Atypical Antipsychotic Quetiapine Research Articles

Factors Influencing Quetiapine Pharmacokinetic Variability: A Review of Population Pharmacokinetics

Abstract: Atypical antipsychotic quetiapine (QTP) exhibits high pharmacokinetic variability and population pharmacokinetic (PopPK) analysis is one of the approaches used to characterize factors influencing QTP pharmacokinetic variability. Though QTP is not regarded as a narrow therapeutic index drug, knowledge of this area is of importance. Thus, this review was conducted to summarize significant predictors for QTP pharmacokinetic variability identified using a PopPK analysis and to explore any knowledge gaps to be investigated. PubMed, Scopus, and CINAHL Complete databases were searched for eligible studies, and 75 articles were identified. Of these, only five studies were included as they were conducted using a nonlinear mixed-effects approach. This review found that only limited predictors for QTP pharmacokinetics were identified, with body weight being a predictor for the volume of distribution and age and γ-glutamyl transpeptidase being predictors for QTP clearance. None of the studies included elderly patients aged >65 years, and thus factors associated with aging were not investigated. Also, most of the participants in the PopPK analyses were from clinical trials which might not reflect real-world patients e.g., the impacts of polypharmacy may not be available. Moreover, while a population pharmacokinetic-pharmacodynamic model explaining QTP exposure and clinical response using the scores of the Brief Psychiatric Rating Scale is available, knowledge relevant to the relationship between exposure and QTP side effects has not been explored. Based on this limited information, future PopPK research encompassing a wide range of patient characteristics is required.

Lamotrigine and quetiapine interaction

Widespread use of the atypical antipsychotic quetiapine has resulted in the increased possibility of its interaction with other concurrently administered psychotropic agents. For example, the antiepileptic lamotrigine, commonly prescribed for the management of bipolar disorder, has a potential drug‐drug interaction with co‐administered quetiapine..

Evaluation of the Impact of the Addition of Atypical Antipsychotics to Continuous Infusion Propofol Therapy

Purpose: The administration of sedatives to critically ill patients is a common practice in intensive care units (ICU) and has been associated with negative outcomes. To mitigate this, atypical antipsychotics are utilized as adjunctive therapy. This study aims to review and quantify overall effectiveness of the atypical antipsychotics quetiapine, risperidone, and olanzapine on reduction in the amount of continuous infusion propofol utilized in the ICU. Methods: This was an observational study that took place from February 27, 2021 to December 31, 2022. The primary outcome of this study was the percentage change in average propofol infusion rate (mcg/kg/min) from baseline to the greater than 24 to 48 hours period after atypical antipsychotic initiation. Secondary outcomes included ICU length of stay, duration of mechanical ventilation, QTc interval monitoring, and continuation of the antipsychotic without a valid indication. Descriptive statistics were utilized for the statistical analysis. Results: A total of 47 patients were included in the study. The average baseline propofol rate was 31 mcg/kg/min, which reduced 8.6% to 28.35 mcg/kg/min over the 0 to 24 hours period, was reduced by 19.4% compared to baseline to a rate of 25 mcg/kg/min during the greater than 24 to 48 hours period, and finally a percent reduction of 54.2% seen during the greater than 48 to 72 hours period to a rate of 14 mcg/kg/min. Conclusions: Patients who received an adjunctive antipsychotic saw resulting propofol rate reductions of 8.6% at 24 hours, 19.4% at 48 hours, and 54.2% at 72 hours. However, research on this topic should not end here, as further investigation with higher-level study design is needed to determine the true impact of these agents for this indication.

The Atypical Antipsychotic Quetiapine Promotes Multiple Antibiotic Resistance in Escherichia coli.

Atypical antipsychotic (AAP) medication is a critical tool for treating symptoms of psychiatric disorders. While AAPs primarily target dopamine (D2) and serotonin (5HT2A and 5HT1A) receptors, they also exhibit intrinsic antimicrobial activity as an off-target effect. Because AAPs are often prescribed to patients for many years, a potential risk associated with long-term AAP use is the unintended emergence of bacteria with antimicrobial resistance (AMR). Here, we show that exposure to the AAP quetiapine at estimated gut concentrations promotes AMR in Escherichia coli after 6 weeks. Quetiapine-exposed isolates exhibited an increase in MICs for ampicillin, tetracycline, ceftriaxone, and levofloxacin. By whole-genome sequencing analysis, we identified mutations in genes that confer AMR, including the repressor for the multiple antibiotic resistance mar operon (marR), and real-time reverse transcription-quantitative PCR (RT-qPCR) analysis showed increased levels of marA, acrA, and tolC mRNAs and reduced levels of ompF mRNA in the isolates carrying marR mutations. To determine the contribution of each marR mutation to AMR, we constructed isogenic strains carrying individual mutant marR alleles in the parent background and reevaluated their resistance phenotypes using MIC and RT-qPCR assays. While marR mutations induced robust activity of the mar operon, they resulted in only modest increases in MICs. Interestingly, although these marR mutations did not fully recapitulate the AMR phenotype of the quetiapine-exposed isolates, we show that marR mutations promote growth fitness in the presence of quetiapine. Our findings revealed an important link between the use of AAPs and AMR development in E. coli. IMPORTANCE AAP medication is a cornerstone in the treatment of serious psychiatric disease. The AAPs are known to exhibit antimicrobial activity; therefore, a potential unintended risk of long-term AAP use may be the emergence of AMR, although such risk has received little attention. In this study, we describe the development of multidrug antibiotic resistance in Escherichia coli after 6 weeks of exposure to the AAP quetiapine. Investigation of mutations in the marR gene, which encodes a repressor for the multiple antibiotic resistance (mar) operon, reveals a potential mechanism that increases the fitness of E. coli in the presence of quetiapine. Our findings establish a link between the use of AAPs and AMR development in bacteria.

Effect of Quetiapine, from Low to High Dose, on Weight and Metabolic Traits: Results from a Prospective Cohort Study

The atypical antipsychotic quetiapine is known to induce weight gain and other metabolic complications. The underlying mechanisms are multifactorial and poorly understood with almost no information on the effect of dosage. Concerns were thus raised with the rise in low-dose quetiapine off-label prescription (i. e.,<150 mg/day). In this study, we evaluated the influence of quetiapine dose for 474 patients included in PsyMetab and PsyClin studies on weight and metabolic parameter evolution. Weight, blood pressure, lipid, and glucose profiles were evaluated during a follow-up period of 3 months after treatment initiation. Significant dose-dependent metabolic alterations were observed. The daily dose was found to influence weight gain and increase the risk of undergoing clinically relevant weight gain (≥7% from baseline). It was also associated with a change in plasma levels of cholesterol (total cholesterol, LDL cholesterol, and HDL cholesterol) as well as with increased odds of developing hypertriglyceridemia, as well as total and LDL hypercholesterolemia. No impact of a dose increase on blood pressure and plasma glucose level was observed. The dose-dependent effect highlighted for weight gain and lipid alterations emphasizes the importance of prescribing the minimal effective dose. However, as the effect size of a dose increase on metabolic worsening is low, the potential harm of low-dose quetiapine should not be dismissed. Prescriptions must be carefully evaluated and regularly questioned in light of side effect onset.

Gender differences in the use of atypical antipsychotics in early-onset schizophrenia: a nationwide population-based study in Brazil

BackgroundThe use of atypical antipsychotics for the treatment of schizophrenia and other mental disorders in populations under 18 years of age is increasing worldwide. Little is known about treatment patterns and the influence of gender differences, which may be a predictor of clinical outcomes. The aim of this study was to investigate gender differences in the use of atypical antipsychotics in patients with early-onset schizophrenia (EOS) assisted by the public health system in Brazil.MethodsWe conducted a cross-sectional study of outpatients with EOS aged 10 to 17 years who received at least one provision of atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine or ziprasidone) from a large Brazilian pharmaceutical assistance programme. Data were retrieved from a nationwide administrative database from 2008 to 2017.ResultsOf the 49,943 patients with EOS, 63.5% were males, and the mean age was 13.6 years old. The patients were using risperidone (62.5%), olanzapine (19.6%), quetiapine (12.4%), ziprasidone (3.3%) and clozapine (2.2%). We found gender differences, especially in the 13–17 year age group (65.1% for males vs. 34.9% for females, p < 0.001), in the use of risperidone (72.1% for males vs. 27.9% for females, p < 0.001) and olanzapine (66.5% for males vs. 33.5% for females, p < 0.001). Only in the 13 to 17 years age group were the prescribed doses of olanzapine (p = 0.012) and quetiapine (p = 0.041) slightly higher for males than for females.ConclusionsOur findings showed gender differences among patients diagnosed with EOS and who received atypical antipsychotics. More attention should be devoted to gender differences in research and clinical practice.

Effects of long-term therapy with quetiapine and olanzapine on parameters of immunity and cytokine levels in patients with schizophrenia

IntroductionThe study of effects of long-term antipsychotic therapy in patients with schizophrenia is relevant.ObjectivesTo study effects of long-term antipsychotic therapy on parameters of immunity and cytokine levels in patients with schizophrenia.MethodsWe examined 20 schizophrenic patients, who received quetiapine (group 1) and 17 - olanzapine (group 2) for more than 6 months before admission in the hospital as the main anti-recurrence therapy. Persons aged 20-63 years with length of the follow-up of the disease ≥1 year were included. The investigations included: phenotyping of immunocompetent cells into CD differentiation clusters by flow cytometry; mitogen-induced, spontaneous production of cytokines (IL2, IFN-γ, IL-4, TNF-α) were identified with use of kits for enzyme-linked immunosorbent assay (ELISA).ResultsIt was shown that patients of group 1 in comparison with group 2 were characterized by lower values of СD3- lymphocytes (p=0.049), higher values of the spontaneous production of IFN-γ (p=0.01), mitogen-induced production of IL-2 (p=0.043) and IL-4 (p=0.059). In all examined low level of mitogen-induced of IFN-γ (p=0.0001) and TNFα (p=0.002; p=0.0001), high level of spontaneous production of TNFα (p=0.001) were revealed in relation to control.ConclusionsIt was found that the acute period of schizophrenia after prolonged treatment with atypical antipsychotics is accompanied by immunological imbalance and dysregulation of the cytokine system. More severe immune disorders when hospitalized during the exacerbation period were revealed in patients who had been receiving antipsychotic therapy with the atypical antipsychotic quetiapine for a long time. This can be associated with the features of the mechanism of action of atypical antipsychotics.DisclosureNo significant relationships.

Informed Consent: Do atypical antipsychotics trigger manic switching in patients with bipolar I disorder?

A 22-year-old newly diagnosed patient with bipolar is discussing with her doctor the safety of starting an atypical antipsychotic as part of her treatment plan for depression. The patient was recently diagnosed with bipolar disorder after years of ups and downs making school and her relationship especially difficult. After seeking out a university student health psychiatrist for a severe depressive episode she was prescribed an antidepressant, which within a few weeks triggered a manic episode that required hospitalization. Since that time she has been compliant with her medications but has fallen into another depressive episode. Her psychiatrist encourages her to begin taking the atypical antipsychotic quetiapine because it may help with her current mood. Given her experience with antidepressants she is apprehensive. She asks, is it possible that a medication like quetiapine could trigger another manic episode?

The atypical antipsychotic quetiapine induces hyperlipidemia by activating intestinal PXR signaling.

Quetiapine, one of the most prescribed atypical antipsychotics, has been associated with hyperlipidemia and an increased risk for cardiovascular disease in patients, but the underlying mechanisms remain unknown. Here, we identified quetiapine as a potent and selective agonist for pregnane X receptor (PXR), a key nuclear receptor that regulates xenobiotic metabolism in the liver and intestine. Recent studies have indicated that PXR also plays an important role in lipid homeostasis. We generated potentially novel tissue-specific PXR-KO mice and demonstrated that quetiapine induced hyperlipidemia by activating intestinal PXR signaling. Quetiapine-mediated PXR activation stimulated the intestinal expression of cholesterol transporter Niemann-Pick C1-Like 1 (NPC1L1) and microsomal triglyceride transfer protein (MTP), leading to increased intestinal lipid absorption. While NPC1L1 is a known PXR target gene, we identified a DR-1-type PXR-response element in the MTP promoter and established MTP as a potentially novel transcriptional target of PXR. Quetiapine's effects on PXR-mediated gene expression and cholesterol uptake were also confirmed in cultured murine enteroids and human intestinal cells. Our findings suggest a potential role of PXR in mediating adverse effects of quetiapine in humans and provide mechanistic insights for certain atypical antipsychotic-associated dyslipidemia.

Effects of the Atypical Antipsychotic Quetiapine on the Immune Response in Aggressive Mice in a Model of Social Stress

Chronic (10 days)administration of the atypical antipsychotic quetiapine (3.75 mg/kg) induced significant suppression of the IgM immune response in mice with aggressive behavior formed as a result of prolonged (14 days in CBA mice, 20 days in C57BL/6J mice) confrontations and in animals with unaltered psychoemotional status. The immunosuppressive action of quetiapine was independent of the genotype of the mice and the route (i.p. or p.o.) and scheme (single or repeated) of administration. Possible serotonin (5-HT) and dopamine (DA) receptor mechanisms of the immunomodulatory effects of quetiapine are discussed.

Reduced clearance of venlafaxine in a combined treatment with quetiapine

Venlafaxine and the atypical antipsychotic quetiapine are often administered concomitantly. Both drugs share several metabolic hepatic pathways. However, pharmacokinetic interactions between venlafaxine and quetiapine have not been studied yet.A therapeutic drug monitoring database containing serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN) was analyzed. Two groups of patients were compared: venlafaxine monotherapy V0 (n = 153) and co-medication with quetiapine, VQUE (n = 71). Serum concentrations of VEN, ODVEN, and active moiety, AM (VEN + ODVEN), metabolite to parent compound ratio (ODVEN/VEN) and dose adjusted serum concentrations were compared using non-parametrical tests without information on CYP2D6 genotype.The two groups did not differ in terms of the daily dosage of venlafaxine, age, or sex. Median serum concentrations in the quetiapine group showed significantly, 15.8% and 29.3% higher values for AM and ODVEN (p = 0.002, Cohen's d = 0,41; p = 0.003, d = 0,44), respectively. Dose adjusted serum concentrations of active moiety and ODVEN revealed comparable differences (p = 0.038, d = 0,32; p = 0.015, d = 0,28) with significantly higher values in the co-medicated group.Significantly higher values for ODVEN and AM suggest a reduced clearance of ODVEN and active moiety when quetiapine is co-administered. This may be a consequence of a reduced metabolism of venlafaxine to the inactive metabolite N-desmethylvenlafaxine via CYP3A4, the main metabolizing enzyme for quetiapine, and a shift towards a higher proportion of the active metabolite ODVEN. Therapeutic drug monitoring is recommended in the case of co-medication to ensure clinical efficacy and patient safety. Although the increase of AM is moderate, we consider it relevant for clinicians given the prevalence of concomitant medication of quetiapine and venlafaxine.

“I love having benzos after my coke shot”: The use of psychotropic medication among cocaine users in downtown Montreal

BackgroundCocaine abuse is a major public health issue due to its role in the HIV and hepatitis C virus (HCV) epidemics in North America. A significant area of concern among people who use cocaine (PWUC), injected or smoked, is their frequent misuse of prescription drugs, particularly psychotropic medication (PM), such as tranquilizers, sedatives, stimulants, and antipsychotics. This paper aims to describe and understand practices of PM use among PWUC in downtown Montreal. MethodEthnographic methods including participant observation and semi-structured interviews were used in an iterative manner. ResultsTwo thirds of the 50 participants were male. They ranged in age from 20 to 60 and most were homeless. A significant proportion of them reported polydrug use patterns that included frequent concomitant opioid use (heroin and/or prescription opioids (PO)). Benzodiazepine-based tranquilizers and the atypical antipsychotic quetiapine were the most frequently used PM. Routes of PM administration were oral, nasal and, to a lesser degree, intravenous. Five main PM use practices were identified: 1) “downers” from cocaine high (benzodiazepines and quetiapine); 2) enhancers of heroin/PO effects (benzodiazepines); 3) reducers or suppressors of heroin/PO withdrawal symptoms (benzodiazepines); 4) enablers of a different type of “trip” (benzodiazepines); and 5) treatment for mental and physical problems (benzodiazepines and quetiapine). ConclusionPM use practices showed several complementary functions that PM fulfill in a context of polydrug use. The soothing and stimulating effects of PM reinforce the patterns of drug use among participants, posing various risks including overdose, HIV/HCV transmission, PM dependence and accidents. The results highlight the need for clinicians to assess clients’ substance use patterns when prescribing PM and to question PWUC about PM use. The findings also underline certain unmet service needs in relation to overdose, HIV/HCV and mental health prevention/treatment among cocaine users.

Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study)

BackgroundApproximately 30–50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group.MethodsThe Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects.DiscussionThe trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies.Trial registrationISRCTN registry: ISRCTN16387615, registered 28 February 2016. ClinicalTrials.gov: NCT03004521, registered 17 November 2016.

The preclinical discovery and development of quetiapine for the treatment of mania and depression

ABSTRACTIntroduction: Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood.Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system.Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP’s anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.

Influence of single-dose quetiapine on fear network activity – A pharmaco-imaging study

ObjectiveAnxiety disorders are among the most frequent psychiatric disorders. Current treatment guidelines recommend antidepressants, the calcium modulator gabapentin, and benzodiazepines as pharmacological treatments. However, delayed onset of action precludes the use of antidepressants as an acute treatment, while benzodiazepines can be recommended only as an emergency treatment due to their inherent risk of dependence. Therefore, an alternative pharmacological agent with acute efficacy is needed. Preliminary evidence points towards possible anxiolytic properties of the atypical antipsychotic quetiapine. The goals of this study were to test the acute anxiolytic properties of quetiapine in patients suffering from arachnophobia in a challenge paradigm, and to assess the effects of quetiapine on the central nervous fear network. MethodsIn a randomized, double-blind, placebo-controlled proof-of-concept study, n=58 arachnophobic patients underwent an fMRI scan while looking at phobia-related and neutral stimuli. Subjective anxiety was evaluated retrospectively in questionnaires. ResultsThe functional imaging data revealed that patients showed stronger amygdala activation to phobia-related than to neutral stimuli. However, no effect of quetiapine on fear network activity was detected. Further, on questionnaire measures, quetiapine significantly reduced somatic anxiety symptoms, but had no effect on general psychological anxiety. ConclusionViewing phobic pictures resulted in a robust amygdala activation in arachnophobic patients. Quetiapine seems to have no influence on activation in anxiety-related brain areas but appears to reduce acute somatic anxiety symptoms in patients with specific phobia. The central nervous correlates of the anxiolytic effects of quetiapine remain to be clarified in future studies.

Teratogenic Potential of Atypical Antipsychotic Drugs, Quetiapine and Aripiprazole in Rats

Teratogenic Potential of Atypical Antipsychotic Drugs, Quetiapine and Aripiprazole in Rats

Comparative evaluation of effect of Olanzapine and Quetiapine on body weight and body mass index (BMI) in psychotic patients at a tertiary care teaching hospital in Nepal

Background: Atypical antipsychotics are currently the most frequently prescribed class of drugs for psychotic illness. Weight gain and obesity are more problematic with atypical antipsychotics than with typical antipsychotics. Since weight gain contributes to non-compliance with treatment and may lead to medical morbidity, it is important to know and compare the weight gain associated with the use of most commonly prescribed atypical antipsychotics olanzapine and quetiapine at our set up. Objective: Comparative evaluation of changes in body weight and body mass index (BMI) of psychotic patients treated with olanzapine and quetiapine in a tertiary care teaching hospital in Nepal. Materials and Methods: This study was conducted in the Department of Neuropsychiatry, Nepalgunj Medical College & Teaching Hospital, Nepalgunj, for a period of 6 months between July to December 2014. A total of 40 patients suffering from psychotic disorders were included in the study and randomly allocated in two groups: Group-I (20 patients) received tablet olanzapine (10–15 mg/day) and Group-II (20 patients) received tablet quetiapine (200–600 mg/day). Patients were followed upto 6 weeks. All values were expressed in mean ± SD. The changes in body weight and BMI were measured at 0 and 6 weeks. Statistical analysis was done by using paired and unpaired T-test. p value < 0.05 was considered significant. Result: Mean weight in group receiving olanzapine at 0 and 6 weeks was 54.59±6.72 kg and 58.75±6.76 kg, respectively and in quetiapine group was 55.37±5.63 kg and 57.18±5.93 kg, respectively (p 0.05). Conclusion: Both olanzapine and quetiapine showed increase in body weight and BMI in psychotic illness patients during the study period. But intergroup comparison revealed no significant difference between the groups.

Delusional Disorder in a Patient with Corpus Callosum Agenesis

Agenesis of corpus callosum is rare and associated neuropsychiatric abnormalities reported are epilepsy, Asperger's syndrome, learning problems, depression, schizophrenia, conduct disorder and conversion symptoms. Schizophrenia is the most common psychiatric disorder reported among corpus callosum agenesis. We report a rare case of delusional disorder with corpus callosum agenesis and seizure disorder. The patient presented with delusions of persecution towards younger brother and mother, disturbed sleep and reduced appetite. She had a history of seizure disorder of ten years duration, which was controlled with carbamazepine and levetiracetam. Neurological examination was normal. On MRI, corpus callosum agenesis was detected. She was put on an atypical antipsychotic quetiapine to which her psychiatric symptoms responded completely.

An effect of quetiapine on the immune system of patients with schizophrenia

To study an effect of the atypical antipsychotic quetiapine on the immune system of patients with schizophrenia with account for treatment efficacy. Quetiapine was administered to 27 patients diagnosed with residual schizophrenia (F20.5) for 6 weeks in dose 200-400 mg/day; dynamic of clinical symptoms was evaluated with PANSS и CGI scales before administration of quetiapine and by week 6 of the treatment. Along with clinical assessments, immune indices were determined. At the end of week 6 of treatment, statistically significant changes of PANSS psychopathological symptoms were noted. According to CGI scale, patients were divided into group 1 with high treatment efficacy (n=17) and group 2 with the low efficacy (n=10). Significant between-group differences before treatment were as follows: the decreased number of lymphocytes of CD3+- CD16+-phenotypes, increased number of HLADR+-lymphocytes and IgA level in group 2. The quetiapine therapy led to the positive dynamic of phagocytosis indices, CD16+-lymphocytes, decrease in the level of IgA. Possible predictors of treatment efficacy were found including the number of mature T (CD3+) lymphocytes, CD16+ natural killers, HLADR+ lymphocytes and IgA concentrations.

Comorbid bipolar disorder and obsessive-compulsive disorder in children and adolescents: Treatment implications.

Apparent comorbidity between bipolar disorder (BD) and obsessive–compulsive disorder (OCD) is a common condition in psychiatry with higher prevalence rates in youths (23.2%, 95% confidence interval [CI] = [11.5%, 41.3%]) compared to adults (13.56%, 95% CI = [10.4%, 16.25%]) (Amerio et al., 2015). The meaning of this comorbidity has not been clarified yet. The treatment of BD-OCD patients remains a great challenge since the gold standard for one disease (serotonin reuptake inhibitors [SRIs] for OCD) can worsen the other (antidepressants can cause mania and/or more mood episodes in BD; Amerio et al., 2014a). The literature on pharmacologic or psychotherapeutic approaches especially in pediatric BD-OCD patients is limited. Therefore, we updated our recent systematic review (Amerio et al., 2014b) and focused specifically on the treatment of BD-OCD comorbidity in children and adolescents. Studies were identified by searching the electronic databases MEDLINE, EMBASE and PsycINFO. We combined the search strategy of free text terms and exploded MeSH headings for the topics of BD, OCD and treatment combined as follows: ((((((‘Therapeutics’[Mesh]) OR treatment*) OR therap*) OR pharmacotherap*) OR psychotherap*)) AND (((((((((‘Bipolar Disorder’[Mesh]) OR Bipolar disorder) OR BD) OR Bipolar) OR Manic depressive disorder) OR Manic depressive) OR Manic)) AND ((((‘Obsessive-Compulsive Disorder’ [Mesh]) OR OCD) OR Obsessivecompulsive) OR Obsessive-compulsive disorder))). Studies published in English through 31 August 2015 were included. Further studies were retrieved from reference listing of relevant articles and consultation with experts in the field. Seven studies were selected (Table 1). In all selected studies, BD-OCD patients received mood stabilizers (lithium, divalproex sodium). In the largest study, 42.1% of comorbid patients required a combination of multiple mood stabilizers and 10.5% a combination of mood stabilizers with atypical antipsychotics (quetiapine, risperidone, aripiprazole). Addition of antidepressant (clomipramine) to mood stabilizers led to clinical remission of both conditions in only one study. In other cases, antidepressants (escitalopram) seemed prone to cause more manic/hypomanic episodes in BD-OCD than in non-comorbid patients. The evidence so far on BD-OCD nosology supports the view that the majority of cases of comorbid BD-OCD are in fact BD cases (Amerio et al., 2014a). Osler’s view that medicine should be treatment of diseases, not of symptoms, is consistent with the approach of mood stabilization as a first objective in apparent BD-OCD patients, as opposed to immediate treatment with SRIs.