1. BACKGROUND AND CLINICAL INFORMATION:
• Bipolar Disorder: mania, hypomania and prophylaxis of Bipolar Disorder
• Recurrent Depressive Disorder: used to augment antidepressants
• Reduction of intentional selfharm and suicidality.
Chief 2 Pharmacist, Saint John of God Hospital, Stillorgan, Co Dublin.
Honorary Senior Clinical Lecturer, Royal College of Surgeons in Ireland.
Switching lithium products:
Priadel tablets are recommended for routine use. The tablets have score- lines therefore they can be divided accurately to provide smaller dosage requirements. If a patient is unable to swallow tablets a liquid may be prescribed. It is essential that a switch from tablets to liquid is prescribed by their Doctor, and calculation confirmed by Pharmacist.
Example: Switching patient from Priadel tablet (Carbonate) 800mg nocte to Priadel liquid (Citrate) = 400mg (10ml) BD morning and night. Lithium level to be checked 5-7 days post- switch.
• ECG : if cardiac history, risk factors for QTc prolongation, concomitant medicines that prolong QTc
• Weight and height
• Urea and Electrolytes
• Serum Creatinine+/-estimated Glomerular Filtration Rate (eGFR)
• Adjusted Calcium
• Thyroid Function Tests (TFTs): include Free T4 and Thyroid Stimulating Hormone (TSH). Patient should be euthyroid before initiation
• Full Blood Count
• Pregnancy test and review of contraception (in women of childbearing age).
Starting dose may usually range from 400mg-800mg OD (nocte) in adults, depending on indication. Elderly patients, those with renal impairment or those below 50kg in weight, often require lower starting dose (eg 200mg), and maintenance doses.
Lithium plasma level should be checked 5-7 days after starting, after every dose change, and after addition/discontinuation of medication that can affect level.
The minimum effective plasma level for prophylaxis in adults is 0.4mmol/L; optimal range is 0.6- 0.8 mmol/L. A level of 0.4mmol/L may be effective in unipolar depression; 0.6 -1 mmol/L in Bipolar Disorder, and levels at the higher end of the range in mania (0.8-1mmol/L).
TFTs, renal function, Calcium level, and weight check, recommended every 6 months; or every 3 months in at-risk patients.
Once stable, serum lithium levels recommended every 3 months for the first year, then every 6 months; or every 3 months in at-risk patients.
At risk patients include:
• Elderly (> 65 years)
• Have received less than 12 months treatment
• Renal impairment (eGFR<60ml/min)
• Impaired Thyroid function at last test
• Raised Calcium level (adjusted) at last test
• Poor symptom control or suspected poor adherence
• Significant change in patient’s sodium or fluid intake
• Last serum lithium level >0.8mmol/L
• Interacting medicines. Key interacting medicines include: ACEI, ARBs, NSAIDs and Thiazide diuretics. (See summary below and BNF/Stockley’s for exhaustive list).
If a decision is made to discontinue lithium, the risk of relapse may be reduced by reducing the dose gradually. It is recommended to reduce the dose slowly over at least 4 weeks or longer, and preferably up to 3 months in Bipolar Disorder; except in medical emergency or overdose.
ALARM BELL INTERACTIONS: THINK “ANTS” (SEE TABLE LEFT)
ADVERSE EFFECTS : ( NOT AN EXHAUSTIVE LIST)
Cardiac: Lithium may cause cardiac arrhythmia, including bradycardia, sinoatrial dysfunction (SA block), abnormal T waves on ECG (T-wave inversion), and STsegment depression.
Dermatological: Lithium may cause acne vulgaris and/or psoriasis (including exacerbation of both) in patients with and without either condition at baseline.
GI: Lithium may cause dyspepsia, diarrhoea, nausea, vomiting, dysgeusia (metallic or salty taste), gastritis and abdominal pain. Some effects (e.g. nausea) may occur early in treatment. Other effects may take longer to develop. Supratherapeutic lithium levels should be suspected with severe nausea, vomiting and diarrhoea.
Hypothyroidism: Lithium has varied effects on Thyroid Hormone production and regulation, including inhibition of Iodine uptake in the Thyroid, inhibition of Thyroid Hormone synthesis and release, and hepatic conversion of free Thyroxine. Patient may present with typical hypothyroidism symptoms including lethargy, impaired cognition, weight gain, dry skin, and cold intolerance. Risk factors include females, older adults, family history of hypothyroidism, and presence of anti-thyroid antibodies.
Hyperparathyroidism and hypercalcaemia: Hypercalcaemia has been reported with Lithium therapy, which may or may not be related to drug-induced hyperparathyroidism. While lithium has been observed to affect Parathyroid Hormone levels after a single dose, long -term exposure is likely required to observe clinically relevant alterations in Calcium homeostasis.
Polydipsia and polyuria: Common adverse effects associated with lithium. Patients may notice increased urinary frequency (> 3 L in 24 hours) due to poor urine concentration; and increased thirst, which is independent of dry mouth effects of lithium.
Renal effects: Up to one-third of patients may develop some degree of decreased kidney function during the course of lithium therapy, with approximately 5% developing significant kidney impairment/failure.
Sexual dysfunction: Studies report rates of the various effects of 5-40 %. Effects can include decreased libido, impaired sexual arousal, and erectile dysfunction. Sexual dysfunction can negatively impact a patient’s quality of life.
Tremor: Lithium can cause tremor in up to 25% of patients, making it one of the most common adverse effects. This is commonly a bilateral, symmetrical hand tremor, which may spontaneously decrease over time as compensatory mechanisms develop within the patient. Course tremor and muscle twitching may be observed in lithium toxicity.
Tremor commonly begins early in treatment, but can develop later in treatment, with or without a dose increase. Risk factors include: higher doses/serum levels, medicines that can increase lithium level, medicines known to induce tremor (e.g. antipsychotic, antidepressants), caffeine and older adults.
Weight gain: Increases of 4 to 7 Kg within the first year have been reported in the literature. Effects on central mechanisms related to weight gain, satiety and metabolism are possible. Increased consumption of highcalorie, sugary beverages from increased thirst with lithium could contribute.
Symptoms of toxicity:
For patients with symptoms of toxicity (eg diarrhoea, vomiting, coarse tremor, mental state changes or falls):
Withhold lithium, refer to GP/Clinic/Hospital for urgent lithium level and U+Es, and seek specialist advice.
Referral to secondary care may be required depending on the severity of symptoms.
LITHIUM THERAPY : A BLUE BOOK FOR SAFETY
• The national patient information booklet has been produced by Audrey Purcell, Chief 2 Pharmacist, Saint John of God Hospital, and supported by Professor Dolores Keating, Chief Pharmacist, and Saint John of God Drug and Therapeutics Committee.
• This initiative is intended to provide and promote safer lithium therapy, and empower patients to engage with their Healthcare Professional to discuss all aspects of lithium therapy, monitoring, and side-effects.
Appropriate information and monitoring is imperative to ensure best outcomes for patients on lithium therapy and reduce likelihood of harm.
• The booklet has been reviewed and endorsed by Ciara Kirke, HSE Clinical Lead, National Medication Safety Programme, and the national print supported by the HSE’s National Quality and Patient Safety Directorate.
• It has been edited and reviewed by the National Adult Literacy Agency and has successfully been awarded the plain English mark by NALA.
• It has been reviewed and endorsed by Saint John of God Hospital Drug and Therapeutics Committee, Irish Medication Safety Network, Irish Pharmacy Union, and the College of Psychiatrists.
The Lithium booklet contains:
• Essential clinical and safety information for patients
• Information on side-effects and signs of toxicity
• Advise on appropriate OTC medicines and contra-indications
• A programme of monitoring to ensure safe and appropriate monitoring
• A record book to record lithium levels and essential blood test results.
Healthcare Professionals provide essential support and are recommended to:
• Ensure patients have a lithium booklet
• Reinforce essential information verbally
• Refer patient to the booklet to be aware of potential side-effects and signs of toxicity
• Ensure the patient understands their own programme of monitoring
• Support patients to engage in appropriate blood test monitoring: keep their record book up to date, and have available at consultations with GP, Consultant, Pharmacist, Nurse.
National launch of the Lithium booklet:
• Saint John of God Hospital, the HSE National Medication Safety Programme and the Irish Pharmacy Union have collaborated to implement a national launch of the booklet.
• Lithium booklets will be distributed from the HSE directly to Hospital Pharmacies, and to Community Pharmacies via the IPU Review. GPs may sign-post patients to Community Pharmacists to avail of a booklet.
• Booklets can be ordered from Saint John of God Hospital: email@example.com
Many thanks to Aoife Carolan, Senior Pharmacist, Saint John of God Hospital, and Ciara Kirke, HSE Clinical Lead, for article peer-review.
References available on request