Leighton Y. Huey

Effects of naloxone-HCI on cortisol levels in patients with affective disorder and normal controls

Abstract Cortisol levels were measured before and after administration of naloxone-HCI in patients with affective disorder ( n = 16) and normal control subjects ( n = 8). On two consecutive days, 20 mg of naloxone-HCI or placebo was administered i.v. over 15 minutes in a double-blind crossover design. Blood samples were collected at 30, 15, and 1 minute(s) both before and after infusion. Cortisol rose from a mean baseline level of 14.8 μg% to a mean peak level of 23.1 μg% following the naloxone administration. Significant cortisol increases were found in both the 15- and 30-minute samples during the naloxone session. There were no differences between patient and normal subject samples or between diagnostic groups. A subgroup of manic patients who had responded to naloxone with a reduction of their manic behavior also had an attenuated cortisol response to naloxone. This proved to be an artifact secondary to variability in the coritisol response in these patients.

On the sensitivity of the tourniquet pain test.

&NA; Twenty‐four chronic pain patients were given, on each of 4 successive days, oral doses of 60 mg morphine, 60 mg codeine, 600 mg aspirin and placebo, using a double‐blind counterbalanced design. Two hours after ingestion, subjective pain estimates and tourniquet pain scores were obtained. Variability of the tourniquet pain scores was too great for differences in response to the analgesics to be significant. However, differences in pain estimates were also too small to discriminate among the drugs, and the lack of sensitivity may be a function of pain chronicity. The tourniquet techniques will continue to be useful until there is a purely objective measure of the severity of clinical pain.

Hypothalamic-pituitary-adrenal regulation, neurotransmitters and affective disorders

Considerable evidence has accumulated indicating that alterations in neurotransmitters may play a role in the etiology of affective disorders on the one hand, and in the regulation of the limbic-hypothalamic-pituitary-adrenal axis (LHPA) on the other. Acetylcholine, norepinephrine, serotonin, GABA, the opioid polypeptides and dopamine have all been implicated in both phenomena. Although some contradictory evidence exists, norepinephrine, opioids, and GABA appear inhibitory, and serotonin and acetylcholine appear excitatory of the LHPA axis. In a correlative study, non-suppression of cortisol by dexamethasone correlated positively and significantly with methylphenidate-induced euphoric and antidepressant responses, and methadone induced growth hormone responses, possibly suggesting catecholamine and opioid receptor hypersensitivity. Although the overall effects of the cholinomimetic, physostigmine, did not correlate with dexamethasone non-suppression, strong positive correlations were found in a subgroup, consisting of affective disorder patients, between non-suppression of cortisol by dexamethasone and the physostigmine response, suggesting cholinergic hypersensitivity in the non-suppressing subjects.

Indications and Guidelines for Plasma Tricyclic Antidepressant Concentration Monitoring

Some tricyclic antidepressants appear to have critical ranges of plasma tricyclic antidepressant concentrations necessary for optimal clinical efficacy. For any given dose of tricyclic medication, there are marked interindividual variations in steady-state tricyclic concentrations. Furthermore, plasma tricyclic concentrations may be influenced by factors such as weight, diet, smoking status, differences in bioequivalence among manufacturers, and the addition or withdrawal of concurrent medications. There has been considerable controversy in the literature about the clinical utility of plasma tricyclic level monitoring. These authors believe that, at present, routine plasma level monitoring probably is not warranted, but that there are a variety of instances where plasma tricyclic concentration determinations may be clinically useful. The authors review methodological issues in plasma tricyclic concentration determinations and suggest guidelines for when such determinations may be clinically appropriate.

Brain Cholinergic Systems and the Pathogenesis of Affective Disorders

Extreme and debilitating fluctuations in mood have long been thought to involve chemical imbalances in the central nervous system. The role of catecholamines in the affective disorders has been emphasized since the pioneering work by Schildkraut and Kety (1967) and others, who noted that drugs which elevate mood and which are effective in the treatment of depression facilitate catecholaminergic transmission in the brain, and conversely, that drugs which may produce depression and that are used in the treatment of manic behavior tend to antagonize the synaptic actions of dopamine and norepinephrine. Measurements of catecholamine metabolites in the urine and cerebrospinal fluid of manic and depressed patients have also produced some evidence consistent with the view that depression is associated with reduced catecholaminergic synaptic transmission (Schildkraut, 1973; Schildkraut and Kety, 1967).

Correlated cholinomimetic-stimulated beta-endorphin and prolactin release in humans

Previous studies, both in animals and humans, have demonstrated that the intravenous or intraventricular administration of endogenous opioids and opiates produce dose dependent increases in plasma concentrations of prolactin. Notably, in humans, intravenous infusion of centrally active cholinomimetic drugs, such as physostigmine or arecoline, may produce significant increases in plasma concentrations of prolactin and beta-endorphin immunoreactivity. In three separate studies, conducted collaboratively between the National Institute of Mental Health and the University of California at San Diego, physostigmine and arecoline associated increases in plasma concentrations of beta-endorphin immunoreactivity were highly correlated with increases in plasma prolactin concentrations. These results are of interest because centrally active cholinomimetic drugs have been variously reported either to have no effect, to increase, or to inhibit anterior pituitary prolactin release. We propose that cholinergic stimulation of hypothalamic beta-endorphin may represent an interesting example of peptidergic modulation of primary neurochemical effects on hypothalamic-pituitary hormonal regulation.

Relationships of mood and interpersonal perceptions.

Abstract The relationship of a patients degree of negative affect to the perception of an interviewers interpersonal skills, including empathy, acceptance, warmth, and genuineness, was evaluated in 20 psychiatric patients. Significant negative correlations were found between the patients negative affect and their perceptions of their interviewers interpersonal skills. These relationships may be of theoretical and therapeutic significance.

The effects of naloxone on methylphenidate-induced mood and behavioral changes: A negative study

The effects of naloxone on IV methyl-0henidate-induced mood, behavior, and neurohumoral changes were assessed in eight psychiatric inpatients. While methylphenidate alone produced anticipated changes, the indications for significant naloxone-methylphenidate interactions were minimal. It is speculated that larger doses of naloxone might be required to produce modification of the psychostimulant effects.