Acute and Long Term Treatment of Manic Episodes in Bipolar Disorder.

Bipolar disorder is a disabling psychiatric disorder which causes premature death and loss of quality of life. Despite the developments, novel treatments are partially effective and insufficient responses to treatment may cause loss of quality of life. Contemporary approaches to treatment planning involve taking the current symptoms and the personal treatment history of the patient into account and tailoring them for the treatment of each patient, i.e. individualized treatment. In this article, effects and side effects of antipsychotics, mood stabilizers and sedative hypnotic medications are reviewed and presented briefly for clinicians. Although novel developments have been observed in the literature about mixed states and psychotic symptoms, evidence-based options are still limited. Efficacy of mood stabilizers may be prolonged and additional medications may also be needed frequently in patients treated with mood stabilizers. Antipsychotics may cause several side effects and cannot be maintained for a long time in some of those patients. These factors may limit the use of mood stabilizers or antipsychotics. Therefore, the experience of the clinician and personal history of the patient still have importance in the procedure.

[Reliability and Validity Study of the Turkish Version of Hypomania Checklist-32-Revised]. / Hipomani Soru Listesi-32-Yenilenmis Sürümün Türkçe Güvenilirlik ve Geçerlilik Çalismasi.

OBJECTIVE: In this study, it is aimed to evaluate the reliability and validity of the Turkish version of Hypomania Checklist-32-Revised. METHOD: The study was carried out with 80 patients diagnosed with bipolar I disorder, 26 patients diagnosed with bipolar II disorder and 42 patients diagnosed with major depressive disorder attending the out- and in-patient psychiatry departments of three university hospitals and one training hospital, and 116 healthy volunteers consisting of university students. Mean duration of illness was 15,1 years for the bipolar disorder group, and 9,3 years for the major depressive disorder group. For concurrent validity, Mood Disorder Questionnaire was used. In the statistical analysis, internal consistency coefficient, item-total score correlation coefficients, exploratory factor analysis, correlation with concurrent scale and ROC curve were calculated. RESULTS: Translation into Turkish and back-translation into English of Hypomania Checklist-32-Revised were performed and thus the semantic harmony of the scale was obtained. In the internal consistency, Cronbach alpha coefficient was 0,914 and item-total score correlations were between 0,235-0.743. Solely the coefficient of item #23 was found as 0,110. In factor analysis, six factors were obtained but a two-factor solution representing 44,5% of the total variance was accepted and first factor represents overactivity and being expansive, second factor represents impulsivity and risky behaviors. Correlation of Hypomania Checklist-32-R with Mood Disorder Questionnaire was r=0,379. In the ROC analysis, the cut off point of the scale was calculated as 14 with a sensitivity of 71,0 and specificity of 69,8. The scale discriminates well between the bipolar group, and depressive and control groups. CONCLUSION: Hypomania Checklist-32-Revised developed for screening hypomania is reported to be reliable and valid in Turkish after cutting out item #23.

[Creativity and bipolar disorder]. / Yaraticilik ve iki uçlu bozukluk.

The relationship between creativity and bipolar disorder has been an intriguing topic since ancient times. Early studies focused on describing characteristics of creative people. From the last quarter of the twentieth century, researchers began to focus on the relationship between mood disorders and creativity. Initially, the studies were based on biographical texts and the obtained results indicated a relationship between these two concepts. The limitations of the retrospective studies led the researchers to develop systematic investigations into this area. The systematic studies that have focused on artistic creativity have examined both the prevalence of mood disorders and the creative process. In addition, a group of researchers addressed the relationship in terms of affective temperaments. Through the end of the 90's, the scope of creativity was widened and the notion of everyday creativity was proposed. The emergence of this notion led researchers to investigate the associations of the creative process in ordinary (non-artist) individuals. In this review, the descriptions of creativity and creative process are mentioned. Also, the creative process is addressed with regards to bipolar disorder. Then, the relationship between creativity and bipolar disorder are evaluated in terms of aforementioned studies (biographical, systematic, psychobiographical, affective temperaments). In addition, a new model, the "Shared Vulnerability Model" which was developed to explain the relationship between creativity and psychopathology is introduced. Finally, the methodological limitations and the suggestions for resolving these limitations are included.

Affective Temperament Profiles of Overactive Bladder Patients.

INTRODUCTION: Overactive bladder (OAB) is generally characterized by urinary urgency with or without incontinence and increased frequency of voiding and nocturia. Although animal studies have demonstrated the relationship between defective serotonergic neurotransmission and OAB, its etiology is still unclarified. Temperament profiles are hypothesized to be related with serotonergic activity and are studied in many psychosomatic disorders. Thus, we assume that OAB is related with a certain type of temperament. METHOD: 29 patients, who were admitted to the urology outpatient clinic at Kocaeli University and clinically diagnosed with OAB syndrome, were recruited for the study. Temperament profiles were evaluated with the Temperament Evaluation of Memphis Pisa Paris and San Diego Autoquestionnaire (TEMPS-A). Depressive, hyperthymic, cyclothymic, anxious and irritable temperament scores in patients were compared with those in 25 healthy controls. RESULTS: Patient and control groups were similar in terms of age (p=.65), sex (p=.64) and educational level (p=.90). Anxious temperament scores were higher (p=.02) and hyperthymic temperament scores were lower (p=.02) in patients with OAB compared to controls. Depressive, cyclothymic and irritable temperament scores were similar in both groups. There was no significant differences between men and women in both groups in terms of different temperament profile scores. CONCLUSION: Hypothetically, there might be an association between anxious temperament and OAB syndrome reflecting serotonergic dysfunction. However, OAB syndrome must be considered from the aspect of the interdependence of psychosomatic implications in a narrow sense and psychosomatic dimensions due to the psychological predisposition in the individual case.

An Unusual Case: The Comorbidity of Mood Disorder and 17-α-Hydroxylase Deficiency.

17-α-hydroxylase enzyme has a crucial role in the steroid biosynthesis and, deficiency of this enzyme is an autosomal recessive monogenic disorder which is one of the two hypertensive form of congenital adrenal hyperplasia. It is characterized with the deficiency in glucocorticoid, adrenal androgen, and sex steroid synthesis with concomitant mineralocorticoid excess due to genetic defect in steroid biosynthesis. The relationship of hormone system physiology with psychiatric signs and syndromes are complex. Any problem in the hypothalamo-pituitary axis may cause psychiatric syndromes. On the other hand, many psychiatric disorders, such as mood-anxiety symptoms, depression, mania, psychosis, and delirium can be seen secondary to the treatment of hormone deficiency. We present the case of a male patient with pseudohermaphroditism who has been followed and treated in Rasit Tahsin Mood Clinic with the diagnosis of mood disorder not otherwise specified and was diagnosed with 46, XY karyotype and 17-α-hydroxylase deficiency after referring to a hospital with delayed puberty. Considering the medical literature, 17-α-hydroxylase deficiency has been evaluated from the aspects of gender-related behavioral disorders, psychological developmental and anxiety disorders. To the best of our knowledge, in the medical literature, this is the first case of 17-α-hydroxylase deficiency associated with mood disorder. Here, the relationship between mood disorders and hypothalamo-pituitary axis is discussed in the light of the literature.

A standardized scoring method for the copy of cube test, developed to be suitable for use in psychiatric populations.

BACKGROUND: Although the 'copy of cube test', a version of which is included in the Short Test of Mental Status (STMS), has existed for years, little has been done to standardize it in detail. The aim of the current study was to develop a novel and detailed standardized method of administration and scoring this test. METHODS: The study sample included 93 healthy control subjects (53 women and 40 men) aged 35.87 ± 12.62 and 127 patients suffering from schizophrenia (54 women and 73 men) aged 34.07 ± 9.83 years. The psychometric assessment included the Positive and Negative Symptoms Scale (PANSS) the Young Mania Rating Scale (YMRS), and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: A scoring method was developed based on the frequencies of responses of healthy controls. Cronbach's α was equal to 0.75 and inter-rater reliability was 0.90. Three indices and five subscales of the Standardized Copy of the Cube Test (SCCT) were eventually developed. They included the Deficit Index (DcI), which includes the Missing Elements (ME) Mirror Image (M) subscales, the Deformation Index (DfI) which includes the Deformation (D) and the Rotation (R) subscales and the Closing-In Index (CiI). DISCUSSION: The SCCT seems to be a reliable, valid and sensitive to change instrument for the testing of psychiatric patients. The great advantage of this instrument is the fact that it only requires paper and a pencil, and is this easily administered and brief. Further research is necessary to test its usefulness as a neuropsychological test.

Antidepressant-associated mania or hypomania: a comparison with personality and bipolarity features of bipolar I disorder.

BACKGROUND: Hypomania/mania during antidepressant treatment is often neglected by clinicians. There are no specific diagnostic criteria for hypomania and mania associated by antidepressant treatment in the bipolar spectrum. The aim of this study is to compare various characteristics of bipolar I disorder and antidepressant-associated mania. METHOD: In this study, 76 bipolar patients who met DSM-IV criteria for bipolar disorder-type I in remission from mania or depression (Group 1; n = 44) and patients with major depression in remission, who had mania associated by antidepressant treatment (Group 2; n = 32), were admitted. All patients were assessed using the SCID I, Bipolarity Index (BI) and a patient data form. First-degree relatives of all patients were evaluated using the Mood Disorder Questionnaire (MDQ). RESULTS: Sociodemographic features of both groups were similar. The rate of major depression in the relatives of Group 2 was significantly higher than in Group 1. The severity of manic symptoms in Group 2 was significantly lower than in Group 1. Those in Group 2 who were diagnosed with their first episode had atypical depressive features. First-degree relatives of patients in Group 1 had higher positive scores on the MDQ. A statistically significant difference was found between the two groups on all dimensions of the BI except family history. LIMITATIONS: This is a cross-sectional study with a relatively small number of subjects. There is no control group of major depressive patients who did not develop mania during antidepressive treatment. CONCLUSIONS: Our results suggest that antidepressant-associated hypomania/mania could be a different subgroup in the bipolar spectrum.

The standardised copy of pentagons test.

BACKGROUND: The 'double-diamond copy' task is a simple paper and pencil test part of the Bender-Gestalt Test and the Mini Mental State Examination (MMSE). Although it is a widely used test, its method of scoring is crude and its psychometric properties are not adequately known. The aim of the present study was to develop a sensitive and reliable method of administration and scoring. METHODS: The study sample included 93 normal control subjects (53 women and 40 men) aged 35.87 ± 12.62 and 127 patients suffering from schizophrenia (54 women and 73 men) aged 34.07 ± 9.83. RESULTS: The scoring method was based on the frequencies of responses of healthy controls and proved to be relatively reliable with Cronbach's α equal to 0.61, test-retest correlation coefficient equal to 0.41 and inter-rater reliability equal to 0.52. The factor analysis produced two indices and six subscales of the Standardised Copy of Pentagons Test (SCPT). The total score as well as most of the individual items and subscales distinguished between controls and patients. The discriminant function correctly classified 63.44% of controls and 75.59% of patients. DISCUSSION: The SCPT seems to be a satisfactory, reliable and valid instrument, which is easy to administer, suitable for use in non-organic psychiatric patients and demands minimal time. Further research is necessary to test its psychometric properties and its usefulness and applications as a neuropsychological test.

Association of MDR1 C3435T polymorphism with bipolar disorder in patients treated with valproic acid.

P-glycoprotein (P-gp), an efflux transporter protein, is an ABC transporter encoded by the multidrug resistance 1 gene (MDR1, ABCB1). The common synonymous C3435T polymorphism in exon 26 is reported to associate with lower P-gp functional expression and drug uptake. Many extended pharmacogenomics, functional, and complex disease association studies focused mainly on this polymorphism. We investigated the association of exon 26 C3435T genetic variants of MDR1 gene with susceptibility to bipolar disorder and serum valproic acid concentration. Totally, 104 patients meeting DSM-IV criteria for bipolar disorder and 169 controls were admitted to the study. There was statistically significant difference between the genotypes of bipolar patients (CT 91.2%, TT 6.8%, and CC 2%) and controls (CT 52.7%, TT 26%, CC 21.3%) although their allelic distribution was similar. The serum valproic acid concentrations of the patients with CT, TT and CC genotypes were 72.92 +/- 20.55, 80.47 +/- 14.01 and 68.29 +/- 12.17 microg/ml, respectively, and there was no significant difference between the C3435T genotypes.

[The factor analytic symptom structure of manic episode and its relationship with affective temperaments]. / Manik dönemin faktör analizine dayanan alt-tipleri ve mizaçla iliskisi.

OBJECTIVE: The aim of this study is to establish the factor analytic dimensions of manic episode, and to investigate relationship between established factors and underlying affective temperament. METHODS: Hundred patients who had been hospitalized in psychiatric clinics of Bakirköy Prof. Mazhar Osman Training and Research Hospital for Psychiatry and Neurology for DSM-IV bipolar disorder manic episode were assessed by Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS) and Positive And Negative Syndrome Scale (positive syndrome sub-scale) (PANSS) and followed by factor analysis. The relationship between factor scores and underlying affective temperaments has been investigated in 72 full remitted patients who had been re-assessed by Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) Turkish version. RESULTS: 7 factors model which accounted 67.48% of the total variance has been emerged by principal component factor analysis. Determined factors were dysphoria, psychomotor acceleration, psychosis, irritability, insight, grandiosity and sexual interest. It has been found linear correlation between hyperthymic temperament and psychomotor acceleration (r=0.255, p<0.05) and, inverse correlation between depressive temperament and sexual interest (r=-0.248, p<0.05). CONCLUSIONS: The results of our study has shown that clinical phenomenology of mania has been formed by independent dimensions of dysphoria, irritability and psychosis, also with relationship between hyperthymic temperament and psychomotor acceleration which is accepted core characteristic of mania.

Predictive factors for time to remission and recurrence in patients treated for acute mania: health outcomes of manic episodes (HOME) study.

OBJECTIVE: To determine the time to remission and recurrence in patients treated for acute mania and the predictive factors associated with these outcomes. METHOD: This observational study, conducted in Turkey from April 2003 to January 2005, included patients with a DSM-IV diagnosis of bipolar I disorder, acute manic or mixed episode who were eligible to have an oral medication initiated or changed for the treatment of the episode. The patients were followed-up for 12 months. RESULTS: A total of 584 patients (mean ± SD age = 33.9 ± 11.2, 55.2% outpatients) were enrolled in 53 centers. Eighty-five percent of patients had a manic episode at baseline, with a mean ± SD duration of 21.6 ± 24.4 days. The baseline mean ± SD Clinical Global Impressions scale for use in bipolar disorder and Young Mania Rating Scale (YMRS) scores were 4.9 ± 0.9 (median = 5.0) and 33.2 ± 9.3 (median = 33), respectively. 539 patients achieved remission and, of those, 141 patients had recurrence. One-year remission and recurrence rates were 99.0% and 35.7%, respectively. Mean ± SD times to remission and recurrence in descriptive statistics were 80.9 ± 73.8 (median = 50) and 159.0 ± 95.5 (median = 156) days, respectively. In Cox regression analysis, psychiatric comorbidities (p = .048), a higher YMRS score (p < .001), and a higher number of previous depressive episodes (p = .009) were statistically significant predictors of a longer time to reach remission. Index episodes of longer duration (p = .033) and mixed type (p = 0.49) were significant predictors of a shorter time to recurrence. Confounding factors like concomitant treatment, comorbidities, and lack of blinding and randomization were other limitations. CONCLUSION: Predictors for a longer time to remission were psychiatric comorbidities, a higher YMRS score, and a higher number of previous depressive episodes. Predictors for a shorter time to recurrence were episodes of longer duration and mixed type.

Development of a standardized scoring method for the Graphic Sequence Test suitable for use in psychiatric populations.

Although the graphic version of the Alternating Sequences Test which was introduced by Luria exists for years little has been done to standardize it. The aim of the current study was to develop a novel and detailed standardized method of administration and scoring. The study sample included 93 normal control subjects (53 women and 40 men) aged 35.87+/-12.62 and 127 patients suffering from schizophrenia (54 women and 73 men) aged 34.07+/-9.83. The psychometric assessment included the Positive and Negative Symptoms Scale the Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale. A scoring method was developed and was based on the frequencies of responses of healthy controls. Cronbach alpha and test-retest and interrater reliability were very good. Two indices and 6 subscales of the Standardized Graphic Sequence Test were eventually developed. The Standardized Graphic Sequence Test seems to be a reliable, valid, and sensitive to change instrument based on Luria's graphic sequence test. The great advantage of this instrument is the fact that it is paper and pencil, easily administered and little time consuming. Further research is necessary to test its usefulness as a neuropsychologic test.

Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder.

BACKGROUND: Manic-depression or bipolar disorder (BD) is a multi-faceted illness with an inevitably complex treatment. METHODS: This article summarizes the current status of our knowledge and practice of its treatment. RESULTS: It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. CONCLUSION: The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule.

Management of acutely ill patients in the hospital setting: focus on quetiapine.

We have considered published work and clinical experience focusing on the atypical antipsychotic quetiapine in order to form a consensus on the most appropriate treatment strategies for hospitalised patients with acute schizophrenia or bipolar disorder. It is important to consider the specific treatment needs of these patients and these are discussed in the context of current treatment guidelines. We will review the efficacy and tolerability of atypical antipsychotics versus conventional antipsychotics and/or benzodiazepines as a first-line treatment, and examine the suitability of oral versus intramuscular formulations in the acute setting. The potentially beneficial properties of specific atypical agents are also considered. Appropriate dosing is particularly important in acutely ill patients as it can help achieve rapid improvement. We will discuss emerging data which show that rapid initiation of quetiapine in patients with acute psychosis or mania is not only as effective as standard initiation, but is also well tolerated. This may be important for treatment in the long term as a positive initial treatment experience can determine patient compliance and treatment adherence. In conclusion, this review recommends that oral atypical antipsychotics should be a first-choice medication for acutely ill cooperative patients in the hospital setting.

Treatment of acute mania.

The DSM-IV criteria for mania require: a distinct period that represents a break from pre-morbid functioning, a duration of at least one week, elevated or irritable mood, at least three to four classical manic signs and symptoms and the absence of any physical factors. Although not specifically mentioned in the ICD-10 or the DSM-IV definitions, delusional, hallucinatory, even first-rank, psychotic experiences can occur in mania. Acute mania can be subdivided into classical pure mania, mania with mood-congruent or mood-incongruent psychosis, mixed state and rapid-cycling mania. One quarter to two thirds of all manic episodes are associated with delusions, while 13% to 40% are associated with hallucinations. Mixed episode is a complex syndrome which is difficult to diagnose, has the most prolonged duration of bipolar episodes and more frequent psychotic profile than pure mania with high suicidality and poor response to drugs. Mixed state mania has been well known since Kreapelin and listed in classification systems with criteria that include both a manic and a major depressive episode nearly every day for at least a one-week period. On the other hand, mixed-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electro-convulsive therapy or light therapy) should not contribute toward a diagnosis of Bipolar I Disorder. Although, theoretically, mania is supposed to be resolved within 1-3 months even without treatment, psychiatric hospitalization is very common in especially severe cases due to functional impairment. Current treatments for mania aim to control the agitation, impulsivity, aggression and psychotic symptoms and to help patients regain their pre-morbid functionality. However, the clinical management of mania is challenging as most patients show syndromal remission but incomplete functional recovery after the first episode of mania.

Electroconvulsive therapy in drug-induced psychiatric states and neuroleptic malignant syndrome.

In the late-stage idiopathic Parkinson's disease (IDP), comorbid conditions such as depression and drug-induced psychosis may be observed. A patient with Parkinson disease, major depression, and paranoid psychosis who developed neuroleptic malignant syndrome (NMS) as the result of the sudden termination of high-dose (1200 mg/d) levodopa treatment is presented in this report. Because the patient did not respond to other treatment modalities, electroconvulsive therapy (ECT) was applied, and a rapid improvement was observed both in the patient's NMS and also in Parkinson's and psychiatric symptoms, with no additional side effects other than transient post-ictal confusions. The application of ECT allowed the patient to remain stable for a 5-year period with a quite low dose of levodopa (300 mg/d). Later, the patient had two episodes of depressive and psychotic symptoms, which were again successfully treated with the ECT. We suggest that ECT might be an effective and life-saving therapy in patients with severe, drug-resistant NMS.

[Reliability and validity of Turkish translation of Young Mania Rating Scale]. / Young mani derecelendirme olçeginin türkiye'de geçerlik ve güvenilirligi.

OBJECTIVE: The reliability and validity of the Turkish translation of the Young Mania Rating Scale (YMRS) were determined in this study, since it is the most common scale used in clinical studies of mood disorders. METHOD: Fifteen male and 15 female inpatients who were diagnosed as having "Bipolar Mood Disorder--Recent Episode Mania", were given YMRS by two experienced psychiatrists, while another experienced psychiatrist gave the Bech-Rafaelsen Mania Scale (BRMS) simultaneously to the same patient population hospitalized in Bakirköy State Hospital for Psychiatric and Neurological Diseases, Psychiatry and Mood Disorders Inpatient Unit 5. The internal consistency of the Turkish version of YMRS was evaluated by the Cronbach's Alpha test, while item/item, item/total, and cross validity correlations were evaluated by the Pearson correlation test. Inter-rater agreement and consistency was evaluated by weighted kappa analysis. RESULTS: The internal consistency coefficient (Cronbach's alpha) was 0.79 for both researchers. Correlations of the items individually with the YMRS total scores were between 0.407 and 0.847. Agreement of the interviewers for the items was between 63.3%-95% and kappa values for the items were between 0.114 and 0.849. Correlation coefficients of YMRS and BRMS of the researchers were 0.72 for the first researcher and 0.71 for the second researcher. CONCLUSION: The Turkish translation of YMRS was found to be valid and reliable.