Effects of haloperidol injection: A Synthesis of Findings from 29 Studies

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Original Abstract of the Article

Major Research Findings

Haloperidol injection is a typical antipsychotic drug used to treat mental illnesses such as schizophrenia and manic states. Haloperidol works by blocking dopamine D2 receptors. This review summarizes various research findings on haloperidol injections.

Haloperidol injection is often used to control agitation and aggression in patients with acute psychosis. 7 Also, haloperidol has been suggested to be as effective as oral atypical antipsychotics in the acute treatment of schizophrenia. 16 However, haloperidol can cause serious side effects such as neuroleptic malignant syndrome and extrapyramidal symptoms. Neuroleptic malignant syndrome is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. 6 Symptoms include fever, muscle rigidity, and cognitive changes. Also, a case report of a 48-year-old man who developed typical clinical symptoms and laboratory parameters of malignant hyperthermia syndrome after injection of haloperidol has been reported. 6 To differentiate NMS from other malignant hyperthermia syndromes, identifying the offending drug and clinical history are essential. 6 Treatment includes withdrawal of the causative medication and intensive care treatment, possibly with administration of dantrolene. 6

Haloperidol may affect dopamine D2 receptor activity and inhibit the recognition of new objects. However, low doses of haloperidol may restore this recognition impairment by adjusting the activity level of dopamine D2 receptors. 8 Also, haloperidol can alter neuronal activity in the striatum and cause extrapyramidal symptoms. 15 Haloperidol induces Nur77 expression in the striatum, and its expression is under the control of protein phosphatase 1 regulation by DARPP-32. Nur77 is an orphan nuclear receptor and a dopamine-regulated immediate-early gene. These findings suggest a new molecular mechanism by which haloperidol may cause extrapyramidal symptoms.

Haloperidol may affect the expression of mRNA related to glutamate and GABA receptors in the brains of offspring when administered to pregnant mice. 2 Intraperitoneal injection of haloperidol to pregnant mice resulted in significantly higher levels of Grik3 and Gabra3 mRNA expression and significantly lower levels of Gria2 and Grin2a mRNA expression in the brains of their offspring. 2 This suggests that haloperidol may affect brain development during the fetal period. 2

Haloperidol may affect dopamine, serotonin, and their metabolism in the striatum of rats. 28 Administration of tryptophan increased the concentration of tryptophan, 5-HT, 5-HIAA, and DA in the striatum. 28 Administration of valine increased the concentration of DOPAC in the striatum. 28 Administration of haloperidol increased the concentration of HVA, 5-HT, and 5-HIAA. 28 These results suggest that haloperidol may affect the balance of neurotransmitters in the brain. 28

Haloperidol may affect dopamine levels, prolactin secretion, and cortisol secretion in the brains of rats. 17 Haloperidol has been shown to decrease dopamine levels in the brains of rats. 17 Also, haloperidol has been shown to increase prolactin secretion and cortisol secretion. 17 However, listening to classical music, such as Mozart's Sonata for Two Pianos (K. 448), has been shown to suppress these effects of haloperidol. 17 Music has been shown to increase dopamine levels in the brains of rats and decrease prolactin secretion and cortisol secretion. 17

Benefits and Risks

Benefit Summary

Haloperidol injection helps control agitation and aggression in patients with acute psychosis. 7 It may also be as effective as oral atypical antipsychotics in the acute treatment of schizophrenia. 16 Low doses of haloperidol may restore recognition impairment by adjusting the activity level of dopamine D2 receptors. 8

Risk Summary

Haloperidol can cause serious side effects such as neuroleptic malignant syndrome and extrapyramidal symptoms. 6 Neuroleptic malignant syndrome is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. 6 Symptoms include fever, muscle rigidity, and cognitive changes. 6 Haloperidol can alter neuronal activity in the striatum and cause extrapyramidal symptoms. 15 Haloperidol may affect brain development during the fetal period when administered to pregnant mice. 2 Haloperidol may affect dopamine levels, prolactin secretion, and cortisol secretion in the brains of rats. 17 Haloperidol has been shown to decrease dopamine levels in the brains of rats. 17 Also, haloperidol has been shown to increase prolactin secretion and cortisol secretion. 17

Comparison Between Studies

Similarities

Many studies have shown that haloperidol affects dopamine D2 receptors and affects brain function. Specifically, it has been shown to affect dopamine levels, neuronal activity, and gene expression in brain regions such as the striatum and hypothalamus. 6 7 21 22 10 24 11 5 16 8 3 2 28 23 29 19 26 27 20 25 1 15 12 9 4 13 17

Differences

Some studies have shown that haloperidol can cause side effects such as extrapyramidal symptoms. 6 15 Other studies have shown that haloperidol can inhibit the recognition of new objects. 8 Also, it has been shown that haloperidol may affect brain development during the fetal period when administered to pregnant mice. 2

Consistency and Contradictions in Results

Many studies have shown that haloperidol affects dopamine D2 receptors and affects brain function, but the extent of its effects and the specific mechanisms vary among studies. Also, haloperidol has been suggested to cause side effects such as extrapyramidal symptoms and the inhibition of new object recognition, but the incidence and severity of these side effects are thought to vary depending on individual constitution and dosage. 6 7 21 22 10 24 11 5 16 8 3 2 28 23 29 19 26 27 20 25 1 15 12 9 4 13 17

Practical Implications

Haloperidol is an effective drug for the treatment of mental illnesses, but it can cause serious side effects. Therefore, it is important to follow your doctor's instructions carefully and be aware of the side effects when taking haloperidol. Also, haloperidol may not be able to be taken or may require caution for pregnant or breastfeeding women, people with liver or kidney disease, and the elderly. Consult your doctor before taking haloperidol. 6 7 16 8 3 2 28 26 25 13

Limitations of Current Research

Research on haloperidol is often based on animal studies and small clinical trials, and it is unclear whether the results are directly applicable to humans. Also, the effects and side effects of haloperidol vary depending on individual constitution and dosage, so more research is needed. 6 7 16 8 3 2 28 26 25 13

Future Research Directions

Further research on haloperidol should include large-scale clinical trials to further investigate its effects and side effects in humans. Also, molecular-level research is needed to elucidate the mechanisms of action and side effects of haloperidol. 6 7 16 8 3 2 28 26 25 13

Conclusion

Haloperidol injection is an effective drug for the treatment of mental illnesses, but it can also cause serious side effects. It is important to follow your doctor's instructions carefully and be aware of the side effects when taking haloperidol. Also, haloperidol may not be able to be taken or may require caution for pregnant or breastfeeding women, people with liver or kidney disease, and the elderly. Consult your doctor before taking haloperidol. 6 7 16 8 3 2 28 26 25 13

Literature analysis of 29 papers
Positive Content
21
Neutral Content
4
Negative Content
4
Article Type
2
2
2
1
29
2.

Effects of gestational haloperidol exposure on mRNA expressions related to glutamate and GABA receptors in offspring.

Author: KumonHiroshi, YoshinoYuta, FunahashiYu, OchiShinichiro, IgaJun-Ichi, UenoShu-Ichi

GABA receptor effects
Glutamate receptor effects

Fetal exposure to haloperidol can affect glutamate and GABA receptors in the brain of offspring mice, with changes in mRNA expression levels in the hippocampus and frontal lobes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An update on management of behavioral and psychological symptoms in dementia.

Author: ChenAnderson, CopeliFrank, MetzgerEran, CloutierAlesia, OsserDavid N

BPSD management
Adverse effects

This article provides updated algorithms for the use of psychopharmacologic agents in geriatric patients with dementia and behavioral and psychological symptoms of dementia (BPSD). The algorithms consider recent research and provide recommendations for emergent, urgent, and non-urgent settings.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

5.

Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors.

Author: SonegoAndreza B, PradoDouglas S, ValeGabriel T, Sepulveda-DiazJulia E, CunhaThiago M, TirapelliCarlos R, Del BelElaine A, Raisman-VozariRita, GuimarãesFrancisco S

Treats tardive dyskinesia

This study investigated the effects of cannabidiol (CBD) on orofacial dyskinesia, oxidative stress, and inflammatory changes induced by chronic haloperidol administration in mice. CBD was found to prevent haloperidol-induced orofacial dyskinesia, reduce microglial activation and inflammatory mediators, and attenuate oxidative stress. These effects were mediated by PPARγ receptors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

[Prolonged neuroleptic malignant syndrome after Haloperidol injection].

Author: WystubN, HeymelS, FritzenwangerM, SchulzeP C, PfeiferR

Neuroleptic malignant syndrome

A 48-year-old man developed symptoms of neuroleptic malignant syndrome (NMS) after receiving haloperidol. NMS is a rare, serious reaction to antipsychotic drugs characterized by fever, muscle rigidity, and cognitive changes. Laboratory tests showed elevated creatine kinase levels and signs of rhabdomyolysis, consistent with NMS. The patient was treated by stopping haloperidol and receiving intensive care.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : German

7.

Efficacy and Safety of Levosulpiride Versus Haloperidol Injection in Patients With Acute Psychosis: A Randomized Double-Blind Study.

Author: LavaniaSagar, PraharajSamir Kumar, BainsHariender Singh, SinhaVishal, KumarAbhinav

Fewer extrapyramidal symptoms
Reduced aggression
Reduced agitation
Less effective than haloperidol

Haloperidol was more effective than levosulpiride injection for psychotic symptoms, aggression, and severity of agitation in acute psychosis. However, extrapyramidal adverse effects were less frequent with levosulpiride as compared with those receiving haloperidol.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

9.

A comparison of the effectiveness of risperidone, haloperidol and flupentixol long-acting injections in patients with schizophrenia--A nationwide study.

Author: YuHsaing-Yuan, HsiaoChih Yin, ChenKao Chin, LeeLan-Ting, ChangWei Hung, ChiMei Hung, Hui LeeI, ChenPo See, YangYen Kuang

Reduced relapses

Risperidone long-acting injection (RLAI) is not superior to haloperidol or flupentixol long-acting injections in terms of effectiveness, but it might have fewer adverse effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials.

Author: KishiTaro, HirotaTomoya, MatsunagaShinji, IwataNakao

Delirium treatment
Dry mouth
Sedation

Second-generation antipsychotics (SGAs) were more beneficial than haloperidol in treating delirium, with regard to both efficacy and safety. However, further research with larger samples is needed.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

11.

D2 dopamine receptor regulation of learning, sleep and plasticity.

Author: FrançaA S C, Lobão-SoaresB, MuratoriL, NascimentoG, WinneJ, PereiraC M, JeronimoS M B, RibeiroS

Learning enhancement
REM sleep regulation

Dopamine and REM sleep are both linked to hippocampus-dependent learning. This study found that blocking dopamine receptors reduced REM sleep and impaired learning in mice. This suggests that dopamine's influence on learning may be mediated through its role in regulating REM sleep.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Length of mechanical restraint following haloperidol injections versus oral atypical antipsychotics for the initial treatment of acute schizophrenia: a propensity-matched analysis from the Japanese diagnosis procedure combination database.

Author: NakamuraMitsuhiro, YasunagaHideo, HaraguchiTadashi, AndoShuntaro, SugiharaToru, HoriguchiHiromasa, OheKazuhiko, MatsudaShinya, FushimiKiyohide

Schizophrenia treatment

The results indicate that atypical antipsychotics were as effective as haloperidol injections in the acute-phase treatment of schizophrenia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Comparison of risperidone oral solution and intramuscular haloperidol with the latter shifting to oral therapy for the treatment of acute agitation in patients with schizophrenia.

Author: FangMaosheng, ChenHonghui, LiLe-Hua, WuRenrong, LiYi, LiuLianzhong, YeMeng, HuangJizhong, ZhuSuoyu, WangGang, ZhangQinge, ZhengHongbo, ZhangLulu, WangBo, ZhouJianchu, ZhaoJing-Ping

Acute agitation treatment
Extrapyramidal symptoms

Risperidone oral solution (RIS-OS) combined with clonazepam was as effective as intramuscular haloperidol in treating acute agitation in patients with schizophrenia. RIS-OS was associated with fewer extrapyramidal symptoms.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Long-term ventilatory adaptation and ventilatory response to hypoxia in plateau pika (Ochotona curzoniae): role of nNOS and dopamine.

Author: PichonAurélien, ZhenzhongBai, FavretFabrice, JinGuoen, ShufengHan, MarchantDominique, RichaletJean-Paul, GeRi-Li

Hypoxia adaptation

This study compared ventilatory patterns and responses to hypoxia in high-altitude pikas and rats. Pikas exhibited a larger tidal volume and lower respiratory frequency than high-altitude rats, and a higher tidal volume and lower expiratory time than low-altitude rats. In pikas, the sensitivity to severe acute hypoxia seemed to be regulated by a peripheral nNOS mechanism.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Validation of a novel social investigation task that may dissociate social motivation from exploratory activity.

Author: DeakTerrence, ArakawaHiroyuki, BekkedalMarni Y V, PankseppJaak

Social motivation assessment

This study validates a new paradigm that assesses social investigation and exploratory activity in rats, providing insight into social motivation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Validation StudyResearch to assess the validity and reliability of new measurement methods or diagnostic tests.

Language : English

22.

Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol.

Author: Bertran-GonzalezJesus, BoschClémentine, MaroteauxMatthieu, MatamalesMiriam, HervéDenis, ValjentEmmanuel, GiraultJean-Antoine

This study found that cocaine and haloperidol, a drug used to treat schizophrenia, activate different signaling pathways in the brain. Cocaine activates pathways in neurons that express the dopamine D1 receptor, while haloperidol activates pathways in neurons that express the dopamine D2 receptor. This finding may help to explain how these drugs exert their effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Dysregulation of the mesolimbic dopamine system and reward in MCH-/- mice.

Author: PissiosPavlos, FrankLauren, KennedyAdam R, PorterDouglas R, MarinoFrancis E, LiuFen-Fen, PothosEmmanuel N, Maratos-FlierEleftheria

This study explores the potential role of melanin-concentrating hormone (MCH) in modulating the function of midbrain dopamine neurons and associated circuitry, given the abundant expression of the MCH receptor in the striatum.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

24.

Comparison of the risk of adverse events between risperidone and haloperidol in delirium patients.

Author: MiyajiShingo, YamamotoKenji, HoshinoSyunya, YamamotoHiroaki, SakaiYoshiro, MiyaokaHitoshi

Delirium treatment
Adverse events
Death

This study investigated the risk of adverse events associated with risperidone and haloperidol in patients with delirium. The incidence of adverse events was significantly lower for risperidone, while the incidence of death during delirium was significantly higher for intravenous or intramuscular haloperidol.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

25.

Evaluation of in vitro release and in vivo efficacy of mPEG-PLA-haloperidol conjugate micelle-like structures.

Author: HansMeredith L, MaxwellChristina, EhrlichmanRichard S, MetzgerKayla, LiangYuling, SiegelSteven J, LowmanAnthony M

Haloperidol delivery
Reduced side effects

This study investigates the properties of polymeric prodrugs of mPEG-PLA-haloperidol, which self-assemble into nanoscale micelle-like structures. These micelles exhibit controlled drug release over a period of days, potentially reducing the sedative side effects of haloperidol compared to acute injections.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

26.

Long-acting neuroleptics used in wildlife management do not impair thermoregulation or physical activity in goats (Capra hircus).

Author: FickLinda, MitchellDuncan, FullerAndrea

Reduced stress-related mortality
Thermoregulation effects

Long-acting neuroleptics did not impair activity or thermoregulation of goats subjected to inescapable thermal challenges.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

27.

Clozapine but not haloperidol treatment reverses sub-chronic phencyclidine-induced disruption of conditional discrimination performance.

Author: DunnMichael J, KillcrossSimon

Cognitive deficit reversal

Phencyclidine (PCP) was found to impair conditional discrimination performance in rats, suggesting a role in cognitive deficits similar to those observed in schizophrenia. Clozapine, an atypical antipsychotic, reversed the PCP-induced deficits, while haloperidol, a typical antipsychotic, did not. This suggests that the prefrontal dopamine (DA) system may play a role in these cognitive deficits.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

28.

Effect of co administration of haloperidol and large neutral amino acids (tryptophan and valine) on rats striatal dopamine, serotonin and their metabolism.

Author: AliObaid, HaleemDarakshan J, ObaidRoohi, KamilNoor, HaleemMohammed A, AhmedSyed Waseemuddin

Less EPS
Treats Schizophrenia
Agranulocytosis

Tryptophan, a serotonin precursor, may modulate the neurochemical changes in the striatum and reduce extrapyramidal effects caused by haloperidol.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

29.

Fyn is required for haloperidol-induced catalepsy in mice.

Author: HattoriKotaro, UchinoShigeo, IsosakaTomoko, MaekawaMamiko, IyoMasaomi, SatoToshio, KohsakaShinichi, YagiTakeshi, YuasaShigeki

Treats Catalepsy

Fyn, a protein involved in tyrosine phosphorylation, was found to play a role in haloperidol-induced catalepsy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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