Gordon Johnson

Dexamethasone suppresion test (DST) and plasma dexamethasone levels in depressed patients

The dexamethasone suppression test (DST) was evaluated in newly hospitalized patients with a DSM-III diagnosis of major depression. Patients with other psychiatric disorders and a normal control group were also studied. Plasma dexamethasone levels were obtained in all patients, and the relationship between plasma cortisol and plasma dexamethasone was examined. Rates of non-suppression in patients with major depression (39%) were not significantly different from those in patients with minor depression (25%), mania (38%), or other psychiatric illnesses (17%). The ranges of dexamethasone levels at 8 a.m. and 4 p.m. were similar between patient groups and controls. However, there was a significant difference in dexamethasone levels between suppressors and nonsuppressors, irrespective of diagnosis, which could not be explained by differences in weight or plasma dexamethasone half-life. Inappropriately high dexamethasone levels were found in some patients with a 1 mg test, a problem that critically affects the sensitivity of the test procedure.

Bipolar Affective Disorder in Adolescence: A 10-Year Study

A descriptive study of bipolar affective disorder in adolescent patients, conducted over a 10-year period, is presented. The diagnosis of 30 subjects referred to an adolescent treatment facility of a major teaching hospital was reviewed using DSM-III criteria, and antecedent symptomatology and signs were documented. Common diagnostic features included schizophreniform phenomenology, motoric and vegetative changes, suicidal and inappropriate sexual behaviour and a stormy first year of illness. A positive family history was frequently noted, as was the relevance of various forms of loss as a precipitant of the first episode. Timely recognition and multidisciplinary management, including the use of lithium, are discussed. It appears that the prognosis of bipolar affective disorder in adolescence is better than was previously believed, probably as a result of earlier diagnosis and more frequent recognition.

Pharmacokinetics of dexamethasone and its relationship to dexamethasone suppression test outcome in depressed patients and healthy control subjects

The pharmacokinetics of dexamethasone (DEX) were studied in 9 drug-free melancholically depressed patients and 10 healthy control subjects matched by sex and age. Each subject received 1 mg of DEX administered orally and by the (i.v.) route at 11:00 PM and serial blood samples were collected over the next 17 hours until 4:00 PM. There were no significant differences between the diagnostic groups and DEX bioavailability, peak plasma level, time to maximum concentration, or in elimination half-life after oral administration. Bioavailability estimates indicated that DEX absorption was incomplete and variable mean = 61%, SD = 14) in controls as well as depressed patients. In both groups there was a wide interindividual variability in plasma DEX levels following both oral and i.v. routes of administration. This variability could not be reliably predicted by differences in age, sex, or weight between subjects. The factors that accounted for most the variability in 4:00 PM plasma DEX levels after oral administration were clearance, bioavailability, and time to reach maximum concentration. Plasma DEX levels were lower in 3 depressed nonsuppressors compared to 3 matched controls who suppressed. No single pharmacokinetic factor was shown to be responsible for the lower DEX levels in the depressed nonsuppressors. These results indicate that plasma DEX levels need to be measured in each individual during the DST procedure so that this information may be taken into consideration when interpreting DST results.

Lithium—Early Development, Toxicity, and Renal Function

The report of the effectiveness of lithium in the treatment of mania by John Cade was followed by a number of studies confirming his observations and developing guidelines for safe and effective use. Premature rejection of lithium on safety grounds denied many patients the benefit of treatment and may have cost more lives than it saved. A similar safety alarm was triggered by reports of kidney damage in the late 1970s. Subsequent reports have questioned the significance of anatomical findings, and functional impairment and relationship to lithium treatment. Recent findings support the conclusion that progressive impairment of glomerular and tubular function in patients during lithium maintenance is the exception rather than the rule and is related more to lithium intoxication, maintenance plasma lithium levels, concurrent medications, somatic illness, and age than on time on lithium. Guidelines for lithium use and monitoring of renal function are outlined.

Renal function and lithium treatment: Initial and follow-up tests in manic-depressive patients

Assessment of renal function was carried out in an unselected sample of patients with bipolar manic-depressive disorder receiving lithium for an average period of 4.5 years. Overall, glomerular filtration rate (GFR) fell within the established normal range based on sex and age, whereas measures of urinary concentrating ability were generally impaired. There was no relationship between duration of lithium treatment and either GFR or impairment of urinary concentrating ability. Moreover, there was no evidence of a progressive impairment of glomerular or tubular function in patients re-tested after 2 years. The results of this study confirm the safety of lithium administration in the majority of patients and emphasize the importance of careful clinical monitoring to avoid lithium intoxication.

Suicidal behavior in bipolar manic-depressive patients and their families

Abstract There is a high risk of suicidal behavior in patients with primary affective disorder. An extensive investigation in patients with primary affective disorder reported attempted suicide in 26% of bipolar patients and 21% of unipolar patients, the highest rate occurring in female bipolar patients. 1 Woodruff et al. 20 found attempted suicide in 14% of unipolar patients as against 32% of bipolar patients with the highest rate in male bipolar patients. Winokur 18 in a study of bipolar manic depressive patients found that 25% of patients had made at least one suicidal attempt and 70% had made threats of suicide at least some time in their lives. Venkabo Rao 16 reported that suicidal ideas occurred in 75% of patients with recurrent affective disorder. Family studies have also reported a high incidence of suicide in the relatives of patients with affective disorder. 8 Mendlewicz et al. 7 studying a matched group of bipolar probands with and without a family history of manic depressive illness, found high rates of suicide in first and second degree relatives but there was no significant difference in relation to sex or family history. The diagnosis of the relative that suicided was not stated. A study of relatives of patients with primary affective disorder 10 reported that 79% of the suicides in first degree relatives were associated with a diagnosis of probable affective disorder and 10% by a diagnosis of probable alcoholism in the relative. Fathers in index cases were more likely to have committed suicide than mothers. A family history of suicide is considered a major risk factor in assessment of potentially suicidal patients, 13 however, the relationship between attempted suicide in patients and suicide or attempted suicide in relatives has received little attention and the nature and predictability of this association is uncertain. The following report concerns an analysis of suicidal behavior in a population of bipolar manic-depressive patients and the relationship of this attempt to suicide or attempted suicide in their first and second degree relatives.

Intensive Nutritional Counselling in Bulimia Nervosa: A Role for Supplementation with Fluoxetine?

Objective: The aims of the paper are to determine whether nutritional counselling is associated with an improvement in bulimic symptomatology, whether this improvement is maintained during post-treatment follow-up, and whether the addition of fluoxetine 3 × 20 mg/day confers additional benefit. Method: Psychological, pharmacological and combined psychopharmacological treatments of bulimia nervosa were reviewed briefly. Sixty-seven patients referred to specialist eating disorder services who fulfilled strict diagnostic criteria were treated with intensive nutritional counselling and randomly assigned to either fluoxetine 3×20 mg/day or placebo. After a 1-week ‘wash-out’, active treatment was given over 8 weeks, followed by post-treatment interviews at 12 and 20 weeks. Results: Both groups of patients improved significantly during treatment. In some respects, the fluoxetine group did slightly better as demonstrated by the items ‘restraint’, ‘weight concern’ and ‘shape concern’ (p<0.05 vs p<0.0001) on the Eating Disorder Examination (EDE). Fluoxetine patients decreased their energy intake and lost a modest amount of weight. They went on to regain weight during the follow-up period, returning to levels higher than they were initially. These patients also appeared more likely to have a recurrence of symptoms, as shown by the fall in percentage of binge-free patients and by changes in the EDE. Conclusion: Nutritional counselling is an effective means of treating bulimia nervosa, with improvement maintained up to 3 months follow-up. The addition of fluoxetine may confer some benefit during active treatment, but its discontinuation may contribute to a higher rate of recurrence of symptoms post treatment. Of course, this study cannot be extrapolated to the efficacy of fluoxetine when used as the only form of treatment in patients for whom intensive nutritional counselling or other structured psychological programs are not available.

Growth hormone and cortisol secretion after oral clonidine in healthy adults

The purpose of this study was to evaluate oral clonidine for testing growth hormone (GH) responsiveness in healthy adults. Oral clonidine (0.15 mg) produced a satisfactory GH response (greater than 4 ng/ml from basal) in eight out of 10 subjects, which is similar to rates reported after an equivalent intravenous dose. Elevated GH levels at baseline occurred in four out of five female subjects; this did not affect the clonidine-induced GH release. There were no significant differences at any time point in plasma prolactin or cortisol levels following clonidine, compared to placebo controls. Adequate plasma clonidine levels (greater than 0.4 ng/ml) were achieved in all subjects, with corresponding reductions in mean arterial blood pressure, but with only minimal adverse effects. Results from this study indicate that oral clonidine is a reliable method for testing GH responsiveness in adult subjects.

Studies of rat brain metabolism using proton nuclear magnetic resonance: spectral assignments and monitoring of prolidase, acetylcholinesterase, and glutaminase

The first application of inversion‐recovery spin‐echo proton nuclear magnetic resonance spectroscopy to the monitoring of reactions in rat brain preparations is presented. The initial report of the assignment of proton spin‐echo nuclear magnetic resonance spectra from rabbit brain homogenates (C. R. Middlehurst et al., J. Neurochem. 42, 878–879, 1984) was used to assist in the assignment of spectra acquired from rat brain homogenates that were obtained from animals killed by cervical fracture or focussed microwave irradiation. Microwave‐irradiated brains were divided into four major anatomical regions. Differences in metabolite levels were detected when spectra from fresh tissue and from various regions were compared. The in situ steady‐state kinetics of prolidase in whole brain homogenate was determined.

The effect of age on cortisol and plasma dexamethasone concentrations in depressed patients and controls

The aim of this study was to identify any relationships between various patient factors such as age, gender and concurrent medication that may affect plasma cortisol or dexamethasone (DEX) concentrations. Multiple regression analysis was used to formulate an equation to predict plasma DEX levels to identify factors that may influence DEX bioavailability. Pre- and post-DST cortisol levels did not increase with age, but DEX levels were higher in elderly depressed patients. Neither gender nor psychotropic medication affected plasma cortisol or DEX levels. There was no indication that pre-DST cortisol levels influenced plasma DEX levels to account for the lower DEX values in non-suppressors. Age was the only significant factor found in this study to influence DEX levels and it could be argued that the dose of DEX should be lowered when administering the DST to elderly patients to reduce plasma DEX variability.