Intramuscular Ketamine Versus Aripiprazole and Escitalopram in the Treatment of Resistant Depression

Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression

The treatment of resistant depression should be optimized aiming at complete remission of symptoms, a complex condition due to several factors. Approximately 1/3 of patients with depressive disorders do not even respond to available antidepressants. Consequently, new molecules with robust action, fast effects and sustained improvement are currently being researched worldwide. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising alternative due to its involvement in neurogenesis, synaptogenesis and consequent rapid improvement of depressive and suicidal symptoms with traditional intravenous (IV) use in sub dose (0.5 mg / kg). The therapeutic response of IV use has been short and requires monitoring in a hospital setting. There are no studies evaluating response to long-term ketamine use. Recent research has focused on identifying other routes of ketamine use such as intranasal and intramuscular (IM). The use of ketamine IM, despite the fact that there are few studies and small samples, can demonstrate efficacy in acute treatment and maintenance of depression, as well as low profile of side effects, greater accessibility potential, reduced costs and risks, patient comfort and possible expansion of resistant depression treatment capabilities in different settings.

Compare the response of ketamine IM versus active control in treatment-resistant depression (TRD [primary outcome]) and find safety and tolerability of ketamine IM, evaluate changes in life quality, cognition and suicidal risk (secondary outcomes)

Inclusion Criteria:

1. Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);

2. Moderate to severe intensity of the disease;

3. Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);

   a. Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,

4. Literate and able to understand the tasks requested;

5. With clinical comorbidities, however compensated;

6. Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.

Exclusion Criteria:

1. Imminent risk of suicide;

2. Patients with psychoactive substance dependence;

3. Intellectual deficit and psychotic symptoms;

4. Bipolar spectrum disorders and other primary psychiatric diagnoses;

5. Allergic to ketamine;

6. Glaucoma;

7. Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;

8. Treatment with irreversible MAOI in two weeks prior to visit 0;

9. Fluoxetine treatment within 4 weeks prior to visit 0;

10. Treatment with others antidepressants;

11. Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;

    a. Lorazepam and zolpidem may be used;

12. Patients who become pregnant will be excluded from the study and referred for obstetric care.