Can lithium cause tremor and Parkinsonism?

Lithium-Induced Tremor and Parkinsonism

Yes, lithium definitively causes both tremor and parkinsonism as recognized adverse effects, even at therapeutic serum levels. These movement disorders can occur independently or together and require careful clinical assessment to distinguish from other causes.

Lithium-Induced Tremor

Lithium tremor is classified as a postural tremor, specifically an exaggerated physiologic tremor 1. This is one of the most common side effects of lithium therapy and occurs frequently in clinical practice 1.

Clinical Characteristics

• Early signs of lithium toxicity include tremor, along with nausea, diarrhea, polyuria-polydipsia, mild ataxia, drowsiness, or muscular weakness 2
• The tremor typically presents as a postural tremor that is most noticeable when the patient extends their arms 1
• Risk factors include polypharmacy, male gender, older age, high doses, and immediate-release preparations 3

Critical Monitoring Considerations

• Patients and families must be warned to discontinue lithium and contact their physician immediately if tremor develops alongside other signs of toxicity 2
• Regular serum lithium monitoring is essential, especially during acute treatment phases, with measurements twice per week until stabilized 4, 5
• The FDA label emphasizes that lithium toxicity occurs at doses close to therapeutic concentrations, making vigilant monitoring crucial 4

Lithium-Induced Parkinsonism

Lithium can cause drug-induced parkinsonism (DIP) that presents with classic parkinsonian features including bradykinesia, tremor, rigidity, and freezing of gait 6. This is a less commonly recognized but clinically significant adverse effect.

Clinical Presentation

• Drug-induced Parkinsonism from lithium manifests with motor symptoms of tremor, rigidity, postural instability, and bradykinesia 7
• Parkinsonian symptoms can develop even with therapeutic serum lithium levels in chronic users, particularly in geriatric populations 6
• The condition may be difficult to differentiate from idiopathic Parkinson's disease without specialized imaging 6

Diagnostic Approach

• DaTscan SPECT imaging can clarify the diagnosis by differentiating drug-induced parkinsonism from neurodegenerative Parkinson's disease 6
• When diagnostic uncertainty exists, dopaminergic imaging assists in differentiating drug-induced from neurodegenerative parkinsonism 7
• Consider that antipsychotic medications can also induce Parkinsonism, which may complicate the clinical picture if patients are on multiple psychotropic agents 7

Management Algorithm

Immediate Assessment

1. Obtain serum lithium level immediately to rule out toxicity 5, 8
2. Evaluate hydration status and check for precipitating factors including dehydration, medication interactions (especially NSAIDs), or renal impairment 5
3. Monitor renal function tests and electrolytes (potassium, magnesium) 5

Treatment Strategy for Tremor

• If tremor is disabling, pharmacotherapy is indicated 1
• Vitamin B6 (900-1200 mg/day) has shown preliminary evidence for treating lithium-induced tremor, with some patients experiencing complete resolution 9
• Beta-blockers may be useful but have limiting side effects 1
• Consider dose reduction if clinically feasible without compromising psychiatric stability 6

Treatment Strategy for Parkinsonism

• Reducing the daily lithium dosage typically improves motor symptoms 6
• Drug-induced Parkinsonism may be treated by adding an anticholinergic agent, adding a dopaminergic agonist (e.g., amantadine), or decreasing the antipsychotic dosage 7
• Early diagnosis and rapid withdrawal of the offending drug improves the possibility of complete recovery 7

Critical Pitfalls to Avoid

• Do not assume parkinsonian symptoms represent negative symptoms of psychiatric illness or catatonia - this is a common misdiagnosis 7
• Do not overlook lithium-induced movement disorders in the clinical setting as they are easily missed 1
• Avoid concomitant NSAIDs which can increase lithium levels and precipitate toxicity 5, 2
• Temporarily suspend lithium during intercurrent illness, IV radiocontrast administration, bowel preparation, or prior to major surgery 5, 8
• Maintain adequate hydration (2500-3000 mL daily) and normal salt intake, especially during initial stabilization 2

Special Populations

Geriatric patients require particularly close monitoring of lithium levels as they are at higher risk for developing parkinsonism 6. The ability to tolerate lithium is greater during acute manic phases and decreases when manic symptoms subside, necessitating dose adjustments 2.