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Lithium's place in treatment
Lithium has been used to treat bipolar disorder for decades and is widely regarded as the standard against which other mood stabilizers are measured. The CANMAT and ISBD 2018 guidelines for bipolar disorder list lithium as a first-line option for acute mania and for maintenance treatment in bipolar I disorder (Yatham et al., 2018). Yet prescribing of lithium has fallen, and concern about its side effects and toxicity is one likely reason (Gitlin, 2016). PMHNPs need to know how to use it safely to offer it with confidence.
Mechanism
Lithium's exact mechanism in mood disorders is not fully understood. Proposed actions include effects on intracellular signaling, such as inhibition of inositol monophosphatase and glycogen synthase kinase-3, which may stabilize neuronal activity over time. Because of this, lithium works gradually, over days to weeks.
Pharmacokinetics that drive safety
- Lithium is not metabolized; it is excreted almost entirely by the kidneys.
- The kidneys handle lithium much like sodium, so dehydration, a low-sodium diet or sodium loss raise lithium levels.
- It has a narrow therapeutic range, so the dose is guided by serum levels drawn about 12 hours after the last dose, once levels have reached a steady state.
Drug interactions
Medications that reduce kidney clearance of lithium can push levels into the toxic range:
| Drug class | Effect |
|---|---|
| NSAIDs | Raise lithium levels |
| ACE inhibitors and angiotensin receptor blockers | Raise lithium levels |
| Thiazide diuretics | Raise lithium levels |
Patients should be told not to start over-the-counter NSAIDs, such as ibuprofen, without asking.
Side effects and their management
Gitlin (2016) separates common side effects that are usually manageable from those that are more distressing or need monitoring:
- Common and usually manageable: thirst and frequent urination, nausea and diarrhea, and tremor. Adjusting dose timing, keeping levels at the lowest effective point in the therapeutic range and, in some cases, prescribing an antidote help.
- More distressing and linked to stopping lithium: weight gain and cognitive slowing.
- Organ effects needing monitoring: kidney effects (usually mild, though a small proportion of patients develop progressive kidney impairment), hypothyroidism (relatively common and easily treated) and hyperparathyroidism.
Toxicity
Early signs include coarse tremor, vomiting, diarrhea and unsteadiness; severe toxicity can cause confusion, seizures and arrhythmias. Toxicity is an emergency, so patients and families should know these signs and stop lithium and seek care if they occur, especially during a vomiting illness or heat exposure.
A monitoring plan
| When | What |
|---|---|
| Before starting | Kidney function, thyroid function, calcium, pregnancy test where relevant, ECG for patients with cardiac risk, weight |
| During titration | Serum lithium levels after each dose change, once at steady state |
| Ongoing | Lithium levels, kidney and thyroid function and calcium at regular intervals; weight; ask about side effects at every visit |
Conclusion
With careful dosing, monitoring and patient education, lithium can be used safely. The PMHNP's role is to explain its benefits honestly, manage side effects early so patients stay on it, and build safety checks into every prescription.
References
Gitlin, M. (2016). Lithium side effects and toxicity: Prevalence and management strategies. International Journal of Bipolar Disorders, 4, Article 27. https://doi.org/10.1186/s40345-016-0068-y
Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., Alda, M., MacQueen, G., Milev, R. V., Ravindran, A., O'Donovan, C., McIntosh, D., Lam, R. W., Vazquez, G., Kapczinski, F., . . . Berk, M. (2018). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disorders, 20(2), 97–170. https://doi.org/10.1111/bdi.12609
