Psychotic depression: the reason for treatment failure with antidepressants

By Dr. Ananya Mandal, MDDec 7 2010

A new study shows that patients with depression who also have psychotic-like symptoms, feelings of being persecuted, or believing others are plotting against them or hearing voices are less likely to respond to antidepressants. The study also showed that bipolar disorder does not appear to be associated with treatment resistance in patients with depression as believed earlier.

The study involved 4,041 patients with depression. The link between bipolar disorder and treatment outcomes was explored. Bipolar disorder makes a person suffer from mood swings that vary from depressive low phases to manic hyperactive phases. Bipolar disorders often stay hidden in apparently just depressed patients and make therapy difficult.

The patients first received the antidepressant citalopram (Celexa), followed by up to three next-step treatments, depending on their responses. At the baseline 1,198 (30 percent) of the patients said they had experienced at least one psychotic symptom, such as believing they had special powers or were being controlled or plotted against in the previous six months. These patients were significantly less likely to respond to treatment. Also 1,524 patients (38.1 percent) said they had experienced at least one symptom of bipolar disorder in the previous six months. Of those symptoms, irritability was associated with poor treatment outcomes. However a history of manic symptoms and family history of bipolar disorder did not affect therapy efficacy in patients of bipolar disorder. The study was published online Dec. 6 in the Archives of General Psychiatry.

The team was led by Dr. Roy H. Perlis, of Massachusetts General Hospital and Harvard Medical School. The authors concluded, “Considered as a whole, our results cast doubt on the frequent assertion that unrecognized bipolar disorder is widespread in clinical practice and particularly in treatment-resistant major depressive disorder…Screening for bipolar disorder among psychiatric patients remains important, as does considering individual risk factors such as family history or age at onset. Still, our findings indicate that, in most individuals presenting with a major depressive episode without a prior manic or hypomanic episode, unrecognized bipolarity does not appear to be a major determinant of treatment resistance.”