Intervention: Mirtazapine
Trial phase: Phase 4
ATC code: N06AX11
SMILES: CN1CCN2c3ncccc3Cc3ccccc3C2C1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 220
Group description: Participants will take Venlafaxine XR + Mirtazapine for up to 28 weeks.
Eligibility criteria:
Inclusion Criteria:

Seeking treatment at the primary or specialty care site, and be planning to continue living in the area of that clinic for the duration of the study
Meets clinical criteria for nonpsychotic MDD, recurrent (with the current episode being at least 2 months in duration), or chronic (current episode greater than 2 years) as defined by a clinical interview and confirmed by the MINI International Neuropsychiatric Interview (MINI)
Screening 17 item HRSD score of 16 or greater
Treatment with antidepressant medication combinations is clinically acceptable
Patient with and without current suicidal ideation may be included in the study as long as outpatient treatment is clinically appropriate

Exclusion Criteria:

Pregnant or breastfeeding
Plans to become pregnant over the ensuing 8 months following study entry or are sexually active and not using adequate birth control
History (lifetime) of psychotic depression, schizophrenia, bipolar (I, II, or NOS), schizoaffective, or other Axis I psychotic disorders
Current psychotic symptom(s)
History (within the last 2 years before study entry) of anorexia or bulimia
Current primary diagnosis of obsessive compulsive disorder
Current substance dependence that requires inpatient detoxification or inpatient treatment
Requiring immediate hospitalization for a psychiatric disorder
Definite history of intolerance or allergy (lifetime) to any protocol medication
History of clear nonresponse to an adequate trial of an FDA-approved monotherapy in the current MDE if recurrent, or during the last 2 years before study entry if chronic
History of clear nonresponse to an adequate trial of any study medication used as a monotherapy, or to one or more of the protocol combinations in the current or any prior MDE
Currently taking any of the study medications at any dose
Having taken Prozac (fluoxetine) or an MAOI in the 4 weeks before study entry
Presence of an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy less than 6 months after study entry)
Currently taking medications or have GMCs that contraindicate any study medications (e.g., seizure disorder)
Requiring medications for GMCs that contraindicate any study medication
Epilepsy or other conditions requiring an anticonvulsant
Lifetime history of having a seizure including febrile or withdrawal seizures
Receiving or have received vagus nerve stimulation (VNS), electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), or other somatic antidepressant treatments
Currently taking or having taken within the 7 days before study entry any of the following exclusionary medications: antipsychotic medications, anticonvulsant medications, mood stabilizers, or central nervous system stimulants (antidepressant medication used for the treatment of depression or other purposes such as smoking cessation or pain are excluded since these agents may interfere with the testing of the major hypotheses under study)
Uncontrolled narrow angle glaucoma
Taking thyroid medication for hypothyroidism may be included only if stable on the medication for 3 months
Using agents within the 7 days before study entry that are potential augmenting agents (e.g., T3 in the absence of thyroid disease, SAMe, St. John's Wort, lithium, buspirone)
Therapy that is depression-specific