Illness risk following rapid versus gradual discontinuation of antidepressants.

OBJECTIVE: Rapid discontinuation of some psychotropic medications is followed by discontinuation symptoms as well as an increased risk of early illness recurrence. Recurrence occurs earlier after rapid than after gradual discontinuation with lithium and antipsychotics. The authors compared illness recurrence after rapid versus gradual discontinuation of antidepressants. METHOD: The authors compared 398 patients with a DSM-IV diagnosis of recurrent major depressive disorder (N=224), panic disorder (N=75), bipolar II disorder (N=62), or bipolar I disorder (N=37). Two-thirds were women, the mean age was 42 years, and patients were treated with antidepressants for a mean of 8.5 months. Antidepressants were discontinued clinically, either rapidly (over 1-7 days; N=188) or gradually (over 14 days or more; N=210), with a mean follow-up duration of 2.8 years; patients who were ill at discontinuation were excluded from the analysis. The authors compared latency to first new illness episodes using survival analysis and Cox multivariate modeling. RESULTS: The latency to first illness with rapid discontinuation was 0.4 times that with gradual discontinuation, and the latency after rapid discontinuation was one-fourth the estimated average previous interepisode interval in the same patients. The effect was similar across antidepressant classes and across years; the pace of discontinuation had less effect with drugs of prolonged half-life. The effect also varied by diagnosis (bipolar I > or = panic > bipolar II > or = major depressive disorder) but not by episodes per year, duration of index illness, use of concomitant treatment, or antidepressant dose or duration. CONCLUSIONS: The recurrence risk for depression or panic was much shorter after rapid than after gradual discontinuation of antidepressants. These findings have implications for both clinical management and the design and interpretation of clinical trials.

Secular trends in first hospitalizations for major mood disorders with comorbid substance use.

In the past half-century, the incidence of major mood disorders reportedly has risen, and onset age, diminished. Substance-use disorders (SUDs) are commonly comorbid with mood disorders and may influence their course and outcome. Since secular relationships of these disorders remain unknown, we evaluated medical records of 421 patients (233 men, 188 women) at first-lifetime admissions for major depression, mania or mixed bipolar episodes at a public hospital in Italy during 1978-2002, updated diagnoses to DSM-IV criteria, and compared selected factors between subjects with vs. without SUDs, seeking evidence of secular trends in SUDs in association with early mood disorders. SUD was diagnosed in 122 patients (29.0%). SUD risk was greatest in young males. Relative risk (RR) of diagnostic association with SUDs ranked: mixed states (RR 1.80), mania (RR 1.06), depression (RR 0.55). Annual rates of comorbid SUD and mood disorders increased continuously over the 25-yr epoch for all substances (r=0.640, p<0.001). Age at onset of illness and at first hospitalization (averaging 36 yr and 38 yr) were unrelated to year of hospitalization in this relatively brief sampling, but patients with SUD were younger at onset and admission, overall. Clinical Global Impression (CGI) ratings of illness severity at hospitalization and discharge were stable across years. These findings indicate a secular increase of comorbid SUD among first admissions for mood disorder, especially in young males, with a parallel increase in the proportion of bipolar disorder diagnoses over the past quarter of a century.