Moderation and mediation in the psychological and drug treatment of chronic tension-type headache: the role of disorder severity and psychiatric comorbidity

Abstract

We evaluated two putative moderators of treatment outcome as well as the role of Headache Management Self-Efficacy (HMSE) in mediating treatment outcomes in the drug and non-drug treatment of chronic tension-type headache (CTTH). Subjects were 169 participants (M=38 yrs.; 77% female; M headache days/mo.=22) who received one of four treatments in the treatment of CTTH trial (JAMA, 2001; 285: 2208-15): tricyclic antidepressant medication, placebo, (cognitive-behavioral) stress-management therapy plus placebo, and stress-management therapy plus antidepressant medication. Severity of CTTH disorder and the presence of a psychiatric (mood or anxiety) disorder were found to moderate outcomes obtained with the three active treatments and with placebo, as well as to moderate the role of HMSE in mediating improvements. Both moderator effects appeared to reflect the differing influence of the moderator variable on each of the three active treatments, as well as the fact that the moderator variables exerted the opposite effect on placebo than on the active treatments. HMSE mediated treatment outcomes in the two stress-management conditions, but the pattern of HMSE mediation was complex, varying with the treatment condition, the outcome measure, and the moderator variable. Irrespective of the severity of the CTTH disorder HMSE fully mediated observed improvements in headache activity in the two stress-management conditions. However, for patients with a mood or anxiety disorder HMSE only partially mediated improvements in headache disability, suggesting an additional therapeutic mechanism is required to explain observed improvements in headache disability in the two stress-management conditions.

Figure 1

Three trial phases: baseline, treatment (administration of stress-management therapy and antidepressant medication/placebo dose adjustment), and evaluation.

Figure 2

Headache Severity as a Moderator Variable. Predicted treatment outcomes (and 95% confidence intervals) when: (A) severity of CTTH disorder is high (M + 1 SD), (B) severity of CTTH disorder is moderate (M), and (C) severity of CTTH disorder is low (M - 1 SD).

Figure 3

Mood or Anxiety Disorder as Moderator Variable. Predicted treatment outcomes (and 95% confidence intervals) for headache disability when: (A) no mood or anxiety disorder is present, and (B) when a mood anxiety disorder is present.

Figure 4

Moderated mediator analysis evaluating Headache Management Self-efficacy (HMSE) at Month 2 as mediator of treatment outcomes at Month 8. Moderator is severity of CTTH disorder when headache activity is the outcome and psychiatric comorbidity when headache disability is the outcome. a = effect of treatment on HMSE at Month 2; b = effect of HMSE at Month 2 on treatment outcome at Month 8; c = direct effect of treatment (i.e. unmediated by HSME at Month 2) on outcome at Month 8; ab = indirect effect of treatment (i.e. mediated by HMSE at Month 2) on outcome at Month 8. Because of the high correlation (r = .84) between baseline headache activity (outcome M₀) and severity of CTTH disorder (the moderator) paths were not adjusted for both these variables when headache activity was the outcome, but only for baseline HMSE (- - - path d) and the identified moderator effects (--- paths f through i) When headache disability was the outcome path estimates adjusted for baseline values (- - - paths d & e) and identified moderator effects (--- d through i).