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“The main message here is that depression is a family affair,” Myrna Weissman, PhD, professor at Columbia University and Chief of the Division of Translational Epidemiology at New York State Psychiatric Institute, told attendees of the 2021 Virtual American Psychiatric Association Annual Meeting. “Especially if you’re dealing with offspring.”

Weissman presented her research on the contributions to the understanding of depression during the session, “Depression in Families: Clinical Opportunities for Breaking the Cycle of Transmission.”

She discussed 3 major topics: studying 3 generations at high risk for depression over 38 years, how treatment has the potential to break the cycle of transmission, and how interpersonal psychotherapy for depression has expanded and been modified during the pandemic.

 She looked at parents with serious major depression (high-risk family) and followed their children and grandchildren, comparing them to those who did not have depression (low-risk family). “I was interested to see what happened to youth who became depressed and to follow them over time.”

She found that high risk families were more likely to pass mood disorders to their offspring, with a peak of onset at adolescence to young adulthood (usually before age 40). Grandchildren with 2 affected previous generations are at 3-fold risk for MDD and an increased risk of suicidal behavior. 

Another interesting find was the effect of religion: mothers for whom religion was very important were 81% less likely to have major depressive disorder (MDD) than mothers who did not find religion as important. Furthermore, religion and spirituality importance in parents was associated with lower risk of suicidal behavior in both boys and girls.

Can treatment prevent the cycle of transmission? Weissman said it is possible if the mothers are treated for depression. One study showed that children’s depression significantly improved after the mother received at least 3 months of treatment.

“The mother’s improvement, regardless of treatment type would help the child clinically. If you have a depressed child, find out about the mom,” Weissman advised.

Weissman’s decades of research concluded that depression is inheritable, but the cycle can be broken. However, the role of environment is still variable.

“Is it nature or nurture?” Weissman posed during the Q+A session. “We cannot at this time determine how much is genetic and how much is environmental because people who are depressed produce environments that can be toxic.”

When evaluating patients for depression, Weissman suggested asking them about key members of their family: their mother, father, and any biological children. Family, she stressed, is key to targeting treatment for depression.

1. van Dijk M, Murphy E, Posner JE, et al. Association of multigenerational family history of depression with lifetime depressive and other psychiatric disorders in children: results from the Adolescent Brain Cognitive Development (ABCD) study. JAMA Psychiatry. 2021.

2. Miller L, Warner V, Wickramaratne P, Weissman M. Religiosity and depression: ten-year follow-up of depressed mothers and offspring. 

3. Weissman M, Pilowsky DJ, Wickramaratne P, et al. Remissions in maternal depression and child psychopathology: a STAR*D-child report. 

Can depression be passed on to future generations, and if it can, how can treatment help? 

Depression: A Family Affair

Not long ago, tranquilization was an important goal of psychopharmacology, and sedation was integral to this therapeutic effect. Major tranquilizers (ie, antipsychotics) sedated psychosis and mania, while minor ones (ie, benzodiazepines) calmed the anxious mind. Even antidepressants were thought to 

, in part because insomnia is a symptom of depression, but also because of concerns that patients might act on suicidal impulses if their energy improved before their depression did.

Those ideas were put to rest in the 1990s, as nonsedating medications proved just as effective as their sedating predecessors. Rather than forewarning suicide, early increases in energy and physical activity are actually a 

 Improved functioning is the goal in psychopharmacology, and sedation usually does not contribute to that goal.

Sedation is sometimes desirable and sometimes not. It is desirable when treating 

, as long as the sedative effects do not linger into the morning. It can also be life-saving when treating acute agitation in emergency situations. Increased activity does not foretell a positive outcome, and may even be a risk factor for suicide, when it is due to adverse effects like 

The simplest way to manage unwanted sedation is to choose medications that are less likely to cause it. 

 ranks psychiatric medications by their sedation risk, based on meta-analyses of clinical trials and data from the US Food and Drug Administration (FDA)

 Although these analyses arrived at fairly consistent conclusions, 

 is still only an approximation. The relative rankings apply within each class, but some classes as a whole are more sedating than others, particularly the antipsychotics.

Surprisingly, the traditional mood stabilizers, particularly lithium, are not nearly as sedating as the antipsychotics. Lithium has been reported to cause sedation in about 1 in 16 to 1 in 27 patients, depending on the study. With most second-generation antipsychotics, this rate is 

 While lithium may not cause much drowsiness, it does cause adverse effects that can be mistaken for sedation, like motoric and cognitive slowing, especially in higher concentrations.

There are 2 nonsedating antidepressants that have stimulant-like properties: bupropion and tranylcypromine. Tranylcypromine is a monoamine oxidase inhibitor (MAOI), but it is structurally related to amphetamine and has dopaminergic effects in the brain. Both of these medications are best dosed in the morning. However, their stimulating effects do not necessarily mean that they will disrupt sleep quality, as we will see later in this review. 

 shows the most and least sedating antidepressants within each class.

Sedation is rarely encountered when treating 

 (ADHD) with traditional stimulants, but it can be a problem with the nonstimulant treatment options. Sedation is a well-known side effect of the α2 agonists, particularly clonidine, but new data suggests that atomoxetine may also carry a high risk. In clinical trials of atomoxetine, only 1 in 20 patients reported fatigue.

 However, in the FDA postmarketing reporting system, atomoxetine ranked second for its propensity to prompt reports of somnolence. (The study ranked atomoxetine against 30 antidepressants since it has an antidepressant structure).

 If fatigue was rare in clinical trials of atomoxetine, why did it prompt so many reports of somnolence? The best explanation for this discrepancy is that peak plasma levels of atomoxetine can be 10-fold higher in CYP2D6 poor metabolizers. Therefore, while fatigue may be rare with this drug, it is likely to be quite severe in patients that do experience it.

When it comes to antipsychotics, finding a nonsedating option is like navigating between the fabled 

. Patients tend to experience akathisia when we select the less sedating options like lurasidone, risperidone, cariprazine, and aripiprazole. The more sedating ones, such as clozapine, olanzapine, quetiapine, and ziprasidone, are less likely to cause 

. When patients cannot tolerate either of these side effects, brexpiprazole and iloperidone are good options, with number needed to harm (NNH) above 30 for both sedation and akathisia.

 Lumateperone is also relatively free of akathisia, and its sedative effects are usually manageable with evening dosing.

Some medications are so sedating that this adverse effect limits their use. This is particularly true when they are taken in the morning, as is often the case for the short half-life medications that are given in divided doses. Quetiapine (half-life, 6 hours), ziprasidone (7 hours), clozapine (12 hours), and trazodone (5 to 9 hours) were all recommended for twice daily dosing when they were first released, based on the half-lives of the drugs. However, pragmatic physicians soon began dosing these medications at night without any loss of efficacy. This strategy is supported by about a dozen clinical trials comparing evening dosing to divided dosing in patients with schizophrenia and mood disorders.

 Asenapine could also be added to that list, as it was originally recommended to be given in divided doses but has a 24-hour half-life.

Sedation can be an asset when these short half-life medications are given at night, as their sedative effects are generally limited to the hours of sleep. The major risk with this strategy is orthostasis, particularly in older patients. For quetiapine, the extended-release version reduces this risk by smoothing over the peak levels.

When switching medications is not an option and evening dosing does not relieve sedation, antidotes may help, but are not consistently helpful. Modafinil and armodafinil improved residual fatigue in both bipolar and unipolar depression, but the benefit was small (effect size = 0.15).

 to improve fatigue in studies of patients with schizophrenia, although those trials were probably underpowered to detect the difference.

 Traditional stimulants have even less evidence of benefit and carry more risks. Concerns about tolerance, addiction, psychosis, mania, and cardiovascular risks significantly limit their use.

Psychiatric medications may cause fatigue through direct sedative effects or by worsening sleep quality. When medications make it difficult for a patient to fall asleep, the effect is usually readily apparent to the patient. When they disrupt sleep quality, the cause is less apparent. Poor sleep quality causes a variety of problems, some of which can be mistaken for symptoms of psychiatric disorders (eg, daytime fatigue, trouble concentrating, irritability, slowed reaction time, and poor problem-solving abilities).

Serotonergic antidepressants can cause both initiation insomnia and restless, fragmented sleep.

 The sedative effects of these antidepressants generally parallel their tendency to disrupt sleep, suggesting that poor sleep quality may be part of the reason that patients feel tired on these medications.

On the other hand, some antidepressants (eg, bupropion, levomilnacipran, and vortioxetine) have low rates of both sedation and insomnia.

 Despite its stimulating effects, bupropion actually improves sleep quality, increasing slow-wave sleep and reducing REM 

 Bupropion can cause difficulty falling asleep, but it does so at about the same rate as the selective serotonin reuptake inhibitors (SSRIs).

 Vortioxetine has not been adequately tested in a sleep lab, but it was 

 to normalize sleep architecture in an animal study and, in a post hoc analysis of a clinical study, it improved subjective reports of sleep quality.

If a patient needs a sedative to fall asleep, mirtazapine and trazodone both achieve this effect without worsening sleep quality. These antidepressants increase the slow waves that characterize the deepest stage of sleep.

 Likewise, the sedating antipsychotics usually do not worsen sleep quality, and may, in fact, improve it (

Quetiapine improved sleep quality, increased sleep efficiency, and reduced nocturnal awakenings in patients with bipolar disorder. Olanzapine, risperidone, and ziprasidone also resulted in improvements in sleep quality, beyond their effects on sleep initiation.19 Lumateperone, which shares a serotonin 5-HT2A receptor antagonist effect with trazodone, was originally developed as a hypnotic before gaining approval in schizophrenia. Taken nightly, in low doses (1-10 mg hs), lumateperone improved sleep without causing next-day sedation.

 These sedating options may provide dual benefits when patients require an antipsychotic for schizophrenia or a mood disorder, but antipsychotics have too many risks to justify their use for insomnia alone.

Sedation may not always be desirable, but it is difficult to avoid in psychiatry. Some of the most sedating medications have unique benefits that may justify their use (

 Evening dosing may improve tolerability, as long as adverse effects that are linked to the peak serum level do not get in the way. Orthostasis, for example, can cause a problem when antipsychotics and some antidepressants (eg, trazodone, mirtazapine, tricyclics, MAOIs) reach peak levels.

On the other hand, it is not necessary to jump to a sedating medication just because a patient has trouble sleeping. Some of these medications, like the SSRIs and the serotonin-norepinephrine reuptake inhibitors, worsen sleep quality. In fact, sleep may improve with an activating medication, either because it deepens sleep quality as bupropion does, or because it helps the patient reset their circadian rhythm. Patients tend to sleep better when they rise at regular times and stay active during the day.

is an instructor in clinical psychiatry at the Wake Forest School of Medicine and the director of the Mood Treatment Center in Winston-Salem, North Carolina. He is editor-in-chief of 

and coeditor of the Bipolar Disorder Section for 

Sedation, an unpleasant, undesirable and potentially dangerous side-effect of many psychotropic drugs.

 Hum Psychopharmacol. 2004;19(2):135-139.

2. Yun L, Fagan M, Subramaniapillai M, et al. 

Are early increases in physical activity a behavioral marker for successful antidepressant treatment?

Managing the Side Effects of Psychotropic Medications. 

2nd ed. American Psychiatric Association Publishing; 2019.

4. Citrome L. Activating and sedating adverse effects of second-generation antipsychotics in the treatment of schizophrenia and major depressive disorder: absolute risk increase and number needed to harm. 

5. Alberti S, Chiesa A, Andrisano C, Serretti A.

 Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysis

Handbook of Diagnosis and Treatment of Bipolar Disorders. 

Acceptability of acute and maintenance pharmacotherapy of bipolar disorder: a systematic review of randomized, double-blind, placebo-controlled clinical trials

8. Cheng JY, Chen RY, Ko JS, Ng EM. Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents-meta-analysis and meta-regression analysis. 

9. Eugene AR. Association of sleep among 30 antidepressants: a population-wide adverse drug reaction study, 2004-2019. 

10. Takeuchi H, Powell V, Geisler S, et al. Clozapine administration in clinical practice: once-daily versus divided dosing. 

11. Chengappa KN, Parepally H, Brar JS, et al. A random-assignment, double-blind, clinical trial of once- vs twice-daily administration of quetiapine fumarate in patients with schizophrenia or schizoaffective disorder: a pilot study. 

12. Raatjes B, Dantz B. Trazodone: the forgotten antidepressant. 

13. Riesenberg RA, Baldytcheva I, Datto C. Self-reported sedation profile of quetiapine extended-release and quetiapine immediate-release during 6-day initial dose escalation in bipolar depression: a multicenter, randomized, double-blind, phase IV study. 

14. Goss AJ, Kaser M, Costafreda SG, et al. Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. 

15. Saavedra-Velez C, Yusim A, Anbarasan D, Lindenmayer JP. 

Modafinil as an adjunctive treatment of sedation, negative symptoms, and cognition in schizophrenia: a critical review

16. Alberti S, Chiesa A, Andrisano C, Serretti A. 

Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysis

17. Ott GE, Rao U, Lin KM, et al. Effect of treatment with bupropion on EEG sleep: relationship to antidepressant response. 

18. Liguori C, Ferini-Strambi L, Izzi F, et al. 

Preliminary evidence that vortioxetine may improve sleep quality in depressed patients with insomnia: a retrospective questionnaire analysis

19. Monti JM. The effect of second-generation antipsychotic drugs on sleep parameters in patients with unipolar or bipolar disorder. 

20. Calsolaro V, Antognoli R, Okoye C, Monzani F. The use of antipsychotic drugs for treating behavioral symptoms in Alzheimer’s disease. 

Schatzberg’s Manual of Clinical Psychopharmacology.

 9th ed. American Psychiatric Association Publishing; 2019.❒

Sedation may not always be desirable, but it is difficult to avoid in psychiatry. Some of the most sedating medications are discussed.

Sedation: The Ups and Downs of a Side Effect

The psychiatrist's armamentarium to treat depression holds promise with a growing arsenal of integrative and pharmacologic options.

Top Treatment Modalities for Depression

BrainsWay’s theta burst 3-minute protocol for the treatment of major depressive disorder (MDD) received 501(k) clearance from the US Food and Drug Administration (FDA). The theta burst protocol utilizes BrainsWay’s Deep Transcranial Magnetic Stimulation (Deep TMS) system, previously FDA-approved for 20-minute treatments of patients with MDD who did not respond to medical therapy.

“Adding our 3-minute treatment protocol to the list of growing solutions available to our provider partners expands the platform nature of this lifechanging technology,” Hadar Levy, Senior Vice President and General Manager of BrainsWay, said to the press. “Many patients and providers can benefit from significantly shorter treatment sessions, and our theta burst protocol can provide these patients with another option to manage their treatment resistant depression.”

In their application to the FDA, BrainsWay submitted safety and efficacy data from a study that enrolled 146 participants with MDD who received either standard deep TMS protocol or 3-minute theta burst protocol. Of the 146 patients, 80 received the 20-minute protocol and 66 received the theta burst 3-minute protocol. Both groups demonstrated statistically significant reductions in depression scores. The results met the equivalence criteria needed for the shorter treatment’s clearance.

The therapy uses BrainsWay’s H-1 coil helmet to excite or inhibit neurons in the prefront cortex using direct magnetic pulses. It is typically delivered 5 days a week for 4 weeks, and then adjusted based on patient response. Both treatments call for the same frequency and number of treatments, but the frequency of the pulses and inter-pulse breaks differ.

“The addition of theta burst to the available protocols further demonstrates BrainsWay’s commitment to expanding the utility of the BrainsWay Deep TMS system,” said Moria Ankri, Vice President of Research & Development. “This protocol shows that innovation need not be revolutionary or radical to have a positive effect on peoples’ lives. Having a 3-minute option for patients has the potential to expand access to care by providing patients with added flexibility in selecting courses of treatment that may fit better with their lifestyle.”

The BrainsWay theta burst protocol will be available on all BrainsWay systems already installed.

1. BrainsWay. BrainsWay receives FDA clearance for three-minute theta burst treatment protocol for major depressive disorder. News release. April 26, 2021. 

https://www.brainsway.com/news_events/brainsway-receives-fda-clearance-for-three-minute-theta-burst-treatment-protocol-for-major-depressive-disorder/

2. Boyle A. FDA clears three-minute depression treatment with Brainsway’s theta burst. BioWorld. April 26, 2021. 

https://www.bioworld.com/articles/506363-fda-clears-three-minute-depression-treatment-with-brainsways-theta-burst

The FDA cleared the way to use this deep transcranial magnetic stimulation system, which may be able to help treat depression in less than 5 minutes. 

Treating Depression in 3 Minutes

Lundbeck announced positive results from the Real-World Effectiveness of Vortioxetine (RELIEVE) study evaluating vortioxetine for the treatment of major depressive disorder (MDD) and how it affected their everyday lives.

“The strong results from this trial show that patients treated with [vortioxetine] experience a significant improvement in overall functioning over a substantial period of 6 months. I think it is an interesting aspect that this study specifically shows an effect of [vortioxetine] on family, work, and social life functioning. At the end of the day, we want to be able to restore brain health, so people can be at their best,” said Johan Luthman, Executive Vice President for Research and Development at Lundbeck.

While the mechanism of vortioxetine is not fully understood, it is an inhibitor of serotonin (5-HT) reuptake. It is also an agonist at 5-HT1A receptors; a partial agonist at 5-HT1B receptors; and an antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors. Vortioxetine is perhaps the first of its kind with this combination of pharmacodynamic activity.

A total of 994 participants were evaluated for depressive symptoms as measured by the 

 (SDS), a tool that assesses impairment patients find in the following areas of their lives: family, social life, home responsibilities, and work/school. Eligible participants included patients with MDD initiating treatment with vortioxetine or switching from another antidepressant to treat a current major depressive episode.

Data were collected at routine clinic visits at baseline, 3 months, and 6 months. Analysis showed significant and meaningful improvements by 6.9 points and 8.6 points respectively after 3 and 6 months on the SDS when compared to prior antidepressant treatment.

The secondary and exploratory endpoints were also met, with a 0.13 improvement on the EQ-5D utility score measuring health-related quality of life for participants, and a 7.4 decrease in depressive symptoms from baseline as measured by the PHQ-9 (Patient Health Questionnaire-9) scale.

The RELIEVE study provides novel insights, as its focus was on patient self-assessment of daily functioning and their own experiences with improvement after treatment with vortioxetine.

Full results will be published in a peer-reviewed scientific journal later in 2021 and presented at future medical conferences. At this time, however, caution is needed, and further research is warranted.

1. Lundbeck. Vortioxetine significantly improves overall functioning in a global real-world study in Major Depressive Disorder. News release. April 22, 2021. 

https://news.cision.com/h--lundbeck-a-s/r/vortioxetine-significantly-improves-overall-functioning-in-a-global-real-world-study-in-major-depres,c3330732

A recent study evaluated the everyday efficacy of this novel treatment for major depressive disorder. 

Real-World Effectiveness: New MDD Treatment

Most health care professionals are aware that medical care in this country varies a great deal based on the patients’ race and ethnicity. We only have to look at the current coronavirus disease 2019 (COVID-19) crisis, in which Black individuals have been 

 both in number of infections and deaths as a result of a myriad of psychosocial, genetic, and environmental factors.

On top of unequal access, some individuals hold discriminatory beliefs about pain experienced by individuals of different racial and ethnic groups. In 1892, S. Weir Mitchell, MD, the father of American neurology, wrote about the experience of pain in White people of Northern European ancestry in comparison with Black and Native American people. He stated, “In our process of being civilized, we have won, I suspect, intensified capacity to suffer. The savage does not feel pain as we do.”

This view of pain was often used to rationalize the mistreatment of enslaved and Native American people: when violence was inflicted on them, they did not suffer as White people did. Pre-Civil War, 19th century New Orleans physician Samuel A. Cartwright, MD, said he identified “dysaesthesia Aethiopis,” an inherited disorder specific to Black individuals that made them insensitive to pain.

These views were perpetuated solely based on racism, without any science to support them. However, we now know that genetics can play a significant role in disease. Different races and ethnicities can be more at risk for certain diseases, such as sickle cell disease among Black people and Tay-Sachs disease among people of Ashkenazi Jewish ancestry. Thus, there is still the question of whether pain is experienced differently by individuals from different backgrounds.

A complicating factor in this discussion is how the experience of pain is affected by culture. It is readily apparent that it is more acceptable in some cultures and societies, often based on race or ethnicity, to complain about pain. How much of this is due to actual differences in the pain experience versus cultural acceptability of reporting pain—nature versus nurture—remains unclear.

 the effects of race and ethnicity on the care individuals received for chronic pain.

 The review identified trends in the effects of race and ethnicity on the experience of pain and how it is treated. Among the multitude of previous studies, one can find many different results, ranging from race and ethnicity playing significant roles to playing virtually no role.

Some studies have reported that Black individuals and people who belong to certain ethnic minority groups have higher pain thresholds, while other studies have 

 Minority patients, especially those from groups in which there are relatively small numbers of represented physicians, may have their level of pain underestimated by their caregivers.

Several studies have examined affects of race or ethnicity on the prescribing of opioids for pain. The most common finding was that Black patients were less likely to be prescribed opioids than White patients; however, it is worth noting that 

 patients were less likely to receive opioids than non-Hispanic White or non-Hispanic Black patients.

 Furthermore, some studies found that Black patients who were prescribed opioids were monitored more closely for misuse than White patients.

In light of the prescription epidemic in this country, resulting in rising rates of misuse and overdoses, it could be argued that more restrictive prescribing and closer monitoring might be a positive thing. If so, Black patients might accidentally benefit from these prescribing patterns. However, there is no indication that physicians are more carefully looking out for their Black patients than for their White patients. Even if the result is positive, there is no apparent intent. Furthermore, research has shown that Black patients and non-White Hispanic patients may have a more difficult time than White patients filling opioid prescriptions, as pharmacies in their neighborhoods may carry 

Unfortunately, there has been a tendency to have limited participation of non-English speakers and immigrants in studies of 

, and this may have resulted in an unrepresentative sample. Considering that pain is a subjective complaint that must be self-reported, limited language skills could impair patients’ ability to convey the presence and severity of pain, all important factors in determining proper treatment protocols.

The extent to which race, socioeconomic status, and 

 contribute to the apparent discrepancies in the management of pain remains unclear. The issue of poor access to health care may extend beyond just the pain itself and may also affect the identification and treatment of underlying disorders that may be causing or exacerbating the pain. This includes mental health issues, most notably depressive and anxiety disorders, which can play important roles in the development and maintenance of 

It is not too surprising that so many factors may explain variances in pain among different racial and ethnic groups. We know that there are many elements involved in the development of pain, especially chronic pain, including genetic, cultural, psychological, and environmental influences. The importance of each factor can vary from individual to individual.

The authors of the current study noted that there are no easy answers to pain management discrepancies, especially between Black and White individuals in the United States. More research is needed to identify the reasons for these discrepancies and the best methods for addressing them. Physicians should be aware of biases, including unconscious ones, and the methods for assessing and managing pain, especially among patients who may belong to different racial and ethnic groups than they do. Viewing all patients as complex individuals whose pain may involve many factors is crucial.

is in private practice in Philadelphia, Pennsylvania.

2. Cartwright SA. Report on the diseases and physical peculiarities of the negro race. In: Caplan AL, McCartney JJ, Sisti DA, eds. 

Health, Disease, and Illness: Concepts in Medicine

Racial and ethnic disparities in the treatment of chronic pain

4. Green CR, Hart-Johnson T. The impact of chronic pain on the health of black and white men. 

5. Hausmann LRM, Gao S, Lee ES, Kwoh KC. Racial disparities in the monitoring of patients on chronic opioid therapy. 

6. Nguyen M, Ugarte C, Fuller I, Haas G, Portenoy RK. 

Access to care for chronic pain: racial and ethnic differences

7. Bauer SR, Hitchner L, Harrison H, Gerstenberger J, Steiger S. 

Predictors of higher-risk chronic opioid prescriptions in an academic primary care setting

8. Hollingshead NA, Vrany EA, Stewart JC, Hirsh AT. 

Differences in Mexican Americans’ prevalence of chronic pain and co-occurring analgesic medication and substance use relative to non-Hispanic white and black Americans: Results from NHANES 1999-2004

9. Becker WC, Starrels JL, Heo M, Li X, Weiner MG, Turner BJ. Racial differences in primary care opioid risk reduction strategies. 

10. Morrison RS, Wallenstein S, Natale DK, Senzel RS, Huang LL. “

We don’t carry that”--failure of pharmacies in predominantly nonwhite neighborhoods to stock opioid analgesics

Pain as a cultural construct considers conscious and unconscious biases, as well as methods for assessing and managing pain in all patient populations, including those with mental health challenges.

Race, Ethnicity, and Chronic Pain

MDD is a highly prevalent mental health condition. There is evidence that, in China, co-occurring somatic symptoms, including headache and stomachache might contribute to misdiagnosis of depression and delayed 

 Previous studies of somatic symptoms in MDD have yielded conflicting or inconclusive results, although there is some evidence for increased gastrointestinal 

 Given growing evidence for the microbiota-gut-brain axis in depressive disorders, GI symptoms might be a marker for 

Huang and colleagues estimated the frequency and clinical correlates of GI symptoms during depressive episodes in a large, nationwide sample of patients with 

 They hypothesized that the presence of GI symptoms would be associated with comorbidity in MDD, including insomnia, hopelessness, anxiety, and suicidal ideation. Study participants were from the National Survey on Symptomatology of Depression (NSSD) in China, which included inpatient and outpatient participants 18 years or older with a current DSM-IV episode of MDD.

Exclusion criteria were a lifetime diagnosis of bipolar or psychotic disorder, imminent risk of suicide or homicide, received electroconvulsive therapy within the past month, current pregnancy or breastfeeding, and substance use disorder over the past year. Patients were interviewed by trained psychiatrists on a broad range of symptoms, including depression and somatic symptoms, over the previous 2 weeks. Sociodemographic and clinical characteristics between patients with different severity of GI symptoms were performed with 1-way analysis of variance. Multiple linear regression analysis was used to analyze associations between GI symptoms and psychopathology, adjusting for potential confounding factors.

A total of 3256 patients (mean age 41, 40% male) were included in the analyses. Of those, 1750 patients (71%) had GI symptoms, with a frequency of several days/week for 38%, more than half of days for 23%, and almost daily for 10%. Patients with more GI symptoms had a significantly increased prevalence of anxiety; insomnia; poor concentration; limb and body pain; hopelessness; anger and irritability; and feelings of failure. In linear regression, suicidal ideation, anxiety, insomnia, anger, feelings of failure, and body pain were independently and significantly associated with GI symptoms in patients with MDD (

The authors concluded that more than 70% of patients with MDD reported GI symptoms during depressive episodes. Strengths of the study include the large, nationwide sample. Limitations include the cross-sectional nature of the study design, unmeasured and residual confounding factors, as well as the absence of data on specific GI symptoms. These findings are germane to investigations of the microbiota-gut-brain axis in depressive disorders.

“Mr S” is a 26-year-old Caucasian male with a history of recurrent major depressive disorder (MDD) and anxiety disorder. The onset of his depressive illness began when he was 19 years old. For the past 2 to 3 months during an exacerbation of his depression, he reports significant nausea and vomiting on a daily basis, particularly in the morning, which was not attributable to increased anxiety. Mr S reports that his gastrointestinal (GI) symptoms did not respond to treatment with either H-2 blockers or a proton-pump inhibitor. Subsequently, his antidepressant was changed to a different selective serotonin reuptake inhibitor, and a low-dose long-acting benzodiazepine was also added for anxiety. Over the next month, he reported significant improvement in not only mood and anxiety, but also nausea and vomiting, such that he was able to return to full-time employment.

Gastrointestinal symptoms are common in the clinical presentation of MDD. GI symptoms may be associated with the onset and clinical severity of depression, which could be a potential ancillary indicator in the management of MDD.

 is professor in the Department of Psychiatry and Health Behavior, Augusta University, 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, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.

1. Smith K. Mental health: a world of depression. 

2. Harshaw C. Interoceptive dysfunction: toward an integrated framework for understanding somatic and affective disturbance in depression. 

3. Bruce-Keller AJ, Salbaum JM, Berthoud HR. Harnessing gut microbes for mental health: getting from here to there. 

4. Guo F, Cai J, Jia Y, et al. Symptom continuum reported by affective disorder patients through a structure-validated questionnaire. 

A study estimates the frequency and clinical correlates of GI symptoms during depressive episodes in a large, nationwide sample of patients with MDD in China.

Gastrointestinal Symptoms During Depressive Episodes

A quick primer on nomenclature, issues to consider, and switching.

Psychiatric Treatment: Side Effects Basics

 and the Columbia University Breakthrough Session, hosts Angela Coombs, MD, and Jennifer Sotsky, MD, discuss the possibilities and promise of psilocybin to treat psychiatric disorders and in enhancing everyday experiences with 

. Landmark studies and new research about the use of hallucinogens includes potential to treat:

Posttraumatic stress disorder
Substance use disorders


Psilocybin (mushrooms) and other hallucinogens from plants and some animal life generate perceptual changes and hallucinations, altered physical sensations, strong emotional reactions, and even dissolution of self.

The question is whether these are 

 or trips and whether they can result in lasting changes in the patient. Over time, some of the brain connections may become disrupted and new circuits may become activated.

Dr Hellerstein is a professor of clinical psychiatry at Columbia University and is conducting clinical trials of psilocybin. His books include 

Heal Your Brain: How the New Neuropsychiatry Can Help You Go from Better to Well

is a board-certified psychiatrist and assistant professor in Clinical Psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute. She serves as the medical director and team psychiatrist at ONTrackNY Washington Heights Community Service clinic. She completed her public psychiatry fellowship and adult psychiatry residency at Columbia University where she was a chief resident and co-organized the curriculum on racial/ethnic mental health disparities. In addition to her clinical work in the public sector, she also works in Columbia's psychiatric emergency room and has a private practice in Upper Manhattan.



is a fellow in consultation-liaison psychiatry at Columbia University Irving Medical Center with a part time private practice. She was formerly a chief resident at Columbia’s psychiatry residency program. Before medical training, she received an MS in Narrative Medicine, an interdisciplinary field that studies illness through a humanities lens. She is co-author of 

Conquering Lyme Disease: Science Bridges the Great Divide

 and has interests in medical education, psychotherapy, and medical humanities.



Columbia University Department of Psychiatry

 for allowing us to present the Breakthrough Session podcast with experts in the field of psychiatry.


Research on psilocybin, LSD, and other hallucinogens as psychiatric treatments are in their renaissance, transitioning from banned and illegal to potentially useful in changing life for the better in some patients. More in this podcast.

David Hellerstein, MD: Psychedelic Treatments for Psychiatric Disorders

The article by John Read, PhD, and colleagues argues in favor of suspending the use of electroconvulsive therapy (ECT) due to a lack of efficacy data and unacceptable adverse effects, specifically, brain damage.

 Unfortunately, the analysis is based on studies conducted prior to the modern era of ECT, and it draws on a limited slice of the available safety and efficacy data for ECT. More recent studies have found key areas of efficacy (

The selection criteria used by Read and colleagues were limited to older studies (1956 to 1985) and critiques of the quality of the data. Thus, the piece is judging clinical trial designs from the 1980s and earlier, using 2019 standards. It is no surprise that the included studies do not utilize methodology developed after the studies were completed. More importantly, the analysis did not include reports that compare different types of ECT, and comparisons of ECT with pharmacotherapy were also not included. This excludes most of the recent meta-analyses and clinical trials of ECT, which have used state-of-the-art clinical trial design. For example, a recent meta-analysis conducted by 

 compared ultrabrief pulse right unilateral (RUL) ECT with brief pulse RUL ECT.

 They found remission rates of 44.9% for brief pulse right unilateral ECT vs 33.8% for ultra-brief pulse RUL ECT (OR, 0.71; 95% CI, 0.51-0.99; P = .045). Their meta-analysis showed that brief pulse caused more cognitive adverse effects than ultrabrief pulse, but there were no data after the acute course.

There is consistent evidence of benefits following state-of-the-art modified ECT.

Major Depressive Disorder