Biomedical subjects

Charles F Caley

Publications and source records attributed to Charles F Caley.

4 recordsLinked to original sources

PubMed2005

Interpreting serum risperidone concentrations.

Risperidone is an atypical antipsychotic commonly used for treatment of schizophrenia and other psychotic disorders. Although therapeutic drug monitoring is not routine for any of the atypical antipsychotics, serum antipsychotic concentrations are measured routinely to assess treatment nonadherence. In humans, risperidone is metabolized by cytochrome P450 2D6 to 9-hydroxyrisperidone; together these constitute the active moiety. Dose-proportional increases in serum concentrations have not been reported for the parent drug, but have been reported for 9-hydroxyrisperidone and the active moiety (i.e., the combined concentrations of risperidone and 9-hydroxyrisperidone). We describe a 34-year-old Caucasian man of Sicilian descent with a history of schizophrenia, disorganized type. He was suspected to be noncompliant with his risperidone therapy. Initially, active moiety risperidone concentrations increased linearly with prescribed dosage increases. However, with continued increases, active moiety concentrations adjusted downward and remained 17-36% below anticipated levels. We propose a method for estimating target active moiety concentrations of risperidone based on dosage-a method that may be used to guide clinicians in assessing nonadherence to risperidone treatment.

Adult↗

PubMed2003

Possible case of mania associated with ma-huang.

Several commercially available weight-loss supplements contain ma-huang, an herb derived from Ephedra sinica. Previous reports have raised awareness that ma-huang supplements may precipitate symptoms consistent with mania in susceptible individuals. A 21-year-old woman required psychiatric hospitalization as a result of acute manic symptoms with psychosis. The emergence of her symptoms coincided with her use of two supplements containing ma-huang. Consumers need to be educated about the potential adverse psychiatric effects of ma-huang in order to make well-informed decisions before using such supplements. A preexisting psychiatric disorder may also increase susceptibility to these adverse effects.

Adult↗

PubMed2002

SSRI efficacy-finding the right dose.

The selective serotonin reuptake inhibitors (SSRIs) are a class of effective, well-tolerated antidepressants. They have a number of benefits compared with the tricyclic antidepressants (TCAs) including improved safety in overdose, reduced side-effect burden, and uncomplicated dosing regimens. To avoid the potential for troublesome side effects with TCAs, doses should be gradually increased over several weeks. Dose titration can be associated with several drawbacks such as patients discontinuing therapy due to a prolonged time to therapeutic response, additional visits to a prescribing healthcare provider, or additional hospitalizations. In contrast, the SSRIs typically do not require dose titration since many patients find the initial dose effective. The ability to prescribe an initial optimum therapeutic dose while avoiding dose-related side effects is important in the treatment of major depression. With this in mind, the authors consider the recommended dose ranges for the five SSRIs: citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

Journal Article↗

PubMed2002

Ziprasidone: the fifth atypical antipsychotic.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of ziprasidone as a treatment for schizophrenia. DATA SOURCES: Information was selected from a MEDLINE search (July 2000-October 2001) of English-language medical literature using ziprasidone as the search term. Manual searches of pertinent journal article references, request for medical information from Pfizer, and access of the Web site of the Food and Drug Administration were also performed. STUDY SELECTION: All available published information regarding the pertinent characteristics of ziprasidone were considered for selection. DATA EXTRACTION: Pharmacology and pharmacokinetic studies were selected to provide a comprehensive description of these characteristics. Clinical investigations were evaluated for design, sample size, diagnosis, duration, and outcome. Data from all investigations were selected by 1 author and reviewed by both authors. DATA SYNTHESIS: Ziprasidone is a benzisothiazolyl piperazine-type atypical antipsychotic that shares the serotonin(2A)/dopamine(2) (5-HT(2A)/D(2)) profile of the available atypical antipsychotics. Ziprasidone has demonstrated in vitro activity as a 5-HT(1A) receptor agonist and as a very weak inhibitor of serotonin and norepinephrine reuptake. These data do not support ziprasidone as being a clinically meaningful inhibitor of serotonin/norepinephrine reuptake. Oral bioavailability of ziprasidone taken with food is approximately 60%, half-life is approximately 6-7 hours, and protein binding is extensive at >99%. Twelve metabolites have been identified, yet only 4 of these are considered to be primary metabolites. Metabolism of ziprasidone by aldehyde oxidase produces its only metabolite with potential pharmacologic activity; CYP3A4 also contributes to the metabolism of ziprasidone. Clinical studies support ziprasidone as efficacious for the treatment of patients with acute exacerbations of schizophrenia or schizoaffective disorder. Daily doses permitted in these clinical trials ranged from 40 to 160 mg, but only doses between 120 and 160 mg/d have been superior to placebo. Future research efforts should be directed toward refractory schizophrenia, cognitive impairment in schizophrenia, affective and anxiety symptoms associated with schizoaffective disorder, and bipolar disorder. Adverse effect characteristics of ziprasidone commonly include headache, nausea, and somnolence; infrequent effects include extrapyramidal symptoms and weight gain. Ziprasidone has been reported to cause an average QTc prolongation of approximately 20 msec; there have only been 2 patients (0.06%) reported by the manufacturer to have a measured QTc interval >500 msec. CONCLUSIONS: Ziprasidone is a safe and efficacious atypical antipsychotic for the acute management of schizophrenia. Efficacy data and most safety data for ziprasidone support its use as a first-line treatment for schizophrenia; however, its potential effects on ventricular repolarization relegate it to second-line status in patients with comorbid cardiovascular risks.

Acute Disease↗