Robert Pohl

Decreased heart rate variability in panic disorder patients: A study of power-spectral analysis of heart rate

We have previously found decreased standard deviations and mean consecutive differences of R-R intervals in panic disorder patients in standing posture, compared with control subjects. In the present study, we used spectral analysis of heart rate variability to examine autonomic function in 21 panic disorder patients and 21 normal control subjects. Patients had a significantly lower standard deviation of heart rate in supine as well as standing postures. Absolute low frequency power (0.01-0.05 Hz) was also significantly lower in panic disorder patients in standing postures. Upon standing, the panic disorder patients had significantly higher relative mid-frequency power (0.07-0.15 Hz). During a standing deep-breathing condition at six breaths per minute, the patients had a significantly decreased absolute and relative mid-frequency (0.07-0.15 Hz) power compared with control subjects. These findings suggest a decrease in cholinergic and a relative increase in adrenergic responsiveness in panic disorder patients compared with control subjects.

Heart Rate Variability in Patients With Major Depression

We have previously reported decreased heart rate variability upon standing in panic disorder patients compared with controls. In this study, we extend our report to include patients with major depression (n = 19). Compared to normal controls (n = 20) and panic disorder patients (n = 30), there was no significant difference in the immediate changes in heart rate upon standing in the depressed group. The standing heart rate variability (R-R variability) was significantly lower in panic disorder patients compared to both normal controls and depressed patients as indicated by the corrected standard deviations, the corrected mean consecutive difference, the corrected standard deviation of the mean consecutive difference of the R-R intervals, and the high frequency variability in successive R-R intervals, suggesting an increased vagal withdrawal in panic disorder patients, especially upon standing. There was no significant difference in any of the heart rate variability measures between depressed patients and normal controls.

Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing.

Abstract: Pregabalin is a new anxiolytic that acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels. The current study evaluated the anxiolytic efficacy of BID versus TID dosing of pregabalin in patients with generalized anxiety disorder. Outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition generalized anxiety disorder and having baseline Hamilton Anxiety (HAM-A) total scores ≥20 were randomized to 6 weeks of double-blind treatment with pregabalin 200 mg/d (BID; N = 78), 400 mg/d (BID; N = 89), or 450 mg/d (TID; N = 88) or placebo (N = 86). Mean improvement in HAM-A total score at last observation carried forward end point was significantly greater on pregabalin 200 (P = 0.006), 400 (P = 0.001), and 450 mg/d (P = 0.005) compared with placebo. Pairwise comparisons of BID versus TID dosing found no difference in HAM-A change score at end point. All 3 pregabalin dosage groups showed significantly greater efficacy versus placebo at end point on the HAM-A psychic and somatic anxiety factor scores. Improvement on both factors was rapid: significance versus placebo was achieved as early as the first assessment at week 1, with ≥30% reduction in HAM-A severity and equal or greater improvement for every subsequent visit in ≥38% of patients in all 3 pregabalin dosage groups (P ≤ 0.001). Pregabalin was well tolerated, and despite the fixed-dose study design, discontinuations caused by adverse events ranged from 9% to 13%-comparable with that observed with placebo (8%). This study demonstrates that pregabalin is an effective treatment of generalized anxiety disorder, with BID dosing showing similar efficacy and comparable tolerability with TID dosing.

Diminished chaos of heart rate time series in patients with major depression

BACKGROUND Depression and anxiety have been linked to serious cardiovascular events in patients with preexisting cardiac illness. A decrease in cardiac vagal function as suggested by a decrease in heart rate (HR) variability has been linked to sudden death. METHODS We compared LLE and nonlinearity scores of the unfiltered (UF) and filtered time series (very low, low, and high frequency; VLF, LF and HF) of HR between patients with depression (n = 14) and healthy control subjects (n = 18). RESULTS We found significantly lower LLE of the unfiltered series in either posture, and HF series in patients with major depression in supine posture (p <.002). LLE (LF/UF), which may indicate relative sympathetic activity was also significantly higher in supine and standing postures in patients (p <.05); LF/HF (LLE) was also higher in patients (p <.05) in either posture. CONCLUSIONS These findings suggest that major depression is associated with decreased cardiac vagal function and a relative increase in sympathetic function, which may be related to the higher risk of cardiovascular mortality in this group and illustrates the usefulness of nonlinear measures of chaos such as LLE in addition to the commonly used spectral measures.

Decreased R‐R variance in panic disorder patients

To investigate autonomic function in panic disorder patients (n= 30), we compared postural changes in heart rate and the R‐R interval variance in patients and normal controls (n= 20). There was no significant difference in the immediate changes in heart rate upon standing between the groups. R‐R variance was significantly decreased during resting supine condition in patients as indicated by the corrected standard deviation of the R‐R intervals. The standing R‐R variance was significantly lower than that of normal controls as indicated by the corrected standard deviations, the corrected mean consecutive difference and the corrected standard deviation of the mean consecutive difference of the R‐R intervals, suggesting an increase in vagal withdrawal in patients, especially upon standing. If this finding is specific to panic disorder patients, it may be a useful peripheral marker for this condition.

Increased QT variability in patients with panic disorder and depression

Abstract This study investigated beat-to-beat QT variability in patients with panic disorder and depression, and normal control subjects using an automated algorithm to compute QT intervals. An increase in QT variability appears to be associated with symptomatic patients with dilated cardiomyopathy and also with an increased risk for sudden death. QT vm (QT variability normalized for mean QT interval) and QT vi (a log ratio of QT variance normalized for mean QT over heart rate variability normalized for mean heart rate) were significantly higher in patients with panic disorder and depression in supine as well as standing postures ( P= 0.002 and 0.0001 for QT vm and QT vi , respectively). In another analysis, QT vi was significantly higher in patients with panic disorder compared to control subjects in supine as well as standing postures during spontaneous breathing as well as 12, 15 and 20 per minute breathing ( P= 0.005). These findings are important especially in view of the recent reports of increased risk for cardiovascular mortality and sudden death in patients with anxiety and depression and the utility of QT vi as a noninvasive measure of temporal repolarization lability.

Pregabalin: a new anxiolytic

Pregabalin (S-[+]-3-isobutylgaba) was designed as a lipophilic GABA (γ-aminobutyric acid) analogue substituted at the 3′-position in order to facilitate diffusion across the blood–brain barrier. It was originally developed as an anticonvulsant agent, however it has been shown to be effective in the treatment of several disorders including hyperalgesia and behavioural disorders. Although its exact mode of action remains unclear, pregabalin interacts with the same binding site and has a similar pharmacological profile as its predecessor, gabapentin (1-[aminomethyl] cyclohexane acetic acid). Its main site of action appears to be on the α2δ subunit of voltage-dependent calcium channels, widely distributed throughout the peripheral and central nervous system. Pregabalin appears to produce an inhibitory modulation of neuronal excitability. In healthy volunteers, it is rapidly absorbed with peak blood concentrations within 1 h and it has a bioavailability of ∼ 90%. In preclinical trials of anticonvulsant activity, pregabalin is three to ten times more potent than gabapentin. It is well-tolerated and associated with dose-dependent adverse effects (ataxia, dizziness, headache and somnolence) that are mild-to-moderate and usually transient. There are no known pharmacokinetic drug–drug interactions reported to date. Preliminary animal and human studies showed beneficial effects in both ethological and conflict models of anxiety, as well as having some sleep-modulating properties. In Phase II and III trials, pregabalin shows promising anxiolytic action when compared to placebo in generalised anxiety disorder, social phobia and panic disorder.

Smoking in patients with panic disorder

We compared smoking prevalence in 217 patients with panic disorder with that in 217 age- and sex-matched control subjects who were obtained by telephone survey from the same neighborhoods. Data were obtained for current smoking habits and smoking status at either the onset of illness (patients) or 10 years previously (control subjects). Patients had been ill for 10.6 (SD = 10.0) years. Female patients with panic disorder had a significantly higher smoking prevalence at the onset of their illness than did control subjects 10 years previously (54% vs. 35%). The current smoking prevalence for female patients was also significantly higher than that of control subjects (40% vs. 25%). Male smoking rates did not differ between patients and control subjects. Caffeine use did not appear to explain these findings. These data suggest a link between smoking behavior and panic disorder in women.

A Comparison of Lactate and Isoproterenol Anxiety States

Both sodium lactate and isoproterenol can produce anxiety symptoms in patients with panic attacks. We administered both substances intravenously under placebo-controlled, double-blind conditions to patients with panic attacks and normal control subjects. We measured changes in anxiety levels using the Hamilton Anxiety Scale, State-Trait Anxiety Inventory, and a Panic Severity Scale. Measurements of respiratory rate and blood pH, pO2, pCO2, HCO3, and base excess were used to determine the relationship of hyperventilation to the symptoms induced by the infusions. Heart rate, epinephrine and norepinephrine levels were measured to determine whether there are changes related to palpitations and chest pain. Finger temperature and galvanic skin response were monitored to see whether any changes correlate with subject reports of hot or cold flashes and sweating. In this presentation, we will describe the clinical and biochemical changes that occur during panic attacks.

Effect of imipramine treatment on heart rate variability measures

Recently, heart rate (HR) variability has received considerable attention, and a decreased HR variability has been linked to a significant risk of cardiovascular illness. We have previously reported such a decreased variability in panic disorder patients. In this study, we report on HR variability in 12 depressed and 6 panic disorder patients at baseline and 1 and 3 weeks of treatment with imipramine as measured by the standard deviation, mean consecutive difference and the standard deviation of the mean consecutive difference of the R-R intervals in supine, supine deep breathing and standing postures. In all subjects, imipramine (mean dose: 70 mg/day) produced a significant decrease in heart rate variability at week 3 as measured by the above variables. This decrease in HR variability during imipramine treatment is probably due to its anticholinergic effects.