Prescribing medications for children
The ultimate goal for children with ESRD is kidney transplant. However, many will live years before transplant occurs, and many may need psychiatric care before and after the transplant. With the exception of recommended dosing of anticonvulsants, 2 treatment reviews do not list any psychotropic medications in their Tables of dosing considerations for children with significant renal impairment.9,10 The review by Trompeter11 predates the dramatic increase in use of psychoactive medications for children with a variety of internalizing and externalizing behavioral conditions.
Pediatric ESRD differs from the adult version in which diabetes mellitus and hypertension are more frequent long-standing comorbid disorders.12 Pediatric psychopharmacology ideally determines dosing on the basis of body surface area instead of body weight, but minimal information is available concerning either application with psychotropic medications.10 For children on dialysis and in need of psychiatric management, rely on the pediatric axiom for dosing: “start low and go slow.”13
Many of the psychotropic medications—with the exception of the typical neuroleptics and somnolent tranquilizers—are used in pediatric psychiatry. In this population, some are relied on more often than others (eg, fluoxetine(Drug information on fluoxetine) is preferred over paroxetine(Drug information on paroxetine) because of its longer half-life and research data that support its indication and use). Conservative initial dosing for pediatric indications would frequently be a 50% to 75% lower dose than the typical adult dose, with allowances to increase dosing during subsequent care, depending on tolerability, response, and changes in clinical status. This is especially the case for stimulant compounds such as amphetamine and methylphenidate(Drug information on methylphenidate), which have a higher proportion of elimination through the kidneys than many other medications.14
Because there are no available data, even the package inserts for the stimulant medications do not specify any dosing adjustments to be made for children with ESRD. It appears that methylphenidate or the clearance of its inactive hepatic metabolite, ritalinic acid, is not as sensitive to the alkalinization of urine as amphetamine products.15
With renal dysfunction and ESRD, lower dosing and slower increases during the clinical use of mixed amphetamine salts and dextroamphetamine is prudent. The alkalinization of urine associated with renal disease reduces the clearance of amphetamine and its metabolites to as low as 1%, while acidification increases clearance and can there-fore reduce levels. Consulting psychiatrists, in coordination with the primary care team and nephrolo-gists, can be of assistance with assessing the indications for and judicious use of psychiatric medications in any child with ESRD and psychiatric comorbidities. Families need to be fully informed as to treatment shortcomings.
Psychopharmacological pearls and renal failure
There are no formal guidelines for the treatment of psychiatric disorders in patients with renal failure, so the following points are based on clinical experience.
• ESRD is defined as a GFR of less than 15 mL/min/1.73 m2, in most cases accompanied by signs and symptoms of uremia
• Individuals with ESRD are in need of dialysis/transplant; some patients may require dialysis or transplant at a GFR of 15 mL/min/1.73 m2 or greater because of symptoms of uremia
• Practitioners who prescribe psychotropic agents should consider obtaining postdialysis blood drug levels to inform decisions regarding dose titration when reference levels are known
• Drug dialyzability is determined by the physical and chemical characteristics of the agent (eg, molecular size, protein binding, water solubility, volume of distribution) and the dialysis procedure (eg, dialysis membrane and flow rates)
• Peritoneal dialysis is generally much less efficient at removing agents than hemodialysis
• An agent incapable of being removed by hemodialysis cannot be removed by peritoneal dialysis
• The predominant form of CKD associated with lithium(Drug information on lithium) therapy is chronic tubulointerstitial nephropathy, which often presents with insidious development of renal insufficiency with minimal proteinuria
• The prevalence of reduced GFR associated with long-term lithium therapy is approximately 15%; a much smaller number of lithium-treated patients eventually have renal insufficiency that leads to dialysis
• Patients with mild to moderate chronic renal insufficiency associated with lithium can expect gradual improvement in GFR after lithium discontinuation
• Uninterrupted lithium exposure decreases the kidney’s endogenous ability for cellular regeneration; although a consensus does not currently exist as to the discontinuation threshold for lithium treatment because of diminished kidney function, it is suggested that repeated serum cre-atinine concentrations exceeding 140 μmol/L (1.6 mg/dL) indi-cate the need for nephrologist consultation
• Individuals with serum creatinine concentrations of more than 2.5 mg/dL are at very high risk for progression to ESRD compared with individuals who have serum creatinine concentrations of less than 2.5 mg/dL. Moreover, in individuals with a creatinine clearance of 40 mL/min or less, there is a higher probability of continued renal deterioration at lithium discontinuation than in those who have a creatinine clearance of more than 40 mL/min
• In patients with ESRD, a reduction in the lithium dose is required to prevent further toxicity, and a single dose of lithium is recommended after dialysis sessions; serum lithium levels obtained before and after dialysis are used to established appropriate dosing
• In treating depression, SSRIs (eg, fluoxetine) appear to be generally safe and well-tolerated; venlafaxine levels markedly increase in patients with renal failure, which theoretically could intensify hypertension, a common morbidity in ESRD; tricyclic antidepressants are generally avoided because of concern for safety and tolerability; duloxetine(Drug information on duloxetine) levels increase markedly in patients who have ESRD compared with patients who have normal renal function, and this medication is not recommended