tacrolimus and Psychotic-Disorders

Topics: Humans; Immunosuppressive Agents; Kidney Transplantation; Psychotic Disorders; Tacrolimus

Bipolar affective disorder type I imparts significant morbidity and disease burden in the population. It is characterized by occurrence of one or more manic episodes which may be preceded or followed by a depressive or hypomanic phase. About half of these manic episodes are characterized by the presence of psychotic features. The condition is further complicated when the patient has multiple comorbid conditions. We report here the case of a Caucasian woman, aged 66 years, previously diagnosed with Bipolar disorder who developed treatment refractory mania with psychotic feature after being on the immunosuppressive agent, tacrolimus, after kidney transplantation.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Prednisone; Psychoses, Substance-Induced; Psychotic Disorders; Severity of Illness Index; Tacrolimus

To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon.. In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis.. In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients' age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m(2), Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174.. NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Topics: Adrenal Cortex Hormones; Adult; Age Factors; Body Mass Index; Brain Diseases; Case-Control Studies; Consciousness Disorders; Delirium; Female; Graft Rejection; Hepatic Encephalopathy; Humans; Immunosuppressive Agents; Intraabdominal Infections; Length of Stay; Liver Transplantation; Male; Mental Disorders; Middle Aged; Mycophenolic Acid; Myelinolysis, Central Pontine; Neurotoxicity Syndromes; Posterior Leukoencephalopathy Syndrome; Postoperative Complications; Preoperative Period; Psychotic Disorders; Risk Assessment; Risk Factors; Seizures; Sex Factors; Stroke; Tacrolimus; Taiwan; Tissue Donors

Topics: Aged; Female; Humans; Immunosuppressive Agents; Neurotoxicity Syndromes; Psychotic Disorders; Renin-Angiotensin System; Tacrolimus

Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects.. The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM).. Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5 ± 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3 ± 2.9, 9.7 ± 3.4, 7.9 ± 3.3, and 7.6 ± 2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7 ± 2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4 ± 4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone.. Tacrolimus concentration of 5 to <8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.

Topics: Adolescent; Adult; Aged; Confusion; Dose-Response Relationship, Drug; Drug Monitoring; Female; Graft Rejection; Headache; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Psychotic Disorders; Renal Insufficiency, Chronic; Retrospective Studies; Seizures; Tacrolimus; Tremor; Young Adult

Among 71 patients, 19 (26.7%) experienced tacrolimus-related complications including 15 neurologic reactions and four problems with nephrotoxicity. Seven of these patients received grafts from cadaveric donors and 12 from living donors. Nine patients were children. The cohort included 5 female and 14 male subjects of mean age 26 +/- 20 (min 6, max 65) years. The common indications for the liver transplantation were cholestatic and metabolic diseases in pediatric patients, and viral hepatitis in adult patients. Blood tacrolimus levels were within the normal range. All patients with neurologic complications received antiepileptic therapy and drug conversion to rapamycin in 4 cases and to cyclosporine (CsA) in 11 cases. Six cases with Wilson disease and all cases with tyrosinemia experienced neurologic complications, which reversed in all but one case. In four cases with nephrotoxicity, we switched to rapamycin. Renal function improved in all cases. Patients with Wilson disease and tyrosinemia were more susceptible to the neurologic side effects of tacrolimus. In these cases we recommend the use of drugs with fewer neurologic side effects. Tacrolimus also has nephrotoxic effects, which can be reversed by converting to rapamycin.

Topics: Cyclosporine; Hepatolenticular Degeneration; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Nervous System Diseases; Postoperative Complications; Psychotic Disorders; Retrospective Studies; Risk Factors; Tacrolimus

Tacrolimus and cyclosporine, both calcineurin inhibitors, can cause neurological side effects. While mild symptoms such as tremor are well recognised, severe complications including seizures and encephalopathy are poorly documented following renal transplantation.. We report a 42 year old man who received a cadaver renal transplant. He received tacrolimus and prednisolone. The course was uneventful for 6 weeks when he became intermittently confused, with unsteady gait and slurred speech. Following a grand mal convulsion he was admitted. He had no focal neurological signs, cerebrospinal fluid was normal; electroencephalogram was consistent with temporal lobe partial epilepsy. The magnetic resonance imaging of brain showed widespread changes with multiple areas of low signal intensity in brain stem and cerebral hemispheres. He was readmitted 3 weeks later after further fits, despite anti-convulsant therapy. He was psychotic with visual hallucinations, and rapidly became obtunded. Although his tacrolimus blood concentration had been kept in the normal range, his symptoms improved dramatically when the tacrolimus was stopped.. Severe central nervous system toxicity from calcineurin inhibitors has been rarely reported in renal transplantation and we found only one report of tacrolimus-induced toxicity in an adult. We believe the condition is frequently undiagnosed. It is a very important diagnosis not to miss as the remedy is simple and failure may result in unnecessary brain biopsy, as well as irreversible injury.

Topics: Adult; Anticonvulsants; Disease Progression; Epilepsy, Temporal Lobe; Hallucinations; Humans; Immunosuppressive Agents; Kidney Transplantation; Magnetic Resonance Imaging; Male; Psychotic Disorders; Tacrolimus