Brain serotonin (5-HT) neuroendocrine function in patients taking cholesterol-lowering drugs.

Brain serotonin (5-HT) neuroendocrine function, plasma tryptophan, and platelet 5-HT content were examined in 20 patients treated in a lipid clinic for hypercholesterolaemia with combined drug and diet therapy and in 20 healthy matched controls. Treatment had produced a substantial decrease in total cholesterol concentrations in the patients, but they still had higher cholesterol and triglyceride levels than control subjects. The patients were somewhat more depressed than controls but did not differ from them in degree of hostility, free or total plasma tryptophan, or prolactin response to 30 mg of d-fenfluramine. This study does not reveal evidence of abnormal brain 5-HT neuroendocrine function in hypercholesterolaemic patients receiving cholesterol-lowering medications and diet.

Osteopenia, pathological fractures, and increased urinary calcium excretion in schizophrenic patients with polydipsia.

Ten male chronic schizophrenic patients with polydipsia and 10 nonpolydipsic controls, matched for gender, diagnosis, duration of illness, age, and race, were studied by dual- and single-photon absorptiometry to estimate bone density of the lumbar spine and radius and by 24-hr urine collections to estimate urinary electrolyte excretion. Bone density was normal in the control group, but was abnormally low in the polydipsic group, which had a markedly increased incidence of fractures. Electrolyte excretion was normal in the control group and in the polydipsic group when water intake was restricted to normal amounts; increased urinary sodium and calcium excretion occurred in proportion to polydipsia. As polydipsia is associated with a number of physiological changes, the cause of the osteopenia is unclear; we suggest that a negative calcium balance caused by increased urinary calcium excretion induced by extracellular space expansion may play an important role in the causation of the skeletal changes.

Sleep deprivation in depression: pattern of relapse and characteristics of preceding sleep.

The pattern of relapse following therapeutic response to 40-hr sleep deprivation (SD) was examined in nine depressed patients. On the night ending SD patients were awakened from polygraphically recorded sleep on one or more occasions, in order to assess the clinical state. All subjects were found to demonstrate a precipitous and full relapse over this night, the timing of the relapse varying considerably between individuals. No association was found between deterioration in the clinical state and characteristics of preceding sleep. These results are consistent with the notion that, in predisposed individuals, some process associated with sleep has a depressogenic effect. However, they necessitate revision of theories of SD and depression that emphasize the infrastructure of sleep.

Thyroid function and response to 48-hour sleep deprivation in treatment-resistant depressed patients.

BACKGROUND: Clinical depression is associated with abnormalities of the hypothalamic-pituitary-thyroid axis. Changes in thyroid function during sleep deprivation may be related to its antidepressant effects. METHODS: Levels of thyroid-stimulating hormone, tri-iodothyronine, tri-iodothyronine uptake, thyroxine, and free thyroxine were measured before, during, and after a 48-hour sleep deprivation in nine treatment-resistant depressed patients. Clinical state was assessed every 4 hours. A retrospective study of 26 similar patients was added for cross-validation. RESULTS: Significant increases in thyroid-stimulating hormone and tri-iodothyronine during sleep deprivation were not correlated with clinical improvement. Sleep deprivation responders had lower tri-iodothyronine uptake levels than nonresponders in both the prospective (p <.02) and the retrospective (p <.03) samples. CONCLUSIONS: The lower tri-iodothyronine uptake values in responders may identify a subgroup of depressed patients who respond to sleep deprivation by virtue of some abnormality of the hypothalamic-pituitary-thyroid axis that is temporarily corrected by sleep deprivation.

Neuroendocrine effects of sumatriptan.

The neuroendocrine effects of the 5-HT receptor agonist, sumatriptan (6 mg subcutaneously), were studied in 11 healthy male subjects using a placebo-controlled, cross-over design. Compared to placebo, sumatriptan significantly lowered levels of plasma prolactin but increased those of plasma growth hormone. There was no effect on plasma cortisol concentrations. The neuroendocrine effects of sumatriptan differ from those of previously described 5-HT-receptor agonists, and may be a consequence of selective activation of 5-HT1D or 5-HT1B receptors. However, the present data cannot exclude the possibility that the neuroendocrine changes reflect nonspecific stress responses or changes in pituitary blood flow.

Myocardial infarction during sleep deprivation in a patient with dextrocardia--a case report.

A patient with dextrocardia who suffered his first myocardial infarction after approximately 26 hours of a diagnostic sleep deprivation protocol is described. The infarction started about 3 hours after a significant improvement in mood, which persisted during and after infarction. Total sleep deprivation may be an acute risk factor for myocardial infarction.

Preventing lithium intoxication. Guide for physicians.

OBJECTIVE: To raise awareness of risk factors for, and symptoms of, lithium intoxication. QUALITY OF EVIDENCE: The literature was searched via MEDLINE from January 1970 to December 1999 using the MeSH headings Lithium, Lithium Carbonate, Drug Toxicity, and Aging. Articles were selected based on clinical relevance and design. Most were case reports, case series, or reviews. MAIN MESSAGE: A case study illustrates both risk factors predisposing patients to lithium intoxication and the symptoms of lithium intoxication. Lithium intoxication can be avoided by conservative dosing, care in combining drug therapies, regular clinical observation, monitoring drug plasma concentrations, and educating patients and caregivers to recognize early signs of intoxication. CONCLUSION: Knowing about lithium intoxication and how to avoid it is most important for family physicians who regularly treat patients receiving lithium.

Polydipsia in chronic psychiatric patients. Body weight and plasma sodium.

Eight chronic psychiatric in-patients with polydipsia, and polyuria, up to 22 litres per 24 hours, were studied by frequent timed body weight and urine volume measurements, and episodic plasma electrolyte estimations. During the day they all showed irregular water retention, with hyponatremia in proportion to the weight gain. During the night they always lost water and weight, returning to their individual lowest weights and to normal plasma sodium. Measurement of weight in chronic psychiatric patients can be used to identify patients with significant polydipsia, to monitor those with the disorder and permit targeted fluid restriction, and to assess the efficacy of treatment procedures such as medication.

Valproate prophylaxis for migraine induced by selective serotonin reuptake inhibitors.

We report the successful use of valproate in a 44-year-old woman with migraine induced by selective serotonin reuptake inhibitors. Valproate should be considered for those patients who develop serious migraine for the first time, or worsening of previous migraine, after the initiation of treatment with selective serotonin reuptake inhibitors and for whom continued treatment with this class of drugs is important.

Flupenthixol in chronic schizophrenic inpatients: a controlled comparison with haloperidol.

Two neuroleptics having different effects at dopamine receptors were administered to chronic schizophrenic inpatients to compare their therapeutic efficacy and ability to produce side effects. Haloperidol appeared to produce lower levels of psychopathology than flupenthixol but similar levels of side effects. No evidence was found that flupenthixol is specifically useful in "activating" chronic patients or in alleviating affective symptoms. Although these are preliminary results, they support the view that D2 receptors may mediate the antipsychotic effects of neuroleptic drugs.

Successful use of propranolol in migraine associated with electroconvulsive therapy.

To date, there have been no reports on the use of propranolol in electroconvulsive therapy (ECT)-induced migraine; we describe a 32-year-old woman who was successfully treated with propranolol for this condition. Over a course of ECT, the patient developed increasingly severe migraine which was refractory to treatment with acetaminophen, codeine, and naproxen. Sumatriptan did not relieve the headache and aggravated the nausea. Successful migraine relief was achieved with a combination of propranolol and naproxen, administered before and after ECT. Propranolol reduced blood pressure and decreased the heart rate, measured before and immediately after ECT. Propranolol, possibly in combination with naproxen, may be useful in both acute and prophylactic treatment of post-ECT migraine.

Prophylactic medication for unipolar depressive illness: the place of lithium carbonate in combination with antidepressant medication.

A meta-analysis of the controlled clinical trials comparing the efficacy of combined lithium-imipramine therapy with each drug alone in the prevention of relapse in patients with unipolar depressive illness shows the combination to be superior to lithium alone (for any relapse, p less than 0.05; for specifically depressive relapse, p less than 0.025) and imipramine alone (for any relapse, p less than 0.025; for specifically depressive relapse, p less than 0.05). The issue of statistical power in studies of this kind is discussed. A single case of unipolar depressive illness is described, in which combined lithium-tranylcypromine therapy was superior to either drug alone. A combination of lithium and an antidepressant should be considered for any patient suffering from this condition who fails to remain well on either drug alone.

Protocols for the use of cyproterone, medroxyprogesterone, and leuprolide in the treatment of paraphilia.

OBJECTIVE: To propose a protocol for minimizing medical complications associated with the use of cyproterone, medroxyprogesterone, and depot leuprolide to treat paraphilia. METHOD: Review of the relevant literature. RESULTS: Certain patient populations should not be treated with these medications, and medical complications associated with each can be detected early and avoided. CONCLUSIONS: For each drug, a series of screening tests prior to use and scheduled testing during use can minimize potential medical complications.

Vasopressin in chronic psychiatric patients with primary polydipsia.

Twelve chronic in-patients with primary polydipsia were studied, during free drinking and after fasting, by concurrent measurements of plasma AVP, serum sodium and osmolality, and urine volume, AVP, osmolality, and creatinine. A majority of the patients showed inappropriately high levels of AVP: plasma AVP estimations demonstrated that seven had Type I SIADH and two had Type II SIADH. Urinary AVP estimations confirmed inappropriately raised AVP in seven of the subjects tested, and there was a significant agreement between the plasma and urine diagnoses. Although able to concentrate their urine in response to fluid deprivation, the patients showed a decreased renal sensitivity to AVP. Despite the mitigating effect of decreased renal sensitivity to AVP, the SIADH seen in these patients appears to contribute to the development of water intoxication caused by polydipsia.

Electrode placement in ECT: cognitive effects.

Forty patients suffering from a major depressive disorder, for whom electroconvulsive therapy (ECT) was clinically indicated, were assigned to one of three electrode placement groups: bitemporal (BT), right unilateral (RU) or bifrontal (BF). Comparisons of these groups in terms of cognitive status showed that the BF placement, which avoided both temporal regions, spared both verbal and nonverbal functions. These differential effects, which were independent of the degree of clinical depression, were not, however, evident three months after the last ECT.

Therapeutic advantage of bifrontal electrode placement in ECT.

Fifty-nine patients suffering from a major depressive episode, for whom electroconvulsive therapy (ECT) was clinically indicated, were randomly assigned to one of three electrode placement groups for treatment with brief pulse, threshold-level ECT: bitemporal (BT), right unilateral (RU) or bifrontal (BF). Comparison of these groups in terms of number of treatments, duration of treatment, or incidence of treatment failure, showed that the bilateral placements were superior to the unilateral; comparison of Hamilton, Montgomery-Asberg, and visual analogue scale scores showed that the bifrontal placement was superior to both bitemporal and unilateral treatment. Bitemporal treatment showed therapeutic results intermediate between BF and RU. Because BF ECT causes fewer cognitive side effects than either RU or BT, and is independently more effective, it should be considered as the first choice of electrode position in ECT.

Electrical dose and seizure threshold: relations to clinical outcome and cognitive effects in bifrontal, bitemporal, and right unilateral ECT.

In patients allocated blindly and randomly to receive bitemporal, right unilateral, or bifrontal electroconvulsive therapy, seizure length, electrophysiologic characteristics (dynamic impedance, seizure threshold, and changes in threshold), and the degree of suprathreshold stimulation were recorded. The relations of these variables to clinical outcome and cognitive effects were determined. There were no differences in seizure length between groups, and there were no significant correlations between seizure length and any measure of clinical response. There were substantial differences between the groups in mean charge per treatment, with the right unilateral group receiving lower doses than either bilateral group. Convulsion time was inversely related to applied charge and the rate of increase in charge. There were no significant correlations between impedance, charge, energy, or rate of increase in charge on the one hand, and clinical improvement on the other. The increase in threshold during the course of treatment was not related to clinical change. Cognitive impairment was related to electrical dose only in the bifrontal group, which showed the least degree of treatment-induced intellectual dysfunction. Compared with bitemporal or right unilateral treatment, bifrontal electroconvulsive therapy yields the best ratio of benefits to side effects and should be given at threshold level to minimize cognitive loss.

Characteristics of responders and nonresponders to brief-pulse right unilateral ECT in a controlled clinical trial.

In a double-blind, randomized controlled study of electroconvulsive therapy (ECT) in patients with major depression, 7 of the 17 patients allocated to the right unilateral group failed to respond to treatment. The nonresponders were subsequently openly treated with bitemporal treatment, which produced an acceptable outcome in these cases of right unilateral treatment failure. This paper describes the clinical outcome, electrophysiological characteristics (impedence, estimated seizure threshold, and change in threshold), and the degree to which stimuli exceeded threshold in the responder and nonresponder groups. Responders had lower seizure thresholds and longer seizures than nonresponders. In comparison with nonresponders, responders showed trends toward greater impedance and treatment at a somewhat greater degree above threshold during the first few treatments. Threshold change with treatment was found not to be related to clinical outcome. Early identification of patients likely to respond to low-dose right unilateral ECT, together with the avoidance of benzodiazepine prescription during ECT, may permit many patients to receive low-dose right unilateral ECT successfully and with a minimum of cognitive impairment.