The controversy arises on the continuation

OVERVIEW
Citation Flint, A, Meyers, B, Rothschild, A, et al. Effect of continuing olanzapine vs placebo
on relapse among patients with psychotic depression in remission: the STOP-PD II
randomized clinical trial. Jama 2019; 322(7): 622-631.
Location  Conducted at 4 medical centers which included University Health Network, Toronto;
University of Massachusetts Medical School;
University of Pittsburgh School of Medicine; and Weill Cornell
Medical College between November 2011 and June 2017.
Funding  Funded by US Public Health Service grants MH 62446, MH 62518,
MH 62565, and MH 62624 from the NIMH. Eli Lilly provided olanzapine and
matching placebo pills and Pfizer provided sertraline;
INTRODUCTION
Background  Psychotic depression is a condition that predisposes patients to high risk of disability
of suicide 1,2
 Studies have upheld the treatment of acute psychotic depression using
pharmacotherapy or electroconslusive therapy, combined with antidepressants and
antipsychotic agents 3,4
 When a patient responds to the antidepressants, he or she must continue treatment with
antidepressants to prevent depression relapse or recurrence 5.
 However, when a patient being treated for psychotic depression using
antidepressant-antipsychotic treatment, it is not clear whether the dosage
should be continued after a patint responds to the treatment
 The controversy arises on the continuation of antipsychotic medication which may
cause severe adverse effects, while the premature discontinuation and put the patient at
risk of relapse.
Previous Trials  STOP-PD: Sertraline in combination with olanzapine was more efficacious than
olanzapine plus placebo. Both treatments resulted in an increase in lipids and weight
in a 12-week study. The odd ratio was 1.28; 95% confidence interval [CI], 1.12-1.47;
P < .001. 41.9% of the participants who underwent a combination of treatments were
in remission within their last assessment compared to those who underwent
monotherapy (23.9%) 6
Potential Impact Psychotic depression is aa complex condition that may cause severe disability or a
lethal disorder. There is little evidence to show the tolerability and efficacy of
continued antipsychotic medication for patients suffering from psychotic depression in
remission. This study seeks to address the knowledge gap.
Objectives  The objective of the study is to explore the clinical effects of continuing antipsychotic
medication incase an episode of psychotic depression has shown response to a
combination of treatment of antipsychotic agent and antidepressants.
METHODS
Study Design  Randomized control trails, double blinded, placebo controlled, parallel, involving two
groups
 Blinded to the investigators and participants until the end of the study and where
possible, even after the study
Inclusion Criteria  18 years and above
 a score of 3 or higher on the delusion
severity item of the Schedule for
Affective Disorders and Schizophrenia
 a score of 2 or higher on any of the 3
conviction items of the Delusion
Assessment Scale 7
Exclusion Criteria  current or lifetime DSM-IV-TR criteria
for any other psychotic disorder, bipolar
disorder, or intellectual disability
 DSM-IV-TR criteria for current body
 DSM-IV-TR defined dementia preceding
the index episode of depression or a 26-
item informant questionnaire on
cognitive decline in the elderly

dysmorphic disorder or obsessive-
compulsive disorder
 type 1 diabetes mellitus
 neurologic disease that might affect
neuromuscular function
 unstable physical illness
(IQCODE) mean score of 4 or higher at
acute phase baseline
 DSM-IV-TR defined substance abuse or
dependence within the preceding 3
months; participants had stable chronic
physical problems.
Interventions  Patients were randomized under double-blind conditions. Which were either to
continue olanzapine or switch from olanzapine to identically appearing placebo pills
over a 4-week taper of olanzapine
 The patients were assessed weekly in both trials for the first 8 weeks, after, there were
assessed once on 4 weeks until the end of the study at 36 weeks, relapse and early
termination.
 When a participant decided to discontinue the study in either of the trials, the
investigators made efforts to ensure that the assessments were made for the entire
course if the randomized treatment or until relapse.
 Participants were randomized either to continue olanzapine (n = 64) or
switch from olanzapine to placebo (n = 62). All participants continued sertraline.
Primary Endpoint  Risk of relapse at 36 weeks
Secondary
Endpoints
 Change in weight, waist circumference, lipids, serum glucose, and hemoglobin
A1c (HbA1c).
Safety Endpoints  Adverse effects were assessed during each visit using Udvalg for Kliniske
Undersogelser scale
 adverse effect was considered present if there was a 2-point increase from RCT
baseline or a score of 3 or 4 and an increase from baseline
 Adverse weight gain was operationalized as measured weight of more than 7% higher
than premorbid weight
 adverse weight loss was operationalized as measured weight more than 7% lower than
premorbid weight
 Other adverse effects include persistent and significant disability, incapacity, suicide
attempts of hospitalization
Statistical Analyses  Cox proportional hazards model was used to compare the risk of relapse across
treatment groups
 Linear mixed models were applied to analyze the anthropometric and metabolic
measures Poison mixed effect regression with an over dispersion parameter was used
to analyze Simpson-Angus Scale scores 8
 post hoc sensitivity analyses was applied to assess the possible effect of statin or
hypoglycemic agent on linear mixed-model metabolic results
 Post hoc analyses was used to compare compare randomized groups on the number of
participants who experienced an incident high metabolic value.
RESULTS
Enrollment  See figure 1. 269 participants were enrolled in the study, 126 were randomized (64 to
sertraline-olanzapine and 62 to sertraline-placebo)
 114 (90.5%) completed the trial while 12, 10% withdrew from the study
Baseline
Characteristics
Details were demonstrated in Table 1 and table 2.
 The characteristics of participants enrolled for the study were average ages of 55.0
years for Sertraline + Olanzapine (n = 64) and 55.7 for Sertraline + Placebo (n = 62).
Men accounted for 42.2% in the combined treatment, and 33.9% in the Sertraline +
Placebo. Women were 57.8% for the Sertraline + Olanzapine and 33.9% for Sertraline
+ Placebo.