Nurse-led self-help for recurrent depression in the primary care setting versus usual care;
a pragmatic randomised trial and economic evaluation

Major Depressive Disorder (MDD) is estimated by the World Health Organization
to be a leading cause for loss of disability-adjusted life years and makes a
major contribution to disability and healthcare costs.1;2 MDD tends to run a
relapsing (symptomatic exacerbation occurring after a response but before
achieving sustained remission during the same episode, mostly within 4-6 months
after recovery) and recurrent (a new episode of depressive illness, mostly
starting 4-6 months after recovery) course.3 Accordingly, interventions to
reduce the disabling effects of depression should be aimed at the prevention of
depressive relapses/recurrences 4 . Henceforth, *relapse/recurrence* is
captured in the term *recurrence*.

Both psychological and pharmacologic therapies are effective in the long-term
treatment of patients with depressive disorders and each has its own merits.
Maintenance treatment with antidepressants (AD) for several years has been the
leading strategy to prevent recurrence in patients with recurrent MDD. However,
the quality of the evidence to support such prolonged treatment is poor. 5-7 A
majority of the patients are not willing tot take AD for a long period of time.
8;9 Therefore, adherence in AD users is estimated at only 50% at best. 8-10
Besides, AD may be contra-indicated because of somatic illness or side effects.
Furthermore, patients* protection from recurrence ceases on discontinuation of
AD 7 and patients might develop resistance against the prophylactic properties
of AD. 11 Last but not least, the optimal duration of the maintenance treatment
has not been studied. Particularly in primary care, recommendations on
maintenance treatment with antidepressants cannot be considered evidence-based.
12

Only more recently attention has turned to psychotherapy in preventing
recurrence in recovered depressed patients. As a rule, persons at risk of
becoming depressed prefer psychological treatments over drugs. According to a
review by Hollon et al (2010), Cognitive Behavioural Therapy (CBT) is
efficacious (*) in the maintenance treatment of recurrent MDD13. A
meta-analysis by Vittengl et al of 28 studies including 1,880 adults,
demonstrated that among acute-phase treatment responders, CBT substantially
reduces the number of recurrences compared to assessment only at the end of
continuation treatment. Preventive cognitive therapy (PCT), a particular type
of CBT, is also effective in the prevention of recurrence in major
depression.14 This preventive cognitive therapy differs from other cognitive
therapies as it mainly focuses on identifying and changing dysfunctional
attitudes, enhancing specific memories of positive experience by keeping a
diary of positive experiences and formulating specific recurrence prevention
strategies.
15

Psychological interventions, like PCT, however, have relatively high costs, are
less readily accessible16 and integrated treatments lack until recently.
Explanations are that psychological interventions are not included in the
Diagnose Behandel Combinatie (DBC; Diagnosis Treatment Combination which is
foundation of the Dutch healthcare costs system) and that most of the cognitive
therapies take place at the specialist level and thus draws on scant resources.
The vast majority of depressed patients however, visit - and are treated by
their primary care physician (PCP) first.17 Because the long-term outcome of
major depression is often unfavourable, and because most cases of depression
are managed by PCP*s,18 there is an urgent need for a (cost)effective,
psychological intervention for patients with recurrent MDD that is readily
accessible at the primary care level. The need for psychological intervention
might be especially pronounced in patients who are adverse to using
antidepressants either because they have shown no treatment response to
pharmaceutical intervention in the past, or have not been very adherent to
pharmaceutical intervention. Only few studies have focused on interventions
aimed at the prevention of recurrences in primary care patients with
depression. 19 This study involves an economic evaluation of nurse-led
self-help for patients at high risk for recurrent MDD in primary care.

Casefinding in this trail should not be a problem as these high risk patients
are often seen by the PCP and are rather easily diagnosed with recurrent
depression in the long term. Hence, inclusion should not be endangered.

The most accessible form of psychological intervention for recurrent depressed
primary care patients is bibliotherapy or self-help intervention, which is
defined as the use of written, audio, or e-learning materials to provide
therapeutic support in mental health service. The patient works the materials
through more or less independently. Research indicates that cognitive
bibliotherapy, has a moderate to large effect in reducing symptoms of
depression and anxiety. 20-23 PCT is especially feasible to deliver in a led
self-help intervention format because of its very structured design.

Self-help interventions can be purely self-administered or can be used as part
of a *guided* therapist-led intervention. A disadvantage of guided self-help
interventions is that they may impose a time burden on PCP*s. Also, PCP*s may
lack the necessary training to administer these interventions. Recent studies
have shown that paraprofessionals, like nurses or prevention-workers, can be
successfully trained to administer forms of CBT-based self-help interventions,
and thus may complement the regular work of the PCP*s. 24;25
In this study, contact with the nurse is mainly supportive or facilitative and
includes no active therapeutic engagement.

Studies show that self-help therapies may be sufficient for several anxiety and
depressive disorders but that some form of support may be essential for
enhancing compliance with the ultimate aim of improving treatment
outcomes.23;26-28 Some form of guidance is likely to be important because the
motivation in remitted patients to actively participate in self-help might be
relatively low and because the therapy might be difficult at certain stages.
Hence, some contact between patients and therapist is generally speaking a good
idea.

From 2008 onwards, ambulatory psychiatric care is included in Dutch healthcare
insurance and PCP*s can employ a mental health nurse in their practices for
four hours a week per PCP. For both cost-effectiveness and pragmatic reasons it
is therefore attractive to let a nurse play a pivotal and facilitating role.

This study focuses on patients at high risk for recurrence. High risk for
recurrence is often defined as having a history of multiple previous depressive
episodes. Several subgroup analyses, based on stratified 29,30 and
non-stratified 15 subsamples, suggested that PCT is more effective in patients
with a history of at least three episodes on a life time basis.
However, recall-bias hampers assessment of the number of previous episodes on a
life-time basis. Therefore it is better to select patients on the number of
episodes during a shorter time frame of, say, the last five years. Altogether;
a high risk for recurrence is established when a patient experienced at least
two depressive episodes in the past five years.

Summarizing, this study aims at evaluating the costs and effects of a nurse-led
self-help cognitive therapy-based preventive intervention for patients at high
risk for recurrent MDD versus usual care alone in the Dutch primary care
setting.

To study whether nurse-led self-help is (cost-)effective for persons with
recurrent MDD in primary care. Effectiveness is defined as significantly less
SCID/DSM-V recurrences in one year follow-up compared to usual care.
Cost-effectiveness is defined from a societal perspective meaning that the
costs of the intervention, health care uptake, patients' out-of-pocket costs
and costs due to productivity losses will be included in the economic
evaluation.

It is hypothesized that adding nurse-led self-help to usual care is clinically
superior to care as usual alone for preventing recurrence in recurrent
depressive disorder. In addition, it is expected that the intervention
dominates the comparator condition in terms of cost-effectiveness.

This study is a randomised controlled trial with randomisation at patient
level. Randomisation at this level makes it attractive for patients as they are
able to receive their care in their own practice. It is also attractive for
practices to participate as they deliver both the intervention and care as
usual alone. Therefore, the inclusion of patients will be easier. Lastly, the
statistical analysis and its outcome is of greater worth because it is more
transparent and well replicable. There will be two parallel groups to evaluate
the costs and effects of nurse-led self-help + usual care for 134 primary care
patients with remitted MDD versus 134 controls (usual care) at 3, 6, 9 and 12
and 15 months follow up. Stratification variables will be the number of
previous episodes (cut-off point at 2 or more previous episodes in the last 5
years) and the type of treatment as usual received for the last episode.
(psychological intervention / AD / no care).

Nurses will deliver the nurse-led self- help. The face-to-face contacts take
place in the primary care practice. The nurses are trained by a professional
from Claudi Bockting*s group. All practice nurses are experienced in offering
cognitive therapy in depressed patients using the Dutch version of the *Coping
with Depression* course (*In de put, uit de put*) 45, based on the work of
Peter Lewonsohn. It takes approximately 1 to 1,5 day to train the nurses.

The investigational treatment in this trial is *nurse-led self-help* based on
PCT; this preventive cognitive therapy has been demonstrated to be protective
in recurrent depression for a period of at least 2 to 5,5 years.44
Patients will be offered a detailed treatment manual of the therapy with
literature, backgrounds and assignments. This self-help book will enable
patients to follow the course of the therapy in their own homes, in their own
time.

Prior to the start of the therapy, a face-to-face meeting with the nurse is
planned at the primary care practice (at a maximum of 45 minutes). This meeting
involves psychoeducation on (the course and treatment of) recurrent depression,
and an introduction to the nurse-led self-help therapy on the basis of the
treatment manual. Apart from this face to face meeting there is weekly
telephone contact (at a maximum of 15 minutes), initiated by the nurse. During
these telephone meetings patients are asked several questions based on a rather
strict protocol. These questions comprise: 1) what is your Q-IDS-SR score? 2)
did you read and understand the literature belonging to that week?, 3) did you
make the accompanying assignments? and 4) what difficulties did you experience
in your assignments ? After these 3 questions, patients are shortly prepared
for next week*s literature and exercises. The contact is of a supportive and
facilitating nature and not of a psychotherapeutic nature.
If a nurse notices depressive symptoms during a regular phone-contact or a
patient brings up feeling depressed, the nurse emphasizes specific parts of the
therapy in order for the patient to cope with these symptoms. Only in the case
of a patient expressing suicidal symptoms, the PCP should be notified. These
procedures are included in the informed consent papers.

This nurse-led self -help psychosocial intervention brings no risks. The burden
in time is relatively small as patients can work through the manual in their
own homes in their own time.