Lithium-induced Tremor Research Articles

Lithium Induced Parkinsonism: A Case Report

AimsLithium is an effective mood stabiliser for the treatment of the bipolar disorder. Its utility is not restricted to acute mania and prophylactic treatment of the bipolar disorder. Another well-known indication for its use is the treatment of refractory depression. Lithium can cause several adverse effects, and typically the side effects are dose-related. Unlike antipsychotic medications, lithium is rarely associated with drug-induced Parkinsonism.MethodsWe present a case of 78 years old gentleman who was assessed due to complaints suggestive of cognitive impairment. His past psychiatric history revealed that he was admitted to a psychiatric inpatient unit with a diagnosis of treatment-resistant depression in 1991. Lithium therapy was commenced during this admission, and he remained on lithium for 27 years. The patient was clinically stable in terms of the symptoms of depression; however, he reported bilateral postural tremors 20 years after the initiation of lithium therapy. Initially, he was diagnosed with lithium-induced tremor; however, in the following months, his symptoms had worsened, and he developed new motor disturbances, although the serum levels of lithium were within the therapeutic range. On examination, he had classic parkinsonian signs of shuffling gait, muscle rigidity in all four limbs and freezing of gait. DaT-SPECT imaging clarified the diagnosis as drug-induced Parkinsonism. As the daily lithium dosage was stopped, the patient's motor symptoms improved significantly; nevertheless, some of the symptoms persisted.ResultsThe pathophysiological mechanism behind lithium-induced Parkinsonism is unclear. The condition may develop with or without frank lithium toxicity and have diverse presentations. Literature suggests that the risk factors for lithium-induced Parkinsonism appear to be the patients' age, duration of lithium therapy, and serum lithium levels. It has been suggested that older patients have a more permeable blood-brain barrier and decreased renal clearance; hence, serum lithium levels can appear therapeutic, but brain lithium levels may be much higher. Pharmacokinetic drug-drug interactions might also contribute; thus, careful monitoring is essential.Drug-induced Parkinsonism improves with discontinuation of the offending medication; however, 10% of patients will develop a persistent and progressive parkinsonian syndrome.ConclusionThis report aims to emphasise the need to consider lithium-induced Parkinsonism when Parkinson Disease symptoms appear in chronic lithium users and close monitoring of lithium levels in geriatric populations. It is essential to recognise the condition, avoid misdiagnosis and prevent inappropriate use of anti-dopaminergic medications.

Clinical evaluation of switching from immediate-release to prolonged-release lithium in bipolar patients, poorly tolerant tolithium immediate-release treatment: A randomized clinicaltrial.

AimThe effect of switching from lithium immediate release (Li‐IR) to lithium prolonged release (Li‐PR) on lithium‐induced tremor after 1 and 12 weeks of treatment was evaluated in a randomized, multicenter, open trial, in bipolar patients from the participating sites with a tremor severity ≥2 (Udvalg for Kliniske Undersøgelser [UKU] rating scale) despite optimal lithium titration.MethodsThe primary endpoint was the evaluation of tremor by means of the UKU scale after 1 week of treatment. Secondary endpoints included manic Young Mania Rating Scale (YMRS) and depressive symptoms (Montgomery–Asberg Depression Rating Scale), a global assessment of the patient's status (Clinical Global Impression), polyuria/polydipsia (UKU item 3.8) and patient‐reported outcomes.ResultsOwing to difficulties in including suitable patients the enrollment phase was closed when 73 patients were randomized. Notwithstanding the lower number of patients, in the modified intention‐to‐treat population (n = 70) the primary endpoint was statistically significant: tremor improved after 1 week in 62.9% in Li‐PR group against 20.0% of patients in Li‐IR group (p = .0006; two‐tailed Fisher's exact test). The difference remained statistically significant after 4 (p = .0031) and 12 weeks (p = .0128). The same analysis performed in the PP population confirmed these results. Among the secondary endpoints, only the factor convenience of the treatment satisfaction questionnaire showed a statistically significant difference between groups. There were no apparent differences in the safety profile of the two formulations.ConclusionsThis study is the first comparative documentation of a potential benefit of the prolonged‐release formulation in reducing the symptom tremor, a well‐known adverse effect of lithium therapy. Indeed, the study results should be interpreted taking into account the sample size lower than planned.

Disabling Parkinsonism following brief exposure to lithium carbonate in amyotrophic lateral sclerosis

We report on a 46-year-old male patient affected by amyotrophic lateral sclerosis (ALS) with bulbar onset. His family and medical history was not relevant. In February 2008, a paper published by Fornai et al. [3] suggested that daily lithium administration at a serum level of 0.4–0.8 mEq/L delays ALS progression in both the animal model and in patients. The patient asked to try this new therapy and lithium was prescribed for compassionate use 4 years after disease onset. On neurological examination we found mild atrophy and fasciculations of the tongue, severe dysarthria, and mild dysphagia. Jaw jerk and glabellar tap were absent. Light lower limb muscle weakness, rare diffused fasciculations, and normal muscle tone were detected. Reflexes were brisk in the lower limbs. Babinski sign was bilaterally found. Functional status was good (ALS-FRS 34/40). The patient started lithium assumption at very low dose (150 mg lithium carbonate/day) for 1 week and then increased to 300 mg/day. Lithium blood level was tested every 2 weeks in order to keep it at the lower therapeutic range (0.3 mEq/L). Associated medications were riluzole 100 mg/day, a-tocopherol 900 mg/day, trihexyphenidyl 4 mg/day (symptomatic of sialorrhea). There was no history of additional medication such as antidepressants or antipsychotics, thiazide diuretics, NSAIDS, or ACE inhibitors. Three months later, the patient began to complain of gait instability and frequent falling. Neurological examination showed festinating gait, diffuse bradykinesia, severe stiffness, and positive cogwheel phenomenon both in the upper and lower limbs. No lithium-induced postural tremor was detected. The lithium value was 0.31 mEq/L, and blood count, electrolytes, and renal and thyroid function were all normal. The patient described no concomitant episode of fever and diarrhea. Lithium was immediately discontinued. A therapeutic attempt with L-dopa was unsuccessful. Eight months after lithium discontinuation, the extrapyramidal features significantly improved, only festinating gait persisted. However, spasticity severely worsened and functional status was largely impaired (ALS-FRS = 20/40). On the brain MRI scans, hyperintensities of the corticospinal tract were detected bilaterally (as expected in ALS). SPECT with 1231-ioflupano (DAT-scan) showed normal dopaminergic function in the basal ganglia. The patient also tested negative for SOD1, TDP-43, and FUS gene mutations. This was a very rare case of acute lithium neurotoxicity with low serum level and in the absence of other intoxication symptoms or association with antipsychotic drugs. Movement disorders have been reported during lithium treatment, and are usually associated with high serum levels. To our knowledge, in only one patient Parkinsonism manifested during lithium treatment alone [2, 4] and in one patient with therapeutic levels [4]. Lithium is known to decrease the amount of dopamine in rat striatum and limbic forebrain and act as an anticholinesterase able to increase central cholinergic activity. Because serum lithium levels do not always reflect L. Mazzini, G. D. Oggioni, N. Nasuelli, S. Servo, L. Testa, and F. Monaco contributed equally to the manuscript.

Potential role of pregabalin in the treatment of lithium-induced tremor: a case report

Pregabalin is a structural analogue of gamma-aminobutyric acid (GABA), one of the key inhibitory neurotransmitters in the brain. It is approved by the United States Food and Drug Administration (FDA) for the treatment of pain related to diabetic peripheral neuropathy, post-herpetic neuralgia, adjuctive therapy for partial onset seizures, and fibromyalgia (US FDA, 2007). Pregabalin has also shown efficacy in other conditions for which it is used off-label, including anxiety (Feltner et al. , 2008). The current report describes the first documentation of the usefulness of pregabalin in treating lithium-induced tremor. In the case described, pregabalin was prescribed as an anxiolytic to an in-patient with treatment-refractory major depressive disorder and generalized anxiety disorder; the beneficial effect on tremor was coincidental and unexpected. However, a pilot randomized, double-blind, placebo-controlled clinical trial demonstrated the efficacy of pregabalin in the treatment of benign essential tremor (Zesiewicz et al. , 2007) and a large multicentre trial (clinicaltrials.gov NCT00584376) is currently in process to evaluate its efficacy and safety for this indication. It is plausible that pregabalin may therefore have a unique role in the treatment of patients with lithium-induced tremor, particularly considering the frequent comorbidities of anxiety in patients treated with lithium (bipolar and major depressive patients). To our knowledge, there have been no published case reports of the use of pregabalin for lithium-induced tremor. Mr A was a 65-yr-old man with a history of major depressive disorder and generalized anxiety …

40 Jahre Beta-Blocker in der Psychiatrie

Beta-adrenoceptor blockers belong to the most successful drug classes of medicine. Mainly they are used in internal medicine. 40 years ago beta-adrenoceptor blockers have occasionally been used in psychiatry for the treatment of anxiety disorders. Over the past four decades, the effects of beta-adrenoceptor blockers in the treatment of schizophrenic and manic psychoses, withdrawal syndromes and aggressive behaviour with temper outbursts has been investigated. Beta-adrenoceptor blockers are also used in the treatment of side-effects of psychopharmacological agents like neuroleptic or antidepressant-induced tachycardias, lithium-induced tremor, antipsychotic-induced akathisia or tardive dyskinesia as well. Since the mid-nineties it has been attempted to improve the efficacy of antidepressant agents by means of the 5-HT-(1a)-receptorantagonist pindolol. Presumedly memory consolidation of traumatic events can be enhanced by adrenergic activation. Therefore some open clinical trials investigated the effects of propranolol, a lipid soluble drug, which crosses the blood-brain barrier easily, to reduce the manifestation of PTSD. The present review presents the results of the literature with respect to the indications for beta-blockers in psychiatry. Considering evidence-based-medicine criteria beta-blockers are indicated to treat lithium-induced tremor, antipsychotic-induced akathisia and to reduce aggressive behavior of patients with brain-injuries.

The Role of ??-Adrenoceptor Blockers in the Treatment of Psychiatric Disorders

Although β-adrenoceptor blockers (in particular, propranolol) have been used in the treatment of psychiatric disorders for many years, their indications, extent of efficacy and place in therapy remain unclear. This overview assess the published reports on the use of these drugs in psychiatric disorders. It can be concluded that β-adrenoceptor blockers may be helpful in the management of some forms of anxiety disorders, including performance anxiety and other types of situational anxiety, especially when somatic symptoms are prominent. In the same way, alcohol (ethanol) withdrawal syndrome of moderate severity, antipsychotic-induced akathisia and lithium-induced tremor seem to be responsive to this drug class. Because of the fact that they are well tolerated, the use of β-adrenoceptor blockers in these disorders should be considered whenever drug treatment is being contemplated. In contrast, the efficacy of high doses of β-adrenoceptor blockers in schizophrenia remains unestablished. However, they may be of benefit in some patients presenting with aggressive behaviour due to organic brain disease. Studies have shown a high rate of improvement in this condition, especially in patients who have previously failed to respond to other treatments. Finally, preliminary results suggest that β-adrenoceptor blockers may be useful as adjunctive medication in the treatment of depression and chronic anxiety, but further investigations are needed in these areas of patient management.

Nadolol for Lithium Tremor in the Presence of Liver Damage

Lithium-induced tremor classically responds to treatment with propranolol. Since it is metabolized in the liver, propranolol may not be the drug of choice in those patients who have compromised liver function or who are recovering from prior liver diseases. Another nonselective beta-adrenergic blocker, nadolol, has no hepatic biotransformation. We present here the first case report of successful treatment of lithium-induced tremor with nadolol, which was selected because the patient had compromised liver function. The patient's liver function tests remained stable with the therapy.

Treating tremor induced by lithium.

Fine hand tremor is a common side effect of lithium. It usually occurs early in lithium treatment but may appear at any time. Lithium-induced tremor can be distinguished from parkinsonian and pseudoparkinsonian tremor by its association with voluntary movement and its lack of response to antiparkinson medications. The acute tremor that sometimes occurs at the beginning of lithium treatment is seen at rest and increases with voluntary movement or with efforts to maintain posture. It is considered a temporary accentuation of normal physiologic tremor and is not associated with the occurrence of extrapyramidal symptoms. In contrast, the tremor of patients receiving long-term lithium treatment has a lower frequency and is some-

Propranolol in the treatment of neuroleptic-induced akathisia.

Fourteen patients with neuroleptic-induced akathisia were treated with propranolol in an open trial. All patients demonstrated substantial improvement of their akathisia; nine of the 14 obtained complete remission. Response was quite rapid, occurring within 24 hours in most cases. Doses required for improvement were low (30-80 mg/day), and side effects were few. Lithium-induced tremor improved considerably, but symptoms of parkinsonism and tardive dyskinesia showed little change. Preliminary results with certain other beta blockers suggest that they are less effective than propranolol in the treatment of akathisia.

Acute lithium-induced tremor.

It has recently been found that tremor in patients on long-term lithium therapy has a lower frequency than that of normal physiological tremor and is likely to have an extrapyramidal component (Tyrer et al, 1981). Other extrapyramidal signs and symptoms have been found with chronic lithium therapy (Shopsin and Gershon, 1975; Baastrup et al, 1976; Branchey et al, 1976; Asnis et al, 1979). These extrapyramidal effects differ from the pseudoparkinsonism produced by antipsychotic drugs in that they do not respond to antiparkinsonian drug treatment (Schou, 1970; Tyrer et al, 1980).

Treatment of lithium-induced tremor and familial essential tremor with essential fatty acids

Treatment of lithium-induced tremor and familial essential tremor with essential fatty acids

Linoleic acid in the treatment of lithium-induced tremor: A pilot trial with negative outcome

Linoleic acid in the treatment of lithium-induced tremor: A pilot trial with negative outcome

Die Behandlung des Lithiumtremors mit dem Beta-Rezeptorenblocker Pindolol

In a cross-over study with Pindolol, 15 mg/day, against placebo, we studied during 4 weeks 22 patients aged between 20 and 65 years who where treated by means of lithium carbonate retard (Quilonum Retard). The tremor was measured twice a week by means of three apparative methods: an accelerometer, a 'hole-plate' and an 'aimed tapping plate', both constructed by Janke, and was also studied by means of a self-evaluation rating-scale. We obtained a positive therapeutic effect of Pindolol on lithium-induced tremor, which was statistically significant by means of the 'hole-plate' and of self-evaluation. Differences in results are discussed.

Severe neurotoxicity and lithium therapy.

The patient, a manic depressive who was treated with lithium for three years, suddenly developed severe neurotoxicity and a glomerulonephritis-like syndrome. The author believes that the lithium toxicity was facilitated by hot weather with excessive sweating, gall bladder pathology with fever, and decreased water and salt intake. The patient improved except for a persistent hypertension. Propranolol not only improved the hypertension but alleviated a lithium-induced tremor as well.

Untersuchungen des lithiumbedingten Tremors mit verschiedenen Messmethoden

The authors discuss the character of lithium-induced tremor. Three various measuring methods are presented: an accelerometer, a hole-plate and an apparatus based on aimed tapping. A fourth apparatus is proposed. The first three methods were applied on 16 patients who received lithium therapy and on a control group consisting of 22 normal persons. The results were statistically evaluated. For registering the postural component of lithium-induced tremor, the first two methods proved themselves worthy of recommendation in quotidian practice. Frequency and amplitude of lithium-induced tremor till the ninth day of drug administration are discussed - and constitute only one aspect of a bigger, still going on, study.

Use of beta-adrenergic receptor blocking drugs in psychiatry.

On the evidence surveyed it is difficult to reach clear-cut conclusions about the value of propranolol or other β-blocking drugs in psychiatry. Studies on anxiety for the most part have been of relatively short duration and, although some workers have claimed benefits for propranolol administration, more recent and better controlled trials have failed to demonstrate advantages over placebo treatment. The possibility remains that control of the autonomic symptoms associated with anxiety to some degree diminishes the patient’s distress in the face of an unpleasant affect. Hence there may be merit in the opinion that the autonomic symptoms appear to act as signals which are interpreted as warnings of impending danger. Such activation in its turn results in the psychological experience of anxiety. Hence, in this group of patients at least, control of the autonomie 1 See subject index in each issue for further indexing terms. symptoms should minimise the extent to which anxiety, as a psychological disturbance, is felt. In other forms of psychiatric disorder, the evidence is less convincing. There is no reason to believe that patients with chronic psychoses will benefit and the effects of propranolol in the treatment of alcoholism appear to be short-lived, although longer trials are clearly warranted. The finding that the drug appears to block the actions of opiates is of considerable interest and one can but hope that more extensive testing of propranolol with narcotic-dependent patients will be carried out. In healthy subjects, propranolol appears to be a relatively safe drug, but its use for the control of hypertension and cardiac symptoms in patients who have experienced former depressive illnesses should probably be strictly limited. Transitory hallucinosis and toxic confusional states have been recorded. They appear to be dose-related and subside when the drug is withdrawn. There appears to be a use for propranolol in the treatment of. lithium-induced tremor and overdosage with tricyclic antidepressants.

LITHIUM‐INDUCED TREMOR

Medical Journal of AustraliaVolume 1, Issue 6 p. 183-183 CORRESPONDENCE LITHIUM-INDUCED TREMOR First published: 01 February 1973 https://doi.org/10.5694/j.1326-5377.1975.tb111316.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume1, Issue6February 1975Pages 183-183 RelatedInformation

Klinische Behandlungsversuche des lithiumbedingten Tremors durch einen β-Rezeptorenantagonisten (Propanolol)

The paper describes the theoretical and experimental basis of lithium action, tremor as the main side effect, and the attempt of treating tremor in Parkinson’s disease by administration of β-receptor blockers. A review is presented of β-receptor and propanolol action, as well as its relation to lithium-induced tremor. 15 of own cases, 10 of which were affected by lithium-induced tremor and the other 5 by psychogenic tremor, were treated by 2 X 40 mg (or 4 X 20 mg) propanolol over a period of 7-28 days under permanent supervision of lithium blood level. The ten lithium-treated patients belong to the following diagnostic groups: manic-depressive psychosis, endogenous depression, ‘vitalised’ neurotic depression and schizo-affective psychosis. Out of the 8 positive results obtained, 3 were satisfactory and 5 excellent. No side effects were observed. Tremor modifications were objectivated by writing and drawing tests. Further possibilities for more detailed studies are discussed.