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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