-
Pharmacotherapy Jan 2009Use of antipsychotic agents has been associated with hyperprolactinemia, or elevated prolactin levels; this hormonal abnormality can interfere with the functioning of... (Review)
Review
Use of antipsychotic agents has been associated with hyperprolactinemia, or elevated prolactin levels; this hormonal abnormality can interfere with the functioning of reproductive, endocrine, and metabolic systems. As antipsychotic agents are increasingly used for both United States Food and Drug Administration-approved and nonapproved indications, many individuals are at risk for developing antipsychotic-induced hyperprolactinemia. First-generation antipsychotics pose the greatest risk of causing this adverse effect; however, second-generation antipsychotics, particularly risperidone and paliperidone, also often increase prolactin secretion. Hyperprolactinemia has short- and long-term consequences that can seriously affect quality of life: menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, infertility, decreased bone mineral density, and breast cancer. Although many of these are definitively connected to elevated prolactin levels, some, such as breast cancer, require further study. Both clinicians and patients should be aware of hyperprolactinemia-associated effects. To prevent or alleviate the condition, tailoring an antipsychotic drug regimen to each individual patient is essential. In addition, the risk of hyperprolactinemia can be minimized by using the lowest effective dose of the antipsychotic agent. If the effects of prolactin are evident, the drug can be changed to another agent that is less likely to affect prolactin levels; alternatively, a dopamine agonist may be added, although this may compromise antipsychotic efficacy. Additional research is needed to clarify the appropriate level of monitoring, the long-term effects, and the optimal treatment of antipsychotic-induced hyperprolactinemia.
Topics: Antipsychotic Agents; Bone Density; Breast Neoplasms; Dopamine Agonists; Female; Humans; Hyperprolactinemia; Menstrual Cycle; Meta-Analysis as Topic; Pituitary Neoplasms; Prolactin; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological
PubMed: 19113797
DOI: 10.1592/phco.29.1.64 -
Current Neuropharmacology 2018Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated. (Review)
Review
BACKGROUND
Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated.
METHODS
Herein, we review the impact of neurotransmitters on metabolic regulation, providing insights into antipsychotic-induced metabolic side effects.
RESULTS
Antipsychotic drugs seem to interfere with feeding behaviors and energy balance, processes that control metabolic regulation. Reward and energy balance centers in central nervous system constitute the central level of metabolic regulation. The peripheral level consists of skeletal muscles, the liver, the pancreas, the adipose tissue and neuroendocrine connections. Neurotransmitter receptors have crucial roles in metabolic regulation and they are also targets of antipsychotic drugs. Interaction of antipsychotics with neurotransmitters could have both protective and harmful effects on metabolism.
CONCLUSION
Emerging evidence suggests that antipsychotics have different liabilities to induce obesity, diabetes and dyslipidemia. However this diversity cannot be explained merely by drugs'pharmacodynamic profiles, highlighting the need for further research.
Topics: Animals; Antipsychotic Agents; Humans; Metabolic Diseases; Receptors, Neurotransmitter
PubMed: 28676017
DOI: 10.2174/1570159X15666170630163616 -
Drugs Jul 2021Schizophrenia is a debilitating illness with a lifetime prevalence estimate of 0.6% and consists of symptoms from the positive, negative, and cognitive domains. Social... (Review)
Review
Schizophrenia is a debilitating illness with a lifetime prevalence estimate of 0.6% and consists of symptoms from the positive, negative, and cognitive domains. Social support, therapy, psychoeducation, and overall case management are very important aspects of the treatment of schizophrenia. However, as abnormalities in neurotransmission are one of the key findings of schizophrenia pathology, pharmacotherapies are cornerstones of the management of schizophrenia. Antipsychotics have been used as the primary pharmacological treatment of schizophrenia. These agents often have a good effect on reducing positive symptoms, but may not markedly improve negative symptoms or cognitive defects. However, at least 20% of individuals with schizophrenia do not experience a substantial response from monotherapy with antipsychotics. Further, despite evolving treatment protocols and advances in early recognition of the disorder, 70% of patients with schizophrenia require long-term, even lifetime, medication to control their symptoms and do not achieve complete recovery. To address these shortcomings, clinicians and research scientists have explored different combinations of treatments, polypharmacy, to improve the treatment of patients. Antipsychotic polypharmacy has been shown to cause more side effects than monotherapy, which is the main reason why most treatment guidelines caution against it. Antipsychotic monotherapy should be strived for and clozapine should be tried at the latest if two monotherapy trials with other antipsychotics have failed and no absolute contraindications exist. If residual symptoms exist despite trials of adequate dose and duration, other reasons that may reduce treatment effect should be ruled out. Long-acting injectables or blood concentration measurements should be considered to affirm compliance and proper serum levels. Antipsychotic polypharmacy should be considered and discussed with patients from whom the aforementioned procedures do not produce a satisfactory treatment result. In some cases, antipsychotic polypharmacy may produce better results than other forms of treatment augmentation, such as benzodiazepines. In particular, combining aripiprazole with clozapine may be effective in reducing treatment side effects or residual symptoms, and this is likely to hold true for combining other partial dopamine D agonists with clozapine as well, although currently scant data exist. More research is needed, both in controlled but also real-world settings, to define optimal antipsychotic polypharmacy and/or other psychotropic treatment augmentation strategies for specific patient groups and situations.
Topics: Antipsychotic Agents; Drug Therapy, Combination; Humans; Practice Guidelines as Topic; Schizophrenia
PubMed: 34196945
DOI: 10.1007/s40265-021-01556-4 -
Lancet (London, England) Sep 2019Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis.
BACKGROUND
Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials.
METHODS
We did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919.
FINDINGS
We identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from -0·89 (95% CrI -1·08 to -0·71) for clozapine to -0·03 (-0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from -0·69 (95% CrI -0·86 to -0·52) for amisulpride to -0·17 (-0·31 to -0·04) for brexpiprazole, for negative symptoms (32 015 participants) from -0·62 (-0·84 to -0·39; clozapine) to -0·10 (-0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from -0·90 (-1·36 to -0·44; sulpiride) to 0·04 (-0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28 317 participants) ranged from -0·16 kg (-0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from -77·05 ng/mL (-120·23 to -33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from -2·21 ms (-4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low.
INTERPRETATION
There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences.
FUNDING
German Ministry of Education and Research and National Institute for Health Research.
Topics: Administration, Oral; Antipsychotic Agents; Comparative Effectiveness Research; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 31303314
DOI: 10.1016/S0140-6736(19)31135-3 -
American Family Physician Jun 2007Schizophrenia is a debilitating mental illness that affects 1 percent of the population in all cultures. It affects equal numbers of men and women, but the onset is... (Review)
Review
Schizophrenia is a debilitating mental illness that affects 1 percent of the population in all cultures. It affects equal numbers of men and women, but the onset is often later in women than in men. Schizophrenia is characterized by positive and negative symptoms. Positive symptoms include hallucinations, voices that converse with or about the patient, and delusions that are often paranoid. Negative symptoms include flattened affect, loss of a sense of pleasure, loss of will or drive, and social withdrawal. Both types of symptoms affect patients' families; therefore, it is important for physicians to provide guidance to all persons affected by the disease. Psychosocial and family interventions can improve outcomes. Medications can control symptoms, but virtually all antipsychotics have neurologic or physical side effects (e.g., weight gain, hypercholesterolemia, diabetes). There is a 10 percent lifetime risk of suicide in patients with schizophrenia.
Topics: Antipsychotic Agents; Diagnosis, Differential; Humans; Nervous System; Prognosis; Schizophrenia
PubMed: 17619525
DOI: No ID Found -
BioMed Research International 2014Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of... (Review)
Review
Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability.
Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Drug-Related Side Effects and Adverse Reactions; Humans; Receptors, Dopamine D2; Schizophrenia
PubMed: 24995318
DOI: 10.1155/2014/656370 -
American Family Physician Mar 2010The use of antipsychotic medications entails a difficult trade-off between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes... (Review)
Review
The use of antipsychotic medications entails a difficult trade-off between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. There is more variability among specific antipsychotic medications than there is between the first- and second-generation antipsychotic classes. The newer second-generation antipsychotics, especially clozapine and olanzapine, generally tend to cause more problems relating to metabolic syndrome, such as obesity and type 2 diabetes mellitus. Also, as a class, the older first-generation antipsychotics are more likely to be associated with movement disorders, but this is primarily true of medications that bind tightly to dopaminergic neuroreceptors, such as haloperidol, and less true of medications that bind weakly, such as chlorpromazine. Anticholinergic effects are especially prominent with weaker-binding first-generation antipsychotics, as well as with the second-generation antipsychotic clozapine. All antipsychotic medications are associated with an increased likelihood of sedation, sexual dysfunction, postural hypotension, cardiac arrhythmia, and sudden cardiac death. Primary care physicians should understand the individual adverse effect profiles of these medications. They should be vigilant for the occurrence of adverse effects, be willing to adjust or change medications as needed (or work with psychiatric colleagues to do so), and be prepared to treat any resulting medical sequelae.
Topics: Antipsychotic Agents; Arrhythmias, Cardiac; Humans; Hyperprolactinemia; Movement Disorders; Receptors, Dopamine D2; Weight Gain
PubMed: 20187598
DOI: No ID Found -
Acta Medica Portuguesa Feb 2019Schizophrenia is a disabling and severe mental illness that affects all social classes and racial and ethnic groups, spreading across every part of the world. It's more... (Review)
Review
Schizophrenia is a disabling and severe mental illness that affects all social classes and racial and ethnic groups, spreading across every part of the world. It's more frequent in males and it usually manifests itself in late adolescence or early adulthood and its early detection by all clinicians is important so that there is a proper referral to specialized psychiatric care. This article intends to update the knowledge regarding the diagnosis, treatment and prognosis of schizophrenia, with an emphasis on the warning signs for a timely referral to psychiatric evaluation. We conducted a literature search across through articles available in databases of scientific articles but also in scientific and technical books specialized in the field of schizophrenia. The clinical presentation of this illness is heterogeneous and complex, with a typical evolution based on several episodes of acute decompensation requiring hospitalization. The diagnosis of schizophrenia relies on some key symptoms, and the various international diagnostic criteria vary in relation to the temporal window with productive symptomatology required to establish a diagnosis. The prognosis is variable, not always deteriorating and is all the better when the treatment is started as early as possible. Treatment requires a multidisciplinary approach and is based primarily on antipsychotic drugs. This medication although very effective for the typical symptoms of this illness, entails some adverse effects with medical consequences that are important in the clinical practice of all doctors of other specialties.
Topics: Age Factors; Antipsychotic Agents; Female; Humans; Male; Prognosis; Schizophrenia; Schizophrenic Psychology; Symptom Assessment
PubMed: 30753806
DOI: 10.20344/amp.10768 -
The New England Journal of Medicine Sep 2005The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study.
METHODS
A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments.
RESULTS
Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects.
CONCLUSIONS
The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lipids; Male; Olanzapine; Patient Compliance; Perphenazine; Piperazines; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome; Weight Gain
PubMed: 16172203
DOI: 10.1056/NEJMoa051688 -
Dialogues in Clinical Neuroscience Sep 2019Despite effective pharmacological treatments for psychotic symptoms (eg, hallucinations, delusions), functional outcomes for people with psychotic disorders are often... (Review)
Review
Despite effective pharmacological treatments for psychotic symptoms (eg, hallucinations, delusions), functional outcomes for people with psychotic disorders are often disappointing. Although it is not included in the diagnostic criteria for psychotic disorders, cognitive impairment is one of the strongest determinants of community functioning in this clinical population, and thus it is an important target for intervention. In this review, we discuss the major areas of research regarding impaired cognition in psychotic illness. The specific topics covered include: (i) the prevalence of cognitive impairment in psychotic disorders; (ii) the profile and magnitude of cognitive impairment in psychotic disorders; (iii) the developmental course of cognitive impairment; (iv) the longitudinal stability of cognitive impairment; and (v) treatment approaches to improve cognitive performance in people with psychotic disorders. .
Topics: Antipsychotic Agents; Cognitive Behavioral Therapy; Cognitive Dysfunction; Humans; Nootropic Agents; Prevalence; Psychotic Disorders; Treatment Outcome
PubMed: 31749648
DOI: 10.31887/DCNS.2019.21.3/amccleery