Risk of First Onset Stroke in SSRI-Exposed Adult Subjects: Survival Analysis and Examination of Age and Time Effects.

OBJECTIVE: Exposure to selective serotonin reuptake inhibitors (SSRIs) has been shown to increase the risk of stroke. In this study, we investigated age and time effects on the risk of first onset stroke in SSRI-exposed (SSRIEXP) adult subjects. METHODS: We analyzed an 8-year cohort from the National Health Insurance Research Database, Taiwan. Patients were defined as SSRIEXP subjects if they received SSRI prescriptions for at least 2 consecutive months during January 1, 2001, to December 31, 2007. Otherwise, they were categorized as SSRI-nonexposed (SSRINONE) subjects. Stroke diagnosis was made according to ICD-9 codes 430-432 (hemorrhagic stroke) and 433-437 (ischemic stroke). RESULTS: Kaplan-Meier survival analysis showed a greater probability of first onset stroke in SSRIEXP than SSRINONE subjects (P < .001). The higher incidence rates in SSRIEXP subjects persisted to the 3 year time point. Ischemic/hemorrhagic stroke cumulative incidence ratios were also higher during the first 3 years in SSRIEXP subjects. Analysis of adjusted hazard ratios indicated that younger SSRIEXP subjects were more likely to experience stroke, with a slight increase of risk in subjects older than 65 years. Stratified analysis of ischemic stroke and hemorrhagic stroke resulted in a similar hazard ratio trend. CONCLUSIONS: Use of SSRIs independently increases the risk of stroke across age strata. The risk is higher in younger adult subjects, and the stroke is more likely to be ischemic than hemorrhagic. The underlying mechanisms of stroke may be related to cerebral microbleeding or an overcorrection of hemostasis function.

Newly diagnosed panic disorder and the risk of erectile dysfunction: A population-based cohort study in Taiwan.

Previous studies indicated that panic disorder is correlated with erectile dysfunction (ED). The primary aim of this study was to explore the incidence rate of ED among panic disorder patients in an Asian country. The secondary aim was to compare the risk of ED in panic disorder patients that were treated with different kinds of antidepressants, and to explore the possible mechanism between these two disorders. We identified 1393 male patients with newly diagnosed panic disorder from the Taiwan's National Health Insurance Database. Four matched controls per case were selected for the study group by propensity score. After adjusting for age, obesity and comorbidities, the panic disorder patients had a higher hazard ratio of ED diagnosis than the controls, especially among the untreated panic disorder patients. This retrospective dynamic cohort study supports the link between ED and prior panic disorder in a large sample of panic disorder patients. This study points out the need of early antidepressant treatment for panic disorder to prevent further ED.

A Case Report of Probable Paliperidone ER-Induced Serotonin Syndrome in a 17-Year-Old Taiwanese Female With New Onset Psychosis.

A 17-year-old female with new-onset psychosis was treated with paliperidone. After increasing the paliperidone dose to 12 mg per day the patient developed a series of side effects; Tachycardia (140 bpm), severe drooling, restlessness, diaphoresis, whole-body tremor, inducible foot clonus, predominant lower limbs rigidity, bilateral pupil dilation, increased bowel sounds with watery diarrhea, and muscle hypertonicity. The symptoms subsided after stopping the paliperidone, and recurred after resuming paliperidone 9 mg per day. To our knowledge, this is the first case of a very clear and close relationship between the symptoms of serotonin syndrome and the use of paliperidone. We have to cautiously consider the diagnosis of serotonin syndrome in potential cases.

A Case Report of Late Onset Mania Caused by Hyponatremia in a Patient With Empty Sella Syndrome.

Recurrent manic-like episodes can be induced by hyponatremia possibly due to empty sella syndrome. In the present case, the patient was proven to have syndrome of inappropriate antidiuretic hormone (SIADH) secretion with manic symptoms that resolved after the normalization of the plasma sodium level.To our knowledge, this is the first case of hyponatremia-induced manic symptoms in a patient with empty sella syndrome. More attention should be paid to late-onset mania, because it may be the sign of a more serious medical problem.

Secondary mania due to AIDS and cryptococcal meningitis in a 78-year-old patient.

We report a 78-year-old man without past psychiatric history who experienced his first manic episode successfully treated with quetiapine and lorazepam, but was ultimately found to have AIDS and Cryptococcus neoformans meningitis. Our presented case highlights the importance of comprehensive differential diagnoses to rule out secondary causes of psychiatric symptoms presenting for the first time in elderly patients.

Duration of Untreated Psychosis and Brain Function during Verbal Fluency Testing in First-Episode Schizophrenia: A Near-Infrared Spectroscopy Study.

A longer duration of untreated psychosis (DUP) has been associated with poor clinical outcomes in patients with schizophrenia (SZ); however, it remains unclear whether this is due to neurotoxic effects of psychosis. The purpose of this study was to use near-infrared spectroscopy (NIRS) to investigate the influence of DUP on brain function using two verbal fluency tests (VFTs) in patients with first-episode SZ (FES). A total of 28 FES patients and 29 healthy controls (HC) underwent NIRS during VFTs. Group comparisons of cortical activity were made using two-tailed t-tests and the false discovery rate method. We then examined the associations between DUP and hemodynamic changes in each channel to identify any effects of DUP on brain cortical activity. During the letter VFT, the HC group exhibited significantly greater cortical activations over bilateral frontotemporal regions compared to FES patients. However, this distinction was not observed while performing a category version of the VFT. In addition, no associations between DUP and brain cortical activity were observed in the FES group during either VFT. In conclusion, we did not find an association between DUP and frontotemporal cortical activities. This might be because neurodevelopmental disturbances result in neurocognitive deficits long before psychotic symptoms onset.

A reduced risk of stroke with lithium exposure in bipolar disorder: a population-based retrospective cohort study.

OBJECTIVES: The risk of stroke is increased in patients with bipolar disorder. Lithium exhibits neuroprotective effects but the association between lithium use and the risk of stroke is unknown. METHODS: A population-based retrospective cohort study was conducted by utilizing the National Health Insurance Research Database in Taiwan. Subjects who had first been diagnosed with bipolar disorder between 2001 and 2006 were identified. A propensity score (PS) for receiving lithium was calculated with variables of age, gender, and comorbidities. The patients with bipolar disorder receiving lithium within the period from diagnosis through to December 2011 were designated as the lithium group (n = 635). A 1:2 ratio was used to select PS-matched subjects with bipolar disorder without lithium use (n = 1,250). Multivariate Cox proportional hazards regression models were used to explore the association, rather than causal inference, of lithium exposure and the risk of stroke. RESULTS: Of the 1,885 subjects, 86 (4.6%) experienced stroke, including 2.8% of the lithium group and 5.4% of the non-lithium group. Lithium use was associated with a significantly reduced risk of stroke [hazard ratio (HR) = 0.39, 95% confidence interval (CI): 0.22-0.68]. Reduced risks of stroke were also associated with the highest cumulative lithium dose [≥720 defined daily dose (DDD), HR = 0.25, 95% CI: 0.10-0.59], the longest cumulative exposure period (≥720 days, HR = 0.20, 95% CI: 0.06-0.64), and the highest exposure rate (≥2 DDD/day, HR = 0.39, 95% CI: 0.21-0.70). CONCLUSIONS: Lithium use was significantly related to a reduced risk of stroke in patients with bipolar disorder.

Risk of depressive disorders in women undergoing hysterectomy: A population-based follow-up study.

OBJECTIVE: The objective of this study was to assess the risk of depressive disorders in women who underwent hysterectomy in Taiwan. METHODS: A retrospective study was conducted in a matched cohort of cases using the National Health Insurance Research Database of Taiwan. Database records from 1689 women who underwent hysterectomy between 2001 and 2005 were included in this study. A control group matched for age and physical comorbidity was selected from the same database (n = 6752). For all cases, medical records were tracked until the end of 2009 to identify whether a depressive disorder was diagnosed during the follow-up period. The hazard ratio (HR) for depression during the observation period was analyzed using multivariable Cox proportional-hazards models, adjusted for age, physical comorbidities, and other socioeconomic factors. RESULTS: The HR for depression was 1.78 times higher for the group that underwent hysterectomy than for the control group (adjusted HR = 1.78; 95% CI = 1.46-2.18, p < 0.001). In addition, HR for major depressive disorder in women who underwent hysterectomy was significantly higher (1.84 times) than for the control group (adjusted HR = 1.84; 95% CI = 1.23-2.74, p < 0.01). CONCLUSIONS: Our study revealed that, in Taiwan, women who underwent hysterectomy had an increased risk of developing depression. Longitudinal studies to follow-up the psychological outcomes in Taiwanese women who underwent hysterectomy will be necessary to confirm our findings.

Successful treatment of treatment-resistant schizophrenia in a 10-year-catatonic patient by augmentation of selective serotonin reuptake inhibitors: a case report.

Although catatonia is a well defined syndrome, the treatment of chronic catatonia remains an unresolved issue. Here, we report a successful treatment of a 30-year-old patient with treatment-resistant catatonic schizophrenia in 10 years by augmentation of selective serotonin reuptake inhibitors (SSRIs).We present a 30-year-old man with treatment-resistant catatonic schizophrenia who failed to respond to the treatment of benzodiazepines and antipsychotics for 10 years. He markedly improved after taking SSRIs. Now, he does not hold odd postures and begins to talk and show more facial expressions.We postulate that the therapeutic effect is related to the enhancement of 5-HT neurotransmission. SSRIs can be a considerable choice to treat chronic catatonia.

Common factors associated with choking in psychiatric patients.

BACKGROUND: Choking is common among psychiatric patients and represents one of the main causes of death in this patient population. PURPOSE: We aimed to identify common factors associated with choking among psychiatric patients. METHODS: The demographic information and medical history of 250 psychiatric patients living in an acute psychiatric ward were retrieved from medical charts, interview records, and check lists. Coughing while eating and swallowing difficulties were assessed based on patient self-reports. The main outcomes were choking while taking drugs (CTD) as observed by nursing staffs and choking experiences during hospitalization (CEH) as reported by the patients. Chi-square tests were used to examine the potential associations among the independent variables. Multiple logistic regression was used to further examine those independent variables found to be significantly associated with CTD to estimate their relative contributions. RESULTS: CEH was reported in 50.8%, and CTD was observed in 17.6% of study participants. Use of anxiolytics, consuming a semiliquid or liquid diet, coughing while eating, and swallowing difficulties were found to be associated with CTD. Coughing while eating was the only independent variable associated with CEH. Further logistic regression on the relationships between CTD and variables including the use of anxiolytics, coughing while eating, and swallowing difficulties showed the independent contributions of these variables in the model. The odds ratios were 12.8 (p = .003), 16.7 (p < .001), and 21.7 (p = .001) for each of the three respective variables. CONCLUSION: The use of anxiolytics, coughing while eating, and swallowing difficulties all potentially contributed to the choking events in our sample. Additional precautions should thus be taken in caring for psychiatric patients who use anxiolytics, who have a history of coughing while eating, or who exhibit swallowing difficulties to prevent choking events.

The epidemiology and progression time from transient to permanent psychiatric disorders of substance-induced psychosis in Taiwan.

INTRODUCTION: Substance-induced psychosis (SIP), including alcohol-induced psychotic disorder (AIPD) and substance-induced psychotic disorder (SIPD), is gradually increasing in importance in clinical practice. However, few studies have investigated the epidemiology and progression time from transient to permanent psychiatric disorders for AIPD and SIPD patients. METHODS: We utilized the National Health Insurance Research Database (NHIRD) to investigate the incidence and prevalence of AIPD and SIPD in Taiwan and determined the timing of AIPD or SIPD followed by the development of persistent psychotic conditions. RESULTS: The average incidence and prevalence were 1.97 and 2.94 per 100,000 person-years for AIPD, 3.09 and 5.67 per 100,000 person-years for SIPD in Taiwan. Moreover, 10.9% to 24.3% of subjects with either AIPD or SIPD had a change in diagnosis to either schizophrenia or affective disorder, and ~50% of patients had a psychotic or affective transformation in their first year after AIPD and SIPD diagnoses. The mean progression time of psychotic or affective transformation was 1.9 to 2.7 years. CONCLUSIONS: SIP is a predictive factor for persistent psychotic and affective transformation, and a three-year follow-up may be an optimal clinical practice to prevent psychotic or affective transformation in 60% of patients.

Prevalence of gastroesophageal reflux disease in major depressive disorder: a population-based study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common physical disease among psychiatric patients. OBJECTIVE: We conducted this study to investigate the prevalence and risk of GERD in patients with major depressive disorder (MDD) in Taiwan. METHODS: We conducted a cross-sectional study using the National Health Insurance Research Database in Taiwan. The study subjects included 4790 patients with MDD and 728,749 people in the general population during 2005. Distributions of GERD as well as age, gender, income, region of residence, and medical comorbidities, such as diabetes mellitus, hypertension, renal disease, hyperlipidemia, and ischemic heart disease, in the 2 groups were examined by χ(2)-tests. Multivariate logistic regression models were used to analyze the associations between MDD and GERD. RESULTS: The 1-year prevalence rates of GERD in patients with MDD and the general population were 3.75% and 1.05%, respectively. The prevalence rate of GERD was significantly higher in patients with MDD in all age, sex, insurance amount, region, and urbanicity subgroups (all p < 0.001). The multivariate logistic regression analysis showed that patients with MDD were significantly associated with an increased rate for GERD ([Odds Ratio] = 3.16; 95% Confidence Interval = 2.71-3.68; p < 0.001). CONCLUSION: The prevalence of GERD was significantly higher in patients with MDD. In clinical practice, psychiatrists should pay attention to the possibility of GERD symptoms, such as heartburn, regurgitation, or dysphagia, and should consider consulting Gastroenterology specialists when clinically indicated.

A randomized controlled trial of an adapted Illness Management and Recovery program for people with schizophrenia awaiting discharge from a psychiatric hospital.

OBJECTIVE: Most research on the Illness Management and Recovery (IMR) program for people with severe mental illnesses has focused on individuals with stable symptoms living in the community, with less attention to persons being treated in an inpatient setting. We evaluated the feasibility and effects of an IMR program adapted for individuals with schizophrenia who were awaiting discharge into the community. METHOD: A randomized controlled trial was conducted at 2 hospitals in Taiwan to compare the adapted IMR program with treatment as usual (TAU). Ninety-seven individuals with schizophrenia were randomized to the adapted IMR program or TAU. Four outcome indicators including illness-management knowledge, attitudes toward medication, insight, and symptoms were assessed at baseline, posttreatment, and at a 1-month follow-up following discharge from the hospital. RESULTS: Participants in the adapted IMR group showed significantly greater improvements at posttreatment and 1-month follow-up in illness-management knowledge, attitudes toward medication, insight, and negative symptoms on the Brief Psychiatric Rating Scale (BPRS) than individuals in the TAU group. There were no significant differences between the 2 groups on other subscales of the BPRS. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This is the first controlled evaluation of a version of the IMR program in an East Asian culture, and the first to evaluate it in an acute care inpatient setting. Our findings support the feasibility and potential benefits of implementing an adapted IMR program, focused on the prevention of relapses and rehospitalizations, during the discharge period of an inpatient treatment stay to prepare individuals to reenter the community.

Antipsychotic formulation and one-year rehospitalization of schizophrenia patients: a population-based cohort study.

OBJECTIVE The authors compared the efficacy of long-acting injectable antipsychotics and oral antipsychotics on rehospitalization rate of community-dwelling patients with schizophrenia who had frequent admissions. METHODS The cohort study of 14,610 patients was conducted by analyzing the Taiwan National Health Research Institutes data. The patients were divided into groups that received oral antipsychotics (risperidone, a different second-generation antipsychotic, or a first-generation antipsychotic) or long-acting injectable antipsychotics (risperidone, haloperidol, or flupenthixol). RESULTS One-year rehospitalization rates of the final cohort of 10,552 patients were the same for both groups (by long-acting injection, 27.3%; by oral administration, 27.3%). Secondary analysis of groups receiving long-acting injectable medication showed that haloperidol resulted in lower rehospitalization rates (haloperidol, 22.5%; risperidone, 27.1%; and flupenthixol, 29.5%). Patients' characteristics, including age, region, and insurance payments were significantly correlated with the risk of relapse (p<.05). CONCLUSIONS Except for injectable haloperidol, long-acting injectable antipsychotics seem not to be superior to oral antipsychotics in reducing rehospitalization.

A pilot study of an illness management and recovery program in discharged patients with schizophrenia.

BACKGROUND: Accumulated evidence supports the effectiveness of equipping chronically ill patients with illness management knowledge and skills. The Illness Management and Recovery (IMR) program developed by the United States government has been widely adopted for persons with mental illness. However, few studies support its effectiveness in patients with schizophrenia. PURPOSE: This pilot study developed a culturally adapted and abbreviated version of the IMR for Taiwanese patients with schizophrenia who were ready for discharge from the hospital. Furthermore, we investigated the impact of the program in terms of illness knowledge, drug attitude, insight, and psychopathology. METHODS: The original IMR was condensed and modified for implementation during participants' preparation for hospital discharge. Using a preexperimental design, pretest and posttest assessments for a single group of 26 participants received the new IMR twice a week for 3 weeks on the four outcome indicators of illness knowledge, drug attitude, insight, and psychopathology. RESULTS: Participants improved in terms of treatment-related illness knowledge, insight, and affective-domain psychopathology (p < .01) after intervention completion. Average participant attendance was 5.45 sessions out of 6 total sessions. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The intensive symptom and medication-focused IMR model for soon-to-be-discharged patients with schizophrenia had positive impacts on illness management. In the future, studies using a two-group randomized controlled design and extended follow-up should be conducted to determine the long-term effects of IMR.

Birth seasonality in schizophrenia: effects of gender and income status.

AIMS: The aim of this study was to examine the correlations of birth seasonality in schizophrenia, considering influences of gender and income status. METHODS: The sample consisted of 1 000 000 people in the general population randomly selected from the Taiwan National Health Insurance Research Database. Data for the birth-year period 1950-1989 were extracted for analysis (n = 631 911; 306 194 male, 325 717 female). Subjects with schizophrenia (2796 male, 2251 female) were compared with the general population. Subgroups divided by birth-year periods (10-year interval), gender, and income status (low, medium, high) were analyzed using both the Walter and Elwood seasonality and chi-squared tests. RESULTS: The winter/spring birth excess in schizophrenia was 5.3% when compared with the general population. There was a statistically significant excess in winter/spring births than summer/autumn births inschizophrenia patients (relative risk [RR], 1.12; 95% confidence interval [CI]: 1.06-1.18). This winter/spring birth excess in schizophrenia was observed only in female subjects (RR, 1.20; 95%CI: 1.10-1.30), not in male subjects (RR, 1.03; 95%CI: 0.98-1.14), in all subgroups of income status, but was most pronounced in the low income subgroup (RR, 1.20, 1.09, 1.13; 95% CI: 1.05-1.37, 1.01-1.17, 1.02-1.25 for low, medium, and high income status, respectively). CONCLUSION: A gender difference with female predominance of the effect of birth seasonality in schizophrenia, and a more pronounced effect in low income status were noted.

Newly diagnosed major depressive disorder and the risk of erectile dysfunction: a population-based cohort study in Taiwan.

INTRODUCTION: The primary aim of this study was to explore the incidence rate of erectile dysfunction (ED) among major depressive disorder (MDD) patients in an Asian country. The second aim was to compare the risk of ED in MDD patients that were treated using antidepressants with a high risk-ED, antidepressants with a low risk-ED, or without treatment. METHODS: We identified 4339 male patients with newly diagnosed MDD using the National Health Database. Four matched controls per case were selected for the study. RESULTS: The mean age of the participants was 42.3 ± 16.9. A higher crude HR of 3.6 (95% CI: 2.8-4.6) was seen in the male patients with MDD. After adjusting for obesity, monthly income, urbanization level, and comorbidity, the MDD patients had a 3.2-fold higher HR for an ED diagnosis than the controls. Patients with untreated depression had the highest risk of ED, compared to the control group (HR=3.9). Patients treated with IHiRA had a medium risk of developing ED (HR=3.6), and patients treated with ILoRA had the lowest risk of ED (HR: 2.5). CONCLUSION: This prospective cohort study found an association between ED and prior MDD. Patients with untreated depression may have the highest risk of developing ED.

The association of selective serotonin reuptake inhibitors use and stroke in geriatric population.

OBJECTIVES: Selective serotonin reuptake inhibitor (SSRI) exposure has controversial results in increasing the stroke risk. With the risk of stroke increased with age, the safety of SSRI use among older adults attracts much concern. METHODS: We analyzed 28,145 subjects older than 65 years from a subset of a 9-year cohort database from the National Health Insurance Research Database, Taiwan. RESULTS: The survival analysis showed a greater probability of stroke in subjects with SSRI exposure after adjusting other covariates. Compared with other variables, SSRI exposure had the strongest effect (hazard ratio: 2.66, 95% confidence interval: 2.21-3.20). The risk was independent to depression-related stroke risk. CONCLUSIONS: The use of SSRIs independently increases the risk of stroke among older patients. SSRIs are still practically safe to most users, providing precautionary measures are taken.

Prevalence of allergic rhinitis in patients with attention-deficit/hyperactivity disorder: a population-based study.

Allergic rhinitis (AR) is common in children. Characteristic symptoms of AR may result in daytime inattention, irritability, and hyperactivity, which are also components of ADHD. Conflicting data in previous studies exist regarding the relationship between ADHD and AR. The aim of this study was to examine the prevalence and risk of AR in ADHD patients in Taiwan. We conducted a cross-sectional study using the National Health Insurance Research Database in Taiwan. The study subjects included 469 patients who received psychiatric care for ADHD in 2005 and the general population (n = 220,599). Distributions of age, gender, and living areas as well as allergic diseases in the general population and in the ADHD group were examined by χ2 tests. Multivariate logistic regression models were used to analyze the risk factors of AR. The prevalence of AR in ADHD group and the general population was 28.4 and 15.2%, respectively. The prevalence of asthma was 9.6% in ADHD group and 6.4% in the general population. Both the prevalence of AR (p < 0.001) and asthma (p = 0.008) was significantly higher in ADHD group than the general population. The multivariate logistic regression analysis showed that ADHD patients had an increased rate of AR than general population (OR = 1.83; 95% CI = 1.48-2.27; p < 0.0001), and asthma was strongly associated with AR (OR = 9.28; 95% CI = 8.95-9.63; p < 0.0001). Our data showed that ADHD patients had an increased rate of AR. Therefore, psychiatrists should be more aware of the comorbidity of AR when treating ADHD patients.