Antipsychotic Combination Therapy Research Articles

The Prevalence of Bruxism and Associated Factors Among Patients with Schizophrenia in Istanbul, Türkiye: A Cross-Sectional Study.

Schizophrenia is a severe and chronic neuropsychiatric disorder that involves profound impairment of psychopathology in cognition, emotion, perception, and other aspects of behavior. Factors, such as the nature of the disease, length of hospital stay, duration of illness, and side effects of psychotropic drugs, may contribute to poor oral health and the risk of developing bruxism in patients with schizophrenia. To evaluate the prevalence of bruxism and associated factors in patients with schizophrenia. This cross-sectional study was conducted in a single center with 211 patients with schizophrenia. Study participants were graded according to "probable" bruxism based on positive clinical inspection, with or without a positive self-report. The type of antipsychotic treatment used in participants was evaluated in three categories: typical antipsychotic monotherapy, atypical antipsychotic monotherapy, and a combination of both. Binary logistic regression models were used to evaluate associations between probable bruxism and different factors. The mean age of the study participants was 51.02 ± 9.29 years, and 112 (52.5%) were males. Probable bruxism was identified in 87 (41.2%) of the study participants. Younger age (AOR = 0.88, 95% CI = 0.838-0.928, P < 0.001), higher duration of illness (AOR = 1.50, 95% CI = 1.278-7.545, P < 0.001), and combination antipsychotic therapy (AOR = 3.042, 95% CI = 1.278-7.545, P = 0.015) were significant factors associated with probable bruxism among patients with schizophrenia on treatment. The relatively high prevalence of probable bruxism in patients with schizophrenia and its relation to antipsychotics was observed. There is a need for more research on the causes and treatment of bruxism in schizophrenia.

Evaluation of the neuroprotective effect of antipsychotics by serum quantification of protein S100B

ObjectiveThis research delves into the intricate interplay between antipsychotic medications and neuroprotection focusing on the S100B protein—a central player in the regulation of neuroapoptotic activity. MethodBlood samples were collected to assess serum S100B protein levels using an immunoassay of immunoelectrochemiluminescence. The first two samples were collected with a 3-month interval between each, and the third sample was obtained 6 months after the previous one. Changes in S100B protein levels throughout the study were assessed using Friedman's ANOVA test. This was followed by the Wilcoxon signed-rank test with Bonferroni correction to account for multiple comparisons. ResultsThis study involved 40 patients diagnosed with severe mental disorders (34 schizophrenia, 4 schizoaffective disorder, 1 bipolar disorder, and 1 borderline personality disorder). These patients had been receiving antipsychotic treatment for an average duration of 17 years. The results revealed that the S100B protein remained within physiological levels (median values 39.0 ng/L for the first sample, median values 41.0 ng/L for the second sample, and median values 40.5 ng/L for the third sample) with no significant changes (p = 0.287), with all anti-psychotic medicaments values consistently below 50 ng/L, a lower value compared to maximum range of 105 ng/L. Importantly, there were no significant differences in S100B protein levels between patients on monotherapy and those on combination antipsychotic therapy (p = 0.873), suggesting that combination therapy did not increase neuroapoptotic activity. ConclusionsThese findings provide compelling evidence for the potential neuroprotective effects of long-term antipsychotic treatment in individuals with severe mental disorders. By maintaining physiological levels of the S100B protein, antipsychotic medications may help protect against neuronal damage and dysfunction. This research contributes valuable insights into the neuroprotective mechanisms of antipsychotic drugs, enhancing our understanding of their potential benefits in the treatment of severe mental disorders.

Pharmacological treatments for psychotic depression

Despite the overall efficacy of antidepressant and antipsychotic combination therapy for the treatment of psychotic depression, data on the most appropriate choice of individual drugs for the combination treatment are limited. Researchers recently conducted a network meta‐analysis to compare the efficacy and safety of various pharmacological treatment options for patients who had major depressive episodes with psychotic features (Oliva et al., 2024).

Antipsychotics in the maintenance phase for psychotic depression.

This study aimed to associate antidepressants with versus without antipsychotics with readmission and suicide in patients with psychotic unipolar depression. Swedish national registers were used to identify inpatients with psychotic unipolar depression, treated 2007-2016. The participants collected antidepressants with or without antipsychotics from a pharmacy within 14 days after discharge and were followed up for 2 years. The primary outcome was hospital readmission due to any psychiatric disorder, suicide attempt, or completed suicide. Cox regression was used to analyze the data, which were adjusted for sex, age, prior admissions, comorbidity, electroconvulsive therapy, and other pharmacological treatments. We identified 4391 patients, of which 2972 were in the antidepressant + antipsychotic combination therapy group, and 1419 were in the antidepressant monotherapy group. After 2 years, 42.3% and 36.6% of patients were readmitted or committed suicide in the combination therapy and monotherapy group, respectively. Monotherapy was significantly associated with a lower risk of reaching the outcome in the main analysis (hazard ratio = 0.86; 95% confidence interval: 0.77-0.95). The results went in the same direction in all sensitivity analyses. Our findings do not indicate any advantage of adding antipsychotics as adjunctive to antidepressants as maintenance treatment. Considering the wide use, known side effects, and the current lack of evidence supporting the benefit, further studies on the effect of antipsychotics in the maintenance phase of psychotic unipolar depression are urgently warranted.

Frequency of sexual dysfunction in outpatients with severe mental illness in Greece.

Patients with psychosis can develop sexual dysfunction, which may be related to the disease itself, psychosocial factors, somatic comorbidities, and the use of psychotropic medication. We aimed to investigate the type and frequency of sexual dysfunction in patients diagnosed with schizophrenia or bipolar disorder in order to assess the side effects of antipsychotics in sexual function. This is a multicenter, cross-sectional study, involving patients diagnosed with schizophrenia (79.3%) or bipolar disorder (20.7%) treated in the Department of Psychiatry and Community Mental Health Centers from November 2018 to December 2019. Patients were enrolled in the study after signed informed consent. Demographic and clinical data were collected from patients through a semi-structured interview. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ) was administered to assess sexual function. A total of 87 outpatients on antipsychotics were recruited in the study. The mean age was 43.6 years, while the mean duration of the disease was 16.9 years. Overall, only 9.1% of patients spontaneously reported sexual dysfunction. Patients treated with oral first-generation antipsychotics had more difficulties in achieving orgasm and decreased erection capacity. In contrast, patients treated with oral second-generation antipsychotics had decreased ejaculation capacity. Patients on antipsychotic combination therapy were associated with higher rates of sexual anhedonia. These results suggest that sexual dysfunction is a side effect of antipsychotic treatment, which was spontaneously rarely reported by patients. It seems essential to obtain a psychosexual clinical history before initiating antipsychotic treatment to evaluate following changes and adopt an individualized strategy to manage sexual dysfunction induced by antipsychotics.

GAMBARAN KEJADIAN EKSTRAPIRAMIDAL SINDROM PADA PASIEN TERAPI ANTIPSIKOTIK TIPIKAL DI RUMAH SAKIT JIWA ACEH

The use of antipsychotics in schizophrenic patients often causes side effects in the form of Extra Pyramidal Syndrome (EPS), namely the presence of uncontrolled muscle movement disorders such as seizures, shaking and so on. The incidence of EPS is more common with the use of typical antipsychotics than atypicals. This study aims to see the incidence of EPS in inpatients with schizophrenia at the Aceh Mental Hospital located in Banda Aceh in 2020. The population in this study were all inpatients who were given typical antipsychotics. While the research sample was 399 samples collected from medical record data of inpatients in 2020, so the study was retrospective with a cross sectional approach. Data collected in the form of patient identity (gender, age), drug therapy (typical antipsychotics) and the incidence of EPS. The results showed that schizophrenic patients who received typical antipsychotic therapy who were hospitalized at the Aceh mental hospital in 2020, were 324 men (81.2%) and 75 women (18.8%), with the highest age range being at 36-45 years amounting to 202 people (50.6%). Typical antipsychotic therapy used in the form of combination of typical-typical and typical-atypical drugs, namely clozapine-trifluperazine (40.6%), chlorpromazine-risperidone (20.3%), haloperidol-chlorpromazine-trifluperazine (16%), haloperidolchlorpromazine (7%), and haloperidol-trifluperazine (5%). The incidence of EPS that occurred was 113 people (28.3%), with the highest number of EPS occurring from the administration of haloperidol-chlorpromazine-trifluperazine combination antipsychotic therapy, which was 61 people (15.3%).

Systematic Review of Real-World Treatment Patterns of Oral Antipsychotics and Associated Economic Burden in Patients with Schizophrenia in the United States.

BackgroundSchizophrenia is a chronic mental disorder associated with substantial morbidity and mortality affecting 0.25–1.6% of adults in the USA. Antipsychotic treatment is the standard of care for schizophrenia, but real-world treatment patterns and associated costs have not been systematically reviewed.ObjectiveWe conducted a systematic review to summarize treatment patterns and associated costs related to oral antipsychotic treatment of patients with schizophrenia in the USA.Data SourcesWe searched Medline (via PubMed) and Embase to identify relevant observational studies published from January 1, 2008, to June 1, 2018; costs were converted to 2018 US dollars.Study EligibilityObservational, real-world studies reporting on patterns of treatment and/or associated costs for adult patients with schizophrenia treated with oral antipsychotics in the USA were included.ResultsEighty-one studies were identified. Frequently prescribed oral second-generation antipsychotics were olanzapine (up to 50.9%), risperidone (up to 40.0%), and quetiapine (up to 30.7%). Suboptimal adherence was common across studies. Antipsychotic switching occurred in about half of patients, while antipsychotic combination therapy occurred in nearly 30%; all were associated with increased medication-related costs. Mean annual direct medical costs differed by treatment, with reported costs of $17,115 to $26,138 for patients treated with olanzapine, $18,395 for risperidone, and $17,656 to $28,101 for quetiapine.LimitationsThis systematic review is limited by the variations in definitions of schizophrenia-related clinical terms used between studies and by the inclusion of studies focused on only the US health care system.ConclusionsIn the treatment of schizophrenia, suboptimal adherence, antipsychotic switching, and antipsychotic augmentation were all associated with high costs of care in comparison to patients who were adherent and did not require antipsychotic switching or augmentation. These findings illustrate the need for the development of new treatments that address efficacy and adherence challenges of currently available therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02232-z.

An Evaluation of the Prescribing of High Dose Antipsychotic Therapy and Combination Antipsychotic Therapy to Inpatients on the General Adult Wards of Mersey Care NHS Foundation Trust

AimsHigh dose antipsychotic therapy (HDAT) is defined as “a total daily dose of a single antipsychotic which exceeds the upper limit stated in the SPC or BNF or a total daily dose of two or more antipsychotics exceeding the SPC or BNF maximum using the percentage method. Previous audits have looked at HDAT on both a national level (the Prescribing Observatory for Mental Health) and within Mersey Care NHS Foundation Trust. This audit aimed to identify the proportion of patients subject to HDAT and review combination antipsychotic strategies and consideration of Clozapine in patients subject to HDAT.MethodsIn August 2021, data were collected from the eight inpatient wards in Mersey Care NHS Foundation Trust. This involved using the Electronic Prescription and Administration system to identify those prescribed antipsychotics. Following this, the patient's electronic record was scrutinised for documentation of the rationale for HDAT, combination antipsychotics and consideration of Clozapine.Results129 inpatients were identified as being prescribed antipsychotic medication. 21 (16.3%) patients were prescribed combination antipsychotic therapy, with four of these patients (3.1%) being prescribed HDAT. For these four HDAT patients, there was no recorded documentation of discussion of the option of Clozapine. The most common antipsychotic combination was Paliperidone depot with oral Risperidone. 38 out of 129 (29.5%) patients had been considered for Clozapine. Reasons for Clozapine being refused included the patient declining, concerns about non-concordance with oral medication, patients having had a neutropenia on an FBC, the patient being reluctant to have regular blood tests and a patient's comorbidities.ConclusionWhen comparing the proportion of patients subject to HDAT (3.1%) to the previous Trust audit in December 2020 (9.1%), there is a recurrent theme that antipsychotic prescribing practice in Mersey Care is safe, with minimal HDAT. Of note, the figure is significantly lower than the proportion of HDAT patients identified in the 2012 national study (28%). In this audit, none of the patients on HDAT had documented consideration of Clozapine. Three of the four patients were soon to be no longer subject to HDAT which may explain this result. Compared to the Trust's HDAT audit in 2020, the percentage of patients on combination antipsychotic therapy has stayed largely the same - 16.3% compared to 17.4%. The Trust needs to strive to continue minimal HDAT prescriptions and ensure that, in those patients subject to HDAT, there is consideration of and documentation of Clozapine being considered.

A systematic review and meta‐analysis of maintenance treatment for psychotic depression

Purpose To perform a systematic review on the use of maintenance treatment to prevent relapse and recurrence in patients with psychotic unipolar or bipolar depression. Methods We conducted an electronic search in December 2019 (and an updated search in July 2021) of four databases (PubMed, Embase, PsycINFO, and Cochrane) to identify controlled studies comparing the relapse rates of patients receiving maintenance treatment for psychotic unipolar depression and psychotic bipolar depression. A meta-analysis was made that included three studies comparing antidepressant (AD) and antipsychotic (AP) combination therapy with AD monotherapy. We used the GRADE tool to assess the quality of evidence. Results We included five randomized controlled trials fulfilling the inclusion criteria, making three comparisons: (a) AD + AP versus AD monotherapy; (b) AD + AP versus AP monotherapy; (c) AD + electroconvulsive therapy versus AD monotherapy. The included studies only examined patients with psychotic unipolar depression. The largest included study reported a statistically significant advantage of AD + AP compared with AD monotherapy. We made a meta-analysis of the three studies comparing AD + AP combination therapy with AD monotherapy, which included 195 patients and 56 events. The meta-analysis did not show a statistically significant difference between these treatments. Conclusions Contrary to the finding of the largest study, we did not find a statistically significant difference between AD + AP combination therapy and AD monotherapy in the meta-analysis. There is insufficient evidence to support the superiority of any treatment modality as maintenance treatment for psychotic depression. Further studies are required.

An audit of high-dose and combination antipsychotic prescribing across the general adult inpatient wards in Mersey Care NHS Foundation Trust

AimsTo review the number of prescriptions of regular high-dose antipsychotics and combination antipsychotic therapy across the eight general adult inpatient wards in Mersey Care NHS Foundation Trust and examine whether these prescriptions followed Trust recommendations for high-dose antipsychotic therapy (HDAT).BackgroundThe two main rationales behind prescribing HDAT are pharmacokinetics differ in individuals and so insufficient amounts of antipsychotic may reach the effect site at maximum dose in some patients and variations in the effect site between patients may mean higher doses are required to achieve therapeutic effect.MethodThe electronic prescription records for all patients on the eight general adult inpatient wards were scrutinised. 121 patients were prescribed antipsychotic medication. Any patients on a combination of regular antipsychotic medication or on HDAT were identified. Any patient on combination therapy or HDAT was studied to determine if Clozapine had been considered. The electronic notes of HDAT patients were analysed to ascertain whether tests recommended by Trust guidelines – BMI, blood pressure (B.P), pulse rate, ECG, FBC, U and Es, LFTs, serum prolactin, serum cholesterol and HbA1c level had been performed prior to initiation and following any dose increase.Result21 of 121 patients prescribed antipsychotic medication were on combination therapy. 11 were subject to HDAT. 8 of the 11 HDAT patients were on combination therapy. Clozapine was considered before initiating HDAT in 9 of the HDAT patients. Clozapine was considered in 13 of the 21 patients on combination antipsychotic therapy, but only two were initiated on Clozapine (combined with Olanzapine or Risperidone).100% of HDAT patients had an ECG prior to initiation of HDAT; only 36% had one after dose increases above BNF maximum. 100% of HDAT patients had their BMI measured before initiation. 91% had baseline B.P and heart rate checked. Of the recommended blood tests, 100% of HDAT patients had baseline FBC, U and Es, LFTs and serum cholesterol. Fewer patients had a baseline HbA1c level (91%) or serum prolactin (46%) measured.ConclusionPrevalence of HDAT across the general adult inpatient wards in the Trust was 9%, much lower than the 28% reported in the HDAT audit completed by the Prescribing Observatory for Mental Health in 2012. Patients within Mersey Care are more likely to be prescribed combination therapy than HDAT. Not every HDAT patient has been considered for Clozapine. There is a need to ensure Trust monitoring guidelines for HDAT patients are being strictly adhered to.

Effects on monotherapy and reduction of antipsychotic drugs by clozapine therapy in Japanese patients with treatment-resistant schizophrenia.

The schizophrenia guidelines in Japan and many other countries describe clozapine as the first-choice drug for patients with treatment-resistant schizophrenia. However, there have been no reports to date on the effects of the introduction of clozapine on the prescription of other antipsychotics and concomitant drugs. In this study, we retrospectively investigated the prescription of antipsychotics and concomitant drugs before vs 6months after and 12months after switching to clozapine. Clozapine was introduced to 62 patients with treatment-resistant schizophrenia, and 51 patients continued on clozapine therapy. Six months after switching to clozapine, there was a significant decrease in the mean number of antipsychotic drugs (2.04±0.75 vs 1.10±0.30: p<0.001) and in the mean chlorpromazine equivalent value (1024±73mg/day vs 781±391mg/day: p<0.001) compared to before switching. Moreover, antipsychotic monotherapy increased from 24% to 90% after switching to clozapine. In addition, the number of concomitant benzodiazepines, anti-parkinson drugs and antidepressants also significantly decreased 6 and 12months after switching to clozapine (p<0.001 for benzodiazepines and anti-parkinson drugs, and p<0.05 for antidepressants). Our study suggests that switching to clozapine may reduce the use of antipsychotic combination therapy, and may also reduce the number of concomitant drugs.

The challenges in schizophrenia treatment in real-life: The uncomfortable truth

Certain percentage of the first-episode schizophrenia patients presents with negative symptoms, which persists over the year and influence treatment outcomes (Galderisi et al. 2013). Treatment of negative symptoms has been a significant continuous clinical challenge. Majority of recently published guidelines recommend antipsychotic monotherapy as the standard of care, recommending antipsychotic combination therapy only after a failed trial with clozapine (George A. Keepers et al. 2020; Faden et al. 2020). However, real-life forces clinicians to look for possible combinations of medications early on, especially to tackle negative symptoms. The systematic review of global prescribing practices covering four decades found the pooled median rate of antipsychotic combination therapy approximately 20% (Gallego et al. 2012). One of the largest retrospective studies every conducted (n = 62,250) assessed rehospitalisation rates and the long-term use of antipsychotic polypharmacy in schizophrenia. Antipsychotic combination treatment was associated with an approximate 10% lower relative risk of psychiatric rehospitalisation compared with antipsychotic monotherapy (Tiihonen et al. 2019). Real-world effectiveness study of antipsychotic monotherapy vs. polypharmacy in schizophrenia from Eastern Europe is also supporting this approach (Katona, Czobor, and Bitter 2014). At the same time antipsychotic combination therapy can increase the total antipsychotic dose burden, frequency of adverse effects, potential drug-drug interactions and incur additional costs. In our recent naturalistic study in schizophrenia outpatients (n=120) with insufficient effectiveness of previous antipsychotics therapy on negative symptoms, we were able successfully switch therapy form several different antipsychotic combinations to monotherapy and gain clinical benefits (Rancans et al, 2020).DisclosureNo significant relationships.

Differences in Treatment of Schizoaffective Disorder and Schizophrenia in Real Clinical Practice in Slovakia

Background: Schizoaffective Disorder (SAD), similarly to schizophrenia, is a potentially chronic mental disorder that negatively affects the functioning of a patient. Various issues in everyday clinical practice often arise from its diagnostic and therapeutic uncertainty. To date, there is a lack of a well-defined therapeutic algorithm used to treat the simultaneously manifesting schizophrenic and affective components. The aim of this study was to compare the therapeutic approaches in schizophrenia and schizoaffective disorders to identify the need of different treatment strategy for these diseases. Methods: In a retrospective study, we evaluated the therapeutic algorithms used in all patients with SAD (n = 99) hospitalized at the Department of Psychiatry, Comenius University in Bratislava, Faculty of Medicine and University Hospital Bratislava throughout the year 2010 and compared them with the therapeutic procedures used in all schizophrenia patients hospitalized in the same year (n = 120). Results: We found similarities between the groups of patients with schizophrenia and SAD in the number, type and length of hospitalizations and general patient management. Differences were identified in terms of the spectrum of used pharmacotherapy. For the treatment of both mental disorders, atypical antipsychotics were used the most. In the treatment of schizophrenia, we found the most frequent use of combined antipsychotic therapy, meaning oral and long-acting injectable forms. Patients with SAD mostly received antipsychotic monotherapy, but its complex effects were supplemented with other psychotropic drugs, mostly mood-stabilizers and anxiolytics. Conclusion: The results of our study show similarities between schizophrenia and SAD in terms of health care utilization, despite the fact that SAD is generally considered to be a “milder” disorder. On the other hand, this study indicates differences in the spectrum of pharmacotherapy used.

Mood stabilizers and/or antipsychotics for bipolar disorder in the maintenance phase: a systematic review and network meta-analysis of randomized controlled trials

We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar disorder in the maintenance phase. We performed two categorical network meta-analyses. The first included monotherapy studies and studies in which the two drugs used were specified (i.e., aripiprazole, aripiprazole once monthly, aripiprazole+lamotrigine, aripiprazole+valproate, asenapine, carbamazepine, lamotrigine, lamotrigine+valproate, lithium, lithium+oxcarbazepine, lithium+valproate, olanzapine, paliperidone, quetiapine, risperidone long-acting injection, valproate, and placebo). The second included studies on second-generation antipsychotic combination therapies (SGAs) (i.e., aripiprazole, lurasidone, olanzapine, quetiapine, and ziprasidone) with lithium or valproate (LIT/VAL) compared with placebo with LIT/VAL. Outcomes were recurrence/relapse rate of any mood episode (RR-any, primary), depressive episode (RR-dep) and manic/hypomanic/mixed episode (RR-mania), discontinuation, mortality, and individual adverse events. Risk ratios and 95% credible interval were calculated. Forty-one randomized controlled trials were identified (n = 9821; mean study duration, 70.5 ± 36.6 weeks; percent female, 54.1%; mean age, 40.7 years). All active treatments other than carbamazepine, lamotrigine+valproate (no data) and paliperidone outperformed the placebo for RR-any. Aripiprazole+valproate, lamotrigine, lamotrigine+valproate, lithium, olanzapine, and quetiapine outperformed placebo for RR-dep. All active treatments, other than aripiprazole+valproate, carbamazepine, lamotrigine, and lamotrigine+valproate, outperformed placebo for RR-mania. Asenapine, lithium, olanzapine, quetiapine, and valproate outperformed placebo for all-cause discontinuation. All SGAs+LIT/VALs other than olanzapine+LIT/VAL outperformed placebo+LIT/VAL for RR-any. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-dep. Aripiprazole+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-mania. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for all-cause discontinuation. Treatment efficacy, tolerability, and safety profiles differed among treatments.

Schizoaffective Disorder: Treatment Considerations

Rigorous studies of treatment efficacy in schizoaffective disorder have been limited by the diagnosis' low diagnostic validity and reliability; thus, no current consensus treatment guidelines exist. Given this limitation, the authors recommend using available data from clinical trials in the mood disorder and psychosis literature to guide clinical practice. Antipsychotic treatment remains the mainstay of pharmacotherapy for illnesses on the schizophrenia spectrum, which includes schizoaffective disorder, both the depressive and bipolar subtypes. For patients with schizoaffective disorder, depressive type, treatment with combination antipsychotic and antidepressant therapy is a reasonable therapeutic starting point. For patients with schizoaffective disorder, bipolar type, antidepressant therapy may be less helpful. Instead, mood stabilizers may be an important component of treatment for people with schizoaffective disorder, bipolar type, particularly if there is irritability or aggression; some mood stabilizers, particularly lithium, may be effective in treating the depressive subtype as well. [ Psychiatr Ann . 2020;50(5):200–204.]

Polypharmacy in schizophrenia.

Schizophrenia is a severe mental disorder characterized by a heterogeneous symptom profile which comprises a clinical platform for widespread use of polypharmacy even though antipsychotic monotherapy is the recommended treatment regimen. This narrative review provides a summary of the current gap between evidence and practice for use of antipsychotic combination therapy in patients with schizophrenia. Antipsychotic polypharmacy is frequently prescribed instead of following international consensus of clozapine monotherapy in treatment-resistant patients. Antipsychotic-benzodiazepine combination therapy clearly has a role in the treatment of acute agitation whereas there is no evidence to support an effect on core schizophrenia symptoms when chronically prescribed. Antidepressants are typically added to antipsychotic treatment in case of persistent negative symptoms. Available evidence suggests that antidepressants may improve negative symptom control in schizophrenia. Combining an antipsychotic with an antiepileptic is not supported by any firm evidence, but individual mood stabilizers have come out positively in single trials. Generally, the evidence base for polypharmacy in schizophrenia maintenance treatment is sparse but may be warranted in certain clinical situations. Therapeutic benefits and side effects should be carefully monitored and considered to ensure a beneficial risk-benefit ratio if prescribing polypharmacy for specific clinical indications.

Dramatic Weight Loss Following Addition of Aripiprazole to Olanzapine in a Patient With Treatment-resistant Schizophrenia: A Case Report

A 26-year-old man with a history of longstanding treatment-resistant schizophrenia gained a substantial amount of weight while being treated with high-dose combination antipsychotic therapy with olanzapine and amisulpride. The patient was switched to combination therapy with olanzapine and aripiprazole to reverse a drug-induced hyperprolactinemia. The patient subsequently lost over 37 lb in weight over a period of 4 months despite no measurable changes in his dietary caloric intake or in his level of physical activity and without any identifiable medical cause on physical investigation. The timing of the weight loss following the addition of aripiprazole and the exclusion of a medical cause point toward a causal relationship between the change in the patient's medication and the dramatic change in his body weight. We propose that, in a subgroup of patients, the addition of aripiprazole to their antipsychotic regime (without stopping the offending antipsychotic in terms of weight gain) can result in very significant weight loss and even the reversal of antipsychotic-induced weight gain.

Efekti tipičnih i atipičnih antipsihotika na kognitivne funkcije kod pacijenata sa psihotičnim poremećajima

Introduction: Although before, the prioritization of positive and negative symptoms of schizophrenia over neurocognitive impairment was of the highest importance, recent scientific achievements suggest that the disrupted neurocognitive functions are the core clinical feature of schizophrenia. Both general and specific cognitive functions are impaired. Earlier studies promoted atypical antipsychotics as the ones with the pro-cognitive effect, but an increasing number of recent studies do not demonstrate their superiority on neurocognitive improvement over typical antipsychotics. Aim: The aim of this study was to compare the effects of atypical antipsychotics and a combination of typical and atypical antipsychotics on cognitive functions in patients with psychotic disorders. Furthermore, the effects on gender and duration of disorder on the cognitive functioning of patients on different types of antipsychotic therapy were evaluated, as well as the effect of anticholinergic biperiden in patients receiving combined antipsychotic therapy. Subjects and Methods: This academic IV phase quasi-experimental clinical study included 50 hospitalized patients at the Clinic for Psychiatry at the Clinical Center of Vojvodina, who were divided into two groups of 25 subjects-one consisted of patients who had been on treatment with atypical antipsychotics for six weeks at least, while the second group included patients who had been on combined therapy with typical and atypical antipsychotics for minimum of six weeks. Within the second group, two subgroups could have been recognized; one with 12 patients who were co-medicated with anticholinergic biperidine, whilst the rest of 13 patients were using only combined antipsychotic therapy. All patients' cognitive functions were tested using the Mini-Mental State Examination (MMSE) and the results have been analyzed and compared using t-test. Results: There were no statistically significant difference in cognitive functioning between patients using atypical or combined antipsychotic therapy (p>0.05). There is no statistically signifi cant effect on gender or duration of disorder on cognitive functioning in the two compared groups (p>0.05). There is a statistically significant negative effect on cognition due to the co-medication with biperiden during combined antipsychotic therapy (p<0.05). Conclusions: Atypical antipsychotics did not show superiority in the improvement of neurocognitive functions over combined therapy with atypical and typical antipsychotics. Further investigations should be carried out in order to determine the exact effect of antipsychotics on cognitive functions.

Changes in antipsychotic drug usage and factors affecting the use of typical drugs based on nationwide health insurance data in South Korea

ObjectivesTo determine changes in antipsychotic drug usage in all South Korean patients with schizophrenia in 2011–2015 and factors affecting their utilisation in 2015.Design and settingRetrospective cohort study using health insurance...

Comparative Safety Profile of Single Versus Combination Antipsychotic Therapy by Using Glassgow Antipsychotic Side Effect Scale (Gass)

Comparative Safety Profile of Single Versus Combination Antipsychotic Therapy by Using Glassgow Antipsychotic Side Effect Scale (Gass)