Diane E. Sholomskas

Response to meta-chlorophenylpiperazine in panic disorder patients and healthy subjects: Influence of reduction in intravenous dosage

As a further test of the hypothesis of serotonin hypersensitivity in panic disorder (PD), the serotonin agonist meta-chlorophenylpiperazine (MCPP) was administered intravenously in a dose of 0.05 mg/kg to 27 PD patients and 22 normal control subjects. This is one-half the dose used in our previous study of PD patients, where the dose may have been too high to provide evidence of hypersensitivity to the agent. Responses of anxiety and nervousness were statistically indistinguishable by analysis of variance in the two groups, replicating our previous findings. Panic attack symptom score (PASS) ratings were significantly higher in the PD group, compared with a trend toward higher PASS ratings in the 0.1 mg/kg study. Cortisol, human growth hormone, and male prolactin responses showed no significant differences in the two groups by analysis of variance. Prolactin responses were significantly blunted in the female patients. The unexpected blunted prolactin response to MCPP in female PD patients may reflect a nonspecific blunting of prolactin response to stress. The PASS data provide some evidence of serotonergic hypersensitivity in PD.

Effects of tryptophan depletion in panic disorder

Tryptophan (TRP) depletion is a useful paradigm for evaluating serotonin (5-HT) function in psychiatric disease. Primate studies have shown that plasma TRP depletion can be induced by the ingestion of an amino acid (AA) mixture lacking TRIP (Young et al ! 989). In this report the AA mixture without TRP reduced cerebrospinal fluid (CSF) TRP by 61% relative to a control AA mixture, which effect was associated with a 34% reduction in 5-hydroxyindole, acetic acid. Oral administration of this AA mixture following a Iow-TRP diet is known to reduce plasma TRP levels in healthy humans by over 80% of baseline levels (Zimmerman et a l i 993). In other clinical studies we have found that TRP depletion by this method produces a transient exacerbation of depressive symptoms in antidepressant-remitted depressed (Delgado et al 1990) and obsessive-compulsive patients (Barr et al 1994); however, to date there have been no studies utilizing TRP depletion in panic disorder (PD) patients. The norepinephrine (NE) and 5-HT systems have been implicated in the pathophysiology of PD (Kahn et al ! 988a, Charney et al 1992). Furthermore, the 5-HT system may provide inhibitory inputs to the principal NE nucleus, the locus coeruleus (AstonJones et ai ! 99 I). If TRP depletion sufficiently reduced presynaptic 5-HT inhibition of NE function in PD patients, this could lead to a transient increase in NE function with accompanying increases in anxiety, blood pressure, and the NE metabolite 3-methoxy-4hydroxyphenylglycol (MHPG).

Chronic mood disorders in depressed outpatients

Abstract The current study was devised to assess the utility of Research Diagnostic Criteria (RDC) categories used to classify minor mood disorders. Similar categories are to be used in the APAs Diagnostic and Statistical Manual, 3rd edition. The patient sample consisted of 64 consecutive admissions to a double-blind trial of amitriptyline, perphenazine and the combination as treatment for depression. Patients who met RDC for a current episode of major depressive disorder were given 4 weeks of pharmacotherapy as treatment. Chronic mood disorders were also assessed using RDC criteria. This evaluation revealed that only 34% met criteria for an episode of major depressive disorder alone, while 36% met criteria for intermittent depressive disorder, 14% for cyclothymic personality and 16% for labile personality in addition to being in a current major depressive episode. These 4 diagnostic subgroups were compared on demographic characteristics, childhood history, psychiatric history, presenting patterns of symptoms and social functioning, and response to treatment. Differences were noted in the subgroups in presenting symptom levels and residual impairment. However, there was no differential response to a brief course of antidepressant pharmacotherapy in patients with and without chronic minor mood disorders. Most patients showed an improvement during the brief course of treatment. Thus, the presence of a chronic minor mood disorder does not appear to be a contraindication for use of medication in patients who also are currently experiencing a major depressive episode.

Effects of the serotonin reuptake inhibitor fluvoxamine on yohimbine-induced anxiety in panic disorder

To assess the effects of the selective serotonin reuptake blocker fluvoxamine on noradrenergic function in patients with panic disorder, an intravenous yohimbine challenge test was administered to eight patients with panic disorder before and after 8 weeks of fluvoxamine treatment and to a parallel group of eight patients treated with placebo. Fluvoxamine treatment reduced yohimbine-induced anxiety while placebo treatment had no effect on this variable. Both fluvoxamine and placebo treatment had little effect on biochemical or physiologic responses to yohimbine.

Lifetime Course of Chronic Depression in Older Men

The lifetime course of illness in older outpatient men who remained symptomatic despite adequate pharmacologic treat ment for depression was examined. A bimodal distribution of age of onset of first major depression was found, with 75% having onset before age 35 years and 25% having onset after age 50 years. At all ages, episodes of chronic depression developed after episodes of major depression and appeared to be partially resolved major depression. In 88% of patients, anxiety disorders developed before age 35 years, preceded onset of other disorders, and continued throughout the patients lifetime. Seventy percent developed alcoholism and 25% had a medical illness that impaired function to a signifi cant degree. The importance of obtaining a lifetime course of illness in older patients is discussed. ( J Geriatr Psychiatry Neurol 1989;2:89-95).