Monitoring of patients treated with lithium for bipolar disorder: an international survey.

BACKGROUND: Adequate monitoring of patients using lithium is needed for optimal dosing and for early identification of patients with (potential) ADEs. The objective was to internationally assess how health care professionals monitor patients treated with lithium for bipolar disorder. METHODS: Using networks of various professional organizations, an anonymous online survey was conducted among health care professionals prescribing lithium. Target lithium serum levels and frequency of monitoring was assessed together with monitoring of physical and laboratory parameters. Reasons to and not to monitor and use of guidelines and institutional protocols, and local monitoring systems were investigated. RESULTS: The survey was completed by 117 health care professionals incorporating responses from twenty-four countries. All prescribers reported to monitor lithium serum levels on a regular basis, with varying target ranges. Almost all (> 97%) monitored thyroid and renal function before start and during maintenance treatment. Reported monitoring of other laboratory and physical parameters was variable. The majority of respondents (74%) used guidelines or institutional protocols for monitoring. In general, the prescriber was responsible for monitoring, had to request every monitoring parameter separately and only a minority of patients was automatically invited. CONCLUSIONS: Lithium serum levels, renal and thyroid function were monitored by (almost) all physicians. However, there was considerable variation in other monitoring parameters. Our results help to understand why prescribers of lithium monitor patients and what their main reasons are not to monitor patients using lithium.

[Instructions for monitoring clinical parameters in the Summary of Product Characteristics (SmPC) for psychotropic drugs: overview and applicability for clinical practice]. / Instructies voor monitoren van klinische parameters in de registratieteksten van psychofarmaca: overzicht en toepasbaarheid voor de klinische praktijk1.

BACKGROUND: The Summary of Product Characteristics (Smpc) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm.
AIM: To evaluate which monitoring instructions are given in the Smpc and to assess the applicability in clinical practice.
METHOD: The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed.
RESULTS: An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable.
CONCLUSION: Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice.

Prevalence of medication use for somatic disease in institutionalized psychiatric patients.

INTRODUCTION: Psychiatric patients may use medications for their psychiatric condition as well as for treating concurrent somatic diseases or somatic side effects of psychiatric medicines. The objective of this study was to estimate the prevalence of use of medication for somatic disease in institutionalized psychiatric patients and changes therein during 2006-2010. METHOD: A cross-sectional study in institutionalized psychiatric patients was performed. Medication use for somatic disease on 10 time points between 2006 and 2010 was investigated and stratified by gender, age, psychiatric medication class and the number of different psychiatric medication classes used. RESULTS: The prevalence of use of medication for somatic disease increased from 67.5% in 2006 to 76.9% in 2010. The median number of medications used for somatic disease per patient was 3 between 2006 and 2010. Approximately one-third (34.1%) of the patients received ≥ 3 medications intended for treating somatic disease in 2006 which increased to 46.3% in 2010. In 2010, the prevalence of medication use for somatic disease was highest for analgesics and antirheumatics (34.0%), acid and bowel related medication (25.6%) and anticholinergic medication (24.2%). Medication use for somatic disease was highest in patients ≥ 60 years (95.3%), patients treated with more than one psychiatric medication class (87.5%) and patients treated with mood stabilizers (90.6%). DISCUSSION: Somatic medication use is high in institutionalized psychiatric patients. More attention is needed for co-use of psychiatric and somatic medications to prevent side effects, drug-disease or drug-drug interactions. More research is needed to investigate if somatic care is optimal in institutionalized psychiatric patients.

Geographical influences upon physical activity participation: evidence of a 'coastal effect'.

OBJECTIVE: To examine the association between geographical proximity to the coast and physical activity participation levels. METHOD: Using stratified random sampling, a telephone survey was carried out in 1994 with 1,000 adults in each of the 16 health service regions in New South Wales (N = 16,178). Physical activity levels were measured through self-report of the frequency and duration of walking, moderate and vigorous activities in the two weeks preceding the survey. Logistic regression modelling was carried out to examine the association between physical activity and 'coastal' location of residence, adjusting for age, sex, employment status, education level and country of birth. RESULTS: After adjusting for other demographic factors, respondents who lived in a coastal postcode were 23% less likely to be classified as sedentary, 27% more likely to report levels of activity considered adequate for health, and 38% more likely to report high (vigorous) levels of physical activity than those who lived inland. Each of these associations was significant at the 0.05 level. CONCLUSIONS: Characteristics of the physical environment in coastal postcodes are related to physical activity participation. IMPLICATIONS: Physical environments may contribute to physical activity participation. Further efforts to conceptualise and measure these environmental influences is warranted. Public health efforts to promote physical activity should consider aspects of the physical environment as part of any intervention.

Discriminant attitudes and beliefs about condoms in young, multi-partner heterosexuals.

Four hundred and eight people aged 15-35 years who reported having more than one sexual partner of the opposite sex in the past year or who thought it likely that they would do so in the next year were surveyed about their sexual behaviour, concern about acquired immunodeficiency syndrome and sexually transmitted diseases and attitudes to condom use. Differences in concerns and attitudes between regular and non- or irregular condom users and between men and women are reported. Three conceptually coherent factors (condom use as positive action; condom use as cue to embarrassment; and condom use as antithetical to good sex) discriminated between users and non-users. Implications for health promotion campaigns designed to promote condom use are discussed.

Studies in the rat on bucindolol, a new antihypertensive agent with beta-adrenoceptor blocking properties.

The properties of a new antihypertensive agent, bucindolol, were studied in the anaesthetized rat. When administered intravenously in the dose range 0.03 to 1.0 mg/kg, bucindolol evoked dose-related decreases in mean arterial blood pressure wtih relatively little change in heart rate. Bucindolol retained nearly 50% of its hypotensive activity after ganglionic blockage with pentolinium. When administered intravenously in a dose of 0.25 mg/kg, bucindolol caused approximately 1000-fold and 100-fold shifts to the right in the dose-response curves for isoprenaline-induced chronotropic activity and hypotensive activity, respectively. The same dose of bucindolol caused a decrease in pressor responsivity to angiotensin II, no significant change in that to noradrenaline, and an increase in that to adrenaline. Bucindolol was an effective hypotensive agent, which under the conditions of test, had relatively little effect on basal heart rate, exhibited no significant alpha-adrenoceptor blocking activity in the dose range tested, had potent beta-adrenoceptor blocking properties, and exhibited an apparent direct relaxant effect on vascular smooth muscle.

Studies in the rat on endralazine, a new antihypertensive drug structurally related to hydralazine.

1. The effects on blood pressure, heart rate and plasma renin activity of a new hydralazine congener, endralazine, were evaluated in anaesthetized rats. Dose-response relationships for endralazine, hydralazine and diazoxide, administered intravenously, were compared, and the interactions of endralazine with the ganglionic blocking agent, pentolinium, or with adrenaline, noradrenaline and angiotensin II were examined. 2. In the dose range 0.05 to 1.0 mg/kg, endralazine produced prompt dose-related reductions in systolic and diastolic blood pressure, with relatively little effect on heart rate. The drug had a pronounced dose-related renin stimulating effect. 3. Endralazine retained approximately 80% of its hypotensive activity after pretreatment with pentolinium, and caused no significant attenuation of pressor responses to adrenaline, noradrenaline or angiotensin II. 4. Endralazine was an effective hypotensive agent, with a prompt onset of action, a prolonged and stable effect, and a potency at least twice that of hydralazine and 20 to 25 times that of diazoxide. The data are consistent with a predominantly direct vasodilator mode of action.

Haemodynamic interactions between alpha- and beta-adrenoceptor antagonists in conscious or anaesthetized rats.

1. The alpha-adrenoceptor antagonist, phentolamine, was administered intravenously, to conscious or anaesthetized rats, before or after the beta-adrenoceptor antagonist, propanolol. 2. The bradycardia which followed the combined administration of propranolol and phentolamine exceeded that induced by propranolol alone, yet the hypotensive effect of phentolamine was attenuated by propranolol. 3. The results are compatible with the concept that a significant part of the hypotensive effect of phentolamine is mediated by stimulation of vascular beta-adrenoceptors.

Profile of a new prazosin congener, BL-5111A. Studies in the rat.

1. The effects on blood pressure and heart rate of prazosin and a structurally-related congener, BL-5111A, were compared in conscious and anaesthetized rats. 2. Both agents induced dose-related falls in systolic and diastolic blood pressure, with relatively little effect on heart rate. The hypotensive potency of prazosin was twenty-fold greater than that of BL-5111A. 3. The hypotensive activity of prazosin was abolished by pretreatment with the ganglionic blocking agent, pentolinium, or the alpha-adenoceptor blocking agent, phentolamine, whereas BL-5111A retained significant hypotensive activity (up to 28%) after either pretreatment. 4. Both prazosin and BL-5111A attenuated pressor responses to noradrenaline, and reversed the responses to adrenaline, prazosin being, in this respect, 6 times more potent than BL-5111A. There was a highly significant relationship between the alpha-adrenoceptor blocking activity of either agents and its hypotensive effect. 5. BL-5111A differed from prazosin in possessing, in addition to its predominant alpha-adrenoceptor blocking action, a minor component of action attributable to direct vasodilatation.

Effects of prazosin on blood pressure and plasma renin activity during onset and withdrawal of action in the anaesthetized rat.

1. The effects of single intramuscular injections of prazosin, 0.1 mg/kg, upon blood pressure, heart rate and plasma renin activity, were studied, over 24 h, in groups of anaesthetized rats, control rats receiving 0.9% saline. 2. Within 6 min of prazosin administration, heart rate fell by 50 beats/min (s.e.m = 19) and blood pressure by 40 mmHg (s.e.m. = 8). Starting levels were regained within 90 min and 16 h of injection, respectively, and thereafter both parameters remained unaltered. Plasma renin activity showed a slight though insignificant rise during the initial hypotension, but subsequently fell to 32% of the control level. 3. The hypotensive response to prazosin, unlike that to the centrally acting agents clonidine or guanfacine, was not followed by overshoots in blood pressure, heart rate or plasma renin activity. Instead, suppression of plasma renin activity was demonstrable after re-establishment of control blood pressure.

Studies in the rat on the haemodynamic overshoot response to withdrawal of guanfacine or clonidine treatment.

1. Normal rats were injected intramuscularly twice daily for either 3 days or 3 weeks with guanfacine (0.1 or 1.0 mg/kg), clonidine (0.01 or 0.1 mg/kg) or 0.9% saline. All were anaesthetized at various times before or after the last injection, and their arterial pressures and heart rates were monitored via a carotid artery catheter. 2. Overshoots in systolic and diastolic pressure and heart rate, reaching peak values as soon as 16 h after the last injection, occurred in all rats withdrawn from guanfacine or clonidine treatment, but in no control rats. 3. Post-withdrawal blood pressures and heart rates of rats which had received the low dose of guanfacine or clonidine were as great as those of rats which had received the ten-fold greater dosage. Moreover, withdrawal responses were as great in rats which had been treated for only 3 days as in those treated for 3 weeks. 4. The dosages and duration of treatments used in these experiments thus did not influence the magnitude of the haemodynamic overshoots provoked by withdrawal of guanfacine or clonidine. However, all groups of rats from which guanfacine was withheld exhibited significantly greater peak overshoots in systolic and diastolic pressure than did those withdrawn from clonidine treatment.

Withdrawal of clonidine: effects of varying dosage or duration of treatment on subsequent blood pressure and heart rate responses.

The influence of the dosage or duration of treatment on the incidence and severity of clonidine withdrawal responses was examined in normotensive rats. Clonidine (0.01 or 0.1 mg/kg i.m.) was administered either in single doses, or twice daily for 3 days or 3 weeks. Rats were then anesthetized and arterial catheters were inserted. Significant overshoots in blood pressure and heart rate, reaching peak values 16 to 26 hr after the last injection, occurred in all clonidine-treated rats, but in no control rats. The overshoots after single injections of clonidine were as great as those after suspension of sustained treatment. Moreover, withdrawal responses were as great after the low dose as they were after the 10-fold greater dose. Only plasma renin activity showed a significantly greater elevation during withdrawal of the high dose of clonidine. Since ganglionic blockade reduced blood pressures and heart rates to the same levels in rats with clonidine withdrawal hypertension as in control rats, the withdrawal overshoots appear to be nervously mediated. Neither the dosage nor the duration of treatment could be shown to determine the magnitude of the response to withdrawal of clonidine.

The beta-adrenoceptor controlling renin release.

The beta-adrenoceptor antagonists, atenolol, metoprolol and propranolol, administered intravenously to anaesthetized rats in doses producing equal beta1-adrenoceptor blocking effects, caused comparable suppression of plasma renin activity (PRA) despite the fact that, at these doses, atenolol and metoprolol exhibited no beta2-adrenoceptor blocking properties. Practolol, an agent specific for beta1-adrenoceptors but possessing intrinsic sympathomimetic activity, caused less marked suppression of PRA. When doses of atenolol, metoprolol, propranolol and butoxamine were selected to achieve equal beta2-blocking effects, PRA was again significantly suppressed by atenolol and metoprolol but not by propranolol or butoxamine. These results do not support the concept that adrenergic release of renin is mediated by beta2-adrenoceptors, but are compatible with the involvement of a beta1-adrenoceptor-mediated mechanism.

Comparative haemodynamic effects of clonidine administered intramuscularly or intravenously to anaesthetized rats.

1. The acute haemodynamic effects of clonidine, 0.001-1.0 mg/kg, administered intramuscularly or intravenously, were studied in anaesthetized rats. 2. The direct pressor potency of clonidine was 100-fold greater following intravenous administration than after intramuscular injection, but hypotensive efficacy was equal by either route.

Interactions between prazosin, clonidine and direct vasodilators in the anaesthetized rat.

1. Prazosin, clonidine, hydrallazine and diazoxide were administered intravenously, alone or in various combinations, to anaesthetized rats. 2. Prazosin and clonidine were equipotent. Their combined hypotensive effects in no instance exceeded the maximum effect attainable with either agent alone. The hypotensive effects of hydrallazine or diazoxide were, in contrast, additive to those of either prazosin or clonidine. 3. Pressor responses to clonidine were antagonized by prazosin. Prazosin may prove useful in hypertensive crises provoked by clonidine.

Comparative haemodynamic effects of clonidine and guanfacine.

Dose-response relationships were established for the acute effects on arterial pressure and heart rate of the antihypertensive agents, clonidine and guanfacine, administered intravenously or intramuscularly to anaesthetized rats. The intramuscular route appeared to be preferable to the intravenous, for the direct pressor potency of each drug was thereby greatly reduced in relation to the hypotensive efficacy. The potency of clonidine was 10-20 times that of guanfacine, but the same maximal fall in blood pressure was obtained with either agent administered by either route. Both agents caused a marked, dose-related suppression of plasma renin activity. When either clonidine or guanfacine was administered twice daily for 3 weeks and then discontinued, a phase of blood pressure overshoot with tachycardia commenced within 24 hr of the last injection. These withdrawal effects were more evident in guanfacine-treated rats than in clonidine-treated rats.

Alpha blocking action of the antihypertensive agent, prazosin.

The vasodilatory and alpha adrenergic blocking properties of prazosin were studied in anesthetized rats and compared with the direct-acting vasodilator, diazoside. The hypotensive activity of diazoxide was unimpaired after ganglion blockade with pentolinium or alpha adrenoreceptor blockade with phentolamine; diazoxide also significantly attenuated angiotensin II pressor responses. In contrast, the hypotensive action of prazosin was completely abolished, over a 10(4)-fold dose range, after ganglion or alpha adrenoreceptor blockade, and this agent failed, even in maximal hypotensive doses, to attenuate angiotensin II pressor responses. In addition, prazosin was shown to possess potent alpha adrenoreceptor blocking properties, significantly attenuating norepinephrine pressor responses and causing reversal of epinephrine pressor responses. These studies in the rat indicate that the hypotensive action of prazosin is not due to a direct relaxant effect upon vascular smooth muscle, but is attributable to alpha adrenoreceptor blockade.

Haemodynamic effects of prazosin.

Parzosin, 0.001 to 10 mg/kg, was administered intravenously to anesthetized normal rats. In the dose range 0.001 to 0.01 mg/kg, the drug induced highly significant, dose-related falls in blood pressure, pulse pressure and heart rate. With doses above 0.01 mg/kg, there was a plateau in hypotensive efficacy and a diminution in negative chronotropic activity. Both actions of prazosin (0.01 mg/kg) were unaffected by vagal blockade with atropine, while hypotensive potency was unimpaired after beta-adrenoreceptor blockade. The vasodilator, diazoxide, lowered blood pressure, widened pulse pressure and caused tachycardia in rats pre-treated with pentolinium. In contrast, all effects of prazosin were abolished by ganglion blockade. These findings, together with the absence of compensatory tachycardia or gross renin hypersecretion during prazosin-induced hypotension, are compatible with an antisympathotonic mode of action for the drug. However, consistent with its effects on cyclic nucleotide distribution, prazosin appears to enhance isoprenaline-induced beta-receptor stimulation.