Table 12.
Lithium Monitoring and Dosing
| Guideline | Dose | Patient monitoring parameters | Specific side effects | Specific drug interactions |
|---|---|---|---|---|
| APA | Required blood level not confirmed | – | Caution with Parkinson’s as may worsen symptoms | – |
| BAP | Referred to a study in which plasma lithium levels of 0.6–1.2 mmol/L were more effective than those outside this range (Bauer et al., 2013a) and a meta-analysis in which most studies used 600–1200 mg/d (not clear recommendations; Crossley and Bauer, 2007) | – | – | – |
| CANMAT | 600–1200 mg/d, dosing 1-2x p/d, aiming for “therapeutic serum levels” (not specified) | – | – | – |
| CPG-S | – | – | – | – |
| ICSI | Referred to studies with usual dose of 300 mg/d administered 3 times during the day, serum levels >0.4 mmol/L (not a clear recommendation; Joffe et al., 1993; Katona et al., 1995; Baumann et al., 1996) | – | – | – |
| MPG | Plasma level 0.4–0.8 mmol/L, increased to 1.0 mmol/L if response suboptimal. 0.6 mmol/L minimum level for prophylaxis/maintenance. See guidelines for recommendations by lithium preparation and advice for impaired renal function. Lithium levels >0.8 mmol/L associated with higher risk of renal toxicity. Toxic effects occur at levels >1.5 mmol/L. Optimal plasma range less clear in unipolar than bipolar depression (Young, 2017). | Baseline: renal, thyroid, and cardiac function estimated GFR and TfTs as a minimum (Morriss and Benjamin, 2008). ECG in all patients with cardiovascular disease risk factors. Weight. Calcium levels desirable. Testing thyroid autoantibodies to aid elimination of hypothyroidism risk. Women advised to use contraception. Serum levels tested after 12 h in patients taking 1 daily dose at bedtime (Goodwin et al., 2016). For middle-aged women, TfTs monitored regularly in first year plus monitoring calcium levels (Livingstone and Rampes, 2006). Plasma lithium, eFGR, and TfTs every 6 mo in all patients and more regularly in special populations. Weight/ BMI monitoring. Calcium level monitoring desirable. Renal function monitored regularly in prolonged treatment (Aiff et al., 2015). | Mild GI upset, tremor, polyurea (Bowen et al., 1991; Ljubicic et al., 2008), thirst, polydipsia. Can cause diuresis and tolerance difficulties in patients with bladder disorder. Contraindicated in severe renal impairment (Gitlin, 1999; Lepkifker et al., 2004). Long-term use associated with impaired renal function, nephrogenic diabetes insipidus, nephrotic syndrome, and both reversible, irreversible kidney damage and increased risk of hypothyroidism (Johnston and Eagles, 1999; Frye et al., 2009; McKnight et al., 2012; Shine et al., 2015). Lithium associated with hyperparathyroidism (McKnight et al., 2012) and chronically elevated calcium levels associated with renal stones, osteoporosis, dyspepsia, hypertension, and renal impairment. May aggravate skin conditions, cause metallic taste, ankle edema, and weight gain. NMS sometimes seen (Gill et al., 2003). Impaired visual adaptation to dark (Metzner et al., 1993). Moderate caution advised in epilepsy as limited evidence of effect on seizures (Wickstrøm et al., 1980). Association with Ebsteins abnormality (though risk may be overestimated; McKnight et al., 2012; Diav-Citrin et al., 2014). Contraindicated in pregnancy. See guidelines for advice on toxicity symptoms and overdose. | Drugs altering renal sodium handling can precipitate lithium toxicity. Includes ACE inhibitors, thiazide diuretics, and NSAIDS. Rare reports of neurotoxicity with carbamazepine. Street drugs can be very toxic if taken erratically. Caffeine cautioned as may decrease lithium levels and withdrawal from caffeine may increase (Baethge et al., 2009). |
| NICE | Plasma levels 0.5–1.0 mmol/L considered therapeutic; toxicity may develop >1.5 mmol/L and can lead to death at 2.0 mmol/L | Baseline and at least every 6 mo: renal function, TFTs. Lithium levels at 1 wk and after every dose change until stable, then every 3 mo. ECG monitoring for patients with high risk of CVD/cardiac symptoms. NICE referred to their bipolar guidelines for further monitoring advice. | Range of cardiac effects: may be important in heart disease, elderly, high lithium levels, hypokalaemia, or those prescribed diuretics, hydroxyzine, and TCAs (Chong et al., 2001). Potential for “sick sinus” syndrome, first-degree heart block, ventricular ectopics, flattened T-waves, and increased QT dispersion, which are common and often subclinical (Reilly et al., 2000). Can also cause hypothyroidism and renal damage, among other effects. | Can interact with commonly prescribed drugs precipitating toxicity. See guidelines for advice on interactions with drugs used during surgery. |
| RANZCP | Trough plasma level (12 h after dosing) between 0.5 and 0.8mmol/L (Berghöfer et al., 2006; Malhi et al., 2011) | Baseline: FBC, renal function, thyroid function, and calcium levels. Check for pregnancy using hCG. At 6, 12, and 24 mo: renal function (urea, creatinine, electrolytes), endocrine (TSH, serum calcium, parathyroid hormones), serum lithium estimations (trough). Lithium should be carefully monitored due to potential for toxicity (Wilting et al., 2005; Lam et al., 2009). | Obesity, metabolic syndrome, hypertension, and diabetes. Small increased risk of fetal cardiac defects (Cohen et al., 1994; McKnight et al., 2012; Diav-Citrin et al., 2014). Recommend treatment with thyroid hormone if hypothyroidism occurs. Cautioned that long-term use associated with serious side effects (Van and Boer, 2006; Malhi et al., 2012). | – |
| TMAP | 300 mg/d titrated by 150 mg/d every 1/2 wk to target dose 600–900 mg/d. Max. based on serum levels considered with tolerability and response, aiming for 0.4–0.6 mmol/L 1–2 times p/d. | ECG at baseline and yearly as indicated. FBC baseline and yearly. TFTs at baseline, TSH every 6 mo/as indicated. BUN at baseline and as indicated (including creatine, glucose, and electrolytes). Urinalysis at baseline and as indicated. Pregnancy test if indicated. Lithium levels 1-wk post initiation, after each change in dose, and as clinically indicated. | Acne, acute renal dysfunction, cognition, diarrhea, dizziness, ECG changes, GI upset, hypothyroidism, nausea, polyuria, sedation, thirst, tremor, and weight gain | ACE inhibitors, caffeine, NSAIDs, osmotic diuretics, theophylline, and thiazide diuretics |
| WFSBP | Trough (12 h post) serum levels 0.6–0.8 mmol/L in acute and maintenance phase. 0.4–1.0 mmol/L may be appropriate depending on response and tolerability. Translates to approximately 900–1200/1500 mg/d lithium carbonate. Single daily dose may increase adherence and reduce side effects (Mosolov et al., 1997). XR formulation better tolerated. Acknowledged that optimal levels may vary (Schou, 1989; Malhi et al., 2011). Specific recommendations made for Asian and elderly populations. | Serum test no earlier than 5–7 days after first dose/changes in dose, 1–4/y, more if indicated. 1–2/y: TFTs, parathyroid function (e.g., blood calcium, and if this is elevated, parathyroid hormone), and renal function (eGFR, creatine; Schou et al., 1997; Livingstone and Rampes, 2006; American Psychiatric Association, 2010; Berger et al., 2013; Severus and Bauer, 2013; Bschor, 2014). Response assessed 2–4 wk post initiation. Monitor for response from 2 to 4 wk (Bschor et al., 2003). | Potential for serotonin syndrome when MAOI/other AD augmented with lithium. Reduced GFR, reduced urinary concentrating ability, polyurea and/or polydipsia, goiter and hypothyroidism, hyperparathyroidism, weight gain, GI symptoms, memory impairment or mental slowness (McKnight et al., 2012). Some patients receiving lithium for ≥10 y may develop rising creatine concentrations, but glomerular and tubular function more commonly affected (Bendz et al., 2010). Hand tremor. Side effects often dose dependent. See guidelines for guidance on how to counteract side effects. | – |
Abbreviations: –, not reported by guideline; AAPs, atypical antipsychotics; ACE, angiotensin-converting enzyme; AD, antidepressant; APA, American Psychiatric Association; BAP, British Association of Psychopharmacology; BUN, blood urea nitrogen; CANMAT, Canadian Network for Mood and Anxiety Disorders; CPG-S, Clinical Practice Guidelines in the Spanish NHS; CVD, cardiovascular disease; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; FBC, full blood count; GI, gastrointestinal; ICSI, Institute for Clinical Systems Improvement; MAOI, monoamine oxidase inhibitors; mg/d, milligrams per day; mmol/L, millimoles per litre; MPG, Maudsley Prescribing Guideline; NICE, National Institute for Health and Care Excellence; NMS, neuroleptic malignant syndrome; p/d, per day; NSAID, non-steroidal anti-inflammatory drug; QT, Q-T interval; RANZCP, Royal Australian and New Zealand College of Psychiatrists; TCAs, tricyclic antidepressants; TFTs, thyroid function tests; TMAP, Texas Medication Algorithm Project; TSH, thyroid stimulating hormone; WFSBP, World Federation of Societies of Biological Psychiatry; XR, extended release.