Psychosomatics 45:34-48, February 2004
© 2004 The Academy of Psychosomatic Medicine
Update on Psychotropic Medication Use in Renal Disease
Lewis M. Cohen, M.D.,
Edward G. Tessier, Pharm.D., M.P.H.,
Michael J. Germain, M.D., and
Norman B. Levy, M.D.
Received Oct. 28, 2002; revision received March 27,2003; accepted April 15, 2003. From the Psychiatric Consultation Service and Renal Transplantation Service, Baystate Medical Center; Springfield, Mass.; the Department of Psychiatry, Tufts University School of Medicine, Boston; Physicians Assistant Program, Springfield College, Springfield, Mass.; ARxGOS Consulting., Keene, N.H.; and Kingsboro Psychiatric Center, Brooklyn, N.Y. Address reprint requests to Dr. Cohen, Tufts University School of Medicine, c/o Baystate Medical Center, S2669, Chestnut St., Springfield, MA 01199; lewis.cohen{at}bhs.org (e-mail).
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ABSTRACT
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Renal failure is a common medical condition, and many patients have comorbid psychiatric disorders. In this review, which is intended as a resource for consultation psychiatrists, the authors discuss pharmacokinetic considerations and provide information about the use of individual psychotropic medications in patients with renal disease. Most psychotropic medications are fat soluble, easily pass the blood-brain barrier, are not dialyzable, are metabolized primarily by the liver, and are excreted mainly in bile. Consequently, the majority of these drugs can be safely used with the end-stage renal disease population.
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INTRODUCTION
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This article provides an update on the use of psychotropic medications in the context of impaired renal function. In preparing this article, we reviewed more than 200 citations, along with product safety and research information from the pharmaceutical firms that manufacture most of the new-generation antidepressants and atypical neuroleptics.1 Psychiatric consultants need to be aware of the enormous prevalence of comorbid renal and psychiatric disorders, and they should be knowledgeable about the use of psychotropic medications in this situation.2 In a recent survey of 133 hemodialysis patients, medication-related problems were identified in 98% of the subjects. The subjects had a mean of six comorbid illnesses (SD=2.3), a mean of 11 different drugs (SD=4.2) were prescribed per patient, and a total of 475 medication-related problems were detected.3
In the United States, there are approximately 300,000 patients with end-stage renal disease (ESRD) whose lives are maintained by peritoneal dialysis and hemodialysis.4 The annual incidence of acute renal failure is approximately 200 per million population, and an additional 8 million individuals are estimated to have chronic renal insufficiency.5 The psychiatric epidemiological literature has glaring limitations, e.g., studies estimating the prevalence of depression among dialysis patients have reported rates ranging from 0% to 100%.6,7 Nevertheless, it is evident that a substantial proportion of the ESRD population has comorbid psychiatric disorders. Subsyndromal depressive syndromes, for example, are likely in about 25% of individuals with ESRD, and major depression in 5%–22% of this population.8,9 Delirium and dementia are common, and disorders associated with significant psychiatric morbidity, such as substance abuse and AIDS, can themselves result in the development of renal failure. In a study of data for 175,000 Medicare patients with ESRD, Kimmel and associates10 found that 9% of the patients were hospitalized for a psychiatric illness during a 1-year period.
Although this article will focus on the use of psychotropic medications, it is important to acknowledge that these medications help only in certain situations. They do not substitute for the skilled provision of psychotherapy and counseling. They cannot replace clarification of complex individual and family matters. It is fortunate that all dialysis programs in the United States are legally mandated to provide access to renal social workers. Ideally, a close working relationship ought to be established to facilitate referrals between dialysis staff, consultation psychiatrists, and community mental health practitioners.
Unfortunately, remarkably few data are available on the metabolism and efficacy of psychotropic agents in patients with renal impairment. Most studies are based on a handful of subjects, and well-controlled psychopharmacological trials are rare. Few in vivo studies of the pharmacokinetics of psychotropic agents in normal or ESRD patients are available. More outcomes research is imperative if psychiatric consultants and nephrologists are to manage this substantial patient population.
Clinical, rather than empirical, experience suggests that the majority of psychotropic medications can be safely used with the ESRD population. Most of these drugs are fat soluble, easily pass the blood-brain barrier, are not dialyzable, are primarily metabolized by the liver, and are excreted in bile.11 Some important considerations and exceptions are noted in the following sections.
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PHARMACOKINETICS
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Pharmacokinetics is defined as the progress and time course of medications as they work their way through the body.8 Not only is a major excretory function altered in renal failure and its treatment by dialysis, but other factors are also changed and significantly affect dosing. The factors that are encompassed by the term pharmacokinetics include bioavailability, drug distribution, protein binding, metabolism, and excretion.
Bioavailability refers to the amount of medication that is absorbed and enters the body. In ESRD, absorption may be affected by gastric alkalinizing, which is caused by excess urea generated by the internal urea-ammonia cycle,12 and by changes in gastrin levels. The use of antacids containing aluminum or calcium may also cause nonabsorbable complexes and chelation, which further diminishes absorption.13
The volume of distribution involves the effects of dilution or concentration of medications in the body. A cachectic person has less fluid and less body mass and a decreased volume of distribution. Consequently, a given dose will result in a greater concentration of medication in his/her body than in a noncachectic person.
The issue of protein binding is especially significant in ESRD.8,10 Most medications are bound in varying degrees to blood albumin. In this state the medication is not available to produce pharmacological effects; it is the free, unbound form that causes efficacy and/or toxicity. Patients with renal failure often have a decreased amount of albumin. Of greater clinical significance is the retention of urea and other substances that compete for plasma protein binding sites; this process typically results in a higher free fraction of plasma protein-bound drug. This effect is particularly important with drugs that both have a high level of plasma protein binding ( 90% in individuals with normal renal function) and are easily displaced from binding sites by urea (e.g., phenytoin and valproic acid [Table 1 and Table 1 (continued)]). All other factors remaining constant, the greater the protein binding of a medication, the lower the dose required in renal failure.
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TABLE 1. Characteristics of Drugs Used in Treating Psychiatric Comorbidity in Patients With Renal Diseasea (continued)
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The degradation, i.e., metabolism, of a medication is probably the area of pharmacokinetics that is least known, particularly since the intermediate products of metabolism are difficult to isolate and identify.8,10 In renal failure there is a general slowing of chemical reduction and of hydrolysis, but there are normal rates of glucuronidation, microsomal oxidation, and sulfate conjugation. Drug metabolites that are pharmacologically active may be retained in patients with renal insufficiency and may cause adverse effects.
Last, an obvious impact of ESRD is that a major avenue of excretion—through the urine—is absent. The substitution of a machine as the means of this function results in intermittent excretion rather than the continual process that occurs in the individual with normal kidney function. Fortunately, most psychotropic medications are metabolized by the liver and eliminated in bile, which is then excreted in feces. Occasionally, drugs are metabolized to pharmacologically active compounds that are excreted in urine and must be accounted for in ESRD (Table 1 and Table 1 (continued)).
To summarize, when psychotropic medications are not tolerated by individual patients, it is usually due to altered pharmacokinetics. Such alterations may be directly related to the demographic characteristics and common problems of patients with ESRD, who are likely to be elderly and to have multiple and severe comorbid disorders, protein deficiency, and marked fluid and electrolyte shifts. These features can individually or in combination influence pharmacokinetics. For example, excess gastric alkalinization is not uncommon among ESRD patients, and this condition can affect drug absorption. Similarly, ascites and edema may influence drug distribution by increasing the apparent volume of distribution, and patients with these conditions may therefore require higher initial doses of medication. On the other hand, the dehydration and muscle wasting that is commonly seen in these patients decrease the volume of distribution, and such patients may require lower dosages of the drugs. Last, the high protein-binding affinity of psychotropic medications in renal failure may leave a larger proportion of a given dose of medicine unbound and consequently more available for efficacy, toxicity, or elimination.
Given these multiple and interacting factors, it is not surprising that dosing often involves trial and error. The Physicians' Desk Reference generally recommends that patients with ESRD be administered no more than two-thirds the ordinary or maximum dose of most psychoactive drugs.92 However, in our clinical experience and in our examination of the literature, we have observed that the majority of patients with ESRD both tolerate and require ordinary doses of most psychotropic medications. Toxicity is usually obvious, and we would caution more against undermedicating patients than against overmedication.
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TRADITIONAL AND ATYPICAL NEUROLEPTIC MEDICATIONS
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Pharmacological treatment of schizophrenia has been revolutionized by the use of the atypical neuroleptics, including clozapine, risperidone, and olanzapine. Unlike traditional neuroleptics, this new generation of major tranquilizers effectively treats the negative symptoms of the disease, such as emotional blunting and apathy. However, little is known about their properties in patients with ESRD, and considerable wariness is necessary. Olanzapine, for example, is largely metabolized by the liver, but its metabolites are excreted in urine.66 Single-dose studies in renal impairment indicate that special dosing is not required, but multiple dose studies have not been conducted. Olanzapine may also aggravate diabetes mellitus,93 a common comorbidity for many ESRD patients. Ziprasidone is probably best avoided in ESRD patients, since the risk of life-threatening arrhythmias related to prolongation of QT intervals is higher with electrolyte shifts. The clearance of risperidone and its active metabolite is reduced by 60% in patients with renal disease.69
It is not uncommon for patients with renal disease to have comorbid delirium, and many of these cases are etiologically complex and require rapid treatment of symptoms such as agitation. Dementia is also becoming more prevalent in this aging population. Pharmacological symptom management of agitation usually entails administration of the traditional neuroleptics, such as haloperidol.94 In acutely hospitalized and delirious patients, haloperidol is commonly administered parenterally—often through a slow, intravenous push.95 Less than 1% of haloperidol is excreted in the urine, and it appears to be a safe medication in ESRD. This method is not formally approved, however, and there have been rare cases of torsade-de-pointes-type arrhythmias. Although we have not observed and are not aware of haloperidol-induced arrhythmias in patients with renal disease, the electrolyte shifts commonly observed in these patients may theoretically render them at higher risk for this adverse event. Thioridazine and mesoridazine are best avoided, given concerns about abnormality in cardiac conduction observed in ESRD patients. Again, while the newer atypical neuroleptic agents hold promise for the future treatment of delirium,96 their effects in delirious, schizophrenic, or demented patients with renal impairment have not been systematically investigated.
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ANTIANXIETY AND SEDATING MEDICATIONS
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Anxiety is one of the most common psychological symptoms seen in this population, and it may be particularly severe during or immediately preceding dialysis treatments.1 Rapid removal of fluid and electrolytes can produce nausea, vomiting, hypotension, and muscular cramps and can also result in considerable anxiety. Generalized anxiety about the future, apprehension about one's ability to adjust to the ongoing demands of treatment and expectations of loved ones, as well as concerns about sexual performance, can all contribute to anxiety. Pharmacological management is either directed at acute episodes of panic and anxiety or at more generalized nervousness. Benzodiazepines are metabolized in the liver, and dose reduction is generally not necessary in ESRD (although for use of midazolam and chlordiazepoxide, cautious dosing may be required due to changes in plasma protein binding associated with those drugs).55,88 It is not unusual to give ordinary doses of diazepam, alprazolam, and clonazepam before or during dialysis treatments. Lorazepam is also often given at ordinary doses, although the half-life of lorazepam may be prolonged in ESRD.55 Considerable variation in pharmacokinetics is observed with buspirone in individuals with ESRD; there is an increase in the half-life of both the parent compound and its active metabolite.77–79 Since the dizziness associated with buspirone could accentuate the postural hypotension that is often observed in ESRD patients, doses of this medication should be carefully titrated. Selective serotonin reuptake inhibitors (SSRIs), which will be discussed in the section on antidepressants, are being increasingly used to treat panic and generalized anxiety disorders.
Insomnia is also quite prevalent in patients with chronic kidney disease and may occur secondary to sleep apnea, restless leg syndrome, cramps, and discomfort associated with peripheral neuropathy. Identification and treatment of these individual conditions will correct many instances of insomnia. Nonpharmacological treatments, e.g., behavioral management and instruction in sleep hygiene practices, should be tried. If these treatments are ineffective, a hypnotic such as temazepam or zolpidem can be used on a short-term basis. Although not officially recommended, time-limited use often becomes regular maintenance treatment for many patients.
Zaleplon is a new nonbenzodiazepine hypnotic agent indicated for short-term treatment of insomnia. The manufacturer maintains that since less than 1% of the drug is excreted by the kidneys, the pharmacokinetics are not altered in patients with renal insufficiency. However, plasma concentrations of zaleplon metabolites are substantially increased in patients with renal impairment, and the medication has not been adequately studied in hemodialysis populations.
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ANTIDEPRESSANT MEDICATIONS
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Reviews of antidepressant management of ESRD have consistently found both SSRI and tricyclic antidepressants to be beneficial.97 Although the greater body of experience is with the tricyclics, these medications have largely been supplanted by the newer generation of antidepressants. Tricyclics ought to be reserved for treatment-resistant depression (or other indications, such as peripheral neuropathy). In ESRD, the hydroxylated metabolites of tricyclics contribute to both the therapeutic and the toxic effects of these drugs. Amitriptyline and imipramine continue to be widely used for analgesia of neuropathic pain, while trazodone is commonly used for insomnia.
SSRIs are remarkably beneficial in ESRD, but their effects have not been sufficiently researched.1,8 Fluoxetine is the best studied medication in this class, and it appears to be both nontoxic and efficacious in patients with ESRD.19 Even in anephric patients, the kinetic profile of single doses of fluoxetine is unchanged. A study of multiple doses concluded that renal function does not significantly alter serum levels of either fluoxetine or norfluoxetine.20,21
Sertraline has not been studied as intensively in this population, but it is also widely prescribed. Like fluoxetine, it is metabolized in the liver, and excretion of the unchanged drug in urine is an insignificant route of elimination. Pharmacokinetic studies of people with mild-to-severe renal impairment and matched comparison subjects have shown no significant differences between groups.22,27 Sertraline has been used to help prevent sudden hemodialysis-related hypotension.28
Citalopram kinetics are similar to those of sertraline and fluoxetine, in that they are minimally changed in patients with ESRD, and dose adjustment is probably not necessary.14,98 By way of contrast, plasma concentrations of paroxetine hydrochloride are increased in people with renal impairment, and the recommended initial dose for patients with severe renal insufficiency (10 mg) is half that for adults with normal kidney function.26,99
Several non-SSRI antidepressant medications should be avoided or used with caution in ESRD. For example, little is known about the pharmacokinetics of nefazodone hydrochloride in patients with chronically impaired renal function.43,44 Careful dose adjustment is also necessary with venlafaxine, which, along with its metabolites, is chiefly eliminated in urine. Venlafaxine's elimination half-life is prolonged and its clearance is reduced in chronic renal insufficiency or ESRD.48 Regular monitoring of blood pressure is recommended for patients who receive this drug. Bupropion hydrochloride has active metabolites that are almost completely excreted through the kidney. The metabolites may accumulate in dialysis patients and predispose these patients to seizures.
Theoretically, care must be taken with patients receiving concurrent low therapeutic index drugs metabolized by cytochrome P450 enzyme systems. A few such drugs used in this population include agents metabolized by cytochrome P450 3A4 (e.g., tacrolimus, sildenafil, cyclosporine), while a number of antidepressants (e.g., nefazodone, fluvoxamine, paroxetine [a weak inhibitor], fluoxetine/norfluoxetine, sertraline, and valproic acid [also a weak inhibitor]) are inhibitors of this isoenzyme.1
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MOOD STABILIZERS
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For many years, lithium has been the primary pharmacologic treatment for bipolar affective disorder. In general psychiatric practice it is being replaced by classic anticonvulsant medications, such as divalproex and carbamazepine. For the minority of bipolar disorder patients with ESRD who require lithium (and do not respond to the anticonvulsants), treatment involves administration of a single dose (usually 600 mg) after each dialysis session. Because it is a small molecule that is readily dialyzed, lithium is entirely eliminated by dialysis, and a single postdialysis dose will result in a steady serum level.100 Ideally, in order to establish the proper dose, serum lithium levels should be obtained immediately before dialysis. Because of a postdialysis redistribution effect, the serum lithium level obtained immediately after dialysis will often be lower than that observed later. Lithium is also used to augment the therapeutic effects of antidepressants in patients with treatment-resistant unipolar depression, and a smaller dose of lithium, e.g., 300 mg, may be given to such patients after a dialysis session.
There has been controversy in the past as to whether lithium is nephrotoxic. New evidence suggests that it indeed can lead to renal insufficiency and even ESRD; however, a recent long-term follow-up study has found that when the drug is discontinued, renal function will often improve.101 If renal impairment is detected in a bipolar disorder patient who is receiving lithium, efforts should be made to substitute other mood stabilizing drugs, although such substitution is not always possible for some sensitive bipolar disorder patients.
Seizures are not uncommon in the renal disease population, and nephrologists are accustomed to prescribing anticonvulsant medications. Valproic acid is likely to be helpful as a mood stabilizer, but psychiatrists should be aware that free serum levels may become elevated in patients with renal disease, and individual cases of pancreatitis have been reported.50,51
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CONCLUSIONS
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In summary, most psychotropic medications are well tolerated and efficacious in the treatment of patients with ESRD and renal insufficiency. There are exceptions for which tolerance and safety are questionable, and we have attempted to identify many of those drugs in this review. Clinical experience is not an adequate substitute for systematic and well-designed empirical research. Particularly for the newer medications, there has been a dearth of investigations, and we hope that this article stimulates additional psychopharmacological research.
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ACKNOWLEDGMENTS
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The authors thank the staff of the Renal Palliative Care Initiative at Baystate Medical Center for their assistance.
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REFERENCES
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- Cohen LM, Germain MJ, Tessier EG: Neuropsychiatric complications and psychopharmacology of end-stage renal disease, in Therapy in Nephrology and Hypertension: A Companion to Brenner and Rector's The Kidney, 2nd ed. Edited by Brady HR, Wilcox CS. Philadelphia, WB Saunders, 2003, pp 731–746
- Levy NB, Cohen LM: End-stage renal disease and its treatment: dialysis and transplantation, in Psychiatric Care of the Medical Patient, 2nd ed. Edited by Stoudemire A, Fogel BS, Greenberg D. New York, Oxford University Press, 2000, pp 791–800
- Manley HJ, McClaran ML, Overbay DK, Wright MA, Reid GM, Bender WL, Neufeld TK, Hebbar S, Muther RS: Factors associated with medication-related problems in ambulatory hemodialysis patients. Am J Kidney Dis 2003; 41:386–393[CrossRef][Medline]
- US Renal Data System: USRDS 2001 Annual Data Report. Bethesda, Md, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2001
- Robertson S, Newbigging K, Isles CG, Brammah A, Allan A, Norrie J: High incidence of renal failure requiring short-term dialysis: a prospective observational study. QJM 2002; 95:585–590[Abstract/Free Full Text]
- Cohen-Cole SA, Stoudemire A: Major depression and physical illness: special considerations in diagnosis and biologic treatment. Psychiatr Clin North Am 1987; 10:1–17
- Kimmel PL, Peterson RA, Weihs KL, Simmens SJ, Alleyne S, Cruz I, Veis JH: Multiple measurements of depression predict mortality in a longitudinal study of chronic hemodialysis outpatients. Kidney Int 2000; 57:2093–2098[CrossRef][Medline]
- Israel M: Depression in dialysis patients: a review of psychological factors. Can J Psychiatry 1986; 31:445–451[Medline]
- Craven JL, Rodin GM, Johnson L, Kennedy SH: The diagnosis of major depression in renal dialysis patients. Psychosom Med 1987; 49:482–492[Abstract/Free Full Text]
- Kimmel PL, Thamer M, Richard CM, Ray NF: Psychiatric illness in patients with end-stage renal disease. Am J Med 1998; 105:214–221[CrossRef][Medline]
- Levy NB: Psychopharmacology in patients with renal failure. Int J Psychiatry Med 1990; 20:325–334[Medline]
- Hurwitz A: Antacid therapy and drug kinetics. Clin Pharmacokinet 1977; 2:269–280[Medline]
- Reidenberg MM: The biotransformation of drugs in renal failure. Am J Med 1977; 62:482–485[CrossRef][Medline]
- Joffe P, Larsen FS, Pedersen V, Ring-Larsen H, Aaes-Jorgensen T, Sidhu J: Single-dose pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis compared with healthy subjects. Eur J Clin Pharmacol 1998; 54:237–242[CrossRef][Medline]
- Wood KA, Harris MJ, Morreale A, Rizos AL: Drug-induced psychosis and depression in the elderly. Psychiatr Clin North Am 1988; 11:167–193[Medline]
- Preskorn SH: Clinically relevant pharmacology of selective serotonin reuptake inhibitors. Clin Pharmacokinet 1997; 32(suppl 1):1–21
- Spigset O, Hagg S, Stegmayr B, Dahlqvist R: Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis. Eur J Clin Pharmacol 2000; 56:699–703[CrossRef][Medline]
- Product Information: Celexa, citalopram hydrobromide. Morris Plains, NJ, Forest Pharmaceuticals, 2000
- Blumenfield M, Levy NB, Spinowitz B, Charytan C, Beasley CM Jr, Dubey AK, Solomon RJ, Todd R, Goodman A, Bergstrom RF: Fluoxetine in depressed patients on dialysis. Int J Psychiatry Med 1997; 27:71–80[Medline]
- Altamura AC, Moro AR, Percudani M: Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 1994; 26:201–214[Medline]
- Levy NB, Blumenfield M, Beasley CM Jr, Dubey AK, Solomon RJ, Todd R, Goodman A, Bergstrom RR: Fluoxetine in depressed patients with renal failure and in depressed patients with normal kidney function. Gen Hosp Psychiatry 1996; 18:8–13[CrossRef][Medline]
- Hale AS: New antidepressants: use in high-risk patients. J Clin Psychiatry 1993; 54(suppl 8):61–70
- Olyaei AJ, deMattos AM, Bennett WM: Prescribing drugs in renal disease, in Brenner and Rector's The Kidney, 6th ed. Edited by Brenner BM. Philadelphia, WB Saunders, 2000, pp 2606–2653
- Aronoff GR, Berns JS, Brier ME, Golper TA, Morrison G, Singer I, Swan SK, Bennett WM (eds): Drug Prescribing in Renal Failure: Dosing Guidelines for Adults, 4th ed. Philadelphia, American College of Physicians-American Society of Internal Medicine, 1999
- Perucca E, Gatti G, Spina E: Clinical pharmacokinetics of fluvoxamine. Clin Pharmacokinet 1994; 27:175–190[Medline]
- Doyle GD, Laher M, Kelly JG, Byrne MM, Clarkson A, Zussman BD: The pharmacokinetics of paroxetine in renal impairment. Acta Psychiatr Scand Suppl 1989; 350:89–90[Medline]
- Schwenk MH, Verga MA, Wagner JD: Hemodialyzability of sertraline. Clin Nephrol 1995; 44:121–124[Medline]
- Dheenan S, Venkatesan J, Grubb BP, Henrich WL: Effect of sertraline hydrochloride on dialysis hypotension. Am J Kidney Dis 1998; 31:624–630[Medline]
- Brater DC: Drug dosing in renal failure, in Therapy in Nephrology and Hypertension: A Companion to Brenner and Rector's The Kidney, 5th ed. Edited by Brady HR, Wilcox CS. Philadelphia, WB Saunders, 1999, pp 641–653
- Sandoz M, Vandel S, Vandel B, Bonin B, Hory B, St Hillier Y, Volmat R: Metabolism of amitriptyline in patients with chronic renal failure. Eur J Clin Pharmacol 1984; 26:227–232[CrossRef][Medline]
- Burke MJ, Preskorn SH: Therapeutic drug monitoring of antidepressants—cost implications and relevance to clinical practice. Clin Pharmacokinet 1999; 37:147–165[CrossRef][Medline]
- Product Information: Anafranil, clomipramine. Summit, NJ, Ciba Pharmaceutical Company, 1995
- Kennedy SH, Craven JL, Roin GM: Major depression in renal dialysis patients: an open trial of antidepressant therapy. J Clin Psychiatry 1989; 50:60–63[Medline]
- DeVane CL, Savett M, Jusko WJ: Desipramine and 2-hydroxydesipramine pharmacokinetics in normal volunteers. Eur J Clin Pharmacol 1981; 19:61–64[CrossRef][Medline]
- Lieberman JA, Cooper TB, Suckow RF, Steinberg H, Borenstein M, Brenner R, Kane JM: Tricyclic antidepressant and metabolite levels in chronic renal failure. Clin Pharmacol Ther 1985; 37:301–307[Medline]
- Pinder RM, Brogden RN, Speight TM, Avery GS: Doxepin up-to-date: a review of its pharmacological properties and therapeutic efficacy with particular reference to depression. Drugs 1977; 13:161–218[Medline]
- Nordin C, Betilsson L: Active hydroxy metabolites of antidepressants: emphasis on E-10-hydroxy-nortriptyline. Clin Pharmacokinet 1995:28:26–40
- Product Information: Asendin, amoxapine. Pearl River, NY, Lederle, 1993
- Product Information: Ludiomil, maprotiline hydrochloride tablets. Summit, NJ, Ciba-Geigy Corp, 1999
- Shibuya T, Matsuda H, Endo T, Chen PO, Sato K, Nishimori T: Pharmacological studies of drug action on CNS, with special reference to effects of maprotiline. Int J Clin Pharmacol Biopharm 1975; 11:192–204[Medline]
- Timmer CJ, Ad Sitsen JM, Delbressine LP: Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet 2000; 38:461–474[CrossRef][Medline]
- Product Information: Remeron, mirtazapine. West Orange, NJ, Organon, 2000
- Greene DS, Barbhaiya RH: Clinical pharmacokinetics of nefazodone. Clin Pharmacokinet 1997; 33:260–275[Medline]
- Seabolt JL, DeLeon OA: Response to nefazodone in a depressed patient with end-stage renal disease. Gen Hosp Psychiatry 2001; 23:45–46[CrossRef][Medline]
- Doweiko J, Fogel BS, Goldberg RJ: Trazodone and hemodialysis (letter). J Clin Psychiatry 1984; 45:361[Medline]
- Otani K, Tybring G, Mihara K, Yasui N, Kaneko S, Ohkubo T, Nagasaki T, Sugawara K: Correlation between steady-state plasma concentrations of mianserin and trazodone in depressed patients. Eur J Clin Pharmacol 1998; 53:347–349[CrossRef][Medline]
- Catanese B, Dionisio A, Barillari G: A comparative study of trazodone serum concentrations in patients with normal or impaired renal function. Boll Chim Farm 1978; 117:424–427[Medline]
- Troy SM, Schultz RW, Parker VD, Chiang ST, Blum RA: The effect of renal disease on the disposition of venlafaxine. Clin Pharmacol Ther 1994; 56:14–21[Medline]
- Lam YWF, Banerji S, Hatfield C, Talbert RL: Principles of drug administration in renal insufficiency. Clin Pharmacokinet 1997; 32:30–57[Medline]
- Lapierre O: Valproic acid intoxication in a patient with bipolar disorder and chronic uremia (letter). Can J Psychiatry 1999; 44:188
- Moreiras Plaza M, Rodriguez Goyanes G, Cuina L, Alonso R: On the toxicity of valproic-acid. Clin Nephrol 1999; 51:187–189[Medline]
- Product Information: Depakene, valproic acid. North Chicago, Abbott Laboratories, 1999
- Product Information: Thorazine, chlorpromazine. Philadelphia, SmithKline Beecham Pharmaceuticals, 1999
- Chetty M, Moodley SV, Mikller R: Important metabolites to measure in pharmacodynamic studies of chlorpromazine. Ther Drug Monit 1994; 16:30–36[Medline]
- Wagner BKJ, O'Hara DA: Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients. Clin Pharmacokinet 1997; 33:426–453[Medline]
- Kudo S, Ishizaki T: Pharmacokinetics of haloperidol—an update. Clin Pharmacokinet 1999; 37:435–456[CrossRef][Medline]
- Shostak M, Perel JM, Stiller RL, Wyman W, Curran S: Plasma haloperidol and clinical response: a role for reduced haloperidol in antipsychotic activity? J Clin Psychopharmacol 1987; 7:394–400[Medline]
- Eggert Hansen C, Rosted Christensen T, Elley J, Bolvig Hansen L, Kragh-Sorensen P, Larsen NE, Naestoft J, Hvidberg EF: Clinical pharmacokinetic studies of perphenazine. Br J Clin Pharmacol 1976; 3:915–923[Medline]
- Knudsen P: Chemotherapy with neuroleptics: clinical and pharmacokinetic aspects with a particular view to depot preparations. Acta Psychiatr Scand Suppl 1985; 72:51–75
- Shvartsburd A, Sajadi C, Morton V, Mirabi M, Gordon J, Smith RC: Blood levels of haloperidol and thioridazine during maintenance neuroleptic treatment in schizophrenic outpatients. J Clin Psychopharmacol 1984; 4:194–198[Medline]
- Product Information: Abilify (Aripiprazole) tablets. Princeton, NJ, Bristol-Myers Squibb Company, 2002
- Stanilla JK, de Leon J, Simpson GM: Clozapine withdrawal resulting in delirium with psychosis: a report of three cases. J Clin Psychiatry 1997; 58:252–255[Medline]
- Olesen OV: Therapeutic drug monitoring of clozapine therapy. Clin Pharmacokinet 1998; 34:497–502[CrossRef][Medline]
- Guitton C, Abbar M, Kinowski JM, Chabrand P, Bressolle F: Multiple-dose pharmacokinetics of clozapine in patients with chronic schizophrenia. J Clin Psychopharmacol 1998; 18:470–476[CrossRef][Medline]
- Product Information: Clozaril, clozapine. East Hanover, NJ, Novartis, 1999
- Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM: Olanzapine: pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet 1999; 37:177–193[CrossRef][Medline]
- Product Information: Zyprexa, olanzapine. Indianapolis, Eli Lilly and Co, 2000
- Product Information: Seroquel, quetiapine. Wilmington, Del, AstraZeneca Pharmaceuticals, 2000
- Heykants J, Haung ML, Mannens G: The pharmacokinetics of risperidone in humans: a summary. J Clin Psychiatry 1994; 55(suppl 5):13–17
- Product Information: Risperdal, risperidone. Titusville, NJ, Janssen Pharmaceutica, 1999
- Ereshefsky L: Pharmacokinetics and drug interactions: update for new antipsychotics. J Clin Psychiatry 1996; 57(suppl):12–15
- Product Information: Geodon, ziprasidone. New York, Pfizer, 2001
- Ochs HR, Greenblatt DJ, Labedzki L, Smith RB: Alprazolam kinetics in patients with renal insufficiency. J Clin Psychopharmacol 1986; 6:292–294[Medline]
- Schmith VD, Piraino B, Smith RB, Kroboth PD: Alprazolam in end stage renal disease. J Clin Pharmacol 1991; 31:571–579[Abstract]
- Laurijssens BE, Greenblatt DJ: Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996; 30:52–76[Medline]
- Garzone PD, Kroboth PD: Pharmacokinetics of the newer benzodiazepines. Clin Pharmacokinet 1994; 16:337–364
- Mahmood I, Sahajwalla C: Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug. Clin Pharmacokinet 1999; 36:277–287[CrossRef][Medline]
- Caccia S, Vigano GL, Mingardi G, Garattini S, Gammans RE, Placchi M, Mayol RF, Pfeffer M: Clinical pharmacokinetics of oral buspirone in patients with impaired renal function. Clin Pharmacokinet 1988; 14:171–177[Medline]
- Garattini SM, Caccia S, Mennini T: Notes on buspirone's mechanisms of actions. J Clin Psychiatry 1982; 43:19–22
- Product Information: Buspar, buspirone hydrochloride. Princeton, NJ, Bristol-Myers Squibb, 1998
- Ochs HR, Rauh HW, Greenblatt DJ, Kaschell HJ: Clorazepate dipotassium and diazepam in renal insufficiency: serum concentrations and protein binding of diazepam and desmethyldiazepam. Nephron 1984; 37:100–104[Medline]
- Amiel M, Bryan S, Herjanic M: Clonazepam in the treatment of bipolar disorder in patients with non-lithium-induced renal insufficiency (letter). J Clin Psychiatry 1987; 48:424
- Joy MS: Clonazepam: benzodiazepine therapy for the restless legs syndrome. ANNA J 1997; 24:686–689[Medline]
- Ochs HR, Greenblatt DJ, Kaschell HJ, Klehr U, Divoll M, Aberthery DR: Diazepam kinetics in patients with renal insufficiency or hypothyroidism. Br J Clin Pharmacol 1981; 12:829–832[Medline]
- Tiula E, Haapenen EJ, Neuvonen PL: Factors affecting serum protein binding of Phenytoin, diazepam and propranolol in acute renal diseases. Int J Clin Pharmacol 1987; 25:469–475
- Tiula E, Tallgren LG, Neuvonen PJ: Serum protein binding of phenytoin, diazepam and propranolol in chronic renal diseases. Int J Clin Pharmacol 1987; 25:545–552
- Product Information: Ativan, lorazepam. Philadelphia, Wyeth Laboratories, 1997
- Bauer TM, Ritz R, Haberthur C, Ha HR, Hunkeler W, Sleight AJ, Scollo-Lavizzari G, Haefeli WE: Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet 1995; 346:145–147[CrossRef][Medline]
- Product Information: Halcion, triazolam. Kalamazoo, Mich, UpJohn Laboratories, 1994
- Product Information: Sonata, zaleplon. Philadelphia, Wyeth Laboratories, 1999
- Product Information: Ambien, zolpidem. Skokie, Ill, GD Searle and Co, 1999
- Physicians' Desk Reference, 57th ed. Montvale, NJ, Thomson PDR, 2003
- Koro CE, Fedder DO, L'Italien GJ, Weiss SS, Magder LS, Kreyenbuhl J, Revicki DA, Buchanan RW: Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. Br Med J 2002; 325:243–245[Abstract/Free Full Text]
- Schmidt RJ, Holley JL: Psychiatric illness in dialysis patients, in UpToDate, vol 8.2. Edited by Rose BL. Wellesley, Mass, UpToDate, 2001 (http://www.uptodate.com/)
- Cassem NH, Hackett TP: The setting of intensive care, in Massachusetts General Hospital Handbook of General Hospital Psychiatry. Edited by Hackett TP, Cassem NH. St Louis, CV Mosby, 1978, pp 326–327
- Schwartz TL, Masand PS: The role of atypical antipsychotics in the treatment of delirium. Psychosomatics 2002; 43:171–174[Abstract/Free Full Text]
- Levy NB, Cohen LM: Central and peripheral nervous systems in uremia, in Textbook of Nephrology, 4th ed. Edited by Massry SG, Glassock R. Philadelphia, Williams & Wilkins, 2001, pp 1279–1282
- Spigset O, Hagg S, Stegmayr B, Dahlqvist R: Citalopram pharmacokinetics in patients with chronic renal failure and the effect of haemodialysis. Eur J Clin Pharmacol 2000; 56:699–703
- Hale AS: New antidepressants: use in high-risk patients. J Clin Psychiatry 1993; 54(suppl 8):61–70
- Port FK, Kroll PD, Rosenzweig J: Lithium therapy during maintenance hemodialysis. Psychosomatics 1979; 20:130–132[Abstract/Free Full Text]
- Braden GL: Lithium-induced renal disease, in Primer on Kidney Disease, 3rd ed. Edited by Greenberg A. San Diego, Calif, Academic Press, 2001, pp 322–324
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