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Results for “Drug Tapering”

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At least 19 recordsLinked to original sources

PubMed1997

Negative myoclonic status due to antiepileptic drug tapering: report of three cases.

PURPOSE: Epileptic negative myoclonus (ENM) has been increasingly recognized in different epilepsies, but the reasons for its appearance and prognosis remain uncertain. We report 3 patients who developed de novo, almost continuous ENM, triggered by antiepileptic drug (AED) tapering, that resolved with treatment. METHODS: Three patients aged 16, 19, and 65 years with a 13- to 36-year history of partial epilepsy were receiving a therapeutic dosage of carbamazepine or phenobarbital plus either clobazam (CLB) or valproate (VPA). None had previously had ENM. Forty-eight to 72 h after CLB or VPA withdrawal, the habitual seizures recurred. The patient also began to report repetitive postural lapses of one or more limbs that interfered with eating or writing. At this time, each patient underwent polygraphy with simultaneous surface electromyography (EMG) of deltoid, biceps, and triceps muscles and of the wrist extensor and flexor bilaterally. RESULTS: In all patients, EEGs demonstrated almost continuous epileptiform discharges whose spatial distribution was similar to that observed before ENM appearance. Polygraphic recordings showed repetitive loss of postural EMG activity in one or more limbs, 100-400 ms in duration, which occurred in conjunction with the spike-waves. One milligram of clonazepam intravenously always terminated ENM status, which has not recurred in the ensuing 9-36 months. CONCLUSIONS: ENM may emerge as a new type of seizure due to tapering of AED therapy. This effect is possibly related to the great activation of epileptiform activity with consequent interference with cortical activity.

Adolescent↗

PubMed1993

Maintenance drug treatment for panic disorder. II. Short- and long-term outcome after drug taper.

Forty-eight patients with panic disorder completing 8 months of maintenance treatment with alprazolam (mean dose, 5.2 mg [n = 27]), imipramine hydrochloride (mean dose, 175 mg [n = 11]), or placebo (mean dose, 8.0 pills [n = 10]) underwent a gradual taper from medication over a 4-week period. A withdrawal syndrome was observed in almost all alprazolam-treated patients but in only a few imipramine- or placebo-treated patients. The clinical worsening of withdrawal symptoms after discontinuation tended to subside over the course of 3 medication-free weeks, but 33% of alprazolam-treated patients were unable to discontinue their medication regimen successfully. Severity of panic attacks at baseline but not daily alprazolam dose appeared as a significant independent predictor of taper difficulty. Forty-nine percent of the total study population continue to receive drug therapy: 82% alprazolam and 18% imipramine. Among patients who received alprazolam during study treatment and at follow-up, the mean daily dose was substantially reduced (6.1 vs 1.6 mg [n = 14]). At follow-up, after 1 year of naturalistic treatment for panic symptoms and combining 8-month completers and study dropouts, there were no significant differences in remission (68% to 71%) or in antipanic medication intake (39% to 56%) at follow-up for the three original treatment groups. However, 8-month study completers compared with study dropouts had a significantly higher remission rate (85% vs 55%).

Adult↗

PubMed1995

Predictors of alprazolam discontinuation with and without cognitive behavior therapy in panic disorder.

OBJECTIVE: In a previous paper the authors reported survival data for 20 panic disorder patients whose therapeutic doses of alprazolam were tapered by one of two methods: slow, flexible drug taper with supportive medical management or the same taper procedure carried out concurrently with cognitive behavior therapy. This report is an analysis of predictors of drug discontinuation success in that study. In addition, between-group comparisons of clinical measures at follow-up are presented. METHOD: The subjects in the previous study (10 in each group) were assessed blindly at baseline, 2 weeks after completion of drug taper, and at 3- and 6-month follow-up. Potential predictors of drug discontinuation success were tested by using logistic regression. Between-group differences in symptom severity at 3-month follow-up were examined by using analyses of covariance. RESULTS: Thirteen subjects (nine receiving alprazolam plus cognitive behavior therapy and four receiving alprazolam only) completed the drug taper on schedule and were still medication free at follow-up. A single variable--baseline-to-posttaper change in anxiety sensitivity--predicted drug status at follow-up in 85% of the cases. At follow-up, subjects in the combined-treatment group were significantly more improved on measures of anxiety, depression, catastrophic thinking related to anxiety, perception of emotional control, and disability than subjects in the drug-only group. CONCLUSIONS: Across groups, reduction in the fear of anxiety symptoms was the best predictor of patients' ability to achieve and maintain drug abstinence. Some implications of that finding for the pharmacotherapy of panic disorder are discussed.

Adult↗

PubMed2001

Late appearance of acute graft-vs-host disease after suspending or tapering immunosuppressive drugs.

BACKGROUND: Graft-vs-host disease (GVHD) is divided into acute and chronic phases based on time and clinical and histological features. The criterion of 100 days after transplantation for separating acute GVHD from chronic GVHD has been challenged on the following points: (1) the lichenoid rash of chronic GVHD may be observed as early as day 31 and acute GVHD may persist after day 100 in some cases, and (2) specific histological features do not consistently separate acute from chronic GVHD defined as the number of days after transplantation. However, the appearance of acute cutaneous GVHD after day 100 is not well established. OBSERVATIONS: Three patients developed a rash with clinical and histological features of acute GVHD between days 153 and 192 after allogeneic bone marrow transplantation or peripheral blood stem cell transplantation. In all patients, the late flare of acute GVHD occurred after tapering or suspending the immunosuppressive regimen with cyclosporine or corticosteroids, and was accompanied by stigmata of chronic GVHD in other target organs. CONCLUSIONS: The rash of acute GVHD may be observed as late as 192 days after transplantation, especially after tapering or suspending the immunosuppressive drugs, and should be considered in the differential diagnosis of late erythematous eruptions after transplantation.

Acute Disease↗

PubMed1999

Psychological strategies for discontinuing benzodiazepine treatment.

Successful discontinuation of therapeutic drugs requires patients to negotiate two potentially difficult phases. First, they must complete the drug discontinuation procedure itself, which may entail coping with rebound and withdrawal symptoms as well as anxiety due to stopping a treatment on which they depend psychologically. Second, they must maintain drug abstinence over time, despite possible exacerbations or recurrences of the disorder that the drug was treating. For optimal success, interventions aimed at assisting patients to discontinue drug use must address both of those tasks. Patients' ability to discontinue benzodiazepines seems to be strongly influenced by cognitive appraisals of the threat represented by symptoms and of their own competence to cope with it without medication. For problems of that kind, cognitive and behavioral techniques such as those developed for the treatment of panic disorder may be especially well-suited. Currently, the most successful approaches to benzodiazepine discontinuation include the following components: (1) assisting with initial drug discontinuation, educating patients about benzodiazepine dependence and withdrawal, and about the kinds of symptoms that can emerge as the drug dose is decreased, combined with a flexible drug taper conducted in supportive collaboration with the patient; and (2) dealing with exacerbations of the illness, and providing disorder-specific cognitive-behavioral treatment as an alternative to the resumption of pharmacotherapy. It seems to be crucial that the drug taper be completed before psychological treatment concludes.

Anti-Anxiety Agents↗

PubMed2002

Outpatient EEG monitoring in the presurgical evaluation of patients with refractory temporal lobe epilepsy.

Most epilepsy centers obtain ictal EEG recordings to localize the epileptogenic zone during presurgical evaluations. Inpatient monitoring is standard practice but is expensive and can be inconvenient. The authors sought to determine whether outpatient monitoring can be safe and effective as the sole method of recording seizures in the presurgical evaluation of patients with refractory temporal lobe epilepsy. They reviewed the data of seven temporal lobectomy patients whose presurgical monitoring was performed entirely outside the hospital. Mean baseline seizure frequency was at least 9.1 seizures per week. An average of 7.4 seizures was recorded over 9.4 days of monitoring. Only one patient had any antiepileptic drug taper; none suffered any complications. After temporal lobectomy on the side of demonstrated ictal onset, postoperative follow-up averaged 5.5 years. At the most recent follow-up, all patients were either seizure free or had only rare disabling or nocturnal seizures (four patients had outcomes in Engel's class I and three patients in Engel's class II). A comparison group who underwent standard inpatient monitoring was similar in average seizure frequency, monitoring duration, number of seizures recorded, and postoperative outcome, although all but one had antiepileptic drugs tapered during monitoring. The authors conclude that there is a subset of patients for whom solely outpatient presurgical EEG monitoring can be used to help plan successful temporal lobectomy.

Adult↗

PubMed1987

Alprazolam effects in children with anxiety disorders.

Children with overanxious and/or avoidant disorder (DSM-III) were treated with alprazolam (Xanax, Upjohn) to determine its safety, clinical and cognitive effects. Ten male and two female patients (age range 8.8 to 16.5 years; mean 11.5) participated in an open clinical trial consisting of a baseline placebo period (1 week), alprazolam therapy (4 weeks), a drug-tapering period (1 week), and a post-drug placebo period (1 week). There was a drug-free follow-up approximately 4 weeks after termination of the study. Dosages were individually adjusted and the daily maximum ranged from 0.50 mg to 1.5 mg. Evaluations included clinical assessments, parent, teacher and self ratings, and cognitive tests. Clinical global improvement with alprazolam therapy was marked in 1 patient, moderate in 6, minimal in 4, and none in 1. Clinician ratings indicated significant improvements of anxiety, depression, and psychomotor excitation. Parent questionnaires indicated significant improvements of anxiety and hyperactivity while teacher questionnaires showed significant improvement of an anxious-passive factor. Significant improvements in the paired associate learning tasks, maze task and the block design tasks were maintained after drug withdrawal suggesting a practice effect. Adverse effects were infrequent, mild and transient. There were no clinically significant changes of laboratory values, blood pressure, pulse or respiration during the 4 weeks of alprazolam administration. Body weight increased significantly (mean increase was 0.87 kg). Double-blind trials with alprazolam are recommended in child psychiatry disorders.

Adolescent↗

PubMed2001

Prospective assessment of tizanidine for spasticity due to acquired brain injury.

OBJECTIVE: To determine if orally delivered tizanidine will control spastic hypertonia due to acquired brain injury. DESIGN: Randomized, double-blind, placebo-controlled, crossover design, with 2 8-week treatment arms separated by a 1-week washout period at baseline. Patients were randomly assigned to receive tizanidine or a matching placebo. SETTING: Tertiary care outpatient and inpatient rehabilitation center attached to a university hospital. PARTICIPANTS: Seventeen persons recruited in a consecutive manner, 9 of whom had suffered a stroke and 8 a traumatic brain injury, and had more than 6 months of intractable spastic hypertonia. INTERVENTION: Over a 6-week period, subjects were slowly titrated up to their maximum tolerated dose (up to 36 mg/d). Following a 1-week drug taper and 1-week period in which no study drug was administered, patients were then crossed over to the other study medication following an identical titration regime. MAIN OUTCOME MEASURES: Subjects were evaluated for dose and effect throughout the trial as well as for side effects. Data for Ashworth rigidity scores, spasm scores, deep tendon reflex scores, and motor strength were collected on the affected upper extremity (UE) and lower extremity (LE). Differences over time were assessed via descriptive statistics, Friedman's analysis, and Wilcoxon's signed-rank. Data are reported as the mean +/- 1 standard deviation. RESULTS: Following 4 weeks of treatment when subjects reached their maximal tolerated dosage, the average LE Ashworth score on the affected side decreased from 2.3 +/- 1.4 to 1.7 +/- 1.1 (p <.0001). The spasm score decreased from 1.0 +/- 0.9 to 0.5 +/- 0.8 (p =.0464), while the reflex score was not statistically significant decreasing from 2.2 +/- 1.0 to 2.0 +/- 1.1 (p =.0883). The average UE Ashworth score on the affected side decreased from 1.9 +/- 1.1 to 1.5 +/- 0.9 (p <.0001). There was no significant change in the UE spasm and reflex scores. While there were positive placebo effects on motor tone, the active drug was still significantly better than placebo for decreasing LE tone (p =.0006) and UE tone (p =.0007). With a reduction in motor tone, there was an increase in motor strength (p =.0089). The average dosage at 4 weeks was 25.2mg/d. CONCLUSION: Tizanidine is effective in decreasing the spastic hypertonia associated with acquired brain injury, which is dose-dependent. There are limitations on its use due to side effects related to drowsiness.

Administration, Oral↗

PubMed1994

Does cognitive behavior therapy assist slow-taper alprazolam discontinuation in panic disorder?

OBJECTIVE: The authors investigated whether cognitive behavioral treatment could facilitate discontinuation of alprazolam therapy and maintenance of drug abstinence among panic disorder patients treated with alprazolam doses sufficient to suppress spontaneous panic attacks. METHOD: Twenty-one outpatients who met DSM-III-R criteria for panic disorder with mild to severe agoraphobia were made panic-free with alprazolam (mean dose = 2.2 mg/day) and were then randomly assigned to receive either supportive drug maintenance and slow, flexible drug taper or an identical medication treatment plus 12 weeks of concurrent, individual cognitive behavioral treatment. Taper in the combined treatment group was sequenced to conclude before cognitive behavioral treatment ended. RESULTS: Twenty subjects completed the study. There was no significant difference between groups in the rate of alprazolam discontinuation (80% and 90%, respectively, in the alprazolam-only group and the combined treatment group). However, during the 6-month follow-up period, half of the subjects who discontinued alprazolam without cognitive behavior therapy, but none of those who were given cognitive behavior therapy, relapsed and resumed alprazolam treatment. CONCLUSIONS: Cognitive behavioral treatment administered in parallel with alprazolam maintenance and taper was effective in preventing relapse after drug discontinuation. The results warrant further research on the thoughtful integration of these two therapeutic modalities.

Adult↗

PubMed1997

Epilepsy management. Issues in medical and surgical treatment.

After a single seizure, about 40% of patients have recurrence. The main features correlating with recurrence are cause, seizure type, EEG findings, family history of seizures and, possibly, the presence of a prior febrile seizure, Todd's paresis, and other abnormal neurologic findings. A number of medications are available for treatment. Withdrawal from medication is successful in 60% to 70% of patients. Several factors favor successful drug taper. These include a seizure-free status for at least 2 years during drug therapy, a single type of seizure (partial or generalized), young age at seizure onset, and an epilepsy syndrome with a tendency to remit. Surgery can be considered in certain patients with surgically remediable syndromes. Candidates typically have seizures that impair consciousness, that cause falling with injury, that have adverse psychosocial or social effects, and that persist after trials of three appropriate medications. A multidisciplinary evaluation should take place at a surgery center with experience and documented success. Favorable results from surgery can be expected in a large proportion of patients.

Anticonvulsants↗

PubMed1995

Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo.

This randomized double-blind study in 342 mildly to moderately depressive outpatients investigated the antidepressant effectiveness and speed of action of lorazepam, alprazolam and amitriptyline versus placebo. Six weeks of drug treatment were followed by a drug taper period, a control period with placebo and a control period without placebo, of 2 weeks duration each. Clinical improvement was assessed by rating scales (Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and patient's self-ratings (Patient's Global Impressions, Self-rating Depression Scale and Visual Analogue Scale). At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo. Compared to placebo, onset of efficacy was earlier on benzodiazepines than on amitriptyline . While tapering by decreasing the dosage, replacing drug with placebo and finally discontinuing placebo, clear withdrawal phenomena were not seen, but 20% of patients, equally distributed to all treatment groups, did not want to stop taking tablets after replacing drug with placebo. Drop-out rate during the treatment period was very low (9%). Significantly interfering adverse effects were seen in 27 patients, without predominance in one of the active drug groups.

Adult↗

PubMed2005

Experience with an adult alcohol withdrawal syndrome practice guideline in internal medicine patients.

STUDY OBJECTIVE: To standardize treatment of alcohol withdrawal syndrome (AWS) in internal medicine patients using an adult AWS practice guideline with a symptom-triggered management approach. DESIGN: Prospective interventional (pilot group) and retrospective (control group). SETTING: University teaching hospital. PATIENTS: Thirty-two internal medicine patients identified as being at risk for AWS and treated according to the AWS practice guideline who were compared with 49 internal medicine patients managed with nonstandardized approaches. INTERVENTION: Patients in the pilot group were assessed using the AWS type indicator. They received lorazepam, clonidine, or haloperidol, based on AWS type indicator assessment and adult AWS practice guideline criteria. MEASUREMENTS AND MAIN RESULTS: Data collected and analyzed were drugs administered to control AWS symptoms, use of sitters and physical restraints, length of hospital stay, and discharge from hospital receiving tapered drug therapy. Pilot patients received 46.6% less benzodiazepine (p=0.001), 20% more clonidine (p=0.01), and 18.2% more haloperidol (p=0.002) than control patients. No drug therapy was required in 19% of pilot patients compared with 2% of controls (p=0.01). Significantly more control (71.4%) than pilot patients (18.8%) were discharged with tapered benzodiazepine therapy (p<or=0.01). No significant differences were found between groups for sitters, restraints, or hospital length of stay. CONCLUSION: This pilot project suggests that internal medicine patients at risk for AWS can be managed with a standardized, symptom-triggered approach using decreased amounts of benzodiazepine in combination with adjunctive agents to treat adrenergic hyperactivity and delirium. Further data are necessary to determine the impact of the practice guideline on patient outcome measurements.

Adult↗

PubMed1990

Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder. Behavioral and biological results.

Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, double-blind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatment with at least partial benefit were crossed over to fluoxetine treatment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive-compulsive disorder and depressive symptoms that were comparable with precrossover ratings completed during clomipramine treatment. A significant exacerbation in obsessive-compulsive disorder and depression ratings as well as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder. Platelet 5-HT concentrations were reduced 95% during both clomipramine and fluoxetine treatment periods. These results suggest that fluoxetine may represent a viable alternative to clomipramine in the treatment of obsessive-compulsive disorder, although further studies with larger sample sizes are needed.

Adult↗

PubMed1993

Double-blind, placebo-controlled study of a once-a-day, sustained-release preparation of alprazolam for the treatment of panic disorder.

OBJECTIVE: The goals of this study were to assess the antipanic efficacy of a new, sustained-release formulation of alprazolam and to assess the safety and tolerability of once-a-day administration of 1-10 mg of sustained-release alprazolam. METHOD: One hundred ninety-four patients with diagnosis of agoraphobia with panic attacks or panic disorder with limited phobic avoidance underwent a 1-week placebo washout before being randomly assigned to groups receiving 8 weeks of double-blind treatment with either sustained-release alprazolam or placebo. RESULTS: There was a significant treatment effect favoring sustained-release alprazolam (highest mean dose = 4.7 mg/day) across almost all measures of anxiety, panic, and phobic avoidance, despite a significantly higher dropout rate in patients receiving placebo. Eighty-five percent of the patients treated with sustained-release alprazolam, compared with 61% of the patients given placebo, reported complete blockade of panic attacks by the end of 6 weeks of treatment. Sedation was the most commonly reported adverse effect. Discontinuation of sustained-release alprazolam was associated with moderate but transient levels of distress in 48% of the patients; discontinuation of placebo led to distress in only 10% of the patients. Nonetheless, there was no difference in the proportion of patients who were able to remain off the study drug for at least 2 weeks. CONCLUSIONS: These results suggest that sustained-release alprazolam is highly effective in the acute treatment of panic disorder at doses comparable to those in the originally marketed compressed tablet of alprazolam. The medication was well tolerated but showed rebound effects during a rapid drug taper after 6 weeks of treatment.

Administration, Oral↗

PubMed1998

Combined pharmacotherapy and cognitive behavior therapy in the treatment of panic disorder.

Cognitive behavior therapy (CBT) has been combined with pharmacotherapy in the treatment of panic disorder in three ways: (1) to treat agoraphobic symptoms in the condition of panic with agoraphobia; (2) to reduce withdrawal effects during drug taper; and (3) to treat panic attacks. Exposure treatment and pharmacotherapy have a modest additive effect, although more patients drop out of exposure therapy combined with imipramine treatment compared with exposure therapy alone. CBT reduces symptoms of withdrawal from alprazolam and other benzodiazepines and improves the outcome of drug treatment. At present, sufficient data are not available to determine whether the effects of CBT combined with drug therapy are additive in treating panic disorder. The results of a large trial are awaited. Current CBT consists of 12 sessions and is not widely offered to patients because of cost considerations. Efforts are being made to decrease the number of sessions necessary by improving cognitive techniques. One of these models is the subject of an ongoing trial. Finally, efforts to educate and counsel patients in the clinical setting regarding the psychopathology of panic attacks may improve the outcome of pharmacotherapy.

Agoraphobia↗

PubMed1992

Long-term beneficial effects of azathioprine addition to ongoing cyclosporine-prednisone protocol in renal transplantation.

Delayed addition of azathioprine (Aza) to an ongoing cyclosporine-prednisone protocol was started 11.3 +/- 9.9 months after renal transplantation in 31 patients. Group I (n = 10) had chronic renal function deterioration due to chronic rejection, group II (n = 11) had repeated or severe acute rejection episodes and group III (n = 10) had cyclosporine (Cs) toxicity despite drug tapering. In group I, SCr had risen over the 6 months prior to Aza addition (P < 0.05), renal function declining at a rate of -0.13 +/- 0.12 SCr(-1). In the 6 months post-Aza, renal function improved at a rate of 0.05 +/- 0.07 SCr(-1), and during the entire follow-up at a rate of 0.05 +/- 0.12 SCr(-1) (P < 0.01) with stable Cs levels. In group II the decline in renal function was greater, though the rate of decline was stopped after Aza. In group III, renal function improved in eight patients. After 23 +/- 12 months of follow-up, 15 patients had improved graft function, two were stable, 12 had worsened (nine on dialysis) and two had died. Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to Cs-prednisone-treated renal allograft patients with chronic rejection or Cs toxicity, with long-term beneficial effects in a high proportion of patients.

Azathioprine↗

PubMed1991

Evidence that addition of azathioprine improves renal function in cyclosporine-treated patients with allograft dysfunction.

Several approaches have been attempted to manage renal allograft dysfunction in cyclosporine-prednisone (CsA-Pred)-treated patients. Conversion to conventional therapy and perioperative triple drug have been associated with high rates of acute rejection episodes, infections, or neoplasms. We report our experience in delayed addition of azathioprine (1-2 mg/kg/day) to CsA/Pred protocol in three groups of patients. Group I (n = 9) had chronic renal function deterioration due to chronic rejection; group II (n = 10) had repeated or severe acute rejection episodes despite adequate CsA levels; and group III (n = 8) had CsA toxicity despite drug tapering. In group I, serum creatinine (SCr) had risen from 2.2 +/- 0.9 to 2.9 +/- 0.7 mg/dl over the 6 months prior to Aza addition (P less than 0.05), renal function declining at a rate of -0.14 +/- 0.12 Cr-1/year. In the 6-month post-Aza, renal function improved at a rate of 0.06 +/- 0.06 Cr-1/year and during the entire follow-up at a rate of 0.04 +/- 0.12 Cr-1/year (P less than 0.05) with stable CsA levels (288 +/- 167 vs. 251 +/- 172 ng/dl, NS). In group II response was worse, though the rate of declining renal function prior to Aza (-0.10 +/- 0.10 Cr-1/year) was almost stopped after Aza. In group III there was very good response to Aza addition, as 7 out of 8 patients improved graft function (baseline SCr 2.5 +/- 0.7 mg/dl vs. 1.9 +/- 0.6 mg/dl at last follow-up, P less than 0.05), with significantly decreased CsA levels (480 +/- 97 vs. 268 +/- 120, P less than 0.05). One patient from group II died from pneumonia, and 6 patients (1 from group I and 5 from group II) lost their grafts. Fifteen patients improved graft function, and 9 worsened after addition of Aza. The bad-responders had significantly higher SCr at baseline compared with the good-responders (3.8 +/- 1.8 vs. 2.7 +/- 0.6 mg/dl, P less than 0.01). Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to CsA-Pred in patients with chronic rejection or CsA toxicity. This is accompanied by low rate of acute rejection, good patient and graft survival, and low rate of infections. A worse outcome can be seen in patients with high-baseline SCr levels, suggesting the need for addition of Aza in the initial chronic graft dysfunction.

Azathioprine↗

PubMed1989

Amelioration of chronic renal allograft dysfunction in cyclosporine-treated patients by addition of azathioprine.

Management of chronic renal allograft dysfunction in cyclosporine-prednisone treated renal allograft recipients remains problematic. We therefore initiated a protocol of azathioprine addition (1.0-1.5 mg/kg/day) to ongoing CsA/Pred therapy. Three groups were treated. Group A (n = 21) had chronic progressive renal dysfunction (serum creatinine greater than or equal to 2.5 mg/dl or more than 15% above baseline) four or more months after transplantation. Group B (n = 8) had frequent or severe rejection episodes occurring despite adequate CsA levels. Group C (n = 7) had constitutional side effects of CsA with or without renal dysfunction persisting despite drug taper or financial difficulty in affording CsA. Aza was initiated 17.8 +/- 2.8 months after transplantation in group A, the mean serum creatinine having risen from 2.55 +/- 27 mg/dl to 3.04 +/- .20 mg/dl (P = .07) over the six months preceding Aza initiation, despite stable and low therapeutic range HPLC whole-blood CsA levels (118 +/- 10 ng/ml vs. 133 +/- 11 ng/ml, P = NS). Renal function declined at a rate of -0.20 +/- .06 Cr1/year in the six-month period before addition of Aza, and then improved at a rate of 0.09 +/- .04 Cr-1/year after addition of Aza (P = .002). These changes in renal function occurred without a decrease in CsA levels (118 +/- 10 six months before Aza vs. 126 +/- 26 six months after Aza, P = NS). In group B Aza was initiated at 58 +/- 8 days after transplantation when mean sCr was 3.56 +/- .29 mg/dl and mean CsA level was 222 +/- 17 ng/ml. At least follow-up 12.7 +/- 2.0 months after addition of Aza, all group B grafts were functioning, mean sCr was 2.69 +/- .31 mg/dl (P = .09 compared with baseline), and mean CsA level was 128 +/- 34 ng/ml (P = .07 compared with baseline). Group C patients had addition of Aza at 43 +/- 19 months after transplantation when mean sCr was 2.97 +/- .60 and mean CsA level was 125 +/- 30 ng/ml; addition of Aza had no influence on the rate of decline in renal function in this group. Of these 36 patients, 6 received therapy for acute rejection over the entire follow-up period of 12.3 +/- 1.4 months after addition of Aza; 4 of these retain graft function. Infectious complications consisted of 2 urinary tract infections, 1 bacterial pneumonia, and one case of otitis media.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗