Serotonin-dopamine Antagonist Research Articles

An analysis of multiple comparisons is conducted to account for correlations among various investigated variables across four categories of antipsychotics

Background: First-generation antipsychotics are dopamine receptor antagonists, while second-generation atypical antipsychotics are serotonin-dopamine antagonists. Aim: The study aims to compare the effectiveness of current anti-psychotic drugs in treating schizophrenia, focusing on their correlation with responsiveness rates in positive, negative, and psychopathological symptoms. Methods: The study focuses on schizophrenia-spectrum disorders in adults and elderly psychiatric patients at the Princess Aisha Bint Al Hussein Medical Centre. The study will assess the initial severity of patients and evaluate the therapeutic effectiveness of four categorical-based oral and LA-APDs: older oral drugs, older oral and depot drugs, newer oral drugs, and newer oral and depot drugs. The reduction percentages in each component will be monitored, and a Chi Square test will be performed to analyze other variables. Pearson or spearman correlations will be used to explore correlation values. Results: Upon aggregating the various symptom categories into a unified score using the Positive and Negative Scoring Scale (PANSS), this study revealed that 63.7% of patients exhibited a positive response, whereas 36.7% of patients did not respond favourably. This equated to 110 out of 303 patients responding, compared to 193 patients who did not respond. The Pearson and Spearman correlations exhibited a statistically significant positive relationship, with values of +0.581±0.038 and +0.574±0.040, respectively (χ 2=131.885, p-value=0.000). Conclusion: Our study concluded that Psychopathological symptom therapy and patient adherence improved significantly. The efficiency of pleasant symptoms decreased significantly, whereas negative symptoms increased slightly.

Mental Illness: Social Dimension, is it Being Systematically Ignored?

For nearly half a century, the predominant focus of research in mental health has been on understanding the biological basis of mental disorders and new drugs. This was a major shift from the first half of the 20th century, when the psychoanalytic model was dominating the scene. Our understanding of the biological basis of many mental disorders has definitely improved in the last few decades with the advances in structural and functional imaging. However, there has not been any major advancement on the therapeutic side, with no significant introductions after the selective serotonin reuptake inhibitors and serotonin dopamine antagonists. Mental disorders have been identified as an important contributor to the global burden of disease, with the burden not shown any fall over the last 3 decades. Thus, there is a need to focus on the social dimension of mental disorders which has been systematically ignored. The strategies may include following a public health approach, dealing with stigma associated with mental disorders, strengthening the mental health services in the community, and improving their accessibility, and promotion of mental health well-being, dealing with disease burden, building resilience, involving families in management, targeting recovery, social prescribing, and using information technology, wherever appropriate.

Comparative efficacy of high-frequency repetitive transcranial magnetic stimulation to left dorsolateral prefrontal cortex as an augmentation strategy versus pharmacological augmentation in non-psychotic, unipolar, treatment-resistant depression: A randomized controlled trial.

Depression causes significant morbidity, disability and mortality, along with socioeconomic losses. Patients with depression who don't remit even with the second trial of anti-depressants need optimization, combination or augmentation strategies. Pharmacological strategies sometimes have unacceptable adverse effects. The aim of this study is to compare the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to left dorsolateral prefrontal cortex (DLPFC) with that of pharmacological augmentation strategies in unipolar non-psychotic treatment-resistant depression. This is a randomized controlled trial. Cases of unipolar, non-psychotic, treatment-resistant depression between ages 20 and 60 years were taken. The study period was from November 2016 to May 2018. Cases diagnosed as per ICD-10 criteria by a qualified psychiatrist. Cases of treatment-resistant depression (100) were divided into two arms by using a random number generator: rTMS arm and treatment as usual (TAU) arm. HF-rTMS to left DLPFC (rTMS group) and pharmacological augmentation with lithium, serotonin-dopamine antagonist, buspirone or thyroxine. In the rTMS arm, 44 patients and in TAU arm 41 completed the study. After 4 weeks of treatment augmentation, rTMS and TAU groups showed response rates of 52% and 46%, respectively. The difference between the two groups in terms of number of responders at the end of 4 weeks is not statistically significant. Additionally, factors associated with good response to rTMS were absence of a family history of psychiatric illness, no concomitant psychoactive substance use, being first episode of depression and mild-moderate severity of illness. The study did not find rTMS augmentation to be significantly better than standard pharmacological augmentation therapies.

Inhibitory Effects of Antipsychotics on the Contractile Response to Acetylcholine in Rat Urinary Bladder Smooth Muscles.

The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10-5 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.

A study to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors and serotonin dopamine antagonists.

Introduction:Hyponatremia can be a common but often overlooked side effects of psychotropics drugs. Most patients with drug-induced hyponatremia are asymptomatic and diagnosis is made incidentally following routine blood tests.Objectives:The aim of the study was to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors (SSRI) and serotonin dopamine antagonists (SDA).Materials and Methods:All inpatients and outpatients who were diagnosed with International Classification of Diseases-10 psychiatric disorders and undergoing treatment with SSRI, SDA, or combination of both for the same, were included in the study after simple random sampling, subject to inclusion and exclusion criteria.Statistical Analysis Used:Categorical variables were observed as numbers and percentages. Continuous variables were evaluated as mean ± standard deviation. A Chi-square test was done to find the association between categorical variables. SPSS (IBM) version 21 was used for data analysis.Results:In 150 patients, we found hyponatremia in 17 patients (11.33%). About 66–75 age group patients had maximum found cases of hyponatremia (66.66%). About 20.31% of females found hyponatremia. Among SSRIs, 16% of individuals had hyponatremia whereas among SDA it was 6%. Patients who were taking both SSRIs and SDA total prevalence of hyponatremia was 12%.Conclusions:Older age groups and females had higher chances of hyponatremia while taking SSRIs and SDAs. Among SSRIs, escitalopram had maximum percentage of hyponatremia, whereas fluvoxamine had minimum. Among SDAs, risperidone had maximum percentage, whereas quetiapine had minimum percentage of hyponatremia. Patients who were taking both fluoxetine + olanzapine or fluoxetine + risperidone had higher percentage of hyponatremia.

Use of Antipsychotics in Dementia Patients: A Descriptive Study

ABSTRACT
 Introduction. Dementia is a chronic progressive syndrome in which there is a decrease in the function of cognitive abilities including memory impairment, thinking ability, orientation, understanding, calculation, language, and assessment but without impaired consciousness. Apart from cognitive impairment, dementia is often accompanied by psychological symptoms and behavioural symptoms so that antipsychotic therapy is needed to overcome this. This study aims to identify the description of the use of antipsychotics in patients with dementia at Dr Mohammad Hoesin Palembang in the period 1 January 2014-31 December 2018.
 Methods. This research was a descriptive study using secondary data in the form of medical records of dementia patients receiving antipsychotic therapy at Dr Mohammad Hoesin General Hospital, Palembang. Samples were taken using a total sampling method.
 Results. There were 29 dementia patients (38.67%) receiving antipsychotic therapy. Most of the dementia patients who received antipsychotic therapy were in the late elderly age (27.59%) and were female (55.17%). The most commonly administered antipsychotic drug is haloperidol from the dopamine receptor antagonist (60%) with the most frequent dose of 0.5 mg (34.48%). Risperidone from the serotonin-dopamine antagonist class is the second most frequently prescribed antipsychotic drug (34.28%) at a dose of 1 mg (17.28%). The mean of haloperidol was 425 days, and risperidone was 295.5 days.
 Conclusion. Although in theory, psychological and behavioural symptoms are often found in dementia cases, not all dementia patients in RSUP Dr Mohammad Hoesin Palembang received antipsychotic therapy. People living with dementia who receive antipsychotic treatment get various types of drugs, dosages, and frequencies.

Electrochemical Analysis of Antipsychotics

Introduction:Schizophrenia is seizures accompanied by severe psychotic symptoms, and a steady state of continuation in the form of periods of stagnation. Antipsychotics are now the basis of treatment for schizophrenia and there is no other molecule that is antipsychotic priority in treatment. Antipsychotics can be classified into two groups; dopamine receptor antagonists such as promazine, fluphenazine etc. and serotonin-dopamine antagonists including risperidone, olanzapine, ziprasidone, aripiprazole etc.Materials and Methods:Electrochemical methods have been used for the determination of antipsychotic agent just as used in the determination of many drug agents. Nearly all of the antipsychotics are electroactive and can be analyzed by electrochemical methods. Electroanalytical methods offer generally high sensitivity, are compatible with modern techniques, have low cost, low requirements, and compact design. Among the most commonly used types, there are cyclic voltammetry, differential pulse voltammetry, square wave voltammetry and linear sweep voltammetry.Conclusion:The aim of this review is to evaluate the main line and the advantages and uses of electroanalytical methods that employed for the determination of antipsychotic medication agents used in schizophrenia. Moreover, applications of the methods to pharmaceutical analysis of Antipsychotics upto- date is also summarized in a table.

Quetiapine in treatment of first episode schizophrenia

IntroductionAlthough there is no cure, schizophrenia is highly treatable disease. Successful first episode schizophrenia (FES) treatment is crucial to minimize personal, vocational and social deterioration. Quetiapine is atypical, second generation antipsychotic, serotonin-dopamine antagonist. Quetiapine is potent blocker of D2, 5HT2A and 5HT1A receptors.ObjectiveTo estimate efficacy of quetiapine in treatment of first episode schizophrenia.MethodsThis study included 70 patients with FES diagnosed by ICD-10 criteria, who are divided into haloperidol (H) 35 patients and quetiapine (Q) group 35 patients. Patients were observed for 6 months in hospital and extra hospital conditions, according to protocol which included Positive and Negative Symptom Schedule Scale (PANSS) and the number of withdrawals attributed to adverse event (AE). Control group was treated with haloperidol 5–20 mg/24 h and experimental group was treated with quetiapine 400–800 mg/24 h.ResultsAverage pretrial PANSS score was 110.1 in quetiapine and 108.5 in haloperidol group. Average PANSS score after 180 days was 50.6 in Q and 60.4 in H group. There is no statistical difference in pretrial scores between groups for PANSS score (P = 0.647). There is significant statistical difference in PANSS score reduction after 180 days in both groups (P < 0.001). There is significant statistical difference in PANSS score reduction between Q and H group after 180 days (P < 0.001). Overall, 8.6% AEs occurred in Q, and 25.8% in H group.ConclusionQuetiapine has shown better efficacy in treatment of FES comparing to haloperidol, with statistically significant lower adverse effects rate.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Intraoperative floppy-iris syndrome associated with use of antipsychotic drugs

ObjectiveWe report 3 cases of intraoperative floppy-iris syndrome (IFIS) during cataract surgery in patients without a history of selective α1-blocker use but with a long-term history of antipsychotic drug use. We reviewed previously reported cases of antipsychotic drug-associated IFIS cases. DesignObservational case series. ResultsIn case 1, bilateral IFIS developed in a 39-year-old man with chronic angle-closure glaucoma. He had used several classes of antipsychotic drugs to treat schizophrenia, including the first-generation antipsychotic drugs haloperidol and chlorpromazine, the dopamine system stabilizer aripiprazole, the dopamine serotonin antagonists olanzapine and quetiapine, and the serotonin dopamine antagonists risperidone and blonanserin for 7 years. In case 2, a 63-year-old woman with schizophrenia had used aripiprazole, quetiapine, and risperidone for more than 10 years. In case 3, a 65-year-old woman with an organic mental disorder had used haloperidol for more than 10 years. At least 5 cases of antipsychotic drug-induced IFIS have been reported in the literature. ConclusionsAny class of antipsychotic drugs can cause IFIS. Although antipsychotic drug-induced IFIS can be mild, surgeons should be alert to the possibility of IFIS when they treat patients with current and past use of antipsychotic drugs.

Lurasidone: an antipsychotic with antidepressant effects in bipolar depression?

Lurasidone is a new serotonin-dopamine antagonist atypical antipsychotic which also appears to be effective in bipolar depression. This paper will briefly review the evidence concerning lurasidone. Lurasidone is an antagonist at dopamine D2, serotonin 5-HT2 and 5-HT7, and partial agonist at 5HT1a receptors; it has no anticholinergic or antihistaminic activity. Rapidly absorbed, it has a half-life of 18 ± 7 hours, will reach steady state in five days and is taken at night with food (absorption is halved on an empty stomach). It is hepatically metabolised with some potential for interactions. Lurasidone is an effective antipsychotic in acute schizophrenia, and non-inferior to quetiapine but not risperidone in 12-month studies. Lurasidone may cause mild sedation, nausea, agitation, insomnia and akathisia (especially at initiation). Risks for weight gain, hyperprolactinaemia and QTc prolongation are low. Lurasidone has demonstrated antidepressant efficacy both as monotherapy and in addition to lithium or valproate in bipolar depression, of a comparable degree to that seen with the combination of olanzapine and fluoxetine. Lurasidone appears to be a "metabolically-friendly" antipsychotic for schizophrenia where weight gain and hyperprolactinaemia are of concern, and may also prove useful in bipolar depression (although not approved for this condition in Australia).

Do Atypical Antipsychotics Really Enhance Smoking Reduction More Than Typical Ones?

Whether atypical antipsychotics (AAs) can enhance smoking reduction in schizophrenic patients remains controversial because of methodological limitations in existing studies. This study explored whether certain types of antipsychotics predict smoking reduction in schizophrenic patients. Three hundred eight smoking, predominantly male schizophrenic patients (271/308 [88.9%]) participated in an 8-week open-label study with antismoking medications (high-dose, low-dose nicotine transdermal patch and bupropion). Antipsychotics were classified into (1) typical antipsychotics (TAs) and (2) AAs, including multiacting receptor-targeted antipsychotics (clozapine, olanzapine, and quetiapine), serotonin-dopamine antagonists (risperidone), D2/D3 receptor antagonists (amisulpride), and partial dopamine receptor agonists (aripiprazole). A general linear model was used to explore whether types of antipsychotic predict changes in the number of cigarettes smoked per day (CPD) and the score of the Fagerstrom Test for Nicotine Dependence (FTND) while controlling for confounding factors. The type of antipsychotic (TAs or AAs) was not significantly associated with smoking cessation (n = 21; χ = 1.8; df = 4; P = 0.77). Regarding smoking reduction, the type of antipsychotic was significantly predictive of a change in the CPD (P = 0.027; partial eta square = 0.055) and FTND scores (P = 0.002; partial eta square = 0.073). The 95% confidence intervals of the estimated means of change in the CPD and FTND scores did not contain zero only among subjects on TAs or clozapine.These findings suggest that TAs and clozapine enhance smoking reduction compared with nonclozapine atypical antipsychotics in schizophrenic patients. The mechanisms underlying the effects of various antipsychotics on smoking reduction remain unclear and warrant future study.

P-197 - Risperidone and divalproex influence brain function networks in pediatric mania

Introduction There is accumulating evidence for the efficacy and effectiveness of divalproex sodium (divalproex) and risperidone in the treatment of pediatric bipolar disorder (PBD). Objectives Clinical neuroimaging studies using appropriate challenge paradigms are a promising strategy for investigating how these medications influence brain function to provide therapeutic benefit. Aims Given that affect regulation is influenced by cognitive operations and vice versa, the current study of pediatric mania adopted a mechanistic orientation in comparing the action of two types of medications on brain function while engaged in memory operations, executive function, and response inhibition. Methods This was a double-blind 6-week fMRI trial with 24 unmedicated manic patients randomized to risperidone or divalproex, and 14 healthy controls (HCs) (mean age: 13.1 ± 3.3years). Response inhibition, affective N back, and affective colormatching fMRI tasks were completed pre- and post-treatment. Results Risperidone, a serotonin dopamine antagonist, impacted frontostriatal circuitry while divalproex, a mood stabilizer, worked on frontotemporal circuitry. This finding was replicated across paradigms. In conjunction, across medication types, increased VLPFC at baseline timepoint predicted better treatment outcome. Conversely, increased amygdala activity at baseline predicted poorer treatment outcome. Conclusions Our study demonstrated how the neural networks were engaged in PBD patients during both cognitive and affective paradigms and while under the influence of an SGA and an anti-epileptic. When risperidone and divalproex are directly compared, there was significantly greater engagement of the frontostriatal regions with risperidone and in the frontotemporal regions with divalproex across all tasks.

Mirtazapine in combination with perospirone synergistically enhances dopamine release in the rat prefrontal cortex via 5‐HT1A receptor activation

The purpose of this study was to elucidate the mechanism underlying the clinical efficacy of mirtazapine-perospirone combination therapy for treatment-resistant depression in a rat model. We studied the effect of combination therapy of the noradrenergic and specific serotonergic antidepressant mirtazapine and the serotonin-dopamine antagonist perospirone on serotonin (5-HT) and dopamine release in the rat medial prefrontal cortex (mPFC) by using microdialysis. Male Wistar rats (250-330 g bodyweight) underwent implantation of a guide cannula in the mPFC, and a microdialysis probe was then inserted into the guide cannula to ensure its final placement in the mPFC. Microdialysis and subsequent chromatographic analysis were performed to estimate the extracellular 5-HT and dopamine concentrations. When they were used individually, perospirone (0.25 mg/kg, intraperitoneally) and mirtazapine (4 mg/kg, intraperitoneally) induced increased dopamine release up to 134% and 190% relative to the pretreatment level, respectively. Their combination therapy synergistically and significantly (P < 0.0001) increased the dopamine concentration up to 397% of the pretreatment level compared with that induced by the individual drugs. This combination-induced dopamine release was attenuated by 5-HT(1A) antagonist WAY 100635 (0.5 mg/kg, intraperitoneally), to a peak dopamine release of 151%. Extracellular 5-HT release in the mPFC was not altered in any of the treatment groups. The large increase in the dopamine concentration in the rat mPFC after the combination therapy was unique and may be responsible for the profound antidepressive effect observed in patients with treatment-resistant depression.

Non-Pharmacological Treatments in a Patient with Dementia Due to Huntington's Disease

Back to table of contents Previous article Next article LETTERFull AccessNon-Pharmacological Treatments in a Patient with Dementia Due to Huntington’s DiseaseHaw-Ming Lee M.D.,Shao-Tsu Chen M.D., M.S.Shaw-Ji Chen M.D., M.S.,Haw-Ming Lee M.D.Search for more papers by this author,Shao-Tsu Chen M.D., M.S.Search for more papers by this authorShaw-Ji Chen M.D., M.S.Search for more papers by this author,Published Online:1 Apr 2010https://doi.org/10.1176/jnp.2010.22.2.247.e17AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Huntington’s disease is a disease with multiple CAG repeats and autosomal-dominant inheritance on chromosome 4p16. 1 There is still no effective treatment for this disease. 2 Moreover, patients with Huntington’s disease can be sensitive to psychotropic medications such as antipsychotic agents, including dopamine antagonists and serotonin-dopamine antagonists. 2 However, the use of nonpharmacological treatments might reduce the need for psychotropic drugs. 3 Here we present the case of a woman with Huntington’s disease who received nonpharmacological treatment in our day hospital. Case ReportThe patient was a 51-year-old woman with a history of good health and 9 years of education. She functioned well as an accounting assistant for 20 years. In recent years, she suffered from insomnia and had difficulty standing and balancing; in addition she experienced mild impairment in the activities of daily life. Assessment of her Mini-Mental State Examination (MMSE) was 16, and her Activities of Daily Life (ADL) score was 60. Chorea was also significantly present. Our neurologist diagnosed Huntington`s disease based on genetic test results. After the diagnosis was made, the patient experienced a severe major depressive episode accompanied by a suicide attempt. Sometimes the patient exhibited aggressive behaviors. Following combined therapy of an antidepressant and an antipsychotic agent, her mood gradually improved and the aggressive behaviors diminished. After 3 weeks of hospitalization, the patient was discharged in a stable mood.The patient’s husband complained of her restlessness (akathisia) and irritability; moreover, he was concerned about side effects of her medications and asked us to change her prescription (risperidone, 2 mg/day, and lamotrigine, 100 mg/day). As the patient complained of dry mouth, body weight gain, and poor tolerance to the newer medication (olanzapine, 10 mg/day, and lamotrigine, 100 mg/day), we reverted to her previous regimen.The patient’s husband continued to monitor her mental condition 24 hours a day. As we were anxious that he would experience burn out, we admitted the patient to our dementia day care unit (MMSE score =10 and Neuropsychiatric Inventory [NPI] score =64). Nonpharmacological treatments in the dementia day care unit included a well-designed schedule of behavior therapy, reminiscence therapy, and art therapy. After 2 months, her MMSE score remained the same and NPI was 21. Furthermore, the patient’s psychotropic medication was decreased to risperidone, 1 mg/day, and lamotrigine, 50 mg/day, with no obvious disturbing behaviors.Discussion This case report demonstrates the therapeutic effects of nonpharmacological treatments in Huntington’s disease. Caregivers of Huntington’s disease patients often complain of their disturbing behaviors, psychotic symptoms, and depressed mood, rather than cognitive impairments. 3 This could explain the beneficial effects of dementia care in our day hospital. Reduced use of psychotropic medications also might be effective. As sensitivities to psychotropic drugs, including antipsychotic agents, are the most important limitations in the treatment of Huntington’s disease, nonpharmacological treatments could play an important role in the treatment program of Huntington’s disease. Integration of pharmacological and nonpharmacological treatments in future studies would be valuable for patients and their families. Department of Psychiatry, Buddhist Tzu-Chi General Hospital and University, TaiwanInstitute of Medical Science, Buddhist Tzu-Chi University, Hualien City, Taiwan

Non-Pharmacological Treatments in a Patient with Dementia Due to Huntington’s Disease

Back to table of contents Previous article Next article LETTERFull AccessNon-Pharmacological Treatments in a Patient with Dementia Due to Huntington’s DiseaseHaw-Ming Lee M.D.,Shao-Tsu Chen M.D., M.S.Shaw-Ji Chen M.D., M.S.,Haw-Ming Lee M.D.Search for more papers by this author,Shao-Tsu Chen M.D., M.S.Search for more papers by this authorShaw-Ji Chen M.D., M.S.Search for more papers by this author,Published Online:1 Apr 2010https://doi.org/10.1176/jnp.2010.22.2.247.e17AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Huntington’s disease is a disease with multiple CAG repeats and autosomal-dominant inheritance on chromosome 4p16. 1 There is still no effective treatment for this disease. 2 Moreover, patients with Huntington’s disease can be sensitive to psychotropic medications such as antipsychotic agents, including dopamine antagonists and serotonin-dopamine antagonists. 2 However, the use of nonpharmacological treatments might reduce the need for psychotropic drugs. 3 Here we present the case of a woman with Huntington’s disease who received nonpharmacological treatment in our day hospital. Case ReportThe patient was a 51-year-old woman with a history of good health and 9 years of education. She functioned well as an accounting assistant for 20 years. In recent years, she suffered from insomnia and had difficulty standing and balancing; in addition she experienced mild impairment in the activities of daily life. Assessment of her Mini-Mental State Examination (MMSE) was 16, and her Activities of Daily Life (ADL) score was 60. Chorea was also significantly present. Our neurologist diagnosed Huntington`s disease based on genetic test results. After the diagnosis was made, the patient experienced a severe major depressive episode accompanied by a suicide attempt. Sometimes the patient exhibited aggressive behaviors. Following combined therapy of an antidepressant and an antipsychotic agent, her mood gradually improved and the aggressive behaviors diminished. After 3 weeks of hospitalization, the patient was discharged in a stable mood.The patient’s husband complained of her restlessness (akathisia) and irritability; moreover, he was concerned about side effects of her medications and asked us to change her prescription (risperidone, 2 mg/day, and lamotrigine, 100 mg/day). As the patient complained of dry mouth, body weight gain, and poor tolerance to the newer medication (olanzapine, 10 mg/day, and lamotrigine, 100 mg/day), we reverted to her previous regimen.The patient’s husband continued to monitor her mental condition 24 hours a day. As we were anxious that he would experience burn out, we admitted the patient to our dementia day care unit (MMSE score =10 and Neuropsychiatric Inventory [NPI] score =64). Nonpharmacological treatments in the dementia day care unit included a well-designed schedule of behavior therapy, reminiscence therapy, and art therapy. After 2 months, her MMSE score remained the same and NPI was 21. Furthermore, the patient’s psychotropic medication was decreased to risperidone, 1 mg/day, and lamotrigine, 50 mg/day, with no obvious disturbing behaviors.Discussion This case report demonstrates the therapeutic effects of nonpharmacological treatments in Huntington’s disease. Caregivers of Huntington’s disease patients often complain of their disturbing behaviors, psychotic symptoms, and depressed mood, rather than cognitive impairments. 3 This could explain the beneficial effects of dementia care in our day hospital. Reduced use of psychotropic medications also might be effective. As sensitivities to psychotropic drugs, including antipsychotic agents, are the most important limitations in the treatment of Huntington’s disease, nonpharmacological treatments could play an important role in the treatment program of Huntington’s disease. Integration of pharmacological and nonpharmacological treatments in future studies would be valuable for patients and their families. Department of Psychiatry, Buddhist Tzu-Chi General Hospital and University, TaiwanInstitute of Medical Science, Buddhist Tzu-Chi University, Hualien City, Taiwan

Olanzapine and pancytopenia with severe folate deficiency

To the editor: Olanzapine, a thienobenzodiazepine serotonin-dopamine antagonist, is a recent atypical antipsychotic agent, with a structural and pharmacologic profile similar to that of clozapine. Although clozapine is effective in refractory schizophrenia, its use is limited by the occurrence of hematologic adverse effects, such as agranulocytosis, which occurs in 0.5–2% of treated patients [1]. Many studies have suggested a better hematologic safety profile for olanzapine, but impaired granulocytopoiesis and thrombocytopenia have recently been reported [2-6]. No case of pancytopenia with megaloblastic anemia has been described with the use of olanzapine. We report a case of pancytopenia with severe folate deficiency in a schizophrenic patient treated with olanzapine. A 56-year-old man, who worked as a painter, was a heavy smoker, had bad dental health, and a history of chronic psychosis was hospitalized on 11 August 2008 with severe pancytopenia, suggested by purpura. He had been living with his brother and had been treated for many years with haloperidol decanoate (3 mg every 3 weeks), loxapine (100 mg/day), amisulpride (800 mg/day), tropatepine (10 mg/day), diazepam (10 mg/day), and clorazepate (50 mg/day). Because of recent worsening of his psychotic symptoms, olanzapine was introduced (20 mg/day) in May 2008. The laboratory data on admission and during the early period of hospitalization are shown in Table 1. The hemogram and reticulocyte count revealed pancytopenia with macrocytic normochromic aregenerative anemia. The folate plasmatic level was dramatically decreased, total protein and cobalamin were slightly decreased, and renal and hepatic functions were normal. Shortly after admission, only olanzapine was discontinued. The patient received probabilist cobalamin supplementation with no immediate hematologic improvement. On 14 August, he began to receive intravenous folate supplementation (50 mg/day). Ten days later, a huge reticulocyte crisis was observed, whereas the white blood cell and platelet counts were significantly increased (Table 1). Meanwhile, the results of bone marrow aspiration confirmed the diagnosis of megaloblastic anemia. The patient was supplemented with folic acid over 2 weeks. Because the medical staff decided against restarting olanzapine, the loxapine dosage was increased to 150 mg/day with a good response. Computerized tomography imaging showed hepatic abnormalities consistent with portal hypertension. On 4 September, the macrocytic anemia recovered and folate supplementation was discontinued. One month after admission, gastric endoscopy revealed grade I peptic esophagitis without esophageal varix. The biopsies were all negative, thus ruling out celiac disease. At this time, his laboratory data only showed a slight macrocytosis with no anemia. At the 3-month follow-up, olanzapine had not been restarted and the patient had a perfect clinical examination, despite discontinuation of folate supplementation. F. Maurier : J.-F. Guichard Department of Internal Medicine, Vascular Medicine and Clinical Immunology, Ste Blandine Hospital, Metz, France

Priapism Associated with Olanzapine

Priapism is a rare but serious adverse effect of psychotropic drugs where antipsychotic agents were implicated in 15 to 26% of priapism associated with medications. Among atypical antipsychotic, clozapine, risperidone and olanzapine have been reported to be associated with the condition. The patient was a 24-years-old male referred to the OPD Clinic at Zare Psychiatry Hospital in 2007 with symptoms of delusion of control, delusion of persecution, delusion of somatic and auditory hallucination, for the last year. He had priapism following the use of olanzapine. Serotonin-Dopamine Antagonist (SDA) should be proscribed with care became of this rare yet serious complication, especially in cases with previous history of priapism following the use of psychotropic drugs.

Contribution of perospirone and risperidone to reduce delirium in senile patients

AbstractBackground: Serotonin–dopamine antagonists (SDAs) inhibit dopaminergic transmission in the mesolimbic system less than in the nigrostriatal dopaminergic pathway, which relates to the extrapyramidal side‐effects of these drugs. The SDAs seem to have an adequate receptor binding profile for the management of the behavioral and psychiatric symptoms of dementia. However, clinicians are discouraged from prescribing SDAs for elderly patients because of an advisory statement from the US Food and Drug Administration that warns about an increased mortality rate among elderly patients treated with atypical antipsychotics.Methods: We conducted a retrospective study involving 16 elderly patients (mean age 84.9 years; range 67–94 years) with delirium who were treated with one of two SDAs, namely perospirone (4–12 mg/day) or risperidone (1–2 mg/day). The time‐course of their psychiatric symptoms was assessed using subcategories of the Delirium Rating Scale (DRS) before treatment and on Days 10 and 24 of treatment.Results: Total DRS scores were significantly decreased from baseline in both treatment groups. Both agents led to significant improvements from baseline in psychomotor behavior and lability of mood. Of interest, perospirone decreased hallucinations and delusions and improved sleep–awake cycle disturbances compared with baseline. No serious side‐effects were seen with either drug.Conclusions: Both perospirone and risperidone are effective in the management of delirium in elderly patients. The improvement in the sleep–awake cycle with perospirone may be derived from its short pharmacological half‐life.

Study of effects of modafinil add-on therapy on excessive day time drowsiness and weight gain in patients on atypical antipsychotics

Byline: T. Sudhakar, G. Rao, P. Prasuna, K. Vijay Sagar Introduction Since the introduction of conventional anti-psychotics in the treatment of various psychotic disorders in late 1950's the quest for better molecules continued. The reasons for the betterment resulted in the introduction of second generation antipsychotics (SGA's) which are supposed to be more patient friendly with lesser extra pyramidal symptoms lesser chances of inducing tardive dyskinesia and better impact on affective, cognitive and negative symptoms of the schizophrenia. The initial enthusiasm about SGA's within 5 yrs had settled down towards skeptical optimism to control the unwanted and potentially endangering metabolic side effects. Among the newer drugs except for Aripriprazole and to some extent Ziprasidone all other drugs produce significant weight gain and predispose the individual for hyperglycemia and hyperlipedemia. They also produce significant day time drowsiness which interferes with patients daily occupational activities. The land mark study on antipsychotic efficacy, safety and tolerability namely CATIE study had clearly shown that 74% of the patients discontinued the treatment before 18months of trial. Intolerability was one of the major reason for the discontinuation, weight gain & metabolic effects with Olanzapine was established in phase II, part of the study. However, the trend for metabolic syndrome is also noticed with Clozapine, Risperidone, Olanzapine and to some extent with Quetiapine, Ziprasidone. The other major side effect that discourages the patient to continue the treatment is daytime drowsiness. Though with dose titration this side effect can be minimized, most of the patients do not continue, because day time drowsiness interferes with their daytime work performance. So, to improve the compliance with atypical antipsychotics and to give the patients a better quality of life, it becomes imperative that we should find various strategies including pharmacotherapy and diet control. Modafinil is a novel, non amphetamine psycho stimulant though it is not a typical sympathomimetic amine and has only weak affinity for dopamine uptake carrier site. It also acts on anterior hypothalamic nucleus and adjacent area. It is currently being promoted for excessive daytime sleepiness that occurs in Narcolepsy and also sleep apnoea. In 5% of cases it is known to produce anorexia and increase the alertness. In this, study we are making an attempt to explore whether, a non amphetamine drug like modafinil for reducing daytime drowsiness, would be of any utility in preventing daytime drowsiness associated with atypical antipsychotics. As this drug also has got anorexia and weight loss as adverse events, it would be worth while to see, whether add on therapy of modafinil with atypical especially Olanzapine, Risperidone, Clozapine (widely prescribed atypicals in India) would in anyway influence the daytime sleepiness, weight gain, hyperglycemia & hyperlipidemia. Review of Literature Atypical Anti Psychotics Versus Conventional Antipsychotics. Conventional antipsychotic agents which have been the mainstay of treatment in Schizophrenia and other psychotic disorders for over forty years have a number of limitations. This had prompted a search for new agents with greater efficacy and fewer side effects. So the serotonin dopamine antagonists (SDA) (Janssen et al ,1988) came into the practice which is at present the mainstay of treatment in patients with schizophrenia and other psychoses. But atypical antipsychotics are also not without side effects. Atypicality mainly refers to infrequent occurence of extrapyramidal syndromes in clinical setting. During recent years, it was found that akathisia is still common and tardive dyskinesia is also not uncommon with atypical drugs as earlier thought. Hence Second Generation Anti psychotics would be a better name that was suggested for this group of drugs. …

Effective Treatment of Coprophagia in a Patient with Schizophrenia with the Novel Atypical Antipsychotic Drug Perospirone

Here we report on a patient with schizophrenia who suffered from medication-refractory coprophagia. Although there were few cases in which psychotropic medication was effective against coprophagia, we encountered a patient with schizophrenia in whom coprophagia rapidly disappeared after treatment with perospirone, a novel atypical antipsychotic drug of the serotonin-dopamine antagonist (SDA) type. Perospirone has a uniquely high affinity for serotonin-1A receptors, and it could be speculated that perospirone, as a serotonin-1A receptor agonist combined with SDA, may have greater efficacy for treatment-refractory symptoms of schizophrenia. Thus, perospirone is an agent with possible efficacy for medication-refractory schizophrenia.