Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind Study Comparing Adjunctive Risperidone Versus Placebo in Major Depressive Disorder That Is Not Responding to Standard Therapy
Brief Summary: The purpose of this trial is to evaluate the efficacy and safety of risperidone versus placebo in subjects with Major Depressive Disorder with sub-optimal response to antidepressant therapy.


Options:
A: Inclusion Criteria:

* Understand and sign the informed consent form
* Age 18-65
* Healthy on the basis of Physical Exam
* Treatment with a single antidepressant 4 weeks prior to study start and willingness to maintain on stable dose of the same antidepressant throughout the study
* Current diagnosis of Major Depressive Disorder
* Judgement of the clinician that the subject has shown a sub-optimal response to the antidepressant

Exclusion Criteria:

* Presence of other serious medical illness(es)
B: Inclusion Criteria:

* non-psychotic unipolar major depressive episode (Diagnostic and Statistical Manual, Fourth Edition \[DSM-IV\]) in the preceding month
* age 25-75
* starting treatment with sertraline clinically indicated
* tolerability to sertraline 25 mg/d ascertained
* can understand and sign informed consent form
* can be contacted by telephone for symptom severity and adverse events

Exclusion Criteria:

* have received antidepressants, mood stabilizers, antipsychotics, psychostimulants, electroconvulsive therapy (ECT) or depression-specific psychotherapies in the preceding month
* history of schizophrenia, schizoaffective disorder or bipolar disorder
* current dementia, borderline personality disorder, eating disorder or substance dependence
* physical disease interfering with sertraline or mirtazapine treatment
* allergy to sertraline or mirtazapine
* terminal physical illness
* currently pregnant or breast-feeding
* high risk of imminent suicide
* requiring compulsory admission
* expected to change doctors within 6 months
* cohabiting relatives of research staff
* cannot understand Japanese
C: Inclusion Criteria:

* Men and women, 18-65 years old
* Currently meet the DSM-IV-TR criteria for moderate to severe MDD without psychotic features.
* Previous failure to respond to adequate trials of one or two ADTs with less than 50% reduction in depressive symptoms during the present episode.

Exclusion Criteria:

* DSM-IV-TR based diagnosis of an axis I disorder, other than MDD, or any axis I disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1
D: Inclusion Criteria:

1. Age \> 60 years.
2. Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV.
3. MADRS ≥ 15.

Exclusion Criteria:

1. Inability to provide informed consent.
2. Depressive symptoms not severe enough (i.e., MADRS \< 15) at the baseline assessments.
3. Dementia based upon DSM-IV criteria as well as a Folstein MMSE score of less than 24. Patients screened out due to dementia will be referred to a memory clinic or to the UPMC Alzheimer's Disease Research Center for evaluation to clarify the presence or absence of a dementia.
4. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID. A recommendation for psychiatric referral will be made in these cases.
5. Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and confirmed by study physician interview.
6. High risk for suicide (e.g., active SI and/or current/recent intent or plan) AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.
7. Contraindication to venlafaxine XR or aripiprazole as determined by study physician including history of intolerance of either venlafaxine XR or aripiprazole in the study target dosage range (venlafaxine XR at up to 225 mg/day; aripiprazole at up to 15mg/day).
8. Failure to respond to at least 6 weeks of venlafaxine (\>225 mg/d) plus aripiprazole (\>10 mg/d).
9. Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English).
10. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)
11. Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician's and study physician clinical judgment. Referral to the patient's personal physician or to a general practitioner will be made in these cases.
12. Subjects taking psychotropic medications that cannot be safely tapered or discontinued prior to study initiation: this would include patients on Monoamine Oxidase Inhibitors (MAOI) who would need to be off the MAOI for 14 days to be eligible for the study to avoid adverse drug interactions. Patients will not be allowed to take antidepressant or atypical antipsychotic medication other than the study medication, unless it is a low dose antidepressant prescribed for chronic pain that would not be medically advisable to stop (e.g., amitryptyline 50mg). If a patient's depression is adequately treated on his/her psychotropic medication, he/she would not be eligible for the study. If a patient failed a trial of venlafaxine (12 weeks of treatment with venlafaxine including at least 6 weeks on 300mg/day), he/she would not be eligible. The following are allowed: benzodiazepines up to 2mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon, eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g., neuropathy). Except for MAOIs, there is really no clinical rationale to exclude patients on specific concomitant medications unless they are medically unstable (in which case they are excluded from participation). As noted, patients on an MAOI would need to be off the MAOI for 14 days to protect from adverse drug interactions.

Answer: A