Which anxiety medications are appropriate and how should they be dosed for a patient with chronic kidney disease (any stage, including dialysis)?

Anxiety Medications in Chronic Kidney Disease

Primary Recommendation

For patients with chronic kidney disease requiring anxiety treatment, nonpharmacologic interventions—particularly cognitive behavioral therapy, exercise, and mindfulness—should be first-line approaches, as pharmacologic options have limited evidence and significant safety concerns in this population. 1

Nonpharmacologic Approaches (Preferred First-Line)

• Cognitive behavioral therapy (CBT) has demonstrated efficacy in reducing anxiety symptoms in hemodialysis patients, though evidence comes from small-scale studies. 1

• Aerobic exercise may improve anxiety symptoms in people undergoing hemodialysis, based on systematic reviews of small studies with mixed but generally supportive results. 1

• Mindfulness, music therapy, and spiritual interventions may reduce anxiety burden, though evidence is limited to small-scale studies. 1

• Manual acupressure has shown short-term benefits as an adjuvant intervention for anxiety and related symptoms in small clinical trials. 1

• These nonpharmacologic approaches offer critical advantages: no adverse effects, no drug interactions, no need for dose adjustments across CKD stages, and lower burden of polypharmacy—all particularly important given the medication complexity in CKD patients. 1

Pharmacologic Approaches (Use With Caution)

Critical Evidence Gap

• No randomized controlled trials exist examining pharmacologic management of anxiety specifically in kidney failure populations (including any stage of CKD or dialysis patients). 1

SSRIs and SNRIs: Limited Evidence and Safety Concerns

• Selective serotonin reuptake inhibitors (SSRIs) have not shown consistent benefit over placebo in small randomized trials of hemodialysis patients treated for depression, and documented increased adverse effects, particularly gastrointestinal. 1

• No existing randomized controlled trials address SSRI use in peritoneal dialysis patients. 1

• Caution is warranted when prescribing SSRIs due to their adverse-effect profile in CKD, including QT prolongation and altered pharmacokinetics. 1

• Duloxetine (an SNRI) should be avoided in patients with severe renal impairment (GFR <30 mL/min) due to increased plasma concentrations of the drug and especially its metabolites in end-stage renal disease. 2

General Prescribing Principles for Psychotropic Medications

• When psychotropic medications are necessary, apply principles for medically fragile patients: start with subtherapeutic doses, uptitrate carefully, and keep efficacy and safety as top priority. 1

• Consider adverse effects specific to kidney failure: QT prolongation, altered pharmacokinetics, and drug accumulation risk. 1

• Drug clearance decreases in CKD, and volume of distribution may increase, necessitating dose adjustments for renally cleared medications. 3

• Polypharmacy in CKD patients increases risk of drug accumulation and adverse events due to altered absorption, distribution, metabolism, and excretion. 4

Specific Medication Considerations

Benzodiazepines (Not Directly Addressed in Guidelines)

• While not specifically discussed in the provided CKD guidelines for anxiety, general principles of drug dosing in CKD apply: calculate creatinine clearance, adjust doses for renally cleared drugs, and monitor closely for adverse effects. 5

• Dose adjustments should be made according to creatinine clearance or GFR using online or electronic calculators, with methods including dose reductions, lengthening dosing intervals, or both. 5

Gabapentinoids

• Low-dose gabapentinoids are mentioned as potential pharmacologic approaches for restless legs syndrome in dialysis patients, which often co-occurs with anxiety. 1

• Gabapentinoids require significant dose reduction in advanced CKD due to renal clearance.

Clinical Algorithm

1. Assess for concurrent symptoms (depression, sleep disturbance, pain) that may contribute to anxiety. 1

2. Initiate nonpharmacologic interventions first: CBT, exercise program (aerobic if tolerated), mindfulness training. 1

3. If pharmacologic treatment becomes necessary:

   • Calculate creatinine clearance or GFR accurately 5
   • Avoid duloxetine if GFR <30 mL/min 2
   • Consider SSRIs with extreme caution, starting at subtherapeutic doses 1
   • Monitor closely for adverse effects, particularly GI symptoms and QT prolongation 1

4. Reassess regularly for efficacy and safety, adjusting treatment as kidney function changes. 3

Common Pitfalls to Avoid

• Do not assume standard psychiatric medication dosing is safe in CKD—pharmacokinetics are substantially altered. 4, 3

• Do not overlook nonpharmacologic options simply because they require more coordination or resources—they are safer and may be more effective. 1

• Do not prescribe duloxetine to patients with severe renal impairment (GFR <30 mL/min) or those requiring dialysis. 2

• Do not fail to calculate renal function before initiating any psychotropic medication and reassess when clinically indicated or at least annually. 5

• Do not ignore the high risk of drug-drug interactions in CKD patients who typically take multiple medications. 6, 4