Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Three-phase Study Designed to Test the Efficacy, Tolerability and Safety of the Combination of Ziprasidone With Selective Serotonin Reuptake Inhibitors (SSRI) for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs.
Brief Summary: The purpose of this study is to see if adding the study drug, ziprasidone, to an antidepressant medication helps improve symptoms of Major Depressive Disorder (MDD). We are studying the drug's effectiveness in treating depression, as well as its safety when it is added to another drug.

Hypothesis A: There will be a difference in the percentage of responders in the two treatment conditions during phase 2; response rates will be higher for the ziprasidone group.


Options:
A: Inclusion Criteria:

* Male and female outpatients of at least 18 years of age, who meet criteria for Major Depressive Disorder (MDD)
* Currently non- or only partially-responsive to an SSRI antidepressant after at least 5 weeks of treatment

Exclusion Criteria include:

* Current primary Axis I disorder other than MDD
* Previous diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders
* Patients judged to be at serious suicidal risk.
* Serious medical illness
B: Inclusion Criteria:

* Male or female subjects between 18 and 65 years of age, with diagnosis of major depressive disorder, as defined by DSM-IV-TR criteria
* The current depressive episode must be equal to or greater than 8 weeks in duration
* Subjects must report a history for the current depressive episode of an inadequate response to no more than three adequate antidepressant treatments

Exclusion Criteria:

* Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug
* Subjects who report an inadequate response to more than three adequate trials of antidepressant treatments during current depressive episode at a therapeutic dose for an adequate duration
* Subjects with a current Axis I (DSM-IV-TR) diagnosis of: Delirium, dementia, amnestic or other cognitive disorder, Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder
* Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder
C: Inclusion Criteria:

* Written informed consent.
* Men or women, 18-65 years of age.
* MDD, current, according to DSM-IV criteria and as diagnosed by the SCID- I/P during the screen and baseline visit of phase 1.
* A HAM-D-17 score \> 14 during the screen and baseline visit of phase 1.

Exclusion Criteria:

* Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine
* Device, tubal ligation, or partner with vasectomy).
* Serious suicide or homicide risk, as assessed by evaluating clinician.
* Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder.
* History of multiple adverse drug reactions or allergy to the study drug.
* The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past).
* Patients requiring excluded medications (see appendix 1 for details).
* Psychotic features in the current episode or a history of psychotic features.
* Prior course of ziprasidone, or intolerance to ziprasidone at any dose.
* Any investigational psychotropic drug within the last 3 months.
* Have failed more than 3 adequate antidepressant trials during the current MDE. Some examples of adequate dosage of an antidepressant trial include either \> 150 mg of imipramine (or its tricyclic equivalent), \> 60 mg of phenelzine (or its monoamine oxidase inhibitor equivalent), \> 20 mg of fluoxetine (or its SSRI-equivalent), \> 150mg of bupropion, \> 300mg of trazodone (or nefazodone), \>75 mg of venlafaxine, \>60mg of duloxetine, or \> 15mg of mirtazapine. A trial of adequate duration was defined as one during which the patient was on any given antidepressant at an adequate dose for a minimum of 6 weeks.
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: C