Lithium treatment: prescribing and monitoring habits in hospital and general practice.

OBJECTIVES: To define current clinical practice of lithium prescribing and monitoring and to compare hospital based practice with general practice. DESIGN: Prospective study of doctors' practice. SETTING: Psychiatric hospital day and outpatient facilities and general practices in Edinburgh and Midlothian district (population 600,000). SUBJECTS: 458 patients taking lithium who had been stabilised and who remained as outpatients during the year of study. 219 were treated by their general practitioner and 190 by the hospital; 49 had shared care or care transferred during the study. MAIN OUTCOME MEASURES: Daily dose, duration of treatment, psychiatric diagnosis, mean annual serum lithium concentration, frequency of occurrence of and response to raised serum concentrations. RESULTS: Compared with hospital doctors general practitioners were more likely to prescribe lithium three or more times daily (43/219 (general practice) v 10/190 (hospital); chi 2 = 18.6, p = 0.001) and to estimate serum concentrations less frequently (4.5 v 5.3 measurements/year; t = 3.04, p = 0.003), and their patients were more likely to experience raised lithium concentrations (39/219 v 17/190; chi 2 = 6.8, p = 0.01). One third of doctors made no response to raised lithium concentrations in the next six weeks. CONCLUSIONS: General practitioners and hospital doctors care for similar types of patients and the stringency of lithium surveillance varies greatly among doctors. Certain aspects of practice give cause for concern and could be improved by following more uniform guidelines.

The effects of lithium discontinuation and the non-effect of oral inositol upon thyroid hormones and cortisol in patients with bipolar affective disorder.

Thyroid and adrenal function was assessed in euthymic bipolar patients, stable on prophylactic lithium for at least 1 year, before and after lithium discontinuation in a randomised double-blind placebo-controlled trial. All hormonal measurements were within the reference range, but a significant increase (P less than 0.001) in plasma thyroxine (T4) levels and a decrease (P less than 0.01) in TSH levels were observed 1 month after lithium withdrawal; cortisol concentrations showed a non-significant decrease in the same period. No relationship could be demonstrated between the magnitude of the change in hormone levels and the probability of relapse of manic symptoms. In the second part of this study, inositol was added for 11 days to the diets of bipolar patients being treated with prophylactic lithium and normal controls. No modification was shown in T4 and TSH in either group before or after inositol administration. Inositol did not alleviate other side-effects such as tremor and thirst in the patient group. This result suggests that short-term dietary inositol is not equivalent to lithium withdrawal and is of no value in reducing hormonal and other adverse effects of lithium prophylaxis.

The efficacy of lithium in prophylaxis of unipolar depression Evidence from its discontinuation.

Forty unipolar patients satisfying DSM-III criteria for major depression who discontinued lithium therapy were retrospectively compared with 105 similar patients who continued the drug and served as a control group. The time to readmission from starting lithium was compared while both groups were still on lithium, and after discontinuation in one group and further continuation in the control group. The progressive increase in the probability of recurrence over two years was the greatest after discontinuation of lithium. For the patients who eventually discontinued lithium, the cumulative probability of recurrence in two years was 0.08 on lithium and 0.58 after stopping it. The probability of recurrence was unchanged over the duration of the study for patients who continued to take lithium. There was no evidence of a lithium withdrawal syndrome within three months of stopping the drug. The results support the view that the everyday clinical use of lithium as prophylaxis is beneficial in unipolar depression.

Psychiatric emergencies, Scotland and the World Cup finals.

Reductions in emergency psychiatric presentations to hospital occurred during and after the finals of the World Cup football competitions, an effect evident in women as well as men, and more marked among the mentally ill than those who were not. Increases in the numbers of schizophrenic and neurotic men presenting before, and alcoholic men during, the competitions can be attributed to the football. The generalised reductions during and after could reflect an indirect effect upon help-seeking, although actual relapse rates of mental illnesses might be affected. These changes could arise from enhancement of national identity and cohesion.

Fluid balance, vasopressin and withdrawal symptoms during detoxification from alcohol.

Nineteen patients were studied during the first 4 days after withdrawal from alcohol. Plasma vasopressin was raised (P less than 0.05) and fluid retention occurred (P less than 0.05), with falls in haematocrit (P less than 0.01) and calculated plasma osmolality (P less than 0.02), which were consistent with expansion of plasma volume. Despite these changes mean total body water was within normal limits although there were substantial inter-individual variations. There was no correlation between any measure of fluid balance and the severity of withdrawal symptoms.

Diagnosis change, lithium use and admissions for mania in Edinburgh.

Admissions for mania have risen significantly in Edinburgh since 1970. Differencing was used to remove time trends; this showed that the rise was not accounted for by diagnosis change (from schizophrenia or personality disorder) or by lithium prescription. The contribution of non-specific factors such as admission policy and the experience of trainee psychiatrists deserves evaluation. If this rise continues there will be significant resource implications for the future.

Efficacy of lithium prophylaxis in clinical practice.

The efficacy of lithium prophylaxis in bipolar affective disorder in clinical practice was investigated. Comparison was made between 41 patients who were prescribed prophylactic lithium after two admissions in two years or three admissions in five years and a group of patients who did not receive lithium. The benefits conferred by the prescription of this drug were modest compared with the results from clinical trials.

Magnetic resonance imaging of the brain in alcoholics: cerebral atrophy, lifetime alcohol consumption, and cognitive deficits.

Magnetic resonance imaging of the brain in 69 detoxified alcoholics revealed that relaxation time (T1) in whole brain and in grey matter and parietal white matter was greater than in age-matched controls. In 48 patients, data on cognitive function and lifetime alcohol consumption were available. With age-controlled, lifetime consumption, and impairment on performance in the cognitive test (a Category Sorting Test) correlated positively with T1 whole brain and in selected regions. Impairment in the cognitive test correlated with increased T1 in whole brain and white matter independently of cerebral atrophy. Alcohol consumption patterns in the following 6 months were unrelated to changes in T1. The excess water implied by the elevated T1 values may be intra- or extracellular. It is uncertain whether or not T1 elevation in alcoholics is a marker of neuronal damage. T1 elevation appears to be a marker of one type of alcohol-related cognitive impairment.

The relationship of cerebral atrophy and T1 in alcoholics: an MRI study.

There was a significant correlation between two measures of cerebral atrophy (the ventricle to brain ratio and the relative cerebral volume) and T1 in 19 detoxified alcoholics. This provides further evidence that T1 is a marker of structural damage in alcoholics although the partial volume effect of CSF may contribute to this finding. This has implications for studies comparing alcoholics to normal controls and suggests that better ways of excluding CSF need to be found.

NMR T1 relaxation time of the brain during alcohol withdrawal and its lack of relationship with symptom severity.

A significant fall in brain T1 relaxation time, consistent with a reduction in brain water of approximately 0.3%, occurred in 19 chronic alcoholic patients admitted for detoxification. There was no correlation between T1 and the severity of withdrawal symptoms and hence no evidence that changes in brain water levels contributed to the abstinence syndrome.

Specificity of the salivary cortisol dexamethasone suppression test across psychiatric diagnoses.

One hundred forty-eight psychiatric inpatients, 12 outpatients, and 17 normal controls were given the 1.0-mg overnight Dexamethasone Suppression Test (DST), with salivary cortisol concentrations being measured as the dependent variable. Based on the Structured Clinical Interview for DSM-III, the patients were diagnosed as having major depression with melancholia (n = 21), nonmelancholic major depression (n = 50), mania (n = 15), schizophrenia (n = 32), dementia (n = 6), substance dependence/abuse n = 18), and miscellaneous (n = 18). Neither the melancholic major depressives nor the entire group of major depressives had significantly higher salivary cortisol pre- or postdexamethasone as compared with all the other patients combined, nor did the melancholic patients have significantly higher cortisol than the nonmelancholic depressives. The inpatients as a group had significantly higher pre- and postdexamethasone cortisol values than the normal controls; cortisol values for the outpatients were intermediate between these two groups. Illness severity (in the depressives), length of time in hospital before the DST, and medication regimen were all unrelated to DST outcome. Thus, in this study, the salivary cortisol DST showed little clinical utility in discriminating major depressives with and without melancholia from other patients with a broad range of psychiatric diagnoses. The test did distinguish between hospitalized psychiatric patients and normal control subjects and between depressed inpatients and depressed outpatients, indicating that hospitalization-related variables contributed to DST outcome.

The predictive power of the salivary cortisol dexamethasone suppression test for three-year outcome in major depressive illness.

Seventy patients satisfying DSM-III and Research Diagnostic Criteria for major depression were given a salivary cortisol dexamethasone suppression test, with samples collected at 0700 h, 1500 h and 2300 h after dexamethasone. The patients were classified as nonsuppressors (mean post-dexamethasone salivary cortisol concentration greater than or equal to 2.0 ng/ml, N = 27) and suppressors (mean post-dexamethasone salivary cortisol concentration less than 2.0 ng/ml, N = 43). At 3-yr follow-up there was no difference in illness outcome as assessed by the life table method or by the length of rehospitalisation for several periods after the index episode. In multiple regression and discriminant function analyses, with outcome as the dependent variable (readmitted within 1 yr, readmitted between 1 and 3 yr, not readmitted), the mean post-dexamethasone salivary cortisol concentration was not significantly predictive of outcome.

Blood pressure, renin-angiotensin-aldosterone axis and cortisol changes during withdrawal from alcohol.

Nineteen patients who had been drinking on the day of admission had significantly raised levels of renin, aldosterone and cortisol and a non-significant increase in angiotensin II. Five patients were hypertensive (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg) at some point during the study and there was a significant tachycardia. Over the first 4 days of abstinence there were falls in all of the measures reaching significance for renin, cortisol, systolic blood pressure and pulse. There were no correlations between blood pressure and any of the hormones measured although there was a significant association between pulse and both aldosterone and cortisol. It is concluded that the activity in the renin-angiotensin axis and hypothalamic-pituitary-adrenal axis is not responsible for alcohol-related changes in blood pressure.

Use of lithium and early relapse in manic-depressive illness.

The proportion of manic-depressive patients readmitted within three months of an index episode was the same irrespective of lithium prescription. The data supports the view that short-term lithium prescription is ineffective, and because of the possibility of difficulties when it is withdrawn, it is suggested that lithium be reserved for long-term prophylaxis.

Rapid recurrence of mania following abrupt discontinuation of lithium.

Fourteen patients with a history of mania satisfying DSM-III criteria were entered into a randomised double-blind placebo-controlled crossover trial, spending four weeks on each of lithium and placebo. All patients had been well and stable on lithium for at least 18 months and were not taking any other psychotropic drugs. Seven patients (50%) had a relapse of their manic illness and a further two had to be withdrawn because they recognised signs of incipient relapse. One of these became overtly manic after restarting lithium. The seven definite and the two possible relapses occurred in the placebo phase; this finding was unlikely to have arisen by chance. The relapses started 13-19 days after placebo substitution. These results have important implications in the management of lithium prophylaxis by all doctors, particularly those who, for any reason, are considering withdrawal of lithium from their patients.

Brain hydration during alcohol withdrawal in alcoholics measured by magnetic resonance imaging.

Twenty-seven patients had a first Magnetic Resonance Imaging (MRI) scan 1-3 days after stopping drinking and a second approximately 2 weeks later with no change in whole brain T1 or T1 in selected brain areas. Six patients whose first scan was over 36 h after the last drink underwent an increase in whole brain T1 in the interval to the second scan. The later the first scan was performed the greater was the increase in T1. These results are compatible with a very early fall in brain water immediately on cessation of drinking (perhaps due to a rebound increase of vasopressin activity) with a return to 'baseline' after two weeks. A third scan after discharge from hospital in 23 individuals who had abstained from alcohol or drank very little did not reveal any further significant change in brain T1.

An NMR study of cerebral oedema and its biological correlates during withdrawal from alcohol.

Five chronic alcoholic patients admitted for detoxification were studied. During the first 24-48 hr of abstinence raised levels of cerebral water (as measured by NMR), vasopressin, renin and supine aldosterone were recorded. Initial vasopressin concentration was correlated (r = 0.88, P less than 0.05) with alcohol consumption in the week prior to admission and was over three times higher in the patients measured after 24-48 hr as compared to less than 24 hr. After one week only supine aldosterone was still raised (P less than 0.05). The results suggest that cerebral oedema occurs during the early stages of abstinence. The role of these changes in the aetiology of withdrawal symptoms, delirium tremens and brain damage remains to be elucidated.

The effect of maternal psychotic illness on a child.

We report the case of an 11-year-old girl who had been living with only her mother, a woman with chronic schizophrenia. The girl had been caught shoplifting with her mother, and had a long history of non-attendance at school. The case emphasises that adult psychiatrists should always consider the impact of chronic parental psychiatric disorder on children, particularly in one-parent families.

Cerebral and brain stem changes after ECT revealed by nuclear magnetic resonance imaging.

Nuclear magnetic resonance images of the brain were obtained in fourteen patients with major depression during a course of ECT. The T1 relaxation time rose immediately after the fit, reaching a maximum 4-6 h later. The T1 values then returned to their original level; no long-term increase occurred over the course of treatment. These results are consistent with an extensive but temporary breakdown of the blood-brain barrier during ECT.

Is there a lithium withdrawal syndrome?

Patients who discontinued lithium after a mean of 29 +/- 21 months prophylaxis were compared with a similar group who were not taking the drug; all had only been in hospital once, and satisfied DSM-III criteria for mania. During the first three months following withdrawal of lithium, significantly more patients relapsed than in the control group; after this period, the rate was identical. These findings suggest that lithium withdrawal exists as a clinical phenomenon and that a period of lithium treatment does not improve the long-term prognosis, once the drug has been stopped.