Risperidone vs. Bupropion ER Augmentation of SSRIs in Treatment-Resistant Depression

Inclusion Criteria:

• Male or female 18 years or older

• DSM-IV diagnosis of major depressive disorder of at least moderate severity, butwithout psychotic features

• Ham-D 17 score of 18 or above

• Have a documentable history of 2 prior adequate trials of antidepressants including anSSRI without sufficient response. A clinically adequate trial is defined as havingtaken a minimum effective dose of an antidepressant for at least 3 weeks without asignificant change in depressive symptoms.

• Must be currently on an serotonin uptake inhibitor (to include venlafaxine orduloxetine) at an adequate dose for at least 3 weeks.

• Ability and willingness to provide consent for participation in the study.

Exclusion Criteria:

• Any medical condition that would preclude treatment with an SSRI, risperidone, orbupropion ER

• Any clinically significant unstable medical condition

• Diagnosis of bipolar disorder or a primary diagnosis of any psychotic disorder

• Current psychotic symptoms (hallucination or delusions)

• Alcohol or drug abuse or dependence in the last 3 months (excluding nicotine andcaffeine dependence/abuse) or abuse within the last month

• Documented non-response to the combination of a novel antipsychotic or bupropion ERand a SSRI

• Concomitant use of any psychotropic other than an SSRI or zolpidem (PRN for sleep)

• Score of 4 on the suicide item of the Ham-D scale and determination by theinvestigator of significant suicide risk

• Known sensitivity to risperidone or bupropion ER