Rudradeo C. Bowen

Efficacy of Divalproex Sodium in Patients with Panic Disorder and Mood Instability Who Have Not Responded to Conventional Therapy

Objective: To determine the efficacy of divalproex sodium in the treatment of psychiatric outpatients with treatment refractory panic disorder and comorbid mood instability. Method: This was an 8-week, open-trial, flexible-dose outcome study conducted at a tertiary care referral centre. Individuals with panic disorder who failed to respond to a cognitive behavioural treatment program and standard antipanic medication, who also suffered from mood instability, were chosen to participate in the study. Divalproex sodium was administered at a flexible dose to reach serum levels of 300 to 600 umol/L (45 to 90 ug/ml) unless limited by tolerance. Patients were rated by self- and rater-administered questionnaires that measured the number of panic attacks, the degree of agoraphobic avoidance, the levels of depression, anxiety, and mood swings, and the perceived sense of well being. Results: Thirteen subjects were enrolled in the study, and 10 subjects completed it. Two dropped out early because of the medications side effects, and 1 was lost within the first month of follow-up. All 10 subjects showed significant improvement in depressive and anxiety symptoms and mood instability. There was also a statistically and clinically significant improvement in panic attacks and measures of quality of life. Conclusions: These findings suggest that divalproex sodium is useful in the treatment of patients with panic disorder and concomitant mood instability, who are refractory to conventional treatment. Double-blind trials will be required to verify these findings.

A controlled trial of cognitive behavioral treatment of panic in alcoholic inpatients with comorbid panic disorder

Patients entering a 4-week inpatient alcoholism treatment program were screened for anxiety symptoms. Those with panic disorder with or without agoraphobia were randomly assigned to two groups. The treatment group received 12 hours of cognitive-behavioral treatment (CBT) for panic disorder in addition to the regular alcoholism treatment program: the control group received the regular program. Dropouts from the treatment group were also followed. Problem drinking and anxiety symptoms were measured at the start of the study, and at 3, 6, and 12 months posttreatment. Abstinence from drinking, and anxiety and mood symptoms improved after treatment in all of the groups; there were few differences in outcome between the groups. We concluded that this particular intervention had not been more effective than the regular alcohol treatment program in reducing problem drinking in those with panic disorder.

Comparison of biochemical properties of platelet monoamine oxidase in mentally disordered and healthy individuals

We have investigated some biochemical properties of platelet monoamine oxidase (MAO) isolated from chronic schizophrenic and agoraphobic patients, nonschizophrenic institutional controls, and healthy volunteers. The enzyme activity level in the healthy population was reasonably constant over at least a 6-week period. High correlations were found between MAO activity assessed for different substrates (p-tyramine, beta-phenylethylamine, and tryptamine). Some heterogeneity of the platelet MAO may exist, however, at least in some of the chronic schizophrenics, since the substrate specificities were changed and the Km values reduced. The half-life of the enzyme at 58 degrees C was 2-3 minutes and the transition temperature derived from Arrhenius plots was 16-17 degrees C with respect to beta-phenylethylamine. Platelet MAO from chronic schizophrenics was not significantly different from control values with respect to temperature effects. SDS-polyacrylamide gel electrophoresis of the 3H-pargyline-MAO adduct revealed that the subunit of platelet MAO is a single band protein with a molar individuals. The adjacent structure of the flavine site of the platelet MAO was chromatographically identical to the penta-peptide isolated from MAOs from other tissues. The response of platelet MAO to thimerosal, a new differential type A MAO inhibitor, could be distinguished not only from type A MAO isolated from human placenta, but also from type B MAO isolated from bovine liver.

A Case of Atypical Psychosis Associated with Alexithymia and a Left Fronto-Temporal Lesion: Possible Correlations

The case history is presented of a man with an atypical psychosis and classical clinical features of alexithymia. On his last admission, the patient presented with starvation and hypernatremic coma. A CT scan, which was done because of the coma, revealed a large left fronto-temporal arachnoid cyst. The significance of this finding is reviewed in the light of previously suggested organic bases for alexithymia and related syndromes. Although the symptom of alexithymia is present, the patients other symptoms do not fit readily into existing diagnostic categories and the resulting diagnostic dilemma is discussed.

Assessment of strategies for coping with anxiety: Preliminary investigations

Abstract Despite much current interest in anxiety disorders and in coping strategies, little information is available about how people spontaneously attempt to cope with anxiety. An initial pool of psychiatric outpatients was surveyed for their coping responses. Items provided by these individuals provided the basis for a classification scheme, derived by successive sorts by several raters. The 14 resulting categories were used to classify a new set of data provided by psychiatric outpatients, anxiety disordered patients, patients from general medical practices, and psychiatric clinicians. Several differences in use of strategies among the groups were observed, as well as relationships between coping strategies typically used and level of anxiety. These findings, and future development and use of the scheme, are discussed.

The Prevalence of Anxiety Disorders Among Patients With Mitral Valve Prolapse Syndrome and Chest Pain

Nineteen patients from a cardiology practice with complaints of chest pain and with mitral valve prolapse syndrome were compared with 26 patients with chest pain but no discernible cardiac disorder. Instruments included a truncated form of the Diagnostic Interview Schedule, the symptom checklist 90 revised (SCL-90-R), the McGill Pain Questionnaire, and life events, physical activity, and family history questionnaires. Neither panic disorder nor self-rated anxiety were more common in the mitral valve prolapse group. This study failed to confirm the reported high association between mitral valve prolapse syndrome and panic disorder.

The effects of a nurse therapist conducted behavioral agoraphobia treatment program on medical utilization

Abstract This study assessed the use of health care services by clients in a panic and agoraphobia treatment program for one year before and one year after treatment/assessment. The graduate group attended the program and complied with homework assignments. A comparison group was composed of those who dropped out after assessment. Results indicated that the graduate group reduced use of general practitioners, assessments, laboratory, home visits, and total services, compared with the comparison group. The data suggest that a nurse-therapist-conducted agoraphobia treatment program reduces the use of medical services in patients who comply.

A study of the catabolism of trace amines in mentally disordered individuals with particular reference to agoraphobic patients with panic attacks.

Platelet MAO activity toward several trace amine substrates and the plasma levels of some trace acids have been investigated. Compared to controls, the agoraphobic patients were found to have significantly increased MAO activity. The substrate specificity in some of the patients appeared to be altered. The plasma levels of p-HPA and m-HPA were significantly lower than those of the control groups.

Deuterium-labelled p-tyramine challenge test and phenolsulfotransferase activity in depressed patients--failure to replicate decreased p-tyramine conjugation in depression.

1. Depressed and normal subjects were challenged with deuterium-labelled p-tyramine and urine was collected for 3 h. 2. Urinary excretion of conjugated p-tyramine was not significantly different between normal, melancholic and non-melancholic depressed subjects. 3. Platelet phenolsulfotransferase activity to p-tyramine (p less than 0.05) and to phenol (p less than 0.005) were significantly lower in the depressed patients.

Longitudinal effect of amitriptyline and fluoxetine treatment on plasma phenylacetic acid concentrations in depression.

Unconjugated (U-PAA), conjugated (C-PAA), and total phenylacetic acid (T-PAA) concentrations in blood plasma and monoamine oxidase (MAO) activity in platelets towards phenylethylamine (PE) were determined in 40 drug-free, depressed patients (23 melancholic, 17 nonmelancholic) from five psychiatric treatment centers, and in 34 normal healthy volunteers. No significant differences were found between controls and all depressed patients or between melancholic and nonmelancholic depressed patients. Treatment of the depressed patients with amitriptyline or fluoxetine over a 6-week period resulted in clinical improvement and in a significant increase in plasma PAA concentrations. A decline in the Beck and Hamilton rating scores during treatment correlated significantly with increases in the concentrations of unconjugated, conjugated, and total phenylacetic acid but not with MAO activity, which did not change during treatment. At each of the three assessment times, however, plasma PAA concentrations and psychiatric rating scores were not significantly correlated. Except for higher end-of-study T-PAA concentrations in the amitriptyline-treated subjects, no significant differences were found between the effects of the two drugs with regard to plasma phenylacetic acid levels, MAO activity, or rating scores.