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“There are many ways not to be happy that do not equal depression.”—

Christian Robbins was 16 when he took his life during the first month of the pandemic. According to 

 and the boy’s father, Christian had suffered a number of pandemic-related losses, including closure of his school; cancellation of a family vacation; and isolation from his friends. Quite understandably, his grieving father has been haunted by the question, “What if the pandemic never happened? Would my son still be alive?”

Of course, it is impossible to know. The Centers for Disease Control reported that between June 24, 2020 and June 30, 2020, about 1 in 4 young adults (aged 18 to 24 years) had seriously considered suicide in the 30 days before completing 

 But attributing a completed suicide primarily to the pandemic is probably a considerable over-simplification. For example, in the case of Christian Robbins, 

 report notes that the young man “had been struggling for months with depression and early symptoms of bipolar disorder.” Moreover, Christian had told his father of “a voice inside [that] was whispering how worthless he was, how he was hated by everyone.”

It is tempting to hypothesize that Christian’s suicide was largely a result of a (bipolar) major depressive episode, possibly complicated by psychotic features. The pandemic and its attendant losses seem likely to have been the immediate precipitants. But 

 suggests other possibilities, and compels us to consider mental and emotional states that are not discussed at all in the DSM-5, to my knowledge, and may confer a high risk of suicide even when the individual does not meet full DSM criteria for a major depressive episode.

Moreover, there are good reasons, at times, to shift our perspective from the strictly clinical to the quintessentially spiritual; specifically, to what some mystics and theologians have called “the dark night of the soul.” First, though, we need to examine 2 closely related concepts that are not part of the DSM’s nosology.

Demoralization is succinctly described in 

Demoralization is a syndrome clinically separated from depression. It is characterized by a combination of distress and subjective incompetence; the loss of meaning and purpose in life; the lack of perceived social support; a sense of being trapped and personal failure; a cognitive attitude of pessimism, and hopelessness/helplessness. Moreover, this psychological state has a significant role in negatively influencing a patient’s quality of life, coping styles, and dignity. It is associated with [suicidal] ideation; a higher wish for hastened death; and a worsening of the prognosis in patients affected by medical illness.

A more existential description of demoralization is provided by psychologist 

: demoralization is “an overarching psycho-spiritual crisis in which victims feel generally disoriented and unable to locate meaning, purpose, or sources of need fulfilment.”

Note that both descriptions involve a loss of meaning and purpose in life. We can easily envision many people suffering emotionally during the current pandemic who may not meet DSM-5 criteria for a major depressive disorder, but who would fit these descriptions of demoralization—and who might well become suicidal because of that mental and emotional state.

 psychiatrist Kenneth Gilbert, MD, described a trait he has observed in many individuals with substance use disorders who wind up fatally overdosing on opioids. He opined that these individuals do not seem to “feel that their own lives are worth protecting” or that “their own lives are worth living.” Gilbert further described such fatal outcomes as deaths of despair and wondered whether “without a sense of meaning or engagement, [these individuals] might have no reason to protect their own lives.”

Despair is understood broadly as “an entire want of hope.”

 I believe Gilbert is correct in conceptualizing this as an existential problem—with important implications for psychiatry. Indeed, 

, and colleagues has linked despair with higher rates of substance misuse and suicidality in young adults.

 Using data from structured interviews, Copeland et al derived 7 indicators of despair: feelings of hopelessness, helplessness, feeling unloved or worthless, experiencing worry, self-pity, and loneliness.

Importantly, whereas many participants with depression also reported despair, most individuals reporting despair did not meet formal criteria for a depressive disorder.

 The import of the Copeland et al study is simply this: we must look beyond the DSM categories of depression if we are to recognize young people (and probably others) who are truly suffering and at risk for substance abuse and suicide.

The phrase, “dark night of the soul” is often used informally to describe an extremely difficult and painful period in one’s life, for example, after the death of a loved one; the break-up of a marriage; or the diagnosis of a life-threatening illness. For many, the loneliness, isolation and fear associated with the coronavirus disease 2019 pandemic is, indeed, a dark night of the soul. There is nothing wrong with these informal usages, and they have obvious links to the concepts of demoralization and despair, as we have defined them. But they differ significantly from the original meaning and context of the phrase, as first conceived by the Spanish mystic, John of the Cross (1541-1597 AD).

John was a member of the Carmelite religious order, which he was trying to reform. The thanks he got was imprisonment by his Carmelite brethren, during which John composed his remarkable poem, “

 (The Canadian singer, Loreena McKennitt, has set the poem quite 

On a dark night,
Kindled in love with yearnings–oh, happy chance!–
I went forth without being observed,
My house being now at rest.

John’s poem is essentially a spiritual odyssey. It recounts “

the journey of the soul from its bodily home to its union with God

 This mystical concept may seem too esoteric to have relevance in clinical psychiatry; but as we will see, the dark night may be understood more existentially, in ways that have considerable relevance to our profession.

, the psychotherapist and former Catholic monk, Thomas Moore, makes an important observation. He writes, “The dark night calls for a spiritual response, not only a therapeutic one.” The dark night calls upon the affected person “to remain in the present, not bound or deluded by the past and not imprisoned in a fixed and defensive idea about the future…the most difficult challenge is to let the process take place, and yet that is the only release from the pressure of the dark night.”

Sadly, not everyone will survive the dark night of the soul. Some of those Moore mentions, like the poet Anne Sexton, will die by their own hand. Those who do survive have come to realize, as Moore puts it, that “life is never as bright and successful and meaningful as you might imagine”.

 And yet, these survivors have found—or rather, created—new meaning in their lives.

Moore cites as an example the pianist Leon Fleischer, who died recently at the age of 92. At the age of 36, Fleischer suffered a mysterious neurological affliction that essentially crippled his right hand and nearly ended his career. None of the treatments he received helped, and Fleischer fell into a 2-year period of despair, to the point of considering suicide. But then, an epiphany: 

, “I suddenly came to the realization that my connection with music was greater than just as a two-handed piano player.”

 Fleischer essentially re-invented himself, becoming a teacher, a conductor, and a performer of the left-handed repertoire for piano. As Moore puts it, “it was the expansion of his musical vision that saved him.”

The Midwife and the Dark Night of the Soul

As therapists, we need, in the first place, to appreciate and recognize the dark night of the soul as it afflicts and transforms our patients. We also need to recognize and assess the degree of demoralization and despair our patients may be experiencing, as these have implications for substance abuse and suicidality.

At the same time, we need to distinguish the dark night of the soul from various states of disease and disorder, such as major depressive disorder—which, in some unfortunate cases, may be the outcome of an unsuccessful spiritual journey. The dark night itself is not a disease, but part of the price we pay for being vulnerable human beings.

We need not be observantly religious to help our patients through their dark night, nor need we enter into the mystical world of John of the Cross. Rather, we can act as midwives to our patients’ inner transformation—supporting and encouraging them as they struggle to give birth, often painfully, to new meaning in their lives. As philosopher Peter Wilberg has put it, this kind of healing: “is no longer identified with mental, emotional or bodily ‘recovery’ but rather, with self–discovery – the birth of a newly felt bodily sense of self…[and] the metaphor of 

 comes from the Greek word “maieutikos,” meaning “of midwifery.” In one of Plato’s “Dialogues” (the 

), Socrates—the son of a midwife—applies the term 

 to his method of bringing forth new ideas by reasoning and dialogue. He thought the technique “

analogous to those a midwife uses in delivering a baby

 The maieutic concept of care does not require us to set aside our medical training or biological knowledge, which are essential parts of our identity as psychiatric physicians. Rather, the metaphor of the midwife enlarges our understanding of medical healing to include our ministering to the soul—especially during its darkest night.

is professor emeritus of psychiatry and lecturer on bioethics and humanities, SUNY Upstate Medical University; clinical professor of psychiatry, Tufts University School of Medicine; and editor in chief emeritus of

 Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

2. Wan W. For months, he helped his son keep suicidal thoughts at bay. Then came the pandemic. 

. November 23, 2020. Accessed December 2, 2020.

https://www.washingtonpost.com/health/2020/11/23/covid-pandemic-rise-suicides/

3. Czeisler MÉ, Lane RI, Petrosky E, et al. Mental health, substance use, and suicidal ideation during the COVID-19 pandemic — United States, June 24–30, 2020. 

4. Bower B. ‘Deaths of despair’ are rising. It’s time to define despair. 

 November 2, 2020. Accessed December 2, 2020. 

https://www.sciencenews.org/article/deaths-of-despair-depression-mental-health-covid-19-pandemic

5. Battaglia Y, Zerbinati L, Piazza G, et al. The use of demoralization scale in Italian kidney transplant recipients. 

 April 1, 2016. Accessed December 2, 2020. 

https://newint.org/columns/essays/2016/04/01/psycho-spiritual-crisis

 Nov. 24, 2020. Accessed December 2, 2020. 

https://www.psychiatrictimes.com/view/dying-dream

9. Copeland WE, Gaydosh L, Hill SN, et al. Associations of despair with suicidality and substance misuse among young adults. 

10. St. John of the Cross. The Dark Night. 

The Collected Works of St. Jon of the Cross

. Trans. Kieran Kavanagh and Otilio Rodriguez. ICS Publications; Revised edition, 1991.

11. Loreena McKennitt. The dark night of the soul. Accessed December 2, 2020. 

https://www.youtube.com/watch?v=MclLF473XtA

12. The Dark Night of the Soul. Accessed December 2, 2020. https://makeheaven.com/st-john-of-the-cross.html

13. Huizenga T. Leon Fleisher, the pianist who reinvented himself, dies At 92. 

https://www.npr.org/sections/deceptivecadence/2020/08/02/702978476/leon-fleisher-the-pianist-who-reinvented-himself-dies-at-92

Phenomenological Medicine and Organismic Therapy

https://existentialmedicine.wordpress.com/phenomenological-medicine-and-organismic-therapy/

15. Maieutic. Merriam-Webster Dictionary. Accessed December 2, 2020. 

https://www.merriam-webster.com/dictionary/maieutic

Pies RW: Care of the soul in the time of Covid-19. 

. March 23, 2020. Accessed December 2, 2020. 

https://www.psychiatrictimes.com/view/care-soul-time-covid-19

Pies RW. Is the country experiencing a mental health pandemic? 

 Oct. 13, 2020. Accessed December 2, 2020.

https://www.psychiatrictimes.com/view/are-we-really-witnessing-mental-health-pandemic

The anatomy of unhappiness is more complex than DSM-5’s categories.

Psychiatry and the Dark Night of the Soul

VistaGen Therapeutics announced that the Korean Intellectual Property Office (KIPO) in the Republic of Korea has granted the patent application for VistaGen’s PH10. PH10 is a nasal spray with therapeutic potential in treating depression. It was initially intended to be a potential stand-alone treatment for major depressive disorder (MDD).

“The Republic of Korea is an important pharmaceutical market. With counterpart patents already issued in the US, Greater China, Europe, and Japan, this patent enhances our patent protection for PH10 and is a key component of our global commercial protection strategy for PH10,” Shawn K. Singh, Chief Executive Officer of VistaGen, said to the press. “Our late-stage development and commercialization strategy for PH10 is similar to our strategy for PH94B, namely, to license these rights in key pharmaceutical markets outside of North America.”

After successfully completing the Phase 2A clinical development, VistaGen is preparing for the Phase 2B clinical development of PH10 as a potential stand-alone treatment for MDD. The patent granted by KIPO is not set to expire earlier than 2034.

“MDD affects more than 264 million adults globally and can have significant emotional, functional and economic impact on those who suffer from the disorder and their loved ones. Recent studies have also shown that there has been an exacerbation of existing depression symptoms, with US adults showing three times as many symptoms of depression during the COVID-19 pandemic we are battling, making the need for better, safer alternatives for depression treatments more imperative. We believe PH10 has the potential to transform the treatment landscape for individuals with MDD in global depression markets, and we believe this patent will help protect and propel global development,” Singh said further.

To hear more from Shawn Singh of VistaGen, see 

1. VistaGen Therapeutics. VistaGen announces Korean Intellectual Property Office decision to grant PH10 patent for treatment of depression. News release. December 10, 2020. 

https://ir.vistagen.com/press-releases/detail/157

VistaGen Therapeutic’s grant application for PH10, an investigational therapeutic agent for the treatment of depression, has been approved.

Korean Intellectual Property Office Grants Patent Application for Depression Treatment

Major depressive disorder (MDD) is the leading cause of global disease burden.

 of MDD in the United States has continued to increase among all age groups.

 Patients with these disorders are twice as likely to suffer from a comorbid substance use disorder (SUD) compared with the general population, and the severity of the S6UD parallels that of MDD.

 The comorbidity poses treatment challenges, and patients have been found to have poor outcomes (eg, increased substance use, more severe disease burden, higher rates of suicide attempts and behaviors), as well as an overall increased mortality.

The tight association between MDD and SUD does not necessarily hint at causation, as substance use can lead to mental health symptoms and conditions; mental illness can lead to self-medicating with substance use; and both conditions may co-occur independently as in the case of overlapping predisposing genetic factors. For patients with the comorbidity treatment gaps exist. 90% of those with SUD do not get MDD treatment, and 55% of those with MDD do not get SUD treatment when addressed independently, while 33% of them get no treatment at all.

Both MDD and SUD are in the DSM-5 and hence it is our responsibility to treat them as part of our routine psychiatric practice. Treating depression and substance use independently and in isolation of each other is incongruent with 

 Guidelines recommend simultaneous and integrated treatment with pharmacotherapy and/or psychotherapy for MDD depending on disease severity.

As for how closely these guidelines are followed, no study to date has investigated whether those with the SUD comorbidity receive similar MDD care to those without SUD among the pharmacotherapy and psychotherapy-based treatment modalities, or the degree to which specific SUDs are differentially associated with the receipt of guideline-specific MDD treatment. 

 Do patients with MDD and comorbid SUD receive similar, guideline-concordant, care as those without SUD?

 of 53,034 patients in whom MDD was diagnosed in the 2017 fiscal year in the US Veterans Health Administration (VHA).

 The patients were all veterans receiving care through the US Veterans Health Administration system. They all had a diagnosis of depression made in 2017.

 Electronic medical record data was reviewed to identify patients from both inpatient and outpatient encounters who were diagnosed with depression using ICD-10 codes and Patient Health Questionnaire (PHQ) screens. The PHQ was required to have been documented within a 30-day window of the depression diagnosis in order to capture active depressive episodes. Exclusionary criteria targeted patients with a past depressive diagnosis or who had received prescription antidepressants (except trazodone) or 

 in the past 12 months prior to the index diagnosis date. Also excluded were those with positive PHQ scores documented between 30 days and 12 months before the index depression diagnosis. Patient with comorbid bipolar disorder, schizophrenia, psychosis, personality disorder or developmental disorders, or those with more than 30 days of inpatient treatment in the last year were also excluded. Patients with comorbid SUD were identified as receiving a SUD diagnosis in the year before the depression diagnosis, as identified using ICD-10 codes meant to capture alcohol, opioid, cannabis, cocaine, stimulants, and other SUDs.

The outcomes measure assessed was adherence to treatment guidelines. For this, the authors used 

Healthcare Effectiveness Data and Information Set

 (HEDIS), which is a set of performance measurement tools developed and maintained by the National Committee for Quality Assurance (

) and widely used to assess where improvements can make a difference. HEIDIS is intended to allow comparisons among various health plans, systems, as well as adherence to national benchmarks and guidelines.

Among patients who received an initial prescription for antidepressants within 90 days of the index, depressive disorders to HEDIS based measures related to pharmacotherapy were applied. These resulted in measurements of adequate acute phase treatment (receipt of an antidepressant prescription within 90 days of diagnosis that provides medication for at least 84 of the 114 days following initial prescription); adequate continuation phase treatment (continuing antidepressant for 180 of the first 231 days following initial script).

) was also examined using metrics analogous to HEDIS. Here they evaluated both acute phase treatment (psychotherapy sessions that occurred within 90 days of the index depression diagnosis), as well as continuous phase treatment (at least 3 psychotherapy sessions in the 12 weeks following the first session). Additionally, the authors considered the confounding element that psychotherapy could be delivered for both depressive disorders and SUDs hence, in the analysis-only sessions for whichdepressive disorders were the primary diagnosis were included.

The authors also aimed to adjust for patient demographics (age, gender, race, geographical locality, and distance from the VA) and clinical characteristics (comorbid mental health disorders, measured by the Elixhauser score for severity).

. Sample characteristics across all described covariates were compared between those with and without SUD. Four multivariate logistic regression models were conducted to assess the associations between the presence of a SUD diagnosis and adequate acute and continuous phase antidepressant or psychotherapy treatment. Adjustments for covariates were done for each model.

The authors estimated percentages of those receiving treatment across each of the depression care metrics (those with and without comorbid SUD) as the marginal means of balanced population based on the model. Associations of specific SUDs with depression treatment were examined via the 4 models with each SUD independently analyzed. Authors also descriptively examined the setting where patients with SUD were receiving depression treatment.

Among the 53,034 participants diagnosed with a new episode of depression during the 2017 fiscal year, 52.9% received antidepressant treatment and 34.9% received psychotherapy within 90 days following diagnosis. Of this cohort, 14.2% had a SUD diagnosis in the year prior to the depression diagnosis.

Patients with SUD comorbidity had more visits in mental health and primary care settings in the year following the depressive diagnosis (average of 14.1 visits [SD 18.1] compared with 10.2 visits [SD 10.9] among those without SUD). Unfortunately, despite this higher opportunity for depression treatment, those with SUD received significantly less guideline-concordant depressive treatment across all metrics.

Before adjusting for covariates, observed rates show acute and continuation-phase antidepressants were provided to 59.4% and 36.3% of those with SUD and MDD versus 66.2% and 44.8% of those with just MDD (

. In terms of psychotherapy, 31.6% and 26.8% of those with SUD received acute and continuation-phase treatment respectively, compared to 35.4% and 32.2% of those with just MDD (

). For those with SUD, most received treatment in metal health clinics (47% psychotherapy [N = 1117]; 59.1% antidepressants [N = 2390]); or in primary care/mental health integration clinics (42.7% psychotherapy [N = 1014] and 31.8% antidepressants [N = 1287]). A very small minority received depression treatment in SUD specialty clinics (3.5% psychotherapy [N = 83] and 2.5% antidepressants [N = 102]).

In terms of patient characteristics, those with SUD were slightly younger, male, African American, homeless, and had comorbid psychiatric conditions. Those without SUDs were more likely to be service connected, live in rural areas, and have more comorbid diagnosed medical conditions.

Patients with SUD had lower odds of receiving guideline-concordant care, specifically 21% lower odds of receiving acute antidepressant treatment, 13% lower odds of initial psychotherapy treatment, 26% lower odds of adequate continuation of antidepressant, and 19% lower odds of continuation of psychotherapy.

Based on predicted probabilities of receipt of guideline-concordant depression treatment, an estimated 55% of individuals with comorbid SUD, compared with 61% without, received adequate acute antidepressant treatment, and 27% of individuals with comorbid SUD, compared with 29% without, received initial psychotherapy. As for cotinuation of treatment, 33% of individuals with comorbid SUD, compared with 40% without, received adequate continuation of antidepressants, and 22% of individuals with SUD, compared with 25% without, received adequate continuation of psychotherapy.

In terms of specific SUDs, lower quality depression care was evident across all evaluated substance types. Alcohol and cannabis use disorders were associated with significantly lower odds of adequate continuation of antidepressants (adjusted OR 0.81, 95% CI = 0.75, 0.88, p < 0.001 and adjusted OR 0.74, 95% CI = 0.63, 0.87, p < 0.001 respectively). Alcohol and cocaine use disorders were associated with lower odds of initiation of psychotherapy for depression (adjusted OR 0.86, 95% CI = 0.81, 0.91, p < 0.001 and adjusted OR 0.78, 95% CI = 0.66, 0.92, p < 0.001 respectively). Alcohol use disorders alone were associated with lower odds of adequate psychotherapy continuation (adjusted OR 0.81, 95% CI = 0.72, 0.90, p < 0.001).

There were also several covariates associated with lower odds of guideline-concordant care. These included homelessness, racial and ethnic minority groups, those in rural areas, and those with high psychiatric disease burden living farther away from a health care facility.

This retrospective review study of patients in the Veteran Healthcare Administration system points to a treatment gap in the delivery of guideline-concordant care for depression among those with SUD compared with those without it.

This study assessed an interesting question: do patients with comorbid MDD and SUD receive different care for depression than those without SUD? Consistent with previous data

 in a large national sample of veteran patients within the VHA system, the authors found that having the comorbid SUD diagnosis is associated with lower quality of depression treatment compared with those without it.

 After accounting for various demographic, medical, and psychiatric factors, patients with SUD had lower odds of adequate acute phase treatment (21% and 13% lower for antidepressant and psychotherapy, respectively) and lower odds of adequate continuation of treatment (26% and 19% lower for antidepressant and psychotherapy, respectively) for depression. This discrepancy in guideline-concordant care for depression comes despite patients with SUD having higher health care utilization (more visits and medical encounters) and hence more opportunities for MDD treatment initiation. Knowledge of this treatment gap is important because SUD and MDD affect each other bidirectionally, and the most effective approaches involve concurrent treatment.

There are several limitations to this study. As the authors point out, this sample is limited to veterans in care within the VHA system. The generalization outside this system, and to civilians with various insurance coverages, is unknown. Additionally, the analysis does not include or account for services rendered outside the VHA system, where it is not uncommon for veterans to seek care from.

The diagnosis of MDD as well as SUD is identified here based on ICD-10 codes entered in the electronic health records, which can at times contain errors or not even be entered at all.

There is no mention of how closely providers actually adhere to the use of screening tools such as PHQ-9. It is also necessary to consider that there are other widely available tools that are not accounted for here. It is important to keep in mind that lack of training in the assessment and treatment of complex presentations such as comorbidity leads to inaccurate beliefs and stigmas, an inability to accurately identify co-occurring disorders,

 a lack of awareness of appropriate referral sources,

 and a lack of preparedness to treat co-occurring disorders.

 The providers caring for these patients are not explicitly defined here as to whether they are highly trained physicians or independently practicing nurse practitioners.

The severity of the MDD is not specifically described here via the use of any objective measure.

 Because engagement (or refusal) in treatment represents a patient-specific barrier, having a significant MDD severity, which patients with SUD comorbidity do, can lead to low motivation and lack of interest and future outlook, and hence would make it less likely for patients to be interested in and pursue treatment as well as adhere to it.

The sample selection criteria (new diagnosis of depression in fiscal year 2017 and a positive PHQ depression screen 30 days surrounding time of diagnosis) may lead to limits of generalizability of findings to the degree that these criteria may not capture most patients with depression (ie, preexisting diagnosis, noncompletion or adherence with depression screen).

Worthy of mention is that in the context of certain substances (ie, stimulant or cannabis), MDD may have psychotic features and hence require treatment with nontraditional modalities such as antipsychotics, rather than antidepressants. Within the limits of the study design it is also difficult to determine whether the MDD is due substance use or withdrawal.

The primary outcome measures here were based on the HEDIS, which has been criticized in the past for how its individual measures provide a narrow view of health care quality and interventions. There is also a question about whether attainment of their measures actually indicate better outcomes. In this study, the indicators of adequate acute and continuous phases of care (which are most often used measures of the quality of depression care) certainly do not encapsulate all features relevant to high-quality depression care. Nonetheless, HEDIS is part of NCQA’s accreditation process and attainment is globally used as incentive for many health plans and 

The data generated here is consistent with the challenges in treating patients with an SUD comorbidity and it points toward the need to better address the rapidly expanding dual-diagnosis population. From here, next steps towards improvement of delivery of care to this population should include efforts at specifically identifying barriers that account to this gap, whether clinician related, institutional or system.

is assistant professor of psychiatry at Dartmouth’s Geisel School of Medicine and Director of Addiction Services at New Hampshire Hospital, Concord, NH. He is Addiction Section Editor for 

. The author reports no conflicts of interest concerning the subject matter of this article.

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1. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. 

2. McCance-Katz E. US Department of Health and Human Services. National Survey on Drug Use and Health. 2019. September 2020. Accessed November 20, 2020. 

https://www.samhsa.gov/data/sites/default/files/reports/rpt29392/Assistant-Secretary-nsduh2019_presentation/Assistant-Secretary-nsduh2019_presentation.pdf

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https://www.drugabuse.gov/sites/default/files/rrcomorbidity.pdf

4. Trivedi RB, Post EP, Piegari R, et al. Mortality among veterans with major mental illnesses seen in primary care: results of a national study of veteran deaths. 

5. Watkins KE, Hunter SB, Burnam MA, et al. Review of treatment recommendations for persons with a co-occurring affective or anxiety and substance use disorder. 

Clinical Guidelines Committee of the American College of Physicians. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians

7. VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder Management of Major Depressive Disorder Working Group:. US Department of Veterans Affairs, US Department of Defense. 2016. Accessed November 20, 2020. https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFINAL82916.pdf

8. Coughlin LN, Pfeiffer P, Ganoczy D, Lin LA. 

Quality of outpatient depression treatment in patients with comorbid substance use disorder

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10. Jordan N, Sohn M-W, Bartle B, et al. Association between chronic illness complexity and receipt of evidence-based depression care. 

11. Hawkins EH. A tale of two systems: co-occurring mental health and substance abuse disorders treatment for adolescents. 

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https://www.va.gov/opa/pressrel/pressrelease.cfm?id=2847

Are patients with depression and substance use disorder getting an appropriate level of care? Our Journal Club piece investigates.

An Inside Look at Depression Treatment Among Patients With Addictive Disorders

Top Medications for Alcohol Use Disorders with Depression

One medication stood out as the most effective in a meta-analysis of alcohol use disorders with depression, but few patients are taking it.

Top Medications for Alcohol Use Disorders With Depression

Spare a thought for anyone spending Thanksgiving all alone. 

 suggests that isolated individuals may long for company in the same way that hungry children long for that apple pie in the oven.

“People who are forced to be isolated crave social interactions similarly to the way a hungry person craves food,” Rebecca Saxe, a senior author of the study, 

. “Our finding fits the intuitive idea that positive social interactions are a basic human need, and acute loneliness is an aversive state that motivates people to repair what is lacking, similar to hunger.”

For the study, Saxe and her co-authors collected 40 participants, individuals aged 18 to 40. The participants underwent a pair of 10-hour test periods. One required a 10-hr fast, and the other required 10 hours of strict social isolation, alone in a windowless room on the campus of the Massachusetts Institute of Technology. After the test periods, the participants were scanned by a magnetic resonance imaging (MRI) scanner and shown pictures of either food or individuals interacting.

“We wanted to see if we could experimentally induce a certain kind of social stress,” Saxe explained to the press. “It’s a stronger intervention of social isolation than anyone had tried before.”

The researchers focused on the substantia nigra, a structure located in the midbrain and associated with hunger pangs. Sure enough, both fasting and isolated participants showed “craving signals.” The strength of the signal also correlated with the participants reports of how hungry or lonely they felt.

Additionally, participants who reported high levels of satisfaction with their social lives outside of the study experienced higher levels of social hunger. “For people who reported that their lives were really full of satisfying social interaction, this intervention had a bigger effect on their brains and on their self-reports,” Saxe said.

At the end of the published study, the authors raised the issue of how much “positive social interaction is sufficient to fulfill our social needs and thus eliminate the neural craving response.”

Whether digital communication alone can satisfy social hunger is an open question, they noted, and an important one.

“In early 2020 millions of humans experienced a sudden, externally mandated period of relative or complete physical isolation from others,” the authors concluded. “This unprecedented upheaval in people’s social routines emphasized the need for a better understanding of human social needs and the neural mechanisms underlying social motivation.”

What do you think? Are you craving company? 

1. Tomova L, Wang KL, Thompson T, et al. Acute social isolation evokes midbrain craving responses similar to hunger. 

Trafton A. Neuroscientists find that isolation provokes brain activity similar to that seen during hunger cravings. Medical Press. November 23, 2020. Accessed November 25, 2020. 

A new study finds that isolation makes us want company on a neural level, in much the same way that hunger makes us want food. 

Craving Company  

Obesity can have a major impact on a patient's overall health, and depression can have an unpredictable effect on a patient's weight. Therefore, they need to be vigilant in their food choices and exercises. Susan J. Noonan, MD, MPH, talks more. 

is a physician consultant and Certified Peer Specialist in the Department of Psychiatry at McLean Hospital and the Massachusetts General Hospital. She is the author of four books and a blog on managing depression, most recently 

Helping Others With Depression: Words to Say, Things to Do

. Dr Noonan offers peer counseling to fellow patients, including physicians and other professionals, and can be confidentially reached through her website at 

Depression can cause weight loss or a loss of appetite... or it could cause weight gain and an increased appetite. Here is some need-to-know information on weight control and mood disorders. 

Weight Control and Mental Illness

Researchers at Washington University School of Medicine in St. Louis discovered in a preliminary study

 that the drug fluvoxamine may prevent some of COVID-19’s most serious complications. Treatment with fluvoxamine may make hospitalization and supplemental oxygen usage less likely.

“The patients who took fluvoxamine did not develop serious breathing difficulties or require hospitalization for problems with lung function,” Eric J. Lenze, MD, the Wallace and Lucille Renard Professor of Psychiatry, and the paper's first author, said to the press. “Most investigational treatments for COVID-19 have been aimed at the very sickest patients, but it's also important to find therapies that prevent patients from getting sick enough to require supplemental oxygen or to have to go to the hospital. Our study suggests fluvoxamine may help fill that niche.”

Fluvoxamine, a selective serotonin-reuptake inhibitor (SSRI), is used commonly to treat obsessive-compulsive disorder (OCD), social anxiety disorder, and depression. Unlike other SSRIs, fluvoxamine interacts strongly with a protein called the sigma-1 receptor, which helps regulate inflammation.

“There are several ways this drug might work to help COVID-19 patients, but we think it most likely may be interacting with the sigma-1 receptor to reduce the production of inflammatory molecules,” said senior author Angela M Reiersen, MD, an associate professor of psychiatry, to the press. "Past research has demonstrated that fluvoxamine can reduce inflammation in animal models of sepsis, and it may be doing something similar in our patients.”

Study supplies were delivered to the self-quarantined participants via a package left at their door. These materials included the study medication, an oxygen saturation monitor, a blood pressure monitor, and a thermometer. Participants used the equipment to confirm vital signs and oxygen saturation of 92% or greater. Data was collected via twice-daily surveys, sent by email, with phone call collection as an alternative for those without internet access.

The study involved 152 randomized participants with mild-to-moderate cases of COVID-19 who were recovering in their homes. The mean age was 46 years and 72% of these participants were women. Of the 152 patients, 76% of them completed the trial. Researchers broke the participants into 2 groups: those treated with fluvoxamine (80 participants) and those given an inactive placebo (72 participants). None of the 80 patients receiving fluvoxamine became seriously ill, whereas 6 of the 72 receiving the placebo experienced serious clinical deterioration, with 4 hospitalized.

“Our goal is to help patients who are initially well enough to be at home and to prevent them from getting sick enough to be hospitalized,” Caline Mattar, MD, an assistant professor of medicine in the Division of Infectious Diseases, reported to the press. “What we’ve seen so far suggests that fluvoxamine may be an important tool in achieving that goal.”

Fluvoxamine was not intended as a COVID-19 medication, but a recent study suggests it may help prevent serious complications for patients with COVID-19. 

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