On Depression

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This special issue of the journal is devoted to articles on Depression. I wish to concentrate on four of them that range broadly in their study objectives and study sites. Rather than simply overview the four studies, I have elected to also focus on issues in each article which invite questions—whether in relation to analyses or interpretations.
In evaluating the impact or efficacy of any therapy, options are to compare it to another therapy, or to a placebo, or to a “waitlist” control group. The last generally produces a distinct group difference and optimizes (if not overoptimizes) the impact of the therapy being tested for one key reason. For patients accepted into a trial and told that they might (subject to random allocation) receive the active treatment only after a delay, a reverse placebo effect should be anticipated. In essence, as the therapeutic gun has not as yet been fired, it might be expected that subjects would feel obliged not to improve, and especially in a psychotherapy trial where powerful specific and nonspecific therapeutic ingredients have not as yet been provided. And yet, Ahola et al. (2017) report, in a Finnish study of those with major depression, that those allocated to a “scheduled waiting” group for 6 months fared no worse over that 6-month interval compared with those who received active psychotherapy, with improvement on depression severity measures during the initial 6 months being comparable for the two groups. Somewhat less surprising was the finding that the groups did not differ after 1 year of psychotherapy—apart from their quantification that those who had been in the waiting group were more likely to return lower anxiety scores.
The authors conclude that their study demonstrated that a scheduled waiting time before therapy is associated with symptom improvement and “does not compromise the clinical conditions of patients with depression.” Their interpretation was that the waiting time “strengthened hope and positive expectations” about the treatment to come (i.e., an “anticipation effect’) and might therefore be “beneficial.”
However, if “major depression” is really that “major” (in terms of symptom severity, impairment, and risk of self-harm), arguing for a 6-month waiting period before initiating therapy (of whatever type) as being beneficial has significant risks. An alternative and provocative interpretation of the findings is that the psychotherapy provided to those in the “immediate-treatment group” lacked efficacy. But perhaps the most likely explanation for the finding is that “major depression” is not, of necessity, a persisting and severe depressive state. Such an explanation is a likely one in this study as patients were drug naive, had received no previous psychiatric treatment, and the referrers were aware that subjects might be allocated to a lengthy waiting list period (and were thus unlikely to have referred those with more gravid conditions). In such circumstances, participants were likely to have a high rate of minor and transient episodes of major depression. Thus, the largely nondifferentiating findings might simply reflect the two groups having experienced comparable rates of spontaneous remission.
In the second study, Bares et al. (2017) examine a key clinical issue—what factors might predict response to an antidepressant drug in those with a depressive disorder. In studies of this nature, and with an early one by Stassen et al. (1993) using a methodology adopted in many subsequent studies, “response” is defined as a 50% reduction in depression severity (at trial end) and “improvement” as a 20% reduction in severity occurring at some earlier (and to be identified) stage of the trial.
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