Combination Of Antipsychotic Drugs Research Articles

Psychopharmacotherapy of late-stage hypochondriac conditions: frequency of use and effectiveness of drugs

To conduct a comparative analysis of psychopharmacotherapy effectiveness in hypochondriac disorders of late age and to identify the optimal combinations of drugs depending on the thymopathic (hypothymic and/or anxiety) components accompanying the main hypochondriac manifestation. One hundred and eight female inpatients, aged from 50 to 88 years, with leading hypochondriac symptoms of non-delusional level were enrolled in the study. All patients were examined clinically and psychopathologically using psychometric scales: the Montgomery-Asberg Depression Rating Scale, the Hamilton Anxiety Rating Scale, the hypochondria rating scale and the UKU side-effect rating scale. Based on the psychometric assessment, the patients were divided into the following groups: group 1 - subjects with hypochondriac symptoms without accented thymopathic component (n=18); group 2 - subjects with a high level of hypothymia (n=49); group 3 - subjects with a high level of anxiety (n=22); group 4 - subjects with a high level of both anxiety and depression (n=19). Hypochondriac disorder without a thymopathic component was treated with monotherapy with antipsychotic drugs in low therapeutic dosages or with a combination of antipsychotic drugs in low therapeutic dosages with tricyclic antidepressants in low and medium dosages. Hypothymic hypochondriac disorders were treated with antidepressants of mainly SSRIs group and of tricyclic structure in combination with typical and atypical antipsychotic drugs in low therapeutic dosages. In these patients monotherapy with antidepressants or a combination of different antidepressants was effective in rare cases only. Hypochondriac disorder with an anxiety component was significantly more often treated by complex therapy with the addition of anxiolytic drugs, as well as a combination of antidepressants with antiptychotic drugs. Mixed hypochondriac states were treated with a combination of antidepressants and antipsychotic drugs or complex therapy with the addition of an anxiolytic drug. Hypochondriac disorders of late age in most cases are accompanied by depressive and/or anxiety symptoms, which must be taken into account for improvement of diagnostic effectiveness and relevant selection of therapy.

Analisis Hubungan Kualitas Hidup Terhadap Penggunaan Kombinasi Obat Antipsikotik Pada Pasien Skizofrenia

Terapi pasien skizofrenia seringkali dimulai dengan pengobatan. Selain terapi dukungan psikososial, pengobatan untuk gejala skizofrenia dapat menggunakan kombinasi obat antipsikotik. Penggunaan kombinasi obat antipsikotik menimbulkan berbagai efek samping maupun interaksi obat yang berpengaruh terhadap kualitas hidup pasien. Tujuan penelitian ini untuk mengetahui hubungan kualitas hidup terhadap kombinasi obat antipsikotik di Puskesmas Sumberpucung. Desain penelitian menggunakan cross sectional secara retrospektif dengan uji statistik deskriptif dan chi square. Terdapat 37 responden yang terbagi menjadi 16 responden menggunakan kombinasi A (klorpromazin, haloperidol) dan 21 responden menggunakan kombinasi B (Haloperidol, Triheksifenidil), (Klorpromazin, Triheksifenidil, Trifluoperazin), (klorpromazin, Triheksifenidil, Haloperidol), (Haloperidol, Klozapin), (klorpromazin, Risperidon), (Triheksifenidil, Risperidon), (Triheksifenidil, Trifluoperazin, Klozapin), (Triheksifenidil, Risperidon, Klozapin), (Klorpromazin, Triheksifenidil, Risperidon), (Haloperidol, Triheksifenidil, Trifluoperazin), (Haloperidol, Trifluoperazin). Wawancara responden terkait kualitas hidup menggunakan kuesioner WHOQOL-BREF yang terbagi dalam 4 domain. Masing-masing domain dianalisis berdasarkan baik dan buruknya kualitas hidup, riwayat penggunaan obat antipsikotik ditinjau dari 3 bulan sebelumnya. Kuesioner telah tervalidasi dan reliabel. Hasil penelitian menunjukkan terdapat hubungan antara kualitas hidup terhadap penggunaan kombinasi obat antipsikotik (p<0,05). Berdasarkan hasil penelitian didapatkan kombinasi B memberikan kualitas hidup yang lebih baik dikarenakan kombinasi B memiliki efek samping yang lebih ringan untuk mengatasi gejala pada pasien skizofrenia.

Stability-indicating high-performance thin-layer chromatographic method for the estimation of antipsychotic drug combination clozapine and aripiprazole

A sensitive and precise high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous estimation of clozapine and aripiprazole in combination. The method employed HPTLC aluminum plates pre-coated with silica gel 60 F254 as the stationary phase, while the solvent system was toluene‒methanol‒ethyl acetate‒ammonia (6.5:2.5:1:0.1, v/v). The RF values were observed to be 0.43 and 0.60 for clozapine and aripiprazole, respectively. Densitometric analysis was carried out in absorbance mode at 218 nm. The method was linear in the range of 200–1600 ng per band for clozapine and 100-800 ng per band for aripiprazole. The stress degradation study was performed, and it was found that clozapine was susceptible to acid hydrolysis, base hydrolysis, and photolytic degradation study. Aripiprazole was susceptible to oxidative stress degradation study. The method was validated and applied successfully for the estimation of both drugs in the synthetic mixture.

Aripiprazole and fluoxetine in the treatment of delusional parasitosis: a case report

Delusional parasitosis is a rare psychiatric symptom that presents with the delusion of being invested with bugs, microorganisms or harmful parasites without any accompanying medical or psychiatric disorders. Delusional parasitosis is included in the “delusional disorder, somatic subtype” in the DSM-5. It is two-fold more frequent in females. High frequency is also related with being married, low education status and low socioeconomical status. Late diagnosis leads to chronical delusions. Typical and atypical antipsychotic drugs are used for treatment. In cases with concurrent depression, use of serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors might be useful. As far as we know, no cases treated with antidepressant and antipsychotic drug combination were reported, in the literature. We report a delusional parasitosis case with acute onset and treated with aripiprazole (5 mg/day) and fluoxetine (40 mg/day). Full remission was achieved in two months.

Antipsychotic Use Pattern in People with Psychotic Disorder Living in Board and Care Facilities.

The aim of this survey is to determine the pattern of antipsychotic drug use in patients with psychotic disorders, living in board and care facilities and to investigate the related factors. We evaluated the antipsychotic drug use pattern in outpatients with psychotic disorders according to DSM-IV, living in board and care facilities. Patients using polypharmacy at least one month were compared with patients using monotherapy in terms of clinical and demographic characteristics. Antipsychotic polypharmacy (with two: 34%, with more than two: 28%) was identified in 62% of the patients. The most frequently prescribed combination was olanzapine+quetiapine (13%), the rate of first and second generation combination was 50%, the rate of second generation antipsychotic combination was 44%, and the rate of first generation anytipsychotic combination was 4% in the two antipsychotic drug combination group. The rate of clozapine use was 3%. Use of polypharmacy was associated with the diagnosis of schizophrenia and schizoaffective disorder, young age, suicidal behavior, multiple hospitalizations, clinical severity, and the need of anticholinergic drug. The ratio of using more than two antipsychotic drug combination is high (28%) in psychotic patients living in board and care, and rate of clozapine use is low, which shows that clinical practice is inconsistent with the treatment guidelines recommendations. It appears that further education to rationale antipsychotic drug use in psychiatric practices is required.

Treatment-resistant, five-year long, postpartum-onset Capgras episode resolving after electroconvulsive therapy.

Postpartum psychosis, which rarely presents with Capgras syndrome (delusional misidentification), requires rapid symptom resolution. First-line drugs have important drawbacks, such as delayed onset of clinical response and secretion in breast milk. In this report, we report successful treatment of a treatment-resistant woman presenting with treatment-resistant Capgras syndrome, with onset during postpartum. A 36-year-old woman had presented with Capgras syndrome during postpartum. For more than five years, she believed her son and other family members were substituted by impostors. All adequately administrated treatments were unsuccessful. We suggested electroconvulsive therapy to overcome treatment resistance. After six electroconvulsive therapy sessions, delusions of doubles subsided and other symptoms improved. She was discharged two weeks later with a mood stabilizer and low-dose atypical antipychotic combination and is well at the one-and-a-half-year follow-up. Electroconvulsive therapy followed by a mood stabilizer-antipsychotic drug combination showed rapid, permanent, and effective control of long-standing Capgras syndrome in a young woman.

Augmentation with amisulpride for schizophrenic patients non-responsive to risperidone monotherapy.

The combination of antipsychotic drugs is a therapeutic resource in clinical practice. This study aimed to evaluate the efficacy and security of adding amisulpride in patients who at least partially responded to risperidone. A 3-month, open, observational study was undertaken to evaluate the effectiveness of adding amisulpride in subjects who scored at least 25 on the brief psychiatric rating scale (BPRS) after risperidone monotherapy. Patients were evaluated with BPRS, the Clinical Global Impressions Severity of Illness scale (CGI-S) and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at baseline, 1 and 3 months. Coadjuvant treatment with amisulpride achieves a statistically significant improvement in mental status over a period of 3 months when measured with BPRS, CGI and UKU scales. The response rate was 70 (45%) in the oral risperidone and 74 (28%) in the parenteral risperidone groups. The addition of amisulpride could lead to an improvement in schizophrenia symptoms in patients that do not, or only partially, respond to risperidone. Further research is required into alternative therapies for poor responders.

La mortalité à l’hôpital psychiatrique de Tunis : étude rétrospective sur 11 ans

Mortality in patients in psychiatric hospitals is reported to be two to three times as high as in the general population. In Tunisia, we do not have any figures on mortality and causes of death in psychiatric inpatients. The aim of our study was to assess the mortality rate in a psychiatric hospital in comparison to the mortality rate in the general population, to determine the patients' profile, and to identify the causes and risk factors for these deaths. We performed a retrospective, descriptive and comparative study. We examined the records of all patients who died during their stay in the different wards of psychiatry at the Razi Hospital in Tunis. We also scrutinized reports of autopsies in the Forensic Medicine unit at Charles-Nicolle Hospital in Tunis over a period of eleven years from January 1st, 2000 to December 31st, 2010. We conducted a descriptive study to calculate the standardized mortality ratio (SMR) aiming to highlight any existing excess mortality among the psychiatric inpatients compared to the general population. This ratio was obtained by dividing the observed number of deaths by the expected number of deaths. In the analytical study, our sample was compared to a control population made-up of randomly selected living patients among those admitted to the Razi hospital in 2010. This study allowed us to investigate the risk factors for premature mortality in psychiatric inpatients. The average rate of mortality was two deaths per 1000 inpatients per year. Twenty-four percent (24%) of deaths involved institutionalized patients. Compared to the general population, premature mortality was noted among patients aged less than 40 (SMR=1.9). The older the patients were, the closer to 1 the SMR was. The average age at death was 51.38 years; 65% of patients were male, 60% had a low socio-economic level, 54% had a comorbid medical condition. Forty-two percent (42%) of deceased patients were diagnosed with schizophrenia with the paranoid form being the most prevalent (44%), 13% had bipolar disorder, 22% had psycho-organic disorders (mental retardation, dementia, delirium). Antipsychotics were the most prescribed psychotropic drugs. High doses were used. Forty percent of cases (40%) consisted of sudden deaths. A cause for death was identified in 80% of cases. In 92% of cases, the death was classified as being "natural". Main causes were respiratory (26%) and cardiovascular (9%). Accidental causes accounted for 8% of deaths. In 20% of cases, the cause remained undetermined. Three factors were identified as independent predictors of mortality among mental patients: age at death (OR=3.9 among patients older than 40), psychiatric diagnosis (OR=2.9 among patients with psychotic or mood disorders compared to other diagnoses) and combination of antipsychotic drugs (OR=6.09 in patients receiving more than two antipsychotics). Young psychiatric inpatients seem to be at high risk of premature death: the SMR in our study was 1.9. It ranged between 2.15 and 6.55 in other similar studies. This increased risk mainly concerns non-natural deaths. The leading natural cause of death in our population was represented by thromboembolic accidents. Such a high thromboembolic risk may be explained by the mental illness itself, by physical restraint as well as by antipsychotic treatment. Diagnosing medical conditions in psychiatric patients is often a daunting task: history of the patient is sometimes unreliable and clinical features might be modified by psychotropic agents. Patient-related risk factors for premature death include poor socio-economic level, access-to-care difficulties, positive family and personal history of mental and/or medical disorders, smoking, substance abuse, unhealthy diet and lack of physical activity. Moreover, iatrogenic effects of psychotropic drugs (combination of antipsychotics was more common in deceased patients than in controls) and inadequate medical care in psychiatric hospitals (lack of ECG devices, in particular) partly account for such a high mortality. Identifying risk factors for deaths in psychiatric hospitals highlights needed changes in psychiatric management strategies taking into account the patient's characteristics as well as the drugs' safety profile. Further studies with larger samples are needed to better highlight risk factors for premature death in psychiatric inpatients. Identifying such risk factors is necessary to develop efficient preventive strategies.

Prescription patterns for patients with schizophrenia in Korea: a focus on antipsychotic polypharmacy.

ObjectiveThis study investigated the prescription patterns for Korean patients with schizophrenia with a particular focus on antipsychotic polypharmacy. All data were gathered from patients presenting at 41 tertiary university hospitals and 8 secondary hospitals.MethodsData from three multicenter studies conducted in Korea were retrospectively reviewed and integrated to identify patients with schizophrenia who had their antipsychotic medication switched to paliperidone extended-release between 2008 and 2009. The rates for antipsychotic polypharmacy, combined use of different antipsychotic classes with a special focus on atypical antipsychotics, and psychotropic polypharmacy using benzodiazepines, mood stabilizers, and other relevant drugs were identified.ResultsOf the 851 Korean patients analyzed in this study, 20.4% (n=173) had been prescribed antipsychotic polypharmacy. Of the 678 patients receiving antipsychotic monotherapy, 6.9% (n=47) were prescribed a typical antipsychotic and 93.1% (n=631) were prescribed an atypical antipsychotic. Of the 173 patients receiving a combination of antipsychotic drugs, only 6.4% (n=11) had been prescribed polypharmacy with typical antipsychotics, while 46.82% (n=81) were prescribed atypical+atypical antipsychotics or typical+atypical antipsychotics. The highest co-prescription rates for other psychotropic drugs in conjunction with antipsychotics included benzodiazepines (30.3%), anticholinergic drugs (28.8%), antidepressants (13.3%), β-blockers (10.1%), and mood stabilizers (8.7%).ConclusionThe present findings demonstrate that the rate of antipsychotic polypharmacy is relatively low in Korea and that Korean clinicians prefer to prescribe atypical, rather than typical, antipsychotic drugs. This suggests that there is a distinct prescription pattern in Korea that is focused on antipsychotic polypharmacy.

Priapism in Antipsychotic Drug Use: A Rare but Important Side Effect

Priapism is a rare but important side effect of antipsychotic drugs which may evolve into a urological emergency. Most antipsychotic drugs are alpha-1 adrenergic antagonists, which is thought to be the principal mechanism involved in antipsychotic-induced priapism. Other aetiologies exist, however. A case is presented with multiple episodes of priapism during the use of several different antipsychotic drugs. The case is representative of many patients treated with antipsychotic drugs, as there were hyperprolactinemia, and illicit drug use, which are known causes of priapism. Moreover, the patient used combinations of antipsychotic drugs. The case thus illustrates the etiological complexity which could delay a diagnosis of antipsychotic-induced priapism, and the problem of establishing a link between priapism and one particular ingredient of a drug combination. The case presents how a treatment regimen was finally established balancing antipsychotic efficacy to acceptable side effects and offers guidance to physicians regarding how antipsychotic-induced priapism may be resolved.

A Randomized, Double-Blind Comparison of Risperidone Versus Low-Dose Risperidone Plus Low-Dose Haloperidol in Treating Schizophrenia

Monotherapy is recommended for schizophrenia treatment, but the risk-benefit issue of antipsychotic drug combination (except for clozapine) remains unclear. Risperidone, an atypical antipsychotic drug, has a lower incidence of extrapyramidal syndrome but higher risks of prolactinemia and metabolic syndrome than haloperidol, a typical agent. This study compared efficacy and safety of risperidone monotherapy versus low-dose risperidone plus low-dose haloperidol in schizophrenia. In this 6-week, double-blind study, patients were randomized to the combination group (2-mg/d risperidone plus 2-mg/d haloperidol, n = 46) or the monotherapy group (4-mg/d risperidone, n = 42). Efficacy assessments included Clinical Global Impression-Severity, Positive and Negative Syndrome Scale and subscales, Calgary Depression Scale, Global Assessment of Functioning, and Medical Outcomes Study Short-Form 36. Safety was rigorously monitored. Response was defined as 30% reduction in the Positive and Negative Syndrome Scale total score. The 2 treatment groups were similar in (1) demographic and clinical characteristics at baseline, (2) response rate, and (3) improvement in various psychopathological measures and quality of life at end point. The monotherapy group had a higher increase in prolactin levels (P = 0.04) and Simpson-Angus Scale scores (P = 0.04) and a higher percentage of biperiden use (P = 0.045). There were no significant between-group difference in changes in weight, vital signs, corrected QT interval, liver/renal function, fasting glucose level, and lipid profiles. The findings suggest that risperidone monotherapy may yield higher prolactin levels than a combination of low-dose risperidone plus low-dose haloperidol. The 2 treatment groups are similar in efficacy, life quality, and other safety profiles. Future long-term studies are warranted.

Risque cardiovasculaire des antipsychotiques, une surveillance nécessaire de l’intervalle QT

Torsades de pointes (TdP), a form of ventricular arrhythmia that can cause ventricular fibrillation and sudden death, may occur during prolongation of the QT interval. QT prolongation has recently been reported with antipsychotic drugs. Physicians should be able to obtain a corrected measurement of the QT interval. QT is measured from the beginning of the QRS complex to the end of the T wave (QTm). This value must then be corrected to take heartbeat into account. The most common formula in current use is Bazett's. In practice, a QTc interval value greater than 500 ms indicates an increased risk of TdP. Safe combinations of antipsychotic drugs have been recommended by the French drug agency (Agence française de sécurité sanitaire des produits de santé). Many other drugs, including psychotropic drugs such as tricyclic antidepressants, can prolong the QT interval. Combinations of these medications with one another, with antipsychotic medications, or with other concomitant factors, such as hypokalemia, also increase the risk. TdP is most often diagnosed only after observing QT prolongation. This underlines the need to monitor QT intervals attentively to prevent the risk of cardiac arrhythmia in patients treated with antipsychotic drugs.

Current and emerging somatic treatment strategies in psychotic major depression

Psychotic major depressive disorder (MDD) is a mood disorder characterized by severe affective and neurovegetative symptoms together with the presence of delusions and/or hallucinations. It is a common disorder seen in a quarter of consecutively admitted depressed patients and is often associated with severe symptomatology, increased suicide risk, poor acute response to antidepressants and poor acute and long-term treatment outcome. It is possible that poor response in psychotic depression is caused by the fact that we have yet to identify the most efficacious treatment protocol for psychotic MDD. Multiple studies have shown that modifications in the treatment paradigm may increase treatment efficacy in psychotic MDD. It has been generally accepted that, during the acute treatment phase, antidepressant–antipsychotic drug combination therapy is more effective than either treatment alone, although this strategy has recently been challenged. The question of the optimal duration of pharmacotherapy in order to prevent relapse and improve long-term (i.e., 5-year) outcome is a focus of current investigation. This article will review currently recommended treatment strategies for the acute, continuation and maintenance phases of therapy. In particular, it will address the role of newer-generation antidepressants, the role of second-generation antipsychotics, the use of mood stabilizers and indications for electroconvulsive therapy. Other possible treatment strategies such as transcranial magnetic stimulation, vagus nerve stimulation, deep-brain stimulation and glucocorticoid receptor antagonists will be discussed. Current recommendations for the prevention of relapse and improvement of long-term outcome will be reviewed.

Multiple Sclerosis (MS) resembling Landau Kleffner (LK) syndrome

Multiple Sclerosis (MS) resembling Landau Kleffner (LK) syndrome

Ascorbic acid and atypical antipsychotic drugs: modulation of amineptine-induced behavior in mice

To provide a detailed characterization of individual kinds of behavior produced by ascorbic acid in combination with typical haloperidol) or atypical (clozapine, sulpiride and remoxipride) antipsychotic drugs, the ‘open-field’ test was selected. Amineptine, an indirect dopamine agonist, was used as an explicit model of dopaminergic activity. Results showed that amineptine (5–10–20 mg/kg i.p.), dose-dependently increased ambulation and rearing. Ascorbic acid (62.5–125–250 mg/kg i.p.) markedly inhibited the behavior of mice as well as the amineptine-induced hyperactivity. A combination of each typical or atypical antipsychotic drug (except clozapine 2.5 mg/kg i.p.) with amineptine (20 mg/kg i.p.) induced a significant increase in ambulation and rearing over that seen with the antipsychotic drugs alone. The combination of antipsychotic drugs with ascorbic acid 250 mg/kg i.p. led to a decrease in open-field parameters when compared with controls. In conclusion, these data provide further in vivo support for the effect of ascorbic acid on dopaminergic system and demonstrate that the antidopaminergic effects of both typical and atypical antipsychotic drugs may be enhanced with concurrent administration of ascorbic acid.