HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia

Schizophrenia is a serious, chronic psychiatric disorder requiring lifelong treatment. Extrapyramidal side effects (EPS) are common adverse reactions to antipsychotic medications. In addition to the dopaminergic system, serotonergic mechanisms, including serotonin (5-HT) receptors, might be involved in EPS development. This study aimed to examine molecular associations of HTR1A, HTR1B, HTR2A, HTR2C and HTR6 gene polymorphisms with acute EPS in 229 male schizophrenia patients, following two weeks of haloperidol monotherapy. The Simpson–Angus Rating Scale for Extrapyramidal Side Effects (SAS), Barnes Akathisia Rating Scale (BARS) and Extrapyramidal Symptom Rating Scale (ESRS) were used to evaluate EPS severity. Genotyping was performed using real-time PCR, following extraction of blood DNA. Significant acute EPS appeared in 48.03% of schizophrenia patients. For the rs13212041 HTR1B gene polymorphism, affecting microRNA regulation of HTR1B gene expression, a higher frequency of TT carriers was found among haloperidol-treated patients with akathisia when compared to the group without akathisia symptoms. In comparison to C-allele carriers, patients carrying the TT genotype had higher akathisia severity, as determined by the SAS, BARS and ESRS scales. These molecular findings suggest potential involvement of 5-HT1B receptors in akathisia development following haloperidol treatment, as well as possible epigenetic mechanisms of serotonergic modulation associated with antipsychotic-induced EPS.

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Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients

Psychopharmacology ◽

10.1007/s00213-006-0622-x ◽

2006 ◽

Vol 190 (4) ◽

pp. 479-484 ◽

Cited By ~ 47

Author(s):

Arzu Gunes ◽

Maria Gabriella Scordo ◽

Peeter Jaanson ◽

Marja-Liisa Dahl

Keyword(s):

Side Effects ◽

Dopamine Receptor ◽

Gene Polymorphisms ◽

Receptor Gene ◽

Extrapyramidal Side Effects ◽

Schizophrenic Patients ◽

Dopamine Receptor Gene ◽

Receptor Gene Polymorphisms

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COMT gene polymorphisms and response to treatment and the incidence of extrapyramidal side effects in schizophrenic patients

Anatolian Journal of Psychiatry ◽

10.5455/apd.240236 ◽

2017 ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Bahman Salehi ◽

Seyed Taheri ◽

Mona Salehi ◽

Bahman Sadeghi ◽

Abdolrahim Sadeghi

Keyword(s):

Side Effects ◽

Gene Polymorphisms ◽

Comt Gene ◽

Response To Treatment ◽

Extrapyramidal Side Effects ◽

Schizophrenic Patients

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Extrapyramidal side effects and functional remission in schizophrenia

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2134 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S195-S196

Author(s):

B. Ghajati ◽

C. Leila ◽

L. Raja ◽

C. Majda

Keyword(s):

Side Effects ◽

Rating Scale ◽

Spectrum Disorder ◽

Extrapyramidal Side Effects ◽

Schizophrenia Spectrum Disorder ◽

Cross Sectional ◽

Schizophrenia Spectrum ◽

The Social ◽

Competing Interest ◽

Social Autonomy

Treating patients with schizophrenia has evolved towards including, as an effective goal, their functional remission. Beyond the discrepancies in this concept definition, a plethora of studies has been conducted trying to identify predictors of functioning in schizophrenia. Among which antipsychotic prescription and related side effects.AimExplore extrapyramidal side effects link with functional prognosis of patients with schizophrenia spectrum disorder.MethodsWe conducted a cross-sectional, retrospective and descriptive study in the psychiatry department “C”, in Razi hospital (Tunis), between October 2014 and March 2015. Sixty patients suffering from schizophrenia spectrum disorder (DSM IV-R) were included. Functional status was explored with the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Assessment Scale (SOFAS) and the Social Autonomy Scale (EAS). Extrapyramidal side effects (EPS) were evaluated using the Simpson and Angus Rating Scale (SAS).ResultsFunctional remission was achieved according to GAF, SOFAS and EAS in respectively: 63,30%, 48,30% and 51,70% of the patients. SAS mean score was 0.898 ± 0.29 (0.4–2). Although SAS showed no significant association with GAF, SOFAS and EAS global scores, patient with less EPS had better autonomy in EAS’ dimension “Relationship with the outside” (P = 0.048).ConclusionEPS may influence functional remission at several levels starting from the neurobiological to the social stigmatization and the treatment adherence levels. Further research in this matter is required.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Double-Blind Evaluation of Domperidone in Acute Vomiting and Dyspeptic Disorders

Journal of International Medical Research ◽

10.1177/030006058100900211 ◽

1981 ◽

Vol 9 (2) ◽

pp. 143-147 ◽

Cited By ~ 13

Author(s):

I Agorastos ◽

N P Zissis ◽

I Kaprinis ◽

G Goulis

Keyword(s):

Side Effects ◽

Rating Scale ◽

Second Phase ◽

Double Blind Trial ◽

Duration Of Treatment ◽

Double Blind ◽

Blind Trial ◽

Therapeutic Results ◽

The Difference ◽

Symptom Rating

The anti-emetic effects of domperidone were evaluated under double-blind conditions in twenty-four patients with acute vomiting randomly assigned to treatment either with 10 mg i.m. domperidone (six females, five males) or with placebo (seven females, six males). The therapeutic results were better with domperidone and the differences from placebo were statistically significant (p < 0.02). In a second randomized, crossover, double-blind trial, domperidone (10 mg t.i.d.) evaluated according to a nine-symptom rating scale, in eighteen dyspeptic patients, proved significantly more effective than placebo. The duration of treatment was 6 weeks and the drugs were crossed-over after 3 weeks. The difference between the two groups was most marked during the second phase of the trial. No side-effects were reported.

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Cross-sectional examination of extrapyramidal side effects in a specialist palliative care inpatient unit

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2018-001504 ◽

2018 ◽

Vol 9 (3) ◽

pp. 271-273

Author(s):

Hannah O'Brien ◽

Fiona Kiely ◽

Aileen Barry ◽

Sarah Meaney

Keyword(s):

Palliative Care ◽

Side Effects ◽

Rating Scale ◽

Demographic Data ◽

Previous History ◽

Inpatient Unit ◽

Screening Tools ◽

Screening Tests ◽

Extrapyramidal Side Effects ◽

Inclusion Criteria

ObjectivesExtrapyramidal side effects (EPSEs) are serious potentially reversible side effects of antipsychotic and other medications that can cause distress for patients. A core principle of palliative care involves optimising quality of life. If side effects of medications are burdensome, it is imperative that we address this issue. The aim of the study was to determine and describe the burden of EPSEs in a specialist inpatient unit.MethodsConsenting patients who met inclusion criteria were assessed for EPSE with two validated screening tests, the Modified Simpson-Angus Scale (MSAS) and Barnes Akathisia Rating Scale (BARS). Additional demographic data were collected including medications associated with EPSE, previous history of EPSE and known risk factors that may predispose a patient to EPSE.Results43% inpatients met inclusion criteria. At least 66% of patients were taking regular medications associated with EPSE. Of those, 25% were taking ≥2 medications associated with EPSE. The MSAS revealed 50% scored <3, 44% scored 3–5% and 6% scored 6–11. Seven patients had at least one ‘not rateable score’. In the BARS (sitting±standing), 94% scored 0/5 and 6% scored 1/5. 12.5% of participants were able to stand for 2 min to complete the BARS.Conclusions50% screened positive for EPSE. The complete BARS was unsuitable for most participants. The MSAS, while allowing a not rateable score, may underestimate EPSE. The frailty of an inpatient unit population impacts on applicability of screening tools and may therefore underestimate the burden of the problem in this population. Development of a population-specific screening tool warrants further investigation.

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Further evidence for the association between 5-HT2C receptor gene polymorphisms and extrapyramidal side effects in male schizophrenic patients

European Journal of Clinical Pharmacology ◽

10.1007/s00228-007-0450-x ◽

2008 ◽

Vol 64 (5) ◽

pp. 477-482 ◽

Cited By ~ 48

Author(s):

Arzu Gunes ◽

Marja-Liisa Dahl ◽

Edoardo Spina ◽

Maria Gabriella Scordo

Keyword(s):

Side Effects ◽

Gene Polymorphisms ◽

Receptor Gene ◽

Extrapyramidal Side Effects ◽

Schizophrenic Patients ◽

Receptor Gene Polymorphisms

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Fatal Overdose with Amantadine

The Canadian Journal of Psychiatry ◽

10.1177/070674378603100814 ◽

1986 ◽

Vol 31 (8) ◽

pp. 757-758 ◽

Cited By ~ 19

Author(s):

P.E. Cook ◽

Stanley W. Dermer ◽

Terry Mcgurk

Keyword(s):

Case Report ◽

Side Effects ◽

Adverse Reactions ◽

Extrapyramidal Side Effects ◽

Fatal Overdose ◽

First Case

The authors describe the first case report in the psychiatric literature of death from an overdose of amantadine hydrochloride used to treat neuroleptic induced extrapyramidal side effects. The pharmacology, adverse reactions and risks of using amantadine are briefly reviewed.

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Drug-Drug-Induced Akathisia: Two Case Reports

Case Reports in Psychiatry ◽

10.1155/2020/9649483 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Grace Owusu Aboagye ◽

Daniel Ankrah

Keyword(s):

Side Effects ◽

Rating Scale ◽

Beta Blockers ◽

Case Reports ◽

First Episode ◽

Extrapyramidal Side Effects ◽

Drug Induced ◽

Fluphenazine Decanoate ◽

Probable Case ◽

Psychotropic Medicines

Extrapyramidal side effects of psychotropic medicines are usually experienced by patients in the first few weeks of initiating therapy. Patients stabilized on these medications who present with distressing complaints akin to akathisia may be triggered by other factors. This report presents two cases of drug-drug-induced akathisia. Case A is a patient with schizophrenia who was being managed with risperidone 2 mg tablet daily for the past 3 years. She fell ill and reported to a nearby clinic where she was prescribed ciprofloxacin and artemether/lumefantrine tablets for the treatment of an infection and malaria. She presented 7 days later to her psychiatrist with complaints of restlessness, tremor, palpitations, insomnia, and resurgence of obsessive thoughts. Case B is a patient who was diagnosed with first-episode psychotic depression and admitted for 10 days. Her medications on admission were fluphenazine decanoate 25 mg depot injection once, olanzapine 10 mg tablet daily, and fluoxetine 20 mg capsule daily. On discharge, ciprofloxacin 500 mg tablet every 12 hours for 5 days and fluconazole 150 mg capsule once were added to her medications for the treatment of a urinary tract infection. She reported back to the hospital a day after discharge with complaints of restlessness, “seizures,” tremor, abdominal discomfort, and weight gain. Both patients were diagnosed with akathisia using ICD-10 classification and the Barnes akathisia rating scale and managed with anticholinergics, benzodiazepines, and beta blockers. Other measures employed in managing the akathisia included reducing the dose of the antipsychotic and/or switching antipsychotics. Despite these management measures, the symptoms of akathisia persisted and only resolved after 4weeks. Upon the resolution of symptoms, Case A continued treatment on olanzapine 5 mg tablet daily and fluoxetine 20 mg capsule daily while Case B continued treatment on risperidone 2 mg tablet daily and fluoxetine 20 mg capsule daily. Using Naranjo’s adverse drug reaction causality assessment scale, Medscape drug interaction checker, and literature review, a possible and probable case of drug-drug-induced akathisia was made for Case A and Case B. This report is to create more awareness about psychotropic-antimicrobial-induced akathisia. The information underpins the need for health professionals to consider adverse drug-drug interactions as the probable cause of extrapyramidal side effects experienced by patients on antipsychotics.

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A Controlled Comparative Trial of a Combination of Opipramol and Clomipramine and a Higher Dose of Clomipramine Alone

Journal of International Medical Research ◽

10.1177/030006057500300106 ◽

1975 ◽

Vol 3 (1) ◽

pp. 26-31

Author(s):

J E Murphy ◽

J F Donald ◽

G Beaumont

Keyword(s):

Clinical Trial ◽

Side Effects ◽

Combination Therapy ◽

Rating Scale ◽

Comparative Trial ◽

Combination Group ◽

Controlled Clinical Trial ◽

Dose Regime ◽

Symptom Rating ◽

Depressive States

Sixty patients suffering from mixed anxiety depressive states were admitted to a comparative controlled clinical trial of a free combination of opipramol 50 mg and clomipramine 10 mg and clomipramine 25 mg. A double-dummy technique was used to ensure blindness and both regimes were administered three times daily. A stratified randomization technique was employed but this did not work effectively as far as severity was concerned producing some imbalance in the groups. Thirty-one patients received the combination therapy and 29 clomipramine alone. Twenty-eight patients on the combination regime and 24 on clomipramine alone completed the study. Amongst the completers the total score, on a 17 symptom rating scale, fell from 19·6 to 6·6 in the combination group and from 23·6 to 9·3 in the clomipramine alone group after 4 weeks treatment. Significantly more side-effects, especially dry mouth, were seen in the clomipramine alone group. After 2 weeks the opipramol/clomipramine regime was significantly more effective in the relief of anxiety whereas the clomipramine higher dose regime brought about a significantly greater improvement in the symptom depressed mood.

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