This study examined the role of process variables in ADM-CM and PL-CM treatments for depression. The most striking finding was that greater provision of FC early in treatment predicted less symptom change among placebo patients. Our confidence in this finding is bolstered by parallel findings for the therapeutic alliance and patient talkativeness (albeit at the level of non-significant trends). There are two classes of explanation for the relation that we found: (1) patient characteristics elicit higher levels support from pharmacotherapists in early sessions; or (2) high levels of support have a deleterious effect in the absence of active medications. Patients with comorbid conditions were less likely to elicit high levels of FC. However, we failed to find any patient characteristic that accounted for the relationship between FC and outcome. While our results were particularly pronounced for females, they could not be accounted for by any patient characteristic examined. Thus, these results raise the possibility that high levels of support have a deleterious effect in the absence of active medications.
While process variables may cause outcome, it is also possible that symptom improvement causes changes in process variables. At week 2, only the alliance was predicted by prior symptom change. However, at week 8 (after more symptom change had occurred), there was evidence that prior symptom change was related to both alliance and adherence (and competence in ADM-CM only). As patients improved, alliances improved and pharmacotherapists were less adherent (and exhibited lower competence in ADM-CM). This pattern is consistent with the possibility that changes in outcome caused changes in process measures—particularly later in treatment. Nonetheless, FC was not predicted by prior symptom change at any point in treatment. Thus, for the one measure found to predict subsequent symptom change in either condition (i.e., FC in PL-CM), we failed to find any evidence to suggest that this measure might be a consequence of symptom improvement.
Interestingly, there were marked differences in mean levels of FC (and the other process variables) across pharmacotherapists. These differences persisted even after accounting for patient characteristics such as comorbidity. These findings tempt us to conclude that the relation between FC and outcome is driven by pharmacotherapists; however, the lack of pharmacotherapist differences in outcomes leaves us unable to make a strong case for this conclusion. Thus, we suspect that the relationship between FC and outcome may have been driven by multiple factors: pharmacotherapists and perhaps either unobserved patient characteristics or complex interactions between pharmacotherapists and patient characteristics.
There are two kinds of accounts that could explain the pattern of data we obtained wherein facilitative conditions predicted poor response to PL-CM, as depicted in . Higher levels of facilitative conditions may reduce the magnitude of the placebo effect or, alternatively, it could be that pharmacotherapists provide higher levels of facilitative conditions to those patients who are least likely to respond to PL-CM. We explored our data for evidence of the latter, and did not find that any patient characteristic could explain the association between facilitative conditions and subsequent symptom change. Nonetheless, it is possible that a variable that we did not measure, or that was measured poorly, could explain the association.
Two Possible Explanations for the Finding that Facilitative Conditions Predicts a Poorer Response to Placebo with Clinical Management.
If high levels of FC, and possibly alliance, are indeed detrimental in brief sessions of PL-CM, how might that be the case? Perhaps more extensive use of FC encourages patients to discuss matters outside of the realm of medication management and leads patients to treat CM more like a formal psychotherapy. It is possible that such interventions are not helpful when sessions are brief and infrequent (as compared to standard psychotherapy treatments) or when a pharmacologically active medication is not provided: Emotional issues may be raised without sufficient therapy time left for developing a resolution. This does not imply that harsh or insensitive treatment will promote better outcomes in PL-CM. All of the pharmacotherapists in our trial sought to establish good working relationships with their patients and the overall level of support was high. It was within this context that PL-CM patients who were offered the highest levels of FC were those who improved the least. Thus, a “kind but efficient” approach on the part of the pharmacotherapist may yield the best outcomes.
Our finding for PL-CM departs markedly from the literature showing that common factors such as the alliance predict subsequent symptom change in psychotherapy (e.g., Barber, Connolly, Crits-Christoph, Gladis, & Siqueland, 2000
). The only known published work that could have addressed this issue for PL-CM was that reported by Krupnick and colleagues (1996)
. However, Krupnick et al. relied on a potentially underpowered interaction to detect the effect of interest. While they failed to find that the alliance-outcome relation differed among their four treatments, they did not report the alliance-outcome relation within PL-CM alone. It would be interesting to examine that relation specifically to compare it to the findings of the current study.
None of the hypothesized specific factors of CM (i.e., adherence and competence) predicted subsequent outcome in either treatment. However, it is possible that the high levels of adherence and competence or the modest reliability of the process measures made it difficult to detect these effects. Furthermore, neither alliance nor therapist-offered FC predicted outcome in the ADM-CM condition. It may be that the positive effects of the pharmacologically active medication override any effects of treatment process; that is, active medication could have produced a positive response in a way that was independent of therapeutic process.
This study has several limitations that merit comment. First, whereas differences between treatments in their impact on process and outcome were observed in the context of a randomized experiment, and as such they provided a suitable basis for drawing causal inferences, differences in patterns of covariation between process and outcome were correlational in nature and are thus open to multiple interpretations. Unidentified third variables may explain these relationships. For example, it may be that some unmeasured patient characteristic both led therapists to provide greater FC in early sessions and produced poorer response to treatment and that there was no direct causal link between the two.
Second, patients who did not complete treatment were excluded from the process ratings. This was done to ensure that measures of patient outcomes would be available for patients at week 8, but we could have accomplished the same purpose by using analyses to estimate the likely scores for dropouts. Similarly, in retrospect, there was no good reason to eliminate a random subset of the tapes just to ensure comparable numbers of cases across the sites. Exclusion of patients who were seen by multiple therapists, however, still strikes us as necessary.
Third, the process measures had only modest reliability. This was a problem and likely reduced our capacity to detect process-outcome relations that truly do exist (Type II errors). However, reliability was comparable to previous research examining clinical management (Hill et al., 1992
; Krupnick et al., 1996
). There is no reason to believe that random error would have introduced bias or generated false relations among study variables. Relatedly, there are limitations associated with using non-expert process raters. We suspect this may be particularly true for judgments of pharmacotherapist competence.
The findings of this study challenge the implicit notion that relational aspects of common factors (at least as they are often conceptualized) are important determinants of positive response in placebo treatments for moderate to severe depression. One possible interpretation of our results is that in a placebo condition, absent active medication or formal psychotherapy, facilitative conditions may have deleterious effects on therapeutic outcome. We believe that understanding the mechanisms by which the placebo effects occur is of importance in its own right. Though the practical utility of this understanding is likely limited because clinicians may not intentionally prescribe an inert pill-placebo in clinical practice, the findings obtained here in the PL-CM condition may also apply to contexts in which the specific medication chosen has no true pharmacological effect.