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.

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 treatment-emergent 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.

[Relationship between Childhood Adversities, Emotion Dysregulation and Cognitive Processes in Bipolar Disorder and Recurrent Depressive Disorder]. / Bipolar Bozukluk ve Yineleyici Depresif Bozuklukta Çocukluk Çagi Travmalari ve Duygu Düzenleme Güçlükleri ile Bilissel Süreçler Arasindaki Iliski.

OBJECTIVE: Cognitive development is susceptible to environmental distress, leading to cognitive distortions. Cognitive distortions may affect clinical course of psychiatric disorders. We aimed to assess whether childhood maltreatment and emotion dysregulation impair automatic thoughts (ATs) and meta-cognitions (MCs) in Bipolar Disorder (BD) and Major Depressive Disorder - Recurrent (MDB-RE) in this study. METHOD: 85 patients with BD, 81 MDD-RE in remission and 86 healthy participants were enrolled. Automatic Thoughts Scale (ATS), Metacognition Questionnaire (MCQ-30), Childhood Trauma Questionnaire (CTQ- 28), Difficulties in Emotion Regulation Strategies Scale (DERS) were the measures used. RESULTS: ATs were determined by CTQ physical abuse (ß=0.34, p<0.01), DERS goals (ß=-0.37, p<0.01), impulse (ß=0.53, p<0.01) and non-accept (ß=0.23, p<0.05) subscales in BD (F=21.08, p<0.01) and CTQ emotional neglect (ß=0.22, p<0.05), DERS strategies (ß=0.39, p<0.05) in MDD-RE (F=9.97, p<0.05). MCs were predicted by sexual abuse (ß=0.46, p<0.01) in BD (F=4.88, p<0.01), and emotional abuse (B=-0.30, p<0.05) in MDD-RE (F= 7.02, p<0.01). CONCLUSION: These results suggest that emotion dysregulation and childhood adversities are associated with cognitive processes such as MCs and ATs in MDD-RE and BD. Cognitive processes can cause various clinical manifestations and emotion dysregulation and childhood traumas should be considered as psychopathological components that can affect the course of mood disorders via various components. Further follow-up studies and larger samples are needed to better understand the effects of these components.

[The treatment of bipolar disorder during pregnancy and the postpartum period]. / Gebe ve Lohusalarda Iki Uçlu Bozuklugun Sagaltimi.

The prevalence of bipolar disorder (BD) in males and females is almost equal. The onset of BD in females typically occurs during the reproductive years, complicating its treatment. Although it was once believed that pregnancy prevents recurrence, studies have shown that recurrence is common and severe during pregnancy. On the other hand, the effects of pharmacological treatment on obstetrical outcome are not well known and some of these agents are considered teratogenic. Thus, the decision to treat pregnant patients with psychotropic agents requires solving an ethical dilemma. Risk-benefit decisions should be made while considering both the risk of relapse of BD and its morbidity, and the risk of fetal exposure to psychotropic medications. Moreover, the risk of recurrence increases dramatically in the postpartum period. It is well known that all of the psychotropic medications studied enter the breast milk. Thus, their effects on infants should be considered while prescribing for a breastfeeding mother. The aim of this review was to discuss the safety profiles of the treatment options for pregnant and breastfeeding BD patients. Firstly, each medication's effects on organ dysgenesis, neonatal toxicity, and neurobehavioral development, and their associated adverse events during pregnancy and the postpartum period are discussed, with a focus on the emerging literature. Given this background, practical suggestions on tailoring treatment in BD patients, from preconception to breastfeeding are highlighted.

Illness perception of dropout patients followed up at bipolar outpatient clinic, Turkey.

Dropout is a common problem in the treatment of psychiatric illnesses including bipolar disorders (BD). The aim of the present study is to investigate illness perceptions of dropout patients with BD. A cross sectional study was done on the participants who attended the Mood Disorder Outpatient Clinic at least 3 times from January 2003 through June 2008, and then failed to attend clinic till to the last one year, 2009, determined as dropout. Thirty-nine dropout patients and 39 attendent patients with BD were recruited for this study. A sociodemographic form and brief illness perception questionnaire were used to capture data. The main reasons of patients with BD for dropout were difficulties of transport (31%), to visit another doctor (26%), giving up drugs (13%) and low education level (59%) is significant for dropout patients. The dropout patients reported that their illness did not critically influence their lives, their treatment had failed to control their illnesses, they had no symptoms, and that their illness did not emotionally affect them. In conclusion, the nonattendance of patients with serious mental illness can result in non-compliance of therapeutic drug regimens, and a recurrence of the appearance symptoms. The perception of illness in dropout patients with BD may be important for understanding and preventing nonattendance.

Electrocardiography changes in bipolar patients during long-term lithium monotherapy.

OBJECTIVE: Cardiovascular side effects of lithium have been reported to occur mainly at higher-than-therapeutic serum levels. We aimed to investigate the impact of the long-term lithium use on electrocardiogram (ECG) parameters in association with the serum levels in patients with bipolar disorder (BD) and in healthy controls (HCs) serving as the reference group. METHODS: The study sample consisted of 53 euthymic BD type I patients on lithium monotherapy at therapeutic serum levels (M = 0.76, S.D. = 0.14, range = 0.41-1.09 mmol/l) for at least 12 months and 45 HCs. A 12-lead surface ECG was obtained from all participants at resting state for at least half an hour for 5-min recording. Heart-rate, Pmax, Pmin, QRS interval, QT dispersion, QT dispersion ratio (QTdR) and Tpeak-to-end interval (TpTe) were measured. RESULTS: Regression analyses revealed that QTdR (B = 14.17, P = .001), TpTe (B = 18.38, P < .001), Pmax (B = 17.84, P<.001) and Pmin (B = 25.10, P < .001) were increased in BD patients who were on chronic lithium treatment than in HCs after controlling for age, sex and strict Bonferroni correction for multiple testing. There were no associations between serum lithium levels and ECG parameters. CONCLUSION: Our findings suggest that the use of lithium is associated with both atrial and ventricular electrical instability, even when lithium levels are in the therapeutic range.

Minor hemoglobins HbA2 and HbF associate with disease severity in bipolar disorder with a likely protective role of HbA2 against post-partum episodes.

BACKGROUND: There exist studies indicating that bipolar disorder (BD) associates with changes in brain blood flow. Human brain with its high demand to oxygen constitutes 2% of the total body weight, while it receives 20% of cardiac output. α and ß globin chains of hemoglobin were recently found in neural tissues, yet no study has questioned blood hemoglobins in BD. METHODS: A total of 120 euthymic BD patients (40 males and 80 females) were analyzed via high performance liquid chromatography (HPLC) to measure minor hemoglobin levels, which were statistically compared with disease characteristics. RESULTS: Minor hemoglobins HbA2 and HbF associated positively with episode density as a measure of disease severity in BD. An increased level of HbA2 meant significantly less postpartum episodes in child bearing women. HbF levels were higher in patients with a positive family history of any psychotic disorder. Sum of HbA2 and HbF correlated with episode density with a stronger significance (p<0.001) supporting intermittent hypoxia hypothesis in BD. LIMITATIONS: The study was conducted only on euthymic patients to avoid likely bigger exogenous effects such as electro-convulsive therapy and diverse drug regimes, yet larger comparative studies are needed to support our current findings. CONCLUSIONS: Higher HbA2 and HbF in more severe bipolar disorder may be compensations against intermittent hypoxias in BD. HbA2 increases following myocardial angina and in mountain dwellers, which may indicate protective roles in extreme conditions. HbF increase may act more as a maladaptation or emerge via haplotypal associations of BD genes and gamma-globin locus at 11p15.5.