Leah Kuntz

According to the results of a new study, individuals seeking treatment for depression with lower incomes, lower education levels, and those who identify as minorities tend to have worse outcomes even when receiving equal access to treatment.

 Jeffrey Mills, PhD, and Jeffrey Strawn, MD, led the University of Cincinnati cross-college collaborative research.

Investigators analyzed data from a large clinical trial, the Combining Medications to Enhance Depression Outcomes study, that enrolled 665 participants seeking treatment for depression. All participants had the same access to treatment without differences due to health insurance or income. The study also controlled for sex, age, and treatment type. Following 12 weeks of antidepressant medication treatment, participants who were nonwhite improved 11.3% less compared to white patients. Participants who were unemployed saw 6.6% less improvement compared to employed patients. Participants the 25th percentile of income distribution had 4.8% reduced improvement when compared to participants in the 75th percentile. Patients who were nonwhite, unemployed, without degree, and in the 25th income percentile had 26% less improvement compared to patients who were white, employed, with a college degree, and in the 75th income percentile.

“We think about these things in terms of access, we think about them in terms of income inequality, and I realize that education does track with those, but just having a college degree while controlling for all of these other factors still had a significant impact,” said Strawn, professor in the Department of Psychiatry and Behavioral Neuroscience in UC’s College of Medicine and a UC Health adolescent psychiatrist.

Strawn also noted that while the findings are still preliminary, results suggest that participants without a college degree had 9.6% less improvement compared to college graduates. Furthermore, previous research indicates that individuals seeking treatment for depression with lower income and less education have worse outcomes because of a lack of access to quality health care, but socioeconomic factors are hard to isolate.

Mills, professor of economics in UC’s Carl H. Lindner College of Business, said that the findings do not negate the fact that a lack of access makes an impact on treatment outcomes, but it does show the importance of including a patients’ home environment when analyzing the effectiveness of treatment.

“If you’re going home to a wealthy neighborhood with highly educated parents or spouse, then you’re arguably in a much better environment for the treatment to be effective than if you’re going to a poor neighborhood with other problems,” said Mills.

Strawn believes future studies should consider socioeconomic variables that may have been previously overlooked.

“When we don’t control for these variables, which we often do not in our clinical trials because of differences in populations, we may miss detecting an effective treatment because its effect is obscured,” Strawn said. “It can potentially jeopardize our treatment development by not accounting for these factors.”

Moving forward, the investigators want to combine data from other depression trials to produce more powerful results with a larger dataset.

Socioeconomic predictors of treatment outcomes among adults with major depressive disorder.

2. Socioeconomic factors affect response to depression treatment. News release. April 15, 2022. Accessed May 6, 2022. 

https://www.newswise.com/articles/socioeconomic-factors-affect-response-to-depression-treatment

Articles

Home environments have a clear impact on depression treatment outcomes. 

The Effect of Socioeconomic Factors on Depression Treatment

Sage Therapeutics and Biogen initiated a rolling submission of a new drug application (NDA) to the US Food and Drug Administration (FDA) for zuranolone in the treatment of major depressive disorder (MDD). Zuranolone is a 2-week, once-daily oral drug for the treatment of MDD and postpartum depression (PPD). The companies submitted the nonclinical module to the FDA and plan to submit all remaining components for MDD in the latter half of 2022.

“Zuranolone has the potential to help address a significant unmet medical need in depression as an innovative option in a therapeutic area where little has changed in the past 30 years,” said Priya Singhal, MD, MPH, Head of Global Safety and Regulatory Sciences and Interim Head of R&D at Biogen. “We are committed to advancing the science and developing new approaches to treating mental health, a major public health challenge that was exacerbated by the COVID-19 pandemic.”

The submission package will include: data from the completed studies of zuranolone in the LANDSCAPE and NEST clinical development programs, data from the ongoing open-label SHORELINE Study in MDD, and data from completed clinical pharmacology studies.

“There are millions of people living with depression and the initiation of the rolling NDA submission brings us one step closer to our goal of offering zuranolone as a potential new treatment option,” said Barry Greene, Chief Executive Officer at Sage. “We believe the results from the LANDSCAPE and NEST programs, in which zuranolone demonstrated rapid and sustained effects and a well-tolerated safety profile in clinical trials, support zuranolone as a potential novel treatment option for MDD, if approved. We look forward to providing an update when the rolling submission for zuranolone in MDD is complete, which we expect to occur in the second half of this year.”

In 2017, zuranolone was granted fast track designation by the FDA in MDD, and breakthrough therapy designation in 2018. Sage and Biogen intend to submit an associated NDA filing for PPD in the first half of 2023.

1. Sage Therapeutics and Biogen initiate rolling submission of new drug application (NDA) to U.S. Food and Drug Administration for zuranolone for the potential treatment of major depressive disorder (MDD). Sage Therapeutics. May 2, 2022. 

https://investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-and-biogen-initiate-rolling-submission-new

Zuranolone, a drug for the treatment of major depressive disorder and postpartum disorder, is on a rolling submission of a new drug application. 

Rolling NDA Submission of Zuranolone for Treatment of Major Depressive Disorder

A recent study sought to understand the relationship between dietary patterns of children and their 

Investigators examined 2 different age groups of children from Spain: 259 preschoolers aged 3 to 6 years old (57 with ADHD and 202 controls) and 475 elementary-school-age children, aged 10 to 12 years old (213 with ADHD and 262 controls). ADHD was assessed in accordance with the DSM-5. Eating data were collected using a food consumption frequency questionnaire. Three types of eating patterns were identified: Western-like, sweet, and healthy.

Western pattern consists of eggs, processed meat, seafood, savory cereals, potatoes, legumes, sodas, and cooked vegetables. Sweet pattern consists of dairy desserts, sweet cereals, preserved fruit, and sweets. 

 consists of nuts, fish (white and oily), raw vegetables, fresh fruit, and olive oil.

The children and adolescents with ADHD were negatively associated with the healthy pattern (p < 0.001) and positively associated with the Western-like diet (p = 0.004). Furthermore, children with inattentive presentation showed lower adherence (12.2%) to a healthy pattern than that of the control group (39.9%) (p < 0.001). The control group had the highest adherence to the Healthy pattern. However, the two groups had a similar adherence to the sweet dietary pattern.

Previous research explored the association between 

 and the Mediterranean diet—a dietary pattern that includes fiber-rich food such as fruits and vegetables, healthy fatty acids, proteins, and more.

 According to 2 studies, there was less healthy eating and lower adherence to the Mediterranean diet in children and adolescents with ADHD than that in controls.

“We hypothesize that children with ADHD have a low-quality diet with a lower intake of fruits and vegetables than that of their peers without the disorder, and that this shows up specifically in children with combined or hyperactive–impulsive (H–I) ADHD presentations. Moreover, we hypothesize that food consumption generally differs from the established recommendations by dietary guidelines,” wrote the authors.

The authors concluded that there is an association between ADHD and dietary habits, and children with inattentive presentation may be at increased risk of unhealthy eating habits.

1. Rojo-Marticella M, Arija V, Alda JÁ, et al. 

Do children with attention-deficit/hyperactivity disorder follow a different dietary pattern than that of their control peers?

2. Rios-Hernandez A, Alda JA, Farran-Codina A, et al. 

The Mediterranean diet and ADHD in children and adolescents.

3. San Mauro Martín I, Blumenfeld Olivares JA, Garicano Vilar E, et al. 

Nutritional and environmental factors in attention-deficit hyperactivity disorder (ADHD): a cross-sectional study.

A recent study found a negative association between children with ADHD and health eating patterns. 

The Relationship Between Unhealthy Eating and ADHD in Children 

The following poster presentations at the American Pharmacists Association (APhA) Annual Meeting & Exposition highlighted a number of changes facing psychiatry today.

Concurrent Benzodiazepine, Opioid Use Risks

Because more than 30% of overdoses involve a combination of benzodiazepines and 

, and more than 115 Americans die from opioid overdose every day, the investigators conducted this study to assess how much patients know about the increased risk of adverse events, overdose, and death associated with taking 

 and opioids concurrently. They also focused on the role of education, surveying study participants both before and after educational intervention. The study included 9 participants (33% male; 66% female; median age 59 years) who had been prescribed a benzodiazepine (Xanax [alprazolam], 77%; Klonopin [clonazepam], 22%; or Ativan [lorazepam], 11%) and an opioid (Norco [hydrocodone/acetaminophen], 55%; Percocet [oxycodone/acetaminophen], 22%; Roxicodone [oxycodone], 11%; or Roxanol [morphine sulfate], 11%). Participants were surveyed both before and after receiving information detailing the increased risks associated with concurrent benzodiazepine and opioid use. Each survey asked them to rank their knowledge of the medications, the potential adverse effects and 

 risk of the medications, and the risks of alcohol consumption on a scale from “unaware” to “minimal” to “good” to “excellent.”

In the presurvey, each knowledge category was divided among “excellent,” “good,” and “unaware” rankings, with “minimal” only appearing in the knowledge of overdose category at a little over 20%. Most participants ranked their knowledge as “excellent” in only the knowledge of medications category (a little more than 40%), with “good” leading the rankings in the potential adverse effects and alcohol consumption categories nearly 60% and a little more than 40%, respectively. Around 20% of participants ranked their knowledge as “unaware” across all 4 knowledge categories. In the postsurvey, no participants ranked their knowledge as “unaware” or “minimal” in any category. In both the knowledge of medications and the potential adverse effects categories, patients ranked their knowledge as “good” or “excellent” at around 80% and around 20%, respectively. In knowledge of 

, the majority of participants (around 90%) ranked their knowledge as “excellent,” with the remaining 10% ranking it as “good,” and 100% of participants ranked their knowledge of overdose—the category with the most varied results in the presurvey—as “excellent.”

Although patient education resulted in clear improvement of self-reported knowledge and understanding, only 1 participant changed their medication regimen to lower the risks of adverse events. According to the investigators, this means that patients are reluctant to change their prescribed medications even with greater awareness of the risks.

“Overall, patients can have a good baseline knowledge, but the results of this study demonstrate how pharmacists can further improve patient understanding… and knowledge of the medications [patients] are currently prescribed,” the investigators concluded.

In their poster presentation, Kafi Friday, BA, PharmD candidate 2023; and Prashant Sakharkar, PharmD, MPH, explained that sexual minorities, or individuals with nonheterosexual sexual orientation, face increasing challenges in achieving health equity, due to stigma and discrimination.

 Via a retrospective cohort study, the investigators sought to examine health disparities and level of depression among 

; compare the prevalence of sexually transmitted infections, 

, illicit drug use, and alcohol use in use in sexual minorities; and determine predictors of depression among sexual minorities.

The study’s results painted a grim picture for sexual minorities: sexual minorities were 3 times more likely to have gonorrhea and chlamydia infection, 65% more likely to use illicit drugs, 52% more likely to be a smoker, 3 times more likely to experience 

, and 2 times more likely to see a mental health clinician.

These findings suggest that depression can be a consequence of health and behavioral disparities. Screening—particularly in females who identify as a sexual minority, smoke, use illicit drugs, are under the age of 45, and are poor—might help in early intervention. Furthermore, the investigators noted future research should examine the association of depression, 

Want to learn more on the advances in psychiatry? Join us this August at the 2022 Annual 

™ World CME Conference. For more information and to register, visit 

1. Baciu A, Negussie Y, Geller A,alWeinstein JN, eds. 

Communities in Action: Pathways to Health Equity.

Catch up on all the latest from the American Pharmacists Association (APhA) Annual Meeting & Exposition.

APhA Conference Addresses Depression, Benzos

What is the current state of the opioid epidemic, and what role does naloxone play in the emergency treatment of patients with known or suspected opioid overdose?

These questions and more were addressed in this installment of the custom Around the Practice video program. Panelists for this important discussion included Matthew A. Torrington, MD; Daniel E. Buffington, PharmD, MBA; Thomas R. Kosten, MD; and Bill H. McCarberg, MD.

“This is not a new epidemic,” said Kosten, adding the opioid crisis started as early as 2015. “One can say it was led by the overprescribing of opiates, but what has taken over [the expanding crisis] is fentanyl.”

www.psychiatrictimes.com/around-the-practice/opioid-abuse-and-the-role-of-naloxone

The panel agreed it has spread across age groups, making it everyone’s problem.

Naloxone may be a solution, Buffington explained, but it may need to be administered several times to counter opioid overdose in emergency situations due to the “increased prevalence of higher-potency fentanyl products” in recent years.

A 27-year-old man presents for evaluation in extreme pain from a car accident. He has a past history significant for substance use disorder, high blood pressure, and diabetes. He takes buprenorphine 2 mg, lisinopril 20 mg, and metformin 500 mg per day. During the next 4 hours, his pain levels vary. Imaging shows a broken ankle, a broken rib, and a small hairline fracture on his clavicle; a CT and MRI show no tissue or brain damage. He gets a cast for his ankle and is started on low-dose opioid therapy—1 oxycodone acetaminophen every 4 to 6 hours as needed for pain for 5 days, until he can see his primary care provider.

This is where the real problems begin, the panel agreed, as the patient is discharged without appropriate pain management. “If you don’t do enough to treat this guy’s pain, you can drive him to the illicit market, and that’s when he becomes the real victim of overdose,” explained Torrington. “I see as a lot of this substandard pain treatment, which makes people—even reasonable people—go to the illicit market to get something else to help them with their discomfort... If we don’t do an adequate job, they’ll take matters into their own hands.”

Acknowledging that this patient is at risk for overdose, the panel discussed the potential use of naloxone.

Kosten recommended 8 mg of naloxone, stating, “If he did go to the illicit market, unfortunately, fentanyl might be in that and you’re going to need a big dose of naloxone to do something.”

McCarberg agreed that this patient is a good candidate for naloxone. “This person has an opioid use disorder—I assume he was given the buprenorphine because of treatment for the opioid use disorder, even though it was a subtherapeutic dose,” he explained. “He’s still drinking, he’s smoking cigarettes, all of which put him at high risk for going outside of the standard prescribing realm to get medication...So he really is high risk given all of these factors together. This is the guy that needs the naloxone and a discussion with the wife or whoever’s the other members of the family about what to look out for if he overdoses.”

A 49-year-old unemployed male truck driver is found semiresponsive, and an opioid overdose is suspected. He has a past medical history of high blood pressure, diabetes, obesity, and chronic pain, as well as opioid use following a previous motor vehicle accident. He smokes 1 pack of cigarettes a day, is recently divorced, and lost his job during the pandemic. During the physical exam, he is hypertensive and unresponsive to sternal rub. During the clinical work-up, he has pinpoint pupils, has gone pale, and has clammy skin. His blood pressure is 60/40 mm Hg. His heart rate is 28 beats per minute.

After confirming his airway is clear, he is given supportive breathing and then 8 mg of naloxone intranasally. He is monitored for opioid withdrawal and/or non–naloxone resistance.

“I think you have to think about longer-term treatment,” Kosten said. “Based on the 8 mg of naloxone that it took to reverse him and what is on the street, he probably did get fentanyl in his system. Then the question is: What do you want to treat him with? Could you treat him with naltrexone?” Kosten posed. “An injectable naltrexone lasts a month, so you do not have compliance problems. If he is not opiate dependent, that’s a real possibility.”

“This person absolutely needs comprehensive individualized multimodal treatment over time that’s biologic, psychologic, social, spiritual, and nutritional to have the best possible chance of overcoming his challenges,” Torrington added. “There are so many things that you could do with this teachable moment, but I’m afraid that in real life, many times this guy wakes up and goes home, and not that much else happens.”

The panel noted it was important to involve the family to prevent negative outcomes.

“I had a recent overdose rescue in my practice, and what struck me was that the wife said, ‘I didn’t know if I should give it or not. I couldn’t tell.’ The question comes up: Should she use it when she’s not sure? Should we be advising family members to use the drug if they’re not absolutely certain that it’s an overdose? The side effects, the risk-benefit profile for using the drug is so much in favor of using the drug if you’re not sure because of the fact that there hardly are any side effects from the drug. There are withdrawal side effects, but if you don’t know, it’s better to use it than to not use it because a side effect or a withdrawal is much better than a death. If you don’t know for sure, error on the side of something that is less harmful to the patient.”

The panel further agreed that to keep patients off the streets looking for medications, care needs to go beyond undertreating pain.

Kosten concluded: “[Providers] have to have an open mind that substance abuse and major psychiatric disorders are not totally divergent—that they, unfortunately, are totally convergent and come together. You can die of suicide. You can also die of an overdose just as easily and a whole lot more quickly.”

is a board-certified family medicine and addiction medicine physician practicing in Culver City, CA. Mr Buffington is president and CEO at Clinical Pharmacology Services in Tampa, FL.

is the Jay H. Waggoner Endowed Chair and professor of psychiatry, pharmacology, immunology, and neuroscience, as well as vice-chair for psychiatry, and codirector of the Dan L. Duncan Institute for Clinical and Translational Research, and a professor of at the Baylor College of Medicine in Houston, TX. He is also on the editorial board for

is founder of the Chronic Pain Management Program for Kaiser Permanente and adjunct assistant clinical professor at the University of California San Diego School of Medicine.

If you missed out on the custom Around the Practice video program on naloxone, we've got you covered. Read a recap here. 

Naloxone as a Tool to Fight the Opioid Epidemic

A recent study determined hyperprolactinemia (HPRL) was not associated with taking antipsychotic drugs with high expected HPRL risk.

HPRL is a side effect of some antidepressants and antipsychotics. HPRL is frequently observed in patients with schizophrenia and can also occur in Hashimoto's thyroiditis due to the prolactoliberin effect of thyroliberin. In women, it may present with decreased libido, infertility, oligomenorrhea/amenorrhea, and galactorrhea; in men, it may present with decreased libido, infertility, gynecomastia, or impotence.

In the recent study, patients with comorbid schizophrenia and Hashimoto's thyroiditis who received antipsychotics were of special interest, as these patients have higher risks of HPRL. Investigators sought to analyze risks of HPRL with antipsychotic treatment, identify an association between the antipsychotic therapy and HPRL in Hashimoto's patients receiving antipsychotic therapy, and explore the association of HPRL in patients with Hashimoto's thyroiditis and schizophrenia during antipsychotic therapy.

Investigators examined 17 participants with comorbid schizophrenia receiving antipsychotic therapy, all euthyroid or with light hypothyroidism. They analyzed different laboratory parameters, including anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies, blood levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and prolactin (PRL).

Results revealed high levels of PRL, and anti-TPO and anti-TG autoantibodies. Patients were then classified into 3 groups by the degree of expected HPRL risk from antipsychotics: without risk, with low risk, and with high risk. The correlation analysis detected an inverse significant correlation (R=-0.51; p=0.037) between expected level of drug-associated HPRL risk and actual PRL levels in the group. At the same time, we detected a positive significant correlation between the levels of PRL and FT4 in the groups (R=0.53; p=0.03). Correlations between PRL levels and other parameters such as TSH, FT3, anti-TPO, anti-TG, anti-TSH receptor antibodies were not statistically significant.

HPRL in the group was not associated with taking of antipsychotic drugs with high expected HPRL risk. Yet, a significant positive correlation existed between the levels of PRL and FT4. Hence, in Hashimoto's thyroiditis accompanied with treated mental illness there are some non-iatrogenic stimulants of prolactogenesis.

“It cannot be ruled out that antipsychotics may interfere with prolactin metabolism, which creates a false effect of a positive correlation between prolactin and free thyroxine levels, in contrast to common HPRL of hypothyroidism,” concluded the authors.

1. Sobolevskaia PA, Churilov LP, Fedotkina TV, et al. 

Hyperprolactinemia and antipsychotic therapy in schizophrenic patients with Hashimoto's thyroiditis.

Clinical presentation of hyperprolactinemia.

A recent study examined hyperprolactinemia and antipsychotic therapy in patients with schizophrenia and Hashimoto's thyroiditis. 