The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review.

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder.

OBJECTIVE: To review the antidepressant efficacy of S-Adenosyl-L-Methionine (SAMe) both in monotherapy and/or in augmentation with antidepressants to better understand its potential role in the treatment of patients with Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). DATA SOURCES: A MEDLINE/PubMed search was carried out by using the following set of keywords: ((SAMe OR SAdenosyl- L-Methionine) AND (major depressive disorder OR depression)). Data Selection and Data Extraction: No language or time restrictions were placed on the electronic searches. Randomized controlled trials and open trials involving humans were here included and analyzed. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. DATA SYNTHESIS: SAMe is an important physiologic compound, playing a central role as precursor molecule in several biochemical reactions. Numerous studies have shown that SAMe may affect the regulation of various critical components of monoaminergic neurotransmission involved in the pathophysiology of MDD. Some findings have suggested its antidepressant efficacy in treating MDD. Several randomized controlled trials have supported that the antidepressant efficacy of SAMe in monotherapy is superior to placebo and tricyclic antidepressants. Recent findings have also demonstrated its efficacy in patients nonresponsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. CONCLUSION: Overall, SAMe is a well-tolerated medication, which may offer considerable advantages as an alternative to antidepressant drugs or as an add-on therapy in the treatment of MDD and TRD. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy of this drug.

Increase in mortality rate in patients with dementia treated with atypical antipsychotics: a cohort study in outpatients in Central Italy.

BACKGROUND: The purpose of this study was to investigate the risk of death among elderly outpatients (>65 years) with a dementia diagnosis treated with atypical antipsychotics. METHODS: We conducted a cohort study of 696 patients who entered the Unit of Alzheimer Evaluation (UVA) of Teramo Hospital in Central Italy, during a 3-year period (January 2007-December 2009). Among these patients, 375 were treated with atypical antipsychotics (quetiapine, risperidone and olanzapine). Data were collected from record files sent to the pharmaceutical service of the hospital. RESULTS: Patients taking atypical antipsychotic medication were associated with a significantly higher mortality rate than patients not taking antipsychotics. The relative risk of death in patients treated with antipsychotics compared to control patients was 2.354 (95% CI 1.704-3.279). The greatest increases in mortality rate occurred close to the last drug supply, and declined exponentially as time passed from the last drug supply in patients who stopped drug assumption. Quetiapine was the most commonly prescribed drug and higher doses of this drug were associated with higher mortality rates. CONCLUSIONS: These results are in line with the April 2005 warning of the Food and Drug Administration (FDA) that among elderly patients with dementia, the treatment of behavioural disorders with atypical antipsychotics is associated with a higher mortality rate. Given the potential risks of mortality with antipsychotics, and since antipsychotic medications may benefit only a minority of patients, new approaches are clearly needed to manage the neuropsychiatric symptoms of dementia.

Treatment of antipsychotic-induced hyperprolactinemia: an update on the role of the dopaminergic receptors D2 partial agonist aripiprazole.

Hyperprolactinemia is an unwanted adverse effect present in several typical and atypical antipsychotics. Aripiprazole is a drug with partial agonist activity at the level of dopamine receptors D2, which may be effective for antipsychotic- induced hyperprolactinemia. Therefore, we analyzed the literature concerning the treatment of antipsychoticinduced hyperprolactinemia with aripiprazole by updating a previous paper written on the same topic. More recent studies were reviewed. They showed that there are two options for the treatment of antipsychotic-induced hyperprolactinemia with aripiprazole. The safest strategy may require the addition of aripiprazole to ongoing treatments, in the case patients had previously responded to antipsychotic drugs and then developed hyperprolactinemia. However, it is advisable to monitor the patients in case relapses and/or side effect, although rare, might occur. Switching drugs should be considered when a patient does not appear to be responding to the previous antipsychotic, thus developing hyperprolactinemia. A cross-taper switch should always be considered, but the risk of a relapse in the disorder may occur more frequently and the patients should be closely monitored. However, limitations must be considered and further studies are needed to definitely elucidate this important issue. Some relevant patents are also described in this review.

Efficacy and safety of long acting injectable atypical antipsychotics: a review.

Schizophrenia is a chronic, severe and recurrent brain disorder that requires continuous, long-term treatment with antipsychotic medication to minimize relapse and provide clinical benefit to patients. For patients with schizophrenia, non-adherence to medication is a major risk factor for relapse and re-hospitalization. Long-acting injectable formulations of second-generation antipsychotics (SGAs-LAIs) provide constant medication delivery and the potential for improved adherence. Currently, three drugs are available for the treatment of schizophrenia, risperidone longacting injectable, olanzapine pamoate and paliperidone palmitate. Several studies have also demonstrated efficacy and safety of such drugs in patients with acute schizophrenia. In the present paper the literature on LAI atypical antipsychotics will be reviewed and practical advice will be given concerning the use of these drugs in the clinical practice.

Update on the adverse effects of clozapine: focus on myocarditis.

Clozapine, an atypical antipsychotic, is a dibenzodiazepine derivative and its therapeutic effects are probably mediated by dopaminergic and serotonergic activity. In accordance to several studies, it appears to be the most effective antipsychotic drug for treatment-resistant schizophrenia. Moreover, clozapine appears to be particularly beneficial in patients with schizophrenia who are suicidal and in those with comorbid substance use disorder. However, despite its efficacy, the general use of clozapine in clinical practice is somewhat limited because of the risk of several serious adverse effects such as agranulocytosis and thromboembolism. Clozapine may be associated with fatal myocarditis and cardiomyopathy in physically healthy young adults. Consequently, the FDA and the drug's manufacturer have strengthened warnings to include that a potentially fatal myocarditis may occur when taking clozapine. In the present paper the literature on clozapine-related myocardis will be reviewed and practical advice will be given concerning the diagnosis and management of such potentially fatal adverse effect.

The Relationships between Cholesterol and Suicide: An Update.

Cholesterol is a core component of the central nervous system, essential for the cell membrane stability and the correct functioning of neurotransmission. It has been observed that cholesterol may be somewhat associated with suicidal behaviours. Therefore, the aim of this paper was to elucidate current facts and views about the role of cholesterol levels in mood disorders. The majority of the studies reviewed in the present paper suggest an interesting relationship between cholesterol (especially lower levels) and suicidality. On the other hand, particularly during the last years, relationships between serum cholesterol and suicidality were doubted on the basis of some recent studies that have not found any correlation. However, the debate on relationships between cholesterol and suicide is open and longitudinal studies on a larger sample of patients are needed to further clarify this important issue.