Lithium Withdrawal Research Articles

Lithium withdrawal

Lithium withdrawal

Severe neuroleptic extrapyramidal motor side effects in manic syndromes triggered by lithium withdrawal

Severe neuroleptic extrapyramidal motor side effects in manic syndromes triggered by lithium withdrawal

Changes in platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in lithium-treated bipolar patients

The activity of monoamine oxidase (MAO) and dopamine-β-hydroxylase (DBH), enzymes involved in monoamine metabolism, were studied in 29 bipolar patients (mean age = 33.12years, SD = 7.27) who were treated with lithium carbonate and in 20 healthy volunteers (mean age = 30.05 years, SD = 6.04). Platelet MAO activity was higher after lithium withdrawal, whereas plasma DBH activity was lower in remitted euthymic bipolar patients compared with normal volunteers. During lithium treatment, platelet MAO activity decreased and plasma DBH activity increased compared with the lithium-withdrawal values. It was also observed that the activities of these enzymes in the bipolar patients during lithium treatment did not differ from those in the volunteers. Thus, platelet MAO and plasma DBH activities differed in unmedicated patients with bipolar affective disorder from those of healthy subjects. Treatment with lithium appeared to have a normalizing effect on MAO and DBH activity levels.

Cerebral oedema after subarachnoid haemorrhage. Pathogenetic significance of vasopressin.

The authors report the frequency, characteristic clinical symptoms, laboratory alterations and diagnostic criteria of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after subarachnoid haemorrhage. The data on 290 patients with subarachnoid haemorrhage (SAH) during a period of years at the Division of Neurosurgery, University Medical School, Szeged, are analysed. Twenty-seven (9.3%) patients developed SIADH. Thirteen (4.5%) patients had severe and 14 (4.8%) had mild SIADH. The problems of the treatment are discussed in detail and the different therapeutic methods are listed: NaCl infusion, water withdrawal and administration of Dilantin, diuretics, mineralocorticosteroids, lithium and demeclocycline. The undesirable side-effects observed accompanying various therapeutic regimen are analysed. The introduction of V2 antagonists into clinical practice appears to be a most perspective procedure. For study of the pathogenesis of SIADH following SAH, the possibility of treatment with V2 antagonists on an experimental model of SAH in rat was created. A significant water retention and increases in brain water and sodium content were observed in rats with SAH. Plasma AVP levels were also elevated after SAH. AVP plays an important role in the development of antidiuresis following water loading and disturbance of the brain water and electrolyte balance after SAH. Water retention and the higher brain water and sodium accumulation could be totally prevented by administration of a V2 antagonist. These results demonstrate that cerebral oedema generated by artificial cerebral bleeding in rats is significantly reduced following the administration of a highly specific V2 antagonist, suggesting a new approach to the treatment of SIADH.

Hyperthyroïdie après arrêt du lithium : coïncidence ou non ?

A 59 year-old manic-depressive woman treated with lithium for 10 years, developed hyperthyroidism three months after lithium withdrawal. The usual side effects on lithium on thyroid function include hypothyroidism and/or development of a goiter. Hyperthyroïdism occurring during lithium therapy is more rarely described. Hyperthyroidism has been exceptionally reported after lithium withdrawal, as in this case (five cases are recorded). The role of lithium in this pathology is controversial. Well-designed prospective studies are needed to clarify this question. Nevertheless, the effects of lithium on the thyroid metabolism are not always harmless and must prompt the clinicians to control the thyroid hormones before, during and after lithium therapy.

Effect of lithium carbonate on activity level and circadian period in different strains of rats

Lithium, an important pharmacological agent for the treatment of manic-depressive illness in humans, is known to lengthen the circadian period in a number of different species. Recent experiments, on the other hand, suggest that pharmacological agents may affect the circadian system indirectly through an increase or decrease of activity. To explore the interaction between pharmacological and activity effects on the circadian system, lithium was administered chronically to three different strains of rats (ACI, BH, and LEW) while wheel-running activity was studied quantitatively. Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Wheel-running activity was monitored for 4 weeks under baseline conditions, followed by 3 weeks with lithium treatment (0.3% Li 2CO 3 administered with food) and 4 weeks with normal food. Treatment with lithium (average intake per day = 3.6 ± 0.2 mg) consistently decreased both the overall level and the circadian amplitute of the activity rhythm. The free-running period τ was slightly lengthened during lithium treatment, while the most dramatic effect on period was observed after lithium withdrawal. Correlation analysis, however, revealed only a small negative correlation between activity level and period length, which proved significantly only for animals of the ACI strain. Our data support the traditional interpretation that lithium lengthens circadian period by a direct pharmacological effect on the circadian pacemaker rather than through indirect effects of activity feedback.

Regression of Thyrotoxic Ophthalmopathy following Lithium Withdrawal

The case of a bipolar patient who developed thyrotoxicosis with severe exophthalmos while on lithium therapy is described. The patient had required two surgical decompressions of the right orbit to relieve pressure, which occurred secondary to progression of the exophthalmos, and was scheduled for further surgery. Lithium therapy was discontinued because of poor compliance to the medication and intolerable polyuria. The exophthalmos improved dramatically within 72 hours of the withdrawal of lithium. A severe form of exophthalmos resulting from lithium therapy has not been described in the literature. The case described here adds to the body of information about the possible causes of thyrotoxic ophthalmopathy.

Adverse effect of lithium withdrawal

Adverse effect of lithium withdrawal

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 < 0.001) in plasma thyroxine (T 4) levels and a decrease ( P < 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 T 4 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.

Lithium withdrawal see Chlorpromazine interaction

Lithium withdrawal see Chlorpromazine interaction

ACUTE LITHIUM TOXICITY—CHOREA, HYPERCALCEMIA AND HYPERAMYLASEMIA

Lithium is widely used in the management of patients with manic depressive illnesses. It is a valuable drug with a good safety record but occasionally causes severe disorders. A 71-year-old woman is described who previously had a good response to lithium carbonate treatment of a manic depressive illness. Because the patient appeared depressed and withdrawn, lithium carbonate dosage was increased. The development of confusion and choreiform movements precipitated hospital admission. The symptoms were relieved when lithium was stopped but recurred with the reinstitution of lithium. Spontaneous choreiform movements were again relieved on lithium withdrawal. Associated with the abnormal movements were alterations in the serum calcium concentrations, a rise in the parathyroid hormone concentration and a rise in the serum amylase concentration without features of acute pancreatitis.

Lithium‐Induced Headache

A 23-year old woman developed headache and papilledema due to benign intracranial hypertension (BIH) while taking lithium carbonate for only seven months because of manic-depressive disease. Having discarded other causes, drug ingestion was the most likely etiology of the syndrome since it was observed that symptoms improved upon lithium withdrawal and worsened when the treatment was restarted. This report shows that BIH may appear as a side-effect of relatively short-term therapy with lithium and, therefore, funduscopic exams should be performed in every patient receiving this drug.

MANIA RECURS WHEN LITHIUM IS ABRUPTLY STOPPED.

Mander and Loudon conducted a double-blind, placebo- controlled crossover trial of lithium withdrawal in 14 patients with mania who had been stable on

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.

Abrupt Lithium Withdrawal May Cause Relapse in Bipolar Patients

Abrupt Lithium Withdrawal May Cause Relapse in Bipolar Patients

Short-term lithium administration to healthy volunteers produces long-lasting pronounced changes in platelet serotonin uptake but not imipramine binding.

Platelet [3H]-5HT uptake, [3H]-imipramine binding and endogenous 5HT levels were measured in healthy volunteers during short-term (20 days) administration of lithium, and following its withdrawal. The Vmax of [3H]-5HT uptake was significantly decreased during lithium treatment. Following lithium withdrawal, platelet [3H]-5HT uptake (Vmax) remained decreased and was followed by a pronounced rebound effect in some of the subjects for up to 3 months. The affinity constant (Km) of [3H]-5HT uptake was not modified. Binding of tritiated imipramine during the same period and platelet 5HT levels measured till 14 days after withdrawal was not affected by lithium treatment. As lithium is devoid of in vitro effects on both 5HT uptake and imipramine binding, it is concluded that the effects of lithium on the 5HT transporter do not reflect a direct effect on the transporter complex. Our results indicate that lithium-induced changes at the level of 5HT uptake in platelets are not correlated with concomitant variations in platelet 5HT content and can be dissociated from modifications at the level of imipramine binding sites within the macromolecular complex of the 5HT transporter. Moreover, platelet 5HT uptake is apparently modulated by lithium, with a similar pattern in healthy volunteers and in manic-depressive patients.

Relapse after lithium withdrawal in schizoaffective psychoses : G. Lenz, A. Lovrek, K. Thau, A. Topitz, E. Denk, C. Simhandl, J. Wancata and R. Wolf Psychiatric Clinic, University of Vienna, Wahringergurtel 18–20, 1090 Vienna, Austria

Relapse after lithium withdrawal in schizoaffective psychoses : G. Lenz, A. Lovrek, K. Thau, A. Topitz, E. Denk, C. Simhandl, J. Wancata and R. Wolf Psychiatric Clinic, University of Vienna, Wahringergurtel 18–20, 1090 Vienna, Austria

The effect of chronic lithium administration and withdrawal on locomotor activity and apomorphine-induced locomotor stimulation in rats.

The effect of chronic lithium administration and withdrawal on locomotor activity and apomorphine-induced locomotor stimulation in rats was studied. Chronic lithium administration caused a decrease in locomotor activity, which might be due to a lithium-induced decrease of exploratory behaviour. Chronic lithium administration had no effect on apomorphine-induced locomotor stimulation. However, apomorphine-induced locomotor stimulation was increased two days after the withdrawal of lithium while no difference was found after four days, suggesting a transient increase in postsynaptic dopamine (DA) receptor sensitivity following lithium withdrawal.

Lithium withdrawal

Lithium withdrawal