The rhythm of recurrent depression: The course of recurrent depression and prevention of relapse using cognitive therapy

Claudi Bockting

Research output: ThesisThesis fully internal (DIV)


In the last two decades there has been growing consensus that Major Depressive Disorder (MDD) is a chronic disease, characterized by multiple recurrences. In this thesis we studied the effectiveness of preventive maintenance psychological treatment and risk factors for recurrence in recurrent depression.

We focus especially on a specific high-risk group of recurrence, i.e. patients in full
remission of multiple previous depressive episodes. The main aim of this thesis was to examine whether augmenting treatment as usual (TAU) with cognitive therapy (CT) would reduce and/or postpone recurrence in patients with recurrent depression during a two year follow-up period. If this proved to be the case, our objective was to examine whether this preventive approach was cost-effective from a societal perspective (including all societal cost). Further, our aim was to examine
which type of persons benefit from preventive CT. Furthermore, illness related characteristics, coping and stress (life events and daily hassles) and autobiographical memory as potential risk factors predictive for recurrence in the total sample, were examined. In addition, we were interested in the influence of illness history on risk factors for recurrence, as proposed by dynamic vulnerability models. These models state that a new depressive episode might cause psychological and/or biological
damage that, results in a change or increase of vulnerability for the next episode.

Finally, our aim was to study continuation and maintenance antidepressant use (AD) in recurrent depression in daily clinical practice and whether AD user profiles before recurrence predict recurrence in patients who used AD for their last depression.

Main findings
Effectiveness of preventive CT
We studied a preventive group program with cognitive interventions
in patients with recurrent depression remitted on medication and/or psychological therapy or no treatment at all. Our findings show that augmenting TAU (which included in our case also no treatment at all) with CT resulted in a significant protective effect, which intensified with the
number of previous depressive episodes experienced by the patient. The beneficial effect observed in the CT group could not be attributed to other psychological treatments or use of antidepressant medication. More specifically, the present findings show that cognitive treatment significantly reduced recurrence for high-risk patients who experienced approximately five or more previous episodes and were in remission following various treatments. CT reduced relapse/recurrence from 72% to 46% (chapter 2).

Cost-effectiveness of preventive CT
Provision of preventive cognitive therapy to remitted recurrently depressed patients was ineffective and inefficient for the total group. However, provision of preventive
CT may be cost effective for a high-risk group of recurrence, i.e. patients with at least 5 previous episodes. In this high-risk group provision of preventive CT was significantly more expensive, but also more effective, resulting in a over 50% probability for CT being cost-effective at €10.000 up to over 95% probability for CT being cost-effective for a willingness to pay €35.000 per relapse prevented. If
we are willing to pay about €10.000 euro (about £6.850) per relapse prevented in this high-risk group, providing additional preventive CT is cost-effective. Decision makers and doctors should consider (re)allocating limited resources (cognitive therapy) to extremely high-risk groups (chapter 3).

Who benefits of preventive CT?
Preventive CT seemed ineffective in patients with life events (as more
frequently reported by women in our study) and in patients with high previous episode numbers characterized by higher levels of avoidant coping. Generic predictors indicate that in CT, as in TAU, patients with more residual depressive symptomatology and higher levels of dysfunctional attitudes
profit less from preventive CT. The finding that preventive CT protects against the influence of a consistently found risk factor for recurrence, i.e. the number of depressive episodes, underlines the potential of psychological preventive interventions. Preventive CT seemed to be especially effective in reducing presumably internally provoked recurrence, but may be quite ineffective in reducing
external provoked recurrence. CT possibly prevents either stress generation (the hypothesis that depressed individuals generate stressful conditions in part by their own actions, attitudes and characteristics) or disrupts kindling effects (the hypothesis that with recurrent episodes of major depression, progressively less environmental stress is required to provoke recurrence). Kindling effects probably cannot be disrupted in patients with higher levels of avoidant coping in combination with high numbers of previous episodes, and patients who experienced life events (Chapter 4).

Risk factors for recurrence and influence of prior episodes
In chapter 5 and 6, illness related characteristics, coping, autobiographical memory and stress (life events and daily hassles) were examined as predictors of recurrence during the two-year follow-up. Risk factors for recurrence were high numbers of previous episodes, more residual depressive symptomatology and psychopathology
and more daily hassles (instead of life events). Although memory specificity was significantly impaired compared to matched controls, it was not predictive for recurrence. Memory specificity may reflect a global cognitive impairment that persists in (formerly) depressed patients, but does not constitute a
trait marker for vulnerability for recurrence. With the exception of the number of previous episodes and residual symptoms we have found little impact of illness related characteristics (like duration of remission from index episode, severity of index episode, and family history) and demographic factors on recurrence. These factors possibly initially act as risk factors for further recurrence, whereas
later, as in this recurrent sample, the illness itself seems to follow its own rhythm regardless of these predictors. In accordance with dynamic vulnerability models, we found predominantly coping related predictors with a decreasing pathogenic effect with increasing episode number. Vulnerability
in participants with very high numbers of previous episodes is to a lesser extent determined by coping related factors. We found some support for dynamic vulnerability models that posit a change of vulnerability with consecutive episodes. Factors that predict recurrence in patients with two previous episodes are not the same for patients with 5 episodes, or even 10 episodes. Researchers
should not only differentiate between first onset and subsequent depression, but also consider both the increasing and decreasing pathogenic influence of lifetime history of depressive disorder. Specific attention should be paid to identify vulnerability factors modifiable by therapeutic interventions in recurrent depression (such as coping related factors). This provides us with the opportunity to
develop tailored preventive interventions. (Chapter 5 and 6).

Continuation and maintenance antidepressant use
Little is known of discontinuation rates of maintenance AD in clinical practice. In our study, the majority of recurrently depressed patients treated with AD discontinue maintenance AD therapy in daily primary and secondary clinical practice. Only 26% of the patients used AD as recommended by international guidelines. Despite continuous use of AD, 60% relapsed in two years. This relapse rate was comparable to the rate of the intermittent-users (64%), even after accounting for the effect of minimal required dosage and non-adherence. In patients who stopped taking AD after remission and who received additional preventive CT, recurrence rates were significantly lower than no AD-using patients treated with usual care (8%
versus 46%) (Chapter 7).

In sum, this study underlines the necessity for a shift from cure to continued care, at least for patients currently diagnosed with a recurrent depression. Despite consensus concerning the chronic recurrent status of depression for some decades, the shift from cure to continued care has not become common practice. Especially in extremely high-risk patients of recurrence (with high numbers of previous episodes) continued care may be necessary. Brief preventive cognitive therapy, in the maintenance phase of depression is effective and cost-effective and should be considered in primary and secondary care.
Original languageEnglish
QualificationMaster of Science
Awarding Institution
  • University of Amsterdam
  • Schene, Aart H., Supervisor, External person
  • Spinhoven, Philip, Supervisor, External person
  • Koeter, Maarten, Supervisor, External person
Award date27-Sep-2006
Publication statusPublished - 27-Sep-2006


  • depressive disorder

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