BOCA RATON, FLA. — Early worsening of symptoms after initiation of fluoxetine for major depressive disorder occurs in approximately 30% of patients and is associated with poorer outcomes and an increased likelihood of discontinuation, Cristina Cusin, M.D., said in a poster presentation at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
Patients should be monitored very carefully in the weeks after new treatment with fluoxetine, she said.
Dr. Cusin and her associates studied 694 outpatients (mean age 39 years) with major depressive disorder. Participants received 20 mg of fluoxetine per day for up to 12 weeks. The investigators assessed participants at regular intervals with a modified Hamilton Depression Rating Scale (mHAM-D) and defined worsening as a 5-point increase in score since the previous visit, occurring at least 1 week after starting treatment. Eli Lilly funded the study.
“Not all patients respond the same way. Some get worse before they get better,” said Dr. Cusin of Massachusetts General Hospital, Boston. Dr. Cusin has no affiliation with Eli Lilly.
A total of 211 patients (30%) had worsening of their depression between weeks 2 and 6. Researchers looked for clinical correlates to predict who might fall into this group. They found no significant differences—based on age, duration of illness, number of previous depressive episodes, baseline mHAM-D scores, or fluoxetine/norfluoxetine plasma levels—between this group and the 483 who reported no worsening.
But an increase in the mHAM-D scores at weeks 2, 3, 4, and 6 was significantly associated with a lower probability of improvement at weeks 8 and 12.