CLINICAL POTENTIAL OF CARIPRAZINE IN THE TREATMENT OF ACUTE MANIA

Cariprazine (RGH-188, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-amine hydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors antagonist–partial agonist properties. Cariprazine has also moderate affinity for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B receptors with pure antagonism and low affinity for 5-HT2A receptors. Randomized, double blind, placebo controlled, flexible-dose (3–12 mg/day) studies have demonstrated cariprazine is effective in both schizophrenia and acute manic episodes associated with bipolar disorder. The incidence of serious adverse events in cariprazine arm was no different than in placebo arm in these studies. The most common adverse events were extrapyramidal symptoms, headache, akathisia, constipation, nausea, and dyspepsia which can be explained with cariprazine’s partial dopamine agonism. Although cariprazine treatment was associated with a higher incidence of treatmentemergent adverse events, particularly akathisia and tremor, common side effects of marketed second generation antipsychotics such as weight gain, metabolic disturbances, prolactin increase or QTc prolongation were not associated with cariprazine, probably due to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. Animal studies show that cariprazine may have additional therapeutic benefit on impaired cognitive functioning with D3 receptor activity, however clinical data is still scarce. The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date

CLINICAL POTENTIAL OF CARIPRAZINE IN THE TREATMENT OF ACUTE MANIA

Cariprazine (RGH-188, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-amine hydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors antagonist–partial agonist properties. Cariprazine has also moderate affinity for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B receptors with pure antagonism and low affinity for 5-HT2A receptors. Randomized, double blind, placebo controlled, flexible-dose (3–12 mg/day) studies have demonstrated cariprazine is effective in both schizophrenia and acute manic episodes associated with bipolar disorder. The incidence of serious adverse events in cariprazine arm was no different than in placebo arm in these studies. The most common adverse events were extrapyramidal symptoms, headache, akathisia, constipation, nausea, and dyspepsia which can be explained with cariprazine’s partial dopamine agonism. Although cariprazine treatment was associated with a higher incidence of treatmentemergent adverse events, particularly akathisia and tremor, common side effects of marketed second generation antipsychotics such as weight gain, metabolic disturbances, prolactin increase or QTc prolongation were not associated with cariprazine, probably due to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. Animal studies show that cariprazine may have additional therapeutic benefit on impaired cognitive functioning with D3 receptor activity, however clinical data is still scarce. The aim of this article is to review the potential use of cariprazine for the treatment of acute manic episodes in the light of the preclinical and clinical trials reported to date

Gebe ve lohusalarda iki uçlu bozukluğun sağaltımı

The prevalence of bipolar disorder (BD) inmales and females is almost equal. the onset of BD in females typically occursduring the reproductive years, complicating its treatment. Although it was oncebelieved that pregnancy prevents recurrence, studies have shown that recurrenceis common and severe during pregnancy. on the other hand, the effects ofpharmacological treatment on obstetrical outcome are not well known and some ofthese agents are considered teratogenic. Thus, the decision to treat pregnantpatients with psychotropic agents requires solving an ethical dilemma.Risk-benefit decisions should be made while considering both the risk ofrelapse of BD and its morbidity, and the risk of fetal exposure to psychotropicmedications. Moreover, the risk of recurrence increases dramatically in thepostpartum period. It is well known that all of the psychotropic medicationsstudied enter the breast milk. Thus, their effects on infants should beconsidered while prescribing for a breastfeeding mother. the aim of this review was to discuss thesafety profiles of the treatment options for pregnant and breastfeeding BDpatients. Firstly, each medication's effects on organ dysgenesis, neonataltoxicity, and neurobehavioral development, and their associated adverse eventsduring pregnancy and the postpartum period are discussed, with a focus on theemerging literature. Given this background, practical suggestions on tailoringtreatment in BD patients, from preconception to breastfeeding are highlighted.İki uçlu bozukluğun yaşam boyu sıklığı her iki cinsiyetteyaklaşık eşittir. Hastalığın başlangıç döneminin kadınların doğurganlık çağıile örtüşmesi sağaltımda ek sorunlara yol açmaktadır. Her ne kadar gebeliğinyinelemeden koruduğuna inanılsa da çalışmalar gebelikte yinelemenin sık veşiddetli olduğunu göstermiştir. Öte yandan, pek çok ilaç sağaltımı seçeneğiningebelikteki etkileri bilinmemekte ve bazıları teratojen olarak kabuledilmektedir. Bu yüzden gebe hastaları psikotrop ajanlarla tedavi etme kararıetik bir çıkmazı çözmeyi gerektirir. Risk-yarar kararı alınırken hem iki uçlubozukluğun yineleme riski ile beraberinde getirdiği morbidite hem de fetusunpsikotrop ilaçlara maruz kalmasının riskleri göz önünde bulundurulmalıdır.Bunlara ek olarak lohusalıkta hastalık yineleme riski çarpıcı bir biçimdeartmaktadır. Tüm psikotrop ilaçların bir ölçüde anne sütüne geçtiği oldukça iyibilinmektedir. Bu yüzden emziren bir anneye ilaç başlanırken bu psikotropilaçların bebek üzerindeki etkileri göz önünde bulundurulmalıdır. Bu derlemenin amacı, gebe ve emziren iki uçlu hastalarda mevcutsağaltım seçeneklerinin güvenlik profillerini gözden geçirmektir. İlk olarak,gebelik ve lohusalıkta her bir ilacın yapısal bozukluk, yenidoğan toksisitesi,nörodavranışsal gelişim ve beklenmeyen olaylar üzerindeki etkileri güncel yazınışığında tartışılmıştır. Bu bilgiler doğrultusunda, gebelik planındanlohusalığa kadar olan dönemde iki uçlu hastaların tedavilerinin düzenlenmesineyönelik pratik öneriler yapılmıştır

STATE OF THE ART PSYCHOPHARMACOLOGICAL TREATMENT OPTIONS IN SEASONAL AFFECTIVE DISORDER

Seasonal affective disorder (SAD) is defined as a subtype of mood disorders in DSM 5, and it is characterized by a seasonal onset. SAD is proposed to be related to the seasonal changes in naturally occurring light, and the use of bright light therapy for depressive symptoms has been shown to reduce them in placebo controlled trials. Cognitive behavioral therapy has also been demonstrated to be effective in SAD. This review article aims to focus on the psychopharmacological treatment options for SAD. According to clinical trial results, first line treatment options seem to be sertraline and fluoxetine, and are well tolerated by the patients. There is some evidence that other antidepressants (e.g. bupropion) might be effective as well. Although clinical trials have shown that some of these antidepressants may be of benefit, a recent review has concluded that there is not enough evidence to support the use of any of these agents for the treatment of SAD yet. Moreover, more studies are still needed to evaluate the effectiveness of other treatment options, e.g., propranolol, melatonin, hypericum, etc. In addition to the above proposed treatments, patients with seasonal depressive symptoms should thoroughly be evaluated for any cues of bipolarity, and their treatment should be planned accordingly