Dosulepin Use in Chronic Kidney Disease
Dosulepin (dothiepin), a tricyclic antidepressant, requires careful consideration in CKD patients due to potential accumulation, anticholinergic effects, and cardiovascular risks, though specific dosing guidance is limited in current guidelines.
General Principles for Medication Use in CKD
The KDIGO 2024 guidelines emphasize that people with CKD may be more susceptible to the nephrotoxic effects of medications and should have benefits versus potential harms carefully weighed 1. This principle applies to all medications, including psychotropic agents like dosulepin.
Key Monitoring Requirements
- Monitor eGFR, electrolytes, and therapeutic medication levels when indicated in CKD patients receiving medications with narrow therapeutic windows, potential adverse effects, or nephrotoxicity 1
- Perform thorough medication review periodically and at transitions of care to assess adherence, continued indication, and potential drug interactions 1
Specific Considerations for Dosulepin in CKD
Renal Clearance and Dosing
Consider GFR when dosing medications cleared by the kidneys 1. Tricyclic antidepressants like dosulepin are primarily metabolized hepatically, but active metabolites may accumulate in renal impairment 2.
- For most clinical settings, validated eGFR equations using serum creatinine are appropriate for drug dosing 1
- Where more accuracy is required for drug-related decision-making (e.g., medications with narrow therapeutic or toxic range), use equations combining both creatinine and cystatin C, or measured GFR 1
Anticholinergic Burden
Dosulepin has significant anticholinergic properties that pose particular risks in CKD patients, who may already experience cholinergic disorders 3. Anticholinergic effects include:
- Urinary retention (problematic in patients with potential uremic complications)
- Cognitive impairment (CKD patients have higher baseline cognitive dysfunction risk)
- Constipation (common in CKD and worsened by anticholinergics)
- Dry mouth and blurred vision
Cardiovascular Considerations
Tricyclic antidepressants carry cardiovascular risks including:
- QT prolongation
- Orthostatic hypotension (particularly relevant given Practice Point 3.4.1 regarding BP management in CKD) 1
- Arrhythmias
CKD patients have markedly increased cardiovascular risk 1, making these cardiac effects particularly concerning.
Practical Dosing Approach
Starting Dose
- Begin with the lowest effective dose (typically 25-50 mg daily for dosulepin)
- Titrate slowly based on clinical response and tolerability
- Monitor for accumulation of active metabolites over time
Monitoring Parameters
- eGFR and electrolytes at baseline and regularly during treatment 1
- ECG monitoring for QT interval changes
- Blood pressure monitoring, particularly for orthostatic changes
- Assessment for anticholinergic side effects
- Cognitive function assessment
Dose Adjustment by CKD Stage
While specific dosulepin guidelines are lacking, general principles suggest:
- CKD G1-G3a (eGFR ≥45): Standard dosing with close monitoring
- CKD G3b (eGFR 30-44): Consider 25-50% dose reduction; monitor closely for adverse effects 2
- CKD G4-G5 (eGFR <30): Use with extreme caution; consider 50% dose reduction or alternative agents 1
Alternative Considerations
Given the risks of tricyclic antidepressants in CKD, consider safer alternatives:
- Selective serotonin reuptake inhibitors (SSRIs) generally have better safety profiles in CKD
- Mirtazapine may be considered with appropriate dose adjustment
- Non-pharmacological interventions for depression should be emphasized
Drug Stewardship Principles
Establish collaborative relationships with pharmacists to ensure proper drug stewardship in CKD patients with complex medication regimens 1, 4. This is particularly important for:
- Identifying potential drug interactions
- Ensuring appropriate dose adjustments
- Monitoring for adverse effects
- Educating patients about medication risks and benefits 1
Common Pitfalls to Avoid
- Do not assume standard dosing is safe without considering renal function 2
- Do not overlook over-the-counter medications and herbal remedies that patients may be taking concurrently 1
- Do not fail to reassess the continued need for dosulepin during medication reviews, especially during acute illness or transitions of care 1
- Consider temporary discontinuation during serious intercurrent illness that increases AKI risk 1
Special Populations
Elderly Patients with CKD
- Patients aged ≥65 with CKD have higher rates of inappropriate drug use 5
- Increased sensitivity to anticholinergic effects
- Higher fall risk with orthostatic hypotension
- Start with lower doses and titrate more cautiously
Patients on Dialysis
- Limited data exists for dosulepin in dialysis patients
- Hemodialysis unlikely to significantly remove tricyclic antidepressants due to high protein binding
- Extreme caution warranted given cholinergic disorders common in dialysis patients 3