Neuroleptic Side Effects Research Articles

Clinical and Sociodemographic Correlations with Neurological Soft Signs in Hospitalized Patients with Schizophrenia: A Preliminary Longitudinal Study.

Schizophrenia is a severe, chronic neuropsychiatric disorder characterized by symptoms that profoundly impact behavior, cognition, perception, and emotions, leading to a reduced quality of life and physical impairment. Given the complexity of schizophrenia, there is a pressing need for clinical markers and tools to predict its course, enhance disease staging, facilitate early intervention, improve differential diagnosis, and tailor individualized treatment approaches. Previous studies focused on the relationship between neurological soft signs (NSS) and factors such as age, illness duration, and symptomatology, indicating NSS as state markers improving in parallel with psychotic symptom remission or predicting treatment resistance. However, there is a lack of consensus on NSS assessment tools, hindering routine clinical monitoring despite diagnostic and prognostic potential. The present longitudinal study involved 81 psychiatric inpatients diagnosed with schizophrenia. Patients were assessed at three time points: baseline, 1 month, and 6 months. The examination included the use of scales to evaluate psychotic and neurological symptoms, as well as the identification of adverse extrapyramidal reactions caused by neuroleptic treatment. The progression of NSS was correlated to both the symptomatology and the sociodemographic data of the patients. The main findings from the present investigation revealed a statistical correlation between NSS and psychopathological symptoms, especially with negative symptoms of schizophrenia. However, it is important to note that neuroleptic side effects only had a limited impact on NSS. Therefore, instead of being linked to extrapyramidal symptoms caused by neuroleptics, NSS appears to be more frequently related with symptoms of schizophrenia. Our findings provide further support for their strong association with the course of schizophrenia, independent of treatment side effects, thus emphasizing their potential as reliable assessment tools in both research and clinical settings.

Somatic symptoms in schizophrenia: Association with socio-demographic and clinical characteristics, disability and quality of life.

There is lack of research on somatic symptoms in schizophrenia. We aimed at finding prevalence and types of somatic symptoms in patients with schizophrenia and assessed their association with socio-demographic and clinical characteristics. We assessed somatic symptoms using Patient Health Questionnaire-15 (PHQ-15) in 93 patients with schizophrenia diagnosed on ICD10-DCR. Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms, WHO Disability Assessment Schedule 2.0, WHO Quality of Life (BREF) Hindi version and Liverpool University Neuroleptic Side-Effect Rating Scale were used to assess psychopathology, disability, quality of life and side effects. Significant somatic symptoms (n ≥5 on PHQ-15) were present in 62 (67.7%) patients with schizophrenia. Forty three (69.4%) had mild (n = 5-9 on PHQ-15), 17 (27.4%) had moderate (n = 10-14 on PHQ-15), and only 2 (3.2%) had severe (n = ≥15 on PHQ -15) somatic symptoms. Mean somatic symptoms score on PHQ-15 was 7.28 (± 3.83); 96.8% reported feeling tired, 76.3% had constipation or diarrhoea, 67.7% trouble in sleeping, 61.3% nausea or indigestion, 52.7% back pain and 51.6% headache. Patients with somatic symptoms were older in age, had longer duration of illness and treatment, and had more negative symptoms. They had higher disability and poor quality of life especially in physical domain. Somatic symptoms are common in patients with schizophrenia and are associated with chronicity, refractoriness and negative symptoms, significant disability and poor quality of life. Thus during routine clinical practice, somatic symptoms should be assessed and managed in these patients.

Genetic Polymorphism in CYP2D6 and its Association with the Safety and Efficacy of Fluvoxamine in Patients with Major Depressive Disorder

Genetic Polymorphism in CYP2D6 and its Association with the Safety and Efficacy of Fluvoxamine in Patients with Major Depressive Disorder

Farmacoterapia de la acatisia aguda inducida por neurolépticos

La acatisia aguda es un trastorno del movimiento bastante molesto, caracterizado por sensación subjetiva y signos objetivos de inquietud motora, que se presenta frecuentemente como efecto adverso de los neuroslépticos; un tratamiento oportuno es necesario para garantizar una buena adherencia al manejo con antipsicóticos y prevenir recaídas.
 Se describe el estado actual de los tratamientos disponibles para la acatisia aguda inducida por neurolépticos, valorando efectividad y tolerabilidad.
 Se realizó una búsqueda electrónica en Pubmed, Science Alert, Springer link, SciELO, Ovid y Elsevier con criterios de selección específicos, obteniendo 87 estudios, de los cuales se escogieron 51 teniendo en cuenta relevancia clínica, nivel de evidencia y actualidad.
 En este artículo se describen los resultados de la búsqueda. Las benzodiacepinas, los betabloqueadores lipofílicos de acción central y los anticolinérgicos son los fármacos más estudiados para el tratamiento de este trastorno del movimiento; los dos primeros han mostrado superioridad, sin embargo, se necesita aún bastante investigación al respecto.
 Palabras clave: Acatisia inducida por medicamentos, agitación psicomotora, antipsicóticos, efectos adversos, trastornos del movimiento, inducidos químicamente (DeCS).

A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects.

Background: Phosphodiesterase 10A (PDE10A) is expressed almost exclusively in the striatum and its inhibition is suggested to offer potential treatment in disorders associated with basal ganglia. We evaluated the selectivity, cytotoxicity, genotoxicity, pharmacokinetics and potential adverse effects of a novel PDE10A inhibitor, CPL500036, in vivo. Methods: The potency of CPL500036 was demonstrated by microfluidic technology, and selectivity was investigated in a radioligand binding assay against 44 targets. Cardiotoxicity in vitro was evaluated in human ether-a-go-go related gene (hERG)-potassium channel-overexpressing cells by the patch-clamp method and by assessing key parameters in 3D cardiac spheroids. Cytotoxicity was determined in H1299, HepG2 and SH-SY5Y cell lines. The Ames test was used for genotoxicity analyses. During in vivo studies, CPL500036 was administered by oral gavage. CPL500036 exposure were determined by liquid chromatography-tandem mass spectrometry and plasma protein binding was assessed. The bar test was employed to assess catalepsy. Prolactin and glucose levels in rat blood were measured by ELISAs and glucometers, respectively. Cardiovascular safety in vivo was investigated in dogs using a telemetry method. Results: CPL500036 inhibited PDE10A at an IC50 of 1nM, and interacted only with the muscarinic M2 receptor as a negative allosteric modulator with an IC50 of 9.2µM. Despite inhibiting hERG tail current at an IC25 of 3.2μM, cardiovascular adverse effects were not observed in human cardiac 3D spheroids or in vivo. Cytotoxicity in vitro was observed only at > 60μM and genotoxicity was not recorded during the Ames test. CPL500036 presented good bioavailability and penetration into the brain. CPL500036 elicited catalepsy at 0.6mg/kg, but hyperprolactinemia or hyperglycemic effects were not observed in doses up to 3mg/kg. Conclusion: CPL500036 is a potent, selective and orally bioavailable PDE10A inhibitor with a good safety profile distinct from marketed antipsychotics. CPL500036 may be a compelling drug candidate.

Prevalence and Associated factors of Tardive Dyskinesia among patients with schizophrenia taking Antipsychotics

1.1. Objective: Tardive dyskinesia (TD) is one of incapacitating side effect of neuroleptics. It has been implicated in the morbidity, functional impairment, stigma and overall poor prognosis of patients with schizophrenia. However, there is little information from Ethiopia. Therefore, we conducted a cross-sectional study among 161 schizophrenia patients who were admitted and on follow up at two public hospitals in Addis Ababa. We assessed TD using the Abnormal Involuntary Movement Scale. Associated factors Were also analyzed. 1.2. Results: Out of the total study participants, 41(25.5%) have TD. Clinical characteristics variables such as depot antipsychotics, combination of antipsychotics, Chlorpromazine equivalent dose of 400 mg or more and substance use were significantly associated with TD (P – value < 0.05). Nearly half of those with TD had moderate to severe TD which has significant negative impact on their day-to-day activities. 1.3. Conclusion: Prevalence of TD among schizophrenia patients taking antipsychotics is high. Root of administration and higher dose of antipsychotic medication and substance use were found to be factors associated. Rational use of antipsychotics and regular screening for TD for patients who takes antipsychotics is recommended.

Improving Medication Adherence in Convalscent Psychiatric Out-Patients Exposed to Psychotomimetic Medications in South-West, Nigeria: The Role of Medication Literacy and `Therapeutic Relationships.

Medication adherence is a growing concern to clinicians and healthcare providers in psychiatric communities, mounting evidence of the prevalence of non-adherence have been significantly associated with undesirable health outcomes and burdensome healthcare expenditure. This study examined medication adherence in psychiatric patients exposed to psychotomimetic medications and how therapeutic relationship predicts the level of medication adherence. This study was a cross-sectional survey design. Snowballing sampling technique was used to select psychiatric out-patients. The total number of participants for this study was thirty-six (36), males (65%) and females (35%). Majority of participants were between the ages of 31-50 years. Participants responded to Morinsky Medication Adherence Scale (α=0.91), Liverpool University Neuroleptic Side-Effect Scale (α= 0.89), and Therapeutic Relationship Scale (patient version) (α=0.71). Three hypotheses were formulated and tested using multiple regression analysis. Results of the multiple regression indicate that psychotomimetic side-effects inversely predicted medication adherence among psychiatric patients exposed to psychotomimetic drugs [β = .35, p <0.01]. Also, the outcome of the results indicated that therapeutic relationship was a significant predictor of medication adherence among psychiatric patients exposed to psychotomimetic drugs [β = .40, p <0.01]. Therefore, it was recommended that therapeutic relationship should be an integral part of the modalities in psychiatric treatment and to adopt best practices by effectively communicating with patients about the importance of adhering to treatment plans; and provide medication support services to patients and family caregivers. This helps to improve, build a sustainable therapeutic relationship (nurse-patient) through empathy and professional intimacy that facilitates diagnosis accuracy, and desired health outcome.

Correlates of high-dose antipsychotic prescription amongst outpatients with Schizophrenia in a Nigerian Hospital

BackgroundTreatment guidelines recommend the use of antipsychotic monotherapy at effective doses for the treatment of schizophrenia, although about a third of the sufferers still receive high-dose antipsychotic treatment. Current evidence suggests that high-dose antipsychotic prescription (HDAP) not only fails to improve outcomes but also increases side effects.AimOur study aimed to determine the prevalence of HDAP and its association with illness severity, medication adherence behaviour and side effects amongst outpatients with schizophrenia.SettingThe Federal Neuro-Psychiatric Hospital, Benin-City, Nigeria.MethodsA cross-sectional study of 320 attendees with schizophrenia at the outpatient department was undertaken. We administered a sociodemographic and antipsychotic medication questionnaire, Mini-International Neuropsychiatric Interview, Positive and Negative Syndrome Scale, Liverpool University Neuroleptic Side Effects Rating Scales and Medication Adherence Rating Scales. High-dose antipsychotic prescription was determined by the ratio of prescribed daily dose to defined daily dose greater than 1.5.ResultsThe prevalence of HDAP was 38.4%. Greater severity of illness, experiencing more side effects and poor medication adherence were significantly associated with HDAP.The major predictors of HDAP were antipsychotic polypharmacy and concurrent anticholinergic use.ConclusionWe conclude that although the use of HDAP amongst patients with schizophrenia remains common, its persistent use should be discouraged.

Accidental Trihexyphenidyl Intoxication in a Seven-Year-Old Child: A Case Report from Senegal

Trihexyphenidyl or Artane® /Parkinane® is an anti-cholinergic drug belonging to the antimuscarinic class. It is used in the treatment of Parkinson’s disease and widely in psychiatry for the management of extrapyramidal side effects of neuroleptics. Its overdose leads to a central and peripheral anticholinergic syndrome. We report here the case of a seven-year-old Senegalese boy who developed signs of intoxication due to accidental ingestion of a high dose of trihexyphenidyl and recovered completely after administration of parenteral antipyretic, gastric lavage and supportive care in a paediatric setting.

Neuroleptic malignant syndrome: clinical expression, complication, course, and atypical clinical picture

BackgroundNeuroleptic malignant syndrome (NMS) is an uncommon and lethal side effect of neuroleptics. The clinical expression of this syndrome is diverse. Even with criteria diagnosis, it is hard to recognize it easily.We report a series of 25 cases of NMS among patients hospitalized in psychiatric service at Oujda for 5 years. We have described the clinical characteristics of NMS in these patients, the treatments received, the management, and the course of this syndrome.ResultsMost of the patients are hospitalized for psychotic or affective disorders according to the Diagnostic and Statistical Manual of Mental Disorders (DSM V) criteria. 92% of patients received conventional neuroleptic, and half of them were under the injectable form. No patient took long-acting injectable antipsychotics. 36% of patients received neuroleptics for the first time. NMS appeared in the first week after the admission in psychiatric service among 24 patients. The most common clinical and biological signs were muscular rigidity, the elevation of creatine phosphokinase (CPK), and alteration of blood pressure. Other symptoms were found in proportion varied between 24% and 72%. 32% of the patients did not develop complications. One patient developed renal failure. All patients recovered, and no deaths were recorded.ConclusionsEarly recognition of NMS help to rescue patient. It is necessary to detect this syndrome even in the absence of main signs such as fever.

Prophylactic Administration of Diphenhydramine to Reduce Neuroleptic Side Effects in the Acute Care Setting: A Systematic Review and Meta-Analysis.

Neuroleptics are commonly prescribed drugs to treat acute conditions (e.g., migraines) in the emergency department, but can cause serious adverse effects. Using diphenhydramine to prevent these adverse effects is very common but remains controversial. We performed a systematic review to determine whether prophylactic administration of diphenhydramine reduces the incidence of neuroleptic adverse effects in patients with acute conditions. Medline, Embase, Cochrane, PsycInfo, and Web of Science were searched for randomized controlled trials evaluating any neuroleptic with diphenhydramine vs. the same neuroleptic with any inactive agent. Primary outcome was incidence of any extrapyramidal adverse effect. Secondary outcomes were akathisia, rescue medication, subjective restlessness, neuroleptic malignant syndrome, and sedation. Independent reviewers scanned identified citations, extracted data, and assessed risk of bias. Meta-analysis was performed using random effect models. Of 1566 identified citations, nine studies (n=1648 patients) met eligibility criteria. Four studies were specifically designed to compare the incidence of neuroleptic adverse effects with and without co-administration of diphenhydramine. Four studies were at high risk of bias. In primary analysis, diphenhydramine had no effect on the incidence of extrapyramidal symptoms (7 studies, n=1393, risk ratio [RR] 0.75; 95% confidence interval [CI] 0.44-1.31) or akathisia (5 studies, n=1094; RR 0.78; 95% CI 0.33-1.82) or any of the secondary outcomes. In subgroup analysis, diphenhydramine was associated with a significant decrease in extrapyramidal adverse effects compared with placebo (4 studies, n=705; RR 0.61; 95% CI 0.41-0.90). Dosage analysis yielded no further information. When compared with placebo, diphenhydramine was associated with a significant reduction of extrapyramidal adverse effects. Overall quality of evidence is low. Further studies are warranted.

The impact of side effects on schizophrenia and bipolar disorder patients' adherence to prescribed medical therapy.

Our study aims to investigate how antipsychotic drugs' side effects impact schizophrenia and bipolar disorder patients and how this affects their adherence to prescribed medical therapy. The study sample consists of 47 bipolar disorder and 45 schizophrenic patients. Data were collected using the Medication Adherence Rating Scale (MARS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The mean total LUNSERS scores showed that bipolar disorder patients had more significant side effects compared with schizophrenic patients (P < .05). There was a moderate negative correlation between the mean MARS scores and mean LUNSERS scores of bipolar disorder patients (P < .05). Nursing care actions and strategies should be planned and implemented to promote adherence to treatment.

Prolactin, flupenthixol decanoate and first episode schizophrenia - clinical and laboratory correlates.

First-episode psychosis (FEP) patients are more sensitive to neuroleptic side-effects such as hyperprolactinemia. We examined the prolactin levels of previously minimally treated patients with first episode schizophrenia over their first year of treatment with flupenthixol decanoate and the relationship between prolactin levels, gender and clinical features of schizophrenia. Prolactin levels were assessed at three monthly intervals in 126 patients with first-episode schizophrenia in a single-site study conducted over 12months during treatment with flupenthixol decanoate according to a fixed protocol. The mean prolactin level for the total sample was 11.91ng/ml (standard deviation [SD]15.52) at baseline. Women had higher levels of prolactin than men at month 3, 6 and 12, reaching statistical significance at month 12 (p = 0.02). At 12months more women than men had hyperprolactinemia (defined as more than 20ng/ml for males, and as more than 25ng/ml for females (p = 0.007). Using a mixed effect model, there was a significant association between prolactin change scores over 12months and gender (p = 0.025) as well as Positive and Negative Syndrome Scale (PANSS) total scores (p = 0.001). In addition female gender (p = 0.04) and age (p = 0.02) correlated with the risk of hyperprolactinemia as categorical variable. In this study treatment with flupenthixol decanoate was associated with relatively low levels of hyperprolactinemia, likely owing to flupenthixol's relatively atypical mode of action, as well as to the low doses used in our study. We found an inverse correlation between total PANSS scores and prolactin levels, which could support the suggested theory of prolactin having antipsychotic properties. Our study confirms the importance of gender on the prolactin raising effects of antipsychotic treatment.

Genetic Polymorphisms Associated With Constipation and Anticholinergic Symptoms in Patients Receiving Clozapine.

Clozapine impairs gastrointestinal motility owing to its anticholinergic and antiserotonergic properties. This commonly leads to constipation and potentially to more severe complications such as bowel obstruction and ischemia. The aim of this study was to determine whether genetic variations in the genes encoding muscarinic and serotonergic receptors (CHRM2, CHRM3, HTR2, HTR3, HTR4, and HTR7) explain the variations in incidence of constipation and anticholinergic symptoms during clozapine treatment. Genes associated with opiate-induced constipation were also included in this analysis (TPH1, OPRM1, ABCB1, and COMT). Blood samples from 176 clozapine-treated, Finnish, white patients with schizophrenia were genotyped. Constipation and anticholinergic symptoms were rated using the Liverpool University Neuroleptic Side Effect Rating Scale self-report questionnaire. In total, 192 single-nucleotide polymorphisms (SNPs) were detected and grouped to formulate a weighted genetic-risk score (GRS). No significant associations between individual SNPs or GRSs and constipation or laxative use were observed. A GRS of 19 SNPs in CHRM2, CHRM3, HTR3C, HTR7, ABCB1, OPRM1, and TPH1 was associated with anticholinergic symptoms in a generalized linear univariate model, with body mass index, clozapine monotherapy, and GRS as explaining variables (permuted P = 0.014). Generalized linear univariate model analysis performed on the opiate-induced constipation-associated SNPs and a single CHRM3 SNP revealed an association between anticholinergic symptoms and a score of 8 SNPs (adjusted P = 0.038, permuted P = 0.002). Two GRSs are able to predict the risk of anticholinergic symptoms in patients receiving clozapine and possibly an increased risk of gastrointestinal hypomotility.

PL03: Prophylactic administration of diphenhydramine to reduce neuroleptic side-effects in the acute care setting: a systematic review and meta-analysis

Introduction: Neuroleptics are commonly used drugs to treat different conditions (e.g. psychosis, migraines) in the acute care setting and the emergency department. Their side effects can be disabling or, worse, fatal. The use of diphenhydramine to prevent those side-effects is widespread, but remains controversial. We performed a systematic review to determine if prophylactic administration of diphenhydramine (PAD) reduces the incidence of neuroleptic side-effects. Methods: Data sources: Medline, Embase, Cochrane Library, PsycInfo and Web of Science were searched. References from reviews that were identified in the search and from included studied were also reviewed for inclusion. Study selection: Randomized controlled trials evaluating any neuroleptic with PAD versus the same neuroleptic alone or with any inactive agent. Primary outcome was incidence of any extra-pyramidal side-effect. Secondary outcomes were akathisia, usage of rescue medication, subjective restlessness, neuroleptic malignant syndrome, sedation and sedation intensity. Data extraction: Independent reviewers scanned identified citations, extracted data and assessed for risk of bias. Data analysis: Meta-analysis was performed using random effect models. Heterogeneity and quality of evidence were assessed using, respectively, I2 and the GRADE approach. Results: Results: Of 1566 identified citations, nine studies (n=1436) met all eligibility criteria. Four studies were specifically designed to assess for neuroleptic side-effects. Four studies were at high risk of bias. In primary analysis, PAD had no effect on the incidence of extra-pyramidal symptoms (7 studies, n=1393 patients, RR 0.70 [0.40-1.22]), akathisia (5 studies, n=1094 patients, RR 0.81 [0.36-1.82]) and sedation (5 studies; n=1079, RR 1,48 [0.90-2.42]). Higher dosage of diphenhydramine was not associated with a greater reduction of extra-pyramidal side-effects. In a sensitivity analysis excluding an outlier study (n=120, RR 6.63 [1.55-28,35]), PAD was associated with a significant decrease in extra-pyramidal side-effects (6 studies, n=1273, RR 0.56 [0,38-0.82]), but not with any of the secondary outcome measures. Conclusion: Conclusion: When excluding an outlier study, PAD was associated with a significant reduction of extra-pyramidal side-effects. However, PAD did not significantly influence the incidence of akathisia. Overall quality of evidence is low. Further studies are warranted. PAD represents an interesting treatment option against neuroleptic side-effects, but its widespread usage whitout strong evidence to support it raises concerns.

The reasons for use of cannabinoids and stimulants in patients with schizophrenia.

Both cannabinoids and psychoactive substances from the group of stimulants can have a significant effect on the induction, course and treatment of severe mental illness. They also can be treated as self-medication. Many patients feel subjective benefits of using psychoactive substances in the areas of social competence, to cope with side effects of neuroleptics, stress accompanying mental illness or to control its symptoms. Our research tries to explain the causes of taking psychoactive substances by patients with schizophrenia. A total of 50 schizophrenia patients using cannabinoids, including 25 of them using also stimulants, took part in our research. They filled out questionnaires about the causes of drug use and subjectively perceived mental complaints. We analyzed medical documentation. It was found that subjects using both cannabinoids and stimulants pointed to spirituality as a cause significantly more often than subjects taking only cannabinoids. Marijuana and hashish were significantly more often taken to improve social relations. In both groups, the most common reasons were: curiosity, the need to relax, problem solving, improving relationships, and remedy for 'shyness'. In the group using only cannabinoids, it was observed that people who felt misunderstood often smoked marijuana to solve problems. Individuals using stimulants often complained of poor concentration. Ignorance of the consequences of using psychoactive substances in people at risk of schizophrenia or in those already ill is an additional risk factor. The results may indicate an increased demand for psychoeducation and social support regarding many areas of life of patients suffering from schizophrenia.

F225. LEVODOPA AUGMENTATION OF ANTIPSYCHOTICS FOR THE TREATMENT OF NEGATIVE SYMPTOMS IN SCHIZOPHRENIA

BackgroundNegative symptoms (i.e., motivation deficits and diminished emotional expression) are prevalent in schizophrenia and consistently linked with functional impairment for affected individuals. Despite advances in psychopharmacology for schizophrenia, there remain no effective treatments for these negative symptoms. Older literature, however, suggests that levodopa in conjunction with antipsychotic treatment can have beneficial effects for patients with schizophrenia. While supporting the safety and potential efficacy of dopamine augmentation, these studies did not evaluate effects within specific symptom domains, particularly negative symptoms. This open-label pilot study was conducted to evaluate the preliminary efficacy and safety of levodopa augmentation of antipsychotics for the treatment of negative symptoms.MethodsTen stable outpatients with schizophrenia between the ages of 18 and 60 were enrolled. All were treated with stable atypical antipsychotic monotherapy for at least eight weeks, and had a minimum total score of 30 on the Scale for the Assessment of Negative Symptoms (SANS). Participants were treated with adjunctive open-label levodopa/carbidopa, with dose titration to levodopa 300mg TID over 38 days as tolerated, and dose maintenance for the remainder of the eight-week trial. Baseline assessments consisted of the SANS, Scale for the Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Calgary Depression Scale for Schizophrenia (CDSS), MATRICS Consensus Cognitive Battery (MCCB), and Quality of Life Scale (QLS) for community functioning. Treatment side effects were evaluated with the Simpson Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS), UKU side effect rating scale (UKU), Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Barratt Impulsiveness Scale (BIS). Participants were reassessed on measures of psychosis and side effects weekly for the first four weeks, and every two weeks thereafter. The SANS and CGI were repeated at weeks 4 and 8, with the MCCB and QLS re-administered at week 8. Statistical analyses included the intent-to-treat sample (i.e., participants who received at least one dose of study medication) and consisted of linear mixed models for change in SANS total score (our primary outcome), and change in other clinical and side effects measures as a result of treatment.ResultsEnrolled participants (eight male and two female) had a mean age of 37.2 years. Seven participants completed the study, with three participants dropping out. The mean final dose of levodopa for study completers was 835.7 mg (SD 170.1). Levodopa augmentation resulted in a significant improvement in negative symptoms, with a mean SANS reduction for study completers of 15.3 (SD 5.7). This equated to a mean SANS improvement of 25.5% (range 17% to 57%), with 43% of study completers experiencing > 20% improvement in SANS score. Notably, significant improvement in negative symptoms emerged after the first four weeks of treatment. There was no significant change in positive symptoms, nor other clinical outcomes or side effect measures.DiscussionOur findings suggest that levodopa augmentation of antipsychotics may be an effective and well-tolerated treatment for negative symptoms in schizophrenia. These findings, however, need replication in larger randomized controlled trials. With the dearth of available treatments for negative symptoms, levodopa augmentation may represent a novel pharmacologic strategy to address this critical unmet therapeutic need for schizophrenia.

Neuroleptic-Associated Hyperprolactinemia: Clinical Manifestations and Effects on Sexual Function

Objectives. To study the clinical manifestations of neuroleptic-associated hyperprolactinemia (NAH) and its influences on sexual functions in patients with mental disorders and prolonged treatment with neuroleptics. Materials and methods. A total of 244 patients were investigated – 140 women and 104 men – with mental disorders and receiving treatment with neuroleptics. Blood prolactin and bioactive prolactin levels were estimated in all patients, these assays in some patients being accompanied by determination of gonadotropins, sex hormones, and sex steroid-binding globulin. Side effects of neuroleptics were assessed using the UKU Side Effects Rating Scale. Impairments to sexual functions were assessed using the Psychotropic-Related Sexual Dysfunction Questionnaire. Results and conclusions. Asymptomatic NAH was detected in 16% of women and 37% of men. In women, NAH led to impairments in the menstrual cycle – oligo- or amenorrhea – and galactorrhea. NAH was accompanied by sexual impairments in both in both men and women. In patients of both genders, NAH was associated with weakening of libido and deterioration of quality of life due to sexual impairment. In addition, women with NAH had delayed onset of orgasm and vaginal dryness during sexual intercourse. In men, NAH was also associated with erectile dysfunction. In contrast to tumor-related and idiopathic hyperprolactinemia, NAH was not accompanied by increases in body weight and the development of obesity, or the development of hypogonadism in patients of either gender.

The nosology of tardive syndromes

Since the original description of side effects of neuroleptics, different terminologies and definitions for tardive dyskinesia (TD) and tardive syndrome (TS) have been used by different authors, and often these two terms have been used interchangeably. This paper proposes a nosology designed to define and clarify various terms and phenomenologies within the TS spectrum.We propose to use the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements, as well as to the analogous repetitive movements that can appear in the limbs, trunk, or pelvis. The repetitive, relatively rhythmic nature of the movements is the common denominator of this phenomenologic category.The term tardive syndrome refers to the spectrum of all persistent hyperkinetic, hypokinetic and sensory phenomenologies resulting from chronic dopamine receptor blocking agents (DRBA) exposure. Thus, TS is an umbrella term.When dystonia is the main feature of TS it is considered to be tardive dystonia (TDyst). Retrocollis appears to be the predominant form of cervical dystonia in this condition. Cranial dystonias, particularly oromandibular dystonia, are also common forms of TDyst. Tardive akathisia refers to the inability to remain still with an urge to move, giving the appearance of restlessness. It is a sensory phenomenon and a common and disabling form of TS. Unlike acute akathisia, tardive akathisia tends to occur late and persists after the drug is withdrawn. In tardive tourettism, the patient exhibits the features of Tourette syndrome with complex motor and phonic tics associated with premonitory urge and relief of tension after performing the tic behavior. Tardive tremor differs from the resting tremor seen in drug-induced parkinsonism in that it is mainly a postural and kinetic greater than resting tremor. Tardive pain has been reported in association with chronic use of DRBA's. The pain involved the mouth, tongue and the genital region. The patients tended to obsess over the pain and usually had some other form of motor tardive syndrome, either tardive dyskinesia, tardive akathisia or tardive dystonia. The term tardive parkinsonism has been proposed for those drug induced parkinsonism patients who have persistent symptoms following discontinuation of the DRBA. However, there is a strong possibility that the DRBA may have simply unmasked subclinical parkinsonism or that there is coincident Parkinson disease developing during the period the patient is taking the DRBA.

Histaminergic gene polymorphisms associated with sedation in clozapine-treated patients

Sedation is a common adverse effect of clozapine treatment, which may be partly related to clozapine binding to histamine receptors in the central nervous system. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the histaminergic system are associated with sedation in clozapine-treated patients. The study population comprised 237 clozapine-treated, Finnish, Caucasian patients that were diagnosed with schizophrenia and 176 were genotyped using Illumina HumanCoreExome-12 BeadChip. Sedation levels were assessed using self-rating questions from the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The relationships between 55 different SNPs in the histaminergic system and adverse sedation effects were examined. SNPs were analyzed separately, and in groups, to formulate a genetic risk score (GRS). A permutation test was performed to avoid type I errors. Eight linked SNPs (r2 = 1) in the HNMT gene were also associated with sedation according to the GLM, adjusted for age, gender and BMI (false-discovery-rate-adjusted p = 0.013). An association on a trend level between a GRS of four different SNPs (recessive histamine N-methyltransferase HNMT rs2737385, additive histamine receptor H1 rs1552498, dominant HRH1 rs17034063 and recessive amine oxidase, copper containing 1 AOC1 rs6977381) and sedation was found (permuted p-value = 0.066) in a generalized linear model (GLM) incorporating age, gender and body mass index (BMI; adjusted R2 = 0.22). Polymorphisms in genes encoding histamine receptors or enzymes related to histamine metabolism may explain individual variation in sedative effects experienced during clozapine treatment.