Data were derived from a previous study, designed to assess for predictors of MDD relapse in among fluoxetine responders. The study was conducted at two sites: the New York State Psychiatric Institute and the Depression Clinical & Research Program of the Massachusetts General Hospital (see McGrath et al., 2006
, for a complete description). Institutional review boards at both sites approved the study, and all participants provided written informed consent.
At screening visit, outpatients between the ages of 18 and 65 were required to meet criteria for MDD diagnosed with the Structured Clinical Interview for DSM-IV -Patient Edition (SCID-I/P; First et al., 1996
) in order to be eligible for the trial. No minimum depression severity score was required for inclusion. Out of the 510 subjects, 434 had a baseline HAMD-17 score greater than 13 (mean = 17.6, SD = 5.05). Medical screening included medical history, physical examination, electrocardiogram, complete blood count, urinalysis, blood chemistry screening, thyroid function tests, and a urine drug screen.
The following criteria were defined as exclusionary: significant suicidal risk, pregnancy, breastfeeding or absence of effective contraception for women, unstable physical disorders, neurological disorders significantly affecting CNS function, including a history of seizures, a lifetime history of any organic mental disorder, psychotic disorder, or mania, substance abuse or dependence active in the previous six months, except for nicotine dependence, concurrent use of medications suspected to cause or exacerbate depression, clinical or laboratory evidence of hypothyroidism without adequate and stable replacement, and a history of non-response to an adequate trial of a selective serotonin reuptake inhibitor (defined as a four-week trial of ≥ 40 mg of fluoxetine or its equivalent daily).
After a one-week medication-free wash out period, patients who continued to meet inclusion criteria at the baseline visit began open-label fluoxetine for 12 weeks. Target dosing of fluoxetine was: 10 mg daily for week 1; 20 mg daily for weeks 2–4; 40 mg daily for weeks 4–8; 60 mg daily for weeks 5–12. Medication management visits were weekly for the first 6 weeks, biweekly for weeks 7–10, and weekly for weeks 11 and 12.
The primary efficacy measure was the 17-item Hamilton Depression Rating Scale (HAMD-17; Hamilton, 1960
). The Anxiety/Somatization factor of the HAMD-17 includes six items: anxiety (psychic), anxiety (somatic), somatic symptoms (gastrointestinal), somatic symptoms (general), hypochondriasis, and insight. Early change in these items of the HAMD-17 was defined as the change in score between baseline and week 1 (baseline minus week 1). The HAMD-17 instrument was administered at each visit by clinical study investigators. The baseline total Anxiety/Somatization factor score of great than or equal to 7 was used to define anxious depression (Fava et al., 2008
Logistic regressions were performed to investigate whether early changes (from baseline to week 1) in the 17-item Hamilton Depression Rating Scale (HAMD-17; Hamilton 1960
) Anxiety/Somatization factor items were associated with meeting criteria for remission (HAMD-17< 8) at endpoint of the acute phase (week 12 or early discontinuation visit). These regressions were adjusted for multiple comparisons using the Bonferroni correction with p <0.008 considered statistically significant at the 95% level for each of the 6 comparisons. For all of the regressions, meeting criteria for remission at endpoint (by last observation carried forward) was the dependent variable, and initial severity of MDD at baseline was an independent variable as well as the change in score from baseline to week 1 of the HAMD-17 anxiety/somatization items. We did not control for chronicity of depression, as it was not a significant predictor of poorer outcome in either the parent study or another study conducted by Fava and colleagues (1997)
. We also used logistic regression to investigate whether anxious depression predicted remission at endpoint, after controlling for severity of depression. All analyses were conducted on the intent to treat (ITT) sample, with the additional criterion that a subject had to have a HAMD-17 score at baseline and at week 1 to be entered into the sample. As a post hoc analysis, to address that there was no HAMD-17 cutoff at baseline for inclusion, the analyses were run with only those participants who had a HAMD-17 score at baseline of > 13 (n = 434). Results were similar and produced no additional significant results; therefore, only the results from the initial sample of participants (n=510) are reported in this paper. Using G*Power, (Erdfelder et al., 1996
) we computed the power needed to detect an effect with a sample size of approximately 500 subjects (p < .05; two tailed). The power was computed as >0.99.