Obsessive-compulsive symptoms in patients with schizophrenia: Relationships with olanzapine pharmacological parameters, psychopathology, and quality of life.

Obsessive-compulsive symptoms (OCS) occur in a substantial portion of schizophrenia patients and have significant impacts on clinical course. This study was intended to investigate the relationships of OCS with pharmacological parameters of olanzapine, psychopathology, and quality of life. Totally 151 schizophrenia patients were recruited, and rated using Yale-Brown Obsessive-Compulsive scale (YBOCS), Positive and Negative Syndrome Scale (PANSS), Montgomery-Åsberg Depression Rating Scale (MADRS), and World Health Organization Questionnaire on Quality of Life: Short Form (WHOQOL-BREF). The concentrations of olanzapine and N-desmethylolanzapine were determined by HPLC. Twenty-five patients (16.6%) revealed the presence of OCS. OCS group had significantly higher olanzapine dose, more numbers of past hospitalizations, higher PANSS total, positive, negative, and general psychopathology scores, and higher MADRS score than those in non-OCS group. The WHOQOL-BREF physical subscale score in schizophrenia patients with OCS was significantly lower. Olanzapine dose, PANSS score, and MADRS score were significantly correlated with YBOCS score. Our findings highlight that OCS is highly prevalent in schizophrenia patients under olanzapine treatment, especially those at high doses. Schizophrenia patients with OCS had higher severity of psychotic and depressive symptoms and poorer quality of life. Clinicians should monitor OCS in patients with schizophrenia receiving olanzapine treatment.

Concurrent antipsychotic use in older adults treated with antidepressants in Asia.

AIM: Depressive disorders are common in old age. Antipsychotics (APs) are often used as an adjunctive treatment with antidepressants (ADs) in this population but its patterns of use in Asia are not known. This study explored the rate of combination of APs and ADs in older adult psychiatric patients in Asia. METHODS: This is a secondary analysis of the database of a multicentre study which recorded participants' basic demographical and clinical data in standardised format in 10 Asian countries and territories. The data were analysed using univariate and multivariate logistic regression analyses. RESULTS: A total of 955 older adult psychiatric in- and outpatients were included in this study. The proportion of concurrent AP and AD use was 32.0%, ranging from 23.3% in Korea to 44.0% in Taiwan. Multivariate logistic regression analysis found that younger age, inpatient status and diagnosis of schizophrenia, anxiety and other mental disorders were significantly related to a higher proportion of concurrent use of APs and ADs. CONCLUSION: Around a third of older adult psychiatric patients had concurrent AP and AD use in the Asian countries/regions surveyed. Considering the uncertain effectiveness and questionable safety of the AP and AD combination in this patient population, such should be cautiously used.

Concurrent benzodiazepine use in older adults treated with antidepressants in Asia.

ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates. METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed. RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants. CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Anticraving therapy for alcohol use disorder: A clinical review.

AIM: In this review, the author focused on anticraving therapy for alcohol use disorder (AUD) defined by DMS-5. A comprehensive review was carried out on the available published papers on anticraving drugs for treating AUD patients. METHODS: The author described all drugs with anticraving benefits for treating AUD patients approved by the Food and Drug Administration of the United States (US FDA) and European Medicines Agency of the European Union. Then, the commonly prescribed anticraving drugs and those under development were also described. RESULTS: The US FDA-approved anticraving drugs included acamprosate and naltrexone, and those approved by European Medicines Agency were gamma-hydroxybutyrate and nalmefene. The author also highlighted topiramate, gabapentin, ondansetron, LY196044, ifenprodil, varenicline, ABT-436, mifepristone, citicoline, and baclofen. The putative mechanisms of action of and the use in clinical practice of those anticraving drugs were also described. CONCLUSION: Although slowly developing, the field of anticraving drugs is getting into shape as a promising entity of a pharmaceutical class of drugs. Then, the author addressed on the underused issues of those recommended, and suggested anticraving drugs by the practice guideline of the American Psychiatric Association. The author urges that clinicians should be more "adventurous" in prescribing those promising drugs because benefits of those anticraving drugs are far-outweighing the possible side effects of anticraving drugs, or the harms of untreated AUD itself.

Physical comorbidities in older adults receiving antidepressants in Asia.

BACKGROUND: The present study explored the patterns of physical comorbidities and their associated demographic and clinical factors in older psychiatric patients prescribed with antidepressants in Asia. METHODS: Demographic and clinical information of 955 older adults were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Standardized data collection procedure was used to record demographic and clinical data. RESULTS: Proportion of physical comorbidities in this cohort was 44%. Multiple logistic regression analyses showed that older age (OR = 1.7, P < 0.001), higher number of depressive symptoms (OR = 1.09, P = 0.016), being treated in psychiatric hospital (OR = 0.5, P = 0.002), living in high income countries/territories (OR = 2.4, P = 0.002), use of benzodiazepines (OR = 1.4, P = 0.013) and diagnosis of 'other psychiatric disorders' (except mood, anxiety disorders and schizophrenia) (OR = 2.7, P < 0.001) were significantly associated with physical comorbidities. CONCLUSIONS: Physical comorbidities in older patients prescribed with antidepressants were common in Asia. Integrating physical care into the treatment of older psychiatric patients should be urgently considered.

A History of the Pharmacological Treatment of Bipolar Disorder.

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

A Bibliometric Analysis of Scientific Production on Second-Generation Anti-Psychotic Drugs in Malaysia.

OBJECTIVE: We carried out a bibliometric study on the scientific papers related to second-generation antipsychotic drugs (SGAs) in Malaysia. METHODS: With the SCOPUS database, we selected those documents made in Malaysia whose title included descriptors related to SGAs. We applied bibliometric indicators of production and dispersion, as Price's law and Bradford's law, respectively. We also calculated the participation index of the different countries. The bibliometric data were also been correlated with some social and health data from Malaysia (total per capita expenditure on health and gross domestic expenditure on R&D). RESULTS: We found 105 original documents published between 2004 and 2016. Our results fulfilled Price's law, with scientific production on SGAs showing exponential growth (r = 0.401, vs. r = 0.260 after linear adjustment). The drugs most studied are olanzapine (9 documents), clozapine (7), and risperidone (7). Division into Bradford zones yields a nucleus occupied by the Medical Journal of Malaysia, Singapore Medical Journal, Australian and New Zealand Journal of Psychiatry, and Pharmacogenomics. Totally, 63 different journals were used, but only one in the top four journals had an impact factor being greater than 3. CONCLUSION: The publications on SGAs in Malaysia have undergone exponential growth, without evidence a saturation point.

A comparison of clinical characteristics of older adults treated with antidepressants in general and psychiatric hospitals in Asia.

AIM: This study compared the demographics, clinical characteristics, and antidepressant prescription patterns between Asian patients aged 50 years and older attending psychiatric hospitals and those attending general hospitals. METHODS: In total, 955 patients (604 in general hospitals, 351 in psychiatric hospitals) aged 50 years or older treated with antidepressants in 10 Asian countries and territories were examined. Patients' demographics, clinical features, and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. RESULTS: Binary logistic regression revealed that high income and diagnosis of schizophrenia were independently associated with psychiatric hospital treatment, whereas outpatient care, diagnosis of anxiety disorders, and multiple major medical conditions were independently associated with general hospital treatment. In addition, tetracyclic and noradrenergic and specific serotonergic antidepressants were more likely to be prescribed in general hospitals. CONCLUSION: Older adults treated with antidepressants showed different demographic and clinical features between general hospitals and psychiatric hospitals in Asia.

Clinical Use of Mood Stabilizers With Antidepressants in Asia: Report From the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) Projects in 2004 and 2013.

OBJECTIVE: As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries. METHODS: This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling. RESULTS: Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalization > outpatient care, psychiatric > general-medical programs, and young age (all P < 0.001), but not with country, sex, or AD dose. CONCLUSIONS: The findings provide a broad picture of contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.

Valproic Acid and Lithium Meditate Anti-Inflammatory Effects by Differentially Modulating Dendritic Cell Differentiation and Function.

Valproic acid (VPA), with inhibition activity mainly toward histone deacetylase (HDAC) and Glycogen Synthase Kinase (GSK)-3, and lithium, with inhibition activity mainly toward GSK-3, are both prescribed in clinical as mood-stabilizers and anticonvulsants for the control of bipolar disorder. This study aims to compare the immuno-modulation activities of VPA and lithium, especially on the differentiation and functions of dendritic cells (DC). Our data show that treatment with VPA or lithium effectively alleviated the severity of collagen-induced arthritis triggered by LPS in mice. Both agents reduced the serum level of IL-6 and IL-10 after LPS challenge in mice. VPA and lithium both induce significant down-regulation of group I CD1 expression and secretion of IL-6 during differentiation of human monocyte-derived immature DC, while they differ in the induction of CD83 and CD86 expression, secretion of IL-8, IL-10, and TNF-α. Upon stimulation of immature DC with LPS, VPA, and lithium both reduced the secretion of IL-6 and TNF-α. However, only lithium significantly increased the production of IL-10, while VPA increased the production of IL-8 but substantially reduce the secretion of IL-10 and IL-23. Treatment with VPA resulted in a reduced capacity of LPS-stimulated DC to promote the differentiation of T helper 17 cells that are critical in the promotion of inflammatory responses. Taken together, our results suggest that VPA and lithium may differentially modulate inflammation through regulating the capacity of DC to mediate distinct T cell responses, and they may provide a complementary immunomodulatory effects for the treatment of inflammation-related diseases. J. Cell. Physiol. 232: 1176-1186, 2017. © 2016 Wiley Periodicals, Inc.

Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder.

Several genes that are involved in the regulation of circadian rhythms are implicated in the susceptibility to bipolar disorder (BD). The current study aimed to investigate the relationships between genetic variants in NR1D1 RORA, and RORB genes and BD in the Han Chinese population. We conducted a case-control genetic association study with two samples of BD patients and healthy controls. Sample I consisted of 280 BD patients and 200 controls. Sample II consisted of 448 BD patients and 1770 healthy controls. 27 single nucleotide polymorphisms in the NR1D1, RORA, and RORB genes were genotyped using GoldenGate VeraCode assays in sample I, and 492 markers in the three genes were genotyped using Affymetrix Genome-Wide CHB Array in sample II. Single marker and gene-based association analyses were performed using PLINK. A combined p-value for the joining effects of all markers within a gene was calculated using the rank truncated product method. Multifactor dimensionality reduction (MDR) method was also applied to test gene-gene interactions in sample I. All markers were in Hardy-Weinberg equilibrium (P>0.001). In sample I, the associations with BD were observed for rs4774388 in RORA (OR = 1.53, empirical p-value, P = 0.024), and rs1327836 in RORB (OR = 1.75, P = 0.003). In Sample II, there were 45 SNPs showed associations with BD, and the most significant marker in RORA was rs11639084 (OR = 0.69, P = 0.002), and in RORB was rs17611535 (OR = 3.15, P = 0.027). A combined p-value of 1.6×10-6, 0.7, and 1.0 was obtained for RORA, RORB and NR1D1, respectively, indicting a strong association for RORA with the risk of developing BD. A four way interaction was found among markers in NR1D1, RORA, and RORB with the testing accuracy 53.25% and a cross-validation consistency of 8 out of 10. In sample II, 45 markers had empirical p-values less than 0.05. The most significant markers in RORA and RORB genes were rs11639084 (OR = 0.69, P = 0.002), and rs17611535 (OR = 3.15, P = 0.027), respectively. Gene-based association was significant for RORA gene (P = 0.0007). Our results support for the involvement of RORs genes in the risk of developing BD. Investigation of the functional properties of genes in the circadian pathway may further enhance our understanding about the pathogenesis of bipolar illness.

Country variations in depressive symptoms profile in Asian countries: Findings of the Research on Asia Psychotropic Prescription (REAP) studies.

INTRODUCTION: This study was to assess differences in the symptom profile of depressive illness across various countries/territories in Asia. The study was a part of the Research on Asia Psychotropic Prescription project. The participating countries/territories include China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand. METHODS: The pattern of depressive symptoms in 1,400 subjects with depressive disorder from 42 psychiatric centers in 10 Asian countries/territories was assessed. We collected information on socio-demographic and clinical characteristics with a standardized protocol and data collection procedure. RESULTS: The most common presentations of depressive symptoms were persistent sadness, loss of interest, and insomnia. Similar findings were found regardless of the region, country, or its income level. Patients with depressive disorder from high-income countries presented significantly more with vegetative symptom cluster (P < 0.05), while those from the upper middle-income countries had significantly more with both mood (P < 0.001) and cognitive symptom clusters (P < 0.01). In lower middle-income countries, patients with depressive symptoms had significantly less mood symptom cluster (P < 0.001) but significantly more cognitive symptom cluster (P < 0.05). DISCUSSION: This study demonstrates that in Asia, despite variations in the initial symptom reported by the patients, across different countries/territories, core depressive symptoms remain the same. Variations have been found in presentation of depressive symptoms with regards to the level of income of countries. Physical or vegetative symptoms were reported more by centers in higher income countries, while depressive cognition and suicidal thoughts/acts were more frequently reported from lower income countries.

International study on antidepressant prescription pattern at 40 major psychiatric institutions and hospitals in Asia: A 10-year comparison study.

INTRODUCTION: Research in prescription pattern of antidepressants in Asia is lacking. This study aims to compare the antidepressants prescription pattern in Asia in 2003-2004 and 2013. METHODS: The Research in East Asia Psychotropic Prescription Pattern on Antidepressants (REAP-AD) had worked collaboratively in 2003-2004 (REAP-AD 2003/2004) and 2013 (REAP-AD 2013) to study the prescription pattern of antidepressants in Asia. The REAP-AD 2013 study was conducted in China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand using a unified research protocol and questionnaire. RESULTS: Forty psychiatric centers participated in REAP-AD 2013 and a total of 2,319 patients receive antidepressants were analyzed. In 2013, 39.6% of the antidepressant prescriptions were for diagnoses other thandepressive disorder compared with 38.4% in REAP-AD 2003/2004. Out of all the antidepressants listed in the Anatomical Therapeutic Chemical Classification index by the World Health Organization Collaborating Center for Drug Statistics Methodology (Oslo), only 38% antidepressants were prescribed in participating centers in 2013 compared with 46% in REAP-AD 2003/2004. The selective serotonin reuptake inhibitors were the most common antidepressant prescribed in the participating centers, which was similar to the 2003-2004 survey. Prescription of newer generation antidepressants had increased in 2013 survey; on the contrary, prescription of tricyclic antidepressants had reduced. DISCUSSION: This study has contributed significantly in relation to the changing patterns of antidepressant use in all the participating Asian centers in the last 10 years. The findings are important in shaping optimal antidepressant prescription and future policy making.

Tramadol-related psychosis in a patient with bipolar I disorder.

INTRODUCTION: Tramadol hydrochloride (HCl) is a centrally acting synthetic opioid analgesic. Psychotic symptoms are relatively rare in reported adverse events. Here, we report a patient who presented with tramadol-related psychotic symptoms. CASE: A 59-year-old female had underlying bipolar I disorder and received lithium treatment with stable affective status. 1 month before hospitalisation, she had been taking tramadol HCl/acetaminophen for joint pain. She then developed obvious persecutory delusion. However, her clinical picture did not meet the criteria of any mood episode. After treatment of risperidone in addition to lithium, she was discharged without any psychotic symptom. She remained euthymic without any psychotic symptom on monotherapy of lithium (300 mg) three tablets once daily. CONCLUSIONS: Tramadol HCl is commonly prescribed in clinical practice and psychotic symptoms related to it are uncommon. We should be careful about the rare but important adverse events while prescribing tramadol HCl.

Hepatotoxicity induced by clozapine: a case report and review of literature.

Clozapine is an effective antipsychotic drug but is associated with serious side effects. Most treatment guidelines give no clear recommendations on regular monitoring of liver function tests, even though up to 60% of patients experience elevations in hepatic transaminases, with 15% to 30% experiencing an elevation two to three times greater than normal. Though elevations in liver function tests are often transient and asymptomatic, there are many reported cases of clozapine-induced hepatotoxicity, with damage to the liver, involvement of multiple organs, and even fulminant liver failure arising with moderate clozapine doses. This case report describes a Chinese woman who developed hepatotoxicity on a low dose of clozapine, and reviews the relevant literature.

Hashimoto's encephalopathy mimicking presenile dementia.

Hashimoto's encephalopathy (HE), which carries kaleidoscopic clinical presentations, is easily misdiagnosed in clinical practice. Early diagnosis and prompt initiation of steroid therapy are associated with good prognosis. We describe a 50-year-old female patient who had subclinical hypothyroidism and who presented herself with gradual cognitive impairment, accompanied with auditory hallucination and delusion. Increased anti-thyroid antibodies titers were found in her serum and cerebrospinal fluid. The HE diagnosis was confirmed using the laboratory test for anti-thyroid antibodies along with the patient's clinical presentation. We treated her with steroid pulse therapy, and the results were favorable. We highlight this case to call for early diagnosis and prompt intervention of HE in clinical practice.

Familiality and clinical outcomes of sleep disturbances in major depressive and bipolar disorders.

OBJECTIVE: Sleep disturbances are frequently observed in major depressive (MDD) and bipolar disorder (BD). This study reported sleep profiles of patients and their relatives versus controls, and examined the familiality of sleep features in mood disorder families. We also evaluated the influences of sleep disturbance on patients' quality of life (QOL), functional impairment, and suicidality. METHODS: We recruited 363 BD and 157 MDD patients, 521 first-degree relatives, and 235 healthy controls, which completed a diagnostic interview, Pittsburgh Sleep Quality Index (PSQI), and QOL questionnaire. The magnitude of heritability of sleep features was calculated and familiality was evaluated by mixed regression models and intraclass correlation coefficient (ICC). The associations between sleep problems and clinical outcomes were examined using multiple regression models. RESULTS: More than three-quarters of mildly-ill patients were classified as "poor sleepers". MDD patients had significantly worse sleep quality as compared to BD patients. Moderate but significant familial aggregation was observed in subjective sleep quality, sleep latency, disturbance, daytime dysfunction, and global score (ICC=0.10-0.21, P<.05). Significant heritability was found in sleep quality (0.45, P<.001) and sleep disturbance (0.23, P<.001). Patients with good sleep quality had better QOL and less functional impairment (P<.05) than poor sleepers. Poor sleep quality and nightmares further increased the risk for suicidal ideation (ORadj=2.8) and suicide attempts (ORadj=1.9-2.8). CONCLUSION: Subjectively measured sleep features demonstrated significant familiality. Poor sleep quality further impaired patients' daily function and QOL, in addition to increasing the risk of suicidality, and thus requires special attention in related clinical settings.

La investigación sobre fármacos antipsicóticos atípicos en España: una evaluación bibliométrica / Mapping the scientific research on atypical antipsychotic drugs in Spain: a bibliometric assessment

Objetivos: Se llevó a cabo un estudio bibliométrico de las publicaciones sobre fármacos antipsicóticos atípicos (AA) realizadas en España. Método: Se usaron las bases de datos EMBASE y MEDLINE y se aplicaron indicadores bibliométricos de productividad y dispersión de artículos (leyes de Price y de Bradford, respectivamente).También se calculó el índice de participación (IP)de los diferentes países y se buscaron correlaciones entre los datos bibliométricos y algunos datos sociales y de salud(gasto total per capita en salud y gasto interior bruto en investigación y desarrollo).Resultados: Se recopilaron 656 artículos originales publicados entre 1988 y 2011. Nuestros resultados constatan el cumplimiento de la ley de Price en la producción científica sobre AA, mostrando un crecimiento exponencial (coeficiente de correlación r = 0,9693 vs. r = 0,9177 después del ajuste lineal).Los fármacos más estudiados fueron la risperidona (181 artículos), la olanzapina (143), la clozapina (94) y la quetiapina (74). La división en zonas de Bradford dio lugar a un núcleo ocupado por las revistas European Psychiatry y European Neuropsychopharmacology (70 artículos). En total se publicaron artículos en 194 revistas diferentes, de las cuales 5de las 10 primeras tenían un factor de impacto mayor de 4.Conclusión: Las publicaciones sobre AA en España han experimentado un crecimiento exponencial en el período estudiado, sin evidencia de que se haya alcanzado un punto de saturación (AU)

Objectives: We carried out a bibliometric study on the scientific publications in relation to atypical antipsychotic drugs (AADs) in Spain. Methods: We used the EMBASE and MEDLINE databases and we applied some bibliometric indicators of paper production and dispersion (Price’s law and Bradford’s law, respectively). We also calculated the participation index of the different countries and correlated the bibliometric data with some social and health data (total per capita expenditure on health and gross domestic expenditure on research and development).Results: We collected 656 original papers published between 1988 and 2011. Our study results fulfilled Price’s law with scientific production on AADs showing exponential growth (correlation coefficient r = 0.9693, vs. r = 0.9177 after linear adjustment). The most widely studied drugs were risperidone (181 papers), olanzapine (143), clozapine (94),and quetiapine (74). Division into Bradford zones yielded a nucleus occupied by the European Psychiatry and European Neuropsychopharmacology (70 articles). Totally 194 different journals were published, with 5 of the first 10 usedj ournals having an impact factor being greater than 4.Conclusion: The publications on AADs in Spain have undergone exponential growth over the studied period, without evidence of reaching a saturation point (AU)

Mapping the scientific research on atypical antipsychotic drugs in Spain: a bibliometric assessment.

OBJECTIVES: We carried out a bibliometric study on the scientific publications in relation to atypical antipsychotic drugs (AADs) in Spain. METHODS: We used the EMBASE and MEDLINE databases and we applied some bibliometric indicators of paper production and dispersion (Price's law and Bradford's law, respectively). We also calculated the participation index of the different countries and correlated the bibliometric data with some social and health data (total per capita expenditure on health and gross domestic expenditure on research and development). RESULTS: We collected 656 original papers published between 1988 and 2011. Our study results fulfilled Price's law with scientific production on AADs showing exponential growth (correlation coefficient r = 0.9693, vs. r = 0.9177 after linear adjustment). The most widely studied drugs were risperidone (181 papers), olanzapine (143), clozapine (94), and quetiapine (74). Division into Bradford zones yielded a nucleus occupied by the European Psychiatry and European Neuropsychopharmacology (70 articles). Totally 194 different journals were published, with 5 of the first 10 used journals having an impact factor being greater than 4. CONCLUSION: The publications on AADs in Spain have undergone exponential growth over the studied period, without evidence of reaching a saturation point.

Taiwan consensus of pharmacological treatment for bipolar disorder.

Bipolar disorder is an important psychiatric disorder with different disease phases. The pharmacological treatment is complicated, and is updated frequently as new research evidence emerges. For the purpose of international collaboration, research, and education, the Taiwan consensus of pharmacological treatment for bipolar disorders was initiated by the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) - the Bipolar Chapter, which was established in August 2010 and approved as a member of International Society of Bipolar Disorder. TSBPN is the country member of the World Federation of Societies of Biological Psychiatry (WFSBP). The development of the Taiwan consensus for bipolar disorder was mainly based on the template of WFSBP Guidelines, with references to other international guidelines including the Canadian Network for Mood and Anxiety Treatments, and British Association for Psychopharmacology. We have also added Taiwanese experts' experience, Taiwan national health insurance data, and the indications for the pharmacological treatment of bipolar disorder given by the Taiwan Department of Health, to emphasize the balance between efficacy and safety, and to make this consensus a concise, empirical, and important reference for clinical psychiatric practice.