Lithium Side Effects for Bipolar Disorder Lead to Lower Prescription Rates

Lithium prescription rates for patients with bipolar disorder have declined during the last decade due to the side effect and toxicity burden associated with the drug, according to a study published in the International Journal of Bipolar Disorders.

Michael Gitlin, MD, from the Geffen School of Medicine, University of California at Los Angeles, reviewed documents through July 2016 that outlined the most common side effects for lithium and the treatment options for the drug, as well as the potential toxic effects on organ function. The most common side effects of lithium include gastrointestinal (nausea and diarrhea), polyuria/polydipsia, tremor, weight gain, cognitive impairment, sexual function, and dermatologic effects (acne and psoriasis). Lithium intoxication includes symptoms ranging from weakness and mild ataxia to confusion, vomiting, and lethargy. Lithium can also cause damage to the kidneys, thyroid gland, and parathyroid gland.

The following are treatment options and best practices for the side effects of lithium, according to the study.

Gastrointestinal side effects: nausea and diarrhea

Nausea may correlate with lithium levels, especially peak levels, so taking lithium after meals, using a multiple daily dose regimen, or using sustained release preparations may diminish the symptom. Diarrhea increases in prevalence in patients through the first 6 months of treatment and is normally associated with lithium toxicity. Clinicians should further treat for lithium intoxication for a patient who presents with diarrhea.


Lithium causes polyuria and polydipsia in up to 70% of long-term patients, making it one of the most common side effects associated with lithium. The presumption is that the thirst associated with lithium is secondary to the obligate renally mediated polyuria. Studies show that once-daily lithium is associated with lower urine volume.


Patients treated with D2 blockers and lithium may present with complex tremor. The type of lithium preparation does not alter tremor prevalence, but higher lithium levels correlate with greater risk of tremor. The most common treatment of tremor is beta blockers, specifically propranolol.

Weight Gain

Patients have reported that while weight gain is the third most common side effect, it is the most bothersome. The likelihood of weight gain should be discussed prior to lithium treatment between the clinician and patient since prevention is easier than treatment. Patients should be encouraged to drink low or noncaloric drinks to treat their thirst. General diet and exercise strategies should, of course, be encouraged. If the patient is taking multiple medications, switching from a treatment with high weight gain liability to another with less weight gain should be considered. The use of adjunctive weight-losing medications, such as topiramate, may be tried if the previous strategies are insufficient.

Cognitive impairment

Lithium may cause anterograde amnesia, slightly slowed motor movement, and diminished creativity; however, those symptoms could be associated with bipolar disorder itself as opposed to lithium use. There are no suggested systematic treatment strategies for lithium-associated cognitive function. A first consideration should be to lower the lithium serum level since cognitive effects seem dose related. Second, a review of other psychotropic medications being prescribed and whether they might contribute to the side effect would be in order. Stimulants should be considered as well.

Sexual function

Sexual dysfunction from lithium has been relatively neglected as a topic of clinical inquiry; however, stable bipolar patients on lithium showed decreased libido and sexual satisfaction. Aspirin 240 mg daily has been shown to reduce overall sexual dysfunction and improve erectile dysfunction. Phosphodiesterase 5 inhibitors should also be considered for those with lithium-associated sexual difficulties.

Dermatologic effects

In mild cases of acne caused by lithium use, dermatologic remedies should be considered. A trial found a positive effect of inositol 6 g daily in decreasing the severity of psoriatic lesions in lithium-treated patients.

Lithium intoxication

Lithium toxicity has been divided into 3 patterns: acute, acute-on-chronic, and chronic. In mild lithium toxicity, symptoms include weakness, worsening tremor, mild ataxia, poor concentration, and diarrhea. With worsening toxicity, vomiting, the development of gross tremor, slurred speech, confusion, and lethargy emerge. In cases of mild toxicity, discontinuation of lithium may suffice. With moderate toxic episodes, fluid infusion with saline diuresis is recommended along with gastric lavage and whole bowel irrigation using polyethylene glycol. In the most severe of cases, hemodialysis should be instituted.

Lithium can cause severe renal damage in the kidneys, and general guidelines for minimizing the risk of renal damage include: monitor serum creatinine and eGFR regularly during lithium treatment at intervals of every 6 months to 1 year; avoid episodes of lithium toxicity, keep mean lithium levels within the low therapeutic range when possible, and consider once-daily dosing.

The prevalence of thyroid dysfunction in lithium-treated patients can be seen in cases of overt hypothyroidism, subclinical hypothyroidism, or goiter without reference to biochemical markers. Thyroid parameters should be checked before lithium is instituted and then monitored after 3-6 months initially and then every 6-12 months. A clinical rule to remember is that hypothyroidism never justified lithium discontinuation. Thyroid hormones should be prescribed to bring abnormal TSH values within the normal range.  

Lithium also increases renal calcium reabsorption and independently stimulates parathyroid hormone release. Mild evaluations of hormone levels in asymptomatic patients can be monitored. With higher levels of the hormone, switching from lithium to a different mood stabilizer, calcimimetic therapy with cinacalcet or local or subtotal parathyroidectomy are the reasonable treatment options.

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  1. Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 17 December 2016. DOI: 10.1186/s40345-016-0068-y

This article originally appeared on Clinical Advisor