Adjunctive Vortioxetine in Schizophrenia

This is a 16-week, randomized, double-blind, parallel group, placebo-controlled study
comparing adjunctive vortioxetine with identically appearing adjunctive placebo pills in 88
stable patients with a research diagnosis of schizophrenia determined with the Structured
Clinical Interview for DSM (SCID). Patient randomization will be stratified by illness
duration (i.e., 5 years) in order to allow for post-hoc analyses examining
whether earlier illness moderates greater negative and /or cognitive symptom reduction in
response to vortioxetine.

Patients with clinical stability for at least 3 months and stable antipsychotic and
psychotropic medication treatment for at least the last 4 weeks and without relevant
depression, positive psychotic symptoms or extrapyramidal symptoms EPS will be eligible.
After written informed consent, patients will undergo a screening visit to confirm full study
eligibility. If all in- and exclusion criteria are fulfilled, patients will undergo a
baseline assessment and then be randomized 1:1 to 16 weeks of adjunctive treatment with
vortioxetine or placebo. Subsequently, patients will be seen at week 1, 2, 4 and monthly for
the next 3 months.

Inclusion Criteria:

1. Outpatient

2. SCID diagnosis of schizophrenia

3. Age 18-65 years old

4. Treated with an adequate dose of one or a maximum of two antipsychotic medications for
at least 3 months, with a stable dose for at least the last 4 weeks, and willing to
continue for up to 16 weeks.

5. No antidepressant treatment for at least 8 weeks prior to randomization.

6. Treatment with other concomitant, non-antipsychotic, psychiatric medications is
allowed, but must be unchanged for at least 8 weeks, with a stable dose for at least
the last 4 weeks, and willing to continue for 16 weeks. Benzodiazepines must not be
given within 8 hours of the cognitive assessment. Treatment with non-psychiatric
medications is unrestricted.

7. PANSS Negative subscore >14 with at least two of the items at a level >/=4 (moderate)

8. PANSS Positive subscore /=4
(moderate)

9. HAMD-17 total score
10. Simpson Angus Score of any item <3

11. English-speaking

12. Competent and willing to sign informed consent

Exclusion Criteria:

1. Structural brain disease

2. Mental retardation by history and estimated IQ <70 (WRAT-III Word Reading)

3. Autism-spectrum disorder diagnosis by history

4. Any serious chronic medical illnesses that in the view of the investigator will
interfere with the patient's ability to comply with the study procedures or that will
interfere with cognition.

5. Active substance abuse or dependence in the past 8 weeks

6. Intolerance to or inefficacy of vortioxetine in the past

7. Acute anger to self or others as per investigator assessment

8. Pregnant or breastfeeding females

9. Unwilling or unable to be sexually abstinent or not using an effective form of birth
control if they are sexually active

10. Current treatment with a Monoamine Oxidase Inhibitor (MAOI)