 208 participants were randomized to the dCBT treatment, which involved up to 6 20-minute sessions using the Sleepio app. At 3 months postpartum, 4% of participants who had the dCBT treatment were rated as likely depressed, in comparison to 18% of the remaining participants, who received usual treatments such as medication or general sleep hygiene tips from their providers. According to Felder, part of what set the dCBT treatment apart from usual care is that it was more individualized and addressed common causes of insomnia.

“The magic of the treatment is what happens between sessions—the tactics the participants put into practice, such as keeping a sleep diary, stabilizing their wake time, spending less time in bed tossing and turning, and prioritizing an adequate wind-down before bed,” Felder said in a press release.

With its focus on the connection between postpartum insomnia and depression, the study’s results are significant, as up to 15% of women are affected by postpartum depression; around 38% of pregnant women experience insomnia; and insomnia is associated with a 30% increased risk of pre-term birth.

“I’ve heard patients say, over and over, that their postpartum mental health began to suffer when their insomnia started, suggesting there is a link,” Felder said in a press release. “We know that postpartum can be a vulnerable time for becoming depressed, and it is possible that this intervention may prevent that.”

Digital therapy for prenatal insomnia may prevent postpartum depression

. News Release. University of California San Francisco. December 15, 2021.

2. Felder JN, Epel ES, Neuhaus J, et al. 

Efficacy of digital cognitive behavioral therapy for the treatment of insomnia symptoms among pregnant women: a randomized clinical trial

 [published correction appears in JAMA Psychiatry. 2020 Jul 1;77(7):768]. 

Study also suggests link between postpartum depression and insomnia.

Research Shows dCBT May Help Prevent Postpartum Depression

worked with experts from multiple areas in psychiatry to bring you discussions of important topics, such as identifying and treating victims of human trafficking; diagnosing and managing fibromyalgia; and ethically evaluating dangerousness in individuals with personality disorders. Here are some highlights from our selection of this year’s Continuing Medication Education (CME) articles:

Psilocybin Revisited: The Science Behind the Drug and Its Surprising Therapeutic Potential

Psilocybin and psilocin are the main psychedelic agents of the psychoactive mushroom genus Psilocybe.

 Historical and cultural use of these psychoactive mushrooms dates back 3000 years in Mexico and the Southwestern regional areas of the present-day United States. Scientifically, psilocybin was isolated and identified in 1958, synthesized in 1959, and used in various experimental research studies in the early 1960s. During that time, psilocybin and other psychedelic agents such as lysergic acid diethylamide (LSD) generated considerable controversy. Outside of recreational use, could they be used safely as therapeutic interventions? 

Fibromyalgia: What It Is and How to Treat It

Fibromyalgia (FM) is one of the most controversial diagnoses in the field of pain management. Some experts believe that it does not exist and actually represents an accidental or purposeful misdiagnosis of other conditions, while others believe that it is badly underdiagnosed.

 The truth likely falls somewhere between these 2 extremes. FM is a real syndrome, but it is also perhaps overdiagnosed, both because many physicians are unaware of the actual diagnostic criteria, and because there may be a desire to avoid diagnosing patients with other conditions that could explain the symptoms of FM—most notably mental disorders. 

Psychiatric Evaluation of the Peripartum Patient

The peripartum period is not necessarily a time of emotional well-being,

 highlighted by the fact that about 1 in 13 women develop new-onset major depressive disorder (MDD) while pregnant.

 (The term “peripartum” in this article refers to pregnant women and women who are up to 1 year postpartum.) In the postpartum period, 1 in 7 women will develop MDD and are at high risk for psychiatric hospitalization.

 Thus, comprehensive psychiatric evaluation of the peripartum patient is an essential skill. The mainstay of assessment remains the clinical interview; as such, careful and systematic psychiatric evaluation during these periods is crucial for diagnosis, risk assessment, and treatment. The general psychiatric evaluation, however, must be expanded and tailored to the needs of the peripartum patient. 

Psychiatrists’ Response to Human Trafficking

Human trafficking is a public health issue that involves exploiting individuals for forced sex or labor. Traffickers perpetuate the cycle of exploitation by utilizing methods such as emotional, economic, or physical abuse; isolation; and threats. Physical, mental, legal, and social sequelae of human trafficking can persist for years after individuals survive their trafficking situations. Individuals with a preexisting history of psychiatric illnesses, including substance use disorders, are especially vulnerable to being trafficked. 

Here is a full list of our CMEs from 2021:

Microglial Involvement With Psychiatric Diseases

Neuropsychiatric Symptoms of Multiple Sclerosis

Opportunities in Managing Treatment-Resistant Depression and Tardive Dyskinesia

Psychological and Cognitive Insight: How to Tell Them Apart and Assess for Each

Different Strokes: How to Spot and Treat Poststroke Depression

Transgenerational Transmission of Resilience After Catastrophic Trauma

Prognostic Considerations in Anti-NMDA Receptor Encephalopathy With Psychiatric Manifestations

Cognitive/Neuropsychological Functioning and Suicidal Behavior: A Review of Research and Implications for Clinical Practice

Be sure to stay up-to-date by subscribing to the 

Do you have a comment on any of these or other articles? Have a good idea for an article and want to write? Interested in sharing your perspectives? Write to us at 

Psychiatric Times featured a wide variety of psychiatric issues in this year’s CMEs.

CMEs 2021: A Year in Review

A recent study found that 45% of Americans report that spending time alone is the best way for them to manage their 

In the study, behavioral health and personal development provider All Points North (APN) Lodge polled 1000 adults in the United States across all demographics about the effects of their depression on them during the holidays and the ways they manage these effects. Of the participants, 46% said they were depressed, and 67% of those with depression said their depression increases during the holidays. The poll also asked participants what triggers their depression during the holidays: 55% reported financial issues, 50% reported the loss of a family member or close friend, and 47% reported comparing themselves to others or seeing other individuals who appear to be happier.

In terms of managing their depression, while the majority of participants reported spending time alone, nearly a third (31%) reported drinking alcohol and/or using drugs; 32% of younger participants—members of Gen Z—reported journaling and writing; and 25% said they do not have a healthy way of managing it at all. When asked about their goals for 2022, 42% of participants reported that they have a mental health goal for the new year. Some of these goals included better alignment in mind, body, and soul (64%); seeking mental health treatment (29%); finding alternative ways to treat or manage their mental health issues (25%); and staying sober (22%).

“The nation is still experiencing depression and trauma from the events that took place these past few years, and the holidays will bring that out even more for some,” said Noah Nordheimer, CEO of APN Lodge, in a press release. “In fact, for many, this time of year is extremely challenging; seasonal and holiday depression are more common than most think. But we are hopeful that if we continue to destigmatize mental health issues, we can ensure that people will have access to the best solutions and therapies for their particular challenge.”

Spending quality time alone is Americans’ top method for managing depression, reveals All Points North Lodge research

. News Release. All Points North Lodge. December 2, 2021. Accessed December 16, 2021.

Research identifies common reasons and coping mechanisms for depression that increases during the holidays.

Study Shows How Patients Manage Holiday Depression

The US Food and Drug Administration (FDA) has approved Caplyta (lumateperone) for the treatment of 

Caplyta, an atypical antipsychotic from biopharmaceutical company Intra-Cellular Therapies, is the only drug approved by the FDA for the treatment of depressive episodes stemming from bipolar I or bipolar II disorder in adults as monotherapy or adjunctive therapy with either valproate or lithium. The drug has shown a consistently favorable profile on weight, extrapyramidal symptoms, and cardiometabolic parameters, according to Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies.

Caplyta is now FDA-approved for depressive episodes from bipolar I and II.

Depression