Depressed In-Patients Respond Differently to Imipramine and Mirtazapine

Abstract

Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression. After a previous report of a marked difference in the response to mirtazapine compared to imipramine, we report here an analysis of different symptom clusters. One hundred seven consecutive in-patients with major depression (Diagnostic and Statistical Manual III-R, DSM-III-R) and a Hamilton Rating Scale for Depression (HRS-D) score of 18 points or more were randomly assigned to double-blind treatment. Two and four weeks after predefined blood levels had been obtained, the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine, the latter being in excess of the 15-45 mg/day range currently advised. Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients (79%) who were not receiving any co-medication. Imipramine was more effective against the clusters related to core symptoms of depression: "depression and guilt", "retardation", and "melancholia", respectively. Mirtazapine showed a biphasic response with regard to the clusters "sleep" and "anxiety/agitation", respectively, which consisted of a marked response after two weeks of predefined blood level, but with a waning of this effect at four weeks. Imipramine produced a more gradual response on these clusters, which was more pronounced at four weeks than with mirtazapine. Two aspects of the present study could be related to this finding: blood level control resulted in optimal treatment with imipramine but not mirtazapine, and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication. These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in-patients.

Relationship between Mirtazapine Dose, Plasma Concentration, Response, and Side Effects in Clinical Practice

“…The mean daily dose of mirtazapine was 76 mg and thus was markedly higher than in pivotal clinical trials [1, 5,14,17 ± 20, 24, 26]. The patients in this study [2,3] had experienced several depressive episodes in the past or were severely ill; thus, it remains unclear whether the cause for the low perform- Original Paper ance of mirtazapine was due to treatment resistance, or whether high doses and thus high plasma concentrations might provide evidence for a curvilinear concentration-response relationship.…”

“…There is only one double-blind study comparing the effectiveness of mirtazapine to imipramine in severely depressed patients. In this study, dosing was adjusted for a target blood concentration range of 50±100 ng/mL mirtazapine and 200±300 ng/ mL imipramine, and imipramine was more effective than mirtazapine [2,3]. The mean daily dose of mirtazapine was 76 mg and thus was markedly higher than in pivotal clinical trials [1, 5,14,17 ± 20, 24, 26].…”

Prevention of the stress-induced increase in the concentration of neuroactive steroids in rat brain by long-term administration of mirtazapine but not of fluoxetine

“…Clinical studies have demonstrated a potent anxiolytic action of mirtazapine (Bruijn et al, 1999;Falkai, 1999;Goodnick et al, 1999;Sheehan, 1999;Thompson, 1999). Our data showing that chronic administration of mirtazapine antagonizes the foot shockinduced increases both in the cortical concentrations of 3α,5α-TH PROG and 3α,5α-TH DOC (present study) as well as in the release of dopamine (Dazzi et al, 2001b) and noradrenaline (Dazzi et al, 2002) in this brain region suggest that these neurochemical effects may contribute to the anxiolytic action of this drug.…”

Amitriptyline for Inpatients and SSRIs for Outpatients with Depression? Systematic Review and Meta-Regression Analysis

“…These findings are in agreement with those provided by Anderson [4], who showed that among inpatients with depression TCA were more effective than SSRIs, and that the overall treatment discontinuation rates were not significantly different. Bruijn and colleagues, who compared imipramine with one of the newer AD drugs, mirtazapine, found better AD properties in severely depressed inpatients treated with imipramine, and suggested a possible role of sedation on these results [7]. Amitriptyline is a very sedative AD, and likely this has had some impact on our results, which are based Fig.…”