AJP Articles Named ‘Top Stories of 2019’ By NEJM Journal Watch Psychiatry

Two articles published last year in the American Journal of Psychiatry have been named “top stories of 2019” by the editorial board of NEJM Journal Watch Psychiatry.

“As always, we looked for high clinical relevance, balanced with solid methodology, and every study we chose focused on improving clinicians' abilities to treat patients, whether by identifying the best options or highlighting the weaknesses of some once-touted approaches,” wrote Peter Roy-Byrne, M.D., editor-in-chief of NEJM Journal Watch Psychiatry, in a post announcing the selection of top journal articles of the year. These are the AJP studies:

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Olanzapine Versus Placebo in Adult Outpatients With Anorexia Nervosa: A Randomized Clinical Trial: Evelyn Attia, M.D., and colleagues found that while the antipsychotic olanzapine may help adults with anorexia nervosa gain some weight, the medication does not appear to reduce obsessionality—a characteristic psychological feature of anorexia nervosa. The findings were based on a trial of 152 adults aged 18 to 65 with anorexia, who were assigned to olanzapine or placebo for 16 weeks. The researchers, who saw the patients weekly, used the Yale-Brown Obsessive Compulsive Scale (YBOCS) interview and several other assessments to determine participants’ obsessionality, eating disorder severity, and other factors over the course of the trial. They found that olanzapine was associated with a significantly greater rate of weight gain than placebo (approximately 1 lb per month for a woman of average height, or 5 feet 5 inches), but there was no significant difference between treatment groups in the rate of change in YBOCS total score or YBOCS subscale scores.

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General Predictors and Moderators of Depression Remission: A VAST-D Report: Sidney Zisook, M.D., and colleagues reported that a patient’s age and hypomanic symptoms may be key indicators for those most likely to benefit from specific, targeted interventions. The researchers studied data from the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study—a trial that examined outcomes in 1,522 Veterans Health Administration patients who received one of three next-step treatments after failing to respond to at least one antidepressant treatment: a switch to sustained-release bupropion, a combination of the current medication with sustained-release bupropion, or augmentation of the current medication with the antipsychotic aripiprazole. The analysis revealed that augmentation with aripiprazole was more effective for patients aged 65 years and older compared with the bupropion regimens. In contrast, for patients with severe mixed hypomanic symptoms, augmentation with aripiprazole or the current treatment combined with bupropion was more effective than switching to bupropion.

For related information, see the American Journal of Psychiatry article “2019 Articles of Import and Impact.”

Changes in Depressive Symptoms at Two-Week Treatment Mark May Predict 12-Week Remission Outcomes

Whether patients with major depressive disorder show improvement (or lack thereof) at the end of their second week on an antidepressant medication may predict whether they will ultimately achieve remission at the end of 12 weeks, a study published in Psychiatric Research & Clinical Practice found.

“For any antidepressant medication trial, it is important to identify as early as possible whether the patient is likely to achieve remission …,” wrote Paul B. Hicks, M.D., Ph.D., of Texas A&M College of Medicine and colleagues. “The present study bolsters the proposed use of the lack of early improvement as a predictor of failure to achieve remission with the current medication.”

The researchers conducted a secondary analysis of data from the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, which involved 1,552 veterans aged 18 and older whose major depressive disorder was unresponsive to at least one course of antidepressant treatment. The study participants were randomly assigned to one of three medication treatment groups: augmentation with bupropion sustained release, augmentation with aripiprazole, or switch to a different antidepressant. The dosage remained relatively constant throughout the trial, though the researchers allowed adjustments to doses as early as the end of the first week. The researchers evaluated participants at baseline and at the end of weeks 1, 2, 4, 6, 8, 10, and 12.

Early improvement was defined as a drop from the baseline depression severity score of 20% or more, as measured by the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C), within the first two weeks of the treatment modification. The researchers then calculated positive and negative predictive values by evaluating whether the participants showed early improvement by the end of the second week and whether they then achieved remission by the end of week 12. The values were determined by categorizing participant outcomes based on whether the patient had a true positive (they showed early improvement and achieved remission), false positive (they showed early improvement but did not achieve remission), true negative (they neither achieved early improvement nor remission), and false negative (they did not show early improvement but achieved remission).

The researchers found that early improvement in patients resulted in a positive predictive value of 38.2% and a negative predictive value of 92.6%; the latter means that if the patient does not show improvement by the end of the second week on a medication, the chance of achieving remission at the end of the 12th week is less than 8%. “The odds of achieving remission, response, and greater than minimal improvement was higher among individuals who exhibited early improvement,” the authors wrote.

They noted, however, that it is also important to analyze the characteristics of the patients who did not experience early improvement but did ultimately achieve remission by the end of the 12 weeks. Those patients were more likely to have lower baseline scores, fewer adverse childhood experiences, lower baseline Beck Anxiety Inventory Score, lower Columbia-Suicide Severity Rating Scale scores, and a higher baseline quality of life.

“A lack of early improvement at the end of week 2 of antidepressant therapy can be used to inform clinical decisions on the likelihood of nonremission of depression during the subsequent 10 weeks, even when dosage optimization is incomplete,” the authors concluded.

For related information, see the American Journal of Psychiatry article “General Predictors and Moderators of Depression Remission: A VAST-D Report.”

(Image: iStock/FilippoBacci)

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Study Suggests Effective Next-Step Treatments for Treatment-Resistant Depression

A new study of predictors and moderators of remission for treatment-resistant major depressive disorder (MDD) found two subgroups of patients who may benefit from specific next-step treatments with aripiprazole or bupropion, according to a report in AJP in Advance.

The study by Sidney Zisook, M.D. (pictured left), a distinguished professor of psychiatry at the University of California, San Diego, and colleagues involved 1,500 mostly older white men with nonpsychotic MDD who were enrolled in the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study. To be included in VAST-D, participants had to have previously failed to respond to at least one course of antidepressant treatment.

VAST-D focused on the effectiveness and safety of three next-step treatment strategies over a 12-week trial: switching to sustained-release bupropion, combining the current medication with sustained-release bupropion, or augmenting the current medication with the antipsychotic aripiprazole. VAST-D participants took a battery of tests, including the Quick Inventory of Depressive Symptomatology—Clinician Rated (QIDS-C), the Clinical Global Impressions severity scale (CGI-S), and the Patient Health Questionnaire (PHQ-9) and had treatment visits at baseline and at weeks 1, 2, 4, 6, 8, 10, and 12.

The first report from the trial revealed that patients who took aripiprazole in addition to the antidepressant they were previously taking had the highest 12-week remission and response rates compared with patients who took bupropion in addition to antidepressants or switched to bupropion.

This latest study focused on helping clinicians predict the most effective treatment strategies for individual patients based on sociodemographic or clinical features, a subject on which Zisook told Psychiatric News there has been very little research to date. These features included age, ethnicity, and employment status; depressive symptom severity, chronicity, and subtype; level of anxiety; mixed hypomanic symptoms; childhood adversity; grief; co-occurring general medical and psychiatric conditions; positive mental health; and quality of life.

The analysis revealed that augmentation with aripiprazole was more effective for patients aged 65 years and older, compared with the bupropion regimens, whereas for patients with severe mixed hypomanic symptoms, augmentation with aripiprazole or combination of current treatment and bupropion was more effective than switching to bupropion.

The researchers also found that most patient demographic features did not predict overall remission at 12 weeks. However, remission was more likely for individuals who were employed, less severely and chronically depressed, less anxious, and not experiencing complicated grief symptoms and who had not experienced childhood adversity. Participants with longer durations of the initial antidepressant medication trial, better quality of life, and positive mental health were also more likely to achieve remission.

“Overall, it’s really a balancing act, and there’s no clear rule that’s going to apply to each patient,” Zisook said. “When considering what’s most likely to be effective versus potential side effects, you should always engage the patient when coming up with next-step treatments—because they’re the ones that need to be compliant in taking the medication. So they should be partners in making the decision.”

For more information, see the Psychiatric News article “Study to Answer What Comes Next When MDD Patients Don’t Respond.”

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Augmentation With Aripiprazole Found Superior When MDD Patients Don't Respond

Augmentation of antidepressant treatment with aripiprazole showed a modest but statistically significant advantage in terms of both remission and response over switching to bupropion in a population of predominantly male veterans with treatment-resistant depression.

That’s the finding from the VA Augmentation and Switching to Improve Depression (VAST-D) Study reported today in JAMA. Lead author Somaia Mohamed, M.D., Ph.D. (pictured left), of the VA Connecticut Healthcare System and colleagues cautioned that further cost-effectiveness analysis is needed given the small effect size and adverse effects associated with aripiprazole.

In comments to Psychiatric News, Mohamed said that since only a third of patients benefit from their first antidepressant treatment, clinicians typically have to choose a new medication on the basis of trial and error. “This study presents the first data indicating that adding an antipsychotic may be more effective than switching to a new antidepressant,” she said. “This study may encourage clinicians to try antipsychotics earlier than they might have otherwise.”

The study was a a multisite randomized trial with Veterans Health Administration (VHA) patients whose condition was unresponsive to at least one course of antidepressant treatment meeting minimal standards for dose and duration. Patients at 35 VA medical centers were randomized to one of three treatments: switch to another antidepressant, bupropion sustained release (switch group); augment current treatment with bupropion sustained release (augment-bupropion group); or augment current treatment with an antipsychotic, aripiprazole (augment-aripiprazole group).

Rates of remission (defined as absence of symptoms) at 12 weeks were 22.3% for the switch group, 26.9% for the augment-bupropion group, and 28.9% for the augment-aripiprazole group. Response (defined as 50 percent reduction in symptoms) was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%) or the augment-bupropion group (65.6%).

In an accompanying editorial, Maurizio Fava, M.D., said the VAST-D study extends findings of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. “Because the VAST-D study was implemented solely in VA sites, the population studied was predominantly male (85%), a significant difference from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D,” he wrote.

Accordingly, the study cannot determine whether the results would have been different in a predominantly female population of patients with MDD. However, a pooled analysis of two trials comparing aripiprazole augmentation with placebo augmentation among patients with MDD and inadequate response to antidepressant therapy found that aripiprazole augmentation was actually more effective for women than men. This argues that the VAST-D study may have underestimated the relative benefit of aripiprazole augmentation.”

For information about VAST-D, see the Psychiatric News article “Study to Answer What Comes Next When MDD Patients Don't Respond.”