Sustaining Remission of Psychotic Depression
Condition: Psychotic Depression
MeSH terms: Depression; Depressive Disorder; Mental Disorders; Psychotic Disorders; Bipolar Disorder; Depressive Disorder, Major
Intervention: Sertraline + Olanzapine; Sertraline + Placebo
Intervention description: Olanzapine 15mg/day. Adjustment of dose to 5mg/day to a maximum of 20mg/day will be permitted if necessitated by significant side-effects or clinical worsening; Taper from current dose of olanzapine to placebo over 4 weeks. Continue placebo for remainder of 36 week study.
Intervention MeSH terms: Olanzapine; Sertraline
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 269.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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)