To the Editor: We are writing to express our concern regarding two articles from the same center by Flavia Gatti, M.D., and colleagues (1) and Raffaella Zanardi, M.D., and colleagues (2) that concluded that selective serotonin reuptake inhibitors (SSRIs) alone are effective in the treatment of delusional depression and that "a new window has opened in the pharmacotherapy of this disorder." Although serotonin has been implicated in the pathophysiology of delusional depression (3), we do not believe that the evidence in the literature supports the use of SSRIs alone for the treatment of delusional depression at this time. Yet some authors (4) are citing these two articles as evidence to argue that SSRIs may be neuroleptics.

The double-blind comparison of sertraline and paroxetine (2) found response rates to sertraline alone higher (75%) than those observed in studies with a tricyclic antidepressant alone (40%) (5) and comparable to the rates observed with ECT (6), a triclyclic antidepressant plus an antipsychotic (5), and an SSRI plus an antipsychotic (7, 8). Is this possible? Had a control group been included in the study, the question of whether SSRIs alone are effective in delusional depression could have been answered. Without a control, it is impossible to draw conclusions.

We wonder if the patients were misdiagnosed. Did they have strictly defined major depression with psychotic features, or did some of them have body dysmorphic disorder, obsessive-compulsive disorder, or borderline personality disorder—disorders that may be characterized by depression plus delusional or near-delusional beliefs or other psychotic or psychotic-like symptoms that preliminary evidence suggests may respond to SSRIs alone (9–11)? It does not appear that a standard diagnostic instrument, such as the Structured Clinical Interview for DSM-III-R—Patient Version, was used to diagnose subjects’ disorders. Finally, while the Dimensions of Delusional Experience Rating Scale has been demonstrated as reliable, to our knowledge, validity data are lacking.

The findings of Dr. Gatti and colleagues (1) and Dr. Zanardi and colleagues (2) are interesting and provocative, but given these apparent methodologic limitations and until further confirmatory data are available, we think that their results should be regarded with caution.