Extrapyramidal Research Articles

Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape.

One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U.S. Food and Drug Administration for treatment of depression (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, and olanzapine-fluoxetine combination). While multiple acute-phase studies have demonstrated the efficacy of these medications in improving depressive symptoms, clinically meaningful improvement (i.e., remission) remains limited, with significant concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia), especially with long-term use. With the rapidly evolving landscape of antidepressant treatments over the past few years, which has witnessed approval of rapid-acting antidepressants (e.g., esketamine nasal spray and dextromethorphan-bupropion combination) and several more in the late-stage pipeline (e.g., zuranolone and psilocybin), it remains to be seen whether the use of atypical antipsychotics will go the way of the older and rarely prescribed antidepressants (such as tricyclics and monoamine oxidase inhibitors). Pragmatic clinical trials are needed to compare the effectiveness of atypical antipsychotics with TRD-specific pharmacotherapies and neuromodulation treatments and to identify the optimal sequencing of these varied approaches for patients with MDD. When using atypical antipsychotics, clinicians and patients are encouraged to use a shared decision-making approach by personalizing treatment selection based on anticipated side effects, tolerability, cost, and feasibility.

Bilateral pretibial edema associated with risperidone: A case report

IntroductionRisperidone is a benzisoxazole derivative and is an antipsychotic drug that is frequently used in psychiatric disorders with high binding to 5HT-2A, D2, α1-adrenergic and α2-adrenergic receptors. It is a second generation antipsychotic and the most common side effects are known as extrapyramidal symptoms, weight gain, sedation, hyperprolactinemia, dizziness, insomnia, anxiety and nausea. Edema has been reported in a few cases as a side effect of risperidone in the literature.Objectives In this case report, we aimed to present a case of peripheral edema developed in a patient using escitalopram combined with risperidone and to review the literature on this subject.Methods A 48-year-old male presented to the outpatient psychiatry clinic with symptoms of difficulty in controlling his irritability and anger, damaging the things around him, depression, loss of interest and desire, sleep disturbance, fatigue, and feelings of worthlessness. The patient also applied to the psychiatry outpatient clinic with similar symptoms 5 months ago, and had been on sertraline 50 mg/day and quetiapine 25 mg/day since then. But it was learned that he did not benefit, so his treatment was adjusted as escitalopram 10 mg/day and risperidone 1 mg/day. The patient, who came to the outpatient clinic control after 1 month and did not describe a similar complaint before, described peripheral edema that developed approximately 2 weeks after he started using psychiatric medication. On examination, 3+ pretibial peripheral edema was detected. Since the patient had a previous history of escitalopram use, it was recommended to continue escitalopram 10 mg/day treatment, and risperidone 1 mg/day was discontinued and he was called for control.ResultsIt was observed that the edema completely resolved within 2 weeks following the discontinuation of risperidone treatment.ConclusionsIn conclusion, risperidone is an antipsychotic frequently used in clinical practice, and edema is a rare but important side effect and can be encountered even at low doses. Despite the low incidence, this side effect should be considered by clinicians. There is a need for controlled studies that explain the relationship between risperidone and edema, elucidate the mechanism of edema and investigate its incidence.Disclosure of InterestNone Declared

Aripriprazole induced severe oculogyric dystonia treated with electroconvulsive therapy(ECT)

IntroductionAripiprazole is the third generation Antipsychotic, and Dopamine serotonin system stabiliser.It is partial agonist at D2 and 5 HT1 A and antagonist at 5 HT2.Most commonly seen adverse effects are Akathesia, fatugue,insomnia and headache the major advanatage is less propensity for extrapyramidal side effects and lmetabolic side eefects.ObjectivesTo report a case of Schizophrenia treated with Aripiprazole 15mg/day developiing occular gyric crisis which was tratment resistant.MethodsWe administered Electroconvulsvive therapy, bidirectional brief pulse constant current 8 ECTS, under General anesthesia with medical fitness .ResultsPatient Showed complete resolution of Dystonia after second ECTs and Showed improvment in Pyschosis Parameterd. Assessment using Naranjo Protocol made.ConclusionsElectroconvulsive therapy therapy is viable alternative to manage Dystonia when medical treatment failsDisclosure of InterestNone Declared

ARIPIPRAZOLE-INDUCED OCULOGYRIC CRISIS (ACUTE DYSTONIA)

IntroductionAripiprazole is a third generation atypical antipsychotic and a dopamine serotonin system stabilizer, effective against positive and negative symptoms of schizophrenia. Within the group of atypical antipsychotics, aripiprazole shows a relatively benign safety profile (e.g. lower metabolic impact, mild effect on cardiovascular parameters), although the reported rate of extrapyramidal side effects is measurable.Oculogyric crisis (OGC) is a rare movement disorder characterized by a prolongued involuntary upward deviation of the eyes, lasting minutes to hours. In most cases, OCG is a drug-induced adverse event with acute or tardive onset often attributable to a functional impairment of dopaminergic neurotransmission.ObjectivesOGC is seldom reported in children and young adults during treatment with aripiprazole, althouh it is commonly used in youths.MethodsWe report a case of an aripiprazole-induced oculogyric crisis in a 19 year old girl who diagnosed with schizophrenia (paranoid).ResultsThere was a complete remission of the OGC’s following aripiprazole dose reduction, suggesting the clinical manifestation was a dose-dependent phenomenon.ConclusionsThe present report should raise awarness among clinicians for this relevant possible adverse event, that can happen also with the use of aripiprazol, not only with typical or more antidopaminergic antipsychotics. Future research in the field should emphasize neurobiological dysfunctions as the basis of EPS/OGC in patients.Disclosure of InterestNone Declared

Neutropenia induced by several second-generation antipsychotics :A case report

IntroductionAntipsychotic medications remain the mainstay of the treatment of various psychiatric disorders, particularly schizophrenia. However, this therapeutic class can induce a range of side effects. Although the treatment with second generation antipsychotics includes a lower risk for extrapyramidal symptoms as compared to first generation antipsychotics, there are numerous adverse events that can result from atypical antipsychotics. Since the introduction of clozapine, there has been increased awareness regarding antipsychotic-induced hematological side effects.ObjectivesThe objective of this case report is to highlight the importance of the management of antipsychotic-induced neutropenia.MethodsWe report a patient with history of schizophrenia who developed neutropenia induced by Haloperidol, Chlorpromazine, Olanzapine, Amisulpride and Aripiprazole.ResultsWe present a case of a 43-year-old male patient with a history of schizophrenia, admitted in our department for the management of a state of agitation in the context of a relapse of his condition. On admission, the patient experienced psychotic symptoms, including delusions and auditory hallucinations, in addition to negative symptoms, such as affective flattening, alogia, avolition and asociality. He was then started on 12 mg of Haloperidol and 200 mg of Chlorpromazine with a white blood cells count (WBC) of 5.98 x 109/L and absolute neutrophil count (ANC) of 2.52 x 109/L (WBC reference range: 4.0-10.0 x 109 /L; ANC reference range: 1.5-7.0 x 109 /L). The patient did not report adverse events on this medication.15 days into hospitalization, a mild neutropenia was detected (WBC=3.92 x 109 /L and ANC=1.01 x 109 /L), leading to a discontinuation of the antipsychotic treatment. No signs of infection were found. After one month, the patient had a normal WBC and ANC. Aripiprazole was discussed as a first alternative and was begun at 5 mg/day and then at 10 mg/day. After one week of treatment with Aripiprazole, the patient’s WBC was normal, but the ANC decreased again leading to a moderate neutropenia (ANC=0.91x 109 /L). The antipsychotic treatment was once again discontinued and the hematological evaluation found no other identifiable cause. Afterwards, neither Olanzapine nor Amisulpride showed significant response to this adverse effect. Finally, the administration of Risperidone led to a positive outcome on the WBC and the ANC.ConclusionsAwareness regarding the hematological side effects of antipsychotics should increase and clinical management of this type of adverse event should be a subject of interest among psychiatrists.Disclosure of InterestNone Declared

The Fall of Icarus: Post-psychotic depression - Apropros a clinical case

IntroductionDepressive symptoms occur in different phases of psychosis, including prodromal, acute and post-psychotic. Post-psychotic depression (PPD) is a phenomenon that presents as a diagnostic and therapeutic challenge. Having been ascribed various descriptions in the past, PPD has been used in a broad manner to describe depressive symptoms that appear in patients with history of psychosis. PPD unveils itself as a separate nosological entity, differing from the adverse effects typically associated with antipsychotics, the negative symptoms of psychosis, and other psychiatric disorders that present with both psychotic and depressive symptoms (e.g. bipolar disorder, schizoaffective disorder, or psychotic depression).ObjectivesThe authors present a case of a 64 year-old man hospitalized due to inaugural psychosis with persecutory and grandiose delusions as well as auditory hallucinatory activity, who began to develop a depressive clinical picture whilst under treatment. A brief discussion on post-psychotic depression, from its clinical presentation to its treatment and implications in prognosis is also presented.MethodsA brief non-systematized literature review using the Pubmed platform as well as presentation of a clinical case.ResultsDepressive complaints are a common complication of psychotic episodes, with the literature estimating that approximately a quarter of psychotic patients present with PPD. Although typically described in association with schizophrenia, recent literature describes PPD occurring alongside other psychotic presentations, including first-episode psychosis. A division between affect and psychosis has been attempted in terms of psychiatric classification, however, the blurred lines between the two continue to contribute to difficulties in differential diagnosis. This becomes a challenge when distinguishing between extrapyramidal symptoms associated with antipsychotics, negative symptoms (i.e apathy, abulia and alogia) and psychiatric disorders with affective-psychotic overlap. Having only recently been considered a distinct clinical entity in psychiatric classification systems, research on its etiology, course, treatment and prognosis are scarce. In regards to the previously described patient, a depressive disorder whilst in treatment for psychosis was identified, and through early recognition of the symptoms treatment with an antidepressant was initiated with favourable response.ConclusionsPPD is a relatively common phenomenon which is gaining more attention in recent literature. As classifications have begun to consider PPD as a distinct clinical entity, as well as unifying defining criteria, further studies can be developed so as to clarify aspects which remain to be defined. The clinician should be aware of this entity as well as the potentially confounding symptom presentations, so as to provide adequate early treatment thus contributing to improved patient outcomes.Disclosure of InterestNone Declared

A novel method for the therapeutic drug monitoring of biperiden in plasma by GC-MS using salt-assisted liquid–liquid microextraction

Biperiden is an anticholinergic agent with central effects. It is used in Parkinson's syndromes and in the treatment of extrapyramidal symptoms that occur with the use of various agents (neuroleptics, antipsychotics). It causes anticholinergic syndrome in high doses. For this reason, therapeutic drug monitoring of biperiden is important. This study, it was aimed to develop a validated GC-MS method for the therapeutic monitoring of biperiden in human plasma. Biperiden and internal standard biperiden-d5 were extracted from plasma using the salt-assisted liquid–liquid extraction method. The method was validated according to the European Medicines Agency (EMA), Bioanalytical method validation guidelines. The lower limit of quantification of the developed method was chosen as 0.5 ng/mL. The calibration curve of biperiden for the method was validated between 0.5 and 15 ng/mL, showing correlation coefficients >0.99. In addition, the developed method was used for the therapeutic drug monitoring of biperiden in real patient plasma.

Usefulness of Low-Dose Olanzapine for Initial and Maintenance Treatments of Very-Late-Onset Schizophrenia-Like Psychosis: A Case Report

In pharmacotherapy for schizophrenia, it is recommended that antipsychotic medications should not be discontinued, and their dosage should not be reduced during the stabilization and maintenance phases. Nevertheless, these drugs also have side effects that can increase extrapyramidal symptoms and mortality in the elderly population. It is yet to be determined whether antipsychotics should be reduced or discontinued in patients with very-late-onset schizophrenia-like psychosis (VLOSLP) during the stabilization and maintenance stages. Therefore, we describe the case of an elderly woman for whom low-dose olanzapine was useful throughout the initial, stabilization, and maintenance phases of VLOSLP. The patient was a 70-year-old woman who had experienced persistent hallucinations and delusions for 3 years. Two years after her diagnosis, except for relapse due to self-discontinuation, she remained in remission of her psychotic symptoms by continuing olanzapine treatment (2.5 mg/day). The standard effective dose of olanzapine was 10 mg/day, and she was able to respond to therapy with a low dose of olanzapine in the initial and subsequent phases of stabilization and maintenance. It is suggested that the discontinuation of antipsychotics should be avoided to avoid recurrence, even if the dose is lower than the standard amount during the stabilization and maintenance phases. Additionally, if the patient progresses to dementia, the treatment approach may vary, and it is imperative to monitor cognitive decline and self-discontinuation of oral medications during the follow-up of VLOSLP.

Succesful Use of Lipid Emulsion Theraphy In a Case of Extremely High Dose Olanzapine Intoxication.

In olanzapine intoxication alterations in consciousness defined as "agitation despite sedation" as well as cardiovascular and extrapyramidal side effects due to anticholinergic effects can be seen. In this case report, we aimed to present a patient who received a very high dose of olanzapine for suicide purposes benefited from intravenous lipid emulsion treatment (LET). A 20-year-old male patient, who received 840 mg of olanzapine for suicide, was brought to the emergency room, when the Glasgow Coma Scale was 5, he was intubated and given a single dose of activated charcoal. Later, he was admitted to the intensive care unit (ICU) intubated. The olanzapine level was measured as 653 μg L-1. The patient was started on LET and woke up at the sixth hour. In addition to the lack of strong evidence regarding the use of LET in olanzapine intoxication, it is seen that lipid therapy has been used successfully in patients. Compared with the cases in the literature, LET was successfully applied in our case, where the blood olanzapine level was very high. Although there is no evidence-based treatment in olanzapine intoxication, we believe that LET has a positive effect on neurological recovery and survival.

Neuroleptic malignant syndrome in fields other than psychiatry

AbstractNeuroleptic malignant syndrome (NMS) is an adverse effect of drugs, mainly neuroleptics. It is characterized by problems related to the autonomic nervous system (such as hyperthermia, diaphoresis, and tachycardia) and extrapyramidal symptoms (such as muscle rigidity and tremor). After onset, NMS progresses rapidly and without treatment, becomes life‐threatening. In recent years, NMS has become better recognized, and treatment has improved; most cases are now curable before becoming dangerous. Most NMS reports are from psychiatrists or neurologists; few are from other specialized clinicians. However, nonpsychiatric clinicians, such as surgeons, emergency physicians, orthopedists, and oral surgeons, sometimes must administer neuroleptic drugs. Although NMS is rare, its effects on patients may be debilitating, and this places a heavy burden on clinicians. Thus, not only psychiatrists but also clinicians in various other fields should understand this illness. This article describes NMS in fields other than psychiatry and its diagnosis, risk factors, and treatment strategies.

Effectiveness and safety of blonanserin in young and middle-aged female patients with schizophrenia: data from a post-marketing surveillance

BackgroundA post-marketing surveillance of blonanserin has been ongoing since September 2018. The aim of this study was to assess the effectiveness and safety of oral blonanserin in Chinese young and middle-aged female patients with schizophrenia in real clinical settings, using the data from the post-marketing surveillance.MethodsA 12-week, prospective, multi-center, open-label, post-marketing surveillance was conducted. Female patients aged 18–40 years were included in this analysis. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the effectiveness of blonanserin in improving psychiatric symptoms. The incidence of adverse drug reactions (ADRs) such as of extrapyramidal symptoms (EPS), prolactin elevation and the weight gain were used to evaluate the safety profile of blonanserin.ResultsA total of 392 patients were included both in the safety and full analysis sets, 311 patients completed the surveillance protocol. The BPRS total score was 48.8 ± 14.11 at the baseline, decreasing to 25.5 ± 7.56 at 12 weeks (P < 0.001, compared with baseline). EPS (20.2%) including akathisia, tremor, dystonia, and parkinsonism were found as the most frequent ADRs. The mean weight gain was 0.27 ± 2.5 kg at 12 weeks from the baseline. Four cases (1%) of prolactin elevation were observed during the period of surveillance.ConclusionBlonanserin significantly improved the symptoms of schizophrenia in female patients aged 18–40 years; the drug was well tolerated and had a low tendency to cause metabolic side effects, including prolactin elevation in these patients. Blonanserin might be a reasonable drug for the treatment of schizophrenia in young and middle-aged female patients.

Adverse drug reactions in geriatric psychiatry—retrospective cohort study of a 6-year period

ObjectiveTo investigate the frequency and characteristics of adverse drug reactions (ADRs) that occurred on the gerontopsychiatric ward of Hannover Medical School over a 6-year period.DesignRetrospective monocentric cohort study.ResultsSix hundred thirty-four patient cases (mean age 76.6 ± 7.1 years; 67.2% female) were analysed. In total, 92 ADRs in 56 patient cases were registered in the study population. The overall ADR prevalence, the ADR prevalence upon hospital admission, and the ADR prevalence during hospitalisation were 8.8%, 6.3%, and 4.9%, respectively. The most frequent ADRs were extrapyramidal symptoms, alterations in blood pressure or heart rate, and electrolyte disturbances. Of note, two cases of asystole and one case of obstructive airway symptoms related to general anaesthesia in the context of electroconvulsive therapy (ECT) were detected. The presence of coronary heart disease was associated with an increased risk of ADR occurrence (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.37–6.22), while the presence of dementia was associated with a decreased risk of ADR development (OR 0.45, 95% CI 0.23–0.89).ConclusionsType and prevalence of ADRs in the present study were largely in accordance with previous reports. By contrast, we did not observe a relationship between advanced age or female sex and ADR occurrence. We detected a risk signal for cardiopulmonary ADRs related to general anaesthesia in the context of ECT that warrants further investigation. Elderly psychiatric patients should be carefully screened for cardiopulmonary comorbidities before initiation of ECT.

Oculogyric crisis induced by risperidone in a child withGRIN1variant

The GluN1 subunit of the N-methyl-d-aspartate (NMDA) receptor is encoded by GRIN1 gene. Mutations in this gene can cause neurodevelopmental disorders with or without hyperkinetic movements and seizures. It can be inherited as either autosomal dominant (NDHMSD) or autosomal recessive (NDHMSR). Patients can present with severe psychomotor delay, seizures, behavioral problems, stereotypies, and oculogyric crisis (OGC). There is emerging evidence regarding the molecular interaction between dopamine and NMDA receptors, cross-talk between dopamine and glutamate signaling, and mutations in GRIN1 could affect both glutamatergic and dopaminergic synaptic transmission. Dopamine antagonists, such as risperidone, which is used to treat behavioral problems, can cause extrapyramidal side effects, including OGC. Here, we present a case of an 8-year-old boy with a GRIN1 variant who was treated with risperidone for severe behavioral problems and experienced an OGC for approximately 30 h. The child had no prior history of such event and experienced no re-occurrences after discontinuing risperidone. This case highlights the importance of exercising extra caution while prescribing dopamine antagonists for patients with GRIN1 mutations and reports the efficacy of memantine in treating seizures and behavioral side effects in such patients. In the era of precision medicine, this case represents a good example of how patient's genetic makeup should be considered in prescribing the right medication for the right patient.

Telehealth As an Option, Not a Requirement-Who May Benefit, and How Do We Decide?

During the COVID pandemic, telehealth has been established as a feasible form of treatment that is at times preferred by both clinicians and older adult patients. As the height of the pandemic fades, yet remains part of everyday life, care has shifted in many practices from primarily video and phone visits (telemental health, or TMH) to a hybrid model that includes both virtual and in person visits. There are both advantages and potential drawbacks to TMH. Advantages include the ability to see patients who are otherwise homebound or find transportation difficult, the ability to see patients without a mask, reduction in no show rate, the potential to get a sense of the patient's home environment, and actively involving family whom the patient would like to include. Potential drawbacks include a loss of aspects of non-verbal communication, inability to perform a physical exam if needed (for example, to assess gait, check or vitals, or evaluate for extrapyramidal symptoms), potential lack of privacy, and a patient's difficulty navigating technology. Clinician related factors may also affect the success of telemental health as a treatment modality. These factors include personal preference, clinicians’ comfort with technology and the suitability of a provider's work environment for this platform. The frame of treatment (medication management versus psychotherapy) is an additional factor that must be considered. There are also individual patient characteristics that may contribute to them being more or less receptive to this modality of treatment. These factors will be highlighted in case examples in the session. Now that clinicians have a choice about meeting virtually or in person, it will be helpful to have a framework for making this decision. In this workshop, we will present guidelines for evaluating the usefulness of video delivered treatment. We will propose factors to be considered by clinicians to evaluate an individual patient's suitability for tele health versus in person or a hybrid model. We will also discuss strategies to overcome potential barriers.

Neurodegeneration with brain iron accumulation: a case series highlighting phenotypic and genotypic diversity in 20 Indian families.

Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term encompassing various inherited neurological disorders characterised by abnormal iron accumulation in basal ganglia. We aimedto study the clinical, radiological and molecular spectrum of disorders with NBIA. All molecular-proven cases of NBIA presented in the last 5years at 2 tertiary care genetic centres were compiled. Demographic details and clinical and neuroimaging findings were collated. We describe 27 individuals from 20 unrelated Indian families with causative variants in 5 NBIA-associated genes. PLA2G6-associated neurodegeneration (PLAN) was the most common, observed in 13 individuals from 9 families. They mainly presented in infancy with neuroregression and hypotonia. A recurrent pathogenic variant in COASY was observed in two neonates with prenatal-onset severe neurodegeneration. Pathogenic bi-allelic variants in PANK2, FA2H and C19ORF12 genes were observed in the rest, and these individuals presented in late childhood and adolescence with gait abnormalities and extrapyramidal symptoms. No intrafamilial and interfamilial variability were observed. Iron deposition on neuroimaging was seen in only 6/17 (35.3%) patients. A total of 22 causative variants across 5 genes were detected including a multiexonic duplication in PLA2G6. The variants c.1799G > A and c.2370T > G in PLA2G6 were observed in three unrelated families. In silico assessments of 8 amongst 9novel variants were also performed. We present a comprehensive compilation of the phenotypic and genotypic spectrum of various subtypes of NBIA from the Indian subcontinent. Clinical presentation of NBIAs is varied and not restricted to extrapyramidal symptoms or iron accumulation on neuroimaging.

Development of sensitive magnetic nanoparticle assisted rapid sandwich assay(s-MARSA) to monitor Parkinson's disease and Schizophrenia pharmacotherapy

Parkinson's disease and Schizophrenia fall under low dopamine neurodegenerative and high dopamine psychiatric disorders respectively. Pharmacological interventions to correct mid-brain dopamine concentrations sometimes overshoots the physiological dopamine levels leading to psychosis in Parkinson's disease patients and, extra-pyramidal symptoms in schizophrenia patients. Currently no validated method is available to monitor side effects in such patients, Apolipoprotein E is one of the CSF biomarkers identified in the recent past that shows an inverse relation to mid-brain dopamine concentration. In this study, we have developed s-MARSA for the detection of Apolipoprotein E from ultra-small volume (2 μL) of CSF. s-MARSA exhibits a broad detection range (5 fg mL−1 to 4 μg mL−1) with a better detection limit and could be performed within an hour utilizing only a small volume of CSF sample. The values measured by s-MARSA strongly correlates with the values measured by ELISA. Our method has advantages over ELISA in having a lower detection limit, a broader linear detection range, shorter analysis time, and requiring a low volume of CSF samples. The developed s-MARSA method holds promise for the detection of Apolipoprotein E with clinical utility for monitoring pharmacotherapy of Parkinson's and Schizophrenia patients.

Acute cervical dystonia induced by one dose of butamirate citrate: A case report and review of literature from Hamad General Hospital Emergency, a tertiary hospital in Qatar

Dystonia is defined as abnormal muscle contraction or twisting or repetitive movements that result in sustained and abnormal posture. Cervical dystonia (CD) is one form of dystonia that involves neck muscles and leads to involuntary movements of the neck and head. Many centrally acting medications such as antipsychotics and antidepressants were reported to cause acute dystonia, as they cause an extrapyramidal side effect. We present the case of a female adult patient who had acute CD after 2 hours of the first dose of butamirate citrate, a centrally acting cough syrup, which rarely causes central nervous side effects. The patient developed neck pain, spasm, and rigidity, which worsened over time. She improved after the first dose of benztropine, an anticholinergic medication which is one of the treatment options for treating CD. This case has shown that even in OTC medications with a good safety profile, critical side effects happen, which indicates that clinicians need to be more attentive to patient’s medication history prior to critical events such as acute CD.

Pimozide Increases a Delayed Rectifier K+ Conductance in Chicken Embryo Vestibular Hair Cells.

Pimozide is a conventional antipsychotic drug largely used in the therapy for schizophrenia and Tourette's syndrome. Pimozide is assumed to inhibit synaptic transmission at the CNS by acting as a dopaminergic D2 receptor antagonist. Moreover, pimozide has been shown to block voltage-gated Ca2+ and K+ channels in different cells. Despite its widespread clinical use, pimozide can cause several adverse effects, including extrapyramidal symptoms and cardiac arrhythmias. Dizziness and loss of balance are among the most common side effects of pimozide. By using the patch-clamp whole-cell technique, we investigated the effect of pimozide [3 μM] on K+ channels expressed by chicken embryo vestibular type-II hair cells. We found that pimozide slightly blocks a transient outward rectifying A-type K+ current but substantially increases a delayed outward rectifying K+ current. The net result was a significant hyperpolarization of type-II hair cells at rest and a strong reduction of their response to depolarizing stimuli. Our findings are consistent with an inhibitory effect of pimozide on the afferent synaptic transmission by type-II hair cells. Moreover, they provide an additional key to understanding the beneficial/collateral pharmacological effects of pimozide. The finding that pimozide can act as a K+ channel opener provides a new perspective for the use of this drug.

Comparative Study of Extrapyramidal Side Effects, Sexual Dysfunctions and Hyperprolactinaemia Using Typical and Atypical Antipsychotic Medications Among Patients with Schizophrenia in Maiduguri.

Extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia are major side effects with the use of antipsychotic medications that impede treatment adherence leading to relapse, increased cost of care and rehospitalization among patients with schizophrenia on antipsychotic medications. The study aims to compare the prevalence of extra-pyramidal side effects (EPSE), sexual dysfunctions (SD) and hyperprolactinaemia (HPRL) among patients with schizophrenia spectrum disorders on typical and atypical antipsychotic medications. The secondary aim is to determine if any associations exist between extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia. A cross-sectional hospital-based survey involving 209 patients with schizophrenia were interviewed with structured instruments for the assessment of sexual dysfunction, EPSE and the estimation of serum prolactin was done using Enzyme-linked Immunosorbent Assay. Frequencies and Chi-square analysis were used to compare differences in EPSE, SD & HPRL. The study revealed non-statistically significant differences as a group between typical and atypical antipsychotic medication in terms of extra-pyramidal side effects, sexual dysfunction and hyperprolactinaemia. However, a significant association was observed when individual drugs were compared with haloperidol causing the highest frequency of hyperprolactinaemia (χ 2 = 14.9, P = 0.011). A significant relationship between sexual dysfunction and hyperprolactinaemia, sexual dysfunction and extra-pyramidal side effects as well as extra-pyramidal and hyperprolactinaemia was found when individual items for sexual functionin were used. The significant relationships between sexual dysfunction only in the domains of sexual desire and arousal with hyperprolactinaemia and extrapyramidal side effects as well as hyperprolactinaemia with extrapyramidal side effects point to a common anti-dopaminergic activity of antipsychotics via different pathways. Prospective studies among a larger sample of patients with schizophrenia are needed to unfold these relationships.

Unique effect of clozapine on adenosine A2A-dopamine D2 receptor heteromerization

The striatal dopamine D2 receptor (D2R) is generally accepted to be involved in positive symptoms of schizophrenia and is a main target for clinically used antipsychotics. D2R are highly expressed in the striatum, where they form heteromers with the adenosine A2A receptor (A2AR). Changes in the density of A2AR-D2R heteromers have been reported in postmortem tissue from patients with schizophrenia, but the degree to which A2R are involved in schizophrenia and the effect of antipsychotic drugs is unknown. Here, we examine the effect of exposure to three prototypical antipsychotic drugs on A2AR-D2R heteromerization in mammalian cells using a NanoBiT assay. After 16 h of exposure, a significant increase in the density of A2AR-D2R heteromers was found with haloperidol and aripiprazole, but not with clozapine. On the other hand, clozapine, but not haloperidol or aripiprazole, was associated with a significant decrease in A2AR-D2R heteromerization after 2 h of treatment. Computational binding models of these compounds revealed distinctive molecular signatures that explain their different influence on heteromerization. The bulky tricyclic moiety of clozapine displaces TM 5 of D2R, inducing a clash with A2AR, while the extended binding mode of haloperidol and aripiprazole stabilizes a specific conformation of the second extracellular loop of D2R that enhances the interaction with A2AR. It is proposed that an increase in A2AR-D2R heteromerization is involved in the extrapyramidal side effects (EPS) of antipsychotics and that the specific clozapine-mediated destabilization of A2AR-D2R heteromerization can explain its low EPS liability.