Cardiovascular Variability in Major Depressive Disorder and Effects of Imipramine or Mirtazapine (Org 3770)

Abstract

Spectral analysis of fluctuations in heart rate (HR) and blood pressure (BP) was applied to assess sympathetic and parasympathetic cardiovascular control mechanisms in patients with unipolar affective disorder before and after treatment with imipramine (IMI) or mirtazapine (MIR). In a double-blind randomized study, 10 patients received treatment with IMI and 10 patients received treatment with MIR. Cardiovascular parameters were studied before and after 4 weeks of treatment: HR and BP (Finapres) were recorded continuously during supine rest (SR) and orthostatic challenge (OC; 60-degrees head-up tilting). During SR and OC, power spectra were calculated for HR and systolic BP. Spectral density was assessed for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.50 Hz). Before treatment, the depressed patients (N = 20) differed from age-matched controls (N = 20) only in their response to OC: the depressed patients showed more suppression of HR variability (both mid- and high-frequency band fluctuations), indicating stronger vagal inhibition, and a reduced increase of BP variability (mid-frequency band fluctuations), indicating reduced sympathetic activation. After 4 weeks of treatment, patients treated with either antidepressant drug showed significant changes of HR (increase) and HR variability (decrease) during SR and OC; the suppression of mid- and high-frequency fluctuations of HR was larger for IMI than for MIR. The increase in HR and decrease in HR variability may be attributed to the anticholinergic properties of IMI (strong) and MIR (weak), resulting in cardiac vagal inhibition. Whereas MIR had no effect on BP or BP variability, IMI specifically reduced mid-frequency band fluctuations of BP as the result of a suppression of central sympathetic activity. Our data confirm and extend previous observations on the presence of autonomic dysfunctions in unmedicated depressed patients: spectral analysis of HR and BP fluctuations suggested that both parasympathetic and sympathetic mechanisms are involved, specifically during OC. The preexisting autonomic cardiovascular dysfunctions were not normalized by antidepressant drugs. In fact, some of the components of the cardiovascular autonomic dysfunction were further aggravated, depending on the pharmacologic profile of the drug under investigation.

Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

“…In total, 140 case-control and 30 treatment 76,83,93,110,116,129,138,141,155,175,[187][188][189][190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205][206] studies were eligible for inclusion in the quantitative synthesis (151 case-control and 43 effect sizes for analysis); 10 of the studies were included in both the case-control and treatment analyses. 76,83,93,110,116,129,138,141,155,175 Four subgroups of disorders (mood, anxiety-related, psychotic and substance dependence disorders) and 2 classes of psychotropic medications (antidepressants and antipsychotics) were included. Table 1 reports study characteristics for case-control and treatment studies, separated by diagnostic group or type of psychotropic medication, respectively (see Appendix 1, Tables S1 and S2, for individual study characteristics).…”

“…‡One study removed 199 owing to overlapping clinical diagnoses between the anxiety and mood disorder subgroups. §One study removed 241 as it was the only study to examine the effects of a noradrenergic and specific serotonergic antidepressant. ¶One study removed 141 owing to inclusion of multiple antipsychotics, and 2 other studies removed as they were the only studies to examine a particular antipsychotic (haloperidol 204 and risperidone 155 ).…”

“…Bär et al 189 Davidson et al 190 188 Dawood et al 110 Khaykin et al 191 Koschke et al 116 Lederbogen et al 192 Prasko et al 76 Rechlin 194 Rechlin 194 Rechlin et al 196 Tucker et al 83 Udupa et al 197 Udupa et al 198 Yeragani et al 201 189 Khaykin et al 191 Lederbogen et al 192 McLeod et al 193 Rechlin 194 Rechlin et al 195 Rechlin et al 195 Rechlin et al 196 Tulen et al 129 Udupa et al 198 Yeragani et al 199 Yeragani et al 200 …”

Depression, anxiety and cardiovascular disease: biological correlations and therapeutic strategies

“…Vari studi controllati hanno dimostrato un'efficacia della mirtazapina equivalente a quella dei TCA, ma con minore percentuale di drop-out (Kasper, 1997). E' stata segnalata una possibile riduzione della HRV, in assenza di effetti pressori (Tulen et al, 1996), oltre ad un'azione antistaminica, responsabile di sedazione e di incremento ponderale, effetto collaterale non favorevole nei pazienti cardiopatici.…”

Anxiety and autonomic regulation in major depressive disorder: an exploratory study

“…The cardiovascular data were derived from a study to the effects of different antidepressants on hemodynamic parameters in depressed patients (Tulen et al, 1996). Because the majority of the depressed patients in this study consisted of women, we restricted our analysis to female patients and age-matched female controls only, in order to exclude sex-related cardiovascular effects.…”