The study was terminated for business reasons and not due to safety concerns.

To assess the safety and tolerability of long-term pimavanserin treatment in subjects with major depressive disorder and inadequate response to antidepressant treatment.

Inclusion Criteria:

1. Completed the antecedent study, Study ACP-103-054 or Study ACP-103-059
2. May benefit from longer term therapy with open-label pimavanserin treatment
3. If the subject is female, she must not be pregnant or breastfeeding. She must also be of nonchildbearing potential OR must agree to use acceptable methods of contraception

Exclusion Criteria:

1. Is determined to be inappropriate for the study
2. Has developed neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or mental disorder, including cancer or malignancies that would affect the patient's ability to participate in the program

Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).

Investigator may publish the study results, relative to their own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the Sponsor for review and comment. The sponsor has 60 days to review and comment.