John M. Rainey

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.

Psychophysiological factors in panic disorder.

Panic disorder patients were compared with normal subjects during intravenous infusion of sodium lactate, isoproterenol, and placebo. Panic attacks meeting the criteria of the Diagnostic and Statistical Manual, vol. 3 [American Psychiatric Association, 1980] occurred during all three conditions in patients and during the lactate and isoproterenol infusions in normals. Patients had significantly higher average levels of skin conductance, heart rate and state anxiety, and significantly lower finger temperatures compared to normal subjects. However, no measure reliably differentiated panic attacks from nonattack periods. It is concluded that the peripheral physiologic responses investigated are neither necessary nor sufficient for the occurrence of panic attacks. It is possible that reports of these attacks represent phobic responses to intense anxiety.

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.

Plasma MHPG levels in lactate and isoproterenol anxiety states

It has been claimed that an increase in brain noradrenergic activity plays a role in panic disorder and that enhanced noradrenergic activity may be reflected by plasma levels of MHPG. We investigated plasma MHPG levels in panic disorder patients at baseline and during lactate- and isoproterenol-induced anxiety states. These infusions and 5% dextrose infusions were given to 10 panic disorder patients and 9 healthy control subjects. Each subject received all three infusions, double-blind, in random order, and at 1-week intervals. When compared to controls, plasma free MHPG levels in panic patients were not elevated at baseline, during lactate or isoproterenol infusions, at the point of panic, or up to 20 min after the onset of panic. MHPG values were also not elevated in subjects who panicked compared to those who did not. MHPG values were significantly lower in three patients who failed to panic with isoproterenol, but the patient panickers had MHPG values similar to those of controls. Significant correlations between MHPG levels and anxiety ratings were infrequent and could be accounted for by chance alone. These results did not support the noradrenergic model for panic anxiety states induced by lactate or isoproterenol.

Dexamethasone suppression test in patients with panic attacks

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Lactate- and isoproterenol-induced panic attacks in panic disorder patients and controls.

In a double-blind study using sodium lactate and isoproterenol infusions to provoke panic attacks, 73 of 86 panic disorder patients and 10 of 45 controls panicked with lactate, and 58 of 86 patients and 4 of 45 controls panicked with isoproterenol. We measured baseline and peak anxiety ratings in 10 controls with lactate-induced panic attacks, 31 controls who did not panic during lactate infusions, and 63 panic disorder patients who did panic during lactate infusions. The controls who panicked with lactate had robust increases in their anxiety ratings very similar to the increases experienced by patients who panicked with lactate.

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.

Central Nervous System Effects of Lactate Infusion in Primates

The concentration of total lactate in cisternal fluid increased threefold, from 12.3 +/- 2.1 to 37.6 +/- 8.9 mg/dl, during a 20-min intravenous infusion of 1 M racemic sodium lactate (10 mEq/kg) in 3 anesthetized, mechanically ventilated baboons. Rises in cisternal lactate lagged behind arterial lactate increases, but occurred during the time interval in which susceptible humans typically panic in response to lactate infusion. Subsequent to cisternal lactate increases, cisternal pH and HCO3- concentration progressively increased during a 105-min interval following lactate infusion. No consistent changes in cisternal pCO2 occurred during or subsequent to lactate infusion. These preliminary findings fail to support the hypothesis that lactate-induced panic is mediated by increasing central nervous system pCO2. Instead, these data demonstrate that lactate can rapidly increase in the central nervous system during lactate infusion, suggesting new lines of investigation for studying the mechanisms responsible for lactate-induced panic.

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.

MMPI differentiation of panic disorder patients from other psychiatric outpatients

A variety of Minnesota Multiphasic Personality Inventory (MMPI) techniques were used to determine differences in psychopathology between 60 outpatient panic disorder patients (PDPs) and 60 demographically matched psychiatric controls (PCs). An empirically constructed panic disorder (Pan) scale correctly classified 72% of PDPs and PCs in the cross-validation sample and 83% of the combined samples, suggesting potential clinical utility and the need for further validation