Lactate induced panic and beta-2 adrenergic activation.
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Biomedical subjects
Publications and source records attributed to R Pohl.
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The authors administered 400 to 1600 mg of monosodium glutamate and placebo to five healthy males while they were medication-free and again while they were receiving the monoamine oxidase inhibitor tranylcypromine, after having received the drug daily for at least 2 weeks. Monosodium glutamate produced no consistent changes in either blood pressure or heart rate in subjects receiving tranylcypromine. Spontaneous hypertensive episodes were observed in two subjects. These blood pressure increases also occurred with tranylcypromine alone and were unrelated to monosodium glutamate administration. Diet was not violated during these episodes.
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The anxiety symptoms, heart rate and blood pressure of 61 patients who panicked during lactate infusions were compared with 25 control nonpanickers. There was no significant difference in the increase in heart rate and blood pressure over baseline between patients and controls. There appeared to be no significant correlation between the subjective anxiety ratings and the measures of heart rate and blood pressure during lactate-induced panic. The symptoms of shortness of breath, feeling frightened or afraid, feeling dizzy and fear of losing control were significantly associated with lactate-induced panic. In addition, the cognitive symptoms of fear of losing control and fear of going crazy appear to be important determinants of lactate-induced panic.
The frequency and severity of separation anxiety for subjects with panic disorder and major depression was compared with that for normal controls. The subjects were diagnosed according to DSM-III criteria. Each subject completed a questionnaire consisting of 9 items derived from DSM-III criteria for separation anxiety disorder. The incidence of separation anxiety and its severity were significantly higher for the panic disorder subjects than for normal controls but there was no significant difference between depressed and panic disorder subjects. Panic disorder subjects with a history of separation anxiety disorder had a significantly earlier onset of panic attacks.
We compared the responses of bulimic subjects to those of panic disorder patients and normal controls during infusions of sodium lactate and isoproterenol in a double-blind, placebo-controlled study. Four of 8 bulimics infused with lactate had panic attacks. Three of 9 bulimics infused with isoproterenol panicked, and 1 bulimic panicked with a placebo infusion. Although bulimics were less likely than panic disorder patients to panic during provocative infusions, their anxiety levels as measured by a panic description scale were as great. A large portion of the anxiety response in bulimics occurred in those who had concurrent panic attacks.
The efficacy of buspirone for panic disorder was tested in 60 patients who met Diagnostic and Statistical Manual of Mental Disorders (3rd ed.) criteria for panic disorder or agoraphobia with panic attacks. Patients were randomly assigned to treatment with buspirone (mean dose 29.5 mg/day), imipramine (mean dose 140 mg/day), or placebo, and treated for 8 weeks after a 4- to 7-day placebo lead-in period. Patients with 4 or fewer attacks per month and those without attacks at the baseline visit were excluded from panic frequency comparisons. Both buspirone and imipramine tended to be better than placebo on total number of panic attacks, global psychopathology, and the Hamilton Anxiety rating scale, but end point differences among treatments were not statistically significant. At the end of the study, 25% of the buspirone patients were panic-free, as were 7% of the imipramine patients and 14% of the placebo patients; again, these differences were not statistically significant. The results of this study were inconclusive, partly because of the relatively small number of patients (10-11) completing the study in each treatment group, and partly because of a robust placebo response in this population. Possible reasons for this high placebo response are discussed, as well as suggestions for changes in study design for future studies.
The authors infused 45 control subjects with sodium lactate. Eight of 10 subjects with lactate-induced panic attacks and 26 of 35 without panic attacks were interviewed. An investigator, blind to the outcome of the infusion study, obtained family histories of 160 relatives. There was a high prevalence of anxiety disorders among first-degree relatives of subjects with panic attacks. There was no significant difference in the prevalence of mood disorders and substance abuse between first-degree relatives of subjects with (N = 45) and without (N = 115) panic attacks. The results suggest that individuals with a family history of anxiety disorders may be vulnerable to lactate-induced panic attacks.
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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.
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.