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Purpose A patient’s death due to severe hematologic adverse effects of the concomitant use of four psychotropic medications is reported. Summary A 40-year-old Caucasian woman with a 9-year history of depression and anxiety (managed with alprazolam) was admitted to a psychiatric hospital for the treatment of acute psychotic symptoms. After nine days, the patient was discharged home on a regimen of lamotrigine, mirtazapine, quetiapine, and venlafaxine. Five weeks later, the development of severe ocular cellulitis, severe oral thrush, and febrile neutropenia necessitated the woman’s urgent rehospitalization; on admission, her white blood cell count was 600 cells/mm 3 , her absolute neutrophil count was 18 cells/mm 3 , and microbial pathogens were isolated in peripheral blood and tracheal aspirate cultures. Despite treatment with antibiotics and filgrastim, the patient developed multiorgan dysfunction and died five days later from septic shock. The woman’s concomitant use of multiple psychotropics and the late recognition of drug-induced agranulocytosis likely contributed to her severe symptoms and ultimate death. The application of the Naranjo scale to this case yielded a score of 6, indicating a probable adverse drug reaction. Although hematologic adverse effects have been reported with the use of each of the four drugs implicated in the woman’s death, this is thought to be the first report of fatal agranulocytosis associated with any of the drugs. Conclusion A 40-year old woman with a history of acute psychotic symptoms developed agranulocytosis and neutropenia after starting therapy that included lamotrigine, mirtazapine, quetiapine, and venlafaxine.

The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients.

Studies indicated that targeting localized serotonin 5-HT2C receptors can treat obesity which is consistent with the role in regulating pathways of food intake and body weight that could lead to obesity. The association of diminished serotonergic activity with metabolic syndrome may have implications for the prevention and treatment of the metabolic syndrome. Antipsychotics are 5-HT2C receptors antagonists that can knock down the satiety centers located in ventromedial nucleus in hypothalamus leading to increased weight gain. The potential for weight gain differs among atypical antipsychotics. While ziprasidone and aripiprazole care thought to be weight neutral, dibenzodiazepines like clozapine and olanzapine are implicated in lot of weight gain that can cause obesity and metabolic syndrome. The amount of body weight gain varies with each drug. The difference in weight gains between quetiapine and each of the other atypical medication was significant in our studies (Mean weight gain was least with quetiapine 9.31b and greatest for olanzapine 20.89 lb). Weight gain was also greater with olanzapine than with clozapine. In the literature survey we observed clozapine has been associated with some of the largest bodyweight gains of olanzapine in the long term use and higher weight gain with clozapine seems to be on shorter duration. For many of the metabolic disorders related to weight gain and obesity, scientists have implicated abdominal visceral fat. An increase in visceral fat, in turn, leads to an increased concentration of free fatty acids in the portal vein. An increased free fatty acid concentration may lead to a decrease in hepatic insulin clearance, insulin resistance, hyperinsulinemia, and hypertension. This sequence of events may lead to diabetes, assorted dyslipidemia, and ultimately to coronary artery disease. The purpose of the study was to evaluate the impact of intervention on improving overall cardiovascular adverse effects of antipsychotic therapy. Long-term metabolic complications such as obesity, diabetes, dyslipidemia, hypertension, and ECG changes were of particular interest but the results from our study has not shown any significant change in clinical practice that lead to reduction in cardiovascular risk. During the study period (8/2009 – 11/2009), 118 treatment recommendations were made by pharmacy students and clinical pharmacist preceptor and most were for new lipid and FBG/HgA1C panel for missing lab values or more accurate assessment of patient’s recent status and 82 recommendations were accepted. As appreciated by the result from this study period, the key limiting factor in accurately assessing effectiveness of consultant intervention is that the treatment decision is ultimately made by the patient’s psychiatrist who reviews the recommendation. However the clinical recommendation from the psychopharmacy consultant may still help to increase overall awareness on part of psychiatrists regarding patients’ current cardiovascular risk. Whether it will lead to active intervention will be dependent on other factors. For example, most of the psychopharmacy recommendations are for lipid and A1C/FBG labs as seen during this study period, but even when the recommendation is accepted, the patient may not necessarily require therapeutic intervention as the lab values often do not show any significant changes or are stable-normal. Or in case the recommendation is not accepted, it may be influenced by the therapy/lab cost or availability of other nonpharmacological interventions (e.g. diet/lifestyle modification) more so than the clinical competency of the recommending pharmacist. Other limiting factors of the study include lack of control group for comparison and need for objective monitoring tool for evaluating overall cardiovascular risk of the patients. For this study period, there was significant cardiovascular reduction seen through clinical pharmacy intervention in high-risk patients receiving antipsychotic. More studies are needed to support clinical pharmacist’s role in improving overall cardiovascular risk associated with antipsychotic therapy but in the meanwhile, interdisciplinary monitoring and careplan in regards to high- risk patients should be continued and American diabetic association recommends serum glucose and serum lipids on quarterly basis for the patients who receive atypical antipsychotics (dibenzodiazepine more so) and that is the standard of care. In the future, there may be several changes that can be made to the study protocol for better assessment of effectiveness of clinical pharmacy intervention. First, one may consider increasing the sample size by increasing the duration and thus more patients to increase the power of the study. Second, recommending pharmacist should leave a written progress note for which other psychiatrist/physicians may be able to refer back to rather than verbal recommendations to one attending psychiatrist as done so far. And lastly, one may consider

Objective: This pilot, twelve-week, open-label study examined the effect of clozapine orally disintegrating tablet or ODT in patients with schizophrenia and schizoaffective disorder utilizing Positive and Negative Syndrome Scale (PANSS) as a long-term outcome measurement tool. Methods: The final study sample consisted of nineteen subjects who were residents a long-term care psychiatric facility in Pomona, California. Subjects were using clozapine ODT (FazaClo®) at the most clinically effective dosage depending on their symptoms and at the discretion of the psychiatrist and psychopharm consultant. PANSS were administered at baseline, week-4, week-8 and week-12. Paired sample t-tests were used to calculate the statistical significance of the mean differences for scores at baseline and week-12. Results: Mean differences from baseline indicated significant improvement on total score, as well as positive, negative, cognitive and general psychopathology subscales after twelve weeks of treatment. The greater average reduction in the negative syndrome subscale across the twelve weeks possibly illustrates the ability of clozapine ODT in improving negative symptoms, including cognitive function which is their ability to participate in their personal care and creative expressions in dance, arts, games, poetry to a greater extent their overall, quality of life and living along with the effect on positive symptoms. Conclusion: Overall, clozapine proved to affect a broad range of psychopathology including cognitive functions in this schizophrenic sample. Objetivo: Este estudio piloto de 12 semanas examinó el efecto de comprimidos oralmente dispersables (OD) de clozapina en pacientes con esquizofrenia o desordenes esquizo-afectivos utilizando la escala Positive and Negative Syndrome Scale (PANSS) como herramienta de medida de resultados. Métodos: La muestra final de estudio consistió en 19 individuos que residían en una clínica siquiátrica de larga estancia en Pomona, California. Los individuos estaban utilizando clozapina OD (FazaClo®) a la dosis más efectiva clínicamente dependiendo de sus síntomas y a discreción del psiquiatra y el consultor psicofarmacéutico. Se administró el PANS Sal inicio, en las emana 4, semana 8 y semana 12. Se utilizaron t-test apareados para calcular la significación estadística de las diferencias de las medias para las puntuaciones basales y en la semana 12. Resultados: Las diferencias medias del valor inicial indicaron mejora significativa en la puntuación total, así como en las subescalas positiva, negativa y de psicopatología general después de 12 semanas de tratamiento. La mayor media de reducción en la subescala negativa tras las 12 semanas posiblemente ilustra la capacidad de la clozapina OD para mejorar los síntomas negativos, incluyendo la función cognitiva que es la capacidad de participare n su cuidado personal y las expresiones creativa sen baile, arte, juegos, poesía y en mayor escalas u calidad de vida general ye l sobrellevar los efectos en los síntomas positivos. Conclusión: En general, la clozapina demostró afectar un amplio margen del a psicopatología, que incluye las funciones cognitiva sen esta muestra de esquizofrénicos.