Antidepressants in Youths: No Link to Suicidal Behavior?

Nancy A. Melville

April 20, 2017

SAN FRANCISCO – Youths treated for anxiety with antidepressants or psychotherapy show similarly increased risks for suicidal behaviors regardless of the type of treatment, new research shows.

These findings add support to evidence that antidepressant medication may not, on their own, cause suicidality but that the mental illness itself that may be the culprit.

"Youth with anxiety disorders who subsequently develop depressive symptoms as adolescents or young adults are at an increased risk of suicidal ideation or behavior, regardless if they receive treatment with an antidepressant or psychotherapy," senior author Dara Sakolsky, MD, PhD, assistant professor of psychiatry at the University of Pittsburgh and associate medical director of Services for Teens at Risk (STAR) at Western Psychiatric Institute and Clinic, in Pennsylvania, told Medscape Medical News.

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

Black Box Warning

The findings are from the Child/Adolescent Anxiety Multi-Modal Extended Long-term Study (CAMELS), which evaluated outcomes of youths and adolescents for up to 5 years after they had undergone treatment for anxiety in the original Child/Adolescent Multi-Modal Study (CAMS). Treatment consisted of either the selective serotonin reuptake inhibitor (SSRI) sertraline (Zoloft, Pfizer), cognitive-behavioral therapy (CBT), a combination of the two, or placebo.

The original study of 488 patients showed that the strongest treatment effects occurred in the patients who received combination treatment, followed by those who received CBT and those who received antidepressants, which had similar effects.

In delving into a multitude of long-term outcomes observed at 5-year follow-up, the investigators examined the relationship between anxiety treatments and subsequent suicide behaviors, outcomes particularly relevant following the issuance of a black box warning on SSRIs by the US Food and Drug Association (FDA) after some studies linked the drugs to suicidal behaviors.

The black box warning was expanded in 2007 to include the important caveat that depression was itself associated with a risk for suicide.

In the follow-up study of 319 youths, aged 7 to 17 years, who were enrolled from the previous CAMS trial, 54.9% of patients used any SSRI medication (sertraline being the most commonly used [37.6%]); 7.8% used any serotonin norepinephrine reuptake inhibitor; 12.2% used other antidepressants; and 43.9% used other medications.

Overall, 33% of patients in the CAMELS follow-up study reported any suicidal events. Of these patients, 32.7% reported suicidal ideation, described as wishing to be dead, and 8.5% reported suicidal behavior, described as preparatory acts or suicide attempts.

The risk for suicidal behaviors was significantly higher in current SSRI users compared to those who had never used SSRIs (odds ratio [OR] 2.72; P = .01) as well as in current users compared to those who had used SSRIs in the past (OR 1.93; P = .02).

There was no significant increased risk for suicidal behaviors, however, among those who used SSRIs in the past and those who had never used the drugs (P = .41).

The suicidal behavior risk relating to overall use of any antidepressant compared to no antidepressant use was also significant (OR, 2.34; P = .001). A similarly increased risk was seen with treatment with psychotherapy compared to no psychotherapy (OR, 2.50; P = .0001).

Other factors found to be associated with an increased risk for suicidal behaviors included extended time between therapy visits, depression severity, and baseline child-reported depression symptoms (P = .05).

Additional findings relating to suicidal behavior outcomes from the CAMELS study, also presented at the meeting, showed that patients who achieved remission in the original CAMS study were at reduced risk for suicidal behaviors in the long-term follow-up and had reduced depressive symptoms.

The analysis also showed that higher depressive symptoms prior to treatment was predictive of all mood outcomes. Family dysfunction and negative life events were predictors of suicidal ideation.

Growing Evidence

The results are consistent with randomized controlled trials conducted since the FDA black box warning that support the theory that treatment-seeking for anxiety or depression is associated with greater risk for suicidal behaviors than SSRI use. Nevertheless, concerns linger in the public, particularly among parents.

"Parents often ask about the long-term consequences of treating anxious youth with an SSRI," Dr Sakolsky said.

"The CAMELS data are reassuring in this regard. They show that appropriate, time-limited use of SSRIs for treatment of anxiety disorders does not increase risk of suicidal thoughts or behavior in the long term."

The black box warning itself helped generate evidence of the benefits vs risk of antidepressant use by demonstrating changes in behavior patterns after the significant decline in prescriptions that followed the FDA warning, Dr Sakolsky said.

One study, for example, showed that after rates of suicide among youths aged 10 to 19 years had declined during a 20-year period, those rates increased abruptly in 2003-2004, an increase that corresponded with the FDA warning, widespread media coverage, and a subsequent drop in SSRI prescriptions.

Another study showed a significant increase in poisonings from psychotropic drugs that corresponded with the drop in antidepressant prescribing after the FDA warnings.

"For that study, psychotropic poisoning was used as a proxy for suicide attempt, because they found it was one of the most reliable measures in their database for describing suicide. So if anything, the study is probably underreporting suicide attempts," Dr Sakolsky said.

She pointed to another study that showed suicide attempts in the 3 months before and after initiation of treatment soared just before treatment and subsided by month 6 to rates below that for the 3 months prior to treatment. Similar patterns were seen for antidepressant therapy and psychotherapy.

"What these large pharmacological epidemiological studies show us is that suicide attempts often initiate rather than follow treatment with SSRIs or therapy, and greater SSRI use is associated with lower rates of suicide attempt and completed suicide," she said.

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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