Sergio De Filippis

Psychiatric comorbidity and suicide risk in patients with chronic migraine.

The aim of this study was to explore the impact of mental illness among patients with migraine. We performed MedLine and PsycINFO searches from 1980 to 2008. Research has systematically documented a strong bidirectional association between migraine and psychiatric disorders. The relationship between migraine and psychopathology has often been clinically discussed rather than systematically studied. Future research should include sound methodologically-based studies focusing on the interplay of factors behind the relationship between migraine, suicide risk, and mental illness.

Genetics of migraine and pharmacogenomics: some considerations

Migraine is a complex disorder caused by a combination of genetic and environmental factors.Although family and twin studies show that there is a genetic component in migraine, no genes predisposing to common forms of the disorder, migraine with and without aura, have been identified. Patients with migraine respond differently to a given drug administered. The efficacy of therapy and the occurrence of adverse drug response are a consequence of individual variability. Genetic profiling of predisposition to migraine should facilitate the development of more effective diagnostic and therapeutic applications. The development of International Hap Map project could provide a powerful tool for identification of the candidate genes in this complex disease and pharmacogenomics research could be the promise for individualized treatments and prevention of adverse drug response.

An improved simple LC–MS/MS method for the measurement of serum aripiprazole and its major metabolite

BACKGROUND AND OBJECTIVES Current liquid chromatographic tandem mass spectrometry (LC-MS/MS) methods to measure serum levels of aripiprazole (Ar) and dehydroaripiprazole (DHAr) are sensitive, but difficult to use in a hospital context. We aimed to develop a rapid LC-MS/MS method allowing reliable level measurement in the presence of co-administered drugs, withdrawing samples from 22 patients with acute agitation receiving 9.75 mg aripiprazole IM injection. METHOD We developed a sensitive and selective HPLC-MS/MS method to measure serum Ar and DHAr levels in a hospital laboratory, requiring minimal sample preparation and inferior sample volume compared to previous LC-MS/MS methods. Analytes were separated on a reversed-phase HPLC (run-time, 10 min). A triple quadrupole tandem mass spectrometer was used for quantitative analysis in positive mode by a multiple reaction monitoring. Samples were drawn 2, 4, 6, and 24h post-injection. RESULTS Calibration curves (2-1000 ng/mL for Ar and 3.5-500 ng/mL for DHAr) were linear, with mean correlation coefficient >0.9998. Within- and between-day precision and accuracy were within 10%. Mean recovery was 95.2 ± 4.5% for Ar and 97.6 ± 7.2% for DHAr. Ar and DHAr peaks were not affected by other co-administered psychotropic drugs. CONCLUSION Our method measured Ar and DHAr concentrations reliably, simply and rapidly without employing many reagents, as currently existing methods.

Neurological soft signs discriminate schizophrenia from bipolar disorder

Background. Although neurological soft signs have been consistently described in patients with schizophrenia, their diagnostic specificity is not well clarified. Methods. To test the hypothesis that neurological soft signs are specifically related to schizophrenia, we examined 305 subjects (patients with schizophrenia-spectrum disorder, n=167; patients with bipolar I disorder, n=88; controls, n=50). Neurological soft signs were assessed using the Neurological Evaluation Scale (NES). Multiple logistic regression analysis was used to compute the diagnostic predictive power of neurological soft signs. Results. Patients in the schizophrenia-spectrum disorder group were found to have significantly greater neurological impairment (NES total score=23.9, standard deviation [SD] 11.2) than those in the bipolar disorder group (NES total score=18.2, SD 7.6; p<0.001). Neurological functioning was closely associated with psychopathology (all p<0.001). The NES total score reliably distinguished patients with schizophrenia spectrum disorders from those with bipolar disorder in 68.7% of the cases (p<0.001). Moreover, a particular set of neurological soft signs showed specificity for the schizophrenia-spectrum disorder diagnostic group. Conclusions. Our findings suggest that schizophrenia and bipolar disorder can be distinguished in terms of neurological impairment. Furthermore, we recommend the utility of neurological soft signs as a useful, quantifiable, sensitive, and inexpensive tool for the diagnostic work-up of schizophrenia. (Journal of Psychiatric Practice 2014;20:147–153)

Gray and white matter trajectories in patients with bipolar disorder

Findings on brain structural abnormalities in patients with bipolar disorder (BP) are inconsistent and little is known about age‐related evolution of these changes. We employed a cross‐sectional, case–control study to compare structural age‐related brain trajectories in patients with BP and healthy control subjects (HC) over a period of approximately 50 years. The primary aim was to understand whether white (WM) and gray matter (GM) abnormalities are present from the beginning of the illness and how they change over time.

Intramuscular Aripiprazole in the Acute Management of Psychomotor Agitation

To assess acute efficacy and safety of 9.75 mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation.

Reduction in expenditures on analgesics during one year of treatment of chronic tension headache with BoNT-A

AbstractThe aim of this study was to investigate the impact of the use of botulinum toxin type A (BoNT-A; BOTOX; Allergan, Inc.; Irvine, CA) as preventive treatment of chronic tension-type headache (CTH) on analgesic use and expenditure.This was a prospective, single-center, 1-year, open-label study of the effect of BoNT-A treatment on acute analgesic use and expenditure in CTH patients.A structured headache questionnaire, which included questions about medication costs, was completed by CTH patients attending a specialist headache clinic in Rome prior to BoNT-A injections. Repeat injections were administered every 3 months for up to 1 year. Patients were required to complete the questionnaire prior to each injections cycle. A pharmacoeconomic analysis was performed at each assessment to determine the effect of BoNT-A treatment on analgesic use and expenditure. Three hundred questionnaire were distributed and 296 (98%) were completed. The study population consisted of 67.8% (201) females and 32.2% (95) males, with a mean age of 46.7±16.1 years.The economic evaluation of the pharmacologic treatment of CTTH was conducted on the 101 (34.12%) patients who gave complete information on posology. Pharmacoeconomic data analysis focused on the whole group using analgesics compared to those who self-prescribed and those who turned to health specialists before and after treatment with BoNT-A. Prior to treatment with BoNT-A the median monthly pharmaceutic expenditure per patient was euro (€) 24.30 for the whole group using analgesics, and € 34.93 and € 18.51 for the “self-prescribers” and the “prescribed by specialist” groups, respectively. Median monthly pharmaceutic expenditure decreased significantly for the whole group (p<0.001), the ”self-prescribers” (p<0.01), and the “prescribed by specialist” group (p<0.002) (3rd month: € 13.3, 9.3, 7.2, respectively; 6th month: € 8.9, 9.0, 4.1, respectively; 9th month: € 5.7, 12.4, 3.0, respectively; 12th month € 4.1, 9.8, 3.4, respectively).BoNT-A treatment produced significant reductions in both analgesic use and expenditure. The data suggest that consultation with a specialist would be helpful in patients with CTTH. Cooperative studies on cost analysis of chronic daily headaches, including both CTTH and chronic migraine, comparing the economic cost package borne by patient and community both before and after treatment with BoNTA, are warranted. However, in the near future additional studies to compare clinical efficacy of BoNT-A in CTTH with its painkiller use/expenditure in the control of pain are needed in order to avoid any possible interference due to placebo effect.

Switching antipsychotic medication to aripiprazole: position paper by a panel of Italian psychiatrists.

Introduction: Patients with schizophrenia or bipolar disorder treated with antipsychotic medication can frequently experience lack of efficacy and persistent side-effects, so much so that switching from one antipsychotic to another with a different side-effect profile has become a recommended strategy for improving the tolerability and safety of long-term antipsychotic treatment. Aripiprazole is an atypical antipsychotic with proven efficacy in schizophrenia and bipolar I disorder, with a pharmacological profile distinct from other available antipsychotics and a side-effect profile that is different from other agents in the class; these characteristics make it a possible alternative in patients requiring a change in antipsychotic treatment due to lack of efficacy or persistent side-effects. Areas covered: A panel of Italian experts in psychiatry met to discuss the appropriateness of current strategies for the switch to aripiprazole in patients with schizophrenia or bipolar disorder once a clinician has decided to adopt this choice and also to propose alternate strategies where required. The strategies for the switch to aripiprazole presented in this position paper consider various scenarios encountered in clinical practice, highlight the importance of tapering the prior antipsychotic based on its pharmacological characteristics and provide detailed guidance throughout the entire switching process. Literature searches were conducted using the PubMed database and the search strategy (aripiprazole and switching); additional references were added from the reference lists of the papers obtained and also from the authors’ knowledge of the topic. Expert opinion: Few studies have addressed the indications for antipsychotic switching and the best practical strategies to achieve the desired goal in the clinical practice setting. Studies on antipsychotic switching should clarify why, when and how a switch should be done. The results should standardize the reasons for switching an antipsychotic, assess the optimal time to switch and evaluate the best ways to switch. Both clinical and pharmacological factors should be considered when a patient needs to switch antipsychotics, and specific guidelines for antipsychotic switching that address all these factors are needed.

Switching long acting antipsychotic medications to aripiprazole long acting once-a-month: expert consensus by a panel of Italian and Spanish psychiatrists.

ABSTRACT Introduction: Aripiprazole long acting once-monthly (AOM) is a long acting atypical antipsychotic with proven efficacy in schizophrenia and with a pharmacological and a side effect profile that is different from other antipsychotics. These and other characteristics make AOM a possible alternative in patients requiring a change in long acting antipsychotic treatment due to issues such as lack of efficacy or persistent side effects. Both clinical and pharmacological factors should be considered when switching antipsychotics, and specific guidelines for long acting antipsychotic switching that address all these factors are needed. Areas covered: A panel of Italian and Spanish experts in psychiatry met to discuss the strategies for the switch to AOM in patients with schizophrenia. Real life clinical experiences were shared and the clinical strategies to improve the likelihood of success were discussed. Expert Opinion: Due to its specific pharmacological and tolerability profile, AOM represents a suitable alternative for patients with schizophrenia requiring a switch to a new LAI treatment because of lack of efficacy or persistent side effects from another LAI. Possible strategies for the switch to AOM are presented in this expert consensus paper in an attempt to provide guidance throughout the entire switching process

Analgesic therapy for headache: consumption, appropriateness and costs

Abstract Headache represents not only an individual disease, but also an important pathology for society because its prevalence in the population is about 50.0%. Its physical, emotional, social and economic impacts are often neglected and it is only recently that headache is being considered in a public health perspective, especially its disabling burden, its treatment and its costs. The aim of this work was to investigate the pharmacological treatment of headache and its costs. An anonymous questionnaire on headache was distributed in a waiting room of a general hospital in Rome, Italy. Both patients and visitors were included in the sample with the exclusion of those who had an appointment at Headache Centre of the hospital. The study was conducted on 294 subjects; the mean age was 46.7 years (SD=16.1). The prevalence of headache was 65.6% (95% CI, 60.0%–71.0%). There was no statistically significant difference between patients and visitors, while there was between men and women (53.0% vs. 79.4%; p<0.05). In the age group 30–49 years, the prevalence was significantly higher than in the other age groups (86.0%; p<0.05). Drugs only to treat headache were used by 67.9% of the sample and Aulin was the most used drug, followed by Novalgina and aspirin used, respectively, by 41.6%, 11.0% and 9.7% of the subjects. The economic evaluation of the pharmacological treatment of headache was conducted on the 101 patients (65.6%) who gave complete information on posology. Since the distribution of costs was strongly skewed to the right due to a few expensive treatments, the mean annual pharmaceutical expenditure per patient is not a good indicator, and we also calculated the median and the mode, the maximum and the minimum. Attention was focused also on two subgroups: those who used self-prescription and those who turned to healthcare specialists. The median annual pharmaceutical expenditure per patient was euro 4.30 for the whole group who used drugs and euro 3.93 and 8.51 for the self-prescription and the prescribed by specialist groups, respectively. In conclusion, considering the possible danger which may arise from inappropriate use of drugs and the costs of therapy, our data suggest that consultation with a specialist would be particularly helpful in patients with headache.