Friday, August 5, 2022

Mental Illness Associated With Higher Levels of Oxidative Stress

People who have mental illness are more likely to have higher levels of oxidative stress in their bodies than those without mental illness, a meta-analysis in JAMA Psychiatry has found. Oxidative stress occurs when there is an imbalance of free radicals and antioxidants in the body. A certain amount of oxidative stress is normal and occurs when the body fights off illness or repairs injury. However, long-term oxidative stress can damage cells, DNA, and RNA, leading to chronic inflammation in the body that raises the risk of numerous conditions like Alzheimer’s disease, cardiovascular disease, diabetes, and Parkinson’s disease.

The study’s findings may help explain why people with mental illness tend to have a higher rate of physical illness, Anders Jorgensen, M.D., Ph.D., of the University of Copenhagen and colleagues wrote.

The researchers analyzed data from 82 studies that compared markers of DNA and RNA damage from oxidative stress in people with mental illness with those in people without mental illness. The studies in the analysis used samples from different cell types, such as cells in urine, cerebrospinal fluid, and plasma, to discover markers of DNA and RNA damage in the body and brain caused by oxidative stress. All told, there were 10,151 patients with mental illness and 10,532 people without mental illness in the meta-analysis.

The researchers found a general trend of higher oxidative stress levels in patients with dementias, followed by psychotic disorders and bipolar disorders compared with people without these conditions. Patients who had major depressive disorder tended to have greater blood cell and plasma or serum DNA markers of oxidative stress, but not urinary DNA or RNA markers, than those without major depressive disorder. The meta-analysis included few studies of people with substance use disorder or anxiety disorders, so the researchers considered their findings inconclusive. However, the studies did not show a specific trend toward increased markers of oxidative stress in the brains of people with mental illness compared with those without mental illness.

“Given that there was an association with [oxidative stress] across many different diagnoses and matrices, and given that [oxidative stress] was not specifically increased in the brain, we consider it more likely to be [a byproduct] of the psychiatric conditions rather than a pathophysiologic factor underlying specific psychopathology,” the researchers wrote. “This finding is consistent with growing evidence showing general, transdiagnostic signs of accelerated aging and age-related illness in psychiatric disorders.”

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Thursday, August 4, 2022

Home-Based Transcranial Direct Current Stimulation May Improve Attention in Adults With ADHD

Adult patients with attention-deficit/hyperactivity disorder (ADHD) who received home-based treatments of transcranial direct current stimulation (tDCS) daily for four weeks showed improved attention compared with patients who received sham stimulation, according to a small study published yesterday in JAMA Psychiatry.

“[T]he need of daily visits to clinics or hospitals has been always a major challenge for the use of tDCS in clinical contexts,” wrote Douglas Teixeira Leffa, M.D., Ph.D., of the Hospital de Clínicas de Porto Alegre in Brazil and colleagues. “Thus, the home-based device opens a new window of opportunity, especially for participants who live in geographically remote areas or have physical or cognitive disabilities that may hinder access to clinical centers.”

Leffa and colleagues recruited patients from the Hospital de Clínicas de Porto Alegre who were aged 18 to 60, met DSM-5 criteria for ADHD (combined or inattentive subtypes), and were not being treated with stimulants. All participants had moderate to severe symptoms of inattention, defined as an inattention score of 21 or higher on the clinician-administered Adult ADHD Self-report Scale version 1.1 (CASRS-I). Sixty-four participants were randomized to receive active or sham tDCS.

All participants received a home-based tDCS device, which was preprogrammed with the number of sessions and stimulation dosage (or sham stimulation). They also received a neoprene cap they could wear to which electrodes were already attached to ensure the stimulation was provided accurately and consistently throughout the study period. At baseline, participants were instructed on using the device and received their first stimulation session while assisted by trained staff. Participants then underwent 30-minute daily sessions of tDCS with a 2-mA direct constant current for four weeks, for a total of 28 sessions. To mimic the sensations commonly reported with tDCS, the sham treatment devices delivered a 30-second ramp up stimulation (from 0-mA to 2-mA), followed by a 30-second ramp down (from 2-mA to 0-mA), at the beginning, middle, and end of the sessions. At baseline and weeks two and four, participants’ inattention was assessed using CASRS-I. The participants were also evaluated for symptoms of hyperactivity-impulsivity, depression, anxiety, and executive function over the course of the study.

Fifty-five participants completed all four weeks of treatment (25 in the tDCS group and 30 in the sham group). At week four, the mean inattention score on the CASR-I in the tDCS group was 18.88, compared with 23.63 in the sham group (higher scores on CASRS-I indicate greater symptoms of inattention). Eleven participants (34.3%) in the tDCS group achieved a 30% reduction in CASRS-I score compared with two participants (6.2%) in the sham group. There were no statistically significant differences in hyperactivity-impulsivity, depression, anxiety, or executive function between the two groups. Adverse events were mostly mild, with participants in the tDCS group reporting skin redness, headache, and scalp burn. Two participants in the tDCS group withdrew due to depressive symptoms and dizziness.

“Our findings support the use of tDCS as a safe and effective treatment for adults with ADHD with no concomitant treatment with stimulants,” the authors wrote. “This is particularly relevant since a vast body of literature describes low long-term adherence rates and persistence to pharmacological treatment in patients with ADHD.”

For related information, see the Psychiatric News article “Noninvasive Electrical Stimulation Shown Effective for ADHD.”

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Wednesday, August 3, 2022

Rapid Shift to Telehealth During Pandemic Helped Patients With OUD Access Buprenorphine

The number of individuals prescribed buprenorphine for opioid use disorder (OUD) during the first year of the COVID-19 pandemic increased steadily after the federal government instituted policies that allowed for greater use of telehealth, according to a report in AJP in Advance.

“The majority of visits shifted to telehealth, with telephone visits outnumbering video visits,” wrote Lewei (Allison) Lin, M.D., M.S., of the University of Michigan Addiction Center and colleagues.

Key policy changes, implemented in March 2020, expanded telehealth access for patients; for example, patients were no longer required to travel to a qualifying “originating site” for telehealth encounters, regardless of geographic location. Later, the government allowed permanent payment for audio-only telehealth encounters.

Lin and colleagues used data from the Veterans Health Administration (VHA) to compare trends in buprenorphine treatment before and after the COVID-19 policy changes were implemented in March 2020. They compared the number of patients receiving buprenorphine from March 2019 to February 2020 (before policy changes) with those receiving buprenorphine from March 2020 to February 2021 (after policy changes).

The main outcome was the monthly number of patients receiving buprenorphine treatment for OUD (at least one day that month). They also examined the number of patients continuing buprenorphine treatment (defined as those who received any buprenorphine in the previous three months) and the number of patients who started treatment (defined as those with no buprenorphine fills covering any days in the previous three months).

The number of VHA patients receiving buprenorphine for OUD increased 14% from 13,415 in March 2019 to 15,339 in February 2021. Between March 2019 and February 2020, the number of patients receiving buprenorphine increased significantly by 103 patients per month. In the first month after the COVID-19 policy changes, there was an immediate increase of 265 patients receiving buprenorphine, the authors noted, and this number continued to increase by 47 patients per month.

The number of patients continuing buprenorphine treatment increased at a rate of 107 per month between March 2019 and February 2020, and the rate continued to increase at 53 patients per month after the policy changes. The number of patients who started treatment decreased overall across both periods, but the rate of decrease was not statistically significant.

“[B]uprenorphine treatment for OUD was maintained during the COVID-19 pandemic through a rapid shift to telehealth, suggesting that any future changes to telehealth policies must be carefully considered, as they could have major implications for patient care,” the authors wrote.

For related information, see the Psychiatric News article “Expanded Buprenorphine Prescribing Authority Gains Traction During Pandemic.”

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Tuesday, August 2, 2022

Switching Antipsychotics During Maintenance Treatment May Not Increase Relapse Risk

Switching stable schizophrenia patients to a different antipsychotic as a maintenance strategy (for example, to reduce side effects) does not increase the risk of relapse, according to a meta-analysis in Lancet Psychiatry. However, keeping patients on a low-dose antipsychotic during maintenance is associated with a greater relapse risk, though it is still superior to stopping medication entirely.

“Although antipsychotic maintenance treatment is widely recommended to prevent relapse in chronic psychoses, evidence-based guidelines do not provide clear indications on different maintenance treatment strategies,” wrote Giovanni Ostuzzi, M.D., Ph.D., of the University of Verona, Italy, and colleagues. “[Our] results are of pragmatic relevance for clinicians and should support the update of evidence-based guidelines.”

Ostuzzi and colleagues pooled data from 98 clinical trials that compared at least two of four maintenance treatment strategies for schizophrenia: keeping patients on the antipsychotic dose used during acute treatment, maintaining patients on a low dose of the antipsychotic (50% of or less than the regular dose), switching to a different antipsychotic, and stopping the antipsychotic altogether and replacing it with placebo. The combined data encompassed nearly 14,000 patients (62% male) with an average age of 39.

Compared with discontinuation, continuing at the regular dose, switching to a different antipsychotic, and continuing at low dose were associated with a 63%, 56%, and 32% reduced risk of relapse, respectively. Contrary to the investigators’ expectations based on current literature, antipsychotic switching was similarly effective at preventing relapse as continuing medication at regular doses. Both strategies were superior at preventing relapse to reducing the dose during maintenance treatment.

“Guidelines should highlight the need to routinely implement a shared decision-making framework that both considers these data and emphasizes subjective, recovery-oriented outcomes and ultimately tailor the choice to patients’ needs and perspectives,” Ostuzzi and colleagues concluded.

To read more on this topic, see the Psychiatric News article “To Minimize Medication Withdrawal, Taper Slowly.”

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Monday, August 1, 2022

Smoking Throughout Pregnancy May Have Long-Term Effects on Offspring’s Brain Development

Smoking throughout pregnancy appears to have lasting effects on the brain development of the offspring, suggests a study of children aged 9 to 11 years published today in JAMA Network Open. Specifically, the study found that continued exposure to maternal tobacco use in utero was associated with lower brain volume.

“[I]nterventions targeting maternal smoking cessation before pregnancy or in early pregnancy may favor normal brain development among children in the long term,” wrote Runyu Zou, Ph.D., of Erasmus University Medical Center Rotterdam and colleagues.

The researchers analyzed data collected as part of the Generation R Study—a prospective population-based study in Rotterdam, the Netherlands, of 9,778 women who gave birth between April 2002 and the end of January 2006. They focused on the MRI data from 2,704 children (average age, 10 years) and the information on tobacco use during pregnancy provided by children’s parents. Mothers were asked about their tobacco use at the time of study enrollment as well as in each trimester; fathers were asked about their tobacco use at the time of study enrollment only. The researchers categorized maternal tobacco use during pregnancy into one of three categories: never during pregnancy, until the pregnancy was known, and continued during pregnancy.

Of the 2,704 mothers in the study, 77.7% never smoked during pregnancy, 13.5% continued smoking throughout pregnancy, and 8.8% stopped smoking after becoming aware they were pregnant (mostly in the first trimester). Children born to mothers who continued smoking during pregnancy showed lower total brain volume as well as lower cerebral gray matter and white matter volume compared with children born to mothers who never smoked during pregnancy, Zou and colleagues wrote. The children exposed to maternal smoking throughout pregnancy also had smaller surface area and less gyrification (the folding of the cortex) compared with the unexposed children. The brain differences seen in children exposed to maternal smoking throughout the pregnancy were not seen in the children born to mothers who stopped smoking early in pregnancy.

“These associations were not explained by paternal smoking nor mediated by smoking-associated DNA methylation patterns at birth,” the authors reported.

“All efforts should be made to help pregnant women quit smoking as well as to stop the use of all other nicotine-containing products before pregnancy or as early as possible during pregnancy,” Mikael O. Ekblad, M.D., Ph.D., of the University of Turku in Finland wrote in an accompanying editorial. “The goal should not only be smoke-free but also nicotine-free pregnancy … .”

For related information, see the American Journal of Psychiatry article “Nicotine Use and DSM-IV Nicotine Dependence in the United States, 2001–2002 and 2012–2013.”

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Friday, July 29, 2022

Suicide, Relapse Risk Lower When Schizophrenia Patients Take Long-Acting Injectables

People with schizophrenia who take long-acting injectable antipsychotics (LAIs) have a lower risk of disease relapse, health care use, and adverse events such as suicide attempts compared with those who take oral antipsychotics, a study in JAMA Network Open has found.

Yue Wei, M.P.H., of the University of Hong Kong and colleagues examined data from the electronic health records of 70,396 adults with schizophrenia who were prescribed at least one LAI and at least one oral antipsychotic between 2004 and 2019. They then compared the rates of different health outcomes during periods when patients were taking only LAIs with the periods when patients were taking only oral antipsychotics.

Compared with treatment with oral antipsychotics, treatment with LAIs was associated with 44% fewer suicide attempts, 37% fewer all-cause hospitalizations, and 48% fewer psychiatric hospitalizations for psychiatric disorders. LAIs were also associated with a 12% reduction in hospitalizations for cardiovascular diseases and a 14% reduction in extrapyramidal symptoms (such as an inability to sit still, involuntary muscle contraction, tremors, stiff muscles, and involuntary facial movements), suggesting LAIs were not associated with more adverse side effects than oral medications. There were no significant differences between LAIs and oral antipsychotics with respect to emergency department visits.

Wei and colleagues wrote that their results build upon those found in other studies.

“Our study adds further insights, as we investigated hospitalizations for different causes and safety outcomes, with findings that [LAIs] were associated with not only fewer disease relapses and less health care use, but also fewer adverse events,” they wrote. “It is worth investigating the medication preference and clinical outcomes of people treated with [LAIs] by performing multinational studies.”

For more information, see the American Journal of Psychiatry article “Maintenance Treatment With Long-Acting Injectable Antipsychotics for People With Nonaffective Psychoses: A Network Meta-Analysis.”

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Be Careful When Entering Arrangements With Purported Telemedicine Companies, HHS Warns

The Department of Health and Human Services (HHS) Office of Inspector General (OIG) has issued a special alert warning physicians and other health care professionals of the fraud and abuse risks associated with arrangements with telemedicine companies.

“OIG has conducted dozens of investigations of fraud schemes involving companies that purported to provide telehealth, telemedicine, or telemarketing services,” according to the alert. In some cases, telemedicine companies paid kickbacks to physicians sometimes described as payment per review, audit, consult, or assessment of medical charts,” OIG wrote. “OIG is aware that many practitioners have appropriately used telehealth services during the current public health emergency to provide medically necessary care to their patients,” the alert continued. However, OIG encourages physicians and other health care professionals to use heighten scrutiny before entering into arrangements with telemedicine companies. The alert outlines seven “suspect characteristics” that could suggest an arrangement that presents a heightened risk of fraud and abuse.

The full alert from OIG is available here. For more information about telepsychiatry, check out APA’s Telepsychiatry Toolkit.

Thursday, July 28, 2022

People With Severe Mental Illness Have Elevated Risk for Multiple Physical Illnesses

People with severe mental illness (SMI)—including schizophrenia, bipolar disorder, and other psychotic disorders—have a significantly greater risk of developing multiple physical illnesses in the first few years after their SMI diagnoses compared with people without SMI, according to a report published in Lancet Psychiatry.

“If we are to positively affect the incidence and disability burden of chronic physical health problems in people with severe mental illness, interventions need to start early,” wrote Naomi Launders, M.Sc., David P. J. Osborn, Ph.D., and colleagues at the University College London.

Launders, Osborn, and colleagues used electronic health records from the UK Clinical Practice Research Datalink (a database containing records of patients seen in U.K. primary care practices) to identify patients aged 18 to 100 years who were diagnosed with an SMI between 2000 and 2018. The study included 68,789 patients with SMI who were matched with 274,827 patients without SMI. The authors examined if participants in the SMI group were diagnosed with up to 24 chronic physical health conditions five, three, and one years before and after they were diagnosed with SMI, as well as at the time of their SMI diagnoses; physical conditions in the matched group were tracked over the same period. The physical conditions include cancer, diabetes, asthma, hypertension, and HIV/AIDS.

At the time of their first SMI diagnoses, 43% of patients with SMI had at least one chronic physical health problem, compared with 38% of the matched group. The most prevalent conditions among SMI patients were asthma, hypertension, diabetes, neurological disease, and hypothyroidism. Five years later, 57% of patients with SMI had one or more physical health condition, compared with 47% of patients without SMI.

Patients with schizophrenia were at higher risk of five of the physical health conditions compared with the matched group at the time of diagnosis. Five years later, these patients had a greater risk of 13 of the physical health conditions, including nearly three times the risk of neurological disease and twice the risk of diabetes. Patients with bipolar disorder or other psychotic disorders had a higher risk of 15 of the physical health conditions compared with the matched group at the time of diagnosis. Five years later, patients with bipolar had a higher risk of 19 conditions, including nearly three times the risk of hypothyroidism and neurological disease, and patients with other psychotic disorders had a higher risk of 16 physical conditions, including nearly four times the risk of neurological disease.

“Chronic physical health problems should not be viewed as the inevitable result of psychotropic medication’s adverse effects and long-term health risk factors such as poor diet, smoking, or drug or alcohol misuse, because many of these conditions are present at the point of severe mental illness diagnosis first being recorded,” the authors concluded. “Potentially, interventions targeted at improving the physical health of people with severe mental illness have been initiated too late relative to disease progression, and we need to consider early intervention for physical health as well as mental health in this population.”

For related information, see the Psychiatric Services article “Improving Physical Health Among People With Serious Mental Illness: The Role of the Specialty Mental Health Sector.”

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