Administration Of Antipsychotic Drugs Research Articles

Treatment-resistant hiccups during general anesthesia possibly caused by remimazolam: a case report

BackgroundPrevious reports have described hiccups during general anesthesia that were possibly induced by drugs, including benzodiazepines. However, there are few reports of hiccups caused by remimazolam.Case presentationA 75-year-old woman underwent corneal transplantation under general anesthesia with remimazolam. She presented with hiccups once the effects of muscle relaxants used during induction wore off, which persisted even after various treatments, such as the administration of antipsychotic drugs. However, when remimazolam administration was terminated after surgery to awaken the patient, the hiccups stopped and did not recur after extubation. Evaluation of predicted blood levels of remimazolam suggests that higher levels of remimazolam might cause hiccups.ConclusionRemimazolam might induce hiccups during general anesthesia. Anesthesiologists should consider administering muscle relaxants or changing the anesthetic in cases of refractory hiccups under general anesthesia.

Effects of chronic haloperidol treatment on the expression of fear memory and fear memory extinction in the cued fear-conditioned rats.

Impairments in emotional memory are frequently observed in several mental disorders, highlighting their significance as potential therapeutic targets. Recent research on the cued fear conditioning model has elucidated the neural circuits involved in fear memory processing. However, contradictory findings have been reported concerning the role of dopamine and the impact of dopamine D2 receptor (D2R) antagonists. There is notably limited knowledge regarding the clinical utility of chronic D2R antagonist treatments. This study aimed to uncover how such treatments affect fear memory processing. We utilized a cued fear conditioning rat model and conducted chronic haloperidol treatment for 14 days. Subsequently, to investigate the effect of chronic haloperidol treatment on fear-conditioned memory expression and extinction, we observed freezing behavior under exposure to a conditioned stimulus for 14 days. Chronic haloperidol treatment suppressed freezing time on the fear memory expression. In contrast, a single haloperidol administration enhanced the freezing time on fear memory expression and delayed extinction. The results of this study suggest that chronic administration of antipsychotic drugs affects fear memory processing differently from single-dose administration. This indicates that the effects of chronic D2R antagonist treatment are distinct from the nonspecific effects of the drugs. This study provides fundamental insights that may contribute to our understanding of therapeutic mechanisms for fear memory disorders related to D2R in the future.

Effects of Chronic Administration of Antipsychotic Drug (Olanzapine) on the Anterior Pituitary Gland of Adult Male Albino Rats and the Potential Protective Role of Hypericum Perforatum

Effects of Chronic Administration of Antipsychotic Drug (Olanzapine) on the Anterior Pituitary Gland of Adult Male Albino Rats and the Potential Protective Role of Hypericum Perforatum

Medication-induced Psychotic Disorder. A Review of Selected Drugs Side Effects.

Medication-induced psychotic disorder (MIPD) is a diagnostic term for a syndrome with symptoms such as hallucinations and delusions directly related to drug intake. The purpose of this review is to report and comment on the current knowledge about pathomechanisms, risk factors, symptoms, and treatment of MIPD caused by selected widely used medications. PubMed, Scopus, and Google Scholar databases were searched for articles on MIPD published prior to January 2021 using search terms 'psychosis' OR 'psychotic disorder' AND 'side effects' combined with certain medications group. The initial search was then narrowed to medications with more pathomechanisms than only direct dopamine-inducing activity that are widely used by clinicians of various medical specialties. Steroids, antiepileptic drugs, antimalarial drugs, and antiretroviral drugs can induce psychosis with persecutory delusions and auditory hallucinations as the most frequently reported symptoms. Mood changes and anxiety may precede psychosis after steroids and antimalarials. Psychiatric history and female sex are risk factors for most of the MIPD. Treatment involves cessation of the suspected drug. Administration of atypical antipsychotic drugs may be helpful, although there is insufficient data to support this approach. The latter should be done with careful consideration of pharmacokinetic and pharmacodynamic interactions. MIPD is a rare condition. The appearance of psychotic symptoms during systemic treatment may be associated with administered medications, psychiatric comorbidity, or be a part of the clinical picture of a certain disorder. Furthermore, sometimes it may be challenging to distinguish MIPD from delirium. Therefore, we consider that the key to proper management of MIPD is a thorough differential diagnosis.

Assessment of coagulation profiles among sudanese psychiatric patients under antipsychotic drugs attending Hassan Allob Mental Hospital, Gezira State, Sudan (2020)

Background: Psychiatric disorder is a mental illness diagnosed by a mental health professional that greatly disorders thinking. A psychotropic drug is a chemical substance that crosses the blood brain barrier (BBB) and acts primarily upon the central nervous system (CNS), where it affects brain function, resulting in change in perception, mood, consciousness, cognition, and behavior. It causes changes in platelet function, plasma coagulation, or fibrinolysis seemed more likely to be responsible for the increase in thrombotic events. Objectives: The aim of this study was to assess the coagulation profiles [Prothrombin Time (PT), International Normalize Ratio (INR), Activated Partial Thromboplastin Time (APTT)] in psychiatric patients under antipsychotic drug administration. Methodology: This is a case-control hospital-based study carried out in Hassan Allob Mental Hospital, Gezira State, Sudan from January to September 2020. A total of 50 psychiatric patients under antipsychotic drug administration as cases (35.52 ± 11.64 years) and 50 normal healthy individuals as controls (32.68 ± 4.85 years) participated in this study. Two ml of venous blood samples were collected from all participants in trisodium citrate container. Coagulation profiles (PT, INR, and APTT) were measured using a Coatron M4 coagulometer. SPSS computer program (v 22.0) was used for data analysis.

Evaluation of the Salivary Flow in Patients with Schizophrenia. A Literature Review

Schizophrenia is a chronic psychiatric disease that affects approximately 1% of the global population. Schizophrenia is characterised by positive, negative and cognitive symptoms. The etiological factors of this psychiatric illness are not fully deciphered, but the most incriminated are genetic factors and environmental risk factors.
 The treatment of schizophrenia has the role of reduction the duration and intensity of episodes and consists in the administration of typical or atypical antipsychotic drugs, antiparkinsonian, anxiolytic, sedatives or antidepressants. Of these, some of the drugs may have side effects that modify patients' salivary flow rates.
 Xerostomy is a subjective sign characterized by a dry mouth sensation and is caused by hypofunction of the salivary glands. According to a series of studies, xerostomia can be an adverse effect of typical antipsychotic medication as well as antiparkinsonian medication. Sialorrhea is caused by hyperfunction of the salivary glands and is characterized by an increased secretion of saliva. This side effect is especially noticeable during the night sleep. Alteration of salivary function creates increased discomfort to the schizophrenic patient, which causes him to give up regular medication.
 The aim of this study is to review the literature on the link between schizophrenia, the treatment of schizophrenia and impaired salivary function.

THE CLOZAPINE EFFECT ON BLOOD GLUCOSE LEVELS, LEUKOCYTES AND PLATELETS IN SCHIZOPHRENIC PATIENTS IN THE MENTAL SERVICE UNIT OF BANYUMAS HOSPITAL

Schizophrenia is a disorder of strange and disordered thoughts, delusions, hallucinations, inappropriate influences, and disorders of psychosocial functioning. One of the management of schizophrenia therapy is the administration of atypical antipsychotic drugs, namely clozapine. Clozapine is an antagonist of serotonin (5-HT2) and dopamine type 2 (D2) receptors. However, the risk of using clozapine provides a risk of side effects in the form of metabolic syndromes such as impaired blood glucose regulation and disorders of blood elements such as leukocytes and platelets. This study aims to determine the effect of using clozapine on blood glucose, leukocyte, and platelet levels in schizophrenia patients at Banyumas General Hospital. This research method was carried out by cross-sectional study in outpatient schizophrenia at Banyumas General Hospital who received clozapine therapy and had met the inclusion and exclusion criteria, taken by consecutive sampling, then examined blood glucose levels, leukocyte counts, and platelet counts before and after giving clozapine therapy. Samples were taken on day 1 and day 10 of drug use. Paired t-test statistical analysis was used to see the effect of using clozapine on glucose, leucocyte, and platelet levels. In the T-test, it was found that there was a relationship between the use of clozapine on the patient's blood glucose levels, the use of clozapine did not have a significant effect on the increase in leukocyte levels and there was also a relationship between the use of clozapine and the patient's platelet levels. The results showed that the patient had an increase in blood glucose levels by a percentage (100%), the patient had leukopenia by a percentage (63.5%), the patient had thrombocytopenia by a percentage (75%), while the other patients had thrombocytosis. Patients with hyperglycemia, leucopenia, and thrombocytopenia were those who used clozapine> 12 months

THE CLOZAPINE EFFECT ON BLOOD GLUCOSE LEVELS, LEUKOCYTES AND PLATELETS IN SCHIZOPHRENIC PATIENTS IN THE MENTAL SERVICE UNIT OF BANYUMAS HOSPITAL

Schizophrenia is a disorder of strange and disordered thoughts, delusions, hallucinations, inappropriate influences, and disorders of psychosocial functioning. One of the management of schizophrenia therapy is the administration of atypical antipsychotic drugs, namely clozapine. Clozapine is an antagonist of serotonin (5-HT2) and dopamine type 2 (D2) receptors. However, the risk of using clozapine provides a risk of side effects in the form of metabolic syndromes such as impaired blood glucose regulation and disorders of blood elements such as leukocytes and platelets. This study aims to determine the effect of using clozapine on blood glucose, leukocyte, and platelet levels in schizophrenia patients at Banyumas General Hospital. This research method was carried out by cross-sectional study in outpatient schizophrenia at Banyumas General Hospital who received clozapine therapy and had met the inclusion and exclusion criteria, taken by consecutive sampling, then examined blood glucose levels, leukocyte counts, and platelet counts before and after giving clozapine therapy. Samples were taken on day 1 and day 10 of drug use. Paired t-test statistical analysis was used to see the effect of using clozapine on glucose, leucocyte, and platelet levels. In the T-test, it was found that there was a relationship between the use of clozapine on the patient's blood glucose levels, the use of clozapine did not have a significant effect on the increase in leukocyte levels and there was also a relationship between the use of clozapine and the patient's platelet levels. The results showed that the patient had an increase in blood glucose levels by a percentage (100%), the patient had leukopenia by a percentage (63.5%), the patient had thrombocytopenia by a percentage (75%), while the other patients had thrombocytosis. Patients with hyperglycemia, leucopenia, and thrombocytopenia were those who used clozapine> 12 months

Effect of antipsychotics on serum lithium levels and white blood cell counts.

Lithium carbonate is used to increase white blood cell counts as a means of counteracting leukopenia caused by the administration of antipsychotic drugs. To evaluate the effect of antipsychotics on the leukocyte‐enhancing effect of lithium, we compared white blood cell counts, serum lithium levels, and lithium dosage in patients receiving antipsychotics and lithium in combination and patients receiving lithium alone. Chlorpromazine equivalent values were used as an indicator of the antipsychotic dose.Lithium serum levels were measured in 41 hospitalized patients. The lithium dose in the combination group (median, 800 mg) was significantly higher than that in group receiving only lithium (median, 400 mg) (P = 0.03). The lithium doses in the combination group receiving ≥1000 mg chlorpromazine equivalents (overdosing; median lithium dose 800 mg) and the combination group treated with 600‐999 mg chlorpromazine equivalents (high dosing; median lithium dose 800 mg) were significantly higher than the group that was not treated with antipsychotic medication, with median lithium dose 400 mg (P < 0.05).There were no significant differences in the white blood cell counts and serum lithium levels.Because of the large variety of antipsychotic drugs used in combination with lithium and the various doses used, it was difficult to evaluate the effects of lithium, with or without antipsychotic administration, on leukocyte count enhancement. We are planning to study a larger number of patients and, since renal function could not be assessed in this study, we will also focus on renal function, including urine output.

Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs.

Antipsychotics (APDs) represent the main pharmacological strategy in the treatment of schizophrenia; however, their administration often may result in severe adverse effects, such as extrapyramidal symptoms. Typically, dystonic movements are considered the result of impaired function and/or abnormalities of dopaminergic neurotransmission/signaling in the basal ganglia. The catechol O-methyltransferase (COMT) gene is located within the 22q11.2 region, and its product is an enzyme involved in transferring a methyl group from S-adenosylmethionine to catecholamines, including dopamine. Studies showed that COMT Val158Met polymorphism modifies enzymatic activity and, consequently, synaptic dopamine concentration in specific brain areas. We identified a patient with 22q11.2 deletion syndrome presenting with cervical and trunk dystonia after paliperidone administration, which persisted even after drug discontinuation. Given the patient’s genetic condition, we hypothesized that the dopaminergic dysfunction had been aggravated by COMT involvement, thus causing dystonia. In line with this hypothesis, we carried out a study on psychiatric patients in chronic treatment with APD to evaluate the distribution of the COMT Val158Met polymorphism and its role in the onset of adverse extrapyramidal symptoms. The study included four patients with dystonia after administration of APDs compared to 17 patients who never presented adverse drug reactions. Our data suggest that the Val/Val and Met/Met polymorphisms of the COMT gene are associated with a protective effect for the development of collateral extrapyramidal symptoms in patients treated with APDs, while the Val/Met genotype could be considered a risk factor for the development of dystonia after APDs administration.

Pharmacotherapy of schizophrenia: Mechanisms of antipsychotic accumulation, therapeutic action and failure

Schizophrenia is a multi-dimensional disorder with a complex and mostly unknown etiology, leading to a severe decline in life quality. Antipsychotic drugs (APDs) remain beneficial interventions in the treatment of the disorder, but vary significantly in binding profile, clinical effects and adverse reactions. The present review summarizes the main principles of APD mechanisms of action with a particular focus on recent findings in APD accumulation and its role in the therapeutic efficacy and treatment failure. High and low doses of APDs were shown to be effective in different dimensions of antipsychotic-like behaviour in rodent models. Efficacy of the APDs correlates with high dopamine D2 receptor occupancy, which occurs quickly after drug administration. However, onset and peak of action are delayed up to several days or weeks. APD accumulation via acidic trapping in synaptic vesicles is considered to underlie the time course of APD action. Use-dependent exocytosis, co-release with dopamine and serotonin and inhibition of ion channels impact on the neuronal transmission and determine effects of APDs. Disruption in accumulating properties leads to diminished APD effects. In addition, long-term APD administration at therapeutic doses leads to treatment failure both in animal models and in humans. APD failure was associated with treatment induced neuroadaptations, including a decline in extracellular dopamine levels, dopamine transporter upregulation, and altered neuronal firing. However, enhanced synaptic vesicle release has also been reported. APD loss of efficacy may be reversed through inhibition of the dopamine transporter or switching the administration regimen from continuous to intermittent. Thus, manipulating the accumulation properties of APDs, changes in the administration regimen and doses, or co-administration with dopamine transporter inhibitors may be considered to yield benefits in the development of new effective strategies in the treatment of schizophrenia.

Prolactin and Estrogen Levels in Postmenopausal Women Receiving Aripiprazole Augmentation Treatment for Depression.

Antipsychotic drugs are well established to alter serum prolactin levels, often resulting in adverse effects including amenorrhea, galactorrhea, osteoporosis, and loss of libido. There is growing preclinical evidence that prolactin-elevating drugs can instigate the progression of precancerous lesions to breast cancer and that genes activated by prolactin are associated with the development and proliferation of breast cancer. Current guides advise a cautious approach (weighing risks and benefits) to the administration of prolactin-elevating antipsychotic drugs in women with a previously detected breast cancer. Aripiprazole is known to be a prolactin-sparing antipsychotic; however, data regarding its effects on prolactin and estrogens in postmenopausal women are lacking. We examined serum hormone levels in n = 66 women who participated in a randomized, double-blind, placebo-controlled, multicenter trial of aripiprazole (high and low doses) added to an antidepressant in adults older than 60 years. Aripiprazole or placebo tablets were administered for 12 weeks as an augmentation strategy in venlafaxine-treated women. The primary outcomes were the difference in prolactin and estrogen levels. There was no significant effect of aripiprazole treatment on prolactin or estrogen levels, including in models that divided groups into low and high doses: prolactin (P = 0.075), estrone (P = 0.67), and estradiol (P = 0.96). Aripiprazole addition to an antidepressant did not alter serum estrogens or prolactin. These findings may be relevant in the treatment of some postmenopausal women with depression.

Standardizing the Effective Correlated Dosage of Olanzapine and Empagliflozin in Female Wistar Rats.

The primary aim of this study was to standardize the correlated effective dosage of the antidiabetic drug empagliflozin (EMPA) and the antipsychotic drug olanzapine (Ola). Atypical antipsychotics are associated with BWG and metabolic disturbances for which many approaches have been used to minimize these issues, including antidiabetic drugs. The antidiabetic drugs have been quite effective in reversing BWG induced by the administration of antipsychotic drugs in patients who have psychosis, schizophrenia and bipolar disorder. The objective of this study was to standardize the correlated effective dosage of EMPA and Ola. The study was carried out for 28 days to represent the chronic effect of Ola on female Wistar rats. Rats were divided into three groups based on the dose they received: control (vehicle), Ola-4 and Ola-8 (4 and 8 mg/kg/OD, respectively), and EMPA-10 and EMPA-20 (10 and 20 mg/kg/OD, respectively). Both doses of Ola produced a significant increase in the percentage of BWG, however, Ola-4 produced a higher BWG. Also, both the doses of EMPA were able to reverse the effect of Ola-induced BWG; however, EMPA-20 produced a higher reversal in BWG and normalized the rat's body weight. We conclude that Ola-4 and EMPA-20 were the most effective dosage for experimental purposes in female Wistar rats. The findings of this study standardized the effective correlated dosage of olanzapine and empagliflozin in female Wistar rats that will help understand the underlying molecular and behavioral mechanisms.

Association of the HTR2C-759C/T polymorphism and antipsychotic-induced weight gain: a meta-analysis

BackgroundAntipsychotic-induced weight gain (AIWG) is a crucial factor for the medication cessation of patients with schizophrenia. Multiple studies have shown that the functional polymorphism -759 C/T (rs3813929) in the HTR2C...

Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats

Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis, but this has not been tested directly in vivo. Here, we investigated synaptic vesicle glycoprotein 2A (SV2A) levels and their relationship to symptoms and structural brain measures using [11C]UCB-J positron emission tomography in 18 patients with schizophrenia and 18 controls. We found significant group and group-by-region interaction effects on volume of distribution (VT). [11C]UCB-J VT was significantly lower in the frontal and anterior cingulate cortices in schizophrenia with large effect sizes (Cohen’s d = 0.8-0.9), but there was no significant difference in the hippocampus. We also investigated the effects of antipsychotic drug administration on SV2A levels in Sprague-Dawley rats using western blotting, [3H]UCB-J autoradiography and immunostaining with confocal microscopy, finding no significant effects on any measure. These findings indicate that there are lower synaptic terminal protein levels in schizophrenia in vivo and that antipsychotic drug exposure is unlikely to account for them.

Tardive Oculogyric Crisis due to Aripiprazole treatment in an adolescent patient diagnosed with Bipolar Disorder

Antipsychotics usage in children and adolescents is becoming widespread. One of the extrapyramidal side effects associated with long-term antipsychotic drug use follow-up is an oculogyric crisis (OGC). OGC is defined as a dystonic reaction commonly observed after typical antipsychotic drug administration. However, there are rare cases which report OGC after atypical antipsychotic use. In this report, we present an adolescent with bipolar disorder who developed OGC after 2 years of aripiprazole and quetiapine use. To best of our knowledge, this case report has been the first case to present the clinical presentation of tardive OGC due to aripiprazole treatment in an adolescent patient. It is important to note that OGC might be observed in the acute phase and it might be as a result of chronic use detected during a clinical follow-up. Safety, tolerability and efficiency of aripiprazole in pediatric populations should be further analyzed in the future studies.

Role of D3 dopamine receptors in modulating neuroanatomical changes in response to antipsychotic administration

Clinical research has shown that chronic antipsychotic drug (APD) treatment further decreases cortical gray matter and hippocampus volume, and increases striatal and ventricular volume in patients with schizophrenia. D2-like receptor blockade is necessary for clinical efficacy of the drugs, and may be responsible for inducing these volume changes. However, the role of other D2-like receptors, such as D3, remains unclear. Following our previous work, we undertook a longitudinal study to examine the effects of chronic (9-week) typical (haloperidol (HAL)) and atypical (clozapine (CLZ)) APDs on the neuroanatomy of wild-type (WT) and dopamine D3-knockout (D3KO) mice using magnetic resonance imaging (MRI) and histological assessments in a sub-region of the anterior cingulate cortex (the prelimbic [PL] area) and striatum. D3KO mice had larger striatal volume prior to APD administration, coupled with increased glial and neuronal cell density. Chronic HAL administration increased striatal volume in both WT and D3KO mice, and reduced PL area volume in D3KO mice both at trend level. CLZ increased volume of the PL area of WT mice at trend level, but decreased D3KO PL area glial cell density. Both typical and atypical APD administration induced neuroanatomical remodeling of regions rich in D3 receptor expression, and typically altered in schizophrenia. Our findings provide novel insights on the role of D3 receptors in structural changes observed following APD administration in clinical populations.

Young spontaneously hypertensive rats (SHRs) display prodromal schizophrenia-like behavioral abnormalities

The Spontaneously Hypertensive Rat (SHR) strain has been suggested as an animal model of schizophrenia, considering that adult SHRs display behavioral abnormalities that mimic the cognitive, psychotic and negative symptoms of the disease and are characteristic of its animal models. SHRs display: (I) deficits in fear conditioning and latent inhibition (modeling cognitive impairments), (II) deficit in prepulse inhibition of startle reflex (reflecting a deficit in sensorimotor gating, and associated with psychotic symptoms), (III) diminished social behavior (modeling negative symptoms) and (IV) hyperlocomotion (modeling the hyperactivity of the dopaminergic mesolimbic system/ psychotic symptoms). These behavioral abnormalities are reversed specifically by the administration of antipsychotic drugs. Here, we performed a behavioral characterization of young (27–50 days old) SHRs in order to investigate potential early behavioral abnormalities resembling the prodromal phase of schizophrenia. When compared to Wistar rats, young SHRs did not display hyperlocomotion or PPI deficit, but exhibited diminished social interaction and impaired fear conditioning and latent inhibition. These findings are in accordance with the clinical course of schizophrenia: manifestation of social and cognitive impairments and absence of full-blown psychotic symptoms in the prodromal phase. The present data reinforce the SHR strain as a model of schizophrenia, expanding its validity to the prodromal phase of the disorder.

Identifying the In Vivo Cellular Correlates of Antipsychotic Drugs.

GPCRs such as 5-HT2A and D2 are implicated in the therapeutic and the side effects of antipsychotics. However, the pattern of brain activity that leads to the behavioral effects of antipsychotics is poorly understood. To address this question, we used the transgenic ‘FosTRAP’ mice (Mus musculus), where a fluorescent reporter marks the cells responsive to the stimulus of interest. Here, the stimulus was an administration of various antipsychotic drugs. In case of typical antipsychotics such as Haloperidol, the c-fos active cells were predominantly found in the striatum, whereas in case of the atypical antipsychotics (Clozapine and Olanzapine), c-fos-induced cells were more numerous in the cortical regions, e.g., orbital cortex, piriform cortex. Curiously, we also observed ependymal cells to be a novel cellular target of atypical antipsychotics. 5-HT2A is considered to be a major target for atypical antipsychotics. Therefore, we bred ‘FosTRAP’ mice with 5-HT2A knock-out (KO) mice and tested their response to the prototype of atypical antipsychotics, Clozapine. Interestingly, the absence of 5-HT2A did not significantly affect the number of c-fos-induced cells in the cortical regions. However, the ependymal cells showed a dramatically reduced response to Clozapine in the absence of 5-HT2A. In summary, the TRAP system has allowed us to identify various region-specific activity induced by antipsychotics and novel cellular targets of the antipsychotics. These results serve as a “proof of principle” study that can be extended to explore the biochemical and physiological changes brought about by antipsychotics and specifically identify antipsychotic-responsive cells in the live tissue.

Effect of a single pre-operative 125 mg dose of methylprednisolone on postoperative delirium in hip fracture patients; a randomised, double-blind, placebo-controlled trial.

Postoperative delirium is common after hip fracture surgery, and may have a neuro-inflammatory cause. We conducted a single-centre, randomised, double-blind, placebo-controlled trial of 117 older hip fracture patients to see if a single, pre-operative intravenous dose of 125 mg methylprednisolone could reduce the severity and/or incidence of postoperative delirium, assessed using the Confusion Assessment Method delirium severity score. Modified intention-to-treat analysis found no significant difference in our primary outcome, median (IQR [range]) cumulative Confusion Assessment Method delirium severity score over the first three postoperative days between the methylprednisolone and placebo groups (1 (0-6 [0-39]) vs. 2 (0-10 [0-32]), p = 0.294). Both the prevalence of postoperative delirium (Confusion Assessment Method delirium severity score ≥ 5, 10/59 vs. 19/58, p = 0.048) and the median (IQR [range]) cumulated postoperative (by day 3) fatigue scores (5 (2-6 [0-11]) vs. 6 (4-8 [0-16]), p = 0.008) were significantly lower in the methylprednisolone compared with the placebo group. There were no significant between-group differences in the rate of completing physiotherapy, postoperative pain, the administration of antipsychotic drugs, infection, length of inpatient stay or 30- and 90-day mortality. No major adverse reactions related to methylprednisolone were recorded. We conclude that a single, pre-operative dose of 125 mg methylprednisolone does not reduce the severity of postoperative delirium, but may reduce both the prevalence of delirium and the severity of fatigue after hip fracture surgery in older patients, enabling remobilisation and recovery.