Nancy A. Melville

April 18, 2017

SAN FRANCISCO – Children treated for anxiety disorders with psychotherapy, antidepressants, or a combination of the two show no significant differences in outcomes or remission at 5-year follow-up. Furthermore, a majority of children experience relapse and chronic anxiety, new long-term data show.

"These data teach us that we need to regularly assess our patients for relapse, because the largest segment [of those treated] relapse, and we need a better mechanism to capture that before they relapse," said Golda Ginsburg, PhD, of the University of Connecticut School of Medicine, in Farmington.

Dr Ginsburg presented the results here at the Anxiety and Depression Association of America (ADAA) Conference 2017.

Five-Year Data

The findings are from the Child/Adolescent Anxiety Multi-Modal Extended Long-term Study (CAMELS), which evaluated a wide range of clinical and functional outcomes of 319 youths who were previously enrolled in the Child/Adolescent Anxiety Multimodal Study (CAMS) study and who were treated for anxiety.

In the CAMS study, 488 patients aged 7 to 17 years were randomly assigned to receive one of four treatments: cognitive-behavioral therapy (CBT) (n = 139); the antidepressant sertraline (Zoloft, Pfizer) (n = 133); a combination of sertraline and CBT (n = 140); or placebo (n = 76).

The results of that study showed that the strongest response, assessed on the Clinical Global Impression–Global Improvement scale (CGI-I) immediately after treatment and at 36-week follow-up, was in the combination therapy group (80.7). Lesser responses were seen in the CBT and sertraline groups (59.7 and 54.9, respectively). Responses in all groups receiving active treatment exceeded those for patients receiving placebo (23.7).

In the follow-up CAMELS, involving 65% of the CAMS patients, the average age of the patients was 17, 44% were male, and the average time since participating in the CAMS study was 6 years.

Follow-up evaluations, conducted annually for 5 years, showed that overall, approximately 50% of patients were in remission following CAMS. Patients who responded in CAMS were significantly more likely to stay in remission than patients who did not respond for the first 3 years of CAMELS (P < .05). There were no differences between the groups at year 4.

"What this tells us is that patients who responded to treatment were more likely to be anxiety free several years later," Dr Ginsburg said.

Further evaluation of outcomes according to the type of treatment patients received showed that although patients in the combination therapy group in CAMS were more likely to achieve remission, the outcomes evened out in subsequent years, with no differences according to treatment type for the remaining 4 years.

By the fifth year, the remission rate in the combination therapy group was similar to that in the placebo group (although youth in the placebo group were offered treatment after 12 weeks in CAMS).

Largest Sample Size to Date

An overall assessment of patients with data from three or more time points (n = 224) in CAMELS showed that only 21.4% were consistently in remission, defined as having no anxiety diagnoses (according to DSM-IV criteria) in follow-up, whereas 29.9% were experiencing chronic anxiety, defined as always meeting diagnostic criteria throughout the follow-up period. Nearly half (48.7%) were categorized as experiencing relapse, defined as fluctuating between meeting and not meeting diagnostic criteria for anxiety during the follow-up period.

There were no significant differences in treatment type for the three categories of patients ― those who relapsed, those in remission, or those having chronic anxiety. Patients who did not respond to treatment (of any type) in the CAMS study were approximately twice as likely to have chronic anxiety in the follow-up, compared to those who responded to treatment.

A thorough evaluation of potential predictors of outcomes showed that those who achieved remission, compared to those with chronic anxiety, were more likely to be male, younger, and have higher overall baseline functioning, lower baseline anxiety severity, better family functioning, and fewer negative life events.

In all cases, the predictors were significant only in comparison to those with chronic anxiety, not those who relapsed.

A separate review of functional outcomes showed an association between treatment response in the CAMS study with improved global functioning, decreased impairment, and enhanced life satisfaction in the CAMELS follow-up.

Interestingly, that analysis was the only one to show a treatment-specific effect, with CBT having significantly greater effect than placebo with respect to quality of life. The benefits were maintained over time.

"The [identification of] these variables may help us understand and make better predictions about which patients are going to need additional intervention," Dr Ginsburg said.

Research on the treatment of anxiety in youths with antidepressants and combination therapy beyond 2 years is lacking. Although longer-term studies on CBT have been conducted, most are from single sites; the new multicenter study represents the largest sample size to date, Dr Ginsburg said.

Overall, the findings paint a picture that is perhaps as encouraging as it is discouraging, she said.

"In looking at the data, I struggle with whether these are or are not good outcomes.

"With remission rates of 50% across each year (in the CAMELS study), you could say that's phenomenal because we started with 100%, so if we can cut by 50% the number of youth of having an anxiety disorder as much as 6 years out, that's pretty impressive," she said.

"And the finding that none of the treatments stood out as having greater long-term effects is actually also kind of [encouraging] because not all of those treatments may be available in some settings.

"On the other hand, a huge percent ― 30% ― are still chronically ill, and the highest percentage of patients were relapsers, who still need help," she added.

Troubling Picture

In commenting on the study, Scott Compton, PhD, associate professor of psychiatry and behavioral sciences at Duke University School of Medicine, in Durham, North Carolina, said the findings paint a troubling picture of anxiety outcomes in youth.

"The data show that only a small percentage of patients maintain improvement over the long term, despite being treated with the best treatments available delivered by experts in the field," he told Medscape Medical News.

"Findings suggest that the majority of children continue to struggle with anxiety," he noted. "For the majority of children with anxiety, the results from this study suggest that anxiety might be best characterized as a chronic disorder that needs to be managed."

With that in mind, further tailoring is needed to more individually address patients' needs, he added.

"As a field, we need to shift our approach away from a 'one protocol fits all' to figuring out how best to sequence treatments for the sizeable percentage of children who do not respond to current evidence-based interventions," Dr Compton said.

There is also a need for maintenance strategies to enhance treatment gains and better identify patients who are at risk for relapse, he added.

"If relapse does occur, we will need to know the most effective treatment options to help get someone back on track, and we also need to figure out how to better manage those with comorbidities."

The CAMS and CAMELS studies were funded by the National Institutes of Health. The authors have disclosed no relevant financial relationships.

Anxiety and Depression Association of America (ADAA) Conference 2017. Presented April 7, 2015.


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