clozapine and Dry-Eye-Syndromes

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

The purpose of this study is to investigate the effects of long-term clozapine usage on tear film stability and corneal topographic parameters.. The study was conducted between March 2014 and November 2014. Thirty patients who were diagnosed of schizophrenia and have been under clozapine treatment for 2.73 ± 0.73 years (range 2-4 years) were involved in this study (group 1). Thirty healthy subjects (group 2) who have statistically similar demographic features compared with the group 1, were involved as a control group. Full ophthalmologic examination with biomicroscopy and indirect ophthalmoscopy was applied. Corneal topographic parameters were measured using the Pentacam HR and Schirmer test was done. Statistical analysis of the subjects was evaluated by using SPSS (for Windows version 16.0; SPSS Inc., Chicago, IL) program.. K1 value was measured as 43.39 ± 0.17 D (43-43.50 D) and K2 value was measured as 43.39 ± 0.06 D (43.30-43.50 D) in groups 1 and 2, respectively. In groups 1 and 2, K2 values were noted as 43.86 ± 0.27 D (43.50-44.50 D) and 43.72 ± 0.18 D (43.50-44.00 D), respectively. Central corneal thickness was found to be 523.93 ± 15.66 µm (495-554 µm) and 550.13 ± 1.03 µm (520-580 µm) in groups 1 and 2, respectively. Corneal apex thickness was 525.86 ± 15.75 µm (497-556 µm) in group 1 and 551.60 ± 14.99 µm (521-581 µm) in group 2. The corneal thickness of thinnest location was 520.93 ± 15.60 µm (492-551 µm) and 548.06 ± 15.17 µm (518-578 µm) in groups 1 and 2, respectively. Corneal volume was determined as 58.13 ± 3.46 mm(3) (52-64 mm(3)) in group 1 and 60.73 ± 3.76 mm(3) (54-66 mm(3)) in group 2. The Schirmer test showed thickness of 3.33 ± 0.72 mm (2-4 mm) and 13.60 ± 1.59 mm (11-16 mm) in groups 1 and 2, respectively. The mean fluorescein break-up time was 5.40 ± 1.50 s (3-8 s) and 12.46 ± 1.40 s (10-14 s) in groups 1 and 2, respectively. There was a statistically significant difference in the Schirmer test, fluorescein break-up time, central corneal thickness, corneal apex, and the thinnest corneal location thickness between the two groups.. Clozapine may induce dry eye syndrome and thus may lead to morphological alterations in corneal parameters through its anticholinergic and antidopaminergic activities. Because of these corneal alterations, one should be aware of evaluating patients having diseases like glaucoma or preoperative selection of corneal refractive surgery candidates.

Topics: Adult; Antipsychotic Agents; Clozapine; Cornea; Corneal Topography; Dry Eye Syndromes; Female; Humans; Male; Schizophrenia