rifampin and Schizophrenia

BACKGROUND Spinal subdural abscesses, also known as empyemas, are rare infectious lesions, the exact incidence of which is unknown. Presentation is typically dramatic, with back pain, fever, motor, and sensory deficits. Rapid identification and surgical intervention with laminectomy, durotomy, and washout provides the best outcomes. While hematogenous spread of an extra-spinal infection is the most common cause of this condition, a significant number of cases result from iatrogenic mechanisms, including lumbar punctures, epidural injections, and surgery. CASE REPORT Here we present 2 cases: 1) an 87-year-old man with type 2 diabetes, schizophrenia, mild cognitive impairment, and symptomatic lumbar spinal stenosis and 2) a 62-year-old man with a prior L3-4 spinal fusion with symptomatic lumbar spinal stenosis. In both cases, patients underwent laminectomy for spinal stenosis and developed epidural abscess. Following successful drainage of the epidural abscess, they continued to be symptomatic, and repeat imaging revealed the presence of a subdural abscess that was subsequently evacuated. Case 1 had significant improvement with residual lower-extremity weakness, while Case 2 made a complete neurological recovery. CONCLUSIONS These cases illustrate patients at increased risk for developing this rare spinal infection, and demonstrate that rapid recognition and surgical treatment is key to cure and recovery. Review of the literature highlights pertinent risk factors and demonstrates nearly one-third of reported cases have an iatrogenic etiology. The cases presented here demonstrate that a subdural process should be suspected in any patient with intractable pain following treatment of an epidural abscess.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Body Mass Index; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Epidural Abscess; Humans; Laminectomy; Lumbar Vertebrae; Male; Middle Aged; Rifampin; Risk Factors; Schizophrenia; Spinal Stenosis; Staphylococcal Infections; Suction; Treatment Outcome; Vancomycin

Increased glycine availability at the synaptic cleft may enhance N-methyl-D-aspartate receptor signalling and provide a promising therapeutic strategy for cognitive impairment associated with schizophrenia. These studies aimed to assess the pharmacokinetics of BI 425809, a potent glycine-transporter-1 inhibitor, when co-administered with a strong cytochrome P450 3A4 (CYP3A4) inhibitor (itraconazole) and inducer (rifampicin).. In vitro studies using recombinant CYPs, human liver microsomes, and human hepatocytes were conducted to determine the CYP isoforms responsible for BI 425809 metabolism. In addition, two open-label, fixed-treatment period, phase I studies in healthy male volunteers are described. Period 1: participants received oral BI 425809 25 mg (single dose) on day 1; period 2: participants received multiple doses, across 10 days, of oral itraconazole or rifampicin combined with a single dose of oral BI 425809 25 mg on day 4/7 of the itraconazole/rifampicin treatment, respectively. Pharmacokinetic and safety endpoints were assessed in the absence/presence of itraconazole/rifampicin and included area under the concentration-time curve (AUC) over the time interval 0-167 h (AUC. In vitro results suggested that CYP3A4 accounted for ≥ 90% of the metabolism of BI 425809. BI 425809 exposure (adjusted geometric mean ratio [%]) was higher in the presence of itraconazole (AUC. Systemic exposure of BI 425809 was altered in the presence of strong CYP3A4 modulators, corroborating in vitro results that CYP3A4 mediates a major metabolic pathway for BI 425809.. NCT02342717 (registered on 15 January 2015) and NCT03082183 (registered on 10 March 2017).

Topics: Adolescent; Adult; Area Under Curve; Cell Line; Cytochrome P-450 CYP3A Inhibitors; Drug Synergism; Glycine Plasma Membrane Transport Proteins; Healthy Volunteers; Humans; Itraconazole; Male; Middle Aged; Nootropic Agents; Organic Chemicals; Rifampin; Schizophrenia; Young Adult

A combination of olanzapine and samidorphan was recently approved by the US Food and Drug Administration for the treatment of patients with schizophrenia or bipolar I disorder. Population pharmacokinetic models for olanzapine and samidorphan were developed using data from 11 clinical studies in healthy subjects or patients with schizophrenia. A 2-compartment disposition model with first-order absorption and elimination and a lag time for absorption adequately described concentration-time profiles of both olanzapine and samidorphan. Age, sex, race, smoking status, and body weight were identified as covariates that impacted the pharmacokinetics of olanzapine. A moderate effect of body weight on samidorphan pharmacokinetics was identified by the model but was not considered clinically meaningful. The effects of food, hepatic or renal impairment, and coadministration with rifampin on the pharmacokinetics of olanzapine and samidorphan, as estimated by the population pharmacokinetic analysis, were consistent with findings from dedicated clinical studies designed to evaluate these specific covariates of interest. Food intake did not have a clinically relevant effect on the pharmacokinetics of olanzapine or samidorphan. Consistent with the known metabolic pathways for olanzapine (primarily via uridine 5'-diphospho-glucuronosyltransferase-mediated direct glucuronidation and cytochrome P450 [CYP]-mediated oxidation) and for samidorphan (predominantly mediated by CYP3A4), coadministration of olanzapine and samidorphan with rifampin, a strong inducer of CYP3A4 and an inducer of uridine 5'-diphospho-glucuronosyltransferase enzymes, significantly decreased the systemic exposure of both olanzapine and samidorphan. Severe renal impairment or moderate hepatic impairment resulted in a modest increase in olanzapine and samidorphan exposure.

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Body Weight; Cigarette Smoking; Cytochrome P-450 CYP3A; Drug Combinations; Female; Food-Drug Interactions; Humans; Liver Failure; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Olanzapine; Racial Groups; Renal Insufficiency; Rifampin; Schizophrenia; Sex Factors; Young Adult

At the University Centre for Chronic Diseases Dekkerswald, a tertiary tuberculosis (TB) referral hospital in The Netherlands, therapeutic drug monitoring (TDM) is used in patients in case of relapse TB, when there is delayed response to TB treatment, and when abnormal TB drug concentrations are suspected for other reasons. In this article, a case series is presented to illustrate the value of individualized TB drug dosing in four patients with low TB drug concentrations. Increased doses of the TB drugs, especially of rifampicin, resulted in adequate peak plasma concentrations and improved clinical response to treatment in these patients, while no adverse events occurred.

Topics: Adult; Aged; Alcoholism; Antibiotics, Antitubercular; Antitubercular Agents; Chromatography, High Pressure Liquid; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Monitoring; Ethambutol; Humans; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Precision Medicine; Pyrazinamide; Recurrence; Rifampin; Schizophrenia; Sputum; Treatment Failure; Tuberculosis; Tuberculosis, Multidrug-Resistant

Topics: Antipsychotic Agents; Antitubercular Agents; Dibenzothiepins; Drug Interactions; Female; Humans; Middle Aged; Rifampin; Schizophrenia; Schizophrenic Psychology; Tuberculosis

Neuroleptic malignant syndrome (NMS), a potentially fatal adverse reaction to neuroleptics, is known to occur more often in the initial stage of antipsychotic treatment. We describe a patient with chronic schizophrenia who, in a few days after the addition of antituberculotic drugs to his antipsychotic regimen, developed probable NMS without pyrexia. We reasoned that rifampin, a strong hepatic enzyme inducer, decreased the plasma chlorpromazine concentration of the patient, with the result of cholinergic hyperactivity and finally, the symptoms of NMS. Therefore, physicians should be aware of drug interactions and the likelihood of NMS, and consider antipsychotic dose adjustment when prescribing drugs that may influence pharmacokinetic properties of antipsychotics in a patient with schizophrenia receiving long-term antipsychotic treatment.

Topics: Adult; Antitubercular Agents; Chlorpromazine; Creatine Kinase; Drug Interactions; Enzyme Induction; Humans; Male; Neuroleptic Malignant Syndrome; Rifampin; Schizophrenia

Topics: Adult; Antibiotics, Antitubercular; Antipsychotic Agents; Clozapine; Drug Interactions; Humans; Male; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Rifampin; Schizophrenia

We assessed the changes of plasma haloperidol concentrations and clinical responses repeatedly up to 4 weeks after coadministration or discontinuation of rifampin in 12 schizophrenic patients taking haloperidol alone (group I) and 5 patients taking haloperidol and antituberculotic drugs (group II). After coadministration of rifampin in group I, daily trough haloperidol concentrations rapidly decreased and reached 63% of baseline level by day 3, 41.3% by day 7, and 30% by day 28. On the other hand, after discontinuation of rifampin in group II, plasma haloperidol concentration increased to 140.7% of baseline level by day 3, 228.7% by day 7, and 329% by day 28. In this study, a 30% or greater change in the clinical rating scale was considered a positive clinical response of the drug interaction. Using this criterion, 50% of the group I subjects responded according to the Brief Psychiatric Rating Scale (BPRS) total score, and 25% responded according to the BPRS subscale for psychiatric symptoms. No positive responses were observed in group II patients. These results strongly suggest that rifampin interacts with the clinical effects as well as the plasma concentrations of coadministered haloperidol, and careful monitoring should be considered when coadministration or discontinuation of rifampin is needed in a schizophrenic patient taking haloperidol.

Topics: Adult; Antibiotics, Antitubercular; Antipsychotic Agents; Drug Interactions; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Rifampin; Schizophrenia; Tuberculosis

Serum haloperidol levels were studied in schizophrenic patients with and without antituberculosis therapy, and the effect of these agents on serum haloperidol level was evaluated. Rifampicin caused significant suppression of serum haloperidol levels in all cases studied (n = 7). The serum haloperidol clearance rate was accelerated in patients taking rifampicin, with a shortened half-life (4.9 h) compared with the control group (9.4 h). Among 18 schizophrenic patients receiving isoniazid, three showed significantly elevated serum haloperidol levels. It is possible that isoniazid can elevate haloperidol levels in some patients depending upon some unknown factors. The elevation of serum haloperidol level was though to be due to prolonged clearance of haloperidol secondary to isoniazid interaction with hepatic enzymes involved in drug metabolism. These observations suggest that haloperidol doses in schizophrenic patients receiving rifampicin or isoniazid must be carefully monitored.

Topics: Adult; Drug Interactions; Haloperidol; Humans; Isoniazid; Metabolic Clearance Rate; Middle Aged; Rifampin; Schizophrenia; Tuberculosis, Pulmonary