Please select the eligibility criteria that correspond to the clinical trial below.
Title: Lamotrigine as an Antidepressant Augmentation Agent in Treatment Refractory Unipolar Depression
Brief Summary: This study is intended to evaluate the efficacy and safety of lamotrigine as an antidepressant augmentation agent in a sample of individuals with major depression and a history of both prior non-response and prospective failure to respond to at least one adequate trial of an antidepressant (for a total of two failed trials).


Options:
A: Inclusion Criteria:

* DSM-IV diagnosis of single or recurrent, non-psychotic, major depressive disorder
* Currently taking a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine for major depressive disorder
* Need for "next-step" treatment based on documented suboptimal outcome from current antidepressant treatment for major depressive episode (at least 6 weeks treatment with a QIDS-C16 \>= 16 or at least 8 weeks with a QIDS-C16 \>= 11; and at least 3 weeks at a stable "optimal" dose
* Age: 18 years of age or older

Exclusion Criteria:

* Prior inadequate response after an adequate treatment trial or clear cut intolerance to either of the study medications (aripiprazole or bupropion)
* Current treatment with bupropion, aripiprazole or any other antipsychotic agent
* Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis not otherwise specified
* Current diagnosis of Dementia
* Current diagnosis of an eating disorder or a seizure disorder
* High suicide risk currently requiring acute intervention (other than outpatient treatment of depression)
* Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care
* Requiring immediate hospitalization for psychiatric disorders
* Physiologic substance dependence requiring detoxification (excluding nicotine) in the past 30 days (substance abuse is not an exclusion criteria)
* Taking any concomitant medication that contraindicates any of treatment options or augmenting agents known to have an antidepressant effect
* Concurrent or recent participation (within the last 30 days) in another conflicting clinical trial with a mental health, investigational drug, or medical device intervention
* Female - pregnant or lactating or planning to become pregnant
* Patient was not able or willing to provide informed consent; or changed mind about participating prior to randomization
* Patient was not referred to the study
B: Inclusion Criteria:

1. Male or female subjects, age 18-65
2. A current primary diagnosis of unipolar major depression based on certain criteria
3. Have a score of \> 18 on the 17-item Hamilton Depression scale
4. A history of prior failure of at least one adequate trial of an FDA-approved antidepressant. The antidepressant failure must have occurred within the current episode of major depression
5. Females of childbearing potential will be allowed as long as they are taking adequate contraceptive precautions

Exclusion Criteria:

1. A primary Axis I diagnosis other than primary unipolar major depression
2. A history suggestive of hypomania or mania during the current episode or during the person's lifetime
3. A history of psychosis, dementia, organic affective disorders or alcohol and/or substance abuse in the previous six months

   * Individuals with a current or past diagnosis of schizoid, schizotypal, borderline or antisocial or any other current or past severe personality disorder
   * Individuals with a current or past diagnosis of schizophrenia or schizoaffective disorder
4. A history of failure to respond to electroconvulsive therapy during the current or any prior lifetime episode of major depression
5. A history of failure of a prior adequate trial of paroxetine or paroxetine-CR for the treatment of Major Depression
6. Significant, coexisting medical conditions that might make it unsafe to take either of the study medications, or in which any average reasonable clinician would assume that the medical condition may, in fact, be exacerbating the current episode of depression or impede the person's ability to recover fully from their depressive illness
7. Presence of significant medical abnormalities on baseline laboratory values or physical examination, including vital signs

   * Individuals with any significant abnormalities of thyroid function
   * Subjects on thyroid supplementation must have been on a stable dose for six months prior to the screening visit
8. Individuals who will require concomitant psychotropic medications, including benzodiazepines

   * Subjects with severe insomnia will be allowed to take a maximum of 10 mg of zolpidem on two nights weekly at the investigator's discretion.
   * Zolpidem may not be taken on the night before the study visit.
   * Each dose of zolpidem should be listed on the concurrent medication case report form
9. Medications likely to cause significant effects on mood and anxiety are also excluded
10. Individuals with a positive urine drug screen for drugs of abuse at the screening visit
11. Use during the time of the study of any medications known to affect the metabolism of lamotrigine

    * Individuals on valproate and carbamazepine will be specifically excluded
    * Investigators should be aware that oral contraceptives have been reported to lower the levels of lamotrigine, but any change in dosing is left to the judgment of the investigator
12. Subjects who have taken other psychoactive drugs within certain time frames of the screening visit
13. The presence of significant risk of suicide
14. Pregnant females or those who are breastfeeding infants
15. A history of hypersensitivity or intolerance to either of the study medications, lamotrigine or paroxetine or paroxetine-CR
16. Subjects initiating or terminating psychotherapy within 12 weeks of the screening visit
17. Individuals who are currently on disability for a psychiatric disorder, or who are in any other way likely to experience considerable secondary gain from the persistence of their psychiatric illness, such as pending legal litigation of any type
18. Individuals who in the opinion of the investigator would not be able to understand or comply with the study requirements
C: Inclusion Criteria:

1. Age 18-65 years inclusive
2. DSM-IV Diagnosis of major depressive disorder
3. If female, nonpregnant/nonlactating
4. If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation)
5. Inadequate response to antidepressants: having a score of ≥14 on the 17-item HAMD or a CGI-S score of ≥ 3 after a retrospective confirmation of an adequate trial of a single antidepressant (defined as an 6-week trial of acceptable therapeutic dose \[40 mg of fluoxetine, paroxetine 30 mg of citalopram, 20 mg of escitalopram, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100 mg of fluvoxamine, 225 mg of venlafaxine XR)
6. Lack of tolerability of antidepressants: Patient reports of side effects that are judged to be clinically meaningful by the investigator
7. HAMD item 2 score ≥ 2 at screening
8. Duration of current MDD ≥ 4 weeks and \< 24 months

Exclusion Criteria:

1. Any Axis I disorder within previous six months of screening except Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder and Simple Phobias
2. MDD with postpartum onset, psychotic features or seasonal features
3. DSM-IV substance abuse or dependence in the previous 6 months
4. Medically unstable as judged by study investigators on clinical and/or laboratory findings
5. Lack of capacity to provide informed, written, consent to investigators
6. Previous intolerance to vilazodone or current use of vilazodone at screening or within 3 months of study entry
7. Significant suicide risk as judged by the investigator based on information collected on the Columbia Suicide Severity Rating Scale (CSSRS)
8. History of augmentation with atypical antipsychotics, lithium, T3 or another antidepressant within 3 months of screening
9. Failure of ≥ 3 adequate trials of different antidepressants for the current episode of MDD
10. Concomitant medications: All medications for pre existing medical conditions will be permitted to continue unchanged provided subjects are on a stable dose of at least 12 weeks. Subjects on concomitant mood stabilizers or atypical antipsychotics will require a 2-week washout prior to screening visit. Subjects on a minimum of 3 month of stable dose of hypnotics (e.g. zolpidem 10 mg per day or benzodiazepine dose of ≤ 2 mg per day of lorazepam or trazodone ≤ 100 mg per day or quetiapine ≤ 100 mg per day) will be allowed to continue their hypnotic medication at the same dose. Quetiapine at doses ≤ 100 mg per day is appropriate only for hypnotic effects. Over the counter medications will be permitted if in the opinion of the investigator, they are not considered to have any significant impact on the study. Any medication that has the potential to cause a clinical significant drug interaction with vilazodone in the judgment of the investigator will require a washout.
D: - Outpatients aged 18 to 75 years old with nonpsychotic major depressive disorder (HAMD score 14 or greater)

Answer: B