Biomedical subjects

Lakshmi N Yatham

Publications and source records attributed to Lakshmi N Yatham.

At least 19 recordsLinked to original sources

PubMed2006

Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies.

In this study, we assessed the changes of endogenous dopamine (DA) levels in response to methylphenidate in 5 patients with idiopathic Parkinson's disease (PD) and 6 healthy controls. Three-dimensional positron emission tomography was performed with the D2 receptor antagonist [11C]raclopride (RAC) at baseline and 1 hour following the administration of oral methylphenidate (0.8 mg/kg) to assess changes in dopamine levels indirectly. Oral methylphenidate produced no significant change in extracellular DA levels in the putamen, as estimated by comparing changes in RAC binding at baseline and 1 hour following its administration in PD subjects and healthy controls. However, there were small changes in RAC binding of opposite direction in caudate and ventral striatal regions compared between the two groups. Although there was no consistent improvement in motor function in the PD group, some patients did experience a subjective high in response to methylphenidate (MP). Failure of oral MP to alter extracellular DA levels in putamen could result from degeneration of presynaptic dopaminergic terminals, with consequent severe reductions in the levels of endogenous DA and dopamine transporter in PD subjects. Our data provide in vivo neurochemical support for the lack of clinical efficacy following MP in PD patients and are also in keeping with reduced DA release following amphetamine in PD subjects.

Administration, Oral↗

PubMed2006

Bipolar disorder and quality of life: a patient-centered perspective.

OBJECTIVES: Several quantitative studies have now examined the relationship between quality of life (QoL) and bipolar disorder (BD) and have generally indicated that QoL is markedly impaired in patients with BD. However, little qualitative research has been conducted to better describe patients' own experiences of how BD impacts upon life quality. We report here on a series of in-depth qualitative interviews we conducted as part of the item generation phase for a disease-specific scale to assess QoL in BD. METHODS: We conducted 52 interviews with people with BD (n=35), their caregivers (n=5) and health care professionals (n=12) identified by both convenience and purposive sampling. Clinical characteristics of the affected sample ranged widely between individuals who had been clinically stable for several years through to inpatients who were recovering from a severe episode of depression or mania. Interviews were tape recorded, transcribed verbatim and analyzed thematically. RESULTS: Although several interwoven themes emerged from the data, we chose to focus on 6 for the purposes of this paper: routine, independence, stigma and disclosure, identity, social support and spirituality. When asked to prioritize the areas they thought were most important in determining QoL, the majority of participants ranked social support as most important, followed by mental health. CONCLUSIONS: Findings indicate that there is a complex, multifaceted relationship between BD and QoL. Most of the affected individuals we interviewed reported that BD had a profoundly negative effect upon their life quality, particularly in the areas of education, vocation, financial functioning, and social and intimate relationships. However, some people also reported that having BD opened up new doors of opportunity.

Adult↗

PubMed2006

Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007.

In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

Acute Disease↗

PubMed2006

Oxcarbazepine in the treatment of bipolar disorder: a review.

OBJECTIVE: To review the data on the efficacy of oxcarbazepine (OXC) in bipolar disorder (BD) and to provide recommendations for clinicians on the use of this medication in treating BD. METHOD: Using the terms oxcarbazepine and bipolar disorder, oxcarbazepine and mania, or oxcarbazepine and bipolar depression, we conducted a computer-aided search of MEDLINE for the years 1950 to 2005. RESULTS: Case reports, retrospective chart reviews, open prospective studies, and double-blind studies reported the efficacy and effectiveness of OXC in treating BD. The data indicate that OXC has efficacy in treating acute mania and may be a useful add-on in treating acute bipolar depression and in BD prophylaxis. OXC is generally well-tolerated. CONCLUSION: We recommend using OXC as monotherapy or as add-on therapy in refractory mania, but we recommend it be used predominantly as an add-on treatment for other phases of BD in patients who have not improved with well-established treatments or in patients who have difficulty tolerating adequate dosages.

Antipsychotic Agents↗

PubMed2006

Polytherapy in bipolar disorder.

Bipolar disorder is a life-long condition that is associated with frequent recurrence/relapse of symptoms. Although putative mood stabilisers, such as lithium, are considered to improve the natural course of bipolar disorder, complete long-term remission is rarely achieved. In order to effectively control mood symptoms and to reduce relapse, clinicians often use polypharmacy to treat patients with bipolar disorder. In this article, we examine the recent literature on treatment strategies in bipolar disorder to determine if combination treatments provide additional benefit over monotherapy for the management of various phases of bipolar disorder. The evidence suggests that for acute mania a combination of lithium or valproate and an atypical antipsychotic is the most effective approach, with approximately 20% more patients responding to the combination than to monotherapy with any antimanic agent. Few studies have examined the use of combination therapy in comparison to monotherapy for bipolar depression. The limited evidence suggests that lithium plus an antidepressant appears to be more effective than lithium alone in those with lower serum lithium concentrations. Similarly, the combination of olanzapine plus fluoxetine is more effective than olanzapine alone. There is consensus that antidepressant monotherapy is not appropriate because of concerns of a manic switch, but monotherapy with lithium or lamotrigine may be adequate for mild to moderate bipolar depression. For maintenance treatment, commonly used agents, such as lithium, valproate or olanzapine appear to be most effective in preventing manic relapses, whereas lamotrigine is more effective in preventing depressive relapses. As a result of these findings, it makes intuitive sense to combine lamotrigine with lithium, valproate or an atypical antipsychotic to achieve better mood stability. However, the efficacy and safety of such combinations have not been systematically compared with monotherapy. Preliminary studies suggest that lithium plus valproate may be more effective than lithium alone in preventing affective relapses. Similarly, the combination of lithium or valproate plus olanzapine seems to be more effective than monotherapy with a mood stabiliser in preventing manic episodes.

Antidepressive Agents↗

PubMed2006

Incidence and time course of subsyndromal symptoms in patients with bipolar I disorder: an evaluation of 2 placebo-controlled maintenance trials.

BACKGROUND: Subsyndromal symptoms in bipolar disorder can cause significant functional impairment and are associated with relapse. METHOD: In this post hoc analysis from 2 randomized, double-blind, 18-month, placebo-controlled maintenance trials for bipolar I disorder (both trials were conducted between August 1997 and August 2001 and used DSM-IV criteria), the incidence, time course, and impact of pharmacotherapy on subsyndromal symptoms were examined. RESULTS: Subsyndromal symptoms occurred in approximately 25% of all visits. Compared with placebo (54.8%), a significantly higher mean percentage of visits in remission were observed with lamotrigine treatment (63.0%, p = .020) but not with lithium treatment (60.0%, p = .165). The median time to onset of subsyndromal symptoms for lamotrigine (N = 223), lithium (N = 164), and placebo (N = 188) was 15, 15, and 9 days, respectively. Compared with placebo, both lamotrigine and lithium significantly delayed the time from randomization to onset of subsyndromal symptoms (p = .046, lamotrigine vs. placebo; p = .033, lithium vs. placebo; p = .763, lamotrigine vs. lithium) and the time from onset of subsyndromal symptoms to subsequent mood episode (p = .037, lamotrigine vs. placebo; p = .023, lithium vs. placebo; p = .845, lamotrigine vs. lithium). Agreement between the polarities of the first-observed subsyndromal symptom and subsequent intervention for mood episode was statistically significant (p < .001). CONCLUSION: Subsyndromal symptoms are common during maintenance treatment and appear to be associated with relapse into an episode of the same polarity. Both lithium and lamotrigine delayed the onset of subsyndromal symptoms and the time from onset of subsyndromal symptoms to subsequent relapse. Further study to assess whether treatment intervention can minimize subsyndromal symptoms or prevent relapse is encouraged.

Adult↗

PubMed2005

Quality of life in bipolar disorder: a review of the literature.

A sizable body of research has now examined the complex relationship between quality of life (QoL) and depressive disorder. Uptake of QoL research in relation to bipolar disorder (BD) has been comparatively slow, although increasing numbers of QoL studies are now being conducted in bipolar populations. We aimed to perform a review of studies addressing the assessment of generic and health-related QoL in patients with bipolar disorder. A literature search was conducted in a comprehensive selection of databases including MEDLINE up to November 2004. Key words included: bipolar disorder or manic-depression, mania, bipolar depression, bipolar spectrum and variants AND quality of life, health-related QoL, functional status, well-being and variants. Articles were included if they were published in English and reported on an assessment of generic or health-related QoL in patients with BD. Articles were not included if they had assessed fewer than 10 patients with BD, were only published in abstract form or only assessed single dimensions of functioning. The literature search initially yielded 790 articles or abstracts. Of these, 762 did not meet our inclusion criteria, leaving a final total of 28 articles. These were sub-divided into four categories (assessment of QoL in patients with BD at different stages of the disorder, comparisons of QoL in patients with BD with that of other patient populations, QoL instrument evaluation in patients with BD and treatment studies using QoL instruments to assess outcome in Patients with BD) and described in detail. The review indicated that there is growing interest in QoL research in bipolar populations. Although the scientific quality of the research identified was variable, increasing numbers of studies of good design are being conducted. The majority of the studies we identified indicated that QoL is markedly impaired in patients with BD, even when they are considered to be clinically euthymic. We identified several important avenues for future research, including a need for more assessment of QoL in hypo/manic patients, more longitudinal research and the development of a disease-specific measure of QoL for patients with BD.

Antimanic Agents↗

PubMed2005

Atypical antipsychotics for bipolar disorder.

Atypical antipsychotic agents have been widely investigated for their efficacy in acute mania. The data to date suggest that olanzapine,risperidone, quetiapine, aripiprazole, and ziprasidone are effective, with no significant differences in antimanic efficacy among these agents. These agents are effective as an alternative to lithium or divalproex as monotherapy or in combination with these mood stabilizers. The data concerning their utility in acute bipolar depression and maintenance treatment of bipolar disorder are limited. The studies to date suggest that olanzapine has modest acute antidepressant properties but probably has efficacy comparable to lithium and divalproex in preventing manic and depressive episodes. Quetiapine seems to have robust antidepressant properties, but these data need to be replicated in further trials before quetiapine can be recommended as a first-line agent for acute bipolar depression. Aripiprazole has shown promise in preventing manic episodes in one 6-month study, but further studies with at least 1-year duration and larger sample sizes are needed before this agent can be recommended as a monotherapy for prophylaxis of bipolar disorder. It is currently unknown if risperidone, aripiprazole, and ziprasidone have any efficacy in treating acute bipolar depression. Similarly, long-term studies are needed to ascertain the role of risperidone, quetiapine, and ziprasidone in the maintenance treatment of bipolar disorder. Overall, the atypical antipsychotic agents as a group represent an effective and relatively safe addition to the armamentarium for the treatment of bipolar disorder.

Acute Disease↗

PubMed2005

Effect of valproate on plasma levels of interleukin-6 in healthy male humans.

Valproate exerts many biochemical and physiological effects and may have a modulating effect on the immune system. The present study aimed to determine whether there is a treatment effect of valproate on plasma levels of the pro-inflammatory cytokine, interleukin (IL)-6, in healthy male humans. Plasma levels of IL-6 were measured in 10 healthy male humans before and after 7 days of treatment with 1000 mg per day of valproate (i.e. 500 mg in the morning and 500 mg in the evening). All the healthy subjects had no past or current psychiatric disorder. They reported to the outpatient clinic at 09.00 h for baseline sampling. Subsequently, they were commenced on valproate 1000 mg per day for 7 days. They took the last dose of valproate at 22.00 h on the day 7, and post-treatment blood sampling for plasma levels of IL-6 was carried out on day 8. An additional blood sample was also taken from each subject at the same time to measure plasma levels of valproic acid for drug compliance. We found a significant increase in plasma levels of IL-6 after the 7 days of valproate treatment in healthy male subjects. Furthermore, there was a significant positive correlation between the changes in plasma IL-6 and blood levels of valproic acid. The findings of this study are consistent with previous studies on subjects with epilepsy, suggesting a modulating effect of valproate on the pro-inflammatory cytokine IL-6 in humans. However, studies with a larger number of participants and employing a double-blind, placebo-control group are required to confirm the findings, and also the levels of other cytokines should be measured to generalize the effect to the immune system.

Adult↗

PubMed2005

Recovery and functional outcomes following olanzapine treatment for bipolar I mania.

BACKGROUND: Typical experimental categorizations of treatment responses in bipolar disorder (BPD) patients may have limited relationship to clinical recovery or functional status, and there is inadequate research on such clinically important outcomes. METHODS: We analyzed data from a study of open continuation of olanzapine treatment following a 3-week placebo-controlled trial involving initially hospitalized adult subjects with DSM-IV BP-I mania to estimate rates and times to symptomatic remission (low scores on standardized symptomatic assessments) and clinical recovery (remission sustained>or=8 weeks), associated clinical factors, and functional outcomes. RESULTS: During treatment with olanzapine for 27.9+/-20.1 weeks, symptomatic remission was attained by 70% of subjects, half by 8 weeks (95% CI 6-10) weeks, and later lost by 82% of remitted subjects; remitted (versus non-remitted) subjects had slightly lower baseline clinical global impression scores and greater trial-completion. Sustained clinical recovery was attained by only 40 of 113 (35%) of subjects, half by 36 (95% CI 20-40) weeks, and later lost by 45%. Subjects with above-median (>12) initial Hamilton-Depression rating scale depression scores were half as likely to recover (p=0.016) and did so much later (36 versus 12 weeks) than those with lower scores. At final assessment, self-rated well being (SF-36 psychosocial functioning scores) improved substantially more among recovered versus non-recovered subjects (mean changes: 87% versus 23%), and two-thirds of recovered subjects remained unemployed-for-pay while half received disability-compensation. CONCLUSIONS: Clinically meaningful symptomatic remission and recovery in relatively severely ill adult bipolar I manic patients were achieved slowly and sustained by only some patients within an average of 7 months of continuous treatment. These clinically relevant outcomes were worse with relatively high initial dysphoria ratings. Well-being was rated higher by recovered subjects, but their ability to work and live independently were markedly impaired. These findings underscore the emerging view that BPD can often be severe, slow to remit, and disabling, particularly in association with prominent depression-dysphoria symptoms. Improved treatments for BPD are needed, guided by longitudinal assessments of clinically meaningful measures of symptomatic recovery and functional outcome.

Adult↗

PubMed2005

Translating knowledge of genetics and pharmacology into improving everyday practice.

Bipolar disorder is associated with significant morbidity and mortality; however, many aspects of this disorder remain poorly understood. It is likely that rapid advances in molecular genetics and neuroimaging will play a major role in advancing our understanding of bipolar disorder in future. Molecular genetics studies have already identified some candidate genes; for example, the BDNF, G72 and XBP1 genes, and chromosomal 'hot spots', which may confer a predisposition to development of bipolar disorder. Such advances may facilitate earlier, easier and more accurate diagnosis and provide novel targets for the treatment of this condition. Brain imaging studies using positron emission tomography and single photon emission computed tomography have shown that reduction in brain 5-hydroxytryptamine type 2 (5-HT(2)) receptors may be associated with prevention of or relief from depressive symptoms. Similarly, other imaging studies suggest that increased dopamine levels in the synapse mediate the symptoms of bipolar mania and that reduction in dopamine transmission through reduction in dopamine synthesis or blockade of dopamine D(2) receptors may be associated with antimanic effects. The ability of atypical antipsychotics to block both 5-HT(2) and D(2) receptors and downregulate 5-HT(2) receptors may explain how these drugs treat both the depressive and manic symptoms of bipolar disorder. Although molecular genetics and imaging techniques are not yet used as clinical tools for bipolar disorder, they provide valuable data to improve the understanding of the pathophysiology of bipolar disorder and should lead to new treatments and potentially episode prevention.

Bipolar Disorder↗

PubMed2005

Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies.

Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.

Adolescent↗

PubMed2005

A positron emission tomography study of the effects of treatment with valproate on brain 5-HT2A receptors in acute mania.

OBJECTIVE: To examine the effects of treatment with valproate on brain 5-HT2A receptors in acute manic patients using positron emission tomography (PET) and [18F]-setoperone. METHODS: Patients with DSM-IV bipolar I disorder-manic episode were recruited. Patients were drug free or drug naïve at the time of baseline PET scan. All patients were treated with valproate and one patient received lithium in addition to valproate for 3-5 weeks following which they had a post-treatment PET scan. The effect of treatment on brain 5-HT2A receptor binding was determined using statistical parametric mapping (SPM) and region of interest (ROI) analyses. Of the 12 manic patients recruited, seven patients had both baseline and post-treatment PET scans. RESULTS: All seven patients improved with treatment and were in remission at the time of the second PET scan. Both SPM and ROI analyses showed that treatment with mood stabilizers had no significant effect on brain 5-HT2A receptor binding in manic patients. CONCLUSION: This study suggests that changes in brain 5-HT2A receptors are not involved in the antimanic effects of mood stabilizers however, we cannot exclude the possibility of 5-HT2A receptor involvement in down-stream signaling pathways.

Acute Disease↗

PubMed2005

Oxcarbazepine add-on in the treatment of refractory bipolar disorder.

OBJECTIVE: To assess the effectiveness and safety of oxcarbazepine (OXC) in bipolar disorder (BD) and related conditions. METHODS: We reviewed medical records of patients given OXC treatment between March 2003 and March 2005 at the University of British Columbia Hospital. Response to treatment was assessed retrospectively using the Clinical Global Impression of Severity (CGI-S), and the Clinical Global Impression of Improvement (CGI-I) scales. RESULTS: OXC was prescribed to 15 patients with bipolar I (n = 12), bipolar II (n = 2) and schizoaffective (n = 1) disorder who presented with depression (n = 9), mania (n = 3), hypomania (n = 1), or mixed state (n = 2). Six patients had Axis II diagnoses and 10 patients had a family history of mood disorders. Psychiatric co-morbidity was found in four patients. The mean daily dose of OXC was 775 +/- 556.11 mg/day and the mean duration of follow-up was 31.60 +/- 41.51 weeks. The OXC add-on led to a significant reduction in symptoms as indicated by reduction in CGI-S scores at 1 and 2 months. Nine of 12 patients at 1 month and seven of 14 at 1 or 2 months were much or very much improved on CGI-I scale. One patient (7%) developed hyponatremia. Six patients (40%) experienced no side effects and three patients (20%) stopped the medication because of side effects. CONCLUSION: OXC was effective and well-tolerated in refractory BD and schizoaffective disorder. These preliminary data are promising but controlled studies are needed to confirm its efficacy in refractory BD.

Adult↗

PubMed2005

Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial.

OBJECTIVE: The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence. METHOD: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214). RESULTS: Symptomatic relapse/recurrence (score > or =15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label co-treatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg). CONCLUSIONS: These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.

Adult↗

PubMed2005

Perceived quality of life in patients with bipolar disorder. Does group psychoeducation have an impact?

OBJECTIVE: A large body of research has now accumulated concerning quality of life (QoL) for patients with major depressive disorder, both in terms of describing levels of well-being and in terms of assessing the impact of treatment interventions. However, there is little information concerning QoL for patients with bipolar disorder (BD), and there is relatively little published evidence concerning the effectiveness of psychological interventions for BD. We aimed to assess the impact of a time-limited psychoeducation (PE) group therapy upon perceived QoL among patients with BD. METHOD: Participants were patients (n = 57) with BD type I or II who were clinically described as euthymic or mildly symptomatic. Treatment intervention was a standardized, 8-week group PE course delivered in a mood disorders program in British Columbia, Canada. Using retrospective chart review and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), we assessed QoL at baseline and at 8 weeks. RESULTS: Mean baseline Q-LES-Q scores were 56%, representing moderate impairment in QoL. Group PE was associated with a 5-point increase in Q-LES-Q scores (where higher scores indicate better QoL). Examination of the questionnaire's subscales revealed that 2 domains (that is, physical functioning and general satisfaction) increased significantly following PE, with the remaining domains showing nonsignificant trends toward improved functioning. Multivariate analysis indicated that only one factor (having had a recent episode of depression) significantly predicted pre- and posttreatment Q-LES-Q scores. CONCLUSION: Patients with BD continue to show impaired QoL even when clinically euthymic. Although preliminary, our results show that group PE is associated with improved QoL in this population, both in terms of general satisfaction and in relation to levels of physical functioning. The use of PE as an adjunct to pharmacotherapy in BD should be further studied with particular emphasis on characterizing the effects of treatment intervention on perceived QoL.

Adult↗

PubMed2005

Diagnosis and management of patients with bipolar II disorder.

Bipolar II disorder is frequently misdiagnosed as major depressive disorder. In particular, correct diagnosis of bipolar II disorder may be delayed by years due to the predominance of depressive symptoms and the relative subtlety of hypomania, which may manifest only briefly and without elevated mood. The prevalence of bipolar II disorder varies from 0.5% to about 5% depending on the criteria used. Diagnosis can be improved by using mood disorder questionnaires, systematic probing, and prospective mood diary charting. There is a dearth of research into treatment of bipolar disorder. The limited available evidence suggests that lithium and lamotrigine may have efficacy in preventing relapse of mood episodes. Acute bipolar II depression could be treated with a combination of a mood stabilizer plus an antidepressant or pramipexole and in rare cases with antidepressant monotherapy. Hypomania will likely respond to monotherapy with antimanic agents. Adjunctive psychosocial treatments may provide additional benefit in patients with bipolar II disorder.

Adaptation, Psychological↗

PubMed2005

Atypical antipsychotics in bipolar depression: potential mechanisms of action.

"Conventional" antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), bupropion, or serotonin-norepinephrine reuptake inhibitors, are not recommended as monotherapy for bipolar depression. Although they are likely to provide effective symptom relief in combination with mood stabilizers, the risk of precipitating a switch to mania often complicates their use even as combination therapy. Recently, 2 psychotropic medications approved for treating acute mania, olanzapine and quetiapine, have also been shown to possess antidepressant activity without destabilizing mood and, as such, are potential mood stabilizers. This article aims to review the mechanism of action of conventional antidepressants and newer agents that are effective in the treatment of bipolar depression. A number of mechanisms have been postulated to play a role in the effective treatment of bipolar depression, including targets as diverse as serotonin (5-HT), norepinephrine, dopamine, gamma-aminobutyric acid (GABA), glutamate, and various second messenger signaling pathways. A review of the data reveals an important point of commonality among the antidepressant treatments, olanzapine, and quetiapine. Antidepressant treatments, such as norepinephrine reuptake inhibitors, SSRIs, and electroconvulsive therapy, induce a reduction of 5-HT(2A) receptors. Both olanzapine and quetiapine not only are antagonists at this receptor but also induce downregulation of 5-HT(2A) receptors. It is possible that the antidepressant efficacy of these agents is mediated by this receptor, while the additional benefit of olanzapine and quetiapine over unimodal antidepressant treatments, in terms of stabilizing mood, may be provided by their concomitant dopamine D(2) antagonism. Further studies should be conducted to examine these hypotheses.

Antipsychotic Agents↗