['depression']
['naltrexone']

        Inclusion Criteria:

        A subject will be eligible for inclusion only if all of the following criteria are met:

          1. Male or female, 18 to 70 years of age, inclusive, at screening.

          2. Able to read, understand, and provide written, dated informed consent prior to
             screening. Participants will be deemed likely to comply with study protocol and
             communicate with study personnel about adverse events and other clinically important
             information.

          3. Diagnosed with Major Depressive Disorder (MDD), single or recurrent, and currently
             experiencing a Major Depressive Episode (MDE) of at least eight weeks in duration,
             prior to screening, according to the criteria defined in the Diagnosis and Statistical
             Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR™). The diagnosis
             of MDD will be made by a site psychiatrist and supported by the Structured Clinical
             Interview for DSM-IV-TR™ (SCID-I/P) or the M.I.N.I International Neuropsychiatric
             Interview a short, structured psychiatric interview.

          4. Has a history of TRD during the current MDE, as assessed by the investigator. TRD is
             defined as failure to achieve a satisfactory response (e.g., less than 50% improvement
             of depression symptoms), as perceived by the participant, to at least two "treatment
             courses" of a therapeutic dose of an antidepressant therapy of at least 8 weeks
             duration. The adequacy of dose and duration of the antidepressant therapy will be
             determined as per the Massachusetts General Hospital Antidepressant Treatment Response
             Questionnaire (MGH ATRQ) criteria. Participants must currently be on a stable (for at
             least 4 weeks) and adequate (according to the MGH ATRQ) dose of ongoing Selective
             serotonin reuptake inhibitor (SSRI) or Serotonin-norepinephrine reuptake inhibitor
             (SNRI) antidepressant therapy, of which total duration must be at least 8 weeks.
             Participants may also have a history of intolerance to at least 2 antidepressant
             medications. These patients with the intolerance history will not be required to be
             currently taking an antidepressant medication.

          5. Meet the threshold on the total Hamilton Depression 17-item Scale (HAMD17) score of
             >/=20 at both screening and baseline visits (Day -5/-14 and Day 0).

          6. In good general health, as ascertained by medical history, physical examination (PE)
             (including measurement of supine and standing vital signs), clinical laboratory
             evaluations, and 12-lead electrocardiogram (ECG).

          7. If female, a status of non-childbearing potential or use of an acceptable form of
             birth control per the following specific criteria:

               1. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant,
                  i.e., permanently sterilized (status post hysterectomy, bilateral tubal
                  ligation), or is post-menopausal with her last menses at least one year prior to
                  screening); or

               2. Childbearing potential, and meets the following criteria:

             i. Childbearing potential, including women using any form of hormonal birth control,
             on hormone replacement therapy started prior to 12 months of amenorrhea, using an
             intrauterine device (IUD), having a monogamous relationship with a partner who has had
             a vasectomy, or is sexually abstinent.

             ii.Negative urinary pregnancy test at screening, confirmed by a negative urinary
             pregnancy test at randomization prior to receiving study treatment.

             iii.Willing and able to continuously use one of the following methods of birth control
             during the course of the study, defined as those which result in a low failure rate
             (i.e., less than 1% per year) when used consistently and correctly: implants,
             injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier
             contraception, sexual abstinence. The form of birth control will be documented at
             screening and baseline.

          8. Body mass index between 18-35kg/m2.

          9. Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive
             behavioral, insight-oriented, et al) and frequency (e.g., weekly or monthly) of the
             therapy has been stable for at least three months prior to screening and if the type
             and frequency of the therapy is expected to remain stable during the course of the
             subject's participation in the study.

         10. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone)
             will be allowed if the therapy has been stable for at least 4 weeks prior to screening
             and if it is expected to remain stable during the course of the subject's
             participation in the study.

        Exclusion Criteria:

        A potential participant will NOT be eligible for participation in this study if any of the
        following criteria are met:

          1. Female of childbearing potential who is not willing to use one of the specified forms
             of birth control during the study.

          2. Female that is pregnant or breastfeeding.

          3. Female with a positive pregnancy test at screening or baseline.

          4. Total HAMD score of <20 at the screen or baseline visits.

        6. Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by
        DSM-IV-TR™), with the exception of nicotine dependence, at screening or within six months
        prior to screening.

        7. Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety
        Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless
        one of these is comorbid and clinically unstable, and/or the focus of the participant's
        treatment for the past six months or more).

        8. History of schizophrenia or schizoaffective disorders, or any history of psychotic
        symptoms in the current or previous depressive episodes.

        9. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise
        specified, within five years of screening.

        10. Any Axis I or Axis II Disorder, which at screening is clinically predominant to their
        MDD or has been predominant to their MDD at any time within six months prior to screening.

        11. Considered at significant risk for suicide during the course of the study according to
        any of the following criteria:

        12. In the judgment of the investigator, the subject is at significant risk for suicidal
        behavior during the course of his/her participation in the study.

        13. Has dementia, delirium, amnestic, or any other cognitive disorder.

        14. Has a clinically significant abnormality on the screening physical examination that
        might affect safety, study participation, or confound interpretation of study results.

        15. Participation in any clinical trial with an investigational drug or device within the
        past month or concurrent to study participation.

        16. Known history or current episode of:

        a. QTcF (a measure of the time between the start of the Q wave and the end of the T wave in
        the heart's electrical cycle-Fridericia-corrected) ≥450 msec at screening (Visit 1) or
        randomization b. Syncopal event within the past year. c. Congestive heart failure (CHF) New
        York Heart Association Criteria >Stage 2 d. Angina pectoris e. Heart rate <50 or >105 beats
        per minute at screening or randomization

        17. Chronic lung disease.

        18. Lifetime history of surgical procedures involving the brain or meninges, encephalitis,
        meningitis, degenerative central nervous system disorder (e.g., Alzheimer's or Parkinson's
        Disease), epilepsy, mental retardation, or any other
        disease/procedure/accident/intervention associated with significant injury to or
        malfunction of the central nervous system (CNS), or a history of significant head trauma
        within the past two years.

        19. Presents with any of the following lab abnormalities w/in the past 6 months:

          1. Thyroid stimulating hormone (TSH) outside of the normal limits and clinically
             significant as determined by the investigator. Free thyroxine (T4) levels may be
             measured if TSH level is high. Subject will be excluded if T4 level is clinically
             significant.

          2. Any other clinically significant abnormal laboratory result at the time of the
             screening exam.

             20. History of hypothyroidism and has been on a stable dosage of thyroid replacement
             medication for less than six months prior to screening.(Subjects on a stable dosage of
             thyroid replacement medication for at least six months or more prior to screening are
             eligible for enrollment.)

             21. History of hyperthyroidism which was treated (medically or surgically) less than
             six months prior to screening.

             22. Any current or past history of any physical condition which in the investigator's
             opinion might put the subject at risk or interfere with study results interpretation.

             23. History of positive screening urine test for drugs of abuse at screening: cocaine,
             amphetamines, barbiturates, opiates.

             24. Chronic use of opiates.
      