Francesco Casamassima

Azienda Ospedaliero-Universitaria Pisana, Pisa, Tuscany, Italy

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Publications (19)34.11 Total impact

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    ABSTRACT: Aim. To confirm the efficacy and tolerability of ziprasidone as adjunctive therapy in bipolar patients partially responding to clozapine or with persisting negative symptoms, overweight, or with metabolic syndrome. Methods. Eight patients with psychotic bipolar disorder were tested with the BPRS, the HAM-D, and the CGI at T0 and retested after 2 weeks (T1). Plasma clozapine and norclozapine levels and BMI were tested at T0 and T1. Results. Ziprasidone was well tolerated by all the patients. BPRS and HAM-D scores were reduced in all patients. BMI was reduced in patients with a BMI at T0 higher than 25. Plasma levels of clozapine and norclozapine showed an irregular course.
    ISRN psychiatry. 01/2014; 2014:904829.
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    ABSTRACT: Introduction: Asenapine is a sublingually administered second-generation antipsychotic with proven efficacy for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Its relatively favorable weight and metabolic profile, as well as the lack of appreciable activity at muscarinic cholinergic receptors and the sublingual administration are of clinical interest. Areas covered: This paper comprises a review and commentary regarding the use of sublingual asenapine in the treatment of acute manic and mixed episodes of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration with other medications are provided. Expert opinion: Asenapine displays quick and reliable effects on manic symptoms, very low risk of depressive switches, efficacy on depressive symptoms during manic and mixed episodes, usually good tolerability and continued longer-term efficacy on residual and subthreshold symptoms. The fast-dissolving sublingual route of administration may favor those who have difficulties in swallowing medications. Also, the sublingual administration reduces the risk of overdose when more than the prescribed tablets are swallowed. The relatively low metabolic risk and the lack of anticholinergic side effects contribute to making this medication a useful tool for the treatment of patients with bipolar disorder.
    Expert Opinion on Pharmacotherapy 01/2013; · 2.86 Impact Factor
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    ABSTRACT: We present the history of four bipolar patients who developed neuroleptic malignant syndrome (NMS) after antipsychotic treatment, focusing on the relationship between NMS and catatonia. In all cases, the administration of antipsychotics has been suspended as soon as fever and autonomic disturbances occurred. A supportive therapy was initiated to stabilize general conditions, then every patient started electroconvulsive therapy (ECT) in combination with benzodiazepines (BDZ). The risk of complications was reduced by the quick adoption of supportive care, whereas the combination of ECT and BDZ was effective in resolving the clinical picture. These cases may provide further support to the hypothesis that catatonia and NMS are disorders pertaining to the same spectrum of illness because the onset or exacerbation of catatonic symptoms coincided with the administration of antipsychotics. Our experience confirms the efficacy and safety of ECT in combination with BDZ as treatment of NMS and residual catatonia.
    The Journal of nervous and mental disease 01/2013; 201(1):36-42. · 1.77 Impact Factor
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    ABSTRACT: INTRODUCTION: several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission. AREAS COVERED: this paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice. EXPERT OPINION: aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic-maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.
    Expert Opinion on Pharmacotherapy 02/2011; 12(3):473-88. · 2.86 Impact Factor
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    ABSTRACT: Emerging evidence from genome-wide association studies (GWAS) support the association of polymorphisms in the alpha 1C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with bipolar disorder. These studies extend a rich prior literature implicating dysfunction of L-type calcium channels (LTCCs) in the pathophysiology of neuropsychiatric disorders. Moreover, calcium channel blockers reduce Ca(2+) flux by binding to the α1 subunit of the LTCC and are used extensively for treating hypertension, preventing angina, cardiac arrhythmias and stroke. Calcium channel blockers have also been studied clinically in psychiatric conditions such as mood disorders and substance abuse/dependence, yielding conflicting results. In this review, we begin with a summary of LTCC pharmacology. For each category of disorder, this article then provides a review of animal and human data. In particular, we extensively focus on animal models of depression and clinical trials in mood disorders and substance abuse/dependence. Through examining rationale and study design of published clinical trials, we provide some of the possible reasons why we still do not have definitive evidence of efficacy of calcium-channel antagonists for mood disorders. Refinement of genetic results and target phenotypes, enrollment of adequate sample sizes in clinical trials and progress in physiologic and pharmacologic studies to synthesize tissue and isoform specific calcium channel antagonists, are all future challenges of research in this promising field. © 2010 Wiley-Liss, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 09/2010; 153B(8):1373-90. · 3.23 Impact Factor
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    ABSTRACT: Neuroleptic malignant syndrome (NMS) represents an iatrogenic form of malignant catatonia, and simple catatonia has been shown to predispose to NMS. The authors present the case of a bipolar patient with catatonic features who developed NMS after receiving haloperidol. Supportive therapy, including rehydration, electrolyte restoration, and blood pressure aids were given, together with antipyretics, antibiotics, and anticoagulants. The patient was also started on bromocriptine and diazepam. Supportive care, diazepam, and dopamine agonists yielded only partial benefit. However, switching from diazepam to lorazepam, in combination with electroconvulsive therapy (ECT) and a long-acting dopamine agonist led to the resolution of NMS. This case sheds further light on the relationship between catatonia and NMS. As noted in the literature, ECT in combination with lorazepam proved to be safe and effective for NMS.
    Psychosomatics 07/2010; 51(4):349-54. · 1.73 Impact Factor
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    ABSTRACT: It is very rare for patients with bipolar disorder to have a single episode of mania or depression over a lifetime and the vast majority of these individuals need long-term prophylactic/maintenance treatment. However, treatment nonadherence is a major issue for close to half of subjects with bipolar disorder who are prescribed medications. Risperidone long-acting injection (LAI) has proven efficacious for the maintenance phase of bipolar disorder and may mitigate the problem of nonadherence in the substantial group of patients for whom this is a significant concern. This paper comprises a review and commentary regarding the use of risperidone LAI in bipolar disorder. The reader will gain an understanding regarding the risks and benefits of risperidone LAI in bipolar disorder. We review the available evidence and discuss the strengths and weaknesses of published studies, providing an opinion about the clinical usefulness of risperidone LAI as well as suggestions for future research. The use of risperidone LAI, through improved adherence, has the potential to ameliorate the course of bipolar disorder.
    Expert Opinion on Pharmacotherapy 07/2010; 11(10):1727-40. · 2.86 Impact Factor
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    ABSTRACT: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1+/-12.0 and 5.4+/-0.5, respectively, were treated with clozapine (mean dose 292.9+/-220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 +/- 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. Total scores at BPRS decreased significantly (from 59.1+/-12.0 to 51.1+/-15.6, p=0.007) after aripirazole augmentation. In particular, the factors "thought disorder" (from 10.4+/-4.4 to 9.0+/-4.5, p=.047) and "anergia" (from 10.0+/-2.7 to 8.0+/-2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation.
    Clinical Practice and Epidemiology in Mental Health 01/2010; 6:30-5.
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    ABSTRACT: Some studies suggest that depressive subtypes, defined by groups of symptoms, have predictive or diagnostic utility. These studies make the implicit assumption of stability of symptoms across episodes in mood disorders, which has rarely been investigated. We examined prospective data from a cohort of 3,750 individuals with bipolar I or II disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder study, selecting a subset of individuals who experienced two depressive episodes during up to two years of follow-up. Across-episode association of individual depressive or hypomanic/mixed symptoms was examined using the weighted kappa measure of agreement as well as logistic regression. A total of 583 subjects experienced two prospectively observed depressive episodes, with 149 of those subjects experiencing a third. Greatest evidence of stability was observed for neurovegetative features, suicidality, and guilt/rumination. Loss of interest and fatigue were not consistent across episodes. Structural equation modeling suggested that the dimensional structure of symptoms was not invariant across episodes. While the overall dimensional structure of depressive symptoms lacks temporal stability, individual symptoms including suicidality, mood, psychomotor, and neurovegetative symptoms are stable across major depressive episodes in bipolar disorder and should be considered in future investigations of course and pathophysiology in bipolar disorder.
    Bipolar Disorders 12/2009; 11(8):867-75. · 4.62 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Journal of clinical psychopharmacology 11/2009; 29(5):504-6. · 5.09 Impact Factor
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    ABSTRACT: Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 05/2009; 153B(1):303-9. · 3.23 Impact Factor
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    ABSTRACT: We report a case of a patient with Fahr disease affected by bipolar disorder type I with psychotic symptoms. The complex clinical picture, characterized by both neurological and psychiatric symptoms, proved to be partially or completely resistant to several pharmacological trials. On the contrary, a marked improvement of clinical picture occurred after a cycle of 10 sessions of electroconvulsive therapy, followed by a complete and sustained resolution of mood, cognitive, motor, and behavioral symptoms during the next 4 years.
    The journal of ECT 03/2009; 25(3):213-5. · 1.19 Impact Factor
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    ABSTRACT: Although manic episodes in older adults are not rare, little published data exist on late-life manic episodes. Resistance to treatment and concomitant neurological lesions are frequent correlates of elderly mania. The aim of this study was to investigate the prevalence of hospitalizations due to mania in patients older than 64 years through a period of 5 years in an Italian public psychiatric ward. Moreover, we aimed at describing clinical presentation of elderly manic episodes. A retrospective chart review was conducted in order to describe clinical presentation of 20 elderly patients hospitalized for manic episode; moreover, we compared age at onset, the presence of family history for mood disorders, psychosis and irritability between the elderly group and a matched group of 20 younger manic inpatients. Seven percent of the whole inpatient elderly people suffered from mania. Half of those patients had a mood disorder age at onset after 50 years and 5 patients were at their first manic episode. Geriatric- and adulthood mania showed similar clinical presentation but younger people had more frequently a mood disorders family history. Half of our older manic inpatients consisted of "classic" bipolar patients with an extension of clinical manifestations into later life; the other half of our sample was heterogeneous, even though it was not possible to identify clearly which patients may have had vascular lesions related to the onset of mania.
    Clinical Practice and Epidemiology in Mental Health 02/2008; 4:22.
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    ABSTRACT: To explore gender differences in bipolar I disorder, we compared the longitudinal treatment outcome and baseline demographic and clinical characteristics of 27 male and 45 female adult subjects who were treated for an acute affective episode and longitudinally followed for a period of up to 48 weeks. Females were more likely to report a history of suicidal gestures and a comorbid panic disorder; males were more likely to present with a comorbid obsessive-compulsive disorder, and there was a trend for a more frequent history of alcohol or substance abuse. No significant differences were found between the genders for the time to remission from the index episode, number of recurrences, and time spent with any clinical or subclinical mood symptom during the 48 weeks of maintenance treatment. Although differences may exist between bipolar I male and female subjects, prospective course does not seem to reveal differences in a 48-week period, at least when similar treatment strategies are adopted.
    Journal of Nervous & Mental Disease 02/2007; 195(1):93-6. · 1.84 Impact Factor
  • Drug Safety 10/2006; 29(10). · 2.62 Impact Factor
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    302 Clinical Neuropsychiatry. 01/2006; 3(5).
  • Drug Safety. 01/2006; 29(10):911-1010.
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    ABSTRACT: Summary Aims Use of combined antipsychotics for patients with psychotic disorders with incomplete response to treatment is common practice in psychiatry. Clozapine is the oldest atyp- ical antipsychotic and is considered to be superior to other such drugs for treating therapy-resistant and chronic schizophrenia. However, treatment is sometimes inef- fective even when the dosage of clozapine is adequate. Furthermore, not all patients tolerate the required dose because of central nervous system and gastrointestinal side- effects. Aripiprazole, a new antipsychotic with partially agonistic activity at both the D2 and serotonin 5-HT1A receptors and antagonistic activity at the 5-HT2A receptor, has proven to be effective, safe, and well tolerated in the treatment of both positive and negative symptoms of schizophrenia or schizoaffective disorders. Clozapine is mainly metabolized via cytochrome P450 1A2, less so via cytochromes P450 2D6 and P450 3A4, whereas aripiprazole is metabolized via cytochrome P450 3A4 and 2D6. There- fore, the different metabolic pathways of the two drugs may represent a benefit in terms of interactions and side-effects. Aripiprazole seems to be particularly suitable for augmenting clozapine, especially when negative symptoms predominate in the clinical picture. To date, there are only a few reports on this subject in the published literature.
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    ABSTRACT: The authors present the cases of three bipolar patients who developed Neuroleptic Malignant Syndrome (NMS) after antipsychotic treatment, both typical and atypical, focusing on relationship between NMS and catatonia. In all three cases, administration of antipsychotics has been stopped at once, when fever and autonomic disturbances occurred. A supportive therapy (including rehydration, electrolyte restoration and blood pressure aids, together with antipyretics, antibiotics and anticoagulants) was prescribed in order to stabilize general conditions. Every patient started then Electroconvulsive Therapy (ECT) in combination with benzodiazepines. High risk of complications and lethal outcome, associated with NMS, were successfully reduced by the tempestive adoption of a supportive care, while combination between ECT and BDZ was effective in resolution of clinical picture. DISCUSSIONS; These cases may provide further evidences about hypothesis of catatonia and NMS as disorders on the same spectrum. In one patient, NMS occurred overlapping with a previous catatonic state, while two others exhibited catatonic features after resolution of NMS. However, catatonic symptoms arose or worsened with administration of antipsychotics, supporting hypothesis of neuroleptic-induced catatonia as a step of progressive development of NMS. Our experience also confirms efficacy and safety of ECT in combination with BDZ as treatment of NMS and residual catatonia.
    Rivista di Psichiatria 47(2):178-85. · 0.20 Impact Factor