Lithium is the oldest agent in the psychiatric formulary and still one of the most examined, for a reason that has nothing to do with tradition: it has a narrow therapeutic index, it is cleared by the kidney, and a long list of everyday medications and everyday events will push a stable patient into toxicity. That combination makes it ideal exam material.
Lithium: what you check and when
Before starting, the expected workup covers renal function, thyroid function, an assessment of cardiac status where clinically indicated, calcium, a pregnancy test where relevant, and a baseline weight. Lithium levels are drawn as a trough - conventionally about twelve hours after the last dose - and rechecked after initiation and after every dose change, then periodically once stable, alongside continued renal and thyroid surveillance.
Long-term, the organs that matter are the kidney and the thyroid. Hypothyroidism is common enough that thyroid function is part of routine monitoring rather than a response to symptoms, and a rise in creatinine is a reason to reassess rather than to continue unchanged. Hyperparathyroidism with hypercalcaemia is the less-remembered third.
Target ranges and monitoring intervals vary by indication and guideline
Therapeutic ranges differ between acute treatment and maintenance, and recommended monitoring intervals differ between guideline bodies and have been revised over time. Confirm the specific numbers you rely on against current prescribing information and the guideline your practice follows, particularly for older adults and for patients with reduced renal function.
Toxicity, and what causes it
Early toxicity is gastrointestinal and neurological: nausea and vomiting, a coarse tremor that is distinguishable from the fine benign tremor of therapeutic use, ataxia, slurred speech and confusion. As it progresses, the neurological picture worsens toward myoclonus, seizures and impaired consciousness.
What matters more for exam purposes is the list of things that raise the level in a patient who has not changed their dose at all:
- Dehydration - vomiting, diarrhoea, fever, heat, exercise, reduced intake. The classic vignette is a stable patient with gastroenteritis or a summer heatwave.
- Sodium depletion - low-sodium diets and diuresis increase lithium reabsorption.
- Thiazide diuretics, ACE inhibitors and angiotensin receptor blockers, and NSAIDs - the three interaction groups worth memorising as a set.
- Declining renal function, including with age.
A lithium question that mentions a stomach bug, a new blood pressure medication, or ibuprofen for back pain has already told you the answer.
Counselling follows directly: maintain consistent fluid and salt intake, do not start over-the-counter anti-inflammatories without checking, report vomiting or diarrhoea, and know the early symptoms of toxicity.
Valproate
Valproate is effective in acute mania and in maintenance, and its examinable content is mostly safety. Hepatotoxicity and pancreatitis are the serious idiosyncratic risks; thrombocytopenia and other haematological effects occur; weight gain, tremor, sedation and hair thinning are common tolerability issues. Liver function and complete blood count monitoring at baseline and periodically are expected.
The reproductive safety profile is the part the exam tests hardest. Valproate carries substantial teratogenic risk, including neural tube defects, and is associated with adverse neurodevelopmental outcomes after in-utero exposure. In people who could become pregnant it is generally avoided where alternatives exist, and where it is used, contraception counselling and folate supplementation are part of the conversation. A stem describing a young woman with bipolar disorder planning a pregnancy is not asking you to optimise a valproate dose.
Lamotrigine
Lamotrigine's niche in bipolar disorder is maintenance with a particular role against depressive episodes rather than acute mania. Its examinable content is almost entirely the rash.
Serious cutaneous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, are the reason lamotrigine is titrated slowly according to a defined schedule. Two consequences follow, and both are examined:
- Any new rash is treated as serious until proven otherwise, particularly early in treatment or after a dose increase, and particularly with mucosal involvement, blistering, fever or systemic symptoms. The default action is to stop and evaluate, not to observe.
- Interactions change the titration. Valproate substantially increases lamotrigine concentrations, so the lamotrigine dose is reduced accordingly; enzyme-inducing anticonvulsants such as carbamazepine have the opposite effect. Restarting after a significant gap in therapy requires re-titration from the beginning rather than resuming the previous dose.
Carbamazepine
Less commonly used but reliably examined for three things: autoinduction of its own metabolism, which lowers levels over the first weeks; hyponatraemia through a syndrome of inappropriate antidiuretic hormone secretion; and serious haematological reactions including agranulocytosis and aplastic anaemia. It is also a potent enzyme inducer, which is why it appears in interaction questions involving oral contraceptives and other agents. Genetic testing for a specific HLA allele associated with severe cutaneous reactions is recommended before starting in patients of certain ancestries; check current labelling for the specifics.
Second-generation antipsychotics in bipolar disorder
Several second-generation antipsychotics are indicated in acute mania, in bipolar depression, or in maintenance, and the exam expects you to treat them as mood stabilisers rather than as a separate category. Their monitoring requirements are the antipsychotic requirements - metabolic surveillance and movement assessment - layered on top of mood monitoring.
The decisions the exam actually asks
| Scenario in the stem | What is being tested |
|---|---|
| Stable on lithium, now has vomiting and diarrhoea | Recognising a toxicity risk and acting before the level is drawn |
| Stable on lithium, started on a thiazide or an NSAID | Interaction awareness |
| Lithium plus a coarse tremor and ataxia | Distinguishing toxicity from benign fine tremor |
| Person of childbearing potential with bipolar disorder | Reproductive safety of the chosen agent |
| New rash three weeks into lamotrigine | Stopping and evaluating rather than observing |
| Lamotrigine added to valproate | Dose adjustment for the interaction |
| Depressed patient with prior hypomania | Not treating bipolar depression with an antidepressant alone |
Write those seven scenarios on a card. If you can answer all seven cold, you have most of this block.
Key points
- Lithium has a narrow therapeutic index and renal clearance; dehydration, sodium depletion, thiazides, ACE inhibitors, ARBs and NSAIDs all raise the level.
- Routine lithium monitoring covers levels, renal function, thyroid function and calcium - not only the level.
- Coarse tremor, ataxia, vomiting and confusion suggest toxicity; a fine tremor alone is common at therapeutic levels.
- Valproate carries substantial teratogenic risk and is generally avoided where pregnancy is possible and alternatives exist.
- Any new rash on lamotrigine is stop-and-evaluate; valproate raises lamotrigine levels and requires dose adjustment.