Disrupting the rythm of depression: effectiveness and cost-effectiveness and mediating factors of preventive cognitive therapy, with or without antidepressants and compared to antidepressants alone, in the prevention of recurrent major depressive disorder.

Disrupting the rhythm of depression: effectiveness and cost-effectiveness and
mediating factors of preventive cognitive therapy in the prevention of
recurrent major depressive disorder.


Major Depressive Disorder is recognized as a recurrent condition. Previously
(ZONPreventieprogramma) we demonstrated the effectivity in a national
multicenter randomized controlled trail of preventive cognitive therapy (CT)
added to treatment as usual (TAU) compared with TAU alone, in remitted patients
with a history of recurrent episodes of major depressive disorder, especially
in patients with multiple previous episodes. Maintenance treatment with
antidepressants is the leading strategy to prevent relapse and recurrence in
patients with recurrent major depressive disorder (MDD) who have responded to
acute treatment with AD (Dutch Multidisciplinary Guideline for Depression,
2005). However, previous studies, including ours, indicated that most patients
(up to 70-80%) in clinical practice are not willing to take this medication
long after remission or take too low dosages (Meijer et al., 2004, Bockting et
al., 2008)). Moreover, as patients need to take medication for several years,
it may not be the most cost-effective strategy. The best established effective
and available alternative is brief cognitive therapy (e.g. Beck, 2004, for a
meta-analysis see Vittengl et al., 2007). However, it is unclear whether the
combination of AD to brief Ct is beneficial. In addition it is unclear whether
brief CT while tapering antidepressants (AD) is an effective alternative for
long term use of AD in recurrent depression. Therefore, we will compare the
effectiveness and cost-effectiveness of brief CT added to maintenance AD versus
maintenance AD alone versus guided tapering or discontinuation of AD with brief
CT.
In addition, we examine whether the prophylactic effect of CT was due to CT
tackling illness related risk factors for recurrence such as residual symptoms
or to its efficacy to modify presumed (psychological) vulnerability factors of
recurrence, e.g. rigid dysfunctional attitudes.

The objective of this study is threefold:

1) compare the effectiveness and cost-effectiveness of brief CT added to
maintenance AD versus maintenance AD alone versus guided tapering or
discontinuation of AD with brief CT.

2) examine whether the prophylactic effect of CT was due to CT tackling illness
related risk factors for recurrence such as residual symptoms or to its
efficacy to modify presumed (psychological) vulnerability factors of
recurrence, e.g. rigid dysfunctional attitudes

3) examine differential predictors of response to the three interventions

A randomized controlled multi center trail including 3 arms:

1) Continuation maintenance-AD
2) Continuation maintenance-AD + brief CT
3) Intention guided tapering maintenance-AD +brief CT

In the treatment arm where AD will be continued GP*s and psychiatrists will be
advised to prescribe continuation/maintenance AD as recommended by national
guidelines (2005) continuing AD at minimal required adequate used dosage (>=20
mg Fluoxetine equivalent). In the treatment arm including guided tapering of AD
GP*s and psychiatrists will be advised to taper AD in 4 weeks to prevent
possible withdrawal symptoms. In this arm patients will be asked for an
intention to taper AD. The patient is allowed to start AD again at any time
during the study (this will be monitored).

For patients randomised to the two CT-arms an 8 sessions preventive cognitive
group therapy (2 hours each) will be delivered by a special trained behavioral
therapist.

The burden associated with participation is not that big and surely
not invasive. All patients using antidepressants will be seen by their
own GP or psychiatrist. After remission they all continued this
medication for at least 8 weeks. Also the group of patients that have
the intention of tapering antidepressant will be seen by their own
GP's or psychiatrists. We will advise to taper antidepressants in 4
weeks to prevent withdrawal symptoms. All patients and GP/psychiatrist
may start medication at any time during the study (this will be
monitored).
When one condition is clearly inferior according to an interim analysis
conducted by an independent statistician at 12 months follow-up, then the third
arm including preventive cognitive therapy and tapering of antidepressants will
be aborted, all participants will be informed, and participants from the
inferior condition will be advised to start again with AD.

There are some possible advantages associated with participation on
the researchproject:
- during 2 years a screening on a disease which is known for its high
percentage of relapse, and
- for 2/3 of the group: a therapy for free.
This cognitive therapy is known to protect against relapse (time to
relapse and the severity in case of a relapse, decreased); Bockting et
al, 2005). A recent meta-analysis points at a prophylactic effect of
CT (Vittengl et al., 2007). The results of this study will give more
information about the (costs)effectiveness of preventive cognitive
therapy on depression and gives us insight in the mediating variables
of relapse. This information can throw new lights in the development
of more effective treatment.