Richard Berchou

Effects of yohimbine on heart rate variability in panic disorder patients and normal controls: A study of power spectral analysis of heart rate

Summary: We studied the effects of yohimbine on heart rate (HR) variability in 13 normal controls and 13 patients with panic disorder. Yohimbine produced a significant increase in SD of HR in standing posture in both patients (p = 0.01) and normal controls (p = 0.025). Panic disorder patients had a significant increase in standing absolute midfrequency (MF) power (0.07–0.15 Hz) after administration of yohimbine (p = 0.002). The ratio of post- to preyohimbine standing MF power (0.07–0.15 Hz) during standing was significantly higher in patients as compared with controls (2.3 ± 1.08 vs. 1.33 ± 0.38; p = 0.01), which suggests an increased responsivity of panic disorder patients to the adrenergic effects of yohimbine

Isoproterenol-induced panic attacks

Eighty-six panic disorder patients and 45 nonpsychiatric controls were infused with isoproterenol at a rate of 1 microgram/min for up to 20 min in a placebo-controlled, double-blind study. Sixty-six percent of panic disorder patients experienced panic attacks during isoproterenol infusions, compared to 16% during placebo infusions. Nine percent of control subjects panicked with isoproterenol, but none panicked with placebo. Patients were more sensitive than controls to the anxiogenic effects of isoproterenol, as measured by subject self-ratings on a panic description scale. The frequency of panic attacks induced in patients was related to the dosage of isoproterenol; 79% of the patients who received a mean of 18.5 ng/min/kg of isoproterenol panicked. The panic attacks experienced by patients during isoproterenol infusions were similar to those experienced during placebo infusions.

Effects of isoproterenol infusions on heart rate variability in patients with panic disorder

Some evidence suggests that patients with panic disorder have a decreased cardiac vagal and a relatively higher sympathetic activity. In this study, spectral analysis of the time series of heart rate before and after isoproterenol infusions was used to study heart rate variability in six panic disorder patients and 11 normal control subjects. These preliminary data reveal a significant increase of sympathovagal ratios only in the patient group after isoproterenol administration. The findings suggest a relative increase in cardiac sympathetic and a relative decrease in cardiac vagal function in patients with panic disorder during isoproterenol infusions.

Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine

A study was performed to determine if the pharmacokinetics of bromocriptine is altered by factors that have been shown to interact with other ergot compounds. The effects on bromocriptine plasma concentrations by bromocriptine coadministration with caffeine and erythromycin were evaluated in five male volunteers. Serial blood samples were obtained during a 12‐hour period after a single 5 mg oral dose of bromocriptine (alone and after 4‐day treatments of either erythromycin estolate, 250 mg four times/day, or caffeine, 200 mg four times/day). There were no significant alterations of bromocriptine pharmacokinetic parameters after caffeine, although statistical power was very low. With the use of erythromycin, the bromocriptine area under the concentration‐time curve standardized to body weight increased significantly by 268%, whereas peak bromocriptine plasma concentration (Cmax) increased to 4.6 times the C from bromocriptine alone. Time to achieve Cmax was not altered by erythromycin. We conclude that erythromycin can markedly increase the systemic bioavailability of bromocriptine, which can lead to increased therapeutic or adverse effects, whereas the effects of caffeine require further study.

Tricyclic antidepressants and monoamine oxidase inhibitors in the treatment of agoraphobia.

The efficacy of tricyclic antidepressants and monoamine oxidase inhibitors for the treatment of agoraphobia and other panic disorders is reviewed with an emphasis on controlled prospective studies. After methodological biases are taken into account, there is strong evidence that antidepressants suppress panic attacks. This effect is not dependent on the presence of concomitant depressive symptoms. The clinical issues of dosage, delay in response, and relapse with discontinuation of treatment are also reviewed.

Pharmacokinetic and pharmacodynamic modeling of L-dopa plasma concentrations and clinical effects in Parkinson's disease after Sinemet.

Eleven parkinsonian patients participated in a pharmacokinetic/pharmacodynamic study in an attempt to model levodopa (L-DOPA) plasma concentrations to clinical effect. Carbidopa 25 mg/L-DOPA 100 mg (Sinemet 25/100) was given orally, and blood samples were obtained before and serially for 4 hours after the dose. Effect measurements were obtained with each blood sample and included tapping score, timed walking, and global assessment of motor function. Mean L-DOPA plasma concentrations were fitted to a one-compartment pharmacokinetic model. A time-wise plot of modeled plasma L-DOPA concentrations versus mean effect measurements revealed a counter-clockwise hysteresis. Effect compartment concentrations were determined by a least squares approach, which determined elimination rate constants by minimizing hysteresis. Half-times for the equilibration between plasma and the effect compartment were 0.39 h for tapping, 0.36 h for walking, and 0.34 h for the global score. Pharmacodynamic data were fit best with an Emax model with baseline effect for tapping (Emax = 53.2 taps/60 s, EC50 = 0.58 microgram/ml) and global score (Emax set at 5.0 by limits of scale, EC50 = 2.53 micrograms/ml). A linear model best described the relationship between predicted effect site concentration and timed walking. L-DOPA plasma concentrations after oral Sinemet did not correlate well with clinical response because clinical response lags behind plasma concentrations. Half-times for equilibration between plasma and the effect site were similar for all of the effects measured.

Sodium lactate infusions after treatment with tricyclic antidepressants: Behavioral and physiological findings

Fourteen patients with panic disorder were infused with sodium lactate both before and after treatment with tricyclic antidepressants. All patients had panic attacks before treatment, and only five after treatment. There was a significant decrease in measures of anxiety prior to and during infusions after treatment. The patients were able to tolerate more lactate during reinfusions. The comparison of reinfusion panickers and nonpanickers revealed that the reinfusion panickers had higher levels of anxiety, as measured by psychological symptoms on the Panic Description Scale, during both their pretreatment and posttreatment infusions. Tricyclic antidepressants appear to increase the threshold for lactate-induced panic attacks.

Sodium lactate increases sympathovagal ratios in normal control subjects: Spectral analysis of heart rate, blood pressure, and respiration

We used spectral analysis of heart rate (HR), blood pressure (BP), and respiration to examine the effects of lactate on cholinergic and adrenergic influences on HR and BP variability, a technique found to be very useful in cardiovascular research. We specifically used high frequency (0.2-0.5 Hz) and midfrequency (0.07-0.15 Hz) powers to study cholinergic and adrenergic activity in nine normal control subjects before and after lactate and placebo infusions. Our results demonstrate a marked decrease in cholinergic activity and a significant increase in sympathovagal ratios of HR modulation after lactate infusions. This altered sympathovagal balance may contribute to the panicogenic effects of lactate in panic disorder patients.

Hematologic side effects of psychotropic drugs

Abstract Although hematologic side effects from psychotropics are rare, they may present as serious or even fatal consequences of treatment. The hematologic side effects of neuroleptics, antidepressants, anxiolytics, and lithium are reviewed here in regard to their clinical presentation, management, and when known their mechanism of action. Except for aplastic anemia, these side effects usually disappear after drug discontinuation without adverse sequelae and rarely require further treatment.

Preinfusion anxiety predicts lactate-induced panic attacks in normal controls.

&NA; Preinfusion anxiety, heart rate, and blood pressure were measured in 31 normal subjects who received sodium lactate infusions. Eight subjects developed symptoms of panic anxiety during these infusions. Preinfusion anxiety as measured by psychologic symptoms of anxiety on the Panic Description Scale was significantly higher in the panickers while heart rate and blood pressure were not.