Researchers in the TMAP developed detailed algorithms for the treatment of major depressive disorder, schizophrenia, and bipolar disorder in the Texas public health system. In a 12-month study of the effectiveness of the algorithm in the treatment of major depressive disorder, Trivedi and associates2 assigned patients with depression to an ALGO group (n = 175) or a TAU group (n = 175). After 3 months of treatment, ALGO patients had significantly fewer depressive symptoms (P = .002), as measured on the Inventory of Depressive Symptomatology–Clinician Rating Scale (IDS-C30), than the TAU group. During the remaining 9 months of treatment, there was no difference in the rate of improvement of the 2 groups (P = .74), but TAU patients never caught up with the initial lead established by the ALGO group.
ALGO treatment, however, does not always produce a significantly better response than TAU. Suppes and col leagues9 studied the clinical response of a group of patients with bipolar disorder who were treated according to the TMAP bipolar algorithm. In the 12-month study, the ALGO group showed significant improvements (P = .03) on the Brief Psychiatric Rating Scale (BPRS-24) compared with the TAU group in the first 3 months. The differences between the 2 groups narrowed considerably from months 3 to 12 as the TAU group’s rate of improvement on the scale increased.
Manic and hypomanic symptoms, measured by the Clinician-Adminis tered Rating Scale for Mania, decreased significantly more in the ALGO group (P = .007) than in the TAU group during the first 3 months of treatment. The ALGO patients continued to do better than the TAU patients from months 3 to 12, but there was no significant difference in the rate of improvement between the 2 groups. ALGO patients demonstrated a significantly greater decrease in psychotic symptoms over TAU patients in the first 3 months of treatment, but the TAU group caught up by month 12. There were no significant differences in the symptoms of depression, measured on the IDS-C30, between the ALGO and TAU groups during the 12 months of the study.
In a second TMAP bipolar study, investigators examined the relationship between the clinical response of patients to treatment and the adherence of their providers to the TMAP bipolar algorithm.10 The authors used a complex formula to calculate the amount of improvement experienced by ALGO-treated and TAU patients. ALG patients who had depression demonstrated statistically significant improvements (P = .005) in symptoms on the IDS-C30 compared with TAU patients during the last 9 months of the 12-month study. The ALGO group also demonstrated greater improvement than the TAU group on the BPRS-24 during that time. ALGO treatment, however, did not produce significant improvements in manic or hypomanic symptoms over TAU. Curiously, providers who had more experience with the TMAP algorithm adhered to it less.
The STAR*D trial was designed to objectively determine an effective 4-level sequence of treatments for outpatients with nonpsychotic, treatment-resistant depression.5 In an initial STAR*D study, 2876 psychiatric and primary care outpatients with depression were treated at level 1 with citalopram(Drug information on citalopram) (Celexa).11 Depression was mea sured using the 17-item Hamilton De pression Rating Scale (HAM-D) and the 16-item Quick Inventory of Depressive Symptomatology, Self-Report. By the end of the study, 790 (27.5%) patients had achieved remission (de fined as a score of 7 or less on the HAM-D). A large proportion of these patients required 8 or more weeks of treatment with an average dosage of 41.8 mg/d of citalopram.
In a subsequent STAR*D trial, 727 patients who did not respond to level 1 treatment were randomly assigned to level 2 treatment with sustained-release bupropion (Wellbutrin), sertraline(Drug information on sertraline) (Zoloft), or extended-release venlafaxine (Effexor).12 About one quarter of these patients achieved remission. The difference in response to the 3 medications was not statistically significant. A second group of 851 patients who did not achieve remission with citalopram in the level 1 trial received level 2 augmentations with sustained-release bupropion or buspirone(Drug information on buspirone) (BuSpar). The proportion of patients who achieved remission was similar for the 2 medications (29.7% for sustained-release bupropion and 30.1% for buspirone).13
Fava and associates14 treated 235 patients who had not responded to level 1 or 2 treatments in either STAR*D trial with mirtazapine(Drug information on mirtazapine) (Remeron) or nor triptyline (Aventyl, Pamelor) for 14 weeks (level 3). Remission rates were 12.3% for mirtazapine and 19.8% for nortriptyline(Drug information on nortriptyline). The differences in out come between the 2 treatments were not statistically significant.