Oxytocin Improves Empathy in Women With Borderline Personality Disorder

Oxytocin—a hormone that facilitates social bonding in animals—can improve empathy in women with borderline personality disorder (BPD), according to a study in Translational Psychiatry. Oxytocin was also associated with an increased desire to become emotionally close to someone.

“BPD patients often report problems establishing and maintaining stable relationships to significant others,” wrote Gregor Domes, Ph.D., of the University of Freiburg, Germany, and colleagues. “Their relationships are characterized by a pervasive fear of abandonment, anxiousness, mistrust, and conflicts, which can culminate in hostile and impulsive behavior.”

Domes and colleagues randomized 51 adult women with BPD and 51 age-matched women without BPD to receive either intranasal oxytocin or placebo 45 minutes prior to completing empathy assessments.

Women with BPD who received placebo scored significantly lower on tests measuring emotional empathy (feeling someone else’s pain), cognitive empathy (understanding someone else’s pain), and approach motivation than women in the control group taking placebo. Women with BPD were especially less responsive to positive emotions (pride, joy) than negative ones (sorrow, depression).

“It appears that BPD patients more easily empathize with people in aversive situations or in distress, while it is difficult for them to be empathic with people in positive social situations,” Domes and colleagues wrote. “This pattern is plausible, as negative emotions and situations are much more familiar to patients with BPD and thus negative emotions might be more easily accessible for BPD patients.”

Though oxytocin had no effect on cognitive empathy scores, the intranasal oxytocin was associated with significantly increased emotional empathy and approach motivation in both BPD and control participants. Further, the women with BPD reached a level of emotional empathy and approach motivation similar to that of the control group.

“These results could provide the starting point for designing controlled clinical trials, focusing on treatment efficiency using [oxytocin] as an add-on treatment to cognitive-behavioral psychotherapy in BPD,” Domes and colleagues concluded.

For related information, see the Psychiatric News article “Experts Offer Guidance for Treating Patients With Borderline Personality Disorder” and the Psychiatric Services article "Treatment of Borderline Personality Disorder: Is Supply Adequate to Meet Public Health Needs?"

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Integrating Brief Screen in ER May Better Identify Youth With Psychosis at Risk of Suicide

Almost half (48%) of children and adolescents with a psychotic disorder said they recently had suicidal thoughts or had in the past considered death by suicide when interviewed in the emergency department (ED) using a brief screening questionnaire, according to a report published this week in Psychiatric Services. Most of these youth did not report a chief complaint related to suicidal ideation or behavior when arriving at the ED.

Notably, half of the children and adolescents who screened positive for suicide using the Ask Suicide-Screening Questions (ASQ) screen were discharged from the ED, including 44% of those who reported having suicidal thoughts within the past few weeks.

“ASQ screening is imperative for the identification of youths at risk for suicide, but it needs to be paired with feasible follow-up intervention services,” wrote Jonathan DeVylder, Ph.D., of Fordham University and colleagues.

DeVylder and colleagues analyzed data on 87 children and adolescents aged 8 to 18 with a psychotic disorder who were screened for suicide risk in the ED using the ASQ at the Johns Hopkins Hospital pediatric ED. Youth were included if they had schizophrenia, schizoaffective disorder, major depressive disorder with psychotic features, or bipolar disorder with psychotic features, as recorded in the electronic health record.

The ASQ includes the following four yes/no questions: (1) In the past few weeks, have you wished you were dead?; (2) In the past few weeks, have you felt that you or your family would be better off if you were dead?; (3) In the past week, have you been having thoughts about killing yourself?; and (4) Have you ever tried to kill yourself? A positive response to any item is considered a positive screen.

The ASQ missed one young person with a suicide-related chief complaint. However, the authors noted that treatment as usual on the basis of chief complaints missed 26 young people that ASQ identified as at risk. The ASQ therefore increased detection of suicide risk almost threefold (2.63 times) relative to the chief complaint alone.

DeVylder and colleagues noted that the risk of suicide is especially pronounced shortly after the onset of psychosis, which tends to occur in adolescence or early adulthood. “This factor further compounds the elevated risk of suicide among adolescents after they are discharged from hospital-based psychiatric care,” they wrote.

For related information, see the Psychiatric News article “Surge in Suicide Prompts Call For Diagnostic Category.”

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Discontinuation of Buprenorphine Too Soon May Increase Risk of Adverse Outcomes

People who are treated with buprenorphine for more than 15 months appear to have superior clinical outcomes in the six months following buprenorphine discontinuation compared with those receiving the medication for shorter periods, according to a study published this week in AJP in Advance. However, there was no difference between the groups in rates of overdoses requiring medical treatment during this period.

“Although the study design cannot establish a causal relationship between longer retention and clinical outcomes, the results suggest that postdiscontinuation benefits may not begin to accrue until well after the six-month mark,” wrote Arthur Robin Williams, M.D., M.B.E., of the Columbia University Medical Center and colleagues. “[T]he results are consistent with a growing literature underscoring the protective effects of long-term pharmacotherapy for opioid use disorder as opposed to short-term use or brief detoxification.”

The researchers analyzed Medicaid claims data from 2013 to 2017 of patients who were 18 to 64 years old when they initiated buprenorphine treatment, were continuously retained on the treatment for at least six months, and maintained Medicaid enrollment for at least six months after discontinuing buprenorphine. The data included health information such as medication prescriptions and use of emergency services and inpatient and outpatient services.

The researchers separated these patients into four groups based on when they discontinued buprenorphine treatment (defined as a gap of more than 60 days after the last filled buprenorphine prescription): after 6 to 9 months (n=4,126), 9 to 12 months (n=2,440), 12 to 15 months (n=1,499), or 15 to 18 months (n=931).

The 15 to 18 months group had significantly lower rates of adverse events compared with the 6 to 9 months group, including fewer emergency department visits (41.2% compared with 48.6%), inpatient hospitalizations (11.3% compared with 13.9%), and opioid prescription claims (19.1% compared with 25.9%).

The rates of medically treated overdoses after discontinuation were about 5% for all groups, the authors wrote, “suggesting that overdose events in the subacute period following buprenorphine discontinuation remain common irrespective of treatment duration.” In fact, the six-month period following buprenorphine discontinuation was a “high-risk period for adverse events, especially among patients with comorbid mental illness,” they added.

They concluded, “Given high rates of early treatment discontinuation among patients who initiate buprenorphine treatment, often exceeding 50% within three to six months, greater efforts at the clinical and systems levels are needed to improve patient retention. Priority should be given to redesigning systems of care to emphasize chronic disease management models under collaborative care teams with emergency response capabilities for reaching patients who discontinue medication or disengage from care.”

For related information, see the Psychiatric Services study “Three-Year Retention in Buprenorphine Treatment for Opioid Use Disorder Among Privately Insured Adults.”

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Study Raises New Questions About How Best to Reduce Risk of Depression Recurrence

The return of depressive symptoms after treatment has ended is common in a number of patients with major depressive disorder (MDD). A study published today in JAMA Psychiatry found that patients who stopped taking antidepressants after recovery from chronic or recurrent depression had higher rates of recurrence than those who continued the medications. The difference in recurrence was observed regardless of whether the initial recovery was achieved with antidepressant monotherapy or a combination of antidepressants and cognitive-behavioral therapy (CBT).

“Maintenance of antidepressant medication treatment was associated with a reduced risk of depressive recurrence, but previous treatment with cognitive-behavioral therapy was not,” wrote Robert J. DeRubeis, Ph.D., of the University of Pennsylvania and colleagues.

The findings were based on data collected in the second of a two-phase study. In the first phase, the researchers compared outcomes of 452 patients with recurrent or chronic MDD randomly assigned to take antidepressants alone with those assigned to take antidepressant in combination with CBT. Patients who recovered from MDD (defined as 26 consecutive weeks without relapse) were invited to participate in phase 2 of the trial, in which they were randomized to continue antidepressant treatment or withdrawn from antidepressants over several weeks. (Patients who had received combination therapy treatment during phase 1 ended their course of CBT treatment when phase 2 began.) A total of 292 patients who participated in phase 1 of the study consented to participate in phase 2. These patients were then followed for three years.

“Antidepressant medication maintenance was associated with lower rates of recurrence compared with medication withdrawal regardless of whether patients had achieved recovery with monotherapy treatment [antidepressant only] in phase 1 (48.5% with medication maintained vs 74.8%) … or combination therapy treatment (48.5% with medication maintained vs 76.7% with medication withdrawn),” DeRubeis and colleagues wrote. “No evidence was found that the provision of CBT during acute/continuation treatment [in phase 1] provided protection against subsequent recurrence. … If anything, the initial advantage of the combination therapy treatment that was observed in phase 1 appeared to decrease during the phase 2 follow-up period.”

Psychiatrist Marlene P. Freeman, M.D., the Abra Prentice Foundation Chair in Women’s Mental Health at Massachusetts General Hospital, summarized several takeaways from the findings in an accompanying editorial. “This study clearly underscores the benefit of maintenance antidepressant treatment for this population and is in line with the body of maintenance studies of antidepressant medications, in which randomized studies consistently report that continuation of the medication on which remission occurred provides protection against recurrence at higher rates than placebo. This said, as a field we need to address the challenges associated with maintenance use of antidepressant medications.”

The study leaves several important questions unanswered, she noted: “It is not known how the combination therapy group who recovered in phase 1 would have fared if randomized to continue or discontinue treatment with CBT. We also do not know if and how much better the combination therapy would have been in preventing relapse in phase 2, which is important because relapse rates were relatively high, even with medication maintenance.”

For related information, see the Psychiatric News article “Tips for Recognizing, Treating Symptoms of SSRI Discontinuation,” by Madhukar H. Trivedi, M.D., and Manish K. Jha, M.B.B.S.

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Psychiatrist Offers Tips for Evaluating, Treating Sleep Problems in Patients

Treating psychiatric patients for sleep disturbances can lead to improvements in their quality of life and mental health, but few mental health professionals receive thorough training on how best to assess common sleep complaints. So wrote John W. Winkelman, M.D., Ph.D., a professor of psychiatry at Harvard Medical School and chief of the Sleep Disorders Clinical Research Program at Massachusetts General Hospital, in an article in JAMA Psychiatry.

“Sleep is a powerful biological drive but, paradoxically, is easily perturbed by a variety of processes. Psychiatric illnesses are one such influence, and … many psychiatric medications either interfere with sleep or can produce hypersomnia,” he wrote. To address sleep disturbances, Winkelman advised mental health professionals to first determine their patient’s chief sleep complaint followed by assessments of psychiatric, medical, neurological, and sleep-specific conditions.

“Treatment of sleep complaints is usually directed toward specific reversible causes when present (e.g., pain, mood or anxiety disorders, restless legs syndrome, sleep apnea, nocturia, thyroid disease) and proceeds to more generic treatments (cognitive-behavioral therapy [CBT], hypnotic medications, stimulants) if the initial approaches are not effective,” Winkelman wrote. “However, given the bidirectional relationship of sleep disturbance and psychiatric illness, such generic treatments may provide independent value for both the sleep disorder and psychiatric illness and should be considered for concomitant initial treatment.”

Winkelman concluded the article with recommendations for several treatment options for patients with insomnia—including cognitive-behavioral therapy for insomnia (CBT-I), recognized as a first-line therapy for patients with this disorder; and pharmacological therapies, including hypnotics for short-term use, and for long-term use, sedating antidepressants (trazodone, mirtazapine, doxepin), anticonvulsants (gabapentin), orexin antagonists (suvorexant), and melatonin agonists.

“Sleep disturbance is very common in patients with psychiatric illnesses, and thorough evaluation often leads to remediable causes. Treatment can improve both immediate quality of life and the course of underlying psychiatric illness,” he wrote.

For related information, see the Psychiatric News article “Overlapping Symptoms Complicate Diagnosis, Treatment of Psychiatric and Sleep Disorders.”

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Ketamine May Benefit Patients in Treatment for Alcohol Dependence

A single infusion of ketamine in combination with psychotherapy may help people with alcohol use disorder to reduce or stop drinking, according to a pilot study published today in AJP in Advance. Compared with participants who received the sedative midazolam, those who received ketamine had a lower likelihood of alcohol use over a three-week period.

“Although alcohol-related costs exceed 1% of the gross national product in developed countries, most affected individuals are not in treatment,” wrote Elias Dakwar, M.D., of Columbia University Medical Center and colleagues. “Of those in treatment, a large number do not respond to available medications or behavioral treatments. More effective pharmacotherapy options are needed, as well as methods to enhance efforts aimed at behavioral modification.”

The study included 40 treatment-seeking adults with a DSM-IV diagnosis of alcohol dependence but no other substance use. All participants received weekly motivational enhancement therapy sessions—focused on strategies to promote motivation and change substance use behaviors—over a five-week period. During the second week of therapy, the participants received one 52-minute infusion of either ketamine or midazolam, followed by an additional motivational enhancement therapy session 24 hours later. (Midazolam was chosen as the active control because it alters consciousness without any known persistent effect on alcohol dependence, the authors noted.)

During the three weeks after infusion, 47.1% of participants in the ketamine group reported drinking alcohol and 17.6% reported drinking heavily on one day (more than four drinks for men and more than three drinks for women), whereas 59.1% of participants in the midazolam group reported drinking alcohol and 40.9% reported drinking heavily on one day. The participants in the ketamine group also had a longer average time before a relapse, which was considered the first heavy drinking day or dropout from the study; six participants dropped out of the study from the midazolam group compared with zero participants in the ketamine group.

“[T]he study findings represent a first step in understanding a potential clinical role for ketamine in the treatment of alcohol use disorder,” the authors concluded. “The question remains whether a single ketamine infusion would promote abstinence in the long term and whether there is indeed synergy with behavioral treatments.”

To read more about the use of ketamine with psychotherapy, see the AJP study “A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial.”

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Eating Disorders Associated With Increased Risk of Pregnancy, Neonatal Complications

Women who have or had an eating disorder are at increased risk of adverse outcomes during pregnancy compared with women without an eating disorder, suggests a meta-analysis in JAMA Psychiatry. Such outcomes include anemia, hyperemesis (characterized by severe nausea and dehydration), and pre-birth hemorrhage. Women with an eating disorder were also found to be at an increased risk of preterm birth and delivering a baby with microcephaly (a smaller than normal head circumference).

“Women with eating disorders should … be recognized as a high-risk population among pregnant women,” wrote Ängla Mantel, M.D., Ph.D., of Karolinska University, Sweden, and colleagues. “[T]hese findings emphasize the importance of developing a reliable antenatal routine enabling identification of women with ongoing or previous eating disorders… .”

Mantel and colleagues analyzed data from the Swedish Medical Birth Registry and other Swedish national health registers looking at demographic data, comorbidities, and complications during pregnancy, delivery, and the neonatal period. The analysis included more than 1 million women who gave birth between January 1, 2003, and December 31, 2014, comprising almost all singleton births in Sweden during this period.

A total of 7,542 women with eating disorders were compared with 1,225,321 women without eating disorders. Eating disorder diagnoses included anorexia, bulimia, and eating disorders not otherwise specified (EDNOS). Women with any of the disorders were further stratified into two groups: those with current eating disorders and those who were diagnosed with eating disorders more than one year before conception.

The analysis revealed the following:

• Women with any eating disorder had nearly twice the risk of hyperemesis.
• Women with anorexia nervosa had a 60% increased risk of pre-birth hemorrhage.
• Women with anorexia had twice the risk of anemia compared with women without eating disorders.
• Women with anorexia nervosa had a 60% increased risk of preterm birth (defined as less than 37 gestational weeks). The risk was smaller for women with bulimia nervosa and women with EDNOS, but significantly higher than in women without an eating disorder.
• The risk of having a baby who was below the sex-specific average weight at birth was increased among women with anorexia nervosa and women with EDNOS compared with women without an eating disorder.
• Women with anorexia nervosa had an almost twofold risk of having a baby with microcephaly. The risk was smaller for women with bulimia nervosa and women with EDNOS, but significantly higher than in women without an eating disorder.

In general, the risks for pregnancy and neonatal complications were higher for women with current eating disorders than those with a history of eating disorders. “Important future research tasks should focus on identifying mechanisms behind the impaired outcomes for women with eating disorders as well as addressing long-term outcome,” the researchers wrote.

For related information, see the Psychiatric News article “Anorexia’s Complex Etiology Opens Path to New Treatments.”

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