What information should be included when obtaining informed consent for lithium treatment in a patient with bipolar disorder and potential pre-existing kidney or thyroid problems?

Informed Consent for Lithium Treatment

When obtaining informed consent for lithium treatment in patients with bipolar disorder, especially those with pre-existing kidney or thyroid problems, you must discuss the target symptoms, expected benefits, common and serious adverse effects (particularly renal and thyroid complications), monitoring requirements, risks of not treating, alternative treatments, and the critical importance of maintaining adequate hydration and salt intake. 1

Essential Components of Informed Consent Discussion

Target Symptoms and Expected Benefits

• Explain that lithium treats acute manic episodes and prevents recurrence of both manic and depressive episodes in bipolar disorder 2
• Discuss that lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties 2
• Clarify that response rates for acute mania range from 38-62%, meaning some patients respond well while others may not respond at all 1, 2
• Explain that therapeutic effects become apparent after 1-2 weeks, with an adequate trial requiring 4-6 weeks at therapeutic doses 2

Common and Expected Side Effects

• Gastrointestinal effects: Discuss that pain, discomfort, diarrhea, nausea, and vomiting are typical complaints, particularly during initial treatment 3
• Tremor: Explain that fine postural and/or action tremor occurs in 4-20% of patients, worsened by high caffeine consumption and concomitant psychotropic medications 3
• Polyuria and polydipsia: Warn that increased urination (up to 3 liters daily) and secondary thirst are common, occurring due to lithium's effect on renal tubules 3, 4
• Weight gain: Inform that 30% of patients experience weight gain of 4-10 kg during long-term treatment 3
• Cognitive effects: Acknowledge that some patients report mild effects on memory, vigilance, reaction time, and concentration at therapeutic serum concentrations 3
• Flattening of affect: Discuss that emotional blunting may occur during treatment 3

Serious Adverse Effects Requiring Immediate Medical Attention

Lithium Toxicity Warning Signs

• Early signs: Educate patients and families to recognize fine tremor, nausea, diarrhea, and mild ataxia as early warning signs 5, 3
• Severe toxicity: Instruct patients to discontinue lithium immediately and contact their physician if coarse tremor, confusion, severe ataxia, drowsiness, or muscular weakness occur 5
• Risk factors for toxicity: Explain that dehydration from sweating, diarrhea, fever, or infection increases toxicity risk and may require temporary dose reduction or cessation 5

Renal Complications (Critical for Patients with Pre-existing Kidney Problems)

• Nephrogenic diabetes insipidus: Warn that reduced urinary concentrating capacity with obligate polyuria and secondary thirst may develop, potentially progressing to nephrogenic diabetes insipidus that may not be reversible after discontinuation, especially in patients with chronic kidney disease 6, 3
• Glomerular function: Explain that glomerular filtration rate falls slightly in approximately 20% of patients, with a small subset at risk for progressive renal insufficiency 3
• Contraindication: Emphasize that lithium should generally not be given to patients with significant renal disease, as the risk of toxicity is very high 5
• Monitoring requirement: Stress that patients with pre-existing kidney problems require more frequent monitoring and potentially lower doses 5

Thyroid Complications (Critical for Patients with Pre-existing Thyroid Problems)

• Hypothyroidism: Explain that lithium inhibits thyroid hormone secretion, with hypothyroidism occurring in 8-20% of patients, more frequently in women and those with pre-existing thyroid autoimmunity 6, 3
• Goiter: Inform that goiter prevalence is 4 times more common in lithium-treated patients compared to the general population 6, 3
• Hyperthyroidism: Mention that Graves' disease and other hyperthyroidisms are sometimes reported, though less common than hypothyroidism 6
• Pre-existing thyroid disorders: Clarify that pre-existing thyroid disorders do not necessarily contraindicate lithium treatment, but require careful monitoring with supplemental thyroid treatment if hypothyroidism develops 5
• Thyroid storm risk: Warn that in rare cases, hyperthyroid patients on lithium may develop thyroid storm, particularly during acute illness or procedures 7

Other Serious Complications

• Hyperparathyroidism and hypercalcemia: Explain that lithium stimulates parathyroid cell proliferation, causing a 4 to 6-fold higher risk of primary hyperparathyroidism than the general population 6
• Neurological effects: Mention rare but serious neurological adverse effects including extrapyramidal symptoms, pseudotumor cerebri, or cerebellar symptoms 3
• Cardiac effects: Note that lithium should generally not be given to patients with significant cardiovascular disease 5

Pregnancy and Breastfeeding Risks

• Pregnancy Category D: Explain that lithium causes an increased perinatal death rate and high malformation rate, particularly cardiovascular anomalies including tricuspid valve abnormalities 5, 4
• First trimester: Emphasize that lithium should be avoided during the first trimester unless the benefit to the mother exceeds the risk to the fetus 3
• Pregnancy planning: Instruct women on lithium therapy to notify their physician before attempting to become pregnant, with careful monitoring of blood lithium levels every three days if continued during pregnancy 4
• Breastfeeding: Explain that lithium is excreted in human milk, and nursing should not be undertaken during lithium therapy except in rare circumstances where potential benefits to the mother outweigh possible hazards to the child 5
• Neonatal sensitivity: Warn that the kidney is particularly sensitive to lithium just after birth 3

Critical Lifestyle and Safety Requirements

Hydration and Salt Intake

• Mandatory requirement: Stress that maintaining a normal diet including salt and adequate fluid intake (2500-3000 mL daily) is essential, especially during initial stabilization 5
• Sodium depletion risk: Explain that lithium decreases sodium reabsorption by renal tubules, which could lead to sodium depletion 5
• Supplementation needs: Instruct that protracted sweating, diarrhea, or infection with elevated temperatures may necessitate supplemental fluid and salt administration 5

Drug Interactions

• Diuretics and ACE inhibitors: Warn that concomitant use causes sodium loss, reducing lithium clearance and increasing serum levels with risk of toxicity, requiring dose decrease and more frequent monitoring 5
• NSAIDs: Explain that NSAIDs (including COX-2 inhibitors) significantly increase steady-state lithium concentrations, with indomethacin and piroxicam having the strongest effect 5
• Neuromuscular blocking agents: Mention that lithium may prolong the effects of neuromuscular blocking agents 5
• Haloperidol: Discuss that combined use with haloperidol has been associated with an encephalopathic syndrome in rare cases, requiring close monitoring 5

Activities Requiring Alertness

• Impairment warning: Caution that lithium may impair mental and/or physical abilities, requiring caution with activities such as operating vehicles or machinery 5

Monitoring Requirements and Time Commitment

Laboratory Monitoring Schedule

• Baseline assessment: Explain that before starting lithium, baseline tests include complete blood count, thyroid function tests (TSH), urinalysis, blood urea nitrogen, creatinine, serum calcium, and pregnancy test in females 2
• Ongoing monitoring: Inform that lithium levels, renal function (BUN, creatinine), thyroid function (TSH), and urinalysis must be checked every 3-6 months during maintenance therapy 2, 6
• Lithium level monitoring: Clarify that therapeutic lithium levels are 0.8-1.2 mEq/L for acute treatment and 0.6-1.0 mEq/L for maintenance, with levels checked after 5 days at steady-state dosing 2
• Frequency during initiation: Stress that serum lithium concentrations should be determined twice per week during the acute phase until levels and clinical condition stabilize 1

Clinical Monitoring

• Initial phase: Explain that weekly visits are typical during the first month to assess response, side effects, and medication adherence 2
• Maintenance phase: Inform that monthly visits are standard once stabilized, with assessment for ongoing symptoms, suicide risk, adverse effects, and adherence 2
• Duration commitment: Clarify that maintenance therapy continues for at least 12-24 months after mood stabilization, with some patients requiring lifelong treatment 2

Risks of Not Treating with Medication

• Relapse risk: Explain that withdrawal of maintenance lithium therapy is associated with dramatically increased relapse risk, especially within 6 months following discontinuation 2
• Noncompliance consequences: Emphasize that more than 90% of adolescents who were noncompliant with lithium treatment relapsed, compared to 37.5% of those who were compliant 2
• Suicide risk: Discuss that untreated bipolar disorder carries significant suicide risk, which lithium specifically reduces 2
• Functional impairment: Mention the impact on psychosocial functioning, relationships, academic/vocational performance, and quality of life without treatment 1

Alternative Treatment Options

Pharmacological Alternatives

• Other mood stabilizers: Discuss valproate as an alternative, particularly effective for mixed or dysphoric mania, with higher response rates (53%) compared to lithium (38%) in some pediatric studies 2
• Atypical antipsychotics: Explain that aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone are approved for acute mania in adults, potentially providing more rapid symptom control 2
• Combination therapy: Mention that combination of lithium or valproate with an atypical antipsychotic may be considered for severe presentations 2

Psychosocial Alternatives

• Cognitive-behavioral therapy: Discuss CBT as having strong evidence for addressing mood symptoms, though typically used as adjunctive treatment rather than monotherapy 2
• Family-focused therapy: Explain that family intervention helps with medication supervision, early warning sign identification, and reducing environmental stressors 2
• Psychoeducation: Emphasize that education about symptoms, course of illness, and treatment options should accompany all pharmacotherapy 2

Patient-Specific Risk Factors

For Patients with Pre-existing Kidney Problems

• Increased toxicity risk: Emphasize that the risk of lithium toxicity is very high in patients with significant renal disease 5
• Hospitalization requirement: Explain that if the psychiatric indication is life-threatening and the patient fails to respond to other measures, lithium treatment may be undertaken only with extreme caution, including daily serum lithium determinations, adjustment to usually low doses, and hospitalization as a necessity 5
• Alternative consideration: Strongly recommend considering alternative mood stabilizers (valproate, atypical antipsychotics) as first-line options 2

For Patients with Pre-existing Thyroid Problems

• Enhanced monitoring: Stress that careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters 5
• Supplemental treatment: Explain that supplemental thyroid treatment may be used if hypothyroidism occurs during lithium therapy 5
• Hyperthyroid risk: Warn that hyperthyroid patients on lithium may experience altered renal tubular function resulting in lithium retention and systemic toxicity 7
• Masked symptoms: Mention that lithium therapy may mask signs of hyperthyroidism by inducing cellular unresponsiveness, potentially delaying recognition of thyroid storm 7

Documentation and Ongoing Consent

• Initial documentation: Record that the patient and family had an opportunity to ask questions and have them answered, and that they understood the nature of the target symptoms and specific risks and benefits of treatment 1
• Ongoing process: Explain that consent is an ongoing process, with review of rationale, past treatment experience, benefits, risks, and alternatives before any dose changes, addition of medications, transition to maintenance phase, or discontinuation trial 1
• Single session completion: Reassure that for most patients and families, the assent and consent discussion can be completed in a single session when the prescriber has adequately prepared them 1

Common Pitfalls to Avoid

• Minimizing risks: Never emphasize benefits while minimizing risks to enhance agreement, as this harms the prescriber-patient relationship if significant adverse effects occur 1
• Incomplete side effect discussion: Ensure the discussion of side effects is detailed enough, as inadequate preparation may damage trust when adverse effects develop 1
• Ignoring patient-specific risks: Always discuss patient- and family-specific risks, such as the potential for added risk in patients with pre-existing kidney or thyroid problems 1
• Omitting rare but serious events: Mention that unexpected, unique, and perhaps even life-threatening events may occur during treatment that may or may not be related to medication 1
• Failing to address media concerns: Specifically address controversies regarding medication use that families may have learned about in popular media 1

Reassurance and Perspective

• Acute phase goal: Explain that the goal of the acute phase is to determine how well the patient responds to lithium, with the vast majority of side effects (stomachaches, sedation, insomnia) responding to dose reduction or discontinuation with little lasting significance 1
• Discontinuation option: Reassure that the prescriber will discontinue lithium if it is not useful or has unacceptable side effects, which may increase comfort with starting medication 1
• Maintenance decision: Clarify that if the patient responds, they will then decide whether to transition to maintenance phase, weighing observed benefit against acute side effects and potential longer-term risks 1