Efficacy of Vitamin B6 in Lithium-Associated Tremor: A Case Series

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To the Editors
Tremor associated with lithium treatment is probably the most prevalent drug-related tremor encountered in clinical practice.1 This tremor can occur within therapeutic doses of lithium and is not limited to lithium intoxication.2 The prevalence of lithium-associated tremor has been estimated to be between 10% and 18% by the Canadian Network for Mood and Anxiety Treatments and up to 65% by the World Federation of Society of Biological Psychiatry.3,4 This tremor is a common complaint of patients receiving lithium. It has a significant social impact5 and may be a major cause of poor adherence to lithium. In fact, the prevalence of patients who cease lithium treatment because of adverse effects has been estimated to be between 18% and 53%.6
Lithium-associated tremor falls into the category of physiological tremor and primarily affects the hands.1 Monitoring of serum lithium levels and switching to an extended-release form can reduce lithium-associated tremors.4 When these strategies are ineffective, adjuvant treatment with β-blockers, especially propranolol, can be administered.7 However, propranolol has contraindications including bronchial asthma, diabetes, sick sinus syndrome, sinus bradycardia, first-degree heart block, congestive heart failure, and chronic obstructive pulmonary disease. Importantly, these medical conditions are prevalent in patients experiencing bipolar disorder. In addition, adverse effects of propranolol include light-headedness, fatigue, impotence, and bradycardia. These contraindications and adverse effects can restrict the prescription of propranolol.
Reducing lithium-associated tremor has the potential to improve patient quality of life, adherence to medication, and overall prognosis of bipolar disorder. Consequently, alternative strategies are being explored. The effectiveness of vitamin B6 at reducing lithium-associated tremor was demonstrated in a preliminary open-label clinical trial.8 However, evidence of vitamin B6 efficiency remains limited. Vitamin B6 is an essential vitamin that plays an important role in amino acid metabolism. It is hypothesized that the antioxidant properties of vitamin B6 could ameliorate movement disorders.8 The 3 natural forms are pyridoxine, pyridoxal, and pyridoxamine. Pyridoxine is the most commonly used form in pharmaceutical preparations and dietary supplements.
Patients included in this case series experienced bipolar disorder type 1 (N = 1) or type 2 (N = 6) according to DSM-IV-TR Criteria without comorbid substance-use disorder. Patients were undergoing lithium monotherapy as a mood stabilizer and experienced tremor, scored as “distressing” on the PRISE-M Scale (Rush and Asberg, unpublished rating scale). Tremor imputation to lithium has been established according to the criteria defined by Morgan and Sethi.9 These criteria are (1) the exclusion of other medical causes of tremor (hyperthyroidism and hypoglycemia), (2) a timed relation to the start of treatment with the medication, (3) a dose-response ratio (ie, increasing the dose of drug aggravates tremor or decreasing the dose improves tremor), and (4) the lack of worsening across time. Patients with eating disorders, malnutrition, impaired intestinal absorption, or avitaminosis were excluded from this case series. A monthly assessment of the tremor was performed by a clinical examination of the hands. The presence of tremor was defined as an oscillation of the end of the hands while the patient was voluntarily maintaining arm posture against gravity. Moreover, we used the PRISE-M Scale as a self-administered questionnaire.
Seven patients (56.6 ± 9.9 years, 4 women and 3 men) were included in this case series. Lithium dosage was 1.2 ± 0.8 g/d at the start of the study. The mean serum lithium level was 0.7 ± 0.2 mEq/L, and mean intraglobular lithium level was 0.2 ± 0.1 mEq/L. The duration of lithium treatment before vitamin B6 averaged 48.6 ± 69.6 months. Patients received adjuvant treatment with pyridoxine (750 mg–1 g per day) for an average of 7.3 ± 5.8 months (1–18 months).
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