Long-acting antipsychotic medications

Antipsychotic medicines are the cornerstone pharmacotherapy for patients with psychotic disorders. Early and continuous management of psychoses improves the quality of life, decreases hospitalization and reduces medical costs. However, many psychotic patients are not fully compliant with treatment, and thus they more often experience a relapsing course with a suboptimal clinical outcome. Long-term parenteral antipsychotic agents may improve compliance by offering clear evidence of medication non-compliance and documented drug administration monitoring. Using injection therapy might be especially beneficial to poorly compliant individuals with their first-psychotic episode and those with severe psychopathology or comorbid substance abuse. The availability of five different antipsychotic drug depot medications offers diverse treatment options which can be individualized for each case.     

Increased cardiovascular risk with second-generation antipsychotic agent switches.

OBJECTIVE: To model the risk of long-term, adverse cardiovascular events after switching from one second-generation antipsychotic medication (SGA) to another in patients with schizophrenia or schizoaffective disorder. DATA SOURCES: PubMed from 1985 to 2004 using the search terms atypical antipsychotics, obesity, weight, diabetes mellitus, dyslipidemia, hypercholesterolemia, lipids, second generation antipsychotics, antipsychotic agents, schizophrenia, metabolic syndrome, cardiovascular disease, and cardiovascular risk factors. STUDY SELECTION: By the authors. DATA EXTRACTION: By the authors. DATA SYNTHESIS: The selection of an SGA for an individual patient should be primarily based upon its therapeutic effectiveness. However, when two medications are clinically equivalent with respect to treatment outcomes, other important consequences of the medication choice should be considered. Depending upon the type of SGA switch, the risk of an adverse cardiovascular event may be lower, as when olanzapine is switched to risperidone, or may increase by as much as 33%, as when risperidone is switched to olanzapine or clozapine. CONCLUSION: Cardiovascular risk likely differs depending upon SGA choice, but limited data make it difficult to predict the metabolic changes associated with switching. Prospective controlled studies are needed to describe the cardiovascular consequences of switching among the antipsychotic agents so that evidence-based strategies can be developed for selection of the optimal SGA.     

Cost-effectiveness of atypical antipsychotic medications versus conventional medication

For almost 50 years, typical antipsychotics were the mainstay of pharmacological treatment for schizophrenia. However, during the last decade, the widespread use of expensive atypical antipsychotic medications has led to a dramatic increase in the proportion of the direct costs of schizophrenia being allocated for medications. Although there is evidence that the atypical antipsychotic clozapine may lead to cost savings in patients with refractory schizophrenia, the cost-effectiveness of the other atypical antipsychotics remains in question. Therefore, long-term randomised, prospective cost-effectiveness studies that compared an atypical to a typical antipsychotic have been reviewed in this paper. There were serious methodological problems with all the studies. In general, those that were based on efficacy trials showed an advantage for atypicals, whereas those based on effectiveness studies found the opposite. It seems that, to the extent that studies mimic real world conditions, they fail to support the cost-effectiveness of the atypical antipsychotics.     

Cost-effectiveness of atypical antipsychotic medications versus conventional medication

For almost 50 years, typical antipsychotics were the mainstay of pharmacological treatment for schizophrenia. However, during the last decade, the widespread use of expensive atypical antipsychotic medications has led to a dramatic increase in the proportion of the direct costs of schizophrenia being allocated for medications. Although there is evidence that the atypical antipsychotic clozapine may lead to cost savings in patients with refractory schizophrenia, the cost-effectiveness of the other atypical antipsychotics remains in question. Therefore, long-term randomised, prospective cost-effectiveness studies that compared an atypical to a typical antipsychotic have been reviewed in this paper. There were serious methodological problems with all the studies. In general, those that were based on efficacy trials showed an advantage for atypicals, whereas those based on effectiveness studies found the opposite. It seems that, to the extent that studies mimic real world conditions, they fail to support the cost-effectiveness of the atypical antipsychotics.     

Effects of antipsychotic medications on sleep in schizophrenia

Schizophrenia is often accompanied by sleep problems. Evidence exists that these sleep difficulties have significant effects on individuals with this disorder. The mainstay of treatment for this condition is the administration of medications that have effects on neurotransmitter systems, which play an important role in sleep-wake function, including histamine, acetylcholine, serotonin, norepinephrine and dopamine. Little systematic attention, however, has been paid to how the sleep effects of these agents might play a role in the course of treatment, function and quality of life of schizophrenia patients. Schizophrenia medications can improve sleep problems and reverse the sleep architectural derangements that are common among patients with schizophrenia and, therefore, have the potential to improve the quality of life and functional capacity of the patient. Conversely, some sleep-wake effects of these medications can impair patient function and quality of life. In this study, we review the effects of schizophrenia medications and discuss their relevance to optimizing the clinical treatment of people with schizophrenia with regard to sleep-wake function.     

The genetics of vascular incidents associated with second-generation antipsychotic administration

Second-generation antipsychotics (SGA) have been associated with risk of stroke in elderly patients, but the molecular and genetic background under this association has been poorly investigated. The aim of the present study was to prioritize a list of genes with an SGA altered expression in order to characterize the genetic background of the SGA-associated stroke risk. Genes with evidence of an altered expression after SGA treatments in genome-wide investigations, both in animals and men, were identified. The Genetic Association Database (GAD) served to verify which of these genes had a proven positive association with an increased stroke risk, and alongwith it each evidence was tested and recorded. Seven hundred and forty five genes had evidence of a change of their expression profile after SGA administration in various studies. Nine out of them have also been significantly related to an increased strokes risk. We identified and described nine genes as potential candidates for future genetic studies aimed at identifying the genetic background of the SGA-related stroke risk. Further, we identify the molecular pathways in which these genes operate in order to provide a molecular framework to understand on which basis SGA may enhance the risk for stroke.     

Priapism associated with typical and atypical antipsychotic medications

Priapism is a urologic emergency, and a urologic consultation should be obtained as early as possible. Its etiologies are numerous and diverse. Patients who use antipsychotic drugs should be informed about the complications of priapism, especially those patients with a history of prolonged erections associated with other alpha-adrenergic blocking agents or a history of sickle cell disease. If antipsychotic medication is considered to be needed in the treatment of patients with a history of priapism, physicians should select a drug with a low peripheral alpha-adrenergic blocking property. Physicians should be aware of this rare but potentially serious complication of antipsychotic drugs. Early intervention and appropriate treatment are essential to prevent permanent impotence and other serious complications.     

Critical review of mechanisms of action of second-generation antipsychotic drugs]

The advent of second-generation antipsychotics (SGA) in the wake of clozapine, the prototype for atypical antipsychotics, represents a breakthrough in the pharmacologic treatment of schizophrenia. There is growing evidence that most of the SGA can offer advantages over first-generation antipsychotics within the effective dose range, such as improvement in negative symptoms and cognitive impairment, fewer extrapyramidal side effects, and less hyperprolactinemia. However, the essential pharmacological properties that confer the different therapeutic effects of the SGA have remained elusive, and the search for novel antipsychotics without dopamine D2 receptor antagonism has not been successful to date, though numerous development strategies continue to be pursued, guided by various pathophysiologic hypotheses. This article provides a brief review and critique of the current predominant theories of mechanisms of action of SGA, including the serotonin-dopamine hypothesis, the "fast-off-D2 theory," and regional specificity. In addition, it focuses on the roles of N-methyl-D-aspartate receptors, dopamine DI receptors, and alpha-adrenergic receptors in the pharmacology of SGA.     

Priapism associated with atypical antipsychotic medications: a review

Priapism defined as persistent, painful and prolonged penile erection, was previously thought to be associated only with the use of the older, conventional first generation or typical antipsychotic medications as well as some other medications, notably, trazodone. The mechanism of priapism associated with antipsychotics is not clear but is thought to be related to alpha-adrenergic blockage that is mediated by the alpha receptors in the corpora cavernosa of the penis. Atypical antipsychotics, also known as second-generation antipsychotics, owing to their favorable side effect profile, are being prescribed with increasing frequency and are not as frequently considered to cause priapism. Some case reports reporting this side effect with their use, however, are found. Pubmed and Ovid databases were searched to obtain all articles and case reports of antipsychotic drug-induced priapism. Key search words included 'priapism', 'antipsychotics' and 'drug-induced priapism'. References of all identified studies were also reviewed. A total of 50 publications were obtained. Most of the atypical antipsychotics have been reported to cause priapism. These cases have occurred in patients shortly after having been started on the antipsychotic medications as well as in those who have been on them for an extended period of time without modification in dosage, and have also occurred sometimes, with the addition of another antipsychotic, lithium or serotonin-specific reuptake inhibitor. Priapism has been documented with nearly all the atypical antipsychotic medications. It is, however, a rarely reported side effect and therefore, underappreciated. Priapism can cause irreversible erectile dysfunction and is a urologic emergency. Clinicians should monitor patients on these medications for this rare, yet significant side effect. Furthermore, caution must be used when adding new drugs to the regimen and patients should be closely monitored for this side effect. Educating patients about the risk of developing priapism would help increase awareness of the side effect and promote early reporting thereby, decreasing long-term morbidity.     

A review of atypical antipsychotic medications for posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) can be a chronic and disabling illness with a limited response to antidepressant treatment, particularly in the case of combat-induced PTSD. The purpose of this study is to review randomized controlled and open-label trials of atypical antipsychotics for the treatment of PTSD. We conducted PUBMED and PILOTS database searches for clinical trials of atypical antipsychotic medications for PTSD in May 2010. Eighteen clinical trials (10 double-blind placebo-controlled, eight open-label) of atypical antipsychotics for PTSD were found and reviewed. Effect sizes of double-blind placebo-controlled trials were small, but were positive for risperidone and quetiapine. Intrusive and hypervigilance symptom subscales showed the most improvement. We concluded that atypical antipsychotic medications have a modest benefit for the treatment of PTSD. Larger randomized controlled trials are needed to clarify the potential utility of these medications in the treatment of PTSD and more rigorous examination of metabolic side effects is warranted.     

Source monitoring improvement in patients with schizophrenia receiving antipsychotic medications

Rationale The absence of a relationship between cognitive deficit treatment response and positive symptom treatment response is often assumed, and few data have shed light on this issue. Most of these data have been collected using standard neuropsychological measures, which are ill-designed to assess the types of neurocognitive disturbances associated with psychotic symptoms. This study investigates the effect of treatment on source monitoring performance and its relation to the reduction of certain psychotic symptoms associated with the inability to identify self-generated mental events, known as "autonoetic agnosia". Objectives To determine whether risperidone, olanzapine, and haloperidol were differentially effective in reducing autonoetic agnosia and whether changes in this aspect of cognition were related to reduction of specific symptoms of psychosis. Methods From a cohort of 49 patients diagnosed with schizophrenia by DSM-IV criteria and randomly assigned to double-blind treatment with risperidone, olanzapine, or haloperidol, 16 patients were identified with symptoms believed to reflect autonoetic agnosia ("target symptoms") as assessed with the Schneiderian Symptom Rating Scale, and then evaluated during a baseline period, and then at 1, 2, and 3 weeks. Autonoetic agnosia was assessed as the ability of a patient to distinguish self-generated words from both experimenter-generated words and pictorially presented words. Results Analysis of patients from all treatment groups found a significant reduction in the number of "target" Schneiderian symptoms. Discrimination for items from the self-generated and heard sources significantly improved with treatment, as did the number of self-generated items that patients remembered as coming from the heard source ("self-hear errors"). The correlation between improvement in recognition of self-generated items and reduction in target Schneiderian symptoms after 2 weeks of treatment suggested a modest relationship between symptom improvement and changes in autonoetic agnosia. Conclusions While the differences between medications were not statistically significant, antipsychotic medication in general was associated with improvements in symptoms and cognitive deficits that may underlie autonoetic agnosia. Improvement of autonoetic agnosia was a weak predictor of positive symptom improvement in a limited sample.     

Switching antipsychotic medications: general recommendations and switching to amisulpride

As more and more novel antipsychotic agents are introduced, the need for practical guidelines on switching these medications is becoming increasingly important. Indications for a switch include situations where the patient or his family/caregiver requests a change in medication, where the patient cannot tolerate current treatment, where they have comorbid physical or psychiatric conditions or where they have achieved only a partial remission, are refractory to treatment or have relapsed. Cross-tapering is generally the most acceptable method of switching, although abrupt withdrawal may be necessary in some cases, such as when a patient develops a severe or acute reaction to their current treatment. Possible problems of switching include the risk of discontinuation reactions and the re-emergence of psychotic symptoms. The pharmacological profile of amisulpride means it has a relatively low potential for interactions with other drugs and may be started while discontinuing the previous antipsychotic. It should be started at the target dose for the patient's current symptoms. A retrospective questionnaire among 60 patients switching to amisulpride treatment was undertaken to identify the characteristics of patients switching antipsychotics and their reasons. Patients were switched from a variety of antipsychotic medications, both traditional (42% of patients) and atypical (58%). Most patients (87%) had at least two reasons for changing medication, with lack of efficacy, adverse events and treatment optimisation before reintegration being the most common. Contrary to recommendations, 89% of patients were switched abruptly between medications. A total of 62% of patients received amisulpride doses in the range 400-800 mg/day and most (72%) required no dose adjustment. The great majority of patients (87%) switched to amisulpride without problems.