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1.
Expert Opin Pharmacother ; 21(3): 253-260, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31957501

RESUMO

Introduction: Lurasidone has been approved in the United States as a monotherapy and adjunct for acute bipolar I depression, as well as an antipsychotic for patients with schizophrenia.Areas covered: Herein, the authors review the pharmacodynamics and pharmacokinetics of lurasidone as well and the major randomized clinical trials. The authors also provide their expert opinion.Expert opinion: Lurasidone has not been studied in patients with mania or bipolar psychosis. It has been studied, both as a monotherapy and adjunctive treatment to lithium or valproate, in acute depression and in prevention of recurrence of any mood episode in patients with bipolar disorder initially treated for bipolar depression or mania. It is approved in the United States for acute bipolar I depression. It has clinically meaningful treatment effect sizes for improvement in depression compared to placebo (0.51 monotherapy, 0.34 adjunct). The number needed to treat (NNT) for response with monotherapy was 5 (for both lower and higher dose groups), and for remission was 6 and 7 (for lower dose and higher dose groups, respectively); the NNT for adjunctive therapy was 7. It has not demonstrated efficacy in relapse prevention when added to a mood stabilizer but is safe in combination with other medications.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Cloridrato de Lurasidona/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Ácido Valproico/uso terapêutico
2.
Artigo em Russo | MEDLINE | ID: mdl-31793547

RESUMO

Antipsychotics are used in the treatment of schizophrenia and other psychoses, as well as bipolar disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and specific types of personality disorders. Due to better tolerability, as well as some advantages of the pharmacological profile, the second-generation antipsychotics are preferred in clinical practice. A special place among antipsychotics is taken by sulpiride, which shows the ability to improve the condition of patients with different types of mental disorders as well as with internal diseases.


Assuntos
Antipsicóticos , Transtorno Bipolar , Transtorno Obsessivo-Compulsivo , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Humanos , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico
3.
J Opioid Manag ; 15(5): 362-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849027

RESUMO

OBJECTIVE: To assess the efficacy of buprenorphine augmentation in treatment of psychotic symptoms in bipolar disorder type I. DESIGN: Bipolar type I patients with manic or depressive episodes and psychotic feature and with opioid dependency comorbidity were randomly included and allocated. Both groups of buprenorphine (4 or 6 mg/d) and placebo were also treated with enough dosages of sodium valproate and risperidone. Psychosis as primary outcome and depressive and manic symptoms as secondary outcome were assessed at baseline and after 1 and 2 weeks. Data were analyzed through t test and repeated measure ANOVA. RESULTS: Twenty-four patients remained in each group. Both groups displayed significant reduction in psychotic, depressive, and manic symptoms during the 2 weeks of study, although there was not any significant difference between them. CONCLUSIONS: Buprenorphine did not add any efficacy to usual treatment of psychotic episodes of bipolar, although did not aggravate psychiatric symptoms.


Assuntos
Antipsicóticos , Transtorno Bipolar , Buprenorfina , Transtornos Psicóticos , Analgésicos Opioides , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Buprenorfina/uso terapêutico , Método Duplo-Cego , Humanos , Transtornos Psicóticos/tratamento farmacológico , Resultado do Tratamento
4.
Presse Med ; 48(11 Pt 1): 1306-1318, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31732367

RESUMO

CONTEXT: Bipolar disorder (BD) is a severe and recurrent mood disorder. It is characterized by episodic changes in mood and energy/activity levels that are increased during mania/hypomania or decreased during depression. Recurrent mania (RM) is a mood disorder, which would be defined by at least two manic/hypomanic without depressive episodes. Despite a rich body of clinical descriptions, RM is still not integrated into the latest editions of disease classifications and continues to be subsumed under BD in clinical practice. OBJECTIVES: We conducted a systematic review of the literature to pool data about RM prevalence within BD groups, identify differences between RM and BD and develop reliable knowledge about specificities of RM. Furthermore, we sought to identify the methodological bias inherent to RM studies. METHOD: Relevant publications were identified by a systematic search of PubMed, Embase, ScienceDirect and PsychInfo databases according to PRISMA criteria, with no limitation of date. The following MESH terms were used: (mania OR manic) AND (unipolar) NOT (depress*) OR ("unipolar mania" OR "unipolar manic" NOT "depress*"). RESULTS: Twenty-three (23) of 186identified studies met eligibility criteria for our systematic review. The total sample included 1118RM subjects among 4796BD subjects. The weighted mean of RM prevalence was 23.2%. Compared to BD, RM was characterized by a predominance of men, an earlier age at illness onset, less rapid cycles and seasonal variations, longer manic episodes, less specific clinical features (suicide attempts, anxious disorders, catatonic symptoms, irritability, hyperactivity, racing thoughts), less family history of depression, more addictive comorbidities and worse response to lithium prophylaxis (P<0.05). However, many studies failed to replicate these significant differences. LIMITS: RM studies were mainly retrospective. The major bias of RM studies were the lack of consensus on the defining criteria for RM and the risk of unreported depressive episodes, both in charts that were reviewed in retrospective studies and in prospective studies with insufficient follow-up duration. CONCLUSION: Although the literature on RM remains sparse, many authors agree that RM should be distinguished from BD. RM would concern almost 1 in 4 BD patients. Furthermore, several clinical variables could differentiate this mood disease from BD and may orient the specific therapeutic choice. However, clinical criteria are still not reliable enough to make a diagnosis of RM. Further studies are required to replicate the results of existing studies and to adjust for the effect of methodological biases.


Assuntos
Transtorno Bipolar/diagnóstico , Depressão/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Depressão/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Compostos de Lítio/uso terapêutico , Masculino , Prevalência , Estudos Prospectivos , Recidiva , Estudos Retrospectivos
5.
Expert Opin Pharmacother ; 20(17): 2063-2072, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31644326

RESUMO

Introduction: Cariprazine, a D3-preferring, dopamine D2/D3 partial agonist, has efficacy in treating both acute phases of bipolar I disorder (BD-I). It has been approved by the FDA for treatment of acute manic, mixed and depressive episodes associated with BD-I.Areas covered: In this review, the authors discuss the unique pharmacological properties and clinical efficacy profile of cariprazine, and their relevance in the context of routine clinical decision-making for BD-I. For the purpose of this review, the authors searched for clinical trials in BD published in the PubMed, Web of Science, Embase and PsychInfo databases as well as for studies registered in the ClinicalTrials.gov database.Expert opinion: Based on evidence from RCTs in manic and mixed episodes, cariprazine in a dose-range of 3-12 mg is effective for treating acute mania and mixed states associated with BD-I. Importantly, evidence from placebo-controlled trials in bipolar depression suggests that cariprazine is also effective as a monotherapy in treating acute bipolar depression in doses of 1.5-3 mg/day. It is overall well tolerated; however, clinicians need to monitor patients for akathisia.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Piperazinas/uso terapêutico , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Agonistas de Dopamina/efeitos adversos , Meia-Vida , Humanos , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Resultado do Tratamento
6.
Psychiatr Danub ; 31(Suppl 3): 554-560, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488790

RESUMO

Bipolar depression (BD) is among the most severe psychiatric disorders. A significant number of patients do not achieve an entirely symptom-free state and experience residual sub-syndromal depression. Most of the treatment options approved for bipolar depression give no rapid symptom improvement. Ketamine is an anaesthetic medication that acts as an antagonist of the NMDA receptor and has antidepressant potential. Due to its unique way of action, ketamine seems to be crucial for the treatment of anhedonia. This review paper aims to provide an overview of the efficacy of ketamine infusions in bipolar depression with a focus on anhedonia Literature suggests that intravenous ketamine 0.5 mg/kg over 40 min weekly could be useful in the treatment of bipolar depression with prominent anhedonia, but there is still a small number of studies that examine the efficacy of ketamine infusions in BD. In conclusion, ketamine should be considered as a valuable treatment option for patients with BD and anhedonia.


Assuntos
Anedonia/efeitos dos fármacos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Depressão/complicações , Depressão/tratamento farmacológico , Ketamina/farmacologia , Ketamina/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Bipolar/complicações , Humanos
7.
Psychiatr Danub ; 31(Suppl 3): 595-603, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488797

RESUMO

BACKGROUND: Bipolar disorder is a mental illness characterised by periods of elevated mood alternating with periods of depression. Long-term relapse prevention in bipolar disorder is challenging, with a significant number of patients relapsing following the initial stabilisation of mood. Initial treatment of the condition is complex and usually occurs in secondary care. Whilst there is no known cure for bipolar disorder, several therapies have been found to be effective in both managing acute episodes and sustaining long-term remission. The key pharmacological therapies in bipolar disorder are lithium salts, antiepileptics and antipsychotics and these will be the focus of this review. AIM: This review seeks to outline the key common pharmacological therapies used in the treatment and relapse prevention of this condition. METHODS: A MEDLINE search was performed, and the available literature was subsequently analysed, including meta-analyses, reviews and original clinical trials. RESULTS: Management strategies can be subdivided into treating acute presentations of mania and depression and maintaining long-term remission. The extensive side effect profile of several antipsychotics means that there are certain patient groups for whom they may be intolerable or contraindicated. Lithium emerges as a highly efficacious maintenance therapy but retains the burden of therapeutic drug monitoring. Antiepileptics play a crucial role in maintaining remission but are linked to serious, albeit rare, side effects. CONCLUSION: Despite the efficacy of the medications discussed in this article, their underlying mechanisms of action remain to be fully elucidated. Nonetheless, these key therapies continue to be essential tools in the management of bipolar disorder.


Assuntos
Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/uso terapêutico , Antimaníacos/uso terapêutico , Humanos
8.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373471

RESUMO

Lithium is a largely used and effective therapy in the treatment of bipolar disorder. Its toxic effects on kidneys are mostly diabetes insipidus, hyperchloremic metabolic acidosis and tubulointerstitial nephritis. Also, a correlation between lithium and minimal change disease has sometimes been described. We report here the case of a patient with severe bipolar disorder on lithium therapy who, without any pre-existing nephropathy, developed nephrotic syndrome and AKI with histopathologic findings pointing to minimal change disease. The patient was treated with symptomatic therapy; the discontinuation of lithium therapy resulted in the remission of AKI and of the nephrotic syndrome, thus suggesting a close relationship between lithium and minimal change disease.


Assuntos
Antimaníacos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Compostos de Lítio/efeitos adversos , Nefrose Lipoide/induzido quimicamente , Síndrome Nefrótica/induzido quimicamente , Lesão Renal Aguda/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/patologia , Suspensão de Tratamento
9.
Expert Opin Drug Saf ; 18(10): 893-913, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364895

RESUMO

Introduction: The use of antidepressants (AD) in the treatment of bipolar depression is one of the most controversial issues in psychopharmacology. For some, AD are useful, but, for others, they should never be used in bipolar depression. Areas covered: This review examines published clinical studies on the use of ADs in bipolar depression, addressing their clinical efficacy and the occurrence of side effects, manic switches, cycle acceleration, and suicidal behavior. Meta-analyzes and review articles on the subject are also discussed. Expert opinion: Approved therapeutic options for bipolar depression are associated with not very high response rates and a high incidence of adverse effects. Patients with bipolar depression present very heterogeneous responses to the use of ADs. Some improve significantly, while others, especially those with concomitant manic symptoms, have had previous episodes of treatment-emergent mania or are rapid cyclers, exhibit manic switches or cycle acceleration. The authors conclude that the real question is not whether ADs should or should not be used in bipolar depression, but which patients benefit from these drugs and which ones are impaired. The concept of bipolar spectrum and a dimensional approach on bipolar/unipolar distinction may be useful for understanding the heterogeneity of responses to ADs.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Seleção de Pacientes , Antidepressivos/efeitos adversos , Transtorno Bipolar/fisiopatologia , Humanos , Resultado do Tratamento
10.
BMC Neurol ; 19(1): 174, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31325958

RESUMO

BACKGROUND: Tardive dyskinesia (TD) is a serious, often irreversible movement disorder caused by prolonged exposure to antipsychotics; identifying patients at risk for TD is critical to preventing it. Predictive models for the occurrence of TD can improve patient monitoring and inform implementation of counteractive interventions. This study aims to identify risk factors associated with TD and to develop a model using a retrospective data analysis to predict the incidence of TD among patients taking antipsychotic medications. METHODS: Adult patients with schizophrenia, major depressive disorder, or bipolar disorder taking oral antipsychotics were identified in a Medicaid claims database (covering six US states from 1997 to 2016) and divided into cohorts based on whether they developed TD within 1 year after the first observed claim for antipsychotics. Patient characteristics between cohorts were compared, and univariate Cox analyses were used to identify potential TD risk factors. A cross-validated version of the least absolute shrinkage and selection operator regression method was used to develop a parsimonious multivariable Cox proportional hazards model to predict diagnosis of TD. RESULTS: A total of 189,415 eligible patients were identified. Potential TD risk factors were identified based on the cohort analysis within a sample of 151,280 patients with at least 1 year of continuous eligibility. The prediction model had a clinically meaningful concordance of 70% and was well calibrated (P = 0.32 for Hosmer-Lemeshow goodness-of-fit test). Age (hazard ratio [HR] = 1.04, P < 0.001), diagnosis of schizophrenia (HR = 1.99, P < 0.001), antipsychotic dosage (up to 100 mg/day chlorpromazine equivalent; HR = 1.65, P < 0.01), and comorbid bipolar and related disorders (HR = 1.39, P < 0.01) were significantly associated with an increased risk of TD. Other potential risk factors included history of extrapyramidal symptoms (HR = 1.35), other movement disorders (parkinsonism, HR = 1.43; bradykinesia, HR = 1.44; tremors, HR = 2.12, and myoclonus, HR = 2.33), and diabetes (HR = 1.13). A modest reduction in the risk of TD was associated with the use of second-generation antipsychotics (HR = 0.85) versus first-generation drugs. CONCLUSIONS: This study identified factors associated with development of TD among patients taking antipsychotics. The prediction model described herein can enable physicians to better monitor patients at high risk for TD and recommend appropriate treatment plans to help maintain quality of life.


Assuntos
Antipsicóticos/efeitos adversos , Discinesia Tardia/induzido quimicamente , Adulto , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Esquizofrenia/tratamento farmacológico
12.
Psychiatr Pol ; 53(2): 223-244, 2019 Apr 30.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-31317955

RESUMO

OBJECTIVES: Antiepileptic drugs (AEDs), which are commonly used as a treatment for acute phases and prevention of relapses in bipolar disorder (BD) and schizoaffective disorder (SAD), have been often associated to adverse outcomes in pregnancy and major congenital malformations (MCM). We aimed to summarize available evidence assessing these outcomes when AEDs are used in pregnant women with BD and/or SAD. METHODS: We searched four databases from inception to 18 January, 2019. We included peer-reviewed observational studies on the use of AEDs in pregnant women with BD or SAD. We excluded studies not reporting data on BD or SAD, not specifying the AED or not assessing pregnancy outcomes or MCM. RESULTS: The pooled records amounted to 2,861. After duplicate removal and inclusion/exclusion criteria application, we included 9 observational studies assessing patients with BD and SAD. The AEDs evaluated were lamotrigine (LTG), valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPR) and gabapentin (GBP). VPA and CBZ were the AED most commonly associated to MCM. LTG showed the best safety profile. Higher rates of complications during pregnancy were observed in treated and untreated women with BD compared to healthy controls. CONCLUSIONS: AEDs may produce adverse outcomes in pregnancy and MCM in children of pregnant women with BD or SAD, showing higher risks at higher doses. LTG could be considered in this type of patients, given the low rate of adverse events. VPA and CBZ use should be avoided during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Transtornos Psicóticos/tratamento farmacológico , Adulto , Transtorno Bipolar/tratamento farmacológico , Carbamazepina/efeitos adversos , Feminino , Humanos , Lactente , Gravidez , Resultado da Gravidez
13.
Psychiatr Pol ; 53(2): 263-276, 2019 Apr 30.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-31317957

RESUMO

In the article, the recommendations of the Polish Psychiatric Association regarding pharmacological treatment of women with bipolar disorder during pregnancy and postpartum period were presented. The issue pertains to every twentieth woman wanting to get pregnant. Before planned pregnancy, it is advisable to obtain a several-month stabilization of psychiatric state, to establish treatment with one mood-stabilizing drug (except for valproate and carbamazepine) or gradual discontinuation of drugs in case of mild course of illness and lack of recurrences in recent two years. In the first trimester of pregnancy, the dose of the mood-stabilizing drug should be reduced (lithium carbonate to 500 mg/day). Depression during pregnancy can be treated with quetiapine or lamotrigine or with antidepressant drug added to a mood-stabilizing drug. Atypical antipsychotics drugs with mood-stabilizing properties can be used in case of (hypo) manic or mixed states. Following the delivery, it is advisable to introduce a moodstabilizing drug as soon as possible to prevent postpartum psychiatric disturbances. In the treatment of postpartum depression, quetiapine can be used or an antidepressant drug added to a mood-stabilizer. Considering breastfeeding, it should be remembered that the infant/maternal ratio of serum drug concentration is low for valproate, olanzapine, quetiapine, sertraline and paroxetine, and high for lithium and lamotrigine. In the case of postpartum psychosis, a hospitalization and antipsychotic treatment are needed.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/prevenção & controle , Guias de Prática Clínica como Assunto , Complicações na Gravidez/prevenção & controle , Transtorno Bipolar/tratamento farmacológico , Feminino , Humanos , Polônia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Sociedades Médicas
14.
Psychiatr Danub ; 31(2): 157-161, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31291219

RESUMO

Schizophrenia and bipolar disorders are serious psychiatric disorders with substantial health risks. Asenapine is a new second-generation antipsychotic, available as a sublingual tablet, approved in Europe for the treatment of moderate-to-severe manic episodes in adults, and in US for manic or mixed episodes of bipolar I disorder in adults and adolescents. In this review, we searched the available literature to appreciate the role of asenapine in the management of psychiatric conditions such as bipolar disorders and schizophrenia and describe its mechanism of action, efficacy and tolerability. Asenapine has demonstrated efficacy in the management of bipolar disorders and schizophrenia, while a possible role in the management of borderline personality disorder and agitation needs further research. Asenapine has favourable side effects profile and combining with other pharmacological treatment in post-traumatic stress disorder has shown promising results. Asenapine fulfils important requirements of efficacy and tolerability as an anti-psychotic. These findings should support psychiatrists and pharmacists in the care of their patients while on asenapine.


Assuntos
Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Transtorno da Personalidade Borderline/tratamento farmacológico , Europa (Continente) , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Estados Unidos
15.
Expert Opin Drug Metab Toxicol ; 15(8): 619-631, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31271537

RESUMO

Introduction: The comorbidity between obsessive-compulsive disorder (OCD) and bipolar disorders (BDs) is a frequent and severe condition characterized by a chronic course, high suicidal risk and tendency towards chronicity and treatment non-response. It represents a real challenge to psychiatrists, while requiring a careful and appropriate therapeutic management consisting in the combination of serotonergic antidepressants (ADs), such as serotonin reuptake inhibitors (SRIs), with mood stabilizers. This combination, like any other, raises the problems related to drug interactions that may lead to pharmacokinetic and pharmacodynamic changes, resulting in the modification of the pharmacologic effect and safety profile of a given compound. Areas covered: The aim of the present paper was to review the literature on the pharmacokinetic and pharmacodynamic changes resulting from the interactions of the different drugs prescribed in the OCD-BD comorbidity. Expert opinion: The literature data on pharmacokinetic and pharmacodynamic changes due to interactions of drugs commonly prescribed in the treatment of the OCD-BD comorbidity are extremely limited, and the information is inferred by findings gathered in psychiatric patients suffering from other disorders. This represents a gap in psychopharmacology that should be filled by specific studies on this important topic.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Antimaníacos/administração & dosagem , Antimaníacos/farmacocinética , Antimaníacos/farmacologia , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacocinética , Antipsicóticos/farmacologia , Transtorno Bipolar/complicações , Interações de Medicamentos , Humanos , Transtorno Obsessivo-Compulsivo/complicações , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/farmacocinética , Inibidores de Captação de Serotonina/farmacologia
16.
Int J Clin Pract ; 73(10): e13397, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31355510

RESUMO

OBJECTIVE: Cariprazine is an oral antipsychotic approved in the US for the treatment of schizophrenia, acute bipolar mania, and most recently, bipolar depression. The aim of this systematic review is to describe the efficacy, tolerability and safety of cariprazine for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults. DATA SOURCES: The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms "cariprazine" AND "bipolar" AND "depression," and by also querying the Web of Science commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information. STUDY SELECTION: Double-blind placebo-controlled studies in adults with bipolar depression. DATA EXTRACTION: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were calculated from the available study reports and other sources of information. DATA SYNTHESIS: Cariprazine differs from other antipsychotics in that it has a 10-fold higher affinity for dopamine D3 receptors than for D2 receptors. Cariprazine's principal active metabolite, didesmethyl-cariprazine (DDCAR), has a half-life of 1-3 weeks and at steady state DDCAR is the predominant circulating moiety. Four double-blind placebo-controlled studies of cariprazine for bipolar depression were found of which three were considered positive and provided data on efficacy; all four studies were used to assess tolerability. Rates of treatment response, defined by a ≥50% reduction from baseline on the Montgomery-Asburg Depression Ratting Scale (MADRS) total score at study endpoint, for the approved doses of 1.5 and 3.0 mg/d (pooled) vs placebo were 46.3% vs 35.9% (NNT 10, 95% CI 7-21). Corresponding rates for remission (defined as MADRS total score ≤10 at endpoint) were 30.2% vs 20.9% (NNT 11, 95% CI 8-22). Discontinuation rates because of an adverse event (AE) were 6.7% for cariprazine (all doses pooled) vs 4.8% for placebo (NNH 51, ns). Product labelling lists the most common AEs as nausea, akathisia, restlessness and extrapyramidal symptoms. Patients receiving cariprazine 3.0 vs 1.5 mg/d were more likely to experience AEs and discontinue the trials because of an AE. CONCLUSIONS: Cariprazine is the fourth agent approved for bipolar depression in the US. The likelihood to experience a benefit (response or remission) is substantially greater than the likelihood to encounter a discontinuation because of an AE. Direct, head-to-head comparisons with the other approved choices for bipolar depression in the "real world" are needed.


Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Método Duplo-Cego , Seleção de Pacientes , Piperazinas/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Resultado do Tratamento
17.
Acta Neuropsychiatr ; 31(4): 193-201, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31159897

RESUMO

OBJECTIVE: Bipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients. The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions. Several studies ranging from clinical to molecular, as well as anecdotal evidence, have placed a spotlight on the potential role of the ECS in the pathophysiology of BD. In this perspective, we present advantages and disadvantages of cannabis use in the management of illness course of BD and provide mechanistic insights into how this system might contribute to the pathophysiology of BD. RESULTS: We highlight the putative role of selective cannabinoid receptor 2 (CB2) agonists in BD and briefly discuss findings which provide a rationale for targeting the ECS to assuage the symptoms of BD. Further, data encourage basic and clinical studies to determine how cannabis and cannabinoids (CBs) can affect mood and to investigate emerging CB-based options as probable treatment approaches. CONCLUSION: The probable role of the ECS has been almost neglected in BD; however, from data available which suggest a role of ECS in mood control, it is justified to support conducting comprehensive studies to determine whether ECS manipulation could positively affect BD. Based on the limited available data, we suggest that activation of CB2 may stabilise mood in this disorder.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Canabinoides/uso terapêutico , Cannabis , Endocanabinoides/fisiologia , Endocanabinoides/uso terapêutico , Afeto/efeitos dos fármacos , Afeto/fisiologia , Encéfalo/efeitos dos fármacos , Humanos , Extratos Vegetais/uso terapêutico , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/fisiologia , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/fisiologia
19.
Acta Neuropsychiatr ; 31(4): 230-234, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169098

RESUMO

BACKGROUND: Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear. METHODS: Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response. RESULTS: Compared to participants with WBC counts of 4.5-10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses. CONCLUSIONS: An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.


Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar , Lítio/uso terapêutico , Fumarato de Quetiapina/uso terapêutico , Adulto , Afeto , Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/imunologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
20.
Expert Opin Pharmacother ; 20(14): 1731-1741, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31159601

RESUMO

Introduction: The peripartum period in bipolar disorder (BD) patients is associated with high risk of relapse. Relapse during this period may affect fetal and child development. The consequences of psychotropic medication during pregnancy are also a major concern. The extent to which mood stabilizers may potentially affect the embryogenesis or the child development varies from high (e.g. valproate) to less clear and more debated (e.g. lithium). Areas covered: This review describes the current state of evidence with respect to the impact of recommended pharmacological interventions for BD during the peripartum period. It compares recent international treatment guidelines for the management of BD during the peripartum period. Last, this review presents a summary of key recommendations for BD women of childbearing age, for BD women during pregnancy and postpartum period from the international guidelines. Expert opinion: Management of the pharmacological treatment for BD patients during the perinatal period is challenging. Although treatment guidelines may be of significant help, high heterogeneity exists across them. Shared decision-making represents a useful patient-centered approach during the perinatal period. Large cohort studies are needed to better identify risk associated to treatment discontinuation or treatment exposure.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Psicotrópicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Transtorno Bipolar/patologia , Feminino , Guias como Assunto , Humanos , Lítio/uso terapêutico , Período Periparto , Gravidez , Medição de Risco
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