Sustaining Remission of Psychotic Depression
Sustaining Remission of Psychotic Depression
The acute phase of this study will monitor the response to a combination of an atypical
 antipsychotic medication olanzapine with an antidepressant medication sertraline in the acute
 treatment of the disorder. It is predicted that this combination will improve symptoms of
 psychotic depression and be associated metabolic side effects. Factors that moderate
 tolerability will be monitored. Improvement in symptoms could take between 4 and 12 weeks,
 followed by a period of 8 weeks during which participants will continue to take the same
 medications to stabilize the remission from symptoms of psychotic depression.

 The maintenance phase will be a randomized, double-blind, placebo-controlled study of
 olanzapine for a period of up to 36 weeks to test whether continuing this combination
 decreases the risk of relapse and whether discontinuing the combination leads to improvement
 in metabolic measures. Subjects who complete the acute phase will be asked to consent
 separately to the randomized maintenance phase.
The original STOP-PD study established that the combination of olanzapine and sertraline was
 significantly better than olanzapine alone in achieving remission of psychotic depression.
 This STOP-PD-II Sustaining Remission study aims to assess the long-term tolerability of
 taking this combination of medications and their efficacy at preventing a relapse of the
 symptoms. The acute phase of the study will monitor the efficacy and tolerability of the
 olanzapine and sertraline combination, including investigation of weight and metabolic
 variables, age effects on treatment response and tolerability, and the association of genetic
 polymorphisms to response or relapse. When subjects are stabilized on these medications for a
 period of 8 weeks they will be invited to participate in the randomized phase of the
 research: the olanzapine will be placebo-controlled, meaning half of the subjects will
 continue to take the olanzapine/sertraline combination and half will take a
 sertraline/placebo combination, for a period of 36 weeks. Symptoms and side effects will be
 monitored regularly throughout this phase. Randomization will be stratified on a 1:1 basis by
 age 60 and above.
Inclusion Criteria:

 1. Aged 18-85 years, inclusive

 2. Diagnosis: Diagnostic Statistical Manual-IV Trade Revision (DSM IV-TR) non-bipolar
 major depression with psychotic features established by both clinical interview with
 research psychiatrist and administration of SCID-IV.

 3. Score >2 on Schedule for Affective Disorders (SADS) delusion severity item

 4. Score >1 on any of the three conviction items of the Delusion Assessment Scale (DAS)
 (does not alter belief in response to reality testing)

 5. 17-item HAM-D score of >20

 Exclusion Criteria:

 1. Current or lifetime DSM-IV-TR history of schizophrenia or other psychotic disorders or
 meeting current criteria for brief psychotic disorder, body dysmorphic disorder or
 obsessive-compulsive disorder

 2. Current or lifetime DSM-IV-TR bipolar affective disorder

 3. History of DSM-IV-TR defined alcohol or substance abuse or dependence within the past
 three months

 4. Dementia or clinically significant cognitive impairment prior to index episode of
 depression, and/or a mean score >3 on 26-item caregiver assessment

 5. Type 1 diabetes mellitus (defined as insulin-dependent diabetes mellitus with onset
 before age 35, and/or diabetes mellitus complicated by prior documented episode of
 ketoacidosis

 6. Acute or unstable medical illness within the past 3 months; current abnormal serum
 free T4; current abnormally low vitamin B4 or folic acid level; medical conditions
 and/or medications for which psychotic or depressive symptoms can be a direct
 manifestation; neurological disease associated with extrapyramidal signs and symptoms;
 epilepsy, if the person has had one or more grand mal seizures within the past 12
 months.

 7. The need for treatment with any psychotropic medication other than sertraline,
 olanzapine or lorazepam; or with an anticonvulsant medication with mood-stabilizing
 properties.

 8. Current pregnancy or plan to become pregnant during the course of the study; breast
 feeding in women with infants.

 9. A documented history of being unable to tolerate olanzapine or sertraline including
 significant bradycardia (heart rate of <50 bpm), and serum sodium level of 129mmol/L
 or below.

 10. History of non-response of the index episode of psychotic depression to at least a
 6-week trial of at least 150mg/day sertraline combined with 15mg/day olanzapine

 11. Patients showing ongoing improvement in current episode of psychotic depression with
 treatment other than sertraline or olanzapine

 12. Patients who are in immediate need of electroconvulsive therapy (ECT) (imminent risk
 of suicide, refusing to eat, catatonic)