To examine in depressed patients who reach a stable depression remission during optimal AD treatment: 1) whether discontinuation is possible; 2) when discontinuation is possible; and 3) in whom discontinuation is possible.
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome involves sustained remission time measured as time of follow-up
without severe depressive symptoms, inpatient admission for depression and
suicide (attempt). Severe depressive symptoms are defined as having an IDS
score>25 (moderately/severely depressed) and meeting DSM-5 criteria for MDD for
2 weeks according the psychiatric MINI interview. Suicide attempt is assessed
using suicide IDS and MINI items followed up with the suicide behaviour
question of the Columbia Suicide Severity Rating Scale (C-SSRS) Screen Version)
and should be confirmed by two OPERA-researchers.
Secondary outcome
Secondary outcomes concern functioning, quality of life, severity of mood,
anxiety and somatic (e.g. side-effects and withdrawal) symptoms and (cost)
effectiveness.
Background summary
Over 1 million Dutch persons currently get an antidepressant (AD) prescribed,
with depression as the main indication. Research shows that maintenance
treatment after depression remission can decrease relapse. However, long-term
AD use can also result in disturbing side effects, medicalization, reduced
autonomy and contrasts with preferences of most patients. Current treatment
guidelines state that AD use should be continued until at least 6 months after
remission to reach a stable depression remission. However, after this period,
it is not clear whether, when and in whom discontinuation of ADs is possible.
Study objective
To examine in depressed patients who reach a stable depression remission during
optimal AD treatment: 1) whether discontinuation is possible; 2) when
discontinuation is possible; and 3) in whom discontinuation is possible.
Study design
Double-blind placebo-controlled trial in which 400 patients are randomized
(1:1) to early discontinuation versus later discontinuation. The trial is
complemented with a non-randomized *external reference* patient group to
evaluate internal validity and generalizability of the trial sample and study
outcomes.
Intervention
The early discontinuation group receives 8 weeks tapering of antidepressants
(either citalopram or sertraline, respectively between 10-40 and 50-200 mg/day)
+ 48 weeks placebo. The later discontinuation group receives 28 weeks AD
continuation + 8 weeks tapering + 20 weeks placebo.
Study burden and risks
Burden of participation involves the time spent on study assessments. An
extensive baseline assessment will be conducted face-to-face at the field
centers. Follow-up assessments after 14, 28, 42, 56 weeks will be face-to-face
at the field centres to conduct standard psychiatric interviews in all
subjects, provide tablet strips, and allow for overall safety checks on general
health of subjects. Follow-up assessments after 7, 21, 35, 49, 80 and 104 weeks
will be done online (or through written questionnaire if preferred by
subjects). Additionally, during the first year of follow-up, we will monitor
depressive and suicidal symptoms, possible withdrawal symptoms and medication
adherence regularly with quick online assessments in-between the regular
face-to-face and online assessments (at 3.5, 10.5, 31.5 and 38.5 weeks). In
those patients who indicate (very) severe depressive symptoms (IDS>25) at an
assessment, either a face-to-face or a phone psychiatric interview (MINI-MDD)
will follow to assess presence of DSM-5 MDD diagnosis. In those patients who
indicate suicidal ideation at an assessment, a (phone) interview (MINI-MDD and
C-SSRS Screener Suicide behaviour section) will follow to determine the
presence of suicidal behaviour. Both these assessments will also allow for
overall safety checks on general health of subjects.
We do not expect an increased risk of participation in the study compared to
treatment in routine clinical practice. Discontinuation of antidepressant after
stable depression remission is already indicated in current treatment
guidelines and will be conducted in line with these guidelines. Antidepressant
discontinuation can cause withdrawal symptoms and increases the risk of
relapse. However, during this study, these risks are not increased compared to
discontinuation of antidepressants in routine daily clinical practice.
Van der Boechorststraat 7
Amsterdam 1081 BT
NL
Van der Boechorststraat 7
Amsterdam 1081 BT
NL
Listed location countries
Age
Inclusion criteria
• Having a stable depression remission as evidenced by reporting an IDS score
<=21 (i.e. no moderate or severe depressive symptoms) during two consecutive
bimonthly assessments and a confirmed absence of a DSM-5 diagnosis of MDD
during 6 months, as observed in the OPERA-MONITOR study.
• Use of sertraline (50, 100, 150 or 200 mg/day) or citalopram (10, 20, 30 or
40 mg/day).
• Willing to be randomized and provide written informed consent.
Exclusion criteria
• Earlier inpatient admission for depression.
• History of >3 prior episodes for which treatment was started.
• Overall treatment period with antidepressant for the last depressive episode
did last more than 18 months (chronic patients are excluded: in this
difficult-to-treat group continuation of antidepressants is recommended as
a-priori relapse risk is known to be high).
• Presence of other clinically overt primary psychiatric conditions that
warrant different medical attention (earlier confirmed psychosis, schizophrenia
or bipolar depression for which medical care has been provided, or alcohol or
drug addiction which is currently treated).
• Insufficient mastery of Dutch language.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-001518-40-NL |
| CCMO | NL70053.029.19 |