After posting (last Thursday) our 1996 article on the efficacy of antidepressant medications for treating depression in youth, several people have asked if I have updated information. Well, yes, but because I’m old, even my updated research review is old. However, IMHO, it’s still VERY informative.
In 2008, the editor of the Journal of Contemporary Psychotherapy, invited Rita and I to publish an updated review on medication efficacy. Rita opted out, and so I recruited Duncan Campbell, a professor of psychology at the University of Montana, to join me.
Duncan and I discovered some parallels and some differences from our 1996 article. The parallels included the tendency for researchers to do whatever they could to demonstrate medication efficacy. That’s not surprising, because much of the antidepressant medication research is funded by pharmaceutical companies. Another parallel was the tendency for researchers to overstate or misstate or twist some of their conclusions in favor of antidepressants. Here’s the abstract:
This article reviews existing research pertaining to antidepressant medications, psychotherapy, and their combined efficacy in the treatment of clinical depression in youth. Based on this review, we recommend that youth depression and its treatment can be readily understood from a social-psycho-bio model. We maintain that this model presents an alternative conceptualization to the dominant biopsychosocial model, which implies the primacy of biological contributors. Further, our review indicates that psychotherapy should be the frontline treatment for youth with depression and that little scientific evidence suggests that combined psychotherapy and medication treatment is more effective than psychotherapy alone. Due primarily to safety issues, selective serotonin reuptake inhibitors should be initiated only in conjunction with psychotherapy and/or supportive monitoring.
The main difference from our 1996 review was that in the late 1990s and early 2000s, there were several SSRI studies where SSRIs were reported as more efficacious than placebo. Overall, we found 6 of 10 reporting efficacy. An excerpt follows:
Our PsychInfo and PubMed database searches and cross- referencing strategies identified 10 published RCTs of SSRI efficacy. In total, these studies compared 1,223 SSRI treated patients to a similar number of placebo controls. Using the researchers’ own efficacy criteria, six studies returned significant results favoring SSRIs over placebo. These included 3 of 4 fluoxetine studies (Emslie et al. 1997, 2002; Simeon et al. 1990; The TADS Team 2004), 1 of 3 paroxetine studies (Berard et al. 2006; Emslie et al. 2006; Keller 2001), 1 of 1 sertraline study (Wagner et al. 2003), and 1 of 1 citalopram study (Wagner et al. 2004).
Despite these pharmaceutical-funded positive outcomes, medication-related side-effects were startling, and the methodological chicanery discouraging. Here’s an excerpt where we take a deep dive into the medication-related side effects and adverse events (N.B., the researchers should be lauded for their honest reporting of these numbers, but not for their “safe and effective” conclusions).
SSRI-related medication safety issues for young patients, in particular, deserve special scrutiny and articulation. For example, Emslie et al. (1997) published the first RCT to claim that fluoxetine is safe and efficacious for treating youth depression. Further inspection, however, uncovers not only methodological problems (such as the fact that psychiatrist ratings provided the sole outcome variable and the possibility that intent-to-treat analyses conferred an advantage for fluoxetine due to a 46% discontinuation rate in the placebo condition), but also, three (6.25%) fluoxetine patients developed manic symptoms, a finding that, when extrapolated, suggests the possibility of 6,250 mania conversions for every 100,000 treated youth.
Similarly, in the much-heralded Treatment of Adolescents with Depression Study (TADS), self-harming and suicidal adverse events occurred among 12% of fluoxetine treated youth and only 5% of Cognitive Behavioral Therapy (CBT) patients. Additionally, psychiatric adverse events were reported for 21% of fluoxetine patients and 1% of CBT patients (March et al. 2006; The TADS Team 2004, 2007). Keller et al. (2001), authors of the only positive paroxetine study, reported similar data regarding SSRI safety. In Keller et al.’s sample, 12% of paroxetine-treated adolescents experienced at least one adverse event, and 6% manifested increased suicidal ideation or behavior. Interestingly, in the TCA and placebo comparison groups, no participants evinced increased suicidality. Nonetheless, Keller et al. claimed paroxetine was safe and effective.
When it came to combination treatment, we found only two studies, one of which made a final recommendation that was nearly the opposite of their findings:
Other than TADS, only one other RCT has evaluated combination SSRI and psychotherapy treatment for youth with depression. Specifically, Melvin et al. (2006) directly compared sertraline, CBT, and their combination. They observed partial remission among 71% of CBT patients, 33% of sertraline patients, and 47% of patients receiving combined treatment. Consistent with previously reviewed research, Sertraline patients evidenced significantly more adverse events and side effects. Surprisingly and in contradiction with their own data, Melvin et al. recommended CBT and sertraline with equal strength.
As I summarize the content from our article, I’m aware that you might conclude that I’m completely against antidepressant medication use. That’s not the case. For me, the take-home points include, (a) SSRI antidepressants appear to be effective for some young people with depression, and (b) at the same time, as a general treatment, the risk of side effects, adverse effects, and minimal treatment effects make SSRIs a bad bet for uniformly positive outcomes, but that doesn’t mean there won’t be any positive outcomes. In the end, for my money—and for the safety of children and adolescents—I’d go with counseling/psychotherapy or exercise as primary treatments for depressive symptoms in youth, both of which have comparable outcomes to SSRIs, with much less risk.
And here’s a link to the whole article: