Antipsychotic Combination Therapy Research Articles

Does Combined Antipsychotic Treatment Provide Better Control on Symptoms in Patients with Schizophrenia than the Monotherapy?

Objective: Combined antipsychotic treatment is frequently used in clinical practice either to improve the symptom control or to reduce the severity of side effects. The expected benefits by combining different antipsychotics include active cross-titration and co-utilization of different administration routes of the therapeutic agents. However, except the add-on therapies to clozapine, there is no objective evidence implying the superiority of combined therapy over monotherapy. Furthermore, there are a number of published case reports of significant side effects accompanying combined antipsychotic usage such as extrapyramidal and metabolic symptoms, seizures, and electrocardiographic abnormalities. It is also argued that switching into a new therapeutic agent might be more beneficial than augmenting the ongoing medication by polypharmacy. Here, we studied on a group of hospitalized schizophrenia patients in a training and research hospital in Turkey whether the Positive and Negative Symptom Scale (PANSS) scores differ between the patients under monotherapy and combined therapy. Methods: Hospital records belonging patients with schizophrenia who were followed up between the years of 2003 and 2013 were retrieved. Schizophrenia diagnoses were re-evaluated and confirmed according to the DSM-IV-TR criteria. All the patients who met the diagnostic criteria and having PANSS subscale scores (n=158) were included in the study. PANSS scores at the time of hospitalization are represented by adding “-before” suffixes, while the ones at the time of discharge by adding “-after”. Results: Our series composed of 158 schizophrenia patients (54 women and 104 men). When the medications were reviewed, we found that 66 patients (41.8%) were treated with a single drug and the atypical antipsychotics were the most commonly used group. Multiple drugs were combined on 92 patients (58.2%) and the most common combination was the “atypical + typical” antipsychotics. PANSS subscales and their comparisons among the groups of monotherapy and combined therapy revealed a slight statistical difference in PANSS negative scores at the time of hospitalization, although we found no significant changes in terms of PANSS scales, in general. Conclusion: In this study, we presented the overall frequency and patterns of our combined antipsychotic therapy in our daily routine work. We only used severity of symptoms in our study, and observed no differences between mono and combined therapy groups in terms of the PANSS evaluation. Further clinical studies with clinical, metabolic, and laboratory data as well as the long follow-ups are needed to uncover if combined therapy proves to be beneficial over monotherapy.

Altered emotional experiences attributed to antipsychotic medications – A potential link with estimated dopamine D2 receptor occupancy

Altered emotional experiences in response to antipsychotics may increase the burden of disease in patients with schizophrenia. In a large cross-sectional study, patients with schizophrenia completed the Subjects Reaction to Antipsychotics questionnaire (SRA) to assess whether they attributed altered emotional experiences (flattened affect or depressive symptoms) to their antipsychotics. Association with antipsychotic D2 receptor affinity and occupancy was examined using logistic regression. We compared antipsychotic-attributed emotional experiences between patients using antipsychotic monotherapy and combination therapy. Of the 1298 included patients, 23% attributed flattened affect to their antipsychotics and 16% attributed depressive symptoms to their antipsychotics, based on the SRA. No differences were observed between antipsychotics in patients on monotherapy. We discuss that within these patients’ relatively low dose range, altered emotional experiences did not appear to relate to the level of D2 receptor affinity of antipsychotic monotherapy. Patients using antipsychotic combination therapy (22%) were more likely to attribute depressive symptoms to their antipsychotics than patients using antipsychotic monotherapy (OR [95%CI]=1.443 [1.033–2.015]); possibly due to higher D2 receptor occupancies as estimated by dose equivalents.

Factors associated with subjective side-effects during clozapine treatment

Objective: Clozapine is associated with subjectively unpleasant or clinically serious side-effects, which may affect treatment adherence. The aims of the study were to explore the association of clozapine+ norclozapine serum concentration and other factors with subjective side-effects in schizophrenia patients. Methods: In this cross-sectional study, 237 patients with a diagnosis of schizophrenia, schizo-affective or other non-organic psychoses completed the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), a self-report scale measuring side-effects of antipsychotics and a clinical questionnaire. Clozapine+ norclozapine serum concentration of 190 patients was measured. Of the patients 80 (33.7%) were on antipsychotic combination therapy. Results: Higher clozapine+ norclozapine concentrations were associated with the depression–anxiety factor of LUNSERS and antipsychotic combination treatments were associated with sympatichotonia–tension factor. Younger patients reported sedation more often than older patients. Conclusion: According to the present results, high clozapine concentrations were associated with depression–anxiety symptoms, but the causality remains unknown.

Audit of combination and high-dose antipsychotic treatment in the community

Aims and methodTo estimate the community prevalence of combination antipsychotic therapy and high-dose antipsychotic treatment via audit. Patients with an ICD-10 diagnosis of schizophrenia were identified through the NHS Greater Glasgow and Clyde Health Board patient information management system and their mental health records examined.ResultsIn audit 1, 135 records were examined. The age range of patients was 24–74 years; 73% were male. Twelve per cent were on combined antipsychotic treatment and 3.7% required high-dose antipsychotics. Sixty-nine per cent of patients had documented in their record the reason for combined antipsychotic treatment compared with 40% on high-dose antipsychotics. In audit 2 (1 year later), 150 records were examined. Demographic details and prescription patterns remained similar to that of audit 1. However, 10% of patients received combined antipsychotic therapy and 2% remained on high-dose antipsychotics. Documented reasons for combination therapy increased to 87%, and to 67% for patients on high-dose antipsychotics.Clinical implicationsWe need robust clinical trials, overcoming the problems of clinical effectiveness and clinical efficiency, to establish the merits of preferred antipsychotic combinations, as combination and high-dose antipsychotic treatments are unlikely to be eliminated in clinical practice in the foreseeable future.

Effectiveness of a Clozapine–Aripiprazole Combination in Tourette Syndrome and Bipolar Spectrum Disorder

Back to table of contents Previous article Next article LettersFull AccessEffectiveness of a Clozapine–Aripiprazole Combination in Tourette Syndrome and Bipolar Spectrum DisorderArmando Piccinni, M.D., Antonello Veltri, M.D., Donatella Marazziti, M.D., Ilenia Moroni, M.D., and Liliana Dell’Osso, M.D.Armando PiccinniSearch for more papers by this author, M.D., Antonello VeltriSearch for more papers by this author, M.D., Donatella MarazzitiSearch for more papers by this author, M.D., Ilenia MoroniSearch for more papers by this author, M.D., and Liliana Dell’OssoSearch for more papers by this author, M.D.Published Online:1 Jan 2013https://doi.org/10.1176/appi.neuropsych.12020032AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Antipsychotic combination is a common strategy used in both bipolar disorder and schizophrenia, although just a few trials are available exploring its effectiveness.1 We report herein the case of a patient suffering from severe Tourette syndrome (TS) and bipolar spectrum disorder who benefited from a combination of clozapine and aripiprazole.Case Report“Mr. FS,” a 39-year-old art-craft worker, had been suffering from TS since his early childhood. During the adolescence, TS was characterized by mouth opening and shoulder rotation, complex motor tics, such as trunk-bending or gyrating, screaming, and complex phonic tics. He was treated with pimozide 8 mg/day, which led to a complete remission of tics for about 20 years, although the clinical picture was complicated by the onset of mood shifts associated with impulsive behaviors and obsessions (numerical obsessions, rituals of order and symmetry, disproportionate aggressiveness).In 2007, when he was 35, he visited us for a major depressive episode with suicidal thoughts, panic attacks, and agoraphobic avoidance. Paroxetine (20 mg/day) led to a fast improvement of mood and anxiety symptoms, albeit being ineffective on tics. Only transient responses were obtained with the association of various drugs (haloperidol, risperidone, olanzapine, amisulpiride) to paroxetine and mood stabilizers (valproic acid, 600 mg/day). After about 2 years of different combinations, a significant improvement was obtained with tetrabenazine 75 mg/day + clozapine 25 mg/day + valproic acid 600 mg/day and fluvoxamine 150 mg/day. This strategy had a good impact only on the affective and obsessive symptoms, while tics remained stable. Therefore, tetrabenazine, fluvoxamine, and valproic acid were tapered down. At the same time, aripiprazole (15 mg/day) was introduced, and, after about 1 month, we observed a dramatic improvement of TS symptoms. The improvement is still maintained at 2-year follow-up, so that currently the patient, who is regularly taking clozapine 25 mg/day and aripiprazole 15 mg/day with no significant side effects, shows a good affective balance, with no impulsive behavior, obsessions, or tics.Clozapine is considered a standard treatment for schizophrenia and bipolar disorder,2 whereas it has been reported to exacerbate obsessions and tics, although this topic is controversial.3 The effectiveness of aripiprazole in bipolar disorder is well documented, and preliminary data do exist for its possible use in obsessive-compulsive (OCD) and related disorders.4 Our case report highlights the possible usefulness of combining clozapine and aripiprazole in TS comorbid with bipolar spectrum disorders, perhaps due to the different and not overlapping pharmacological profile of these two antipsychotics. Aripiprazole has much higher affinity for D2 receptors than clozapine and, since it behaves as a 5-HT2A antagonist and 5-HT2C partial agonist, may have a robust anti-obsessional (and perhaps anti-tic) activity.5Further controlled studies are necessary to investigate the benefits of antipsychotic polypharmacy in patients suffering from both bipolar and OCD spectrum disorders.Dept. of Clinical and Experimental Medicine University of Pisa Pisa, ItalyCorrespondence: Armando Piccinni, M.D.; e-mail: a.[email protected]unipi.itReferences1 Tapp A, Wood AE, Secrest L, et al.: Combination antipsychotic therapy in clinical practice. Psychiatr Serv 2003; 54:55–59Crossref, Medline, Google Scholar2 Rybakowski J: Maintenance treatment of bipolar disorders. Neuro Endocrinol Lett 2005; 26 Suppl 1:49–65Google Scholar3 Bastiampillai T, Dhillon R, Mohindra R: Exacerbation of tics secondary to clozapine therapy. Aust N Z J Psychiatry 2008; 42:1068–1070Medline, Google Scholar4 Pessina E, Albert U, Bogetto F, et al.: Aripiprazole augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a 12-week open-label preliminary study. Int Clin Psychopharmacol 2009; 24:265–269Crossref, Medline, Google Scholar5 Shapiro DA, Renock S, Arrington ER, et al.: Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 2003; 28:1400–1411Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByFrontiers in Behavioral Neuroscience, Vol. 13Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology, Vol. 26, No. 2 Volume 25Issue 1 Winter 2013Pages E45-E45 Metrics PDF download History Published online 1 January 2013 Published in print 1 January 2013

The treatment of psychotic depression: Is there consensus among guidelines and psychiatrists?

BackgroundPsychotic depression (PD) is a prevalent, severe, under-diagnosed and often inadequately treated mental disorder, which has received disproportionally little attention by clinicians, researchers and the pharmaceutical industry. Consequently, the evidence base for optimal clinical practice regarding PD is limited. The aim of this study was to investigate the degree of consensus among international treatment guidelines on PD and to determine whether a potential lack of consensus would be reflected in the clinical practice of Danish psychiatrists. Methods1.Review and comparison of international guidelines on the treatment of PD.2.Questionnaire based survey regarding Danish psychiatrists’ treatment of PD. ResultsThe nine international treatment guidelines considered in the review have contrasting opinions on the optimal treatment for PD: 6 of 9 suggest antidepressant (AD)+antipsychotic (AP) combination therapy, 3 of 9 recommend AD monotherapy and 5 of 9 find electroconvulsive therapy (ECT) equally appropriate as first line treatment. The 113 surveyed psychiatrists displayed the same lack of consensus. Their preferred treatment was either AD+AP combination therapy (42%), AD monotherapy (31%) or ECT (21%). The first line choices of ADs and APs were tricyclic antidepressants (51%) and quetiapine (62%), respectively. LimitationsThe survey data are subjected to a potential selection bias as the respondents are likely to represent the more informed fraction of psychiatrists. ConclusionsOur results indicate that both treatment algorithms and clinical practice regarding PD are highly heterogeneous. This finding emphasizes the need for further studies on the treatment of psychotic depression.

Comparison of Polypharmacy in Schizophrenia and Other Psychotic Disorders in Outpatient and Inpatient Treatment Periods: A Naturalistic One Year Follow-up Study

Objective: Polypharmacy of antipsychotic drugs has been increasing although there are not enough evidence based data and recommendations in the treatment algorithms. The current study differs from cross-sectional studies as it aimed at observing the same patient population during their in-and out-patient periods for one year follow-up and investigated the frequency of polypharmacy and related factors in terms of clinical correlates and equivalent doses.Method: The patients admitted to Psychiatry Service of Dışkapı Yıldırım Beyazıt Trainig and Research Hospital, Ankara in the 2008–09 period with the diagnosis of schizophrenia and other psychotic disorders (n=261) were reviewed and patients with regular follow up visits in the outpatient clinic (n=192) were included in the study. At the end of the first year, participants were evaluated for their treatment compliance, use of polypharmacy, drug doses, and severity of the disorder.Results: The rate of polypharmacy was 52.1% (n=100) at the time of discharge from hospital while it was 44.3% (n=85) during the one year-follow up visit (χ2=2.97, df=1, p=0.001). The polypharmacy and monotherapy groups were not statistically different in terms of comorbidity, disorder and treatment duration, number of previous hospitalizations, type of admission, and general medical condition. However, the monotherapy and polypharmacy groups were statistically different in terms of the use of antipsychotic type. The ratio of patients with severe disorder was statistically higher in the inpatient group. While the clinical severity impression (CGI) of patients in remission did not change during the follow-up period, the moderate to severe patient groups' severity increased during that time. Drug compliance of the polypharmacy group was statistically lower than the monotherapy group both in the inpatient (χ2 =12.99; df=1; p=0.001) and outpatient (χ2 =12.81; df=1; p=0.001) periods. Adverse event frequency was the same for both groups. Adverse events and lack of efficacy were the most frequent reasons for drug prescription change. Both inpatients and outpatients receiving antipsychotic combination therapy had statistically higher equivalent antipsychotic drug doses. Severity scores of inpatients receiving combination therapy were higher than the patients receiving other drug regimensConclusion: Use of polypharmacy is limited in good clinical practice guidelines but surveys on clinical practices show that the use of polypharmacy is more frequent than the suggested levels in the guidelines. On the other hand, use of clozapine and long-term effective antipsychotics are below the incidence of suggested groups. In order to guide clinicians better, schizophrenia treatment algorithms need to emphasize the use of clozapine and long acting antipsychotics more.

Does pharmacology explain dosing adjustments during antipsychotic combination therapy under naturalistic clinical conditions?

Introduction: Dopamine D2 receptor blockade by antipsychotics is thought to mediate their effects on positive symptoms of schizophrenia. Therefore, the combination of two antipsychotics with similar affinity for the D2 receptor (1) should result in additive effects on psychotic symptoms or (2) could be used to decrease the dosage of the first antipsychotic. Methods: We tested this hypothesis in a retrospective analysis of all plasma samples submitted for therapeutic drug monitoring (TDM) by the University Hospital Innsbruck from April 01 to September 30, 2008, in patients diagnosed with schizophreniform disorders (ICD 10 codes F20 to F29). Results and Discussion: The addition of a second antipsychotic (amisulpride, aripiprazole or clozapine) resulted in a decrease in the dosage and in the plasma level of the first antipsychotic (clozapine or risperidone) only in those patients whose antipsychotic plasma levels under monotherapy with the first antipsychotic were within the recommended therapeutic level, i.e., only in patients who were adequately dosed and showed sufficient compliance under monotherapy.

P02-306 - Mental retardation and long- acting injectable risperidone: Clinic evidence during 7 years

Antipsychotics are frequently used in the Intellectual Disability when displayed conduct disorder or specific psychiatric disorders such as disruptive behavior disorder as disruptive disorders, neurodevelopmental disorders such as autism, various psychotic disorders, disorder Impulse Control Disorders, etc. The long-acting Injectable risperidone is a drug which by its nature from the beginning makes the maintenance treatment of these patients. In a study conducted by our team in 2007 was described the good therapeutic response to long-acting injectable risperidone (LAIR) in psychiatric disorders in this population.ObjectivesIn depth study of the use of long-acting injectable risperidone in this specific population on the basis of a previous study on a sample of 60 Pack. To describe the demographic characteristics of the new sample of 80 patients, type of Mental Retardation and the most common psychiatric diagnoses. To analyze the therapeutic response to treatment by comparing the clinical course before and after treatment with long-acting injectable risperidone (episodes of aggression, hospitalization, emergency room visits, mechanical restraint, disruptive behavior ...). The dose of long-acting injectable risperidone used, the presence of antipsychotic combination therapy, side effects, etc. are analized. We analyze the information on family overload in relation to treatment with Long- acting injectable Risperidone in a part of the sample.ResultsThe study of a sample of 80 patients of both sexes, with diagnosis of mental retardation treated with LAIR is in the process of statistical analysis. But it is possible to appreciate the good therapeutic response and high tolerability of patients to treatment.

Combined Venlafaxine and Olanzapine Prescription in Women with Psychotic Major Depression: A Case Series

Patients with psychotic major depression suffer prolonged duration and greater severity of illness, including an increased likelihood of recurrent episodes and resistance to conventional pharmacotherapies. They do not respond to placebo and respond poorly to antidepressant or antipsychotic monotherapy. On the other hand, as has been demonstrated, they do respond well to antidepressant and antipsychotic combination therapies. Different combinations of drugs were studied, but little is known up to now with regard to the combination of venlafaxine and olanzapine. The following paper presents three separate case studies of female patients suffering from psychotic unipolar major depression, all of whom were admitted to a psychiatric ward and successfully treated with a combination of venlafaxine and olanzapine.

Antipsychotics combined use pattern among schizophrenic inpatients in Tangshan region

Objective To investigate rates and clinical associates of combined antipsychotic therapy in hospitalized patients with schizophrenia during 1986 ～ 2006. Methods Hospital charts of schizophrenic inpatients who discharged from six psychiatric hospitals in Tangshan in 1986,1996,2001, and 2006 were reviewed. Demographic and clinical character and prescription information at time of discharged of patients' was coded by trained investigators with a special designed form. Results The rates of combination antipsychotic therapy in the four years mentioned above were 13.2%, 18. 1% ,32.7%, and 28.9% ,respectively and the difference was statistically significant( x2 = 76.431, P ＜ 0.01; linear by linear x2 = 25. 542, P ＜ 0.01 ). Combined antipsychotic therapy in schizophrenic inpatients in Tangshan region show a increasing trend. There is significant difference of rate of combined antipsychotic therapy between hospitals. Combined antipsychotic therapy were associated with duration of illness,numbers of prior psychiatric hospital admission,hospital from which patients discharged,and discharged year. Key words: Schizophrenia ; Inpatient ; Antipsychotics ; Polypharmacy ; Predictors ;

Polypharmacy in schizophrenia - therapeutic option or a sign of despair?

International guidelines on schizophrenia and worldwide experts in psychiatry recommend and insist on monotherapy with an antipsychotic medication for schizophrenic patients. Studies about the clinical practice of these guidelines show that all over the world most schizophrenia patients receive two or more antipsychotics. Further more combinations with antidepressants, mood stabilizers or benzodiazepines is also common. Regarding to local national differences polypharmacy rates are increasing and achieve rates between 50 and 90% of schizophrenic patients, exhibiting therefore a major international trend towards polypharmacy. Although in some cases combination therapy brings advantages, such as enhancing or speeding up the antipsychotic effect, there are still a lot of disadvantages in a polypharmacy treatment regiment, such as interactions of the drugs being involved, the greater risk of adverse reactions and the lack of compliance to treatment regiment. Small, randomised controlled studies with regard to antipsychotic combination therapy exist. In summary they exhibit a positive outcome for combinations of antipsychotics with different receptor profile. Altogether according to the study results combinations can be divided in irrational (e.g. clozapine and quetiapine), and rational ones, which provide a greater efficacy (e.g. clozapine and amisulpirid). Augmentation with antidepressant agents in case of persisting negative symptoms and with mood stabilizers in patients with additional affective symptoms can be recommended. Further randomised controlled studies are necessary to recommend combination strategies on a higher level of evidence for treatment resistant schizophrenia patients. In the speech given, I would try to give you an overview and discuss current data and trends in combining antipsychotic or other psychotropic treatment in schizophrenia.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of Adjunctive Aripiprazole for Schizophrenia or Schizoaffective Disorder Inadequately Treated With Quetiapine or Risperidone Monotherapy

Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder. In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score. 323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P = .942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (-12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (-18.7 ng/mL vs -1.9 ng/mL; P < .001) but not in the quetiapine subgroup (-3.01 ng/mL vs +0.15 ng/mL; P = .104). The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia. clinicaltrials.gov Identifier: NCT00325689.

P03-28 Antipsychotic combinations in an acute psychiatric unit

Introduction:Available data does not recommend antipsychotic drug combinations in treatment of psychotic symptoms and monotherapy is nowadays considered the option with the highest scientific evidence. Nevertheless, antipsychotics combination is a common practice in countries such as USA (40-60%), Japan (90%) and Spain (50-70%).Aims:To determine antipsychotic combinations frequency in patients with a diagnosis into the psychotic spectrum admitted in an acute psychiatric unit. to determine the differences among these combinations according to diagnosis. to analyze which are the associations more commonly prescribed as well as the theoretical basis that supports them according to receptorial profiles.Methods:Demographic and clinical data of patients with a psychotic-spectrum diagnosis admitted to the Doctor Peset University Hospital acute unit during 2004-2007 were retrospectively analyzed. We observed the percentage of patients treated with more than one antipsychotic drug, as well as the combinations more frequently prescribed.Results:Out of 677 analyzed patients, 302 were treated with an antipsychotic combination therapy (45%). the associaton most commonly prescribed was an oral atypical antipsychotic + an intramuscular atypical antipsychotic (121 patients). According to diagnosis, 50% from each diagnostic group was treated with a combination antipsychotic therapy.Conclusions:There is a high percentage of inpatients treated with more than one antipsychotic. We found no significant differences by diagnosis nor any clearly-defined key according to receptorial profiles.

Patient factors associated with receipt of combination antipsychotic drug therapy in the treatment of schizophrenia

Although discouraged in available treatment guidelines, combination antipsychotic prescribing (CAP) is a common practice in the treatment of schizophrenia. Patient characteristics may be associated with this type of treatment. A dataset (N = 363) derived from parallel randomised controlled trials was interrogated to identify factors associated with the receipt of CAP, and a logistic regression analysis was used to predict the occurrence of CAP. Significant predictors of CAP were longer illness, low global functioning score and high treatment adherence rating. Co-prescribed patients received a higher combined dose.

Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open‐label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidone

To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner. In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks. Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9 mg; risperidone 3.14 mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5 mg; risperidone 5.50 mg). Body weight, prolactin, and total cholesterol increased significantly. Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer- term monotherapy are warranted for refractory schizophrenia.

Differential pharmacological regulation of drug efflux and pharmacoresistant schizophrenia

Pharmacoresistant schizophrenia is a significant impediment to the successful management of the disease. The expression and function of P-glycoprotein (P-gp) has recently been implicated in this phenomenon. P-gp is a multidrug efflux transporter that prevents drug substrates from crossing the blood-brain barrier (BBB). Although the direct interaction between individual antipsychotic agents and P-gp has been demonstrated, the effect of antipsychotic drug combinations used in disease management on P-gp transport function remains to be elucidated. This could have important clinical implications in some individuals as dosage adjustments based on plasma drug concentration changes may not always be appropriate if drug-drug interactions and the resulting changes in drug concentration in the brain are not considered. This paper introduces the potential impact that combination antipsychotic therapy may have on P-gp function at the BBB and discusses the consequences of this in the prevention and circumvention of unfavourable therapeutic response in schizophrenic disorders.

Polypharmazie in der Behandlung der Schizophrenie

Current standards for the pharmacological treatment of schizophrenia favour antipsychotic monotherapy. Most atypical antipsychotics developed in recent years meet the statutory requirement of being at least as effective as Haloperidol. Nevertheless, pharmacoepidemiological data show an increase in polypharmacy. The importance of the studies is underlined by the fact that 40 - 50 % of schizophrenic inpatients and up to 90 % schizophrenic outpatients receive antipsychotic combination therapies. Treatment resistance, reduction of dose-related side effects caused by antipsychotic monotherapy or the effect on concomitant symptoms of schizophrenia, such as comorbid depression, might justify combination therapy or augmentation strategies. Apart from the high costs, polypharmacy is associated with reduced patient compliance and an increased risk of undesired pharmacological effects. Since polypharmacy is increasingly common further educational measures in psychopharmacology should be getting more attention. Due to the very small number of controlled studies that exist at present this report will focus on case reports of the most frequent as well as some of the lesser prescribed combination therapies. Finally, conclusions will be discussed in relation to therapy recommendations.

Combination antipsychotic therapy in psychiatric outpatient clinics in Taiwan

Objective The purpose of this study is to survey the use of combination antipsychotic therapy (CAT) in the psychiatric outpatient clinic of a general hospital. Methods Patients who received at least 2 antipsychotics in the psychiatric outpatient clinic of a general hospital in 1 month (August 1-31, 2003) were identified, and their retrospective chart review was performed. Using a questionnaire, we surveyed the clinicians on why 2 antipsychotics were prescribed, why long-term CAT was used, and whether the problems were solved by CAT. Results We studied 957 patients diagnosed with schizophrenia and related disorders in 1 month. A total of 119 patients (12%) were prescribed at least 2 antipsychotics. Among these 119 patients, 91 (76%) were prescribed 2 types of first-generation antipsychotics (FGAs), and 15 patients (16%) were prescribed a second-generation antipsychotic medication and a low-dose FGA medication. The clinicians' main reasons for CAT were to treat insomnia (84%) and psychotic symptoms (83%). Conclusions The results of this study revealed that 12% of the patients received CAT in the clinical practice. Most patients were prescribed 2 FGAs. The clinicians' reasons for prescribing CAT in Taiwan were to treat insomnia and psychotic symptoms.

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.