Verinder Sharma

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2009

The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

An MRI study of subgenual prefrontal cortex in patients with familial and non-familial bipolar I disorder

BACKGROUND Over the past few years there has been an interest in the use of magnetic resonance imaging (MRI) to study specific brain regions in bipolar disorder. The present study compared the grey matter volume in the subgenual prefrontal cortex in patients with familial and non-familial bipolar disorder and normal control subjects. METHODS MRI brain scans were performed on 12 patients with bipolar I disorder including six patients with a positive family history of bipolar disorder as well as eight control subjects. RESULTS There was a significant reduction in the grey matter volume in the right subgenual prefrontal cortex, but not in the left subgenual prefrontal cortex. A family history x sex interaction with right prefrontal cortex volume was also observed as a trend. For females, a positive family history was associated with reduced right prefrontal cortex volumes; for males, a positive family history was associated with increased right prefrontal cortex volumes. LIMITATIONS Small sample size, reduced statistical power. CONCLUSION These data add to the emerging literature on structural changes in the subgenual prefrontal cortex in bipolar disorder, especially in patients with a positive family history.

Bipolar II Postpartum Depression: Detection, Diagnosis, and Treatment

Research on postpartum mood disorders has focused primarily on major depressive disorder, bipolar I disorder, and puerperal psychosis and has largely ignored or neglected bipolar II disorder. Hypomanic symptoms are common after delivery but frequently unrecognized. DSM-IV does not consider early postpartum hypomania as a significant diagnostic feature. Although postpartum hypomania may not cause marked impairment in social or occupational functioning, it is often associated with subsequent, often disabling depression. Preliminary evidence suggests that bipolar II depression arising in the postpartum period is often misdiagnosed as unipolar major depressive disorder. The consequences of the misdiagnosis can be particularly serious because of delayed initiation of appropriate treatment and the inappropriate prescription of antidepressants. Moreover, no pharmacological or psychotherapeutic studies of bipolar postpartum depression are available to guide clinical decision making. Also lacking are screening instruments designed specifically for use before or after delivery in women with suspected bipolar depression. It is recommended that the treatment of postpartum bipolar depression follow the same guidelines as the treatment of nonpuerperal bipolar II depression, using medications that are compatible with lactation.

Missed bipolarity and psychiatric comorbidity in women with postpartum depression

OBJECTIVE To investigate the diagnostic profile of women referred for postpartum depression. METHODS Fifty-six women seen consecutively with the referral diagnosis of postpartum depression were administered structured instruments to gather information about their DSM-IV Axis I diagnoses. RESULTS In terms of frequency of occurrence, the primary diagnoses in this sample were: major depressive disorder (46%), bipolar disorder not otherwise specified (29%), bipolar II disorder (23%), and bipolar I disorder (2%). A current comorbid disorder, with no lifetime comorbidity, occurred among 32% of the sample; by contrast, lifetime comorbidity alone (i.e., with no currently comorbid disorder) was found among 27%. Both a lifetime and a current comorbidity were found among 18% of the women, and 23% had no comorbid disorder. The most frequently occurring current comorbid disorder was an anxiety disorder (46%), with obsessive-compulsive disorder (62%) being the most common type of anxiety disorder. For lifetime comorbidity, substance use (20%) and anxiety disorders (12%) were the two most common. Over 80% of patients who scored positive on either the Highs Scale or the Mood Disorder Questionnaire met the diagnostic criteria for a bipolar disorder. CONCLUSION The results suggest that postpartum depression is a heterogeneous entity and that misdiagnosis of bipolar disorder in the postpartum period may be quite common. The findings have important clinical implications, which include the need for early detection of bipolarity through the use of reliable and valid assessment instruments, and implementation of appropriate prevention and treatment strategies.

A closer look at inpatient suicide

BACKGROUND We examined the risk factors for suicide among inpatients in an Ontario provincial psychiatric hospital. METHODS Forty-four inpatients who had committed suicide during their hospital stay from 1969 to 1995 were compared with a group of inpatient controls matched for sex, age and date of admission. The diagnosis for each patient was reviewed by the authors. RESULTS Suicide victims were more likely to have had a mood disorder, family history of psychiatric problems, mention of suicide risk in chart notes and a previous suicide attempt. Two findings necessitated further scrutiny: The most common diagnosis among inpatients who committed suicide in this study was a mood disorder and not schizophrenia as previously reported. A large proportion of patients (24) had experienced a rapidly fluctuating clinical course prior to the time of suicide. CONCLUSIONS The implications of these findings, including the possible role of antidepressants in the induction of cycling prior to suicide, are discussed.

Pregnancy and bipolar disorder: a systematic review.

OBJECTIVE The postpartum period is generally considered a time of heightened vulnerability to bipolar disorder; however, there is controversy about the effect of pregnancy on the course of bipolar disorder. This article reviews the literature on the relationship between pregnancy and bipolar disorder and suggests areas for future research. DATA SOURCES AND STUDY SELECTION Three electronic databases, MEDLINE (1966-2010), PsycINFO (1840-2010), and EMBASE, were searched on April 30, 2010, using the following keywords: pregnancy, bipolar disorder, manic depressive disorder, suicide, hospitalization, pharmacotherapy, and psychotherapy. The reference lists of articles identified were also searched. All relevant papers published in English were included. RESULTS A total of 70 articles were identified and included in the review. Evidence from studies using nonclinical samples, some retrospective studies, and studies on psychiatric hospitalization rates is suggestive of a positive effect of pregnancy on bipolar disorder; however, recent studies conducted at tertiary care facilities have reported high rates of recurrence following discontinuation of mood stabilizers. CONCLUSIONS Understanding the relationship between pregnancy and bipolar disorder has implications for perinatal treatment and etiologic understanding of the disorder. Research is urgently needed to estimate the prevalence of bipolar disorder during pregnancy, using both clinical and nonclinical samples.

Loss of response to antidepressants and subsequent refractoriness: diagnostic issues in a retrospective case series

BACKGROUND The loss of response to antidepressant drugs is not an uncommon phenomenon. While some patients respond to changes in the drug regimen, others develop resistance to various treatment modalities. METHOD I describe 15 cases who had a loss of response to repeated trials of antidepressants before developing a chronic and severe, refractory depression. RESULTS These patients had failed to respond to various treatment strategies including substitution with other antidepressant drugs, augmentation with agents such as T3 and lithium; and finally electroconvulsive therapy (ECT). Following discontinuation of antidepressants and treatment with mood stabilizers, there was a sustained improvement. Notably some of the patients who had earlier failed to respond to mood stabilizers in combination with unimodal antidepressants improved upon discontinuation of antidepressants and continued treatment with mood stabilizers. LIMITATIONS Open trial, retrospective design and small sample size. CONCLUSION These clinical findings suggest that some refractory depressives represent cryptic bipolar disorders. Prospective validation is necessary to support this conclusion.

Teratogenesis associated with antibipolar agents

ObjectiveTo review the teratogenic effects associated with the use of Food and Drug Administration-approved agents for bipolar disorder.MethodsA PubMed search of all English language articles published from January 1966 to December 2008 was conducted. The key search terms included all major bipolar agents, cross-referenced with: teratogenicity, teratogen, safety, pregnancy, fetus, bipolar disorder, and malformation. The search was augmented with manual reviews of relevant article reference lists as well as http://clinicaltrials.gov and http://www.fda.gov (both last accessed in April 2008). Several pregnancy registries were also reviewed to determine malformation rates as well as teratogenesis attributable to each agent. Articles selected for review were based on author consensus, adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality.ResultsValproate is associated with the highest rate of major congenital malformations (6.2%–16%). The relative risk of neural tube defects with valproate and carbamazepine is reported as approximately 1%–5% and 0.5%–1%, respectively. Preliminary evidence suggests that the relative risk for oral clefts (cleft lip or palate) is increased with lamotrigine relative to other antiepileptic drugs (AED) (ie, approximately 0.4%). The rate of major congenital malformations is higher in fetuses exposed to AED polytherapy (ie, ≥2 drugs) in comparison with AED monotherapy. Adverse neurobehavioral effects are insufficiently reported for most agents. In-utero exposure to valproate is associated with a greater risk of developmental difficulty requiring special education interventions as well as decreased verbal IQ scores. The risk of Ebstein’s anomaly associated with lithium use is increased relative to the general population. The major congenital malformation rate with chlorpromazine and atypical antipsychotics is not established as being higher than a non-exposed group; the teratogenic risks associated with the olanzapine-fluoxetine combination are unknown.ConclusionsWell-characterized risks are associated with valproate, carbamazepine, lamotrigine, and lithium. The risks associated with psychotropic drug use need to be understood in the context of significant rates of relapse and associated morbidity when discontinuing bipolar treatment during pregnancy.

A Systematic Review of the Association Between Psychiatric Disturbances and Endometriosis

We read with great interest the article by Pope et al., an interesting review that examined the existing empirical findings about the association between endometriosis and psychiatric conditions. We agree that our knowledge of this association is limited because of methodological differences and the limited number of controlled studies in the published literature. Although we appreciated the reported methodology, we take the opportunity to point out several elements which would let us further realize the results of this study. First of all, we observed that only four of the identified studies used clinical diagnostic criteria to assess for psychiatric diagnosis. Nevertheless, the diagnosis of any psychiatric condition requires the use of a specific validated test, as we recently did. Second, the characteristics of the cohort varied between studies: some included women with a diagnosis of endometriosis whereas others used a sample of women with chronic pelvic pain secondary to endometriosis. We believe that future research studies should include only patients with a diagnosis of endometriosis obtained through the visualization of lesions at the time of laparoscopy and histological analysis, according to the most updated international guidelines. Additionally, it might be helpful to divide the patients by disease stage, according to the American Fertility Society classification, in order to obtain more information regarding a possible correlation between endometriosis severity and psychiatric comorbidity. Third, of the reported three studies using a comparator group, one used a healthy control group, and the others consisted of women with chronic pelvic pain due to another medical condition. Moreover, several studies showed a close correlation between psychiatric disorders, such as anxiety and depression, and medical conditions. Considering this last point, it would not be possible to accurately state whether the psychiatric disorder could be clearly related to endometriosis or to other comorbidities, impairing the validity of results. Based on this element, we strongly suggest that future studies should exclude patients with other underlying conditions both in endometriosis and control groups. Fourth, none of the studies reported about other pharmacological, surgical, or psychosocial treatment, although it is widely accepted that some of the medications for endometriosis are associated with adverse side effects, including psychiatric symptoms. For example, oral contraceptives have been associated with decreased psychosexual arousal or negative changes in mood. Furthermore, gonadotropin-releasing hormone agonists have been found to be associated with emotional lability and depression. As the use of different hormonal therapies in some patients with endometriosis may influence the onset and progress of psychiatric disorders, prophylactic treatment with an antidepressant may reduce the risk for the experience of treatment-induced depressive symptoms. Finally, we believe that future studies should consider separately the patients with “endometriosis and chronic pelvic pain” and “endometriosis and infertility.” These two complaints adversely affect quality of life and mental health of patients, causing emotional distress, social isolation, relationship difficulties, and worse job performance; these last points could also modulate the relationship between endometriosis and psychiatric disorders. Moreover, chronic pelvic pain and infertility require specific and individualized pharmacological and psychosocial treatments. In conclusion, considering the impact of endometriosis on psychological health and the paucity of papers on this topic, we take the opportunity to solicit further studies in order to find clearer evidence and to provide the best evidence-based treatment for the patients.

Seasonality of manic depressive illness in Canada

OBJECTIVE The objective of the study was to determine if a seasonal pattern existed for hospital admissions of manic depressive illness to a Ontario provincial psychiatric hospital. METHOD Admission records were reviewed for the 75 year period of the study. In the analysis factors including: mood state on admission, gender and the influence of psychotropic medications were considered. RESULTS For mania and depression there was no statistically significant seasonal pattern of admissions. For mixed state admissions peaked in the summer. CONCLUSIONS The results of this study contradict the seasonal pattern traditionally reported in the literature. The limitations of this study, which include changes in diagnostic criteria over time and admission date not identical to onset of affective episode, need to be acknowledged.