No abstract available.

The Suicide Prevention Law passed last March will be enacted beginning in April 2012, after the establishment of enforcement regulations. The suicide rate of Korea is 31/100,000, about 3 times the mean of the Organisation for Economic Co-operation and Development countries, and is still going up rapidly. Suicide is the 4th most common cause of death in Korea. As the suicide rate abruptly increased after the mid-1990s, there was little time to prepare effective strategies for suicide prevention, including personnel, programs, and networks. This is also partly due to the strong stigma and negative attitude against suicide and suicide prevention, which has prevented the exploration of the reason for the high suicide rate and recent increase. The Suicide Prevention Law requires comprehensive suicide prevention activities of the central and local governments, and support for those who attempt suicide, victims, and their families. Its successful implementation will be highly dependent on active participation of doctors for screening and prevention of high risk groups, including patients with depression and chronic physical illnesses and those who have psychosomatic symptoms from various stressful life events.
Cause of Death ; Depression ; Humans ; Jurisprudence ; Korea ; Mass Screening ; Social Control, Formal ; Suicide

Polypharmacy has recently become usual practice in the treatment of patients with mood disorders. In this article, we review the results of recent studies on metabolic drug interactions between anticonvulsants, atypical antipsychotics, and antidepressants. Important drug interactions in clinical practice may be summarized as follows. First, valproate may increase the serum level of carbamazepine and its active metabolite carbamazepine-epoxide, quetiapine, and lamotrigine. In particular, in combined regimens of lamotrigine and valproate, the dose of lamotrigine needs to be downwardly titrated, due to the potential risk of skin lesions. Second, there are numerous carbamazepine-associated interactions that need careful monitoring, because carbamazepine is a well-known inducer of CYP1A2, CYP2C9, and CYP2C19. Thus, in patients receiving carbamazepine, clinically significant decreases in serum levels may be found for drugs metabolized by these enzymes. Third, atypical antipsychotics are primarily metabolized by CYP2D6 and CYP3A4, thereby compromising the use of inhibitors of these enzymes. Fourth, most selective serotonin-reuptake inhibitors (SSRIs) are actually inhibitors of diverse enzyme systems, indicating at least potential problems with increased serum levels. While paroxetine, fluoxetine, and fluvoxamine strongly inhibit CYP enzymes, citalopram, venlafaxine, mirtazapine, and bupropion do so weakly. In conclusion, understanding drug-drug interactions is essential in planning individualized pharmacotherapy with diverse therapeutics. In treating patients with mood disorders, special concern should be paid to combination therapy using valproate, carbamazepine, and some SSRIs.
Anticonvulsants ; Antidepressive Agents ; Antipsychotic Agents ; Bupropion ; Carbamazepine ; Citalopram ; Cyclohexanols ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 CYP2D6 ; Dibenzothiazepines ; Drug Interactions ; Fluoxetine ; Fluvoxamine ; Humans ; Mianserin ; Mood Disorders ; Paroxetine ; Polypharmacy ; Skin ; Triazines ; Valproic Acid ; Quetiapine Fumarate ; Venlafaxine Hydrochloride

OBJECTIVE: The pharmacotherapy of bipolar disorder not otherwise specified (BP-NOS) has been insufficiently studied. The aim of this prospective naturalistic study was to explore the effectiveness of lamotrigine adjunctive treatment in patients with BP-NOS. METHODS: Data from 50 patients diagnosed with BP-NOS were analyzed. On the basis of the prospective mood chart methodology, the efficacy of lamotrigine adjunctive treatment was assessed by changes in the mean Clinical Global Impressions-Bipolar Version (CGI-BP) depression scores. A paired t-test was used to test the statistical significance of the changes in CGI-BP depression scores. Repeated-measures analysis of variance (RM ANOVA) with simple effect analysis was performed to explore the sequential changes during a 52-week period. Cohen's d was calculated to measure the magnitude of the treatment effects on the changes in depression severity. Time to lamotrigine discontinuation was also calculated using the Kaplan-Meier estimates. Lamotrigine-associated adverse events were monitored every two weeks. RESULTS: A significant decrease, with a large effect size (Cohen's d=1.6), in the mean CGI-BP depression scores was associated with lamotrigine adjunctive treatment in intent-to-treat analysis (t=8.7, df=49, p<0.001). Twenty-four patients (48.0%) completed 52-week lamotrigine adjunctive treatment. Analysis of the data obtained from those completing the treatment revealed a large effect (Cohen's d=4.0) on improvement in the severity of depression (t=16.8, df=32, p<0.001). Sixty percent of patients achieved remission (n=30), and 64% of patients (n=32) showed some clinical response to lamotrigine adjunctive treatment. The mean time to lamotrigine discontinuation was 31.3+/-3.1 weeks (CI=25.2-37.4). Lamotrigine adjunctive treatment was well tolerated, with no serious rashes reported. CONCLUSION: Lamotrigine seems to be effective in the management of depressive symptoms in BP-NOS. Long-term use of lamotrigine was generally safe and well tolerated. Large-scale controlled trials might be needed to confirm the findings of this naturalistic study.
Bipolar Disorder ; Depression ; Exanthema ; Humans ; Prospective Studies ; Triazines

OBJECTIVES: To investigate the pattern of subclinical hypothyroidism (SCH) in patients with bipolar disorders managed by lithium or valproic acid. METHODS: The study participants were 106 patients with DSM-IV bipolar disorders receiving planned maintenance treatment at the Mood Disorders Clinic of Seoul National University Bundang Hospital (aged between 17 and 64, mean duration of follow-up = 875.65 days). Using the bipolar disorder registry, thyroid function data were analyzed to assess the frequency of and the risk factors for SCH in patients managed by lithium (n = 64) or valproic acid (n = 42) for more than 5 months. RESULTS: Overall frequencies of SCH were 20.3% (13/64) in the lithium group, 14.3% (6/42) in the valproic acid group, and between the two groups there is no difference (p = 0.43). No differences were observed in the potential risk factors for SCH between the two groups including age, sex, subtype of bipolar disorder, baseline TSH, and concomitant antipsychotic use. In cases with SCH, thyroid-stimulating hormone (TSH) showed a tendency to increase at 3 month after the initiation of lithium or valproic acid. A gradual increase in the number of patients showing SCH was found within the first 3 years of medication. CONCLUSIONS: With regular monitoring and careful assessment, there was no difference in the risk of SCH between lithium and valproic acid maintenance. The risk of mood stabilizer-associated SCH may gradually increase within 3 years following the commencement of medication, thereby mandating close monitoring for the first 3 years of treatment. Further studies with large sample size would be needed to confirm these findings.
Bipolar Disorder* ; Diagnostic and Statistical Manual of Mental Disorders ; Follow-Up Studies ; Humans ; Hypothyroidism* ; Lithium* ; Mood Disorders ; Risk Factors ; Sample Size ; Seoul ; Thyroid Gland ; Thyrotropin ; Valproic Acid*

OBJECTIVES: Autobiographical memory (ABM) is a special type of episodic memory, containing events that have occurred in a personal life. Overgeneral tendency of ABM refers to the retrieval of memory with only general and categorical descriptions rather than specific events. ABM specificity in depression and posttraumatic stress disorder is a robust finding with relation to cognitive vulnerability, affect regulation, problem-solving ability. It is also implicated in bipolar disorder with frequent relapses. In this study, we investigated whether ABM specificity was related to manic or euthymic mood states in patients with bipolar disorder. METHODS: Forty bipolar patients with manic and euthymic episodes and 25 healthy controls participated in this study. Prompted by 5 positively and 5 negatively valenced emotional cue words, each participant was instructed to recall positive or negative memories and describe them in detail. The one-way ANOVA was used to compare ABM scores and post-hoc analyses were done. RESULTS: Comapred to the healthy persons, the bipolar patients reported significantly more general than specific negative memories in both manic and euthymic episodes (p = 0.003). However, there was no significant difference between manic and euthymic patients (p = 0.074). CONCLUSIONS: These results suggest that overgeneral tendency of negative ABM may be a trait abnormality in bipolar disorder. Moreover, this phenomenon might be related to underlying cognitive deficits or affect regulation irrespective of the mood state.
Bipolar Disorder ; Cues ; Depression ; Humans ; Memory ; Memory, Episodic ; Recurrence ; Sensitivity and Specificity ; Stress Disorders, Post-Traumatic

Data from clinical studies are needed for psychiatrists to make quick and scientific decisions based on the best available evidence in clinical settings. Various methods of clinical studies are useful for clinicians to have reliable answers to unmet clinical needs. Although randomized controlled trials may provide high-quality information about major issues, well-designed, naturalistic and observational studies often give us unbiased explanation for real-world phenomena. Adequate selection of clinical variables and appropriate number of participants are key factors of well-designed clinical studies. Statistical methods can add an extra dimension to initial design of clinical studies. Given ethical issues in clinical studies on psychiatric disorders, special regards should be paid to participants' ability to provide informed consents. New strategies of clinical studies need to be developed to meet clinical needs and protect the rights and welfare of study participants.
Ethics, Research ; Human Rights ; Psychiatry

OBJECTIVES: Stigma resistance is an individual capacity to fight the stigma of mental illness and is an issue of ongoing research regarding the stigma. The aim of this study was to evaluate predictors of stigma resistance in patients with bipolar disorder. METHODS: Demographic, clinical, and psychosocial data were collected from 102 bipolar patients in a university mental hospital. Stigma resistance was measured using a subscale of the Internalized Stigma of Mental Illness Scale. Patients completed self-reported questionnaires including items on self-esteem, hopelessness, social support, and social conflict. RESULTS: Stigma resistance showed positive association with functioning, self-esteem, and social support, and showed negative association with depressive symptoms, hopelessness, and social conflict. In multivariate analysis, stigma resistance was predicted by sex, education, and self-esteem. Self-esteem was the strongest predictive factor of stigma resistance. CONCLUSION: In accordance with previous studies, self-esteem was a central role of predicting stigma resistance. A program for improving self-esteem and its related psychosocial factors will be helpful to enhancing stigma resistance in bipolar patients.
Bipolar Disorder* ; Depression ; Education ; Hospitals, Psychiatric ; Humans ; Multivariate Analysis ; Psychology ; Self Concept

OBJECTIVES: Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. METHODS: PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. RESULTS: Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. CONCLUSIONS: Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.
Animals ; Genes, Reporter ; Humans ; Lithium Chloride ; Lithium* ; PC12 Cells* ; Pheochromocytoma ; Phosphorylation* ; Phosphotransferases ; Signal Transduction ; Transcription Factors ; Valproic Acid*

OBJECTIVE: The current study explored the relationship between the polarity of the first episode and the timing of eventual diagnosis of bipolar I disorder, and associated clinical implications. METHODS: Twelve years of clinical data from the medical records of 258 inpatients meeting DSM-III-R or DSM-IV criteria for bipolar I disorder were analyzed. Subjects were divided into two groups according to the polarity of the first episode: those with depressive polarity (FE-D), and those with manic polarity (FE-M). Comparisons were made between the two groups on variables associated with the timing of diagnosis and related outcomes. RESULTS: In population with bipolar I disorder, a significant longer time lapse from the first major mood episode to the confirmed diagnosis was associated with the FE-D group compared to the FE-M group [5.6 (+/-6.1) vs. 2.5 (+/-5.5) years, p<0.001]. FE-D subjects tended to have prior diagnoses of schizophrenia and major depressive disorder while FE-M subjects tended to have prior diagnoses of bipolar disorder and schizophrenia. A significantly higher rate of suicide attempts was associated with the FE-D group compared to the FE-M group (12.7 vs. 1.7%, p<0.001). CONCLUSION: The results of this study indicate that first-episode depressive polarity is likely to be followed by a considerable delay until an eventual confirmed diagnosis of bipolar I disorder. Given that first-episode depressive patients are particularly vulnerable to unfavorable clinical outcomes such as suicide attempts, a more systematic approach is needed to differentiate bipolar disorder among depressed patients in their early stages.
Bipolar Disorder ; Depressive Disorder, Major ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Inpatients ; Medical Records ; Schizophrenia ; Suicide