Euthyroid sick syndrome in psychiatric inpatients.

Numerous disorders are associated with euthyroid sick syndrome (ESS). This retrospective study examines the incidence and circumstances of ESS among 3188 psychiatric inpatients. There were 324 patients (10.2%) who met strictly defined criteria for ESS. Of these, 95 were hyperthyroxinemic (HT), 6 were hypothyroxinemic, 179 had mildly elevated thyroid-stimulating hormone (HTSH), and 47 had suppressed TSH. All were classified by DSM-III-R discharge diagnoses, encompassing five categories. chi 2 tests of significance of the 95 HT and 179 HTSH subjects revealed the following: 1) no relationship with age or gender; 2) the frequencies of HT and HTSH differed significantly (p < .05 and p < .01, respectively) across the five psychiatric categories; 3) HT frequency was highest in mood disorders (HT in mood versus others p < .02); and 4) HTSH frequency was highest in substance abuse (HTSH in substance abuse versus others p < .02). In conclusion, ESS is common in psychiatric inpatients, especially HT and HTSH; pathophysiologic mechanisms may vary according to psychiatric diagnosis.

Potential abnormalities in molecular forms of growth hormone in schizophrenia: a pilot study.

Growth hormone has been investigated in numerous studies involving patients with schizophrenia but has been measured only by radioimmunoassay (RIA). There have been no consistent abnormalities differentiating patients with schizophrenia from normal controls. In the current study, growth hormone (GH) variants were measured by Western blotting techniques, which resulted in the quantitation of 4 GH size variants: 27K (27,000 Daltons), 22K, 20K, and 17K. In the entire sample of 17 schizophrenic subjects, all GH variants were significantly higher than in the 14 normal controls. While there were no significant differences between the 2 groups in RIA GH values, the RIA values were generally higher in the schizophrenic group. In a subset of 12 schizophrenic patients whose RIA values were approximately equal to the controls, both the 27K and 22K GH variants remained significantly higher in the patient group. In the schizophrenic group, none of the GH variants or RIA GH changed significantly after 1 week of treatment with neuroleptic medication. These preliminary results suggest that certain GH forms may be elevated in schizophrenia, but further studies are needed.

Desamino-D-arginine-vasopressin (DDAVP) in Alzheimer's disease.

Fourteen Alzheimer subjects participated in a parallel group study of desamino-D-arginine-vasopressin (DDAVP, desmopressin). All subjects received one week of single-blind placebo. Then on a double-blind basis, the active group received DDAVP intranasally in doses starting at 30 micrograms per day and increasing over a 3 week period to 180 micrograms per day; the control group received an identical placebo. Using a repeated measures ANOVA, three measures out of thirty-one were found to be statistically significant for DDAVP treatment: the Hamilton depression scale and the affect and interpersonal subscales of the SCAG. However, the magnitude of these changes was probably too small to be clinically significant. Except for one subject who transiently became hyponatremic (Na of 120) and confused while receiving 180 micrograms of DDAVP, there were no adverse effects. There were no significant group changes in sodium, potassium, plasma osmolality, blood pressure, and weight.

Desglycinamide-9-arginine-8-vasopressin (DGAVP, Organon 5667) in patients with dementia.

Vasopressin peptides have been shown to facilitate learning and memory in both animals and humans; however, the effectiveness in humans is controversial. In a double blind parallel group study, 17 demented subjects (either Alzheimer's or alcoholic) were given either desglycinamide-9-arginine-8-vasopressin (DGAVP) 92 micrograms intranasally TID or an identical placebo for 1 week after having received 1 week of placebo. To our knowledge, this is the first report of DGAVP being used in subjects with dementia. The DGAVP group had a statistically significant improvement on the Buschke list learning of low imagery words. However, for various reasons discussed in the paper, we feel this finding needs to be replicated before any definite conclusions can be drawn. Since there were no other appreciable behavioral effects of this DGAVP regimen, our results should be considered negative. There was no evidence of any DGAVP-related adverse effects, except for possible weight gain.

Clinical relevance of drug interactions with lithium.

Although lithium continues to be regarded as the treatment of choice for bipolar disorders, the clinical use of this mood stabiliser is associated with an extremely narrow therapeutic range. Relatively minor increases in serum concentrations may induce serious adverse sequelae, and concentrations within the therapeutic range may result in toxic reactions. The safety of combining lithium with other medications, therefore, is a major concern, and extensive clinical experience has served to identify several significant drug interactions. Lithium removal from the body is achieved almost exclusively via renal means. As a result, any medication that alters glomerular filtration rates or affects electrolyte exchange in the nephron may influence the pharmacokinetic disposition of lithium. Concomitant use of diuretics has long been associated with the development of lithium toxicity, but the risk of significant interactions varies with the site of pharmacological action of the diuretic in the renal tubule. Thiazide diuretics have demonstrated the greatest potential to increase lithium concentrations, with a 25 to 40% increase in concentrations often evident after initiation of therapy. Osmotic diuretics and methyl xanthines appear to have the opposite effect on lithium clearance and have been advocated historically as antidotes for lithium toxicity. Loop diuretics and potassium-sparing agents have minor variable effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been associated with lithium toxicity, although the relative interactive potential of specific NSAIDs is difficult to determine. Small prospective studies have demonstrated large interindividual differences in lithium clearance values associated with different NSAIDs. A growing body of evidence also suggests that ACE inhibitors may impair lithium elimination, but further investigations are needed to identify patients at risk. Anecdotal reports have linked numerous medications with the development of neurotoxicity without an apparent effect on the pharmacokinetic disposition of lithium. Antipsychotics, anticonvulsants and calcium antagonists have all be implicated in a sufficient number of case reports to warrant concern. As these medications have all been commonly coadministered with lithium, the relative risk of serious interactions appears to be quite low, but caution is advised.

The effect of haloperidol on aldosterone secretion.

Haloperidol (0.02 mg/kg, intravenous) did not stimulate aldosterone secretion in six normal controls or in six schizophrenic subjects. This is contrary to our hypothesis, which was based on the finding that peripheral D2 receptor antagonists stimulate aldosterone secretion, including haloperidol in rats and chlorpromazine in man. We speculated that a different dose of haloperidol would stimulate aldosterone in man. As expected, prolactin release was markedly stimulated in both groups of subjects, but no difference was found between groups.

High initial nortriptyline doses in the treatment of depression.

BACKGROUND: Guidelines for doses of nortriptyline are generally somewhat vague and usually recommend a fairly wide dose range. Additionally, the safety and utility of beginning treatment at higher initial doses have not been adequately investigated. METHOD: Nortriptyline treatment was initiated with a 75- to 125-mg dose depending on weight in 26 depressed inpatients in an open-label study. RESULTS: The mean Hamilton Rating Scale for Depression score decreased by 45% within 1 week (p < .001) and remained essentially unchanged at the end of Week 2. Orthostatic hypotension was the side effect of major concern since it is virtually the only significant cardiovascular effect in young healthy individuals treated with tricyclic antidepressant medication. Only 2 patients developed orthostasis, which required additional treatment with fludrocortisone, and no patients were dropped from the study due to side effects. None of the patients evidenced significant ECG changes. Twenty-one patients (81%) reached therapeutic drug levels on the initial dose regimen by the end of Week 1. CONCLUSION: Subjects tolerated high initial doses well and appeared to reach significant benefit within the first week. However, double-blind controlled studies are needed before any definitive conclusions can be drawn.

Usefulness of screening EEGs in a psychiatric inpatient population.

Many clinicians presume that a screening electroencephalogram (EEG) is useful in differentiating psychiatric from neurologic disorders. In a retrospective review of 698 charts of psychiatric inpatients, the authors assessed the usefulness of screening EEGs. Usefulness was defined as leading to a change in diagnosis or treatment. While 31% of screening EEGs were abnormal, only 1.7% of cases led to a change in diagnosis that might otherwise have been missed. It is unclear whether the EEG is a useful screening test on the basis of these results. Caution is warranted in interpreting these results because of the inaccuracies inherent in any retrospective review. Prospective studies are needed to better define EEG's usefulness in psychiatry.

Trazodone and priapism.

The association of priapism with trazodone is reviewed based on data reported to the Food and Drug Administration. The data suggest that priapism may be most likely to occur within the first 28 days of treatment and that the majority of cases occur with doses of 150 mg/day or less. All age groups appear to be vulnerable to this adverse effect. Patients should be informed of this potential side effect and instructed to discontinue the medication if any unusual erectile problems develop.

Alprazolam as an antidepressant.

Alprazolam appears to be an effective antidepressant in the treatment of outpatients who have a diagnosis of major depressive disorder. The authors have reviewed six controlled double-blind studies of alprazolam in the treatment of depression. Four of the six studies included only outpatients and clearly demonstrated a clinical effectiveness comparable to that of the tricyclics but with fewer, less severe side effects and better tolerance. The other two studies involved both inpatients and outpatients, so no conclusions can be drawn regarding the effectiveness of alprazolam in an inpatient population; further controlled studies are needed to answer this question. No satisfactory explanation exists for the mechanism of alprazolam's proposed antidepressant action.

Antidepressants and the elderly.

The pharmacologic treatment of depression in the elderly is often complicated by cardiovascular disease and other medical illnesses. Both the tricyclic antidepressants and the monoamine oxidase (MAO) inhibitors have adverse effects that are potentially dangerous in this age group. Second generation antidepressants may have fewer cardiovascular and anticholinergic side effects, but many do not offer any real advantage over the older drugs. In practical terms, the choice of antidepressants for use in elderly patients will be based largely on their degree of tolerance for unwanted effects.

Elevated baseline and postdexamethasone cortisol levels. A reflection of severity or endogeneity?

This study investigated whether elevated baseline and postdexamethasone cortisol levels were more strongly related to severity of depression or presence of endogenous symptoms. In 43 inpatients with major depressive disorder, a positive correlation was found between the total score on the Hamilton Rating Scale for Depression and 8.00 a.m. and 4.00 p.m. baseline and 8.00 a.m. and 4.00 p.m. postdexamethasone cortisol levels. Only the 8.00 a.m. postdexamethasone cortisol level was significantly correlated with the number of Research Diagnostic Criteria (RDC) endogenous items present. Despite a statistically significant relationship between severity and endogeneity, our results suggest elevated baseline and postdexamethasone cortisol levels may be more closely related to severity of depression, rather than the presence of a cluster of symptoms referred to as endogenous.

TRH stimulation test and depression.

A thyrotropin-releasing hormone (TRH) stimulation test was performed in 52 male inpatients with major depressive disorder. Twenty-nine percent of the 52 subjects had a delta thyroid-stimulating hormone (delta TSH) less than 5 microU/ml. The cerebrospinal fluid (CSF) amine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA), were measured in 29 subjects, and a dexamethasone suppression test (DST) was performed in 48 subjects. Of the three CSF amine metabolites, only MHPG correlated significantly with baseline TSH and none correlated with delta TSH. The baseline TSH correlated positively with the TSH response at 30 minutes. Neither baseline TSH nor delta TSH correlated with cortisol levels before or after dexamethasone. The correlation between CSF MHPG and serum TSH suggests a relationship between central norepinephrine and baseline TSH.

CSF amine metabolites and depression.

Cerebrospinal fluid (CSF) amine metabolites were measured in 37 male subjects with major depressive disorder. Scores on the Hamilton Rating Scale for Depression (HRSD) correlated significantly with 5-hydroxyindoleacetic acid (5HIAA) and with homovanillic acid (HVA). In addition, the single suicide item of the HRSD correlated significantly with 5HIAA. Further, 5HIAA and HVA correlated significantly with each other. There was a significant positive correlation between HVA and two HRSD items, the depersonalization/derealization item and the paranoid item. Since lumbar CSF metabolite concentrations may reflect central nervous system activity of parent amines, these data suggest a relationship between depression and decreased dopaminergic and serotonergic activity.

Lower prolactin bioactivity in unmedicated schizophrenic patients.

In previous work, prolactin (PRL) abnormalities of a lower bioassay (BA) to radioimmunoassay (RIA) ratio were found in schizophrenic patients. This line of research was extended in seven male patients with schizophrenia who were neuroleptic-free; seven male control subjects were also studied. PRL values were assessed by RIA and Nb(2) BA techniques. The schizophrenic group had a significantly lower PRL BA as compared to normal controls and a lower PRL ratio of BA/RIA. The lower ratio is consistent with an earlier finding and suggests that schizophrenic patients have different molecular forms of PRL than control subjects. This difference could be due to a disordered tuberoinfundibular dopamine system or the long-term effects of neuroleptic medications.

Growth hormone response to growth hormone releasing hormone in depression and schizophrenia.

Growth hormone releasing hormone, a 44-amino acid peptide (GHRH-44), was administered (1 micrograms/kg i.v.) to 6 normal controls, 10 schizophrenic subjects, and 7 depressed subjects. A significantly lower growth hormone (GH) response was found in the schizophrenic and depressed groups. Two molecular forms of GH, 22K GH and 20K GH, were also measured but did not further differentiate the three groups of subjects.

Prolactin bioassay in schizophrenia before and after neuroleptics.

Fifteen drug-free schizophrenic male inpatients and 14 normal control subjects were studied. The schizophrenic subjects had a significantly lower ratio of bioassay prolactin to radioimmunoassay prolactin before neuroleptic treatment than they did after treatment. The ratio was lower in the drug-free patients as compared with normal controls. These findings suggest that neuroleptic medications may alter the molecular forms of serum prolactin. The results also suggest that drug-free schizophrenic patients may have a different pattern of prolactin variants than normal subjects and that this difference could be secondary to a disordered tuberoinfundibular dopamine system or long-term effects of neuroleptic drugs.

Bioassayable and immunoassayable prolactin responses to thyrotropin-releasing hormone: use of the Nb2 lymphoma cell bioassay.

The peak prolactin response to thyrotropin-releasing hormone (TRH) varies among patients. "Exaggerated" responses have been described and linked to ovulatory dysfunction. Herein we describe our initial observations on bioassayable prolactin (BA-PRL) versus immunoassayable prolactin (RIA-PRL) in women with normal baseline RIA-PRL concentrations but with varying peak RIA-PRL responses to TRH. Twenty-three women of reproductive age with baseline RIA-PRL of =25 ng/mL were administered 500 microg of TRH, and baseline and peak RIA-PRL concentrations were determined. Aliquots of the baseline sample and the sample representing the peak RIA-PRL were used for measuring BA-PRL by means of the Nb2 lymphoma cell bioassay. For each sample, BA/RIA-PRL ratios were determined. Positive correlations were found between peak RIA-PRL and baseline BA/RIA-PRL ratios (P<0.05) and also between baseline and peak BA/RIA-PRL ratios (P<0.001). Negative correlations were found between baseline RIA-PRL and both baseline and peak BA/RIA-PRL ratios (P<0.001 and P<0.05, respectively). We conclude that (1) the lactotroph response to TRH in women with normal RIA-PRL may, in part, be governed by the amount of biologically active prolactin at baseline and (2) the relative proportion of BA-PRL to RIA-PRL produced at baseline is maintained at peak response. Finally, in light of the greater availability of bioactive prolactin in women with exaggerated TRH responses, our findings support the use of bromocriptine in those patients with such responses and ovulatory dysfunction.

Psychiatric correlates of repetitive rhythmic blinking on a routine EEG.

Our findings suggest that EEG tracings dominated by repetitive rhythmic blinking (RRB) may be indicative of a functional rather than an organic brain disorder. Evaluation of organicity in psychiatric patients is the most common reason for obtaining an EEG. As a normal EEG does not totally rule out organic involvement, such findings as the presence of RRB on the record may strengthen the value of EEG in such evaluations. More research is necessary to further delineate the relation between increased blinking and functional psychiatric disorders.

Reliability of diagnoses made by psychiatric residents in a general emergency department.

The reliability of psychiatric diagnoses made by psychiatric residents in the general emergency department of a university hospital was assessed by comparing those diagnoses with the inpatient discharge diagnoses of patients referred to the hospital's inpatient service from the emergency department. In both settings diagnoses were based on DSM-III-R criteria, but structured diagnostic instruments were not used. Retrospective review of the records of 190 inpatients over a six-month period showed excellent to moderate concordance between principal axis 1 diagnoses in four categories--major depression, schizophrenic disorders, bipolar disorder, and substance abuse and dependence disorders. Kappa values ranged from .64 for major depression to .87 for substance abuse and dependence disorders.