Sudarshan Kriya Yoga Program in Posttraumatic Stress Disorder: A Feasibility Study.

BACKGROUND: Sudarshan Kriya Yoga (SKY), a breath-based yoga intervention, has demonstrated safety and efficacy in posttraumatic stress disorder (PTSD) patients subsequent to natural disaster or war, but has not been explored in civilians with PTSD from a wider range of trauma. We hypothesized that it would be feasible to conduct a clinical trial of SKY in PTSD resulting from a wide range of trauma. METHODS: Outcomes were feasibility measures including rates of enrollment and retention, adherence to study protocol; as well as changes in PTSD symptoms, other mood symptoms, and physiological measures. Male and female participants aged 18-75 years were enrolled in a feasibility trial. They attended a 6-day learning phase of SKY followed by 7 sessions over 11 weeks as an adjunct to their usual treatment. RESULTS: Forty-seven participants were screened and 32 were enrolled over 9 months. Consistent with retention rates of other PTSD trials, 13 withdrew from the study prior to week 12. Twenty-one participants met intervention attendance requirements, completed 95% of planned study assessments and were included in final analyses. Participants experienced clinically significant decrease in PTSD symptoms on the posttraumatic stress disorder checklist (PCL-5) scores at week 12 mean difference, Mdiff (standard deviation [SD]) = -10.68 (14.03), P = 0.004; Cohen's d = 0.58, which was sustained at week 24 Mdiff (SD) = -16.11 (15.20), P < 0.001; Cohen's d = 0.91. CONCLUSIONS: It is possible to conduct a clinical trial of SKY in a routine psychiatry clinic serving patients with PTSD due to a wide range of trauma. Future studies should include an RCT design.

Can We Improve Physical Health Monitoring for Patients Taking Antipsychotics on a Mental Health Inpatient Unit?

BACKGROUND: Patients with severe mental illness are at risk of medical complications, including cardiovascular disease, metabolic syndrome, and diabetes. Given this vulnerability, combined with metabolic risks of antipsychotics, physical health monitoring is critical. Inpatient admission is an opportunity to screen for medical comorbidities. Our objective was to improve the rates of physical health monitoring on an inpatient psychiatry unit through implementation of an electronic standardized order set. METHODS: Using a clinical audit tool, we completed a baseline retrospective audit (96 eligible charts) of patients aged 18 to 100 years, discharged between January and March 2012, prescribed an antipsychotic for 3 or more days. We then developed and implemented a standard electronic admission order set and provided training to inpatient clinical staff. We completed a second chart audit of patients discharged between January and March 2016 (190 eligible charts) to measure improvement in physical health monitoring and intervention rates for abnormal results. RESULTS: In the 2012 audit, thyroid-stimulating hormone (TSH), blood pressure, blood glucose, fasting lipids, electrocardiogram (ECG), and height/weight were measured in 71%, 92%, 31%, 36%, 51%, and 75% of patients, respectively. In the 2016 audit, TSH, blood pressure, blood glucose, fasting lipids, ECG, and height/weight were measured in 86%, 96%, 96%, 64%, 87%, and 71% of patients, respectively. There were statistically significant improvements (P < 0.05) in monitoring rates for blood glucose, lipids, ECG, and TSH. Intervention rates for abnormal blood glucose and/or lipids (feedback to family doctor and/or patient, consultation to hospitalist, endocrinology, and/or dietician) did not change between 2012 and 2016. CONCLUSIONS: Electronic standardized order set can be used as a tool to improve screening for physical health comorbidity in patients with severe mental illness receiving antipsychotic medications.

Quality Review in Psychiatry.

This position paper has been substantially revised by the Canadian Psychiatric Association's Professional Standards and Practice Committee and approved for republication by the CPA's Board of Directors on August 31, 2016. The original position paper1 was developed by the Professional Standards and Practice Council and approved by the Board of Directors on April 9, 1994.

Academic detailing among psychiatrists - feasibility and acceptability.

Purpose Research has shown that academic detailing (AD), which includes repeated in-person educational messages in an interactive format in a physician's office, is among the most effective continuing medical education (CME) forms for improving prescribing practices and reducing drug costs. The purpose of this paper is to investigate AD's feasibility and acceptability as an educational tool among psychiatrists and its ability to facilitate positive changes in antipsychotic prescribing. Design/methodology/approach All psychiatrists practicing in Southwestern Ontario, Canada were invited to participate. Participants (32/299(10.7 percent)) were provided with two educational sessions by a healthcare professional. Participants evaluated their AD visits and completed a pre- and post-AD questionnaire measuring various prescribing practice aspects. Findings A total of 26 out of 32 (81.3 percent) participants completed the post-AD evaluation; most of them (61.5 percent, n=16) felt that AD gave noteworthy information on tools for monitoring side-effects and 50.0 percent ( n=13) endorsed using these in practice. In total, 13 participants (50.0 percent) felt that the AD sessions gave them helpful information on tools for documenting polypharmacy use, which 46.2 percent ( n=12) indicated they would implement in their practice. No significant differences were found between participants' pre- and post-assessment prescribing behaviors. Practical implications There is great need for raising AD program's awareness and improving physician engagement in this process locally, provincially and nationally. Originality/value To the authors' knowledge, this is the first AD program in Canada to target specialists solely. Participant psychiatrists accepted the AD intervention and perceived it as a feasible CME method.

Genetic Determinants of Clozapine-Induced Metabolic Side Effects.

OBJECTIVE: Atypical antipychotics are linked to a higher incidence of metabolic side effects, including weight gain, dyslipidemia, and diabetes. In this study, we examined the prevalence and potential genetic predictors of metabolic side effects in 60 adult patients on clozapine. METHOD: Genetic variants of relevance to clozapine metabolism, clearance, and response were assessed through targeted genotyping of cytochrome P450 enzymes CYP1A2 and CYP2C19, the efflux transporter ABCB1, the serotonin receptor (HTR2C), leptin (LEP), and leptin receptor (LEPR). Clozapine levels and other potential confounders, including concurrent medications, were also included in the analysis. RESULTS: More than half of the patients were obese (51%), had metabolic syndrome (52.5%), and 30.5% were overweight. There was a high prevalence of antipsychotic polypharmacy (61.9%). With multivariable linear regression analysis, LEP -2548G>A, LEPR c.668A>G, and HTR2C c.551-3008 C>G were identified as genetic predictors of body mass index (BMI) after considering effects of clozapine dose, blood level, and concurrent medications (adjusted R2 = 0.305). Metabolic syndrome was found to be significantly associated with clozapine level and CYP2C19*2 and LEPR c.668 G alleles. Clozapine levels in patients with metabolic syndrome were significantly higher compared to those without metabolic syndrome (1886 ± 895 vs. 1283 ± 985 ng/mL, P < 0.01) and were associated with the CYP2C19*2 genotype. No association was found between the genetic variants studied and lipid or glucose levels. CONCLUSION: This study confirms a high prevalence of metabolic side effects with clozapine and suggests higher clozapine level and pharmacogenetic markers in CYP2C19, LEP, LEPR, and HTR2C receptors as important predictors of BMI and metabolic syndrome.

Asenapine for the Treatment of Psychotic Disorders.

OBJECTIVE: A systematic review was conducted to examine the efficacy, tolerability, and acceptability of asenapine compared with other antipsychotics in the treatment of psychotic disorders. METHODS: Four databases, 8 trial registries, and conference presentations were searched for randomized clinical trials of asenapine versus any comparator for the treatment of any psychotic illness. Primary outcome measures were changes in the Positive and Negative Syndrome Scale (PANSS) total score and the incidence of withdrawal due to adverse effects. RESULTS: Eight randomized clinical trials, encompassing 3765 patients, that compared asenapine with placebo ( n = 5) and olanzapine ( n = 3) were included. No differences were found between asenapine and olanzapine in terms of changes to PANSS total or PANSS negative subscale scores. Patients taking asenapine were more likely to experience worsening schizophrenia and/or psychosis than were those taking olanzapine. No differences were found between asenapine and olanzapine in rates of discontinuation due to adverse drug reactions or lack of efficacy, but those taking asenapine had higher rates of withdrawal for any reason than those taking olanzapine. Asenapine caused less clinically significant weight gain or increases in triglycerides than olanzapine and was more likely to cause extrapyramidal symptoms than olanzapine. In comparison to placebo, either no difference or superiority was demonstrated in favour of asenapine on all efficacy measures. CONCLUSION: The current evidence is limited, as asenapine has been compared only with placebo or olanzapine. In the randomized clinical trials analysed, asenapine was similar or superior to placebo and similar or inferior to olanzapine on most efficacy outcomes. While asenapine demonstrated fewer adverse metabolic outcomes than olanzapine, rates of extrapyramidal symptom-related adverse effects were higher.

Topiramate for acute affective episodes in bipolar disorder in adults.

BACKGROUND: Bipolar disorder is a common recurrent illness with high levels of chronicity. Previous trials have suggested that the anticonvulsant topiramate may be efficacious in bipolar disorder. This is an update of a previous Cochrane review (last published 2006) on the role of topiramate in bipolar disorder. OBJECTIVES: To assess the effects of topiramate for acute mood episodes in bipolar disorder in adults compared to placebo, alternative pharmacological treatment, and combination pharmacological treatment as measured by treatment of symptoms on specific rating scales for individual episodes. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Controlled Trials Register to 13 October 2015, which includes records from the Cochrane Central Register of Controlled Trials (CENTRAL) all years; MEDLINE 1950-; EMBASE 1974-; and PsycINFO 1967-.We performed handsearching, reviewing of grey literature and reference lists, and correspondence with authors and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing topiramate with placebo or with active agents in the treatment of acute mood episodes in adult male and female patients with bipolar disorder. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and methodological quality assessment. For analysis, we used odds ratio (OR) for binary efficacy outcomes and mean difference (MD) for continuously distributed outcomes. MAIN RESULTS: This review included six studies with a total of 1638 male and female participants, of all ethnic backgrounds in both inpatient and outpatient settings. In five studies, participants were experiencing a manic or mixed episode, and in the other study the participants met the criteria for a depressive phase. Topiramate was compared with placebo and alternative pharmacological treatment as both monotherapy and as adjunctive treatment.Moderate-quality evidence showed topiramate to be no more or less efficacious than placebo as monotherapy, in terms of mean change on Young Mania Rating Scale (YMRS) (range 0 to 60), at endpoint 3 weeks (MD 1.17, 95% confidence interval (CI) -0.52 to 2.86; participants = 664; studies = 3; P = 0.17) and at endpoint 12 weeks (MD -0.58, 95% CI -3.45 to 2.29; participants = 212; studies = 1; P = 0.69; low-quality evidence). For the same outcome, low-quality evidence also showed topiramate to be no more or less efficacious than placebo as add-on therapy (endpoint 12 weeks) (MD -0.14, 95% CI -2.10 to 1.82; participants = 287; studies = 1; P = 0.89) in the treatment of manic and mixed episodes. We found high-quality evidence that lithium was more efficacious than topiramate as monotherapy in the treatment of manic and mixed episodes in terms of mean change on YMRS (range 0 to 60) (endpoint 12 weeks) (MD 8.46, 95% CI 5.86 to 11.06; participants = 449; studies = 2; P < 0.00001).For troublesome side effects experienced of any nature, we found no difference between topiramate and placebo as monotherapy (endpoint 12 weeks) (OR 0.68, 95% CI 0.33 to 1.40; participants = 212; studies = 1; P = 0.30; low-quality evidence) or as add-on therapy (endpoint 12 weeks) (OR 1.10, 95% CI 0.58 to 2.10; participants = 287; studies = 1; P = 0.76; low-quality evidence). In terms of participants experiencing side effects of any nature, we found no difference between topiramate and an alternative drug as monotherapy (endpoint 12 weeks) (OR 0.87, 95% CI 0.50 to 1.52; participants = 230; studies = 1; P = 0.63; low-quality evidence) or as add-on therapy (endpoint 8 weeks) (OR 1.57, 95% CI 0.42 to 5.90; participants = 36; studies = 1; P = 0.50; very low-quality evidence).We considered five of the studies to be at low risk of selection bias for random sequence generation, performance, detection, attrition, and reporting biases, and at unclear risk for allocation concealment and other potential sources of bias. We considered the McIntyre 2000 study to be at high risk of performance bias; unclear risk of bias for random sequence generation, allocation concealment, blinding of outcome assessment, and other potential sources of bias; and at low risk for attrition bias and reporting bias. AUTHORS' CONCLUSIONS: It is not possible to draw any firm conclusions about the use of topiramate in clinical practice from this evidence. The only high-quality evidence found was that lithium is more efficacious than topiramate when used as monotherapy in the treatment of acute affective episodes in bipolar disorder, and we note that this evidence came from only two studies. Moderate-quality evidence showed that topiramate was no more or less efficacious than placebo as monotherapy when a 3-week endpoint was used, but the quality of the evidence for this outcome at a 12-week endpoint dropped to low. As we graded the quality of the evidence for the other findings as low and very low, it was not possible to draw any conclusions from the results.To best address this research question, if investigators see the indication in so doing, more double-blind randomised controlled trials could be conducted that are more explicit with regard to methodological issues. In particular, investigators could compare placebo, alternative, and combination treatments (including a wide range of mood stabilisers), atypical antipsychotics for manic and mixed episodes, and antidepressants in combination with mood stabilisers or atypical antipsychotics for depressive episodes.

Is Valproate Depressogenic in Patients Remitting from Acute Mania? Case Series.

Valproate is an effective antimanic agent and is recommended as a first-line medication in the treatment of acute mania. Current evidence based guidelines recommend that valproate should be given as a loading dose as it produces a rapid antimanic and antipsychotic response with minimal side-effects. However, no clear guidelines are available on the appropriate dosing or serum levels of valproate in the continuation or maintenance phase of bipolar disorder. We present 4 clinical cases to hypothesize that the higher doses of valproate, such as those used in the treatment of acute mania, may cause a depressive switch. So consideration should be given to reducing the dose of valproate if a patient develops depressive symptoms following recovery from the manic episode, as a therapeutic strategy. The cases also indicate that relatively lower doses and serum levels of valproate are effective in the maintenance phase compared to those needed in the acute manic phase of bipolar disorder. This is the first set of case series that questions the depressogenic potential of valproate in patients remitting from an acute manic episode. It highlights that different doses and serum levels of valproate may be therapeutic in different phases of bipolar disorder.

Research experience in psychiatry residency programs across Canada: current status.

OBJECTIVE: To determine the current status of research experience in psychiatry residency programs across Canada. METHOD: Coordinators of Psychiatric Education (COPE) resident representatives from all 17 psychiatry residency programs in Canada were asked to complete a survey regarding research training requirements in their programs. RESULTS: Among the 17 COPE representatives, 15 completed the survey, representing 88% of the Canadian medical schools that have a psychiatry residency program. Among the 15 programs, 11 (73%) require residents to conduct a scholarly activity to complete residency. Some of these programs incorporated such a requirement in the past 5 years. Ten respondents (67%) reported availability of official policy and (or) guidelines on resident research requirements. Among the 11 programs that have a research requirement, 10 (91%) require residents to complete 1 scholarly activity; 1 requires completion of 2 scholarly activities. Eight (53%) residency programs reported having a separate research track. All of the programs have a research coordinator and 14 (93%) programs provide protected time to residents for conducting research. The 3 most common types of scholarly activities that qualify for the mandatory research requirement are a full independent project (10 programs), a quality improvement project (8 programs), and assisting in a faculty project (8 programs). Six programs expect their residents to present their final work in a departmental forum. None of the residency programs require publication of residents' final work. CONCLUSIONS: The current status of the research experience during psychiatry residency in Canada is encouraging but there is heterogeneity across the programs.

Periventricular white matter integrity and cortisol levels in healthy controls and in euthymic patients with bipolar disorder: an exploratory analysis.

BACKGROUND: Bipolar disorder is associated with both white matter abnormalities and hypothalamo-pituitary-adrenal axis dysfunction. In a post-hoc analysis of diffusion tensor data, the relationship between cortisol levels and white matter structural integrity was explored in healthy controls and in euthymic patients with bipolar disorder. METHODS: Healthy control subjects and patients with bipolar disorder, prospectively verified as euthymic, underwent diffusion tensor MRI: fractional anisotropy and mean diffusivity data in fifteen regions of interest were obtained. Morning and evening salivary cortisol levels (SCLs) were measured. RESULTS: Significant negative partial correlations were found between fractional anisotropy and evening SCLs in control subjects in four periventricular regions. This pattern was absent in bipolar patients, possibly due to the presence of an excess of extracellular fluid manifested as a significant increase in mean diffusivity in those regions. LIMITATIONS: This is an exploratory, post-hoc analysis of data with relatively small sample sizes. Lithium treatment and past substance abuse in the bipolar group are potentially confounding factors in this study. CONCLUSIONS: These preliminary data show an inverse relationship between evening cortisol levels and a measure of periventricular white matter integrity in healthy controls. This relationship appears disrupted in bipolar patients, possibly due to periventricular osmoregulatory dysfunction, the effects of medication or past substance use. Future research should further investigate the influences of cortisol on oligodendrocyte function, white matter integrity and brain osmoregulation in bipolar disorder.

Physical health of patients with severe mental illness: an intervention on medium secure forensic unit.

PURPOSE: Patients with severe mental illness (SMI) treated with antipsychotic medication are at increased risk of metabolic side-effects like weight gain, diabetes mellitus and dyslipidaemia. This study aims to examine the feasibility of maintaining a physical health monitoring sheet in patients' records and its impact on physical health of patients with SMI, over a period of one year. DESIGN/METHODOLOGY/APPROACH: A physical health monitoring sheet was introduced in all the patients' records on a 15-bedded male medium secure forensic psychiatric rehabilitation unit, as a prompt to regularly monitor physical health parameters. An audit cycle was completed over a one year period. The data between baseline and re-audit were compared. FINDINGS: At baseline, 80 per cent of the patients were identified as smokers, 80 per cent had increased body mass index (BMI) and 87 per cent had raised cardiovascular risk over the next ten years. Appropriate interventions were offered to address the risks. At re-audit, the physical health monitoring sheets were up to date in 100 per cent of patients' records. The serum lipids and cardiovascular risk over the next ten years reduced over time. No significant change was noted on the parameters including BMI, central obesity, high blood pressure and smoking status. RESEARCH LIMITATIONS/IMPLICATIONS: This was a pilot study and was limited by the small sample size, male gender only and the specific nature of the ward. PRACTICAL IMPLICATIONS: There is a need for improved access to physical health care in long-stay psychiatric settings. A more robust lifestyle modification programme is required to positively influence the physical health parameters in this cohort of patients. ORIGINALITY/VALUE: Introduction of a physical health monitoring sheet in patients' records led to regular screening of cardiovascular risks and subsequent increased prescribing of hypolipidaemic agents in individuals with severe mental illness.

Valproate in acute mania: is our practice evidence based?

PURPOSE: This audit was conducted on acute psychiatric in-patient wards with the aim of establishing if valproate prescribing in acute mania followed evidence-based guidelines with particular emphasis on formulations used and whether accelerated valproate dosing was employed. DESIGN/METHODOLOGY/APPROACH: Case notes from 43 (42 percent male) patients admitted with mania and subsequently discharged on valproate were reviewed. Valproate formulation, weight measurement (necessary for dose-calculation in accelerated dosing), initial valproate dose and increments, serum valproate monitoring and other prescribed psychotropic agents were noted. FINDINGS: Most (95 percent) patients received sodium valproate (epilim chrono/generic), the remaining received valproate semi-sodium (depakote). All but one patient received antipsychotic medication in combination. Weight was recorded in only four (9 percent) patients. The mean valproate daily dose after the first week was 1,027mg (sd = 408). It took 29 (sd = 42) days to reach the maximum daily dose (1,426 mg sd = 467) from valproate initiation. Serum levels were monitored in 34 (79 percent) cases, but the mean period between valproate initiation to the first serum level test was 38 (sd = 47) days. A significant positive correlation was found between days taken to reach maximum dose and hospital stay (Spearman's rho = 0.41, n = 43, p = 0.006, two-tailed). PRACTICAL IMPLICATIONS: Accelerated valproate dosing was not common practice, which may have resulted in suboptimal efficacy, probably leading to combination treatment. ORIGINALITY/VALUE: This study highlights the need for adequate initial dosing and dose increments when treating manic patients and suggests current practice is not evidence-based. Local prescribing policy and national guidelines' influence on practice are discussed.

Oxcarbazepine for acute affective episodes in bipolar disorder.

BACKGROUND: Oxcarbazepine, a keto derivative of the 'mood stabiliser' carbamazepine, may have efficacy in the treatment of acute episodes of bipolar disorder. Potentially, it may offer pharmacokinetic advantages over carbamazepine. OBJECTIVES: To review the efficacy and acceptability of oxcarbazepine compared to placebo and other agents in the treatment of acute bipolar episodes including mania, mixed episodes and depression. SEARCH METHODS: Electronic databases were searched up to 2 September 2011. Specialist journals and conference proceedings were handsearched. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published and unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) which compared oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the acute treatment of bipolar affective disorder were sought. Participants with bipolar disorder of either sex and of all ages were included. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports individually by two review authors. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI). MAIN RESULTS: Seven studies were included in the analysis (368 participants in total). All were on mania, hypomania, mixed episodes or rapid-cycling disorder. Overall, their methodological quality was relatively low.There was no difference in the primary outcome analysis - a fall of  50% or more on the Young Mania Rating Scale (YMRS) - between oxcarbazepine and placebo (N=1, n=110, OR =2.10, 95% CI 0.94 to 4.73) in one study, conducted in children; no studies were available in adult participants.In comparison with other mood stabilisers, there was no difference between oxcarbazepine and valproate as an antimanic agent using the primary outcome (50% or more fall in YMRS, OR=0.44, 95% CI 0.10 to 1.97, 1 study, n=60, P=0.273) or the secondary outcome measure (differences in YMRS between the two groups, SMD=0.18, 95% CI -0.24 to 0.59, 2 studies, n=90, P=0.40). No primary or secondary efficacy outcome measures were found comparing oxcarbazepine with lithium monotherapy.As an adjunctive treatment to lithium, oxcarbazepine reduced depression rating scale scores more than carbamazepine in a group of manic participants on the Montgomery-Åsberg Depression Rating Scale (MADRS) (SMD=- 1.12, 95% CI -1.71 to -0.53, 1 study, n=52, P=0.0002) and on the Hamilton Depression Rating Scale (HDRS) (SMD=- 0.77, 95% CI -1.35 to -0.20, 1 study, n=52, P=0.008).There was a higher incidence of adverse effects, particularly neuropsychiatric, in participants randomised to oxcarbazepine compared to those on placebo (1 study, n=115, 17% to 39% of participants on oxcarbazepine had at least one such event compared to 7% to 10% on placebo).There was no difference in adverse events rates between oxcarbazepine and other mood stabilisers or haloperidol. AUTHORS' CONCLUSIONS: Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability. Studies predominantly examine the treatment of mania: there are data from subgroup analysis on mixed affective, hypomania and rapid-cycling states.From the few studies included in this review, oxcarbazepine did not differ in efficacy compared to placebo in children and adolescents. It did not differ from other active agents in adults. It may have a poorer tolerability profile compared to placebo. No data were found on outcomes relevant to patients and clinicians, such as length of hospital admission.  There is a need for adequately powered randomised controlled trials of good methodological quality to inform us of the therapeutic potential of oxcarbazepine across the spectrum of acute episodes in bipolar disorder.

Ganser's syndrome subsequent to ophthalmic herpes zoster in an elderly woman.

A case of a 79-year-old woman, who was admitted to a hospital subsequent to a mechanical fall and ophthalmic herpes zoster infection, is presented. She also presented with features of giving approximate answers, fluctuating consciousness, somatic conversion symptoms and probable hallucinations. A presumptive diagnosis of Ganser's syndrome was made. The patient made nearly a full recovery from the above symptoms in about 3 months. However, she continued to have cognitive impairment for which a further diagnosis of vascular cognitive impairment was offered.

Hematological effects of valproate in psychiatric patients: what are the risk factors?

BACKGROUND: Sodium valproate is an anticonvulsant that is also one of the common treatments used for bipolar disorder. The present study was conducted in psychiatric patients with the aim of examining the effects of valproate on hematological parameters and to explore any association with sex and age. METHODS: A list of all psychiatric patients who underwent valproate level estimation in the years 2004-2008 in Newcastle upon Tyne was drawn from the biochemistry database of the local hospital. The names and date of births of these patients were used to draw corresponding hematological data, including hemoglobin, white blood cell count, mean corpuscular volume (MCV), and platelet count, conducted on the same day or within a week of the valproate level measurement. RESULTS: : The data from 126 patients were analyzed. The prevalence of thrombocytopenia (platelet count, <150,000/microL) was found to be approximately 5%. In female subjects, a significant negative correlation was found between serum valproate level and platelet count; also, a positive correlation between valproate level and MCV was found. Neither correlation was found in male subjects. The risk of a low platelet count was found to be significantly increased at serum valproate level above 80 microg/mL in female subjects. The regression analysis in female patients showed a trend toward fall in platelet count and an increase in MCV with increasing age. CONCLUSIONS: In psychiatric patients on valproate therapy, close monitoring of full blood count is required in women particularly at valproate serum level above 80 microg/mL. This may be particularly important in older patients.

White matter microstructural abnormalities in euthymic bipolar disorder.

BACKGROUND: Abnormal diffusion parameters are reported in specific brain regions and white matter tracts in bipolar disorder. AIMS: To investigate whether these abnormalities are generalised, and thus evident in large regions of white matter. METHOD: Diffusion parameters were measured at several regions in the corpus callosum and in deep/periventricular white matter in 28 currently euthymic patients with bipolar disorder and controls. White matter hyperintensity loads were assessed. RESULTS: Comparing the whole data-sets using the sign test, in the group with bipolar disorder, mean diffusivity was greater at all 15 sites (P<0.001) and fractional anisotropy was reduced at 13 (P<0.01). The effect of diagnosis was significant for callosal mean diffusivity and fractional anisotropy and for deep/periventricular mean diffusivity (MANCOVA). Comparing individual regions (Mann-Whitney U-test), prefrontal and periventricular mean diffusivity were significantly increased; callosal and occipital fractional anisotropy were significantly reduced. Former substance use and lithium were possible confounding factors. Periventricular white matter hyperintensities were associated with significantly increased periventricular mean diffusivity in individuals with bipolar disorder. CONCLUSIONS: Generalised white matter microstructural abnormalities may exist in bipolar disorder, possibly exacerbated by past substance use and ameliorated by lithium.

Incontinence and mood disorder: is there an association?

A variety of psychiatric disorders including depression have been reported in patients suffering from incontinence. It is uncertain if the association between incontinence and depression is causal or is related to a third common factor. We report the case of a 48-year-old man who presented with incontinence of urine and faeces along with a severe depressive episode. No organic cause could be identified for the incontinence. The depressive symptoms as well as the incontinence resolved with treatment with reboxetine and aripiprazole. However, the patient developed a manic episode. This case supports the hypothesis that incontinence and depression may share a common pathogenesis. The authors review the literature to investigate this linkage. The combination of aripiprazole and reboxetine should be used cautiously when treating first episode depression as it can induce a manic switch. Previous reports of manic switch with aripiprazole and reboxetine are reviewed.