Pharmaceutical perspective of neuropathic pain management for primary care providers.

Neuropathic pain (NP) is a chronic condition that affects ~ 1% of the general population globally. Several conditions such as chronic diabetes, herpes zoster (HZ), cancer, HIV, stroke, multiple sclerosis, physical compression or damage of nerves and certain surgical procedures can lead to neuropathy and related pain. The condition is difficult to treat with traditional analgesic drugs. Typically, non-traditional analgesics are used in treating pain in this condition such as antidepressants and antiepileptic drugs. Opioids are useful in some patients, but the risk of addiction and the risk of both short-term and long-term adverse effects make it a low priority drug class in the treatment of NP. In the current review we discuss the pharmacology and pharmaceutical care aspects of various classes of drugs used in the treatment of NP, counselling points for these drug classes, and future prospects in the treatment of NP.

Emerging evidence for the role of pituitary adenylate cyclase-activating peptide in neuropsychiatric disorders.

Stress activates many brain nuclei and causes acute changes in several physiological and behavioral responses to restore homeostasis in affected organisms. While this response is protective, chronic stress exposure causes the sustained activation of these nuclei, leading to maladaptive physiological changes that underlie pathological mood and affective states. Hence, chronic stress may produce anxiety and mood disorders by promoting neuronal plasticity within these stress-responsive nuclei. A growing body of evidence attributes neuropeptide systems in mediating not only the physiological stress response but also pathological states that develop following chronic stress exposure. Recent preclinical data suggest that pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptors (PAC1, VPAC1, and VPAC2) play an important role in the behavioral and endocrine responses to stress, as well as in mood and affective disorders. Human studies also point out the significance of the PACAP/PAC1 receptor system in these disorders. For instance, PACAP through PAC1 receptor up-regulates the expression of DISC1 (disrupted in schizophrenia 1) and impedes its association with its interacting protein. Interestingly, the DISC1 gene mutation is linked to schizophrenia and depression. Moreover, a link between PACAP blood titer and fear physiology, post-traumatic stress disorder (PTSD) diagnosis and symptoms has been reported in heavily traumatized female patients. Additionally, in the peripheral blood, methylation of the gene encoding the PAC1 receptor is also associated with PTSD. This book chapter describes the emerging evidence that entails PACAP in the stress response and stress-mediated neuropsychiatric disorders.

A retrospective cohort study of the prevalence of anxiety and agitation in schizophrenic smokers and the unmet needs of smoking cessation programs.

Achieving abstinence in schizophrenic smokers using a combination of medications and cognitive behavioral therapy is feasible; however, abstinence rates are significantly lower compared to the general population and studies are scanty. Additionally, maintaining sustained abstinence and preventing relapse is a major limiting factor and represents key tasks in managing tobacco dependence in schizophrenic patients. Several theories have been postulated to explain the higher tendency of tobacco use among schizophrenic individuals. Schizophrenic patients may use nicotine as a "self-medication" strategy to improve negative symptoms of schizophrenia. However, studies suggest that although nicotine may act as an anxiolytic acutely, chronic use of nicotine may lead to increased anxiety with the possibility of increased catecholamines, which is confirmed with the prevalence of tachycardia and hypertension in smokers in general. On this basis, the main objective of our present study was to assess anxiety in schizophrenic smoking and nonsmoking patients by comparing the number of anxiety and agitation episodes and evaluating the amount of antianxiety/antiagitation medication used by each group. A separate objective was to document the unmet needs of smoking cessation programs in treating schizophrenic patients. Consequently, in the present retrospective cohort study, it was observed that schizophrenic smokers tend to have higher anxiety episodes and utilize as-needed medications at a higher frequency compared to nonsmokers for the relief of anxiety and agitation symptoms. Further research is warranted to examine these results on a larger scale.

Minimizing cardiovascular adverse effects of atypical antipsychotic drugs in patients with schizophrenia.

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.

Fatal agranulocytosis associated with psychotropic medication use.

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.

Positive and Negative Syndrome Scale as a longterm outcome measurement tool in patients receiving clozapine ODT- A Pilot Study

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 (AU)

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 (AU)

Positive and Negative Syndrome Scale as a long-term outcome measurement tool in patients receiving clozapine ODT- A Pilot Study.

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.