Ensayos clínicos

Inclusion Criteria:

• Male or female, between 18 and 65 years of age.
• Structured Clinical Interview for DSM-IV-TR confirmation of a major depressive episode disorder without psychotic features.
• Index episode greater than 1 month, but no more than 2 years.
• Moderate symptom severity score as quantified by PHQ-9 total score  >15, a score ≥ 4 on the Clinical Global Impression Illness Severity Scale (CGI-S) and a score ≥ 20 on the Montgomery Åsberg Depression Rating Scale (MADRS) at screening and at baseline (just prior to first acute phase ketamine infusion).
• Current episode is treated with an FDA approved antidepressant with or without augmentation (FDA approved atypical antipsychotic, second antidepressant, stimulant, non-lithium mood stabilizer, thyroid hormone).
• Bipolar type I or type II patients must be on an anti-manic mood stabilizer (antipsychotic or valproate at therapeutic dose).
• Treatment must remain at stable dose for the acute phase.
• Utilizing the Antidepressant Treatment History Form (ATHF), treatment resistance, not intolerance, of at least 1 treatment in index episode and a 2nd lifetime treatment quantified as a score of 3 on the ATHF with a confidence rating of 3 (moderate).
• Negative drug urine screen except for allowable drugs that they have been prescribed such as benzodiazepines.
• Negative pregnancy test.
• For women of child bearing years, practicing 2 forms of birth control.

Exclusion Criteria:

• Inability to provide written informed consent and pass (80%) 10-item comprehension assessment related to study goals, risks, and benefits.
• Structured Clinical Interview for DSM-IV TR confirmation of schizophrenia, schizoaffective disorder, or presence of psychotic symptoms.
• Structured Clinical Interview for DSM-IV TR confirmation of any anxiety disorder, OCD, and attention deficit disorder, or clinical diagnosis of personality disorder, that upon review by the study psychiatrist, of all available information (SCID, electronic health record), is the primary diagnosis for seeking treatment.
• Clinically significant signs of suicidality from any of the following assessments:
  • Response ≥ 2 on QIDS-C question #12;
  • Yes response on Columbia Suicide Severity Scale (CSSR) Question #3 (ideation without plan or intent) ,Question #4 (ideation with intent, but no plan), or Question # 5 (ideation, intent, and plan);
  • Suicide attempt within the past year, as defined by the Columbia-Suicide Severity Scale
• Patients with a BMI > 40.
• Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression.
• Ongoing prescription of > 4 mg lorazepam equivalents daily, or morning dosing of any benzodiazepine.
• Current treatment with CYP3A4 inducers carbamazepine and modafinil.
• Current use of naltrexone.
• Abnormal TSH, fasting serum calcium, creatinine, or clinically significant laboratory test abnormality.
• Patients with chronic renal failure, significant renal disease.
• Any current drug and alcohol use disorder (excluding nicotine); complete (not partial) and sustained (≥1 year) remission can be randomized.
• Maintenance opiates (prescribed and illicit) within the past 12 months.
• Use of methamphetamine, cocaine, or cannabis, or abuse of stimulant(s) within the prior 12 months or lifetime history of ketamine abuse.
• Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study.
• Diagnosis of complex regional pain syndrome.
• History of recurrent urinary tract infections (> 3 lifetime).
• History of traumatic brain injury or developmental delay.
• Clinical diagnosis of delirium or encephalopathy within the prior 12 months.
• Cognitive disorder (mild and major categories).
• Prior participation in another study of ketamine for depression within the prior 3 months.
• History of poor tolerability to ketamine (any route of administration) when previously administered.
• Patients currently taking lithium and patients with a history of lithium intolerance.
• Inability to secure safe transportation after ketamine infusions (driving restricted).
• Imprisonment or involuntary psychiatric hospitalization.