Psycholeptics. Lithium
ATC code: N05AN01 (Lithium)
Brand names
Lithobid, Eskalith, Lithonate, Lithotabs, Cibalith-S
Exact mechanism unclear; affects second messengers (inositol triphosphate, GSK-3β), modulates serotonergic and dopaminergic transmission. First-line for bipolar disorder, reduces suicide risk. Narrow therapeutic window 0.6–1.2 mmol/L; overdose causes neurotoxicity and nephrotoxicity.
First line
For acute mania, lithium is effective as monotherapy or combined with antipsychotics. 2019 Cochrane review (McKnight) confirmed efficacy with NNT approximately 6 for clinical response. Onset is 5–7 days, so combination with a rapid-acting antipsychotic or benzodiazepine is common in the acute phase.
First line
Lithium is the first-line maintenance therapy for bipolar disorder type I and II. CG185 2023 and RANZCP 2022 list lithium as the drug of choice for long-term mood stabilization in adults. Reduces manic episodes by 60–70% and depressive episodes by 30–40%. For acute mania, comparable to valproate and atypical antipsychotics. Lithium is unique in reducing suicide risk in bipolar disorder (Cipriani 2013 meta-analysis demonstrated all-cause mortality reduction).
Narrow therapeutic range: 0.6–1.2 mmol/L. Regular monitoring of plasma level, renal function, and thyroid is mandatory.
Sources
Adjunct
Lithium is used as augmentation in patients with treatment-resistant unipolar depression. and recommend adding lithium to an antidepressant when adequate monotherapy fails. Meta-analyses show NNT approximately 5 for remission. Target blood level 0.4–0.8 mmol/L (lower than for bipolar disorder).
In Russia, the treatment-resistant depression indication is not registered directly in GRLS; use is off-label per clinical guidelines.
Not recommended
Lithium use without therapeutic drug monitoring is unacceptable. Narrow therapeutic range (0.6–1.2 mmol/L) and toxicity at levels above 1.5 mmol/L require regular monitoring every 3–6 months and with any change in dose, diet, or comedications. Without TDM the drug is not prescribed.
Lithium and sodium compete for reabsorption in proximal renal tubules. Reduced plasma sodium (salt-restricted diet, fluid loss, diuretics) increases lithium reabsorption and plasma concentration, precipitating toxicity. Patients are advised to maintain stable salt intake (about 4–6 g/day) and dietary sodium, increase fluid intake in heat or exertion. With acute diarrhea, vomiting, or fever, temporarily withhold and check level.
Source: FDA: Lithobid (lithium carbonate) prescribing information (2021)
2 pairs found. Sorted from critical to minor.
Mechanism
Фуросемид и тиазидные диуретики снижают почечный клиренс лития, концентрация в плазме растет на 25–40%.
Management
Контроль лития через 5–7 дней после старта диуретика, далее каждый месяц. Альтернатива – петлевые диуретики с осторожностью.
Mechanism
снижают почечный клиренс лития, концентрация в плазме растет на 20–60% за неделю.
Management
Избегать длительного курса . Если без них нельзя – парацетамол. При сочетании контроль лития через 5–7 дней.
Boxed warning
FDA boxed warning: lithium toxicity is closely related to serum concentration and can occur at levels close to therapeutic. Regular plasma monitoring is mandatory. Use without TDM capability is not permitted. Administer with caution in patients at risk of dehydration, renal impairment, hyponatremia.
FDA category D. First-trimester use increases Ebstein anomaly risk (10–20-fold relative risk, absolute risk 0.1–1%). Decision to continue therapy is made jointly with psychiatrist and obstetrician, weighing relapse risk against fetal risk. If continued, fetal echocardiography at 16–20 weeks. Before delivery, lithium dose is reduced by 30–50% to prevent neonatal toxicity.
Passes into breast milk at 40–50% of maternal plasma level. LactMed lists lithium as generally incompatible with breastfeeding: accumulation risk in infant with toxicity (lethargy, hypotonia, cyanosis). If breastfeeding is necessary, monitor infant lithium level.
lithium is evaluated for the following indications with varying evidence strength: Bipolar disorder (evidence tier A), Acute psychomotor agitation (evidence tier A), Treatment-resistant depression (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of lithium (≥ 1 in 100): Fine hand tremor, Polyuria and polydipsia (nephrogenic diabetes insipidus), Nausea, diarrhea at initiation, Weight gain, Subclinical hypothyroidism, Metallic taste. See the Safety section for uncommon and serious reactions.
FDA category D. FDA category D. First-trimester use increases Ebstein anomaly risk (10–20-fold relative risk, absolute risk 0.1–1%). Decision to continue therapy is made jointly with psychiatrist and obstetrician, weighing relapse risk against fetal risk. If continued, fetal echocardiography at 16–20 weeks. Before delivery, lithium dose is reduced by 30–50% to prevent neonatal toxicity.
Passes into breast milk at 40–50% of maternal plasma level. LactMed lists lithium as generally incompatible with breastfeeding: accumulation risk in infant with toxicity (lethargy, hypotonia, cyanosis). If breastfeeding is necessary, monitor infant lithium level.
lithium is contraindicated in: Hypersensitivity to lithium; Severe renal impairment (eGFR < 30 mL/min); Severe cardiovascular disease; Addison disease; Severe dehydration. Full list in the Safety section.
FDA boxed warning: lithium toxicity is closely related to serum concentration and can occur at levels close to therapeutic. Regular plasma monitoring is mandatory. Use without TDM capability is not permitted. Administer with caution in patients at risk of dehydration, renal impairment, hyponatremia.
second half is true: with regular TDM, renal and thyroid monitoring, lithium is safe and effective. There really is no need to fear it. But without monitoring, the risk of irreversible toxicity is high.
in most patients, renal function changes are minimal with proper use. Chronic kidney disease develops in some patients after over 15–20 years of therapy, offset by reduced suicide risk and bipolar relapse.
NICE 2023 and RANZCP 2022 retain lithium as first-line maintenance therapy in BD. The unique suicide-reducing effect has not been replicated by other agents.