First-line atypical antipsychotics for schizophrenia are appropriate – with psychosocial interventions

2001 ◽  
Vol 25 (8) ◽  
pp. 287-288 ◽  
Author(s):  
A. M. Mortimer
Keyword(s):  
Side Effects ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Treatment Resistance ◽  
Psychosocial Interventions ◽  
First Line ◽  
Conventional Antipsychotics ◽  
Increased Risk ◽  
Loss Of Libido ◽  
The Individual

Conventional antipsychotics, historically the mainstay of schizophrenia treatment, were ineffective in many patients, at least 30% fitting treatment-resistance criteria (Kane & Lieberman, 1987). All had the same mechanism of action: none was any more effective in the individual than any other. Therapeutic nihilism accepted poorly controlled positive symptoms and disabling negative symptoms: nearly all patients suffered side-effects (Barnes & Edwards, 1993), particularly extrapyramidal side-effects (EPS) and hyperprolactinaemia. Conventional antipsychotics raise prolactin to a range associated with sexual dysfunction or even macroprolactinoma: effects in men include erectile dysfunction and hypospermatogenesis; in women, galactorrhoea, oligo- or amenorrhoea, hirsutism and increased risk of osteoporosis. In both men and women there is loss of libido, and a link between hyperprolactinaemia and weight gain.

Current use of atypical antipsychotics

2002 ◽  
Vol 17 (S4) ◽  
pp. 377s-384s ◽  
Author(s):  
F. Müller-Spahn
Keyword(s):  
Side Effects ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Term Treatment ◽  
Dopamine Neurons ◽  
Positive Symptoms ◽  
Onset Of Action ◽  
Conventional Antipsychotics ◽  
Long Term Treatment ◽  
Insufficient Response

SummaryIn terms of the phenomenology of schizophrenia, there are four targets for drug treatments: positive symptoms, negative symptoms, affective dysfunction, and cognitive dysfunction. Because of the side-effects of both conventional antipsychotics and the new atypicals, there still is a need to search for better-tolerated antipsychotics. Conventional antipsychotics have two principal limitations: 30–40% of patients have an insufficient response to them, and they have a large variety of adverse effects. Side-effects will reduce patients’ compliance with treatment, as well as their immediate quality of life, and may therefore unfavorably affect rehabilitation. Four principal features differentiate atypical from conventional antipsychotics, yet have not been established for all atypicals: fewer extrapyramidal side-effects, greater efficacy in the treatment of negative symptoms, specific pharmacological receptor binding profiles, and greater selective effect on the mesolimbic dopamine neurons than on nigrostriatal neurons. The pharmacological profile of amisulpride is completely different to that of other atypical antipsychotics. It has a high selectivity for D2 and D3 dopamine receptors, and thus would be expected to be devoid of unwanted side-effects associated with action on other neurotransmitter systems. It acts preferentially on the mesocortical and mesolimbic systems. It has an earlier onset of action than haloperidol. Amisulpride is a compound with a dual mode of action. At low doses it blocks presynaptic dopamine autoreceptors, inducing an increased dopaminergic neurotransmission, and at high doses it blocks postsynaptic dopaminergic activity. It is at least as effective as haloperidol, flupenthixol, and risperidone in controlling positive symptoms, as well as having efficacy for negative symptoms. It has less propensity to induce weight gain than do other atypical antipsychotics. For the 60–80% of patients with schizophrenia who require long-term treatment, drug tolerability is crucially important, as it will improve compliance, and therefore reduce relapse rate.

scholarly journals Extrapyramidal syndromes caused by antipsychotics

2012 ◽  
Vol 65 (11-12) ◽  
pp. 521-526 ◽  
Author(s):  
Milana Poznic-Jesic ◽  
Aleksandar Jesic ◽  
Jasmina Babovic-Filipovic ◽  
Olga Zivanovic
Keyword(s):  
Adverse Effect ◽  
Side Effects ◽  
Atypical Antipsychotics ◽  
Antipsychotic Therapy ◽  
Conventional Antipsychotics ◽  
Repetitive Movements ◽  
Extrapyramidal Syndromes ◽  
The One ◽  
The Individual ◽  
Continuous Use

Introduction. Extrapyramidal syndromes are significant side effects of antipsychotic therapy due to their severity, frequent occurrence and complications. This paper gives a brief summary of the literature with the emphasis on epidemiology, etiology, diagnosis and differential diagnosis, as well as the treatment of extrapyramidal disorders induced by antipsychotics. Dystonia. Sustained muscle contractions cause twisting and repetitive movements or abnormal postures. It may appear either as an acute or delayed, i.e. tardive sign. The incidence of dystonia is 2-3% among the patients treated with antipsychotics, and 50% among the ones cured with conventional antipsychotics. Akathisia. The main feature of this curious adverse effect is the psychomotor restlessness and the inability to remain motionless. Although akathisia is not very frequent, its incidence and prevalence ranges from 5 to 50% among the treated patients. It is most probably a result of the blockage of dopaminergic receptors. Parkinsonism. The most frequent secondary Parkinsonism is the one caused by drugs. The characteristic parkinsonian signs regress 4 to 16 weeks after the discontinuation of antipsychotic therapy. In the era of atypical antipsychotics this adverse effect appears less frequently. Tardive dyskinesia. Involuntary choreatic movements may appear days and months after the introduction of continuous use of antipsychotics. The individual susceptibility may play the major role in the development of this side effect. Conclusion. Numerous studies have compared conventional and atypical antipsychotics as well as atypical ones with one another in order to decrease the risk of development of extrapyramical side effects as well as to prevent their occurrence and improve their treatment.

The Science of Antipsychotics: Mechanistic Insight

CNS Spectrums ◽  
2003 ◽  
Vol 8 (S2) ◽  
pp. 5-9 ◽  
Author(s):  
Carol A. Tamminga
Keyword(s):  
Side Effects ◽  
Tardive Dyskinesia ◽  
Side Effect ◽  
Negative Symptoms ◽  
New Drugs ◽  
Receptor Subtypes ◽  
Side Effect Profile ◽  
Cognitive Symptoms ◽  
Conventional Antipsychotics ◽  
New Antipsychotics

ABSTRACTWith the introduction of conventional antipsychotics in the 1950s, clinicians began to expect effective treatment of positive symptoms of schizophrenia. However, these drugs do not resolve negative and cognitive symptoms of schizophrenia and are also associated with serious side effects, including extrapyramidal side effects (EPS) and tardive dyskinesia. In 1989, clozapine was introduced and labeled the first new antipsychotic owing to its improved efficacy and side-effect profile. Clozapine proved effective in alleviating many of the positive, negative, and cognitive symptoms of schizophrenia, without causing inevitable EPS or tardive dyskinesia. Over the past decade, a number of different new antipsychotics have been developed. These drugs have an affinity for multiple dopamine-receptor subtypes as well as serotonin, norepinephrine, and glutamate receptors, allowing for better treatment outcomes. The antagonism of the 5-HT2A receptor may be responsible for improvement in negative symptoms and decrease in EPS. In addition to providing enhanced efficacy, the affinity of the new drugs for multiple receptors introduces new side effects not seen with the conventional agents, including weight gain. Each new antipsychotic has a unique receptor-binding profile that corresponds to its pharmacologic and side-effect profile. Understanding the differences in mechanisms of action of new antipsychotics will allow physicians to better choose treatment that meets the needs of each individual patient.

scholarly journals Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kyle J. Burghardt ◽  
Kristen N. Gardner ◽  
Joshua W. Johnson ◽  
Vicki L. Ellingrod
Keyword(s):  
Insulin Resistance ◽  
Bipolar Disorder ◽  
Fatty Acid ◽  
Side Effects ◽  
High Risk ◽  
Atypical Antipsychotics ◽  
Fatty Acid Desaturase ◽  
Metabolic Side Effects ◽  
Increased Risk ◽  
Bipolar Patients

Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226) or bipolar disorder (n=94) were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

Receptor mechanisms of antipsychotic drug atypicality

1998 ◽  
Vol 13 (S1) ◽  
pp. 5s-8s
Author(s):  
GP Reynolds
Keyword(s):  
Side Effects ◽  
Animal Models ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Mechanisms Of Action ◽  
Antipsychotic Treatment ◽  
Extrapyramidal Side Effects ◽  
Treatment Resistant ◽  
Pharmacological Profile ◽  
New Compounds

SummaryRecent advances in antipsychotic treatment of schizophrenia have offered several new compounds which avoid many of the limitations of the classical antipsychotics. These so-called ‘atypical’ antipsychotics have fewer extrapyramidal side effects, greater efficacy against negative symptoms and greater efficacy in otherwise treatment-resistant patients. However, the mechanism of action of these atypical antipsychotics is still unclear. The several receptors currently implicated in the pharmacological profile of these atypical antipsychotics include subtypes of those for dopamine, serotonin, noradrenaline, and acetylcholine among others. The current hypotheses for possible mechanisms of action of atypical antipsychotics are discussed along with the experimental correlates of antipsychotic efficacy in animal models.

Improvement of positive and negative symptoms in patients with schizophrenia, under risperidone long acting injection (RLAI) treatment

2011 ◽  
Vol 26 (S2) ◽  
pp. 1457-1457
Author(s):  
E. Moruzzi
Keyword(s):  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
List Type ◽  
First Line ◽  
Violent Behaviour ◽  
Treatment Change ◽  
First Line Therapy ◽  
Long Acting ◽  
Persistent Disability ◽  
Positive And Negative Symptoms

IntroductionEarly treatment intervention and prevention may minimize the morbidity and persistent disability caused by schizophrenia that occurs over patients’ lifetimes.Atypical antipsychotics with improved tolerability and less likely to cause movement disorders and secondary negative symptoms, are generally used as first line therapy.Risperidone long acting injection (RLAI) is currently the only available long acting atypical antipsychotic, combining the better tolerability of an atypical with the benefits of injectable delivery.ObjectiveTo assess the maintained efficacy and safety of risperidone long acting injection after a direct treatment change from any antipsychotic medication in patients with schizophrenia.MethodsAdults with schizophrenia received injections of long acting risperidone 25, 37.5, 50 mg in 14 days interval for 6 months.Efficacy was measured by:.PANSS (Positive and negative symptoms scale).CGI-S (Clinical Global Impression- Severity).GAF (Global Assessment Functioning)Tolerability was measured with TEAE (Treatments emergent adverse events)ResultsIn this study, negative and positive symptoms were significantly improved. Clinical deterioration was substantially ameliorated between baseline and endpoint. Compared to baseline there were significant decreases in the occurrence of suicidal ideation and violent behaviour. Also, the treatment showed good safety and tolerability.ConclusionsRLAI treatment was associated with a very good efficacy, tolerability, and an excellent improvement of functionality.

The Age of Atypical Antipsychotics

1996 ◽  
Vol 9 (2) ◽  
pp. 113-117
Author(s):  
Ronald Pies
Keyword(s):  
Side Effects ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
D2 Receptor ◽  
Receptor Occupancy ◽  
Clinical Development ◽  
Pharmacological Management ◽  
Regional Brain

Atypical antipsychotics (AAPs) have led to refinements in the pharmacological management of schizophrenia and related disorders. Most AAPs produce fewer extra- pyramidal side effects than conventional agents, and appear to ameliorate "negative symptoms" to a greater degree. In general, many AAPs have a higher ratio of 5HT2 to D2 receptor occupancy than do conventional neuroleptics. This ratio may confer some of the "atypical" qualities to these agents, though regional brain selectivity may also be involved. Although clozapine and risperidone are the two AAPs clinicians now have available, many other similar agents are close to clinical development. Copyright © 1996 by W.B. Saunders Company

Risk of Death with Atypical Antipsychotic Medications for Dementia

2018 ◽  
Author(s):  
Adam P. Mecca ◽  
Rajesh R. Tampi
Keyword(s):  
Side Effects ◽  
Atypical Antipsychotic ◽  
Odds Ratio ◽  
Clinical Case ◽  
Atypical Antipsychotics ◽  
Meta Analysis ◽  
Antipsychotic Medications ◽  
Risk Of Death ◽  
Increased Risk ◽  
Atypical Antipsychotic Medications

This chapter provides a summary of a landmark meta-analysis that investigated the risks of atypical antipsychotic use to treat psychosis, aggression, or agitation in patients with dementia. The chapter briefly reviews the study design, as well as implications and limitations. A relevant clinical case concludes the chapter. In summary, atypical antipsychotic use for 6 to 26 weeks was associated with increased risk of death (Odds Ratio of 1.54 for antipsychotic vs placebo). There were no differences in risk between individual medications, disease severity, indication for antipsychotic, or treatment setting. In patients with psychosis, agitation, or aggression due to dementia, the efficacy of atypical antipsychotics is questionable and their use comes with considerable risks of side effects and adverse events.

Maximizing response to first-line antipsychotics in schizophrenia

2018 ◽  
Author(s):  
Robert C. Smith ◽  
Stefan Leucht ◽  
John M. Davis
Keyword(s):  
Side Effects ◽  
Negative Symptoms ◽  
Antidepressant Drug ◽  
Adjunctive Treatment ◽  
Antipsychotic Treatment ◽  
Inadequate Response ◽  
First Line ◽  
Adequate Dose ◽  
Efficacy Outcome ◽  
Meta Analyses

The choice of first-line antipsychotic treatment for patients with schizophrenia should balance considerations of differential efficacy of antipsychotics against the relative risk of different side effects. In terms of efficacy, recent meta-analyses have shown that antipsychotics are not equivalent in efficacy. Clozapine, amisulpride, olanzapine, and risperidone show small to moderate, but statistically significant, differences, indicating greater efficacy compared to a number of other antipsychotics on some primary efficacy outcome measures. Amisulpride and cariprazine have the strongest evidence for greater efficacy for treating negative symptoms relative to other antipsychotics. In terms of side effects, clozapine and olanzapine have among the highest weight gain potential and amisulpride has more effects on QTc prolongation and prolactin elevation than other commonly used antipsychotics. Adjunctive treatment with an antidepressant drug may improve response in patients with schizophrenia who also have severe depressive or negative symptoms. For a patient with an inadequate response to an adequate dose and duration of the initial antipsychotic choice, switching to another antipsychotic with a different receptor profile may improve response, although evidence is limited. There is little evidence to support using doses above the therapeutic range other than in exceptional circumstances.

Is it worth while changing clinically stable schizophrenic out-patients with mild to moderate residual symptoms and/or side effects from conventional to atypical antipsychotics? A prospective, randomised study with olanzapine

2004 ◽  
Vol 19 (8) ◽  
pp. 516-518 ◽  
Author(s):  
Björn Appelberg ◽  
Katinka Tuisku ◽  
Grigori Joffe
Keyword(s):  
Side Effects ◽  
Atypical Antipsychotics ◽  
Residual Symptoms ◽  
Randomised Study ◽  
Conventional Antipsychotics ◽  
Schizophrenic Outpatients ◽  
Prospective Randomised Study

AbstractFifty clinically stable, schizophrenic outpatients, suffering from residual schizophrenic symptoms and/or neurological side effects, were randomised to either continue their conventional neuroleptic(s) or change it to olanzapine. After 12 weeks patients on olanzapine exhibited significant improvement in neurological side effects and psychotic symptomatology as compared to patients on conventional antipsychotics.

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