Nocturnal urinary cortisol excretion over a randomized controlled trial with paroxetine vs. placebo combined with relaxation training or aerobic exercise in panic disorder.

INTRODUCTION: Data on basal hypothalamo-pituitary-adrenomedullary (HPA) function over controlled treatment trials with serotonergic drugs in anxiety disorders are still rare. METHODS: 29 patients with panic disorder participating in a 10 week randomized, controlled trial (paroxetine vs. placebo with exercise or relaxation; N=60) collected urine for cortisol excretion over 3 consecutive nights before start and before termination of the treatment episode. Urinary cortisol was measured by radioimmunoassay. Efficacy measures were the Clinical Global Impression Scale (CGI) and the Panic and Agoraphobia Scale (P&A). 83% were female (p<.05 vs. males). 55% received additional aerobic exercise, and 45% relaxation. 55% received paroxetine treatment, and 45% placebo. Significantly fewer males received placebo treatment (p<.05). RESULTS: All subjects improved significantly. Cortisol excretion did not differ between treatment groups or at pre-/post measurements. Females showed a significantly higher variability of cortisol excretion compared to males, at pre-(p<.005) and post (p=.015) assessments. Males displayed a trend to lower basal HPA function at end of treatment (p=.08). HPA variability after treatment showed a trend to be higher in the paroxetine (p=.052) -who clinically improved significantly better- compared to the placebo group. No relationship between HPA activity and treatment response or with exercise was detected. DISCUSSION: HPA function shows significant gender differences, with females having a higher HPA function variability. Future studies on HPA function in treatment trials should address gender and medication effects.

NAG level differences in panic disorder and agoraphobia.

It is not clear if panic disorder (PD) and agoraphobia are variants of the same disorder or distinct diseases. A laboratory test could help resolve this issue. Research has shown that levels of the urinary lysosomal enzyme N-acetyl-beta-glusosaminidase (NAG) differ between patients with various psychiatric disorders. This study examined whether NAG levels would be similar in PD and agoraphobia, suggesting the two disorders may be the same disorder, or different, suggesting they may be distinct diseases. Differences found could suggest either qualitative or quantitative distinctions between these disorders. Ninety-one agoraphobics were compared to 24 patients with panic disorder. NAG levels were significantly lower in panic patients compared to agoraphobic patients 9.7+/- 8 versus 22+/- 21; P< .005. These data provide limited support for the hypothesis that PD and agoraphobia may be distinct diseases.

Urinary pH in panic disorder.

Urinary pH was evaluated in panic disorder (PD) patients compared with both psychiatric and healthy control subjects. Fourteen PD patients, eight major depressive disorder (MDD) patients, and 14 healthy control (HC) subjects were examined. All patients were drug-free and met DSM-IV diagnostic criteria. The PD patients had lower urinary pH and higher levels of anxiety than both MDD and HC subjects. Additionally, urinary pH inversely correlated with anxiety levels. Although preliminary, these findings suggest that PD patients have lower urinary pH than MDD and HC subjects. Future studies that simultaneously examine both urinary and blood pH in larger numbers of PD patients and patients with other anxiety disorders, before and after treatment, need to be conducted.

Diurnal variation of cortisol in panic disorder.

In patients with panic disorder (n=23), daytime salivary cortisol levels were determined in 2-h spans on 3 consecutive days and compared with 23 age- and sex-matched healthy controls. Additionally, nocturnal urinary free cortisol levels were measured. Daytime salivary cortisol levels were numerically higher in the patients, although the difference did not reach statistical significance. In a subgroup of 14 patients with higher illness severity (as expressed by a score >/=22 on the Panic and Agoraphobia Scale), salivary cortisol levels were significantly higher than in the controls. Mean nocturnal urinary cortisol levels were significantly higher in the whole group of patients and also in the more severely ill subgroup when compared with controls. Cortisol elevations seem to be more pronounced during the night and occurred mainly in more severely ill panic patients.

Extreme anxiety/panic disorder.

A 45 year old man is referred to a specialist psychiatric centre. For 3 years he has been experiencing worsening impending fear of death and anxiety which he describes as 'panic attacks'. During these episodes he often experiences palpitations and becomes sweaty. These episodes have not been relieved despite several courses of electroconvulsive therapy. On examination, the man is alert and orientated. He has a normal blood pressure of 125/75 mmHg and electrocardiogram reveals a pulse rate of 102 beats per minute. A psychiatrist orders a number of routine tests to rule out organic disease.

Urinary excretion of cortisol, norepinephrine, testosterone, and melatonin in panic disorder.

Nocturnal urinary cortisol, norepinephrine, epinephrine, testosterone, and melatonin secretion patterns were studied in male patients with DSM IV/ICD-10 panic disorder (n = 16) over two series of 5 consecutive nights each. Night-time urinary excretion of cortisol, norepinephrine, and epinephrine was significantly elevated in drug-free patients compared to normal individuals (n = 13). Measurements were repeated after 4 weeks, and the same differences were found again. There were high correlations between the first and the second series of measurements. Testosterone and melatonin levels did not differ between panic patients and controls.