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1.
J Pharmacol Sci ; 151(1): 9-16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36522124

RESUMO

Tardive akathisia is a movement disorder characterized by internal restlessness with an uncontrollable urge to move, leading to repetitive movements. It is a common side effect of long-term treatment with dopamine D2 receptor antagonists. In the present study, we analyzed the FDA Adverse Event Reporting System and IBM MarketScan Research Database to find a drug that can be used concomitantly with dopamine D2 receptor antagonists and still reduce the risk of akathisia. Acetaminophen was determined to be the most effective akathisia-suppressing drug. In an experimental validation of the hypothesis, chronic treatment of rats with haloperidol caused akathisia symptoms, including increased stereotyped behavior and locomotor activity, and decreased immobility time. Acute treatment with acetaminophen significantly attenuated haloperidol-induced akathisia. In the ventral striata of these rats, acetaminophen prevented haloperidol-induced decrease in the number of c-Fos+ preproenkephalin+ neurons. These results suggest that acetaminophen is effective in suppressing tardive akathisia by activating indirect-pathway medium spiny neurons.


Assuntos
Acatisia Induzida por Medicamentos , Antipsicóticos , Animais , Ratos , Acatisia Induzida por Medicamentos/tratamento farmacológico , Acatisia Induzida por Medicamentos/etiologia , Acatisia Induzida por Medicamentos/prevenção & controle , Haloperidol/efeitos adversos , Dopamina , Acetaminofen/efeitos adversos , Agitação Psicomotora/etiologia , Agitação Psicomotora/complicações , Antagonistas dos Receptores de Dopamina D2 , Antipsicóticos/efeitos adversos
2.
Clin Neuropharmacol ; 45(4): 89-94, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35696611

RESUMO

OBJECTIVES: The prevalence of akathisia is variably reported in the literature and its psychiatric impact is little studied. The aim of this study was to establish the prevalence, the associated factors, and the psychiatric impact of akathisia among patients undergoing antipsychotic treatment. METHODS: A cross-sectional descriptive study was carried out at the Department of Psychiatry A, at Razi Hospital, in Tunis. It included patients with psychosis, undergoing antipsychotic treatment, from June 2016 to February 2017. Akathisia was diagnosed according to the Barnes Akathisia Scale. RESULTS: The prevalence of akathisia was 19.5% (n = 24, schizophrenia/schizoaffective disorder, n = 20; bipolar disorder, n = 4). The delay between the diagnosis of the disease and the onset of akathisia was 7.1 ± 8.8 years. Among the sample of patients with akathisia, 20/24 were on monotherapy of which 14 on conventional antipsychotics and six on atypical antipsychotics. Patients with akathisia were on atypical (8/24), low-potency conventional (4/24), or high-potency conventional (17/24) antipsychotics. The average dose of antipsychotics in chlorpromazine equivalent was 2294.5 ± 3037.7 mg. After adjusting for confounders, the only factor significantly positively associated with the diagnosis of akathisia was the dose of antipsychotics prescribed ( P = 0.01). The following psychiatric manifestations were reported by patients with akathisia: dysphoria/irritability (16/23), anxiety (18/24), sadness (15/24), suicidal thoughts (11/24), heteroaggressivity (8/23), sleep disturbances (16/24), and suicidal attempts (9/24). CONCLUSIONS: Despite the high psychiatric and social burden of akathisia, it remains largely underdiagnosed and undertreated, because in part of its subjective component.


Assuntos
Antipsicóticos , Esquizofrenia , Acatisia Induzida por Medicamentos/tratamento farmacológico , Acatisia Induzida por Medicamentos/epidemiologia , Acatisia Induzida por Medicamentos/etiologia , Antipsicóticos/efeitos adversos , Estudos Transversais , Humanos , Prevalência , Agitação Psicomotora/tratamento farmacológico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico
3.
J Integr Neurosci ; 21(1): 17, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35164453

RESUMO

Locomotor hyperactivity induced by psychotomimetic drugs, such as amphetamine and phencyclidine, is widely used as an animal model of psychosis-like behaviour and is commonly attributed to an interaction with dopamine release and N-methyl-D-aspartate (NMDA) receptors, respectively. However, what is often not sufficiently taken into account is that the pharmacological profile of these drugs is complex and may involve other neurotransmitter/receptor systems. Therefore, this study aimed to assess the effect of three antagonists targeting different monoamine pathways on amphetamine- and phencyclidine-induced locomotor hyperactivity. A total of 32 rats were pre-treated with antagonists affecting dopaminergic, noradrenergic and serotonergic transmission: haloperidol (0.05 mg/kg), prazosin (2 mg/kg) and ritanserin (1 mg/kg), respectively. After 30 min of spontaneous activity, rats were injected with amphetamine (0.5 mg/kg) or phencyclidine (2.5 mg/kg) and distance travelled, stereotypy and rearing recorded in photocell cages over 90 min. Pre-treatment with haloperidol or prazosin both reduced amphetamine-induced hyperactivity although pre-treatment with ritanserin had only a partial effect. None of the pre-treatments significantly altered the hyperlocomotion effects of phencyclidine. These findings suggest that noradrenergic as well as dopaminergic neurotransmission is critical for amphetamine-induced locomotor hyperactivity. Hyperlocomotion effects of phencyclidine are dependent on other factors, most likely NMDA receptor antagonism. These results help to interpret psychotomimetic drug-induced locomotor hyperactivity as an experimental model of psychosis.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Acatisia Induzida por Medicamentos/prevenção & controle , Anfetamina/farmacologia , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fenciclidina/farmacologia , Psicoses Induzidas por Substâncias/prevenção & controle , Antagonistas da Serotonina/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Acatisia Induzida por Medicamentos/etiologia , Anfetamina/administração & dosagem , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Masculino , Fenciclidina/administração & dosagem , Psicoses Induzidas por Substâncias/etiologia , Ratos , Ratos Sprague-Dawley , Antagonistas da Serotonina/administração & dosagem
4.
Brain Res Bull ; 179: 83-96, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34920034

RESUMO

Repeated psychostimulant administration results in behavioral sensitization, a process that is relevant in the early phases of drug addiction. Critically, behavioral sensitization is not observed in all subjects. Evidence shows that differential neuronal activity in the dorsolateral striatum (DLS) accompanies the expression of amphetamine (AMPH) locomotor sensitization. However, whether individual differences in DLS activity previous to AMPH administration can predict the expression of locomotor sensitization has not been assessed. Here, we examined DLS neuronal activity before and after repeated AMPH administration and related it to the susceptibility of rats to sensitize. For that, single-unit recordings on DLS medium spiny neurons (MSNs) were carried out in freely moving male Sprague Dawley rats during repeated AMPH administration. We also examined differences in neurostructure that could accompany sensitization. We quantified the density of the inhibitory postsynaptic marker gephyrin (Geph) in the entopeduncular nucleus (EP) and globus pallidus (GP). A higher burst firing and a lower percentage of correlation between MSNs post-Saline firing rate vs. locomotion predicted the expression of locomotor sensitization. Moreover, during the AMPH challenge, we observed that burst firing decreased in sensitized rats, in contrast to non-sensitized rats in which burst firing was maintained. Finally, a higher Geph density on GP but not EP was observed in non-sensitized rats after AMPH challenge. These results indicate that initial differences in DLS burst firing might underlie the susceptibility to express locomotor sensitization and suggest that the potentiation of dorsal striatum indirect pathway could be considered a protective mechanism to locomotor sensitization.


Assuntos
Acatisia Induzida por Medicamentos , Anfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Neurônios GABAérgicos/efeitos dos fármacos , Globo Pálido/efeitos dos fármacos , Neostriado/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacos
5.
J Clin Psychopharmacol ; 41(6): 667-672, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34735099

RESUMO

PURPOSE/BACKGROUND: The aim of this study was to examine the association between genetically predicted CYP2D6 phenotypes and extrapyramidal symptoms (EPSs). METHODS/PROCEDURES: Data from the Tolerability and Efficacy of Antipsychotics trial of adolescents with first-episode psychosis randomized to aripiprazole versus quetiapine extended release were studied. Extrapyramidal symptom assessments included the Simpson-Angus Scale and the Barnes Akathisia Rating Scale. Patients were CYP2D6 genotyped. Plasma concentrations of antipsychotics and antidepressants were analyzed. FINDINGS/RESULTS: One hundred thirteen youths (age, 12-17 years; males, 30%; antipsychotic naive, 51%) were enrolled. Poor metabolizers had a significantly higher dose-adjusted aripiprazole plasma concentration (±SD) compared with normal metabolizers at week 4 (24.30 ± 6.40 ng/mL per milligram vs 14.85 ± 6.15 ng/mL per milligram; P = 0.019), but not at week 12 (22.15 ± 11.04 ng/mL per milligram vs 14.32 ± 4.52 ng/mL per milligram; P = 0.067). This association was not found in the quetiapine extended release group. No association between CYP2D6 genotype groups and global Barnes Akathisia Rating Scale score or Simpson-Angus Scale score was found in any of the treatment arms. IMPLICATIONS/CONCLUSIONS: Our results do not support routine use of CYP2D6 testing as a predictor of drug-induced parkinsonism or akathisia risk in clinical settings. Further studies with larger samples of CYP2D6 poor metabolizers are needed.


Assuntos
Acatisia Induzida por Medicamentos/etiologia , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Sistema Enzimático do Citocromo P-450/genética , Doença de Parkinson Secundária/induzido quimicamente , Transtornos Psicóticos/tratamento farmacológico , Fumarato de Quetiapina/efeitos adversos , Adolescente , Antipsicóticos/administração & dosagem , Antipsicóticos/sangue , Aripiprazol/administração & dosagem , Aripiprazol/sangue , Criança , Preparações de Ação Retardada , Feminino , Genótipo , Humanos , Masculino , Fumarato de Quetiapina/administração & dosagem , Fumarato de Quetiapina/sangue , Índice de Gravidade de Doença
6.
Behav Brain Res ; 415: 113506, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34352292

RESUMO

Recent preclinical studies have reported that pretreatment with the novel and highly-selective dopamine D3 receptor (D3R) antagonists R-VK4-40 or VK4-116 attenuates the abuse-related behavioral effects of oxycodone while enhancing its analgesic properties. However, whether these observed effects are generalizable to the broad class of D3R antagonists and/or extend to opioids other than oxycodone has not been extensively explored. The present study sought to assess the impact of pretreatment with another selective D3R antagonist, PG01037, on several behavioral effects of morphine in mice. C57Bl/6 J mice were pretreated with PG01037 (0-10 mg/kg) and tested for 1) hyperlocomotion induced by acute morphine (5.6-56 mg/kg), 2) locomotor sensitization following repeated morphine (56 mg/kg), 3) antinociception following acute morphine (18 mg/kg), and 4) catalepsy following administration of PG01037 alone or in combination with morphine (56 mg/kg). PG01037 dose-dependently attenuated morphine-induced hyperlocomotion and morphine-induced antinociception at doses that did not alter basal locomotion or nociception alone, but did not prevent the induction of locomotor sensitization following repeated morphine administration. Moreover, PG01037 did not induce catalepsy either alone or in combination with morphine. These results suggest that attenuation of acute opioid-induced hyperactivity may be a behavioral effect shared among D3R-selective antagonists, thus supporting continued investigations into their use as potential treatments for opioid use disorder. However, PG01037 is unlike newer, highly-selective D3R antagonists in its capacity to reduce opioid-induced antinociception, indicating that modulation of opioid analgesia may vary across different D3R antagonists.


Assuntos
Acatisia Induzida por Medicamentos/tratamento farmacológico , Benzamidas/farmacologia , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Entorpecentes/farmacologia , Nociceptividade/efeitos dos fármacos , Piridinas/farmacologia , Receptores de Dopamina D3/antagonistas & inibidores , Animais , Comportamento Animal/efeitos dos fármacos , Benzamidas/administração & dosagem , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/administração & dosagem , Entorpecentes/administração & dosagem , Piridinas/administração & dosagem
7.
Psychopharmacol Bull ; 51(3): 72-78, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34421146

RESUMO

Akathisia is a movement disorder affecting the trunk and limbs, characterized by subjective and objective restlessness. Key signs include continual, repetitive rocking, leg shuffling, and fidgeting. Antipsychotic-induced akathisia is optimally managed by reducing the medication dose or switching to a second generation antipsychotic that is less prone to inducing akathisia. However, since medication changes are often not feasible, we review the available classes of rescue agents for akathisia symptoms. The fitting acronym, "B-CALM", which stands for Beta-blockers, Clonazepam, Anticholinergics, cLonidine and Mirtazapine, will assist prescribers in facile recall of evidence-based treatment options for akathisia. Pharmacological agents such as mianserin, trazodone, Vit B6, amantadine, gabapentin, and pregabalin have also been examined as treatment options for antipsychotic-induced akathisia. Although initial exploratory reports on these agents have been promising, the current evidence is insufficient. Akathisia has a good prognosis when managed early in the course of treatment. A variety of safe rescue agents are available for the management of this condition, however, current evidence best supports the use of propranolol and mirtazapine.


Assuntos
Acatisia Induzida por Medicamentos , Antipsicóticos , Mirtazapina/uso terapêutico , Propranolol/uso terapêutico , Acatisia Induzida por Medicamentos/tratamento farmacológico , Antipsicóticos/efeitos adversos , Humanos , Agitação Psicomotora
8.
Eur Rev Med Pharmacol Sci ; 25(14): 4746-4756, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34337722

RESUMO

OBJECTIVE: Akathisia is among the most troubling effects of psychiatric drugs as it is associated with significant distress on behalf of the patients, and it limits treatment adherence. Though it most commonly presents during treatment with antipsychotic drugs which block dopamine D2 receptors, Akathisia has also been reported during treatment with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), stimulants, mirtazapine, tetrabenazine and other drugs. MATERIALS AND METHODS: This article was designed as a narrative review on akathisia with a focus on its clinical presentation, pathophysiology and management. A PubMed search for akathisia was conducted which returned 8481 articles. RESULTS: Akathisia is experienced as severe restlessness commonly accompanied by dysphoria and purposeless movement which relieves subjective tension. It has been attributed to an imbalance between dopaminergic and noradrenergic neurotransmission in the basal ganglia. Acute akathisia commonly resolves upon treatment discontinuation but tardive and chronic akathisia may persist after the causative agent is withdrawn and prove resistant to pharmacological treatment. Even drugs which induce no other extrapyramidal side effects (such as clozapine, quetiapine, aripiprazole and cariprazine) may induce akathisia. A high index of suspicion should be maintained in patients with motor disabilities, drug-induced parkinsonism and those under mechanical restraint. Propranolol and low-dose mirtazapine are the most thoroughly studied pharmacological interventions for akathisia, though benzodiazepines, voltage-gated calcium channel blockers (gabapentin, pregabalin) and opioids may be effective. CONCLUSIONS: Pharmacological management may pose a challenge in chronic akathisia. Rotation between different pharmacological management strategies may be optimal in resistant cases. Discontinuation of the causative drug and use of b-blockers, mirtazapine, benzodiazepines or gabapentinoids for symptomatic relief is the basis of management.


Assuntos
Acatisia Induzida por Medicamentos/diagnóstico , Acatisia Induzida por Medicamentos/terapia , Antipsicóticos/efeitos adversos , Clorpromazina/efeitos adversos , Acatisia Induzida por Medicamentos/fisiopatologia , Animais , Dopamina/deficiência , Humanos
10.
Ugeskr Laeger ; 183(21)2021 05 24.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34060465

RESUMO

This case report describes a 57-year-old male with symptoms of tardive akathisia after long-term metoclopramide treatment. As metoclopramide is a dopamine receptor antagonist, it has the potential to cause drug-induced movement disorders, including akathisia, which is characterised by an inner restlessness resulting in a need for constant movement. Tardive akathisia, in contrast to acute akathisia, evolves after prolonged exposure to the triggering medication and can be a permanent condition. Treatment duration of metoclopramide should be restricted, and awareness of neurological side effects is important.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Metoclopramida , Acatisia Induzida por Medicamentos/etiologia , Antagonistas de Dopamina/efeitos adversos , Humanos , Masculino , Metoclopramida/efeitos adversos , Pessoa de Meia-Idade , Agitação Psicomotora
11.
Artigo em Espanhol | LILACS | ID: biblio-1380306

RESUMO

La acatisia es uno de los eventos adversos inducidos por antipsicóticos más prevalentes y puede generar severa angustia en quien lo experimente. Se caracteriza por inquietud psicomotora objetiva y subjetiva. Pertenece al gran paraguas de los "síntomas extrapiramidales", sin embargo, tiene sus particularidades clínicas lo que representa un desafío clínico, tanto en su diagnóstico como en su manejo específico. La presente revisión sintetiza la información disponible a la fecha y ofrece al clínico recomendaciones para prevenir, reconocer y manejar esta complicación frecuente de una de las familias de psicofármacos de mayor prescripción clínica en la actualidad.


Abstract. Akathisia is one of the most prevalent antipsychotic-induced adverse events and causes severe distress in those who experience it. It is characterized by objective and subjective psychomotor restlessness. Usually classified under the great umbrella of extrapyramidal symptoms; however, it has its own clinical peculiarities, which might represent a challenge for the clinician in diagnosis as well as specific management. This review synthesizes the information available to date on antipsychotic-induced akathisia and offers the clinician recommendations to prevent, recognize and treat this prevalent complication of one of the most widely prescribed psychotropic medications today.


Assuntos
Humanos , Antipsicóticos/efeitos adversos , Acatisia Induzida por Medicamentos/terapia , Guia de Prática Clínica
12.
Clin Toxicol (Phila) ; 59(8): 698-704, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33295809

RESUMO

BACKGROUND: Toxicity from antimuscarinic agents precipitates a constellation of signs and symptoms; two of the most significant are agitation and delirium. Benzodiazepines are commonly used for treatment; physostigmine is also effective but is underutilized due to concerns for safety and short duration of action. The objective of this study was to compare lorazepam to physostigmine for the treatment of antimuscarinic delirium and agitation. METHODS: This was a blinded, randomized clinical trial in patients presenting for antimuscarinic toxidrome. Inclusion criteria were: ≥10-<18 years old, at least one central and two peripheral antimuscarinic symptoms, delirium and moderate agitation. Subjects were randomized to either (1) lorazepam bolus (0.05 mg/kg) followed by a 4-h normal saline infusion, or (2) physostigmine 0.02 mg/kg bolus followed by a 4-h physostigmine infusion (0.02 mg/kg/h). Primary outcomes were the control of delirium and agitation after bolus and during the infusion. RESULTS: Ten (53%) subjects were enrolled in the lorazepam arm, 9 (47%) in the physostigmine arm. Diphenhydramine was the most common agent ingested (16, 84%). Fewer patients receiving physostigmine had delirium after the initial bolus (44% vs 100%, p = 0.01) and at the 4th hour of infusion (22% vs 100%, p < 0.001) compared to patients who received lorazepam. There was a significant decrease in agitation scores in the physostigmine arm compared to the lorazepam arm after the initial bolus (89% vs 30%, p = 0.02), but no difference at the 4th hour of infusion (p > 0.99). There were no seizures, bradycardia, bronchorrhea, bronchospasm, intubation, or cardiac dysrhythmias. CONCLUSION: Physostigmine was superior to lorazepam in controlling antimuscarinic delirium and agitation after bolus dosing, and control of delirium after a 4-h infusion. There were no serious adverse events in either treatment arm. Physostigmine bolus and infusion should be considered in adolescent patients with significant delirium and agitation from antimuscarinic agents.


Assuntos
Acatisia Induzida por Medicamentos/tratamento farmacológico , Delírio/tratamento farmacológico , Lorazepam/uso terapêutico , Antagonistas Muscarínicos/toxicidade , Fisostigmina/uso terapêutico , Adolescente , Ansiolíticos/uso terapêutico , Delírio/induzido quimicamente , Difenidramina/toxicidade , Método Duplo-Cego , Feminino , Humanos , Tempo de Internação , Masculino , Resultado do Tratamento
13.
Expert Opin Pharmacother ; 22(4): 415-426, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33126812

RESUMO

Introduction: Schizophrenia is a very disabling condition that may result in a significant impairment of individual, professional, and social adjustments. Antipsychotics (APs), the first-line treatment for schizophrenia, in many cases modify the course of the disease, by reducing the institutionalization risk, at the price of severe and invalidating side effects. Cariprazine is one of the latest second-generation APs (SGAs) acting as a partial agonist of type 2 and 3 dopamine receptors, which was recently approved for the treatment of adult schizophrenia.Areas covered: The authors provide a critical review and commentary on the currently available data on the effectiveness and tolerability of cariprazine in schizophrenic patients, with a particular focus on its specific target symptoms.Expert opinion: Cariprazine appears significantly effective on both acute and maintenance treatment of schizophrenia, and in improving positive, negative, and cognitive symptoms, slightly more than other SGAs. It shows a good safety and tolerability profile, with akathisia being its most common side effect. Although further independent studies are needed to clarify its precise advantages over other SGAs, cariprazine seems a promising compound not only in schizophrenia, but also in a broad range of psychiatric conditions, including perhaps bipolar and addictive disorders.


Assuntos
Antipsicóticos/uso terapêutico , Piperazinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Acatisia Induzida por Medicamentos/etiologia , Humanos
14.
Scand J Med Sci Sports ; 31(2): 427-438, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33038020

RESUMO

An estimated 4-6% of fitness center visitors uses anabolic-androgenic steroids (AAS). Reliable data about adverse reactions of AAS are scarce. The HAARLEM study aimed to provide insight into the positive and negative effects of AAS use. One hundred men (≥18 years) who intended to start an AAS cycle on short notice were included for follow-up. Clinic visits took place before (T0 ), at the end (T1 ), and three months after the end of the AAS cycle (T2 ), and one year after the start of the cycle (T3 ), and comprised a medical history, physical examination, laboratory analysis, and psychological questionnaires. During the follow-up period, four subjects reported a serious adverse event, that is, congestive heart failure, acute pancreatitis, suicidal ideation, and exacerbation of ulcerative colitis. All subjects reported positive side effects during AAS use, mainly increased strength (100%), and every subject reported at least one negative health effect. Most common were fluid retention (56%) and agitation (36%) during the cycle, and decreased libido (58%) after the cycle. Acne and gynecomastia were observed in 28% and 19%. Mean alanine transaminase (ALT) and creatinine increased 18.7 U/l and 4.7 µmol/L, respectively. AAS dose and cycle duration were not associated with the type and severity of side effects. After one-year follow-up (T3 ), the prevalence of observed effects had returned to baseline. There was no significant change in total scores of questionnaires investigating wellbeing, quality of life, and depression. In conclusion, all subjects experienced positive effects during AAS use. Four subjects experienced a serious adverse event. Other side effects were mostly anticipated, mild, and transient.


Assuntos
Anabolizantes/farmacologia , Androgênios/farmacologia , Acne Vulgar/induzido quimicamente , Adulto , Idoso , Acatisia Induzida por Medicamentos/etiologia , Anabolizantes/efeitos adversos , Androgênios/efeitos adversos , Biomarcadores/sangue , Colite Ulcerativa/induzido quimicamente , Depressão/induzido quimicamente , Progressão da Doença , Ginecomastia/induzido quimicamente , Insuficiência Cardíaca/induzido quimicamente , Humanos , Libido/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Países Baixos , Pancreatite/induzido quimicamente , Estudos Prospectivos , Ideação Suicida , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
15.
J Pharmacol Sci ; 145(1): 42-51, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357778

RESUMO

Schizophrenia significantly limits social functioning with positive and negative symptoms and cognitive dysfunction. Blonanserin (LONASEN®), a novel second-generation antipsychotic approved for treating schizophrenia in Japan in 2008, reportedly shows beneficial effects on cognitive function as well as positive and negative symptoms, with potential for improving social functioning. To understand the safety and effectiveness of blonanserin in the real clinical practice, five Japanese post-marketing surveillances have been conducted and published to date. In this article, we reviewed all the Japanese post-marketing surveillances and discussed the clinical usefulness of blonanserin in patients with schizophrenia having diverse clinical characteristics. Adverse drug reactions, such as akathisia and extrapyramidal symptoms, were common in all surveillances. However, those specific to second-generation antipsychotics, such as weight gain and abnormalities in glycometabolism or lipid metabolism, were rarely observed. In addition, no adverse drug reactions apart from clinical trial results were found. Brief Psychiatric Rating Scale total scores in all surveillances significantly lowered at the last evaluation than at baseline. These results were consistent through 1-year of treatment, suggesting that effectiveness is maintained even after long-term use. In conclusion, blonanserin is considered a beneficial drug in real clinical practice for patients with schizophrenia having diverse characteristics.


Assuntos
Antipsicóticos/administração & dosagem , Piperazinas/administração & dosagem , Piperidinas/administração & dosagem , Vigilância de Produtos Comercializados , Esquizofrenia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Acatisia Induzida por Medicamentos/etiologia , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacologia , Doenças dos Gânglios da Base/etiologia , Criança , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Piperazinas/farmacologia , Piperidinas/efeitos adversos , Piperidinas/farmacologia , Segurança , Resultado do Tratamento , Adulto Jovem
16.
Anesth Analg ; 132(2): 353-364, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33177329

RESUMO

Emergence agitation (EA) is a self-limited state of psychomotor excitement during awakening from general anesthesia. EA is confined to the emergence period as consciousness is restored, which sharply distinguishes it from other postoperative delirium states. Sporadic episodes of EA may become violent with the potential for harm to both patients and caregivers, but the long-term consequences of such events are not fully understood. Current literature on EA in adults is limited to small-scale studies with inconsistent nomenclature, variable time periods that define emergence, a host of different surgical populations, and conflicting diagnostic criteria. Therefore, true incidence rates and risk factors are unknown. In adult noncardiac surgery, the incidence of EA is approximately 19%. Limited data suggest that young adults undergoing otolaryngology operations with volatile anesthetic maintenance may be at the highest risk for EA. Currently suggested EA mechanisms are theoretical but might reflect underblunted sympathetic activation in response to various internal (eg, flashbacks or anxiety) or external (eg, surgical pain) stimuli as consciousness returns. Supplemental dexmedetomidine and ketamine may be utilized for EA prevention. Compared to the civilian population, military veterans may be more vulnerable to EA due to high rates of posttraumatic stress disorder (PTSD) manifesting as violent flashbacks; however, confirmatory data are limited. Nonetheless, expert military medical providers suggest that use of patient-centered rapport tactics, PTSD trigger identification and avoidance, and grounding measures may alleviate hyperactive emergence phenomena. Future research is needed to better characterize EA in veterans and validate prophylactic measures to optimize care for these patients. This narrative review provides readers with an important framework to distinguish EA from delirium. Furthermore, we summarize current knowledge of EA risk factors, mechanisms, and adult management strategies and specifically revisit them in the context of veteran perioperative health. The anesthesiology care team is ideally positioned to further explore EA and develop effective prevention and treatment protocols.


Assuntos
Acatisia Induzida por Medicamentos/etiologia , Anestesia Geral/efeitos adversos , Anestésicos Gerais/efeitos adversos , Delírio do Despertar/induzido quimicamente , Transtornos de Estresse Pós-Traumáticos/complicações , Saúde dos Veteranos , Veteranos/psicologia , Acatisia Induzida por Medicamentos/diagnóstico , Acatisia Induzida por Medicamentos/prevenção & controle , Acatisia Induzida por Medicamentos/psicologia , Período de Recuperação da Anestesia , Delírio do Despertar/diagnóstico , Delírio do Despertar/prevenção & controle , Delírio do Despertar/psicologia , Humanos , Saúde Mental , Medição de Risco , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Violência
18.
J Clin Psychopharmacol ; 40(6): 611-614, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044356

RESUMO

BACKGROUND: Akathisia is a distressing extrapyramidal complication that follows the use of antipsychotic medications. Early treatment of neuroleptic-associated akathisia (NAA) is of great importance because it may lead to poor therapeutic response and ultimately treatment noncompliance. Considering the lack of adequate response of some patients to conventional treatments and the assumption that serotonin might be involved in the pathophysiology of the disease in addition to dopaminergic mechanisms, we aimed to evaluate the effectiveness of trazodone as an antidepressant agent with strong antagonistic effects on serotonin receptors in the treatment of akathisia. METHODS: In a double-blind clinical trial, 52 patients receiving antipsychotic medications who were diagnosed to have mild to severe NAA using Barnes Akathisia Rating Scale were treated with trazodone 50 mg daily for 5 days and compared with the placebo control group. RESULTS: Patients receiving trazodone did not show a significant difference compared with the control group in terms of the severity of akathisia symptoms until the third day of the study. In contrast, at the end of the fifth day, there was a significant improvement in objective (P = 0.01) and subjective (P = 0.001) symptoms of akathisia and the global clinical assessment of akathisia scale (P = 0.001). Moreover, there was no clear difference between trazodone and placebo group in terms of adverse effects. CONCLUSIONS: Considering the antagonistic effect of trazodone on postsynaptic 5-hydroxytryptamine2A receptors as a possible mechanism of efficacy of this agent in the treatment of NAA, this study suggests that trazodone might be an effective and relatively safe drug.


Assuntos
Acatisia Induzida por Medicamentos/tratamento farmacológico , Antipsicóticos/efeitos adversos , Atividade Motora/efeitos dos fármacos , Trazodona/uso terapêutico , Adulto , Acatisia Induzida por Medicamentos/diagnóstico , Acatisia Induzida por Medicamentos/etiologia , Acatisia Induzida por Medicamentos/psicologia , Antidepressivos de Segunda Geração/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Trazodona/efeitos adversos , Resultado do Tratamento
20.
Parkinsonism Relat Disord ; 79: 60-64, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32871538

RESUMO

Most movement disorders in psychiatric patients are induced by neuroleptic antipsychotic medications, all of which are dopamine D2 receptor blocking drugs. These include: acute onset disorders: dystonic reactions, akathisia and the neuroleptic malignant syndrome (NMS); non-acute onset parkinsonism; and the tardive syndromes. However, many other medications, when used at recommended doses, also induce movement disorders, with tremor being the most common. With the exception of serotonin syndrome, they are rarely as severe or disabling as the neuroleptic extrapyramidal syndromes may be. The serotonin reuptake inhibiting (SSRI) drugs are associated with the serotonin syndrome, a life-threatening disorder, but may also cause tremor and akathisia. While SSRI's have been thought to occasionally cause a tardive dyskinesia-like syndrome, this almost never occurs without prior or concurrent neuroleptic exposure as well. There also are few reliable data to support an association between antidepressants and parkinsonism. Valproic acid has been shown to cause parkinsonism, and lithium may as well, in addition to both having the well-known side effect of tremors. Myoclonus and asterixis are usually induced by toxic levels of medications but may appear with therapeutic levels, particularly with anticonvulsant mood stabilizers, and clozapine. Ataxia rarely occurs with non-toxic levels of drug, particularly anticonvulsants, benzodiazepines and lithium.


Assuntos
Acatisia Induzida por Medicamentos/etiologia , Antidepressivos/efeitos adversos , Antimaníacos/efeitos adversos , Discinesia Induzida por Medicamentos/etiologia , Transtornos Mentais/tratamento farmacológico , Doença de Parkinson Secundária/induzido quimicamente , Transtorno do Comportamento do Sono REM/induzido quimicamente , Tremor/induzido quimicamente , Humanos
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