Lower Risk Of Extrapyramidal Symptoms Research Articles

Extrapyramidal Effects of First and Second Generation Antipsychotics: A Review

Antipsychotics are essential for treating major psychiatric disorders like schizophrenia. Second-generation antipsychotics were developed to reduce the risk of extrapyramidal symptoms (EPS) caused by antipsychotic medications. While second-generation drugs have a lower risk of EPS than first-generation treatments, studies show that they can still cause EPS, with clozapine being the least risky and risperidone the most. A literature search of PubMed and Scopus databases until April 2023 found that high doses, a history of past EPS, comorbidities, and specific second-generation medications can increase the risk of EPS. The choice of a first-generation comparator also influences study findings. Although the prevalence and severity of EPS vary with antipsychotics, these medications have not met expectations in terms of tolerability. EPS is still a clinical issue, even in the era of second-generation antipsychotics. This review offers a concise overview of EPS induced by antipsychotics.

Patterns of Adult Neuromyelitis Optica Spectrum Disorder Patients Compared to Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Neuromyelitis optica spectrum disorders (NMOSDs) are central nervous system inflammatory conditions, now recognized to involve the brain, often identified by aquaporin-4 (AQP4) antibodies. We aimed to summarize the characteristics of adult NMOSD patients compared to multiple sclerosis (MS). A computerized search was conducted on MEDLINE via PubMed, Web of Science, and ProQuest using the relevant keywords. Three independent reviewers performed two-stage screening and data extraction. The Review Manager 5.4 program (Cochrane Collaboration, Windows, London, UK) was used for the analysis. The Joanna Briggs Institute (JIB) tool was used for the quality of included studies. Twenty-three articles were included. NMOSD patients were associated with older age at presentation and higher Expanded Disability Status Scale (MD = 3.88, 95% CI: 1.80 to 5.97, P = 0.0003) and (MD = 1.15, 95% CI: 0.58 to 1.72, P < 0.0001), respectively. The risk of NMOSD in females was significantly higher than MS (OR = 2.21, 95% CI: 1.41 to 3.46, P = 0.0005). Patients with NMOSD were associated with a lower risk of extrapyramidal symptoms (OR = 0.26, 95% CI: 0.11 to 0.60, P < 0.01), brainstem involvement symptoms (OR = 0.32, 95% CI: 0.16 to 0.64, P < 0.01), and developing brain lesions compared to MS (OR = 0.08, 95% CI: 0.03 to 0.18, P < 0.00001). The current evidence suggests that both NMOSD and MS have different demographic, clinical, and lesion characteristics. There is a need for additional validation of the identified differences compared with MS due to the lack of long-term systematic imaging investigations in NMOSD.

Long-Term Lumateperone Treatment in Bipolar Disorder: Six-Month Open-Label Extension Study

AbstractIntroductionApproved therapeutics for bipolar depression are associated with a range of undesirable side effects. Lumateperone (LUMA), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. The efficacy of LUMA in bipolar depression was previously established in two Phase 3 trials, as monotherapy (NCT03249376) and as adjunctive to lithium or valproate (NCT02600507).A recent Phase 3 multi-center trial, Study 401 (NCT02600494) investigated the efficacy and safety of LUMA in bipolar depression and comprised a 6-week, randomized, double-blind, placebo-controlled period and a 6-month open-label extension (OLE) period. Here, we report the results of the OLE period, examining long-term safety.MethodsPatients, aged 18–75 years, with a clinical diagnosis of bipolar I or II disorder who were experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and a Clinical Global Impression Scale-Bipolar Version, Severity [CGI-BP-S] score ≥4) were eligible for Study 401. Patients who completed the double-blind study were eligible for direct rollover into the OLE or were re-screened if completing the double-blind period prior to the initiation of the OLE. During the OLE, LUMA 42 mg was administered once-daily in the evening for 25 weeks.The primary objective was safety and tolerability of LUMA as measured by incidences of adverse events (AEs) and changes in laboratory parameters, cardiometabolic measurements, electrocardiogram (ECG), and vital signs. The secondary objective was improvement/maintenance of symptoms of depression as measured MADRS and CGI-BP-S Total scores.ResultsA total of 127 patients were enrolled in the OLE, with 74 (58.3%) completing the study. Treatment-emergent AEs (TEAEs) occurred in 73 patients (57.5%) with 54 (42.5%) experiencing a drug-related TEAE. TEAEs that occurred in ≥5% of patients were headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability. Most TEAEs were mild or moderate in severity. Extrapyramidal-symptom-related TEAEs were rare. Most patients who had normal metabolic laboratory values at baseline remained normal during the treatment period. Mean changes in blood pressure, pulse rate, ECG, and body morphology were minimal. Symptoms of depression improved as measured by the mean change from baseline to Day 175 in MADRS Total score (−8.9) and CGI-BP-S Total score (−2.3).ConclusionIn patients with bipolar depression, long-term LUMA treatment was generally well tolerated with low risk of extrapyramidal symptoms, weight gain, and cardiometabolic effects. These data further support the safety, tolerability, and effectiveness of LUMA in patients with bipolar depression.FundingIntra-Cellular Therapies, Inc.

Quetiapine: off-label prescribing in a community mental health team

AimsQuetiapine is an atypical anti-psychotic medication licensed for the treatment of schizophrenia, bipolar disorder and adjunctive use in major depressive disorder. It's off-label use in low doses is increasing, possibly due to its sedative qualities, tolerability, low risk of extrapyramidal symptoms and to limit the unnecessary use of benzodiazepines. However, previous research highlights the risk of metabolic consequences even in low doses. Our aim is to establish the prescribing patterns and off-label use of quetiapine within a complete comminity mental health team population (CMHT).MethodThe GR1 CMHT provides care to a population of 25,000 people in a mixed urban and rural area. Multi-disciplinary case notes for all registered patients were reviewed for a one-year period. A database was created to include sociodemographic details, diagnosis, and medication. The proportion of patients prescribed quetiapine was identified and the dosage divided into multiple increments. The team's consultant reviewed and verified all ICD-10 diagnoses. Quetiapine dose by diagnosis was examined using descriptive statistics.ResultOf 246 registered patients, 62 (25% of CMHT caseload) were prescribed Quetiapine. Quetiapine was prescribed across a range of disorders including psychotic 17 (27%), mood 18 (29%), anxiety 14 (22 %), personality disorders 11 (18%) and others 2 (3%). Doses spanned between 25 mg – 800 mg daily. 19 patients (31%) were prescribed less than 25 mg, 20 patients (32%) between 25 mg and 100 mg and 23 patients (37%) above 100 mg. In psychotic and mood disorders, dosage varied widely between the low and high range. Furthermore, of the psychotic disorders, 11 (65%) were prescribed a second antipsychotic medication. For diagnoses in which the prescribing indication was clearly off-label, the dosages were predominantly low (100 mg or less).ConclusionQuetiapine was commonly prescribed in our patient population. Its frequent off-label use in low doses suggests that its prescription was for its additional qualities. Our findings highlight the importance of assessing the risk-benefit profile for every patient given the potential side effects, involving patients in the consultation of its off-label use and appropriate monitoring.

TPN672: A Novel Serotonin-Dopamine Receptor Modulator for the Treatment of Schizophrenia.

TPN672 [7-(2-(4-(benzothiophen-4-yl) piperazin-1-yl)ethyl)quinolin-2(1H)-one maleate] is a novel antipsychotic candidate with high affinity for serotonin and dopamine receptors that is currently in clinical trial for the treatment of psychiatric disorders. In vitro binding study showed that TPN672 exhibited extremely high affinity for serotonin 1A receptor (5-HT1AR) (K i = 0.23 nM) and 5-HT2AR (K i = 2.58 nM) as well as moderate affinity for D3R (K i = 11.55 nM) and D2R (K i = 17.91 nM). In vitro functional assays demonstrated that TPN672 acted as a potent 5-HT1AR agonist, D2R/D3R partial agonist, and 5-HT2AR antagonist. TPN672 displayed robust antipsychotic efficacy in rodent models (e.g., blocking phencyclidine-induced hyperactivity), significantly better than aripiprazole, and ameliorated negative symptoms and cognitive deficits in the sociability test, dark avoidance response, Morris water maze test, and novel object recognition test. The results of electrophysiological experiments showed that TPN672 might inhibit the excitability of the glutamate system through activating 5-HT1AR in medial prefrontal cortex, thereby improving cognitive and negative symptoms. Moreover, the safety margin (the ratio of minimum catalepsy-inducing dose to minimum effective dose) of TPN672 was about 10-fold, which was superior to aripiprazole. In conclusion, TPN672 is a promising new drug candidate for the treatment of schizophrenia and has been shown to be more effective in attenuating negative symptoms and cognitive deficits while having lower risk of extrapyramidal symptoms and hyperprolactinemia. SIGNIFICANCE STATEMENT: TPN672 is a promising new drug candidate for the treatment of schizophrenia and has been shown to be more effective in attenuating negative symptoms and cognitive deficits while having a lower risk of extrapyramidal symptoms and hyperprolactinemia. A phase I clinical trial is now under way to test its tolerance, pharmacokinetics, and pharmacodynamic effects in human volunteers. Accordingly, the present results will have significant impact on the development of new antischizophrenia drugs.

Acute Onset of Abdominal Muscle Dyskinesia ("Belly Dancer Syndrome") From Quetiapine Exposure: A Case Report

Belly dancer syndrome, also called belly dance syndrome or belly dancer dyskinesia, is a kind of abdominal dyskinesia with painful sensation. Its etiology is still unclear and there are few studies reporting its association with antipsychotics. Quetiapine is an atypical antipsychotic that causes lower risk of extrapyramidal symptoms than typical antipsychotics. Here, we presented the first case of belly dancer syndrome in a 71-year-old woman with major depressive disorder after short-term use of quetiapine.

Movement Disorders in Children and Adolescents Receiving Antipsychotic Pharmacotherapy: A Population-Based Study.

To describe a cohort of young users of risperidone and quetiapine in the province of Manitoba (Canada) and assess the risk for movement disorders in the two treatments. This was a population-based study conducted on all residents of the province of 19 years of age and younger who received prescriptions for risperidone or quetiapine between April 1, 1996, and March 31, 2011. Incident rates of antipsychotic use were reported. The risk for movement disorders in patients treated with quetiapine compared with those treated with risperidone was assessed by time-to-event analysis using Cox proportional hazards models. Between April 1, 1996, and March 31, 2011, 23,888 youth (age ≤19 years) were prescribed an antipsychotic agent. Among them, 8756 were identified as new incident users. After applying exclusion criteria, 2594 individuals comprised the cohort of users of risperidone and quetiapine. The use of quetiapine was associated with a lower risk of extrapyramidal symptoms (EPSs) adverse events. The unadjusted and adjusted hazard ratios (95% confidence interval [CI]) for quetiapine versus risperidone were 0.83 (0.56-1.25) and 0.53 (0.34-0.83), respectively. EPS diagnoses have been detected in children treated with quetiapine; however, the risk of movement disorders appears to be higher with treatment with risperidone. Clinicians should always take into consideration the risk-benefit before treating children with antipsychotic medications and should be vigilant of the onset of drug-induced adverse events.

Oral olanzapine: a guide to its use in adults with schizophrenia or bipolar I disorder

Olanzapine, an atypical antipsychotic, is a well-established option for the first-line treatment of schizophrenia, and as first-line or adjunctive therapy in the acute or preventative treatment of manic or mixed episodes associated with bipolar I disorder. The use of olanzapine is associated with better or similar efficacy than other commonly used antipsychotics, which may result in lower rates of treatment discontinuation. Treatment may generally be initiated at therapeutic dosages. Relative to other antipsychotics, olanzapine has a lower risk of extrapyramidal symptoms, but a greater risk of weight gain.

1124 – A multicentric, retrospective data collection from patients diagnosed with schizophrenia switched to solian® in romanian practice- switch study

Objective The primary objective was to assess the reasons for antipsychotics switch to amisulpide and to evaluate the outcome at 6±1 months following the switch from any antipsychotic drug(s) to amisulpride (Solian®). Methods This is an open, non-randomized, multicentric, retrospective, non-interventional study that included 1165 subjects who were already stabilized on amisulpride for at least 6±1 months. These patients were previously switched from other antipsychotic to Solian®. Data were collected retrospectively on the patients’ status 6±1 months ago and their present status. Results Reasons for switching previous antipsychotic treatment: inadequate control of symptoms in 79.3% of the patients, relapse of the disease under treatment 54.5%, adverse reactions 61.9%, reduced compliance 49.1%, comorbities 7.7%, patients request 28%, family request 24.5%, high cost 1.8%. Reasons for choosing Solian®: quality of life improvement 20.3%, cognitive function preservation 18.7%, better efficacy on positive symptoms 18.7%, better efficacy on negative symptoms 15.1%, low risk of extrapyramidal symptoms 12.3%, reduced weight gain 9.8%, minimal interactions with other drugs 4.2%. The compliance was significantly improved (61%), moderately improved (16%), unchanged (7.6%). Adverse reactions were significantly improved (53.5%), moderately improved (18.5%), unchanged (8.9%), minimum worsening (0.2%), medium worsening (0.1%). The efficacy was significantly improved (69.8%), moderately improved (19.2%), unchanged (2.2%), minimum worsening (0.1%). Conclusions The main reasons for antipsychotic switch were the inadequate control of symptoms, relapse of the disease under treatment and adverse reactions. Psychiatrists’ evaluation of the switch outcome at 6±1 months following the switch underlined significant improvement of compliance, adverse reactions and treatment efficacy.

A 6-Week, Randomized, Multicentre, Open-Label Study Comparing Efficacy and Tolerability of Amisulpride at a Starting Dose of 400 mg/day versus 800 mg/day in Patients with Acute Exacerbations of Schizophrenia

It has been suggested that neither dose titration nor the use of a loading dose was required for amisulpride and that 800 mg/day could be given from the first day with a low risk of extrapyramidal symptoms (EPS). However, no direct study of the need for dose titration has been conducted. This study aimed to compare the efficacy, tolerability and subjective experience of amisulpride between a group receiving an initial dose of 800 mg/day (AMI-800 group) and a group titrating up from an initial dose of 400 mg/day (AMI-400 group) over a period of 6 weeks. A total of 68 patients with acute exacerbations of schizophrenia participated in this 6-week randomized, multicentre, open-label study of amisulpride. Thirty patients were randomly assigned to the group that received an initial dose of 400 mg/day, which was then titrated up during the first 4 weeks following a fixed schedule. Thirty-eight patients were randomly assigned to the group receiving an initial dose of amisulpride 800 mg/day, which they took until the end of the fourth week. During the fifth and sixth weeks, the doses were adjusted flexibly in both groups. Our primary outcome measures were the Clinical Global Impression (CGI) scale and the changes over time in the total and subscale scores of the Positive and Negative Syndrome Scale (PANSS). We found no significant between-group differences in clinical improvement on the CGI and the PANSS. However, when responders were defined as those patients who experienced at least a 30 % reduction in the PANSS total scores obtained at baseline, a higher proportion of those in the AMI-800 group met the criterion for responsiveness from week 4 (week 4: 68.4 % vs 40.0 %, p = 0.02; week 6: 71.1 % vs 43.3 %, p = 0.02). Irrespective of treatment group, significant proportions of patients developed hyperprolactinaemia (86 %) and EPS (35 %). However, no statistically significant differences in the overall incidence of adverse events were observed between the two treatment groups. There were also no group differences in subjective quality of life and attitudes toward antipsychotic medication. These results suggest that it may be useful to begin therapy, especially for acute exacerbations of schizophrenia, with an initial dose of amisulpride 800 mg/day to obtain maximal efficacy without any significant side effects.

Unexpected effect of aripiprazole on nociceptive pain

Aripiprazole (ARP) is an antipsychotic that acts as a modulating partial agonist of the dopamine-2 (D2) receptor, approved for the treatment of schizophrenic disorders [DeLeon et al. 2004] and recently for the treatment of manic mixed episodes associated with bipolar type I disorder [Aitchison et al. 2009; Dhillon, 2012]. Compared with other antipsychotics, its safety and tolerability (low risk of extrapyramidal symptoms [EPS], weight gain and hyperprolactinemia) encourage its use in psychiatric patients with comorbidities. Five psychiatric patients with severe painful internal comorbidities showed unexpected pain improvements during effective treatments of their psychopathological conditions by ARP monotherapy (from 2.5 to 15 mg daily). Pain was assessed regularly in relation to the fact that is considered the ‘fifth vital sign’. These patients had developed nociceptive painful syndromes that responded poorly to opioid and/or non-steroidal anti- inflammatory drugs therapy. They had no symptoms related to non-nociceptive (neurological) pain. With reference to pain and psychology, patients showed a moderate improvement after 2 weeks of treatment and a significant improvement after 4 weeks, as demonstrated by CGI (Clinical Global Impression for severity and improvement scales with endpoints labelled 1 ‘normal, not at all ill’ to 7 ‘among the most extremely ill patients’ and 1 ‘very much improved’ to 7 ‘very much worse’, respectively) and NRS-o (0–10 oral Numeric Rating Scale: visual scale anchored with the endpoints labelled ‘no pain’ near the ‘0’ number and ‘extreme pain’ near the ‘10’ number) scales’ scores used for the assessment of psychopathological state and pain level, respectively (Table 1). No changes in the internal condition, which could account for the improvements concerning pain, were observed. Table 1. Sample features These clinical observations suggest the involvement of brain dopamine (DA) transmission in nociceptive pain pathways as a result of the ‘modulation’ of the dopaminergic system by ARP, although ARP-mediated antagonism on 5HT2A receptors [DeLeon et al. 2004] known as facilitating spinal nociception [Oyama et al. 1996], is possible. The activation of nigrostriatal (dorsal nucleus caudate and putamen) DA D2 receptor-mediated neurotransmission is positively associated with individual variations in subjective ratings of sensory and affective qualities of pain with an increased threshold as outcome [Scott et al. 2006]. In contrast, mesolimbic (nucleus accumbens) DA activation, which may have an impact on both D2 and D3 receptors, is exclusively associated with variations in the emotional responses of the individual during pain challenge (increases in negative affect and fear ratings) [Stahl, 2002]. The ARP antipsychotic mechanism is based on the blockade of mesolimbic D3 receptors, whereas nigrostriatal D2 receptor-mediated activity is not changed by it [Oyama et al. 1996]. So its effect could result in a direct involvement on reduction of pain perception even if a positive unspecific role on pain threshold psychological-mediated is possible. However, these effects on pain perception could be particularly evident owing to the poor effectiveness of common pain treatments in our sample. This is the first report about the relationship between aripiprazole and subjective experience of pain.

Improvement of tardive dyskinesia and dystonia associated with aripiprazole following a switch to quetiapine: case report and review of the literature

Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole. We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy. There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear.

Analysis of Adverse Drug Reactions of Atypical Antipsychotic Drugs in Psychiatry OPD

Background:Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS). However, these drugs have separate set of adverse drug reactions (ADRs). Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment.Materials and Methods:A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex), who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients’ responses were recorded in the case record form.Results:Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93) were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4–6 mg/day) and olanzepine (at 10–15 mg/day), gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2–3 months after treatment) course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3–9 months) use.Conclusion:The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized.

Androgen Insensitivity and Liability to Drug-Induced Extrapyramidal Symptoms

Androgen insensitivity syndrome (AIS) is a disorder of sex development characterized by variable defects in virilization of individuals with 46,XY karyotype. It is caused by mutations in the X chromosome androgen receptor gene, which, depending on their specific location, result in complete or partial peripheral androgen resistance. This case report highlights a possible increased liability of patients with AIS to drug-induced extrapyramidal symptoms (EPS). A 28-year-old patient with partial AIS was admitted to the hospital because of paranoid ideation. At puberty onset, she had undergone bilateral orchiectomy; estrogen replacement therapy was prescribed but stopped 2 months later against medical advice. During her hospitalization, severe EPS manifested following initiation of risperidone 2 mg/d. She was later switched to sertindole 12 mg/d with a satisfactory response and no motor side effects. Patients with AIS may have an increased susceptibility to drug-induced EPS, which may be caused by striatal dysfunction that is possibly associated with resistance to androgens during critical periods of early brain differentiation or direct effects of androgen receptor gene mutations on nigrostriatal function and development. Clinicians should cautiously treat psychosis in patients with AIS, preferably with antipsychotic compounds that have a low risk of EPS.

Prescriptions Into Practice: Aripiprazole (Abilify): A Novel Atypical Antipsychotic Medication

In the past, treatment of psychosis was centered on conventional agents, whose tolerability was limited by extrapyramidal side effects (EPS). The past decade has seen emergence of newer antipsychotic agents, first with clozapine and then with risperidone, olanzapine, quetiapine and ziprasidone. In general, while demonstrating similar efficacies to traditional agents, use of these compounds may be associated with lower risk of extrapyramidal symptoms (EPS) and possibly less cognitive impairment and better effects on negative symptoms. However, evolving evidence suggests that several drugs in this class may be associated with significant weight gain, lipid, and other metabolic abnormalities. Aripiprazole, a quinolinone derivative, is an atypical antipsychotic drug, displaying clinical efficacy similar to that of haloperidol and risperidone and superior to that of placebo in numerous clinical trials. Aripiprazole use is also associated with lower rate of clinically significant weight gain compared with other atypical antipsychotics. Patients receiving aripiprazole may experience EPS at a rate similar to that seen with placebo. Within the antipsychotic medication class, the introduction of aripiprazole may provide an alternative therapeutic option to traditional antipsychotics without some use limiting side effects of other atypical medications.

The Cost-Effectiveness of Atypicals in the UK

Background In 2002, the National Institute for Health and Clinical Excellence (NICE), recommended atypical antipsychotics over conventional ones for first-line schizophrenia treatment, based on their lower risk of extrapyramidal symptoms. Objective To estimate the incremental cost-effectiveness of atypical relative to conventional antipsychotics for the treatment of schizophrenia in the UK. Methods A discrete event simulation (DES) model was adopted to reflect the treatment of schizophrenia in the UK. The model estimates symptoms (using the Positive and Negative Symptom Score [PANSS]), psychiatrist visits, pharmacological treatment and treatment location, number and duration of psychotic relapses, level of compliance, quality-adjusted life-years (QALYs), and side effects over a 5-year time period. Probabilistic sensitivity analyses were carried out. Following NICE's “atypical” recommendation, the cost-effectiveness of atypical versus conventional antipsychotics was estimated in a scenario analysis, assuming both groups differ only in side-effect profile. Results When comparing conventional and atypical antipsychotics, the model predicts that the latter would decrease 5-year costs by £1633 per patient and result in a QALY gain of 0.101. The probabilistic sensitivity analysis suggests these results are robust. The sensitivity analyses indicate that incremental costs and effects are most sensitive to the differential efficacy of atypicals and conventionals, as measured by PANSS. When it is assumed that the only differences between atypicals and conventionals are found in side-effect profiles, the incremental cost-effectiveness ratio of the atypicals is £45,000 per QALY gained. Conclusion According to this DES model for schizophrenia, atypical antipsychotics are cost-effective compared to the conventional antipsychotics. The assumptions used in the model need further validation through large naturalistic based studies with reasonable follow-up to determine the real-life differences between atypicals and conventional antipsychotics.

Ziprasidone-induced tardive laryngeal dystonia: a case report

Tardive laryngeal dystonia, a rare form of dystonic syndrome, was only reported to be induced by typical antipsychotics. Here, we report one case of ziprasidone-induced tardive laryngeal dystonia in a schizophrenic female patient, who showed dysphonia, hoarseness and dyspnea after taking ziprasidone 120 mg/day for 8 months. These symptoms were significantly improved after discontinuing ziprasidone and increasing the dose of trihexyphenidyl for 1 week. Although atypical antipsychotics are associated with a lower risk of extrapyramidal symptoms, caution should be taken for any tardive dystonic movement when using these medications.

Acute and Long-Term Adverse Effects of Antipsychotics

Antipsychotics have become the cornerstone of management for many severe mental disorders. Primarily developed for the treatment of schizophrenia, several antipsychotics have been indicated for bipolar mania, bipolar depression, and irritability associated with autistic disorder. Antipsychotics are also used off label for psychotic or refractory depression; refractory anxiety disorders; and conditions associated with agitated or aggressive behaviors. Due to the severity and chronicity of severe mental disorders, the broad range of potential treatment targets, and the relative ease of use of second-generation antipsychotics (SGAs), which are associated with a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia (TD), prescribing rates have increased considerably over the last decade. With increased utilization of these medications comes a greater responsibility to appropriately recognize, monitor, and manage side-effect clusters that can adversely affect physical and mental outcomes.

Olanzapine and Blepharoclonus

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.Sir: Olanzapine is an atypical neuroleptic associated with low risk of extrapyramidal symptoms (EPS).1 However, recent case reports2-4 suggest that some patients developed abnormal movements while taking olanzapine. Incidence of motor eyelid complications associated with atypical antipsychotics is uncommon, and only a few case reports of blepharospasm or Meige's syndrome have been reported with risperidone and olanzapine.4†‹†‹

Phosphodiesterase inhibitors—Are they potential neuroleptic drugs?

It was suggested that phosphodiesterase (PDE) inhibitors may be potential neuroleptic drugs with a low risk of extrapyramidal symptoms. In the study presented, we compared the effects of the neuroleptics, haloperidol, and risperidone and the PDE10A inhibitor papaverine as well as the PDE4 inhibitor rolipram on retrieval of conditioned avoidance responding in the pole-jumping task and on locomotor activity. After acute administration, the substances used reduced locomotor activity dose-dependently. Both PDE inhibitors interfered with conditioned avoidance responding, suggesting neuroleptic-like effects. Risperidone showed a favourable profile of action. In all the doses tested, no signs of unspecific impairments in the performance of the instrumental task occurred. The profile of rolipram was similar. In the doses tested, only minor impairments in the performance of the instrumental task were found. Rolipram showed a similar effect to risperidone, suggesting therapeutic usefulness as an atypical neuroleptic. However, the use of this substance is limited by its emetic effects in therapeutically relevant doses.