First-generation Antipsychotic Drugs Research Articles

A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain.

Second-generation antipsychotics are mainly used in both acute and long-term treatment of major psychiatric disorders. Although better tolerated than first-generation antipsychotic drugs, they can frequently induce weight gain and metabolic disorders, of these, olanzapine is one of the drugs more likely to induce these side effects. There is consistent evidence of the role of gut microbiota in modulating the gut-brain axis with complex crosstalk with the host involving satiety signaling pathways, food intake behavior, and weight and metabolic regulation. Second-generation antipsychotics induce important gut microbiota modification thus contributing together with the central and peripheral receptors blockade mechanism to weight gain induction and metabolic impairment. These drugs can alter the composition of gut microbiota and induce dysbiosis, often reducing the concentration of Akkermansia muciniphila, a bacterium that is also decreased in patients with diabetes, obesity, metabolic syndrome, or chronic inflammatory diseases. Probiotic administration can be a safe and well-tolerated approach to modulate microbiotaandoffer an integrative strategy in psychiatric patients suffering antipsychotic side effects. Multiple strain probiotics and Akkermansia muciniphila alone have been administered both in mice models and in clinical populations demonstrating efficacy on antipsychotic-induced metabolic impairment and showing a contribution in reducing induced weight gain.Akkermansia muciniphila can improve several parameters altered by olanzapine administration, such as weight gain, insulin resistance, hyperglycemia, liver function, systemic inflammation, and gut barrier function. Although we do not have jet trials in the psychiatric population, this probiotic may be a complementary approach to treating olanzapine-induced weight gain and metabolic side effects.

THE FIRST GENERATION AND SECOND-GENERATION ANTIPSYCHOTIC DRUGS AND THEIR PHARMACOLOGY IN TREATMENT OF SCHIZOPHRENIA

Schizophrenia is a complex and severe psychiatric disorder that affects millions of people worldwide. Antipsychotic drugs have been widely used for the treatment of schizophrenia for over 60 years. The first-generation antipsychotic drugs (FGAs) were introduced in the 1950s and revolutionized the treatment of schizophrenia. However, their use is associated with a number of adverse effects, including Extrapyramidal Symptoms (EPS) and Tardive Dyskinesia (TD). Second-generation antipsychotic drugs (SGAs), also known as atypical antipsychotics, were developed in the 1990s and have become the preferred treatment for schizophrenia due to their lower incidence of EPS and TD. They also have a broader range of therapeutic effects, such as improving negative symptoms and cognitive impairment associated with schizophrenia. This review article summarizes the pharmacology of both FGAs and SGAs, including their mechanism of action, pharmacokinetics, and adverse effects. The efficacy and safety of these drugs in the treatment of schizophrenia are also discussed. In addition, this review examines the controversy surrounding the use of SGAs and their potential metabolic side effects, such as weight gain, hyperlipidemia, and diabetes. Despite the availability of SGAs, FGAs still have a role in the treatment of schizophrenia, particularly for patients who are unresponsive to SGAs or experience intolerable side effects. Furthermore, research continues to identify new pharmacological targets and treatment strategies for schizophrenia. Understanding the pharmacology and clinical use of antipsychotic drugs is essential for optimizing the treatment of schizophrenia and improving patient outcomes.

Bacillus Calmette-Guérin Vaccine Attenuates Haloperidol-Induced TD-like Behavioral and Neurochemical Alteration in Experimental Rats.

Tardive dyskinesia (TD) is a hyperkinetic movement disorder that displays unusual involuntary movement along with orofacial dysfunction. It is predominantly associated with the long-term use of antipsychotic medications, particularly typical or first-generation antipsychotic drugs such as haloperidol. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis are major pathophysiological mechanisms of TD. The BCG vaccine has been reported to suppress inflammation, oxidative stress, and apoptosis and exert neuroprotection via several mechanisms. Our study aimed to confirm the neuroprotective effect of the BCG vaccine against haloperidol-induced TD-like symptoms in rats. The rats were given haloperidol (1 mg/kg, i.p.) for 21 days after 1 h single administration of the BCG vaccine (2 × 107 cfu). Various behavioral parameters for orofacial dyskinesia and locomotor activity were assessed on the 14th and 21st days after haloperidol injection. On the 22nd day, all rats were euthanized, and the striatum was isolated to estimate the biochemical, apoptotic, inflammatory, and neurotransmitter levels. The administration of the BCG vaccine reversed orofacial dyskinesia and improved motor function in regard to haloperidol-induced TD-like symptoms in rats. The BCG vaccine also enhanced the levels of antioxidant enzymes (SOD, GSH) and reduced prooxidants (MDA, nitrite) and pro-apoptotic markers (Cas-3, Cas-6, Cas-9) in rat brains. Besides this, BCG treatment also restored the neurotransmitter (DA, NE, 5-HT) levels and decreased the levels of HVA in the striatum. The study findings suggest that the BCG vaccine has antioxidant, antiapoptotic, and neuromodulatory properties that could be relevant in the management of TD.

Investigating the symptomatic and morphological changes in the brain based on pre and post-treatment: A critical review from clinical to neuroimaging studies on schizophrenia.

Pharmacological treatment for schizophrenia has been a long-standing concern. As a severe neuropsychological illness, schizophrenia is always a challenging disorder to unravel its pathophysiology. Since it exhibits both positive and negative symptoms, such as hallucination and delusion, as well as social isolation and cognitive impairment, following the symptomatic changes is a crucial task for clinicians. Although various pharmacological treatments are available in the form of antipsychotics, however, their actual consequences need to be examined with the observable changes in symptoms as well as the unobservable changes in brain functioning. This study is a first of its kind to critically investigate both clinical and neuroimaging studies to find out the changes being observed in schizophrenia patients after clinical intervention with various antipsychotics. We observed several symptomatic changes being reported in clinical studies incorporating clinical trials of various first-generation and second-generation antipsychotic drugs. Alongside, we encapsulated several neuroimaging studies showing functional and structural changes in the brain of schizophrenia patients triggered by a variety of drugs. The basal ganglia, frontal lobe, temporal lobe, cuneus, and middle occipital gyrus are some of the notable brain regions that were observed to show subtle functional and structural changes. This critical review paper may pave the way for future research into the study of the pathological and morphological changes in the brains of schizophrenia patients as they progress through the course of medicinal therapy.

Antipsychotic drugs and risk of acute pancreatitis: A nationwide case-control study.

Use of antipsychotic drugs, especially second-generation agents, has been suggested to cause acute pancreatitis in multiple case reports; however, such an association has not been corroborated by larger studies. This study examined the association of antipsychotic drugs with risk of acute pancreatitis. Nationwide case-control study, based on data from several Swedish registers and including all 52,006 cases of acute pancreatitis diagnosed in Sweden between 2006 and 2019 (with up to 10 controls per case; n = 518,081). Conditional logistic regression models were used to calculate odds ratios (ORs) in current and past users of first-generation and second-generation antipsychotic drugs (dispensed prescription <91 and ≥91 days of the index date, respectively) compared with never users of such drugs. In the crude model, first-generation and second-generation antipsychotic drugs were associated with increased risk of acute pancreatitis, with slightly higher ORs for past use (1.58 [95% confidence interval 1.48-1.69] and 1.39 [1.29-1.49], respectively) than for current use (1.34 [1.21-1.48] and 1.24 [1.15-1.34], respectively). The ORs were largely attenuated in the multivariable model-which included, among others, alcohol abuse and the Charlson comorbidity index-up to the point where only a statistically significant association remained for past use of first-generation agents (OR 1.18 [1.10-1.26]). There was no clear association between use of antipsychotic drugs and risk of acute pancreatitis in this very large case-control study, indicating that previous case report data are most likely explained by confounding.

Case Report: Management strategy of rare case first-generation antipsychotic drug induced neglected femoral neck fracture in schizophrenia patients

Background: The early onset of femoral neck fracture is commonly treated by bone grafting surgery. However rare cases of neglected femoral neck fractures in schizophrenic patients need to be treated by arthroplasty because of the rapid destruction of the femoral head within the acetabulum. Case presentation: We report a rare unique case of first-generation antipsychotic drug-induced neglected femoral neck fracture in a 41-year-old man presenting after a month complaining of not being able to walk due to falling in a ditch. X-ray examination findings revealed total destruction of the femoral head within the acetabulum with no acetabulum dysplasia detected. Ordinarily, it should be treated with a bone grafting procedure since no dysplasia was detected and it was an early onset case. However, arthroplasty was chosen because the femoral head was destructed. Three months post-surgery x-ray shows the acetabulum dysplasia and lytic lesion that confirm drug-induced bone destruction by the first-generation antipsychotic drug. Conclusions: We suggest that even though rare, first-generation antipsychotic drugs neglected femoral neck fractures in schizophrenia patients can be successfully treated by arthroplasty supported by the patient’s compliance. Bone mineral density (BMD) test is also suggested to monitor the bone density of schizophrenia patients.

Assessment of Plasma Glucose and Lipid Profile Dysregulation among Patients on Antipsychotics in Sokoto

Background: Antipsychotic drugs used in the treatment of psychotic disorders have been implicated in negative effects on the blood glucose and lipid profile levels of patients. Methods: We studied the anthropometric parameters and then the plasma glucose and lipid profile levels of one hundred and seventy-two (172) patients between the ages of 18 and 45 years; who are on various oral antipsychotics. Also, forty (40) treatment-naïve psychiatric patients and forty (40) healthy controls were included in the study. The results were analysed using standard methods. Results: The mean plasma glucose level was significantly higher (p&lt;0.05) in psychiatric patients on oral antipsychotic drugs compared to controls. The mean plasma glucose level of treatment-naïve psychiatric patients was also significantly higher (p&lt;0.05) compared to that of healthy controls. Furthermore, there was a significant increase in plasma glucose levels of patients on second-generation antipsychotic drugs compared to those on first-generation antipsychotic drugs. The lipid profile of patients on antipsychotic drugs showed a similar trend. There were significant increases in the plasma levels of Total Cholesterol (TC), Low-Density Lipoprotein (LDL), Triglycerides (TG) and a significant decrease in the plasma level of High-Density. However, the plasma TG levels were significantly higher in the typical antipsychotic drugs group. Lipoprotein (HDL) levels of individuals that were on antipsychotics were significantly decreased when compared to healthy controls Conclusion: The lipid profile and plasma glucose concentration were altered by oral antipsychotic drugs in Sokoto, Nigeria. Therefore, it may be clinically expedient to vigorously assess the plasma glucose and lipid profile levels of all patients that are on oral antipsychotic drugs and interventions planned as appropriate. Keywords: Antipsychotic drugs, lipid profile, glucose, Cholesterol, Lipoprotein

Comparative efficacy, tolerability, and acceptability of pharmacological interventions for the treatment of children, adolescents, and young adults with Tourette's syndrome: a systematic review and network meta-analysis

In clinical practice guidelines there is no consensus about the medications that should be initially offered to children and young people with Tourette's syndrome. To provide a rigorous evidence base that could help guide decision making and guideline development, we aimed to compare the efficacy, tolerability, and acceptability of pharmacological interventions for Tourette's syndrome. For this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, PubMed, Web of Science, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov, for published and unpublished studies from database inception to Nov 19, 2021. We included double-blind randomised controlled trials of any medication administered as a monotherapy for at least 1 week against another medication or placebo in children and adolescents (aged ≥4 years and ≤18 years), adults (>18 years), or both, diagnosed with Tourette's syndrome according to standardised criteria. We excluded studies that exclusively recruited participants with comorbid attention-deficit hyperactivity disorder or obsessive-compulsive disorder. The primary outcome was change in severity of tic symptoms (efficacy). Secondary outcomes were treatment discontinuations due to adverse events (tolerability) and for any reason (acceptability). Pharmacological interventions were examined considering medication categories and medications individually in separate analyses. Summary data were extracted and pooled with a random-effects network meta-analysis to calculate standardised mean differences for efficacy and odds ratios for tolerability and acceptability, with 95% CIs. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was pre-registered in PROSPERO (CRD42022296975). Of the 12 088 records identified through the database search, 88 records representing 39 randomised controlled trials were included in the network meta-analysis; these 39 randomised controlled trials comprised 4578 participants (mean age 11·8 [SD 4·5] years; 3676 [80·8%] male participants) and evaluated 23 individual medications distributed across six medication categories. When considering medication categories, first-generation (standardised mean difference [SMD] -0·65 [95% CI -0·79 to -0·51]; low certainty of evidence) and second-generation (-0·71 [-0·88 to -0·54]; moderate certainty of evidence) antipsychotic drugs, as well as α-2 agonists (-0·21 [-0·39 to -0·03]; moderate certainty of evidence), were more efficacious than placebo. First-generation and second-generation antipsychotic drugs did not differ from each other (SMD 0·06 [95% CI -0·14 to 0·25]; low certainty of evidence). However, both first-generation (SMD 0·44 [95% CI 0·21 to 0·66]) and second-generation (0·49 [0·25 to 0·74]) antipsychotic drugs outperformed α-2 agonists, with moderate certainty of evidence. Similar findings were observed when individual medications were considered: aripiprazole (SMD -0·60 [95% CI -0·83 to -0·38]), haloperidol (-0·51 [-0·88 to -0·14]), olanzapine (-0·83 [-1·49 to -0·18]), pimozide (-0·48 [-0·84 to -0·12]), risperidone (-0·66 [-0·98 to -0·34]), and clonidine (-0·20 [-0·37 to -0·02]) all outperformed placebo, with moderate certainty of evidence. Antipsychotic medications did not differ from each other, but there was low to very low certainty of evidence for these comparisons. However, aripiprazole (SMD -0·40 [95% CI -0·69 to -0·12]) and risperidone (-0·46 [-0·82 to -0·11]) outperformed clonidine, with moderate certainty of evidence. Heterogeneity or inconsistency only emerged for a few comparisons. In terms of tolerability and acceptability, there were no relevant findings for any of the efficacious medication categories or individual medications against each other or placebo, but there was low to very low certainty of evidence associated with these comparisons. Our analyses show that antipsychotic drugs are the most efficacious intervention for Tourette's syndrome, while α-2 agonists are also more efficacious than placebo and could be chosen by those who elect not to take antipsychotic drugs. Shared decision making about the degree of tic-related severity and distress or impairment, the trade-offs of efficacy and safety between antipsychotic drugs and α-2 agonists, and other highly relevant individual factors that could not be addressed in the present analysis, should guide the choice of medication for children and young people with Tourette's syndrome. None.

Assessment of Protective Effects of Carvacrol on Haloperidol-Induced Oxidative Stress and Genotoxicity in Human Peripheral Blood Lymphocytes.

Haloperidol is a first-generation antipsychotic drug that has several indications in a wide range of mental conditions. The extensive prescription of haloperidol is correlated with some less-known adverse effects such as genotoxicity. Carvacrol is a monoterpenoid mainly found in oregano and thyme. It has the potential to scavenge free radicals in addition to increasing antioxidant defense enzyme activities and glutathione levels. In this study, we attempted to explore the possible potential of haloperidol in inducing genotoxicity in human peripheral lymphocytes as well as the protective role of carvacrol against this effect. The lymphocytes were divided into separate groups as follows: control group (cosolvent and NS); carvacrol group (5 μM); haloperidol group (25, 50, and 100 ng/ml); haloperidol (25, 50, and 100 ng/ml) + carvacrol (5 μM); positive control (0.8 μg/ml Cisplatin). After 24 hours of treatment, we conducted a cytokinesis-Block micronucleus test and an alkaline comet assay in order to determine genetic damage. Additionally, we measured glutathione and MDA levels as the biomarkers associated with oxidative stress. Significant increases in the levels of genotoxicity biomarkers (micronucleus frequency, DNA percentage in tail and tail moment) were observed in haloperidol-treated cells. The result of our oxidative stress tests also demonstrated that haloperidol had the potential to induce oxidative stress via reducing the levels of glutathione and increasing lipid peroxidation. Treatment with carvacrol significantly decreased the genotoxic events. It can be presumed that the induction of oxidative stress by haloperidol is the critical event associated with haloperidol-mediated genotoxicity. Therefore, using carvacrol as a natural antioxidant protected human lymphocytes against haloperidol genetic damage.

Cost-Effectiveness of Second-Generation Injectable Antipsychotic Drugs

&#x0D; For adults with bipolar I disorder, the second-generation antipsychotic injectable drug aripiprazole is less costly and more effective over a patient’s lifetime, compared to the second-generation antipsychotic oral drug cariprazine. For adults with bipolar I disorder, aripiprazole injections are more effective compared to the second-generation antipsychotic oral drug asenapine; the cost-effectiveness over a patient’s lifetime depends on the willingness to pay. These results are based on 1 economic evaluation.&#x0D; No cost-effectiveness studies were found comparing second-generation to first-generation antipsychotic injectable drugs.&#x0D;

Antipsychotic Drug-Induced Increases in Peripheral Catecholamines are Associated With Glucose Intolerance.

The second-generation antipsychotic drugs are widely used in the field of psychiatry, for an expanding number of different conditions. While their clinical efficacy remains indispensable, many of the drugs can cause severe metabolic side-effects, resulting in an increased risk of developing cardiometabolic disorders. The physiological basis of these side-effects remains an ongoing area of investigation. In the present study, we examined the potential role of peripheral catecholamines in antipsychotic-induced glucose intolerance. Adult female rats were acutely treated with either the first-generation antipsychotic drug haloperidol (0.1, 0.5 or 1 mg/kg) or the second-generation drugs risperidone (0.25, 1.0 or 2.5 mg/kg), olanzapine (1.5, 7.5 or 15 mg/kg) or clozapine (2, 10 or 20 mg/kg) or vehicle. Fasting glucose levels were measured and then animals were subjected to the intraperitoneal glucose tolerance test. Levels of peripheral norepinephrine, epinephrine and dopamine were concurrently measured in the same animals 75, 105 and 135 min after drug treatment. All antipsychotics caused glucose intolerance, with strongest effects by clozapine > olanzapine > risperidone > haloperidol. Plasma catecholamines were also increased by drug treatment, with greatest effects for norepinephrine and epinephrine caused by clozapine > risperidone > olanzapine > haloperidol. Importantly, there were strong and statistically significant associations between norepinephrine/epinephrine levels and glucose intolerance for all drugs. These findings confirm that increases in peripheral catecholamines co-occur in animals that exhibit antipsychotic-induced glucose intolerance, and these effects are strongly associated with each other, providing further evidence for elevated catecholamines as a substrate for antipsychotic metabolic side-effects.

Comparison of the Effect of Olanzapine, Haloperidol and Quetiapine on the Resolution of Individual Delirium Symptoms in ICU Patients: A Double-blind, Clinical Trial Study

Introduction: Considering that haloperidol is a first-generation antipsychotic drug known as the primary treatment for delirium, it causes extrapyramidal side effects, and olanzapine and quetiapine are second-generation antipsychotic drugs without extrapyramidal side effects. In this study, we compared the effects of olanzapine and quetiapine with haloperidol on the resolution of individual delirium symptoms.&#x0D; Materials and Methods: In a double-blind clinical trial study, 90 patients admitted to the ICU in three groups received haloperidol at a dose of 2.5 mg/day, while in the second group, patients received olanzapine at an amount of 2.5- 10.5mg/day. In the third group, they received quetiapine at a dose of 12.5 to 75 mg daily. Then, patients' sedation levels were measured according to RASS criteria, and their disease severity was evaluated according to APACHE II criteria.&#x0D; Results: During 15 work shifts in the first, second, third, seventh, and tenth days, sedation scores in all three groups decreased significantly (p-v &lt;0.05), and all three drugs were effective in subsiding patients' agitation in 10 days. In the evening and night of the first day, the sedation score in the quetiapine group was higher than the other two groups; however, after the treatment period and in the work shifts of the seventh and tenth days, the patients in the quetiapine group had the lowest sedation score on the RASS scale. Also, after starting drug treatment in the three groups, the mean severity of the disease was significantly different in the three groups (p-v &lt;0.05), so that on the third and seventh day, the olanzapine group had the lowest and the haloperidol group had the highest disease severity. But on the tenth day, the severity of the disease was lowest in the patients in the quetiapine group.&#x0D; Conclusion: As a result of this study, it was found that quetiapine, olanzapine, and haloperidol had the most significant effect in improving the sedation level of patients with delirium according to RASS criteria, respectively, and the use of atypical antipsychotic drugs had more favorable outcomes than typical ones in controlling patients' delirium.

Letter to the Editor: Rethinking The Cost Of Antipsychotic Treatment: The Average Cost Of The Drugs Used In Turkey In 2020.

Letter to the Editor: Rethinking The Cost Of Antipsychotic Treatment: The Average Cost Of The Drugs Used In Turkey In 2020.

Amisulpride: What’s Old Can Be New in the United States

Amisulpride: What’s Old Can Be New in the United States

Atypical Dyskinesias under treatment with antipsychotic drugs: Report from the AMSP Multicenter Drug Safety Project

Objectives Aim of this study was to describe atypical dyskinesias (AtypDs) occurring during treatment with antipsychotic drugs (APDs). AtypDs are dyskinesias showing either an unusual temporal relationship between onset of treatment and start of the adverse drug reaction (ADR) or an unusual presentation of clinical symptoms. Methods Data on the utilization of APDs and reports of severe APD-induced AtypDs were collected using data from the observational pharmacovigilance programme – ‘Arzneimittelsicherheit in der Psychiatrie (English: drug safety in psychiatry)’ (AMSP)– from 1993 to 2016. Results A total of 495,615 patients were monitored, of which 333,175 were treated with APDs. 67 cases (0.020%) of severe AtypDs under treatment with APDs were registered. The diagnoses of schizophrenic disorders as well as organic mental disorders were related to significantly higher rates of AtypDs. Second-generation antipsychotic drugs (SGAs) showed slightly higher rates of AtypDs (0.024%) than high-potency (0.011%) or low-potency first-generation antipsychotic drugs (FGAs; 0.006%). In 41 cases (61.2%) two or more drugs were found to cause AtypDs. Conclusions Our study indicates that AtypDs are rare ADRs. SGAs may have a higher risk for the occurrence of AtypDs than FGAs. Clinicians should be aware of this ADR and patients should be monitored and examined carefully.

Aripiprazole ameliorates scopolamine-induced amnesia in mice

Aripiprazole, a known third generation anti-psychotic drug. The drug has shown to have lesser side effects on extrapyramidal system and enhance memory when compared with the first-generation anti-psychotic drugs. However, studies on the impact of aripiprazole on scopolamine-induced memory impairment in mice have been poorly reported. This study was designed to investigate the impact of aripiprazole on scopolamine-induced amnesia in mice. Thirtysix (36) mice weighing between 20-23g were randomly divided into six groups. Group 1 was given 10 ml/kg distilled water. Group 2 received 3 mg/kg scopolamine alone. Group 3 was given 1 mg/kg donepezil. Group 4 received 0.5 mg/kg aripiprazole. Group 5 was given 0.3 mg/kg aripiprazole. Group 6 received 0.1mg/kg aripiprazole. Thirty minutes after administration of either aripiprazole or donepezil, scopolamine (3 mg/kg) was administered, intraperitoneally. The administration was for 7days, during which their memory was assessed using Morris water maze and Y-maze models. The results showed that the anti-amnesic effect of aripiprazole appeared to be dosedependent; the animals administered with 0.5 mg/kg aripiprazole showed the greatest improved memory performance against scopolamine-induced amnesia. The hippocampal and prefrontal cortex tissues displayed anti-amnesic potential of aripiprazole. Aripiprazole seems to improved memory performance against scopolamine-induced memory impairment in mice.&#x0D; Keywords: Aripiprazole; Anti-amnesic; Scopolamine; Memory

Sex differences in pharmacological treatment of major depressive disorder: results from the AMSP pharmacovigilance program from 2001 to 2017

Data on drug prescription for outpatients with major depressive disorder (MDD) suggest women are more likely to be treated with psychotropic drugs, while data on sex differences regarding pharmacological treatment of psychiatric inpatients are currently not available. Drug utilization data from the program “Drug Safety in Psychiatry” (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) of 44,418 psychiatric inpatients with MDD were analyzed for sex differences between 2001 and 2017. Sex differences were analyzed using relative risks (RR) and 95% confidence intervals (95% CI). Time trends were analyzed by comparing the first (2001–2003) with the last time period (2015–2017). In general, men and women were equally likely to use psychotropic drugs. Monotherapy was more common in men. Women were more likely to utilize ≥ 4 psychotropic drugs. Antidepressant drugs (ADDs) were the most prescribed drug class. Men had a higher utilization of noradrenergic and specific serotonergic antidepressants (RR 1.15; 95% CI 1.12–1.19), especially mirtazapine (RR 1.16; 95% CI 1.12–1.19), but also of other ADDs such as bupropion (RR 1.50; 95% CI 1.35–1.68). Males had a slightly higher utilization of second-generation antipsychotic drugs (RR 1.06; 95% CI 1.03–1.09) and were less often treated with low-potency first-generation antipsychotic drugs (RR 0.86; 95% CI 0.83–0.90). Tranquilizing (e.g., benzodiazepines; RR 0.89; 95% CI 0.86–0.92) and hypnotic drugs (e.g., Z-drugs; RR 0.85; 95% CI 0.81–0.89) were less utilized in the treatment of male patients. Not all sex differences were stable over time. More sex differences were detectable in 2015–2017 than in 2001–2003. Findings suggest that certain psychotropic drugs are preferred in the treatment of men vs. women, however, sex differences found in this study are not as large as in ambulatory settings. To make evidence-based sex-specific recommendations in the treatment of MDD, differences in drug response and tolerability need to be further researched.

Analytical determinations of haloperidol and its combinations in pharmaceutical dosage forms and biological matrices

Haloperidol is a highly potent, first-generation antipsychotic drug used for the treatment of several disorders. It exerts its antipsychotic effect through the strong antagonism in the dopamine D2 receptor. Effective analytical procedures are required for clinical and pharmaceutical studies. In this review, a variety of analytical techniques and associated methodologies for the determination of haloperidol are detailed including spectrophotometry, spectrofluorimetric, nuclear magnetic resonance spectroscopy, thin layer chromatography, electrophoresis, liquid chromatography, and gas chromatography. HPLC is the most widely used technique.

Leukopenia Related to Haloperidol in a Case of Chronic Untreated Schizophrenia

Haloperidol is a commonly prescribed first-generation antipsychotic drug in psychiatric practice. It is usually well tolerated and presents with few side effects such as sedation, antiparkinsonian features, and hypotension. Few cases have been reported on leukopenia with haloperidol, none from India. We present a case where a patient with untreated schizophrenia for 9 years developed leukopenia (total leukocyte count [TLC] = 2800 cells/mm3) at 20 mg of oral haloperidol, in our inpatient setting. He chiefly presented with fever. The causality of adverse drug reaction (ADR) was attributed to haloperidol and using the Naranjo algorithm, the score recorded was 8, suggesting probable causal association. Hartwig's Severity Assessment Scale showed the severity of the ADR to be Level 4 (moderate severity). There was prompt reversal after drug discontinuation (TLC = 7000 cells/mm3 at discharge). Risk factors, possible mechanisms, and role of monitoring are discussed.

Enhancement in Phospholipase D Activity as a New Proposed Molecular Mechanism of Haloperidol-Induced Neurotoxicity.

Membrane phospholipase D (PLD) is associated with numerous neuronal functions, such as axonal growth, synaptogenesis, formation of secretory vesicles, neurodegeneration, and apoptosis. PLD acts mainly on phosphatidylcholine, from which phosphatidic acid (PA) and choline are formed. In turn, PA is a key element of the PLD-dependent secondary messenger system. Changes in PLD activity are associated with the mechanism of action of olanzapine, an atypical antipsychotic. The aim of the present study was to assess the effect of short-term administration of the first-generation antipsychotic drugs haloperidol, chlorpromazine, and fluphenazine on membrane PLD activity in the rat brain. Animals were sacrificed for a time equal to the half-life of the antipsychotic drug in the brain, then the membranes in which PLD activity was determined were isolated from the tissue. The results indicate that only haloperidol in a higher dose increases the activity of phospholipase D. Such a mechanism of action of haloperidol has not been described previously. Induction of PLD activity by haloperidol may be related to its mechanism of cytotoxicity. The finding could justify the use of PLD inhibitors as protective drugs against the cytotoxicity of first-generation antipsychotic drugs like haloperidol.