Researchers reported on Sept. 21, 2024 at the annual meeting of the European College of Neuropsychopharmacology.

Lead researcher Tommaso Barba, PhD candidate from Imperial College, London, said, “This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression.  In previous work we had found that both treatments led to comparable improvements in alleviating symptoms of depression at the 6-week mark, such as sadness and negative emotions.  However, this work shows that psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work and social functioning. These results appeared to be maintained over a 6-month follow-up period. In addition, in previous work we had found that psilocybin also improves sexual drive, in contrast to SSRIs which tend to lower libido in many patients. So overall it seems psilocybin might give additional positive mental health benefits.”

As background, the authors noted that SSRI drugs (selective serotonin reuptake inhibitors), such as Prozac, Paxil and Zoloft, are widely used to treat depression, but about a third of patients don’t respond to such treatment.

“SSRIs work well, but not for everyone,” Barba said. “They are also associated with some side effects. However, this work implies that psilocybin generally seems to offer a real alternative, and perhaps additional benefits, to people who are worried about taking conventional antidepressants.”

The researchers undertook a 6-month phase 2, randomized trial with 59 subjects diagnosed with moderate to severe depression.

They treated 30 of the subjects with a single dose of psilocybin and 29 subjects with a six-week course of escitalopram.

All subjects received similar psychological support of around 20 hours.

Both groups showed significant improvement in depressive symptoms up to 6 months after treatment. Notably, the subjects treated with psilocybin reported greater improvements in social functioning and psychological connectedness.

“This is important because improving connectedness and having greater meaning in life can significantly enhance a person’s quality of life and long-term mental health,” said co-first author Dr. David Erritzoe, Clinical Director and Deputy Head of the Centre for Psychedelic Research, Imperial College, London.

Erritzoe added, “Psilocybin is still an experimental drug; it has not yet been approved for general use. It is administered in highly controlled and protected environments: these precautions are not found in recreational psychedelic use, which is known for having unpredictable and potentially harmful effects, especially for vulnerable people struggling with mental health issues.”

Overall, individuals with past-month prescription amphetamine use had a greater likelihood of new-onset psychosis or mania than individuals without past-month use. The risk was highest in those taking 30 mg or more of dextroamphetamine (which corresponds to 40 mg of Adderall), according to the study.

Previous studies have linked stimulants to psychosis and mania risk; however, information had been lacking on whether dosing impacted risk.

“Stimulant medications don’t have an upper dose limit on their labels, and our results show that it is clear that dose is a factor in psychosis risk and should be a chief consideration when prescribing stimulants,” said lead study author Lauren Moran, MD, a pharmacoepidemiology researcher at McLean Hospital. “This is a rare but serious side effect that should be monitored by both patients and their doctors whenever these medications are prescribed.”

Moran said the study was born out of her past clinical observations as an inpatient psychiatrist. She and her McLean colleagues would regularly see patients coming in experiencing first episodes of psychosis, and their medical records would reveal they were prescribed high doses of stimulants by their doctors.

Researchers reviewed electronic health records of Mass General Brigham patient encounters between 2005 and 2019, focusing on adults aged 16 to 35, the typical age of onset for psychosis and schizophrenia. All patients were admitted to McLean Hospital following referrals from other hospitals in the Mass General Brigham healthcare system. The researchers identified 1,374 cases of individuals presenting with first-episode psychosis or mania, compared to 2,748 control patients with a psychiatric hospitalization for other conditions like depression or anxiety. They conducted a comparison analysis of stimulant use over the preceding month and accounted for other factors, including substance use, in order to isolate the effects of stimulants.

They found the attributable risk percentage among those exposed to any prescription amphetamine was nearly 63% and for high dose amphetamine was 81%. These findings suggest that among people who take prescription amphetamine, 81% of cases of psychosis or mania could have been eliminated if they were not on the high dose. While a significant dose-related risk increase was seen in patients taking high doses of amphetamine, no significant risk increase was seen with methylphenidate (Ritalin) use, which is consistent with previous research, including a 2019 study led by Moran.

While the study does not prove causality, the researchers note there is a plausible biological mechanism in neurobiological changes that include a release of higher levels of the neurotransmitter dopamine from amphetamines, that parallel dopaminergic changes observed in psychosis.

Limitations of the study include inconsistencies with how electronic health records are kept. Additionally, with the research taking place in a psychiatric hospital in the Boston area that sees many patients with psychosis, it may make these findings less generalizable to other parts of the country.

Moran said the findings need not create alarm but should lead to extra caution when these medications are prescribed, especially for those who have risk factors for psychosis and mania.

“There’s limited evidence that prescription amphetamines are more effective in high doses,” said Moran. “Physicians should consider other medications our study found to be less risky, especially if a patient is at high risk for psychosis or mania.”

Authorship: In addition to Moran, Mass General Brigham co-authors included Joseph P. Skinner, BA (BWH), Ann K. Shinn MD, MPH (McLean), Kathryn Nielsen (McLean), Vinod Rao, MD, PhD (MGH), Trevor Taylor, MD, MPH (MGH), Talia R. Cohen (McLean), Cemre Erkol, MD (McLean), Jaisal Merchant, MA (McLean), Christin A. Mujica, MA (McLean), Roy H. Perlis, MD, MSc, (MGH) and Dost Ongur, MD, PhD (McLean).

Funding: This work was funded by a grant from the National Institute of Mental Health (NIMH), R01 MH122427.

Disclosures: Perlis received personal fees from Genomind, Burrage Capital, Psy Therapeutics Inc, Circular Genomics Inc, and Vault Health unrelated to the submitted work. Dr. Ongur received honorariums for scientific presentations to Neumora Inc. and Guggenheim LLC unrelated to the submitted work. Dr. Moran is employed by Sage Therapeutics (unrelated to this work and after study completed and submitted for publication). All other authors report no financial relationships with commercial interests.

Paper cited: Moran, LV et al. “Risk of Incident Psychosis and Mania with Prescription Amphetamines,” American Journal of Psychiatry. DOI: 10.1176/appi.ajp.20230329

The new study found that the pandemic didn’t lead to increases in postpartum depression or anxiety diagnoses. But it did prompt a 15% increase in the number of privately insured new moms filling prescriptions for antianxiety medications like Valium, Xanax, Ativan and Klonopin.

The researchers didn’t find an increase in SSRI prescriptions, though.

SSRIs, or selective serotonin reuptake inhibitors, are the gold standard for treating both depression and anxiety disorders. But these drugs, which include medications like Zoloft, Prozac and Lexapro, take time to work.

Benzodiazepines, also known as benzos, are sometimes used as a stopgap during the month or two it takes for an SSRI to start working. But they aren’t a substitute for SSRIs. And they carry significant risks of dependence and abuse.

“What concerns me the most is not what we found but what we didn’t find,” said Grace Bagwell Adams, lead author of the study and an associate professor in UGA’s College of Public Health. “You can’t tell me there wasn’t more depression and anxiety in this population during the pandemic. And historically, even pre-COVID, postpartum depression and anxiety has always been underdiagnosed. But we didn’t find an increase in diagnoses.”

Postpartum depression, anxiety largely underdiagnosed. The pandemic didn’t help.

One in 10 women experience postpartum depression or anxiety in the first six months after giving birth. The majority aren’t properly diagnosed and don’t receive treatment for the conditions.

The researchers analyzed data from more than 518,000 privately insured postpartum women from January 2016 through December 2020. Despite reported increases in anxiety and depression across the board after the onset of the pandemic, the researchers found no evidence of an increase in diagnoses of postpartum depression or postpartum anxiety.

This suggests that the underdiagnosis and undertreatment of these conditions was exacerbated by the pandemic-induced health care crisis, the researchers said.

Many insurers only cover one postpartum visit, typically at about six weeks after giving birth. Health care providers are supposed to screen for depression and anxiety at these visits.

But during COVID, it’s likely that many women didn’t have that appointment, Bagwell Adams said. Or if they did, it may have taken place via telehealth, which isn’t always ideal for discussing difficult mental health challenges.

“One of the top causes of maternal mortality is suicide,” Bagwell Adams said. “When these women don’t get diagnosed and they don’t receive proper treatment, they die. And it’s not that postpartum women didn’t see their doctor in time. It’s that they aren’t being listened to.”

Benzos aren’t a substitute for SSRIs when it comes to depression

After the birth of her son during the pandemic, Bagwell Adams experienced that lack of communication firsthand at her postpartum checkup.

“We had a chat, and I told him I was basically crippled by anxiety and depression,” she said. “He was like, ‘Let’s get you something to help calm you down.’ I thought he was going to send me home with an SSRI.”

Instead, her doctor prescribed a benzo.

As someone who’s dealt with anxiety for years, Bagwell Adams knew that wasn’t going to cut it. After some back and forth with her doctor, she was prescribed Lexapro. But many patients wouldn’t know to push back like she did.

“The thing I get really worried about it is that this is what we found for the cream of the crop in terms of insurance coverage,” Bagwell Adams said. “The women in this sample have private insurance. This is the best-case scenario for the United States, and that doesn’t look good.”

Combining opioids with benzos likely increased. That combination can be deadly.

Another concerning side effect of increased benzo prescriptions is interactions with other medications, particularly opioids.

More than seven out of every 10 women who give birth via C-section and one in four who deliver vaginally are prescribed opioids for pain management. And previous research shows that opioid prescriptions for postpartum women increased during the COVID-19 pandemic.

But combining opioids with benzos can be deadly. And the likelihood that some of the women who filled benzodiazepine prescriptions were simultaneously taking pain medications is high, the researchers said.

“For me, this study highlights more questions than answers,” Bagwell Adams said. “There’s something bigger happening here that is really disconcerting when it comes to treating women in general and postpartum women in particular.”

Published in Archives of Women’s Health, the study was funded in part by a grant from the National Institute on Drug Abuse. Co-authors include Emily Lawler and Amanda Abraham, from UGA’s School of Public and International Affairs; Shelby Steuart, a doctoral graduate of UGA’s School of Public and International Affairs who is now a postdoctoral researcher at the University of Chicago, and Hailemichael Shone, of Indiana University.

Researchers from Rutgers Health and other institutions analyzed New York State Medicaid records for more than 141,000 patients receiving any psychiatric medication.  Nearly 400 of them received at least one potentially dangerous combination t for one month or longer. Doctors refer to these as severe drug-drug interactions, and their use is typically considered “contraindicated” or recommended against.

Senior study author Lawrence Kleinman, professor of pediatrics at Rutgers Robert Wood Johnson Medical School, cautioned that while some children whose illness is resistant to usual treatments may receive more benefit than the risk from the combination, “Good practice demands that patients and caregivers be informed of and assent to risks and benefits, including informing them that the intended pair of medications is typically contraindicated.”

The study, published in BMC Primary Care, analyzed 2014 prescription data for New York Medicaid enrollees under 21. While the overall rate of these potentially dangerous combinations is small —about 3 in 1,000 children who filled any mental health medication prescription had at least one month of prescription overlap, and 5 per 1,000 had any overlap — these cases represent significant potential for harm or death. Kleinman noted that New York State Medicaid had previously implemented a program to reduce harmful drug interactions, suggesting numbers might be higher in other populations.

Polypharmacy (use of multiple medications) is very common, with nearly 38 percent of patients in the study filling two or more medications with at least one month overlap, generating more than 11,000 distinct drug combinations.

The study offered some reassurance: the most commonly filled mental health medications were stimulants typically used for conditions such as attention-deficit/hyperactivity disorder, and these were never combined with other drugs to create severe interaction risks. Most contraindicated combinations involved the antipsychotic drug ziprasidone, which can increase the risk of potentially fatal heart rhythm abnormalities such as QT interval prolongation or serotonin syndrome when paired with certain medications. Kleinman noted, “Because of this risk, the FDA has warned that ziprasidone should not be prescribed with other drugs that have demonstrated QT prolongations.”

About 32 percent (364) of the 1,121 patients prescribed ziprasidone also received a contraindicated partner medication for at least 30 days. It rose to 54 percent when considering prescription overlap of any duration.

Other common risky combinations involved antidepressants such as fluoxetine (Prozac) and trazodone paired with various antipsychotic medications, risking life-threatening QT interval prolongation and serotonin syndrome.

Researchers analyzed prescription claims data for all New York State Medicaid enrollees younger than 21 in 2014, identifying 84 distinct behavioral and mental health medications. They flagged combinations with severe interactions according to established drug interaction databases.

The team examined different durations for overlapping prescriptions: one day, 15 days, or 30 days. Even at the 30-day threshold, 392 young patients received contraindicated combinations, rising to 651 for any overlap.

Contraindicated combinations were more common in adolescents and young adults than younger children, with no children under 6 receiving risky combinations. While boys were more likely to receive any mental health medication, there was no gender difference in potentially dangerous pair usage.

Of over 20,000 clinicians prescribing psychiatric medications, 386 prescribed at least one contraindicated pair. Most were psychiatrists rather than pediatricians, which Kleinman suggested may be because psychiatrists likely see patients with more severe mental illness.

Kleinman added that insufficient research into treating mental illness in children  often left clinicians and families “flying blind.”

Among the study’s limitations was the age of its data. Prescribing patterns may have changed, especially post-COVID-19. Also, researchers couldn’t determine if patients took all medications as prescribed or if prescribers and parents made intentional, informed decisions about risky combinations.

Nevertheless, Kleinman emphasized the need for ongoing monitoring of prescription patterns to prevent potential harm. He suggested health systems and insurers implement systems to flag these rare but concerning cases for review.

“We believe that our data and this methodology could serve as the beginning of such efforts,” Kleinman said. “Ultimately, such ongoing monitoring could reduce harmful prescription combinations and medication-related adverse events.”

They found that 1 in 8 caregivers had difficulty accessing mental health services for their children between 2016 and 2019. But those who lived in states with the most comprehensive mental and behavioral health coverage laws were about 20% less likely to report trouble accessing care than those who lived in states with the least comprehensive laws.

Caregivers of Black and Asian children were more likely to report poor access to mental and behavioral health care, as were caregivers of children who experienced more adverse childhood events (ACEs).

“Unfortunately, in my own practice, I regularly see children who are unable to access needed mental health care, and their symptoms continue to worsen until they reach a crisis point,” said first author Ashley Foster, MD, a pediatric emergency care physician at UCSF Benioff Children’s Hospital San Francisco. “That inspired me to study whether more comprehensive laws about mental health insurance coverage can influence whether kids can get the care they need, and that is exactly what we found.”

The study appears Aug. 12 in JAMA Network Open.

While legislation appears to influence access, it also matters how well states enforce their laws.

“Even when families have insurance, mental and behavioral health providers may refuse to accept certain insurance types – or insurance altogether,” Foster said. “For those who do access care, there may be high co-pays or deductibles, which can affect perceptions of access.”

To counter this, the authors wrote, states should invest in community-based mental health services, develop a workforce that better reflects the state’s cultural diversity and support reimbursement for tele-mental health care. States also should define the disorders that must be covered by insurance, such as autism and attention-deficit hyperactivity disorder.

Authors: Additional co-authors include Jennifer A. Hoffmann, MD, MS, of Ann & Robert H. Lurie Children’s Hospital of Chicago; Megan Douglas, JD, of Morehouse School of Medicine; Michael C. Monuteaux, ScD, Kathrine E. Douglas, MD, and Joel D. Hudgins, MD, MPH, of Boston Children’s Hospital; Teal W. Benevides, PhD, MS, OTR/L, of Augusta University; and Amanda M. Stewart, MD, MPH, of Children’s National Hospital.

Funding: None.
Disclosures: None.

For their study, the researchers analyzed data from the Centers for Disease Control and Prevention’s 2022 National Health Interview Survey of 27,651 U.S. adults. The researchers measured the prevalence of medical debt among those with depression or anxiety—both currently and in the past over their lifetime—and evaluated the relationship of medical debt with delayed and forgone mental health care over the previous 12 months.

Among adults with current depression and medical debt, 36.9 percent delayed mental healthcare and 38 percent did not seek out care in the previous 12 months. In comparison, for those reporting current depression and no medical debt, 17.4 percent reported delaying mental health care in the previous 12 months and 17.2 percent reported forgoing it altogether in the past 12 months.

Among adults with current anxiety and medical debt, 38.4 percent delayed care and 40.8 percent did not seek care in the previous 12 months. For adults reporting current anxiety and no medical debt, 16.9 percent reported delaying care and 17.1 percent reported forgoing care in the previous 12 months.

The results were published online July 17 in JAMA Psychiatry.

“The prevalence of medical debt in the U.S. is already quite high, and the prevalence was significantly higher among adults with depression and anxiety,” says study lead author Kyle Moon, a PhD student in the Bloomberg School’s Department of Mental Health. “On the flip side, a relatively high number of adults with no medical debt also report delaying or forgoing mental health care, and medical debt appears to compound the problem.”

The study found that 27.3 percent of adults with current depression and 26.2 percent with current anxiety reported having medical debt going back 12 months, versus 9.4 percent of adults without current depression and 9.6 percent without current anxiety.

The researchers captured medical debt and delaying or foregoing mental health care from responses to the following CDC survey questions:

• In the past 12 months, did you have problems paying or were unable to pay medical bills?
• During the past 12 months, have you DELAYED getting counseling or therapy from a mental health professional because of the cost?
• During the past 12 months, was there any time when you needed counseling or therapy from a mental health professional, but DID NOT GET IT because of the cost?

To ascertain current depression or anxiety, the researchers used the Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7 scales, respectively. A score of 10 or greater corresponds to moderate or severe symptoms with both scales. Both were administered as part of the CDC’s 2022 National Health Interview Survey.

Consumer credit report data shows that medical debt is the biggest contributor to personal debt, which impacts access to health care treatment. The inability to pay medical debt has been shown to cause delays to needed care, especially when it comes to seeking treatment for mental disorders: Less than half of U.S. adults with mental disorders receive treatment.

Medical debt remains common despite insurance coverage: Over 90 percent of individuals in this study were insured, yet 19.4 to 27.3 percent reported having medical debt over the last 12 months.

The researchers also looked at adults who reported having been diagnosed with depression or anxiety in their lifetime. Among adults with a lifetime depression diagnosis and medical debt, 29 percent delayed care because of cost, while 29.4 percent did not seek out mental health care at all. Among adults with a lifetime diagnosis of anxiety and medical debt, 28 percent reported delaying care, and 28.2 percent forwent care altogether.

“Health systems have a critical role to play,” says Moon. “They could expand services for patients by improving the processes to determine patient eligibility for financial assistance.”

The authors note that economic stressors and financial strain are risk factors for both depression and anxiety. This means that while medical debt may be a risk for poor mental health, illness and disability are also risk factors for medical debt. The authors suggest further studies to evaluate state policies that can protect against medical debt and break down barriers to seeking mental health care for those who need it.

“Medical Debt and the Mental Health Treatment Gap Among U.S. Adults” was written by Kyle Moon, Sabriya L. Linton, and Ramin Mojtabai.

Those who experienced loneliness were among the most impacted.

“During the pandemic, loneliness almost tripled the risk of depression in older adults with diabetes,” says clinical pharmacist and first author ZhiDi Deng. “This not only highlights the impact of quarantines and lock-downs on individuals’ mental health. It also shows us that there is room for improvement on how we can better deliver services to older adults with diabetes in future public health crises.”

Although not as severely impacted as those with a history of depression, one in eight older adults with diabetes who had no history of depression prior to the pandemic were depressed in the autumn of 2020. “The pandemic has taken a significant toll on the mental health of everyone, particularly older adults with chronic conditions such as diabetes,” says co-author Grace Li, a research assistant at the University of Toronto’s Institute for Life Course and Aging (ILCA). “It’s important for primary health providers to be vigilant for signs of depression among their older patients, even those who were doing well in the past.”

The researchers identified several other factors that were associated with a higher risk of depression among those with diabetes, such as being female, having functional limitations or chronic pain, and experiencing family conflict.

They also reported some unexpected findings. The researchers found that those who were separated, divorced, or widowed had lower odds of recurrent depression during the pandemic than those who were married or in common-law relationships. “This is different from research conducted before the pandemic that indicated married individuals usually are less depressed,” said co-author Dorina Cadar, Senior Lecturer in Neuroepidemiology and Dementia at the Centre for Dementia Studies at Brighton and Sussex Medical School and the director of the Cognitive Epidemiology, Dementia, and Ageing Research lab. “We hypothesized that participants who were married during the pandemic experienced worse mental health because the need to stay for extended periods of time in close living proximity during the lockdowns or quarantine could possibly exacerbate any relationship conflicts. Our findings indicate that those who were experiencing family conflict during the pandemic had more than triple the risk of depression during the pandemic.”

The second unexpected finding was that those with higher income prior to the pandemic had a greater risk of depression during the pandemic than those who were poorer.  In pre-pandemic research, higher income is associated with a lower prevalence of depression.

“We hypothesized that this finding may have been influenced by the generous response of the Canadian government with the Canadian Emergency Response Benefit (CERB), which may have had a protective impact on the mental health of low-income Canadians. CERB provided Canadians who lost employment during the pandemic with a $2000 monthly income. For some low-income individuals and households, this would actually increase their monthly income, thereby reducing financial-related stress among this population,” said co-author Maria Rowsell, a research assistant at the University of Toronto’s ILCA.

The study was conducted using data from the Canadian Longitudinal Study on Aging (CLSA) surveys. The CLSA is a large national longitudinal study involving older Canadians with diabetes. This study identified 2,730 individuals with diabetes in the CLSA sample. In this group, 1,757 individuals had no pre-pandemic history of depression, and 973 had a pre-pandemic history of depression. The study was published online this month in the journal Archives of Gerontology and Geriatrics Plus.

“The long-term implications of the pandemic extend far beyond physical health,” said senior author Professor Esme Fuller-Thomson of the University of Toronto’s Factor-Inwentash Faculty of Social Work and Director of the ILCA. “It is important to improve access to mental health services for people with diabetes, particularly during periods of increased stress. Interventions that have shown promising results to support the mental health of individuals with comorbid depression and diabetes include cognitive behavioural therapy and psychoeducation.  We need to improve access to these important services.”

Depression is the leading cause of disability worldwide and is associated with disruptions to several brain and psychological processes, including impaired learning and memory. Physical activity, especially aerobic exercise, has been found to reduce depressive symptoms, but until now the processes behind this have been poorly understood.

In a new review article published in Translational Psychiatry, researchers propose a novel hypothesis to understand the antidepressant effects of exercise. They believe that the process may hinge on motivation, which is very important for alleviating a number of symptoms of depression, such as anhedonia (a lack of interest or joy in life’s experiences), low energy and ‘brain fog’.

The team summarised research papers that explored the mechanisms of depression in both humans and animals and concluded that depression, especially anhedonia, is associated with elevated inflammation (caused by the body’s immune response). Importantly, inflammation is also linked to disrupted dopamine transmission. These biological changes may represent key processes leading to changes in motivation, and in particular a lower willingness to exert physical or mental effort.

Meanwhile, exercise reduces inflammation, boosts dopamine function, and enhances motivation. The researchers believe that this could be an important reason as to why exercise exerts an antidepressant effect.

Lead author, Dr Emily Hird (UCL Institute of Cognitive Neuroscience) said: “The antidepressant effect of aerobic exercise has been convincingly demonstrated through randomised controlled trials, but its mechanism is not well understood. This is, in part, because it likely involves a variety of biological and psychological processes.

“For example, alongside its positive effect on inflammation, dopamine and reward processing, exercise also reduces oxidative stress and improves self-esteem and self-efficacy.

“However, we are proposing that exercise – particularly aerobic activities that make you sweaty and out of breath – decreases inflammation and boosts dopamine transmission, which in turn increases the desire to exert effort, and therefore boosts motivation generally.”

The team hope that this understanding of how exercise reduces symptoms of depression will help to inform the development of new treatment strategies – such as personalised exercise programmes.

Dr Hird said: “Understanding the mechanisms that underly the antidepressant effects of physical activity in depression could also inform our understanding of the mechanisms causing depression and the development of novel intervention strategies, in particular personalised intervention, and social prescribing.”

To further test their hypothesis, the researchers advise that large randomised controlled trials need to be conducted that assess the antidepressant effects of exercise, whilst also measuring the effect on variables including inflammation, dopamine transmission and motivation.

It would also be important to investigate any potential barriers to exercise.

Dr Hird said: “Addressing barriers to exercise – particularly in people with depression – is crucial, as regular physical activity may be able to alleviate symptoms, enhance mood and empower individuals on their path to recovery. As part of this, finding strategies to encourage exercise is key.”

The team are now running a trial based on the hypothesis proposed in the review, which will involve 250 participants aged 18 to 60 and is funded by a Wellcome Mental Health Award.

The review paper was funded by the Rosetrees Trust.

But first and foremost, current prescribing practice for these drugs, which include sedatives, anti-anxiolytics, antidepressants, antipsychotics, and melatonin, needs to be a lot safer, they insist.

The numbers of these drugs being prescribed to children and young people has been rising steadily, along with a tendency to prescribe them for longer periods, note the editorialists.

They cite previously published UK studies, showing that the prescribing rate of antipsychotics for children rose more than 3% every year between 2000 and 2019, while the prescribing rate of antidepressants more than doubled among 12-17 year olds between 2005 and 2017.

Another study shows that more than 56,000 under-17s were taking melatonin in 2022, which represents an increase of 168% on the equivalent figures for 2015.

The UK is not alone when it comes to the growing reliance on these drugs to treat children’s mental health issues, the editorialists point out.

They cite data from a large US household survey showing a sharp rise in the numbers of young people being prescribed a cocktail of these drugs, despite mounting concerns about the safety and effectiveness of such an approach.

The safety of psychotropic use in children is poorly researched, emphasise the editorialists. But safety concerns about antipsychotic prescribing to children in foster care, in particular, have prompted the American Academy of Child and Adolescent Psychiatry to issue guidelines for clinicians, advocating a ‘start low, go slow’ approach.

These medications need to be regularly reviewed and discontinued at the earliest opportunity, say the editorialists. But the evidence suggests that clinicians in primary care don’t feel confident enough to taper the dose and frequency, while hospital doctors feel that inpatient stays aren’t long enough for this to be started.

“If psychotropic prescribing is to become a mainstay of the management of childhood mental health problems, and there is a limited evidence base to support such use, it needs to be safer,” write the editorialists.

“There is a need to better understand the level of risk that psychotropics pose, what doses are considered safe in different age groups, and at what point physical health monitoring should become mandatory,” they add.

And they conclude: “Better joined-up oversight and shared decision-making, involving young people and their families in discussions about medication both in primary and secondary care, to ensure that treatments are not continued when no longer required, is vital.”

Now, a new study offers hope that while they wait to get care, patients could still get some relief by using evidence-based smartphone apps and wearable devices to track sleep and activity.

The study shows that depression and anxiety symptoms, and suicidality, all decreased measurably when patients were assigned to mobile applications that incorporated mindfulness practices, cognitive-behavioral therapy skills, or prompts that encouraged mood-enhancing activities.

The study, conducted at Michigan Medicine, the University of Michigan’s academic medical center, is published in JAMA Network Open. It involved just over 2,000 patients scheduled to get care in coming weeks from a mental health provider at outpatient U-M Health or U-M student clinics.

Adam Horwitz, Ph.D., the U-M Medical School psychologist who is the paper’s lead author, called the results encouraging, with implications for individuals and clinics alike.

“Having this type of option, especially for people who are motivated enough to seek an appointment and wait for it, could be very valuable when providers have long wait lists,” said Horwitz, who is an assistant professor in the Department of Psychiatry. “These individuals want to be doing something about their mental health but don’t yet have access, so this suggests that providing them with some sort of digital option when their motivation is already high, and they are ready to do something, could begin to make a difference.”

Combining app prompts and wearable device data

Nearly all the patients completed standardized mental health assessments both at the start of the study and after six weeks of using the app they had been randomly assigned to install on their smartphone. All participants also wore a study-provided Fitbit or their own Fitbit or smartwatch, to track sleep and physical activity.

The study randomly assigned most participants to one of two commercial apps – Silvercloud, which is based on cognitive behavioral therapy principles, and Headspace, which coaches users in mindfulness techniques. Both apps have been shown separately to help alleviate mental health symptoms, but have never been tested against one another.

Some study participants were randomly assigned to receive a customized version of the study app called MyDataHelps, either alone or together with one of the commercial apps. Those randomized to receive this app received positive encouraging prompts twice per day based on their activity tracker data — for example, applauding them for walking or getting a good amount of sleep, or suggesting a simple act to improve their mood.

Improvement in all groups

Surprisingly, no matter what group they were in, the participants’ scores on standard mental health scales changed for the better by the end of the study period.

At the start of the study, depression scores on average were just under 13 on the 27-point PHQ-9 scale; all groups dropped by two to three points by six weeks. Scores on the 21-point GAD-7 anxiety scale dropped by 1.5 to 2 points across the board.

Meanwhile, scores on measures of protection against suicide risk increased slightly, with the most improvement among participants using Headspace. Scores on the suicide risk measurement dropped slightly across the board, indicating lower risk for suicidal behavior.

Most of the study participants had their initial appointment with a U-M mental health provider before the end of that six-week period, but the drop in mental health scores was similar for those who hadn’t yet started professional treatment.

More research ahead

Horwitz notes that the newly published study, called PROMPT, helped inform the development of a much larger study called COMPASS based at U-M that just got $17.9 million in funding from the National Institute of Mental Health.

The COMPASS study will involve not only smartphone apps, wearable activity trackers and standardized mental health assessments, but also genetic tests and other types of data collection. It will involve thousands of U-M Health and U-M student clinic patients who are waiting for their first mental health-related appointment.

Both PROMPT and COMPASS seek to help researchers develop a more personalized approach to mental health care.

They hope to identify which characteristics make someone more likely to respond positively to different forms of treatment or support, so they can use this knowledge to reduce the time it takes to find the approach that helps each individual.

Future directions

Horwitz notes that people seeking mobile-based mental health support have many apps to choose from – and that most of those apps haven’t gotten scrutiny through objective research. Headspace and Silvercloud have more objective evidence behind them than most of these apps, he notes.

He and his colleagues were surprised but encouraged to see improvement in the group using the customized version of MyDataHelps, too.

Part of the reason may have to do with the study population: people who were motivated to seek help for mental health concerns, had already been on a waiting list to get scheduled, and now had been scheduled and were waiting to be seen.

Because mental health conditions can wax and wane in their symptom severity, apps that support someone during an especially low-mood or high-anxiety time could be important for helping them endure the time until their first appointment.

Horwitz notes that the study participants’ clinical providers didn’t have access to their app data. But, he said, this might be a potential option for clinics moving forward if patients want to grant that access by allowing their app to share a summary with their clinic.

Data from mental health apps could even potentially help providers or systems understand which patients need the most-intensive approaches to psychiatric care, and which might be able to do all right with less-intensive care. That could also improve the waiting list situation for all patients, he notes.

He likens this to a relay race.

“If we can use apps to give the patient a bit of momentum on understanding and managing their symptoms, even before they get to clinic, then perhaps that will help them get more out of therapy once they get to clinic and pass the baton from the app to a professional provider,” he said. “The apps don’t have the same effect as therapy, but doing something while waiting is still important.”

In addition to Horwitz, the study’s authors are Elizabeth D. Mills, Ph.D., of the U-M Department of Anesthesiology, Srijan Sen, M.D., Ph.D., and Amy S.B. Bohnert, Ph.D. Sen, a professor of psychiatry, directs the U-M Eisenberg Family Depression Center and is a member of the Michigan Neuroscience Institute; Bohnert is co-director of the U-M Opioid Research Institute and a professor of anesthesiology. Bohnert and Sen are two of the three leaders of the COMPASS study.

The PROMPT study was funded by Precision Health at U-M and the Eisenberg Family Depression Center as well as the National Institute of Mental Health (MH131761).

Comparative Effectiveness of Three Digital Interventions for Adults Seeking Psychiatric Services, JAMA Network Open, DOI:10.1001/jamanetworkopen.2024.22115

The findings are published July 2 in Annals of Internal Medicine.

Antidepressants are among the most commonly prescribed medications in the U.S., with 14% of U.S. adults reporting using an antidepressant. Weight gain is a common side effect, which could affect patients’ long-term metabolic health and cause some to stop taking their prescribed treatment, leading to poor clinical outcomes. Although antidepressants overall are associated with weight gain, specific antidepressant medications may affect weight differently.

The new findings, led by investigators from the Harvard Pilgrim Health Care Institute reveal which common antidepressants are associated with the most and least weight gain following medication initiation.

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” said lead author Joshua Petimar, Harvard Medical School assistant professor of population medicine at the Harvard Pilgrim Health Care Institute. “Clinicians and patients can use this information, among other factors, to help decide on the right choice for them.”

Researchers used electronic health record prescription data from eight health systems in the U.S. participating in PCORnet, the National Patient-Centered Clinical Research Network, to conduct the study using data from 183,118 adults ages 18-80 years who were new users of antidepressants. While randomized control trials are considered the most rigorous method for comparing the effects of different medications, they are prohibitively costly and time consuming. In this case, the study team emulated a randomized trial by designing their ideal, hypothetical trial and aligning the data to match that trial as closely as possible.

Study investigators compared weight at 6, 12, and 24 months after initiation of eight common antidepressants: sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, and venlafaxine.

Results showed that bupropion users gained the least amount of weight compared to users of other antidepressants. Bupropion users were approximately 15-20% less likely to gain a clinically significant amount of weight than those taking the most common medication, sertraline. The researchers considered weight gain of 5% or more as clinically significant. Results also showed a large percentage of patients were taking a medication that led to greater weight gain than alternatives that are commonly available in the same class or subclass. For example, sertraline, escitalopram, and paroxetine are all selective serotonin reuptake inhibitors (SSRI), the most common type of antidepressant, but escitalopram and paroxetine were each associated with an approximate 15% higher risk of gaining a clinically significant amount of weight than sertraline in the first 6 months.

“Although there are several reasons why patients and their clinicians might choose one antidepressant over another, weight gain is an important side effect that often leads to patients stopping their medication,” said senior author Jason Block, a general internal medicine physician and Harvard Medical School associate professor of population medicine at the Harvard Pilgrim Health Care Institute. “Our study found that some antidepressants, like bupropion, are associated with less weight gain than others. Patients and their clinicians could consider weight gain as one reason for choosing a medication that best fits their needs.”

Paper cited:
Petimar J, Young JG, Yu H, Rifas-Shiman SL, Daley MF, Heerman WJ, Janicke DM, Jones WS, Lewis KH, Lin PD, Prentice C, Merriman JW, Toh S, Block JP. Medication-Induced Weight Change Across Common Antidepressant Treatments (In Press). Annals of Internal Medicine.

Scientists found that more than 40 per cent of people who were well and not at risk of relapse managed to come off the medication with advice from their doctors.

They also discovered patients who could access online support and psychologists by phone had lower rates of depression, fewer withdrawal symptoms, and reported better mental wellbeing.

More than ten per cent of adults in the UK are taking antidepressants for depression with more than half using them for longer than two years, according to NHS figures.

The study, which was published in JAMA Network Open, was led by the universities of Southampton, Liverpool and Hull York Medical School.

Professor Tony Kendrick from Southampton was the lead author of the research, funded by the National Institute for Health and Care Research (NIHR).

He said the findings are significant as they show high numbers of patients withdrawing from the drugs do not need costly intense therapy sessions.

He added: “This approach could eliminate the risk of serious side-effects for patients using antidepressants for long periods who have concerns about withdrawal.

“Offering patients internet and psychologist telephone support is also cost-effective for the NHS.

“Our findings show that support not only improves patient outcomes but also tends to reduce the burden on primary health care while people taper off antidepressants.”

The scientists behind the study enrolled 330 adults who have been taking the medication for more than a year for a first episode of depression, or more than two years for a recurrence of the illness.

Co-author Una Macleod, Professor of Primary Care Medicine at Hull York Medical School, said: “Many patients are taking antidepressants for depression for longer than two years, when they probably no longer need them.

“The evidence in our study is clear and suggests the UK should establish a national helpline, by phone and online, to help people intending to come off the medication.”

The new study is the latest in a seven-year research programme, named REDUCE, led by the universities to investigate the long-term effects of withdrawing from antidepressants.

Professor of General Practice Mark Gabbay, a co-author from the University of Liverpool, said the research shows that many patients do not need intense face-to-face therapy sessions while withdrawing.

He added: “This is the first study to demonstrate that stopping inappropriate long-term antidepressant treatment is possible at scale without psychological therapy.

“Antidepressants are recommended only for up to two years in most cases, and people are running the risk of increasing side effects as they get older.

“From our findings, we are calling for active family practitioner reviews for antidepressant discontinuation to be promoted.”

Read the study in full at jamanetwork.com/journals/jamanetworkopen/fullarticle/2820202.

IMAGE: NEARLY HALF OF LONG-TERM ANTIDEPRESSANT USERS CAN QUIT THE DRUGS WITH GP SUPPORT AND ACCESS TO INTERNET OR TELEPHONE HELPLINES ALONE

view more CREDIT: UNIVERSITY OF SOUTHAMPTON