Challenges in the Acute and Maintenance Treatment of Psychotic Depression

How long patients with major depression with psychotic features successfully treated with an antidepressant and an antipsychotic need to stay on the antipsychotic is not known, said Anthony Rothschild, M.D., at APA’s 2014 annual meeting today during the symposium, “The NIMH Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II): Background and Early Results From the Sustaining Remission Trial.”

Rothschild, editor of the Clinical Manual for Diagnosis and Treatment of Psychotic Depression, is the Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry at the University of Massachusetts Medical School.

Rothschild said that major depression with psychotic features (psychotic depression) is a severe disorder associated with considerable morbidity and mortality. Although ECT has well-established efficacy as a treatment for psychotic depression, its use is limited by several factors: a high rate of relapse following completion of ECT, lower rates of response in nonacademic centers, significant disparities in its availability, and the fact that many patients prefer pharmacologic treatment because they find the concept of ECT and the potential side effects of cognitive impairment unacceptable.

Because of these limitations, the pharmacologic treatment of psychotic depression is common. APA’s practice guideline for the treatment of depression and other expert guidelines recommend the combination of antidepressant and antipsychotic medications as an alternative to ECT in the treatment of psychotic depression.

The recently completed NIMH Study of the Pharmacotherapy of Psychotic Depression (STOP-PD), which involved collaboration of the speakers at today’s symposium (Drs. Alastair Flint, Barnet Meyers, Benoit Mulsant, Rothschild, and Ellen Whyte), was the first NIMH-funded, randomized, controlled trial to examine the efficacy and tolerability of combination therapy using newer antidepressant and antipsychotic medications in the acute treatment of psychotic depression. The combination of sertraline and olanzapine was significantly more efficacious than olanzapine monotherapy, and the two treatments had comparable tolerability.

Rothschild said that determining the optimal continuation and maintenance therapy for individuals with psychotic depression is of special concern due to the high rate of relapse observed in naturalistic follow-up studies of psychotic depression, including relapse after ECT. Other concerns include a relapsing or chronic course, high mortality rates, a high risk of extrapyramidal symptoms and tardive dyskinesia with first-generation antipsychotics, risk of metabolic syndrome with atypical antipsychotics, an increased use of health care services, and a high rate of disability.

Rothschild said, however, that it is not known whether the antipsychotic medication needs to be continued once an episode of psychotic depression has responded to combined antidepressant-antipsychotic treatment. On one hand, premature discontinuation of antipsychotic medication has the potential risk of relapse of a severe, disabling disorder. On the other hand, the unnecessary continuation of antipsychotic medication exposes a patient to potential adverse effects. An NIMH study to address the question of how long a patient with psychotic depression who is in remission needs to stay on the antipsychotic medication is under way at Weill Medical College of Cornell University, the University of Pittsburgh School of Medicine, the University of Massachusetts Medical School, and the University of Toronto Department of Psychiatry; preliminary data from this NIMH study were presented at the symposium.

In addition to the Clinical Manual for Diagnosis and Treatment of Psychotic Depression, Rothschild is editor of The Evidence-Based Guide to Antidepressant Medications and The Evidence-Based Guide to Antipsychotic Medications. APA members may purchase these books at a discount by clicking on the titles.