Whole Body Hyperthermia and Major Depression (MDD)

Inclusion Criteria:

1. Male or female outpatients aged 18-65.
2. Able to understand the nature of the study and able to provide written informed consent prior to conduct of any study procedures.
3. Currently meets DSM-IV-TR diagnosis of Major Depressive Disorder, single or recurrent episode, without psychotic features, as the subject's primary psychiatric disorder.
4. In the investigator's opinion, has met DSM-IV-TR criteria for Major Depressive Disorder for at least 4 weeks prior to signing consent.
5. Able to communicate in English with study personnel.
6. Has a Hamilton Depression Rating Scale (HDRS)-17 score ≥18 at both the screening and baseline visits.
7. For women of child-bearing potential (i.e., one who is biologically capable of becoming pregnant), must be willing to use a medically acceptable form of birth control or practice abstinence for the duration of her participation in the trial.
8. Women will be selected on the basis of a history of regular menstrual cycle ranging in length from 25-32 days with a maximum of three days variation month-to-month. Menstrual phase will be determined by self-report. Study intervention (WBH or sham-WBH) will be delivered during follicular phase of the menstrual cycle.

Exclusion Criteria for MDD patients:

1. Symptoms of depression which, in the investigator's opinion, are better accounted for by a diagnosis other than Major Depressive Disorder.

2. Any of the following diagnoses, as identified by the psychiatric evaluation or study assessments:

   • A current DSM-IV-TR Axis I diagnosis of Dementia; or
   • Antisocial or Borderline Personality Disorder or other current DSM-IV-TR Axis II diagnosis that would suggest potential noncompliance with the protocol; or
   • A lifetime history of Schizophrenia, Schizoaffective Disorder, or a Bipolar Disorder Type 1; or
   • A current (or within 12 months prior to the Screening visit) diagnosis of Posttraumatic stress disorder, Obsessive Compulsive Disorder, claustrophobia that would impair ability to be in the Heckel HT3000 hyperthermia device, or Panic Disorder
   • A current (or within 12 months prior to the Screening visit) diagnosis of Anorexia Nervosa or Bulimia Nervosa; or
3. Subject has met DSM-IV criteria for Substance Abuse in the 3 months prior to screening visit, or non-remitted Substance Dependence in the 6 months prior to screening visit.
4. A diagnosis of an anxiety disorder that is considered by the investigator to be of greater source of distress or functional impairment than the patient's depressive symptoms. Subjects with comorbid anxiety disorders not excluded above and considered to be of secondary importance will be permitted in the study.
5. Previously failed to respond in the current depressive episode to treatment with 2 or more prior antidepressant medication trials of at least 6 weeks' duration (as identified by treatment records).
6. Participation in concurrent formal cognitive-behavioral therapy, interpersonal therapy or behavior marital therapy. Continuing participation in non-specific supportive therapy that was started at least 6 weeks prior to the screening visit will be permitted.
7. Initiation of any form of psychotherapy during the trial, or in the 6 weeks prior to the screening visit.
8. Individuals with a history of having difficulty swallowing food or large capsules will be excluded. The ingestible temperature capsules will not be used in subjects with any known or suspected obstructive disease of the gastrointestinal tract including, but not limited to esophageal stricture, diverticulosis and inflammatory bowel disease (IBD), peptic ulcer disease, Crohn's disease, ulcerative colitis; previous gastrointestinal surgery Also, those subjects suffering from alcoholism, diabetes mellitus, and uncontrolled hypertension will be excluded.

9. Subject has a medical condition or disorder that:

   • Is unstable and clinically significant, or:

   • Could interfere with the accurate assessment of safety or efficacy of treatment, including:

     1. individuals who are using prescription drugs that may impair thermoregulatory cooling, including diuretics, barbiturates, and beta-blockers, or antihistamines,
     2. individuals with cardiovascular conditions or problems (hypertension, hypotension, congestive heart failure, or impaired coronary circulation) or those who are taking medications that might affect blood pressure,
     3. individuals with chronic conditions/diseases associated with a reduced ability initiate thermoregulatory cooling, including Parkinson's, multiple sclerosis, central nervous system tumors, and diabetes with neuropathy,
     4. hemophiliacs/individuals prone to bleeding,
     5. individuals with a fever,
     6. individuals with hypersensitivity to heat,
     7. individuals with recent acute joint injury,
     8. individuals with enclosed infections, be they dental, in joints, or in any other tissues,
     9. individuals with silicone implants; silicone does absorb far infrared energy. Implanted silicone or silicone prostheses for nose or ear replacement may be warmed by the far infrared waves. Since silicone melts at over 200°C (392°F), it should not be adversely affected by the usage of an infrared heating. Nevertheless, the effects of infrared heating on all silicone composites used in implants are not known, and therefore individuals with silicone implants will be excluded from this study.
     10. Clinically significant abnormal findings on screening laboratory tests or physical exam.

11. Presence of clinically significant suicide risk, based on the investigator's opinion, or a Columbia Suicide Severity Risk Scale (C-SSRS) suicidal ideation score of 4 or 5. Any suicide attempt within 3 months of the Screening visit is exclusionary.

12. Use of any psychotropic medications for 4 weeks (8 weeks for fluoxetine) prior to initiation of the study, with the exception of hypnotic medications (zolpidem, zaleplon, eszopiclone or diphenhydramine).

13. Need for any non-protocol psychotropic medication during the trial, with the exception of hypnotics used up to four nights per week.

14. Use of any psychoactive dietary or herbal products in the 2 weeks prior to screening visit 2, or at any time during the trial.

15. Subject has received vagus nerve stimulation, electroconvulsive therapy, or transcranial magnetic stimulation within the six months prior to the screening visit.

16. Women who are pregnant (HCG pregnancy test at screening, lactating, <1 year post-partum or who plan to become pregnant during the study.

17. Current participation in any clinical trial that might impact results of this one, which includes participation in another clinical trial for depression, as well as drug trials with agents that might affect mood or regulation of body temperature.

18. Reasonable likelihood for non-compliance with the protocol or any other reason, in the opinion of the Investigator, prohibits enrollment of subject into the study.

19. Obesity and overall size of subject. It will be up to the PI's discretion will consider BMI, waist circumference, and body fat composition when determining eligibility and safety of the individual.