Drooling mouth: A rare complication of oral lithium therapy at subtherapeutic level

INTRODUCTION

Lithium is effective in treating acute manic and depressive episodes, as well as reducing the risk of suicidal thoughts and actions and mood episode recurrence.^[1] Lithium therapy is the most commonly recommended long-term prophylactic (recurrence-preventing) treatment for bipolar disorder and unipolar depression.^[2,3] It is unclear how precisely the ion lithium works. One way that lithium protects cells at the cellular level is through the phosphatidylinositol system, which involves inhibiting the enzyme inositol monophosphatase. Additional pathways involve controlling the expression of growth factor genes, modifying G proteins, and influencing neuronal plasticity by interacting with signal transduction cascades downstream, which include inhibiting glycogen synthase kinase 3 and protein kinase C.^[4] The therapeutic window for lithium is narrow, and serum lithium levels need to be checked frequently. The various categories of negative side effects linked to lithium use include renal, sexual symptoms, neurological, thyroid, gastrointestinal, cognitive, cardiovascular dermatological, as well as metabolic. A few appear during the first few days of lithium treatment, and the majority either go away or get better with time. However, during any phase of lithium therapy, some unfavorable side effects can occur, and some of them may be major contributors to lithium non-adherence.^[5,6] Treatment with lithium frequently causes dyspepsia, nausea, vomiting, and diarrhea as side effects. Patients have also reported weight gain, tremors, increased thirst, polyuria, and acne since starting treatment.^[6] Patients in neuropsychiatry often experience salivation or drooling as a side effect of many antipsychotic medications, such as clozapine and direct as well as indirect cholinergic agonists used to treat dementia and myasthenia gravis. Salivary hypersecretion, dental malocclusion, postural issues, and incapacity to detect salivary spills are additional contributing factors. Numerous physiological and psychological issues, such as perioral chapping, dehydration, foul breath, and speech disturbance resulting in social anxiety, can be caused by hypersalivation.^[7] One uncommon side effect of lithium that has not been extensively documented in the literature is hypersalivation.

CASE REPORT

A 32-year-old male, with a known case of recurrent depressive episode, on lithium therapy (tablet lithium 300 mg BD) along with antidepressant (tablet escitalopram 20 mg) for the past 6 months, reported to the hospital with complaints of low mood, loss of interest in daily activities, and sleep disturbance. He also complained of hypersalivation for the past 15–20 days, which increased during the night. There were no indications of dental or oral pathology upon examination of the oral cavity. The individual denied a history of hypersalivation before. His serum lithium level was measured at a subtherapeutic level of 0.33 mEq/L (normal serum level: 0.6–1.2 mEq/L). The patient was educated about the possible cause of sialorrhea and psycho-educated about the various treatment options. Initially, tablet trihexyphenidyl 2 mg was added for the treatment of sialorrhea. Individuals reported a decrease in excessive salivation after 2 to 3 days. However, as an individual was still symptomatic with depressive features and tablet lithium had caused side effects even at the subtherapeutic level, tablet lithium was eventually stopped, and instead, tablet divalproex sodium 500 mg BD was started. The symptoms of excessive salivation were completely resolved after stopping lithium. Subsequently, coping skills training and problem-solving skills were discussed, and he was engaged in psychotherapy on the lines of cognitive behavioral therapy. The individual showed improvement in his mood symptoms. After 3 weeks, he was discharged from the hospital in satisfactory condition.

DISCUSSION

In our study, hypersalivation occurred at the subtherapeutic level of 0.33 mEq/L. This matches another case report by Johnson et al. in which the serum level was <0.3 mEq/L at the onset of hypersalivation.^[8] Only a small number of studies have shown that sialorrhea can occur at serum levels between 0.85 and 0.9 mEq/L.^[9,10] Consequently, sialorrhea can develop below normal serum levels as well as at toxic serum levels (1.5 mEq/L and higher).

In our case study, sialorrhea started to occur 5 months after therapy was started. In a comparable case report, it started 1 month after the start of lithium therapy.^[11] According to a case report by Donaldson,^[9] sialorrhea appeared 10 days after the start of therapy. Khalil et al.^[10] reported sialorrhea in a case report within 3 days of starting lithium therapy. These variations suggest that sialorrhea can occur at any time after initiation of lithium therapy.

The degree of hypersalivation is directly correlated with serum lithium levels.^[11] The central nervous system’s metabolism of catecholamines is impacted by lithium levels, but the peripheral nervous system is unaffected. It is well known that the secretion of lithium ions by the salivary glands can result in chronic localized irritation.^[11,12] In addition, it is recognized to activate the emetic zone’s central chemoreceptors. There are reports that lithium causes a brief increase in urine aldosterone, which causes salivation to increase. Lithium’s direct impact on salivary gland secretion is another possibility.^[11,12]

In Halder et al.’s case report,^[13] adding an anticholinergic medication caused a reduction in hypersalivation. In our case report, anticholinergic medications helped reduce sialorrhea, but complete remission was achieved after lithium therapy was stopped. In a case report by Khalil et al.^[10] stoppage of lithium therapy was important for the complete remission of hypersalivation.

CONCLUSION

One uncommon side effect of lithium therapy is sialorrhea. Sialorrhea may disturb sleep; some patients may describe a choking sensation at night. Although a benign side effect, hypersalivation can be distressing to the patient. It is a socially stigmatizing condition that may lead to anxiety and reduced self-esteem in patients, resulting in non-adherence to treatment and relapse of mood disorder. Sialorrhea has been reported in cases where there were no signs of lithium toxicity, and the lithium serum level was at a subtherapeutic level. Thus, a patient who reports symptoms of hypersalivation after lithium therapy has been started should be thoroughly evaluated for his symptoms. Although anticholinergic agents can improve lithium-induced sialorrhea, sometimes dose reduction or even complete stoppage of lithium therapy and switching to another mood stabilizer may be required for complete remission of symptoms.