What are the consequences of taking Lithium (lithium carbonate) not as prescribed, particularly for patients with a history of bipolar disorder or other psychiatric conditions?

Consequences of Not Taking Lithium as Prescribed

Failing to take lithium as prescribed dramatically increases the risk of relapse, with over 90% of noncompliant patients experiencing mood episode recurrence compared to only 37.5% of those who maintain adherence, and abrupt discontinuation specifically triggers rebound mania within 6 months in the majority of cases. 1

Immediate Risks of Nonadherence

Relapse and Mood Destabilization

• Withdrawal of maintenance lithium therapy is associated with an increased risk of relapse, especially within the 6-month period following discontinuation. 1
• More than 90% of adolescents who were noncompliant with lithium treatment relapsed, compared to 37.5% of those who were compliant. 1
• The greatest risk of relapse occurs in the first 8-12 weeks after discontinuing medication, with close follow-up encouraged for at least 2-3 months after stopping. 1

Loss of Anti-Suicide Protection

• Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect that is independent of its mood-stabilizing properties. 1, 2
• This unique anti-suicidal effect is lost when lithium is discontinued or taken inconsistently. 2

Risks of Abrupt Discontinuation vs. Missed Doses

Abrupt Cessation

• Lithium should be tapered gradually over 2-4 weeks minimum, never discontinued abruptly, to minimize the risk of rebound mania. 1
• Abrupt lithium withdrawal can trigger rapid relapse into mania or depression, often more severe than the original episodes. 1
• Slow tapering of lithium over 2-4 weeks minimum is recommended to minimize rebound risk in patients with bipolar disorder. 1

Intermittent Nonadherence

• Inadequate duration of maintenance therapy leads to high relapse rates, and premature discontinuation of effective medications is a common pitfall. 1
• Patients who restart lithium after discontinuation may not respond as well as they did initially, a phenomenon sometimes called "lithium discontinuation-induced refractoriness." 3

Toxicity Risks from Erratic Dosing

Overdose Potential

• Lithium itself carries significant overdose risk and requires careful third-person supervision in patients with suicidal history, as lithium overdoses can be lethal. 1
• Lithium has a narrow therapeutic window requiring close clinical and laboratory monitoring. 2
• Taking multiple doses at once (to "catch up" on missed doses) can rapidly lead to toxic lithium levels, causing confusion, coarse tremor, ataxia, seizures, and potentially fatal outcomes. 1

Chronic Intoxication

• Chronic lithium intoxication is one of the most common serious adverse drug events, particularly in older individuals. 4
• The incidence rate ratio of serious adverse drug events was significant at 3.36 for patients ≥65 years compared to younger patients. 4

Long-Term Consequences of Poor Adherence

Progressive Illness Course

• Withdrawal of maintenance therapy dramatically increases relapse risk, with over 90% of noncompliant patients relapsing versus 37.5% of compliant patients. 1
• Patients with multiple severe episodes, rapid cycling, or poor response to alternative agents should be counseled that indefinite treatment may be necessary. 1

Renal Complications

• Probably the most important negative effect of lithium, occurring mostly after 10-20 years of administration, is interstitial nephropathy. 5
• Lithium has adverse effects on the kidneys, thyroid gland and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests. 6
• Erratic dosing patterns may contribute to fluctuating lithium levels that stress renal function over time. 5

Critical Clinical Considerations

Monitoring Requirements

• Lithium treatment should only be initiated in settings where personnel and facilities for close monitoring are available. 2
• Baseline monitoring for lithium should include complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females. 1
• Ongoing monitoring for lithium should include lithium levels, renal and thyroid function, and urinalysis every 3-6 months. 1

Patient Education Imperatives

• Patients and their families must be educated on the early signs of lithium toxicity, including fine tremor, nausea, and diarrhea, and should seek immediate medical attention if coarse tremor, confusion, or ataxia develop. 1
• Psychoeducation about symptoms, course of illness, treatment options, and the critical importance of medication adherence should accompany all pharmacotherapy. 1

Common Pitfalls Leading to Nonadherence

Side Effect Management

• Thirst and excessive urination, nausea and diarrhea and tremor are rather common side effects that are typically no more than annoying even though they are rather prevalent. 6
• Weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage and more likely to be associated with lithium nonadherence. 6
• A simple set of management strategies that involve the timing of the lithium dose, minimizing lithium levels within the therapeutic range and, in some situations, the prescription of side effect antidotes will minimize the side effect burden for patients. 6

Inadequate Patient Support

• Family intervention helps with medication supervision, early warning sign identification, and reducing access to lethal means in patients with suicide risk. 1
• Third-party medication supervision for lithium dispensing should be implemented given overdose history, and limited quantities with frequent refills should be prescribed to minimize stockpiling risk. 1