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BMC Medicine Jun 2019Atypical antipsychotics, also known as second-generation antipsychotics, are commonly prescribed as treatment for psychotic disorders in adults, as well as in children... (Review)
Review
BACKGROUND
Atypical antipsychotics, also known as second-generation antipsychotics, are commonly prescribed as treatment for psychotic disorders in adults, as well as in children and adolescents with behavioral problems. However, in many cases, second-generation antipsychotics have unwanted side effects, such as weight gain, potentially further increasing risk for morbidities including obesity, diabetes, and cardiovascular disease. While various mechanisms for this weight gain have been proposed, including effects on metabolic hormone signaling, recent evidence points to the importance of the gut microbiome in this process. The microbial communities residing within the gut are affected by second-generation antipsychotics and can confer weight gain.
MAIN TEXT
This review summarizes recent findings and presents data linking second-generation antipsychotics, gut microbiota alterations and weight gain. The review focuses on children and adolescent populations, which have not previously received much attention, but are of great interest because they may be most vulnerable to gut microbiome changes and may carry long-term metabolic effects into adulthood.
CONCLUSIONS
We present correlations between second-generation antipsychotics, gut microbiota alterations and weight gain, and suggest some mechanisms that may link them. A better understanding of the underlying mechanisms may lead to the design of improved treatments for psychotic disorders with fewer harmful side effects.
Topics: Antipsychotic Agents; Child; Female; Humans; Male; Microbiota; Obesity; Psychotic Disorders; Weight Gain
PubMed: 31215494
DOI: 10.1186/s12916-019-1346-1 -
Dialogues in Clinical Neuroscience Mar 2016The mesolimbic dopaminergic reward system is responsible for the negative affective symptomatology of schizophrenia, which may be related to a low dopamine tonus within... (Review)
Review
The mesolimbic dopaminergic reward system is responsible for the negative affective symptomatology of schizophrenia, which may be related to a low dopamine tonus within the ventral striatum. The monetary incentive delay (MID) task can be used to study the response of the ventral striatum to incentive stimuli. We show that activation of the ventral striatum is low in patients with schizophrenia, and that this low activation is related to primary and secondary negative symptoms induced by neuroleptics, also known as antipsychotics. Switching from first-(typical) to second-generation (atypical) antipsychotics increased activation of the ventral striatum due to less blocking of dopamine D2 receptors. This and similar studies show that functional magnetic resonance imaging (fMRI) tasks are suitable to investigate important aspects of antipsychotic mechanisms.
Topics: Antipsychotic Agents; Delay Discounting; Humans; Magnetic Resonance Imaging; Reward; Schizophrenia; Schizophrenic Psychology; Treatment Outcome
PubMed: 27069385
DOI: 10.31887/DCNS.2016.18.1/gjuckel -
Journal of Psychiatry & Neuroscience :... Jul 2014In the field of schizophrenia research, as in other areas of psychiatry, there is a sense of frustration that greater advances have not been made over the years, calling... (Review)
Review
In the field of schizophrenia research, as in other areas of psychiatry, there is a sense of frustration that greater advances have not been made over the years, calling into question existing research strategies. Arguably, many purported gains claimed by research have been "lost in translation," resulting in limited impact on diagnosis and treatment in the clinical setting. There are exceptions; for example, we would argue that different lines of preclinical and clinical research have substantially altered how we look at antipsychotic dosing. While this story remains a work in progress, advances "found in translation" have played an important role. Detailing these changes, the present paper speaks to a body of evidence that has already shifted clinical practice and raises questions that may further alter the manner in which antipsychotics have been administered over the last 6 decades.
Topics: Antipsychotic Agents; Humans; Psychopharmacology; Schizophrenia
PubMed: 24467943
DOI: 10.1503/jpn.130191 -
Schizophrenia Bulletin Jun 2022
Topics: Antipsychotic Agents; Humans; Psychotic Disorders; Recurrence; Schizophrenia; Secondary Prevention
PubMed: 35536691
DOI: 10.1093/schbul/sbac045 -
The Keio Journal of Medicine Dec 1994This is a review paper covering the American current status of pharmacotherapy of schizophrenia. The author lists all available antipsychotic agents on the market in the... (Review)
Review
This is a review paper covering the American current status of pharmacotherapy of schizophrenia. The author lists all available antipsychotic agents on the market in the United States and describes the American prescribing pattern of antipsychotic agents. This includes a brief history of antipsychotic use in America, acute treatment and chronic maintenance with antipsychotic drugs, the recent advent of atypical antipsychotic agents, and management of antipsychotic-induced side-effects. The characteristics of prescribing American antipsychotics in America are described, and they are then compared with Japanese prescribing practices. The author also makes brief remarks about the uncovered issues in antipsychotic pharmacotherapy and about atypical antipsychotic agents in the context of the future pharmaceutical development.
Topics: Antipsychotic Agents; Drug Utilization; Humans; Schizophrenia; United States
PubMed: 7861689
DOI: 10.2302/kjm.43.192 -
Acta Pharmaceutica (Zagreb, Croatia) Dec 2014Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the... (Review)
Review
Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM) of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.
Topics: Antipsychotic Agents; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Medication Adherence; Schizophrenia; Severity of Illness Index
PubMed: 25531781
DOI: 10.2478/acph-2014-0036 -
The Journal of Clinical Psychiatry Dec 2016How antipsychotic drugs compare in schizophrenia, and especially in medication-refractory schizophrenia, is a subject of considerable interest. Two network meta-analyses... (Review)
Review
How antipsychotic drugs compare in schizophrenia, and especially in medication-refractory schizophrenia, is a subject of considerable interest. Two network meta-analyses and 1 direct comparison meta-analysis recently compared antipsychotics in schizophrenia patients with and without documented treatment resistance. One network meta-analysis of antipsychotic drugs in non-refractory patients found clear efficacy advantages for clozapine, amisulpride, olanzapine, and risperidone. One network meta-analysis of antipsychotic drugs in refractory patients found a clear efficacy advantage for olanzapine; surprisingly, in this meta-analysis, clozapine was superior to first-generation but not second-generation antipsychotics. One direct comparison meta-analysis found clozapine generally superior to first- and second-generation antipsychotics, with advantages more clearly apparent in studies that were 3 months in duration or less. Drug discontinuation and adverse effect data from these meta-analyses are presented, and issues arising from the results are briefly discussed. At the risk of oversimplification, it appears that clozapine retains its preeminence in medication-refractory schizophrenia and that clozapine and olanzapine are both associated with superior efficacy outcomes in non-refractory patients. Interestingly, haloperidol, generally considered a reference neuroleptic and a reference comparator drug, fared poorly in most comparisons.
Topics: Antipsychotic Agents; Drug Resistance; Humans; Medication Adherence; Meta-Analysis as Topic; Schizophrenia
PubMed: 28086018
DOI: 10.4088/JCP.16f11328 -
Drug Design, Development and Therapy 2016Three-monthly injections of paliperidone palmitate (PP-3M) represent a new and recently introduced long-acting antipsychotic therapeutic option. This review focuses on... (Review)
Review
AIMS
Three-monthly injections of paliperidone palmitate (PP-3M) represent a new and recently introduced long-acting antipsychotic therapeutic option. This review focuses on available data relating to the efficacy and safety of PP-3M and its position in the current therapeutic scenario.
METHOD
An analysis of PubMed, Scopus, and ISI Web of Knowledge databases was conducted, and all available papers on PP-3M, including poster presentations, were selected and considered for the purpose of the present review.
FINDINGS
to date, three full papers have been published, the first, a Phase 1 randomized, open label study investigating the pharmacokinetics, safety, and tolerability of the drug; the second, a Phase 3 double blind study vs placebo focusing on efficacy and tolerability; and the last relating to the practical use of PP-3M. The five posters identified describe data reported in the above-cited papers. Overall, the pharmacokinetic findings obtained in these studies highlight the feasibility of administering PP-3M on a 3-monthly basis, subsequent to the administration of four 1-monthly injections of PP at doses 3.5 times higher than the stabilized dose of 1-monthly injections of PP (ie, 175, 300, 450, and 525 mgs). The published studies highlight a significantly longer time to relapse compared to placebo, and significantly better results compared to placebo for all secondary end-points (Positive and Negative Syndrome Scale, Clinical Global Impression-Severity Scale, Personal and Social Performance Scale scores), in addition to reasonably good safety and tolerability profiles.
CONCLUSION
PP-3M emerges as a potential candidate for use as a first-line long-acting agent in the maintenance treatment of patients with schizophrenia. Further studies should however be conducted to confirm this expectation. In view of its efficacy, tolerability, and safety, together with the longer timespan between injections, PP-3M currently represents one of the best available options, and may contribute towards addressing the issue of poor adherence, even in early psychosis.
Topics: Antipsychotic Agents; Humans; Paliperidone Palmitate; Schizophrenia; Time Factors
PubMed: 27307704
DOI: 10.2147/DDDT.S86301 -
Schizophrenia Bulletin Mar 2014Atypical antipsychotic medications have been the first line of treatment for adolescents with psychosis in the past couple of decades. Till the late 90s, there were very... (Meta-Analysis)
Meta-Analysis Review
Atypical antipsychotic medications have been the first line of treatment for adolescents with psychosis in the past couple of decades. Till the late 90s, there were very few randomized controlled trials (RCTs) on the treatment of adolescents with psychosis, although a fifth of schizophrenia starts during adolescence. Most of the treatment guidelines for adolescents with psychosis were derived from data on adults. In the past 10 years, there has been increasing number of studies on adolescents with psychosis. The current paper summarizes the findings of trials on adolescents with psychosis in 4 groups: (a) atypical antipsychotic medications vs placebo, (b) atypical antipsychotic medication vs typical antipsychotic medications, (c) one atypical antipsychotic medication vs another atypical antipsychotic medication, and (d) Low dose vs standard dose of atypical antipsychotic medication. We included 13 RCTs, with a total of 1112 participants. Although our review suggest that atypical antipsychotic medications are as effective as typical antipsychotic medications as regards clinical efficacy, atypical antipsychotic medications have a preferred side effect profile and lesser drop-out rate from trials. Obviously, this is extremely important as treatment adherence is key to successful remission of psychotic symptoms and also in some case prevent relapse of illness. Treatment with olanzapine, risperidone, and clozapine is often associated with weight gain. Aripiprazole is not associated with increased prolactin or with dyslipidemia. Adolescents may respond better to standard-dose as opposed to lower dose risperidone, but for aripiprazole and ziprasidone, lower doses may be equally effective. Future trial should be longer term and have uniform ways of reporting side effects.
Topics: Adolescent; Antipsychotic Agents; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 24361758
DOI: 10.1093/schbul/sbt196 -
The International Journal of... May 2023Schizophrenia is a disabling disorder that profoundly affects functioning and quality of life. While available antipsychotics have improved outcomes for patients with...
BACKGROUND
Schizophrenia is a disabling disorder that profoundly affects functioning and quality of life. While available antipsychotics have improved outcomes for patients with schizophrenia, they are relatively ineffective for negative and cognitive symptoms and are associated with a range of troublesome side effects. A significant unmet medical need for more effective and better-tolerated therapies remains.
METHODS
A roundtable consisting of 4 experts in the treatment of patients with schizophrenia convened to discuss the current treatment landscape, unmet needs from patient and societal perspectives, and the potential of emerging therapies with novel mechanisms of action (MOAs).
RESULTS
Key areas of unmet need include optimal implementation of available treatments, effective treatment of negative and cognitive symptoms, improvements in medication adherence, novel MOAs, avoidance of postsynaptic dopamine blockade-related adverse effects, and individualized approaches to treatment. With the possible exception of clozapine, all currently available antipsychotics primarily act by blocking dopamine D2 receptors. Agents with novel MOAs are urgently needed to effectively target the full range of symptoms in schizophrenia and facilitate an individualized treatment approach. Discussion focused on promising novel MOAs that have demonstrated potential in phase 2 and 3 trials include muscarinic receptor agonism, trace amine-associated receptor 1 agonism, serotonin receptor antagonism/inverse agonism, and glutamatergic modulation.
CONCLUSIONS
Results from early clinical trials of agents with novel MOAs are encouraging, particularly for muscarinic and trace amine-associated receptor 1 agonists. These agents offer renewed hope for meaningful improvement in the management of patients with schizophrenia.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Drug Inverse Agonism; Quality of Life; Clozapine
PubMed: 36932673
DOI: 10.1093/ijnp/pyad011