Adverse Effects Of Antipsychotics Research Articles

Adverse reactions to antipsychotics in Parkinson disease: an analysis of the Spanish pharmacovigilance database.

Although antipsychotics are well known for causing a plethora of adverse drug reactions (ADRs), the main concern when used to treat psychosis in Parkinson disease (PD) has traditionally been motor function worsening. The limited number of patients included in clinical trials contributes to underreport less common ADR. The aims of this study were to describe ADR to antipsychotics occurring in patients with PD notified to the Spanish Pharmacovigilance System and to contrast them with published reports. All notifications from the Spanish Pharmacovigilance System for the last 30 years (1984-2014) where an antipsychotic was considered suspicious of the ADR in patients who were also on dopaminergic therapy were reviewed. In addition, a systematic search of MEDLINE (1966-2014) was conducted with the following Medical Subject Headings (MeSH) terms: "Parkinson disease" and "antipsychotic agents" or "psychotic disorders" and "drug-related side effects" or "adverse reactions." Forty-four notifications were selected for evaluation. Quetiapine was the most frequently implicated drug since 2002, and previously clozapine was the drug implied in higher number of notifications. The most severe ADR was neuroleptic malignant syndrome, which was described in 5 patients (3 cases related to quetiapine, one to haloperidol, and another to olanzapine). Some previously unreported ADRs caused by antipsychotic drugs in patients with PD have been described for the first time in this study, although there are in general well-known antipsychotic adverse effects. It is remarkable that some notifications involve the use of drugs not recommended in these patients.

Long-term Lurasidone Treatment is Not Associated with Clinically Significant Elevations of Prolactin- or Hyperprolactinaemia-related Adverse Events: a Post-HOC Analysis

Introduction Elevation of prolactin level is a known adverse effect of antipsychotics. Long-standing hyperprolactinaemia may inhibit reproductive function by impairing gonadal steroidogenesis and is associated with a number of adverse effects such as galactorrhoea, amenorrhoea, gynecomastia, impotence and decreased bone mineral density. Lurasidone is a recently approved atypical antipsychotic agent for the treatment of schizophrenia. Aims/Objectives To compare the incidence of treatment-emergent adverse events (TEAEs) related to hyperprolactinaemia in patients treated with lurasidone or active comparators. Methods Pooled data from two 52-week studies that evaluated the long-term safety and efficacy of lurasidone compared with quetiapine XR or risperidone in patients with schizophrenia were reviewed post-hoc for prolactin levels and TEAEs considered to be related to hyperprolactinaemia. Results Prolactin levels decreased marginally in the lurasidone group (median -8.00 pmol/L, N=624) and quetiapine XR group (median -17.39 pmol/L, N=85), and increased in the risperidone group (median 385.00 pmol/L, N=199) (LOCF). The incidence of markedly abnormally high prolactin values (≥5× upper limit of normal) was 2.0%, 1.4% and 4.0% in the three groups, respectively. The hyperprolactinaemia-related TEAEs breast mass, gynecomastia, breast enlargement, breast tenderness, hypogonadism, infertility, pituitary tumors and mammary gland tumors were absent from all groups. Low rates (≤2.5%) of galactorrhoea, amenorrhoea and erectile dysfunction were seen in the lurasidone and risperidone groups, while no TEAEs were recorded in the quetiapine XR group. Conclusions This post-hoc review shows that long-term treatment with lurasidone was not associated with a clinically significant increase in prolactin levels and the incidence of associated TEAEs was low.

"First do no harm." A systematic review of the prevalence and management of antipsychotic adverse effects.

We aim to identify the prevalence and management strategies of nine clinically important categories of antipsychotic adverse effects, namely: extrapyramidal symptoms; sedation; weight gain; type II diabetes; hyperprolactinaemia; metabolic syndrome, dyslipidaemia; sexual dysfunction; and cardiovascular effects. Antipsychotic drugs are widely prescribed for schizophrenia and other mental disorders. The adverse effects of antipsychotics are common, with a potential negative impact on adherence and engagement. Despite this, the scientific study of the prevalence or management of adverse antipsychotic effects is a neglected area. A systematic review was undertaken using pre-defined search criteria and three databases, with hand searching of citations and references. Inclusion was agreed on by two independent researchers after review of abstracts or full text. Quality analysis of included studies was conducted using pre-agreed criteria. In total, 53 studies met inclusion criteria, revealing the following: (1) antipsychotic polypharmacy was associated with increased frequency of adverse effects, and (2) a longer duration of treatment is associated with greater severity (e.g. higher BMI); (3) clozapine was more strongly associated with metabolic disturbance than other antipsychotics in three studies and olanzapine was associated with the most weight gain in three studies; (4) hyperprolactinaemia was more common in women than men, but 50% men noted sexual dysfunction versus 25-50% in women; (5) despite clinical guideline recommendations there is a low rate of baseline testing for lipids and glucose; and (6) seven studies described adverse effect management strategies, but only two examined their efficacy - one found a significant reduction in weight with non-pharmacological group therapy and the other found a significant reduction in dyslipidaemia with statins. Antipsychotic adverse effects are diverse and frequently experienced, but are not often systematically assessed. There is a need for further scientific study concerning the management of these side effects.

P.1.a.013 Acute onset schizophrenia: adenosine receptors polymorphisms – correlation with psychopathology and adverse effects of antipsychotics

P.1.a.013 Acute onset schizophrenia: adenosine receptors polymorphisms – correlation with psychopathology and adverse effects of antipsychotics

Mechanism of Action of Antipsychotic Medications

Article AbstractA variety of antipsychotic medications exist for treating patients with schizophrenia. Knowledge of pharmacokinetics (the body's effect on the drug) and pharmacodynamics (the drug's effect on the body) can help clinicians select antipsychotics and make timely dose adjustments to improve patient outcomes. Currently, the only known effective mechanism to reduce positive psychotic symptoms is dopamine D2 blockade. However, several relevant dopamine pathways exist, and increasingly sophisticated insight into the role of subsections of the striatum has helped link dopamine D2 blockade in specific pathways to the beneficial and adverse effects of antipsychotics, including extrapyramidal side effects (EPS) and secondary negative or cognitive effects. Antipsychotics with low D2 affinity (partial D2 agonism) that modulate dopamine transmission via blockade of histamine or cholinergic receptors or that bind more tightly to serotonin 5-HT2A receptors than D2 receptors generally have less risk for EPS. However, some of the mechanisms that balance dopamine tone can be associated with sedation, central and peripheral anticholinergic effects, weight gain and metabolic abnormalities. Thus, treatment selection needs to be individualized based on the pharmacokinetic and pharmacodynamic profiles of available antipsychotics as well as their effects in a given patient with past treatment response patterns, comorbidities, and preferences. Importantly, new medications with either additional or exclusive nondopaminergic pharmacologic mechanisms need to be developed that can address not only positive symptoms of schizophrenia but also negative and cognitive symptoms, which do not appear to be primarily related to dopamine dysfunction.See the entire activity.

Adverse effects of antipsychotics on micro-vascular endothelial cells of the human blood–brain barrier

Although the mechanisms of action of antipsychotics (APs) on neuronal function are well understood, very little is known about their effects on cells of the blood–brain barrier (BBB); one function of which is to limit the access of these amphiphilic compounds to the central nervous system. To address this question we have investigated the cytological and functional effects of four APs: chlorpromazine (CLP), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ), at concentrations typical of high therapeutic dosage on a human brain microvascular endothelial cell (HBMEC) model of the BBB. At ~10µM all four APs impaired the ability of HBMECs to reduce MTT which was followed by decreased Trypan blue exclusion and increased Lactate dehydrogenase release. These effects were associated with oxidative stress which was partly reversed by incubation in 10mM glutathione. At their EC50 concentrations for MTT reduction, all four APs disrupted cellular ultrastructure and morphology. HAL, CPZ and CLZ increased Caspase -3, -8 and -9 activity, chromatin condensation and fragmentation, data indicative of apoptosis. These events were associated with decreased transcytosis of Evans blue and increased transendothelial potential difference and electrical resistance of this BBB model. These findings suggest that at high therapeutic concentrations, CPZ and CLZ are likely to incur cytoxic effects and apoptosis of BBB endothelia with an impairment of barrier functionality. Such events may underlie the aetiology of neuroleptic associated cerebral oedema and neuroleptic malignant syndrome.

SENTIA: a systematic online monitoring registry for children and adolescents treated with antipsychotics.

IntroductionDespite drastic increases in antipsychotic prescribing in youth, data are still limited regarding their safety in this vulnerable population, necessitating additional tools for capturing long-term, real world data.MethodsWe present SENTIA (SafEty of NeurolepTics in Infancy and Adolescence; https://SENTIA.es), an online registry created in 2010 to track antipsychotic adverse effects in Spanish youth <18 years old currently taking or initiating with any antipsychotic treatment. SENTIA collects information on sociodemographic, diagnostic and treatment characteristics, past personal medical/psychiatric history, healthy lifestyle habits and treatment adherence. Additionally, efficacy and adverse effect data are recorded including the Children’s Global Assessment Scale; Clinical Global Impressions scale for Severity and Improvement, the Safety Monitoring Uniform Report Form, Simpson-Angus Scale, Abnormal Involuntary Movement Scale, vital signs, blood pressure, and EKG. Finally, fasting blood is drawn for hematology, electrolytes, renal, liver and thyroid function, glucose, insulin, lipid, prolactin and sex hormone levels. Initially, a diagnostic interview and several psychopathology scales were also included. Patients are assessed regularly and followed even beyond stopping antipsychotics.ResultsSince 01/17/2011, 85 youth (11.5 ± 2.9 (range = 4-17) years old, 70.6% male) have been included at one inaugural center. After a mean duration of 17 ± 11 (range = 1-34) months, 78.8% are still actively followed. For feasibility reasons, the diagnostic interview and detailed psychopathology scales were dropped. The remaining data can be entered in <30 minutes. Several additional centers are currently being added to SENTIA.ConclusionsImplementation of a systematic online pharmacovigilance system for antipsychotic adverse effects in youth is feasible and promises to generate important information.

Antipsychotics for acute and chronic pain in adults.

This is an updated version of the original Cochrane review published in Issue 4, 2008. The role of antipsychotics as adjuvant analgesics is a subject of longstanding controversy. Neuroleptanalgesia (that is a state of quiescence, altered awareness, and analgesia produced by a combination of taking an opioid analgesic and an antipsychotic), an established term for the management of acute pain, was shown to negatively influence disease course and total mortality in unstable angina patients. Nevertheless, antipsychotics are used to treat chronic pain (for example chronic headache, fibromyalgia and diabetic neuropathia). With atypical antipsychotics, a new class of antipsychotics, both fewer extrapyramidal side effects and additional benefits may be available. To assess the analgesic efficacy and adverse effects of antipsychotics in acute or chronic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, and EMBASE in October 2011 and January 2013. Randomised controlled trials (RCTs) of adults prescribed any dose of an oral antipsychotic for acute or chronic pain, where subjective pain assessment was described as either the primary or a secondary outcome, were included in this review. Data were extracted by two independent review authors, and results were compared for differences. Discrepancies were resolved by discussion. All trials were quality scored according to the methods set out in section six of the Cochrane Handbook for Systematic Reviews of Interventions. A total of 770 participants were involved in the 11 included studies. Data from five included randomised double-blind studies showed beneficial effects of antipsychotics in the treatment of acute and chronic pain. Quantitative analysis of these studies showed a significant reduction of mean pain intensity after administration of the antipsychotic compared to placebo or another active compound, weighted mean difference (WMD) -1.78 (95% CI -2.71 to -0.85) for the continuous data; and relative risk (RR) 0.43 (95% CI 0.25 to 0.73), number needed to treat to benefit (NNT) 2.6 for the dichotomous data. Nevertheless, the test for heterogeneity was significant for both the continuous data (P = 0.0007) and the dichotomous data (P = 0.04). Obviously this makes the calculated NNT less reliable and caution is warranted when interpreting these results.The most frequently reported adverse effects were extrapyramidal (that is involuntary movements, parkinsonism and akathisia) and sedating effects. The recent search found five new studies which were all excluded, so the review remains the same as previously.Antipsychotics might be used as an add-on therapy in the treatment of painful conditions. Nevertheless, extrapyramidal and sedating side effects have to be considered before using antipsychotics for treating painful conditions.Results for antipsychotics in the treatment of different painful conditions are mixed and most sample sizes in the reviewed RCTs are small. Further studies on atypical antipsychotics in larger double-blind placebo-controlled studies that include standardised pain assessment and documentation are warranted.

Addressing Barriers to Using Long-Acting Injectable Antipsychotics and Appropriately Monitoring Antipsychotic Adverse Effects

Addressing Barriers to Using Long-Acting Injectable Antipsychotics and Appropriately Monitoring Antipsychotic Adverse Effects

Antipsychotics can be withdrawn from many older people with dementia, though caution is needed for people with more severe neuropsychiatric symptoms

Question: Is the withdrawal of antipsychotic medication in older people with dementia and neuropsychiatric symptoms (NPS) feasible, safe and effective? Outcomes: Primary outcomes: success of withdrawal strategy, defined as remaining...

Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis

Hyperprolactinemia is frequent in patients with schizophrenic psychoses. It is usually regarded as an adverse effect of antipsychotics but has recently also been shown in patients without antipsychotic medication. Our objective was to test whether hyperprolactinemia occurs in antipsychotic-naive first-episode patients (FEPs). In the framework of the European First Episode Schizophrenia Trial (EUFEST), 249 out of 498 FEPs were eligible for this study, of whom 74 were antipsychotic naive. All patients were investigated regarding their serum prolactin levels with immunoassays standardized against the 3rd International Reference Standard 84/500. Twenty-nine (39%) of the 74 antipsychotic-naive patients showed hyperprolactinemia not explained by any other reason, 11 (50%) of 22 women and 18 (35%) of 52 men. Hyperprolactinemia may be present in patients with schizophrenic psychoses independent of antipsychotic medication. It might be stress induced. As enhanced prolactin can increase dopamine release through a feedback mechanism, this could contribute to explaining how stress can trigger the outbreak of psychosis.

Review: evidence on the comparative effectiveness and adverse effects of antipsychotics in young people is limited

Review: evidence on the comparative effectiveness and adverse effects of antipsychotics in young people is limited

Economic Grand Rounds: Economic Costs of Failure to Monitor Adverse Effects of Second-Generation Antipsychotics: An Underestimated Factor

Since 2003, the U.S. Food and Drug Administration as well as the American Diabetes Association, the American Psychiatric Association, and others have called for routine monitoring of cardiometabolic risk factors for patients of all ages prescribed second-generation antipsychotic medications. This survey of major public and private mental health treatment systems in 2010 found that adherence to such guidelines was limited. The authors describe some of the impediments to widespread monitoring of cardiometabolic risk factors among psychiatric patients taking second-generation antipsychotics and advocate for a nationwide commitment to providing the organizational and financial supports necessary to ensure systematic screening of cardiometabolic health among such patients.

Metabolic syndrome and type 2 diabetes in chronic institutionalized patients with schizophrenia

Introduction Schizophrenia is a life-threatening illness with a mortality rate that is twice as high as that of the general population. Over 60% of deaths in schizophrenic patients are due to natural causes such as cardiovascular illness. Patients with schizophrenia and schizoaffective or bipolar disorder may have a predisposition to metabolic syndrome that is exacerbated by a sedentary life, poor dietary habits, possible limited access to care, and antipsychotic drug-induced adverse effects. It has been found that the prevalence rate of metabolic syndrome among schizophrenic patients ranges from 32 to 51%, with a two- to three-fold higher mortality rate due to heart attack compared with those without metabolic syndrome. Aim and objectives The current study aimed at detecting the prevalence and patterns of metabolic syndrome in chronic institutionalized patients with schizophrenia, comparing patients with metabolic syndrome - defined by different criteria- and lastly trying to find the predictor factors for metabolic syndrome and for diabetes mellitus. Methods Ninety-five patients with schizophrenia and schizoaffective disorder were recruited from long-stay hospital wards, were interviewed using structured clinical interview, and were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders , 4th ed . They were subjected to a cross-sectional assessment by psychopathological rating scales including positive and negative syndrome scale, mini mental state examination, and clinical global impression – severity index scale and also to anthropometric measurement taking (BMI and waist circumference). Sociodemographic and clinical characteristics as well as treatment history were collected from data files. Cases were classified into four groups according to the International Diabetes Federation criteria: definite cases with metabolic syndrome (IDF criteria); the high-risk group (lacking one criterion); risky cases with risk for central obesity; and patients with no apparent risk. Data were collected and statistically analyzed. Results Twenty-two patients (23.15%) had definite metabolic syndrome according to IDF criteria, 47 patients (49.4%) had high risk, 17 patients (17.8%) had risk factors of metabolic syndrome, and only nine cases (9.4%) had no apparent risk for metabolic syndrome. Sociodemographic and clinical characteristics and psychopathological rating scores were not predictors for metabolic syndrome, nor for diabetes mellitus. BMI and waist circumference had the highest sensitivity, predictive value, and diagnostic accuracy for metabolic syndrome compared with the presence of diabetes, hypertension, or dyslipidemia. Diabetes mellitus occurred earlier and was of longer duration compared with other metabolic disturbances. Conclusion (1) The high risk of MS among patients with chronic schizophrenia mandates careful monitoring and elimination of risk factors. (2) BMI and WC as well as blood sugar and lipid profile are considered simple measures for detecting risk factors. (3) Attempts towards toward eliminating risk factors such as poor lifestyle, obesity, and metabolic disturbances is vital for long stay hospitalised patients.

Antipsychotic drug toxicology in children

Introduction: There is an increasing use of antipsychotic drugs, particularly those of second- and third-generation, for a wide range of behavioral and affective disorders in pediatric and psychiatric practice. Limited data are available, however, regarding their safety and effectiveness, although children may be more vulnerable than adults to antipsychotic adverse effects because of developmental physiological changes that may affect their pharmacodynamic and pharmacokinetic profiles.Areas covered: This review covers the antipsychotics now specifically approved in major markets for children as well as those that are used in these patients for unapproved or off-label indications taking into account the potential differences in drug disposition and metabolism among children, adolescents and adults. MEDLINE and EMBASE international databases were searched for studies concerning the pharmacokinetics, efficacy and safety of first-, second- (‘atypical’) and third-generation antipsychotic agents.Expert opinion: Few studies have systematically monitored the safety of antipsychotics in young populations. Data concerning long-term side effects are especially limited, and a systematic benefit–risk evaluation is needed. When prescribing antipsychotics, physicians should, therefore, monitor patients closely for metabolic adverse events, hyperprolactinemia, extrapyramidal symptoms and corrected QT prolongation. Dose selection should include a careful consideration of the drugs' pharmacokinetic profiles and, when these are lacking therapeutic drug monitoring should be implemented as it is often a valid tool to optimize pediatric psychiatric practice.

P03-307 - Psychosocial particularities for adherence concept at chronic schizophrenia patients

BackgroundConcept of therapeutic adherence in schizophrenia describes the level of agreement between patient's medication taking and the psychiatrist expectations. The literature data reveal the facts that therapeutic adherence is low in the case of chronic evolution of schizophrenia. The sociological concept follows the notion of adherence to treatment for the schizophrenic patient in the patient-family-psychiatrist relation.MethodsTo find the level of understanding the concept of therapeutic adherence at the level of schizophrenic patients, their families and psychiatrists, we used a scale with 5 items. This scale was applied to a lot of 30 schizophrenic patients, 30 members of family or caregivers and 30 psychiatrists. The items referred to efficacy of pharmacological therapy, adverse effects of antipsychotics, administration form of antipsychotic (daily or long action), accessibility to medication, the direct relationship between patient and therapeutically team in the moment of taking medication.ResultsFor the patients: relationship between patient and psychiatrist, administration form and accessibility to medication.For the family: accessibility to medication, adverse effects, efficacy of therapy.For the psychiatrist: adverse effects, efficacy of therapy and accessibility to medication.DiscussionFor the patients the relation with therapeutically team is the most important element of adherence and is significant correlated with the long action antipsychotics therapy. The concept of adherence must be individualized depending to patient, family and psychiatrist. The results of this study can be a prerequisite for further research. Decrease of adherence to antipsychotics treatment suggests the switch to a long action antipsychotic.

Adverse effects of antipsychotic drugs: survey of doctors’ versus patients’ perspective

Almost no data are available on whether patients and doctors have similar or dissimilar opinions on the presence and level of distress due to antipsychotic adverse effects. The aim of this survey is to compare doctors' versus patients' perspective on the presence and level of distress due to antipsychotic adverse effects in a sample of patients under the care of the South-Verona mental health services. All patients exposed to antipsychotic drugs during a census period of 6months were identified. For each included subject, socio-demographic, clinical and treatment data were extracted. Patients' perspective on antipsychotic adverse effects was measured by means of the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The LUNSERS was similarly employed to measure doctors' perspective on antipsychotic adverse effects. During the recruitment period, 243 patients taking antipsychotic drugs were enrolled. The correlation between the total LUNSERS score reported by patients and doctors was very low (correlation coefficient 0.22, 95% confidence interval 0.15-0.30). On average, patients perceived more adverse effects and with a significant higher distress than doctors. Multivariate analyses found no factors simultaneously associated with both patient and doctor ratings of adverse effects. Our study suggests that doctors, researchers and health care providers should increasingly consider patient and doctor perspectives as two complementary dimensions that may provide different insights in the evaluation of antipsychotic drugs. Integrating different points of view may represent a way to develop a better therapeutic alliance that might decrease the likelihood of nonadherence.

Risperidone-Induced Sialorrhea: Dose-Related?

Sialorrhea has been reported as an adverse effect of antipsychotics, notably clozapine. The physical and psychosocial complications of sialorrhea can cause problems ranging from mild, inconvenient symptoms to problems with adherence, or even life-threatening conditions. We herein present a case of reversible sialorrhea that developed in a female patient with schizophrenia on high doses of risperidone. On a low dose, the patient's symptoms resolved. We conclude by proposing a potential mechanism for risperidone-induced sialorrhea (RIS) and further hypothesize that RIS is dose-related.

Diagnosis and treatment of akathisia in a cancer patient who cannot stand up or sit down, because of poor performance status: Factors that make the diagnosis of akathisia difficult, and diagnosis clues

Akathisia is a common adverse effect of antipsychotics and, less commonly, antidepressants. Akathisia can cause great discomfort and is often described by the patient as a most distressing sensation; however, the condition is often underdiagnosed or misdiagnosed. In oncological settings, neuroleptics and antidepressants that induce akathisia are also administered. However, reports of akathisia in oncology settings are few and a case of akathisia in a bedridden patient has not been reported as far as we know. A 72-year-old man with esophageal cancer who could not sit down or stand up was administered 5 mg/day haloperidol to relieve agitation as a symptom of major depressive disorder. Three days after the administration of haloperidol, the agitation had become worse. Careful observation revealed that the patient sometimes showed slight rubbing movement of the lower extremities and slight twisting movements of the body, which were not observed before the administration of haloperidol. The patient moved his body and lower extremities to relieve restlessness, which had developed after the administration of haloperidol. Although symptoms were atypical, akathisia was suspected and discontinuation of haloperidol resolved the symptoms. In patients with poor performance status, clues leading to the correct diagnosis of akathisia might be absent, which would not be the case in patients who were able to walk, stand up, or sit down. Careful observations of patients before and after the administration of drugs that may cause akathisia may be required to ensure correct diagnosis.

Hypothesis of behavioral and psychological symptoms of dementia

Hypothesis of behavioral and psychological symptoms of dementia