Intervention: Diazoxide
Trial phase: Phase 1 | Phase 2
ATC code: C02DA01 | G01AE10 | V03AH01
SMILES: CC1=NS(=O)(=O)c2cc(Cl)ccc2N1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 6
Group description: Subjects received 200-400 mg daily of diazoxide orally for three weeks; the dose was adjusted depending on side effects and response.
Eligibility criteria:
INCLUSION CRITERIA:

18 to 65 years of age.
Women of child bearing potential must have a negative serum pregnancy test and confirmed (by the investigator) use of two effective methods of contraception (see below).
Each subject must be capable of understanding all required tests and examinations and must sign an informed consent document.
Subjects must fulfill DSM-IV criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Subjects must be experiencing a current major depressive episode of at least four weeks duration.
Subjects must have an initial score of at least 20 on the MADRS at screening and at baseline of study Phase I.
Subjects must have a current or past history of lack of response to two adequate antidepressant trials (may be from the same chemical class) operationally defined using the modified-Antidepressant Treatment History Form (ATHF).

EXCLUSION CRITERIA:

Current psychotic features or a current or past diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV.
Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for caffeine or nicotine dependence) within the preceding three months.
Head injury that results in loss of consciousness exceeding five minutes (for the imaging component of the study).
Subjects with a DSM IV Axis II diagnosis of borderline or antisocial personality disorder.
Pregnant or nursing women or women of child bearing potential not using two medically accepted means of contraception (including oral, injectable, or implant birth control, condoms, a diaphragm with spermicide; intrauterine devices (IUD); tubal ligation; abstinence; or partner with vasectomy).
Serious, unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
Subjects with hyperthyroidism or clinical hypothyroidism.
Subjects with one or more seizures without a clear and resolved etiology.
Clinically significant abnormal laboratory tests (including blood glucose).
Diabetes
Fasting plasma glucose concentration >120 mg/dl
Upright diastolic blood pressure <60mmHg on three occasions 30 minutes apart (based on scheduled research measurements).
Treatment with a reversible MAOI within four weeks of study Phase II.
Treatment with fluoxetine within five weeks of study Phase II.
Treatment with any other disallowed concomitant medication 14 days before randomization.
Treatment with clozapine or ECT within one month of randomization.
Lifetime history of deep brain stimulation.
Subjects who, in the investigator's judgment, pose a current serious suicidal or homicidal risk.
Positive HIV test
Contraindications to MRI (metal in body, claustrophobia, etc)

No structured psychotherapy will be permitted during the study.

Definition of treatment-resistance

All subjects are required to have previously failed to respond to two adequate antidepressant trials (may be from the same chemical class). Adequacy of antidepressant trials will be determined via the clinician administered modified ATHF.