RESPONSE OF ANXIETY AND AGITATION SYMPTOMS DURING NEFAZODONE TREATMENT OF MAJOR DEPRESSION

A meta-analysis of six randomized, placebo-controlled, double-blind tr ials was carried out to evaluate the effectiveness of the new antidepr essant nefazodone in relieving symptoms of anxiety and agitation assoc iated with major depression. Nefazodone blocks serotonin, (5-HT2) rece ptors and selectively inhibits serotonin (5-HT) reuptake. This pharmac ologic profile may confer clinical benefits that differ from those of other antidepressants, such as tricyclics (TCAs) and serotonin selecti ve reuptake inhibitors (SSRIs). The data base included 817 patients wi th major depression and baseline 17-item Hamilton Rating Scale for Dep ression (HAM-D-17) scores greater than or equal to 18; 345 received pl acebo, 288 imipramine, and 184 nefazodone. Both nefazodone and imipram ine exhibited antidepressant efficacy compared with that of placebo, i rrespective of baseline anxiety levels. Statistically significant impr ovement in Hamilton Rating Scale for Anxiety (HAAM-A), HAM-D anxiety f actor, HAM-D psychic anxiety item, and HAM-D agitation item scores was observed with both active treatments. Nefazodone-treated patients sho wed significantly greater improvement in somatic anxiety (HAM-D item 1 1) ratings than placebo-treated patients from Week 4 through end of tr eatment (p less than or equal to .01), while imipramine-treated patien ts did not differ from placebo patients on this item. Nefazodone-treat ed patients improved more rapidly (as early as Week 1) than imipramine - and placebo-treated patients on agitation (HAM-D item 9) (p less tha n or equal to .01). Nefazodone was found to have an excellent safety p rofile and was well tolerated, with 5% of nefazodone patients prematur ely discontinuing treatment for adverse experiences compared with 17% for imipramine and 5% for placebo treatment. Nefazodone did not induce unwanted activating side effects during treatment as may be the case with TCAs and SSRIs.