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Weight gain mitigation with topiramate in mood disorders.

OBJECTIVE: To review the evidence of weight loss with use of topiramate in patients with mood disorders. DATA SOURCES: Literature search included MEDLINE (1966-December 2003), International Pharmaceutical Abstracts (1970-December 2003), and EMBASE (1980-December 2003). Search terms included topiramate, weight loss, adverse effect, mood disorders, bipolar disorder. DATA SYNTHESIS: Weight gain is a common adverse effect of many agents used to treat mood disorders. Topiramate has been evaluated in the management of some mood disorders, and weight loss may be a beneficial side effect in these patients. Case reports, letters to the editor, prospective investigations, and retrospective observational studies were reviewed to identify evidence of weight loss with topiramate use in patients with mood disorders. CONCLUSIONS: Current evidence suggests an association between topiramate and weight loss. Based on the limited data, controlled studies need to be conducted to define the role of topiramate in patients with mood disorders who would also benefit from weight reduction.

Anticonvulsants↗

Trauma-related distress and mood disorders in the early stage of an acute traumatic hand injury.

The aim of the study was to estimate the incidence of trauma-related distress and mood disorders in the early stages after acute traumatic hand injuries and identify characteristics associated with these reactions. Data were obtained from 112 patients by means of mailed questionnaires and medical records. Nearly half of the patients had increased levels of intrusive and avoidance symptoms, indicating trauma-related distress. One-third showed signs of a mood disorder. Mood disorders were associated with the need for help with activities of daily living, pain and avoidance symptoms. The study showed that emotional problems in the early stages after injury are related to the consequences of both the injury and the traumatic experience. Negative reactions to the sight of the hand were associated with both trauma-related distress and mood disorders, suggesting that observation of the reactions to the sight of the hand could help to identify patients in need of psychological support.

Activities of Daily Living↗

Predictors of response to treatment in children and adolescents with mood disorders.

Depression and bipolar disorder are frequently chronic disorders, with onset often beginning in childhood. Mood disorders are becoming more recognized in children and adolescents, and treatment of these disorders has received much attention, particularly in the past 10 years. Recent studies have demonstrated efficacy of antidepressant medications (particularly SSRIs) and specific psychotherapies (primarily CBT). Rates of remission (little or no symptoms) in these studies, however, have remained quite low (35% to 40% in most acute studies). Furthermore, recurrence is common in this population, and affects 40% to 50%. Early onset mood disorders are also associated with increased risk of developing other psychiatric disorders, substance abuse, and suicide, and having poor academic, work, and social functioning. The lifelong implications are serious. Identifying factors that may predict response to treatment, both in general and to specific treatments, may lead to improved outcomes for these patients. Unfortunately, studies have typically been inconsistent. Most studies do not identify demographic variables as predictive of outcome, although older age has been associated with poor prognosis in several studies. Psychosocial factors have yielded some results, particularly with regard to family environments. Generally, intact families with positive interaction styles and less dysfunction have been associated with better outcomes. Psychiatric disorders among parents not only predicts the development of the disorder, but is also associated with poorer prognosis. Finally, several clinical factors have been linked to poorer outcome in children and adolescents with mood disorders. More frequent episodes, increased severity (particularly suicidality and psychosis), and comorbid disorders are likely to lead to fewer recoveries, longer episodes, and increased rate of recurrence. Recent attention has focused on mediators and moderators of outcomes to treatment. In general, the theory is that enumerable factors contribute to the course of an individual's mood disorder, but that by identifying some of the variables that have more impact may allow for more specific or modified treatments to improve outcome. Many of the predictive factors explored in this article are examples of mediators and moderators that affect outcome. Each one alone may not provide definitive answers for predicting response to treatment, but each must be taken into account at the outset of treatment. It is clear that treatments must be individualized for each patient. Furthermore, selecting only one treatment exclusively for patients may hinder progress. The first step is to attempt to identify some of the underlying causes and the consequences of the disorder itself (i.e., decreased social interaction). The next step in successful treatment is to address both the causes and consequences of the disorder, through medication, psychotherapy, skills training, family intervention, or any other methods needed to assist the child to begin functioning better in all domains (social, academic, work, family, and so forth). Such a biopsychosocial approach to treatment of these disorders will likely improve overall outcome.

Adolescent↗

Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics.

Mood disorders have traditionally been conceptualized as neurochemical disorders, but there is now evidence from a variety of sources demonstrating regional reductions in central nervous system (CNS) volume, as well as reductions in the numbers and/or sizes of glia and neurons in discrete brain areas. Although the precise cellular mechanisms underlying these morphometric changes remain to be fully elucidated, the data suggests that mood disorders are associated with impairments of structural plasticity and cellular resilience. Recent preclinical and clinical studies have shown that signaling pathways involved in regulating cell survival and cell death are long-term targets for the actions of antidepressants and mood stabilizers. Antidepressants, lithium, and valproate indirectly regulate a number of factors involved in cell survival pathways, including CREB, BDNF, Bcl-2, and MAP kinases, and may thus bring about some of their delayed long term beneficial effects via underappreciated neurotrophic effects. The future development of treatments that more directly target molecules involved in critical CNS cell survival and cell death pathways thus hold promise as novel, improved long-term treatments for mood disorders.

Animals↗

Olanzapine therapy in treatment-resistant psychotic mood disorders: a long-term follow-up study.

BACKGROUND: Recent studies suggest a role for the atypical antipsychotic olanzapine in the acute treatment of psychotic mood disorders, but long-term data are unavailable. The purpose of this naturalistic study was to determine the long-term effectiveness and tolerability of olanzapine as add-on therapy in psychotic mood disorders. METHOD: Hospital records were reviewed for 125 inpatients at the state psychiatric hospital in Buffalo, N.Y., who received at least 6 weeks of add-on olanzapine treatment for psychotic mood disorders (schizoaffective disorders [bipolar and depressive type], bipolar disorders [I, II, and NOS], and major depressive disorder). A group of schizophrenic patients served as a control group (N = 50). Baseline measures, including age, gender, number of hospitalizations in the 2 years prior to olanzapine treatment, concomitant medications, the Clinical Global Impressions scale (CGI), and the Global Assessment of Functioning-Equivalent (GAF-EQ) and Kennedy Axis V psychological impairment, violence, social skills, and activities of daily living subscale scores, were obtained. Follow-up information was obtained from the patients at least 6 months after initiation of olanzapine or by chart review and discussion with the treating psychiatrist. Patients with a diagnosis of psychotic mood disorders were compared with patients with the non-affective psychotic disorder (schizophrenia) on a variety of outcome measures. RESULTS: Follow-up information was available on 102 patients (82%). Mean follow-up was 15 months; 50 (49%) of the 102 patients remained on olanzapine treatment at follow-up (32 psychotic mood disorder, 18 schizophrenic). The primary reason for discontinuation in both groups was lack of response. Both the psychotic mood disorder and schizophrenic groups had comparable outcomes on the CGI and GAF-EQ. Improvement on the Kennedy Axis V psychological impairment and social skills subscales was seen only in the psychotic mood disorders group (p < .01); both groups showed significant (p < .02) improvement in the violence subscale. Sustained mood-stabilizing effect was evident in only 7/27 (26%) of the psychotic mood disorders patients continuing on add-on olanzapine treatment at follow-up. CONCLUSION: Lack of response was the primary reason for discontinuation of add-on olanzapine in both groups. Mood symptoms predicted a better response to add-on olanzapine in patients with psychotic mood disorders on selective outcome measures. However, only 26% of the patients with psychotic mood disorders sustained a clinically meaningful mood-stabilizing effect with add-on olanzapine treatment at follow-up.

Adult↗

Association analysis of a functional G protein beta3 subunit gene polymorphism (C825T) in mood disorders.

The guanine nucleotide-binding proteins (G proteins), heterotrimers consisting of alpha, beta and gamma subunits, convey signals initiated by the activation of many neurotransmitter receptors. Evidence for involvement of the G proteins in mood disorders relies on the effects of mood stabilizers and antidepressants on G protein function. In addition, abnormalities in the expression of G proteins have been demonstrated in mood disorder patients. Therefore, we tested the hypothesis that a functional polymorphism (C825T) in the G protein beta3 gene subunit (GNB3) confers susceptibility to mood disorders. A population-based association study was utilized, and GNB3 was genotyped for 144 mood disorder patients and 153 normal controls. The results reveal that it is not likely that the C825T polymorphism in the GNB3 gene subunit is involved in mood disorder pathogenesis. Further studies of the associations between other G protein subunits and mood disorder are needed to fully elaborate the involvement of this protein in mood disorders.

Adult↗

Glia mechanisms in mood regulation: a novel model of mood disorders.

INTRODUCTION: Recent evidence in clinical and preclinical studies has implicated glutamate neurotransmissions in pathophysiology of mood disorders. The regulation of amino acid neurotransmission, i.e., glutamate and gamma-aminobutyric acid (GABA) involves coordinated mechanisms of uptake and transport within a tripartite synaptic system that includes neurons and glia. Newly appreciated role of the glia, more specifically astrocytes on neuronal functions combined with reported postmortem abnormalities of glia in patients with mood disorders further supports the role of glia in mood disorders. MATERIALS AND METHODS: This report presents some of our preliminary results utilizing glia-selective toxins and other pharmacological tools to suppress glial function within the limbic system to study the resulting behavioral abnormalities, and thus, elucidate glial involvement in the development of mood disorders. RESULTS AND DISCUSSION: We demonstrate that chronic blockade of glutamate uptake by a glial/neuronal transporter antagonist L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) within the amygdala, a key area implicated in mood regulation, results in dose-dependent reduction in social exploratory behavior and disrupts circadian activity patterns consistent with symptoms of mood disorders. Similarly, the selective astrocytic glutamate transporter type 1 (GLT-1) blocker dihydrokainic acid (DHK) injected into the amygdala also results in reduced social interaction that is blocked by selective glutamate N-methyl-D-aspartate (NMDA) type receptor antagonist AP5. The results are discussed in the context of glial and glutamate mechanisms in mood disorders and potential therapeutic avenues to address these mechanisms.

Affect↗

Smoking is associated with schizophrenia, but not with mood disorders, within a population with low smoking rates: a matched case-control study in Bucaramanga, Colombia.

When comparing current smoking in schizophrenia patients versus the general population, the average odds ratio (OR) was 5.3 in a meta-analysis of 42 studies from 20 nations. Limited tobacco access can eliminate this strong association in some nations. Out of the 42 ORs, 37 were significantly higher than 1. Of the 5 non-significant ORs, three came from Colombian studies comparing current smoking prevalences in schizophrenia versus those in the general population (18%). However, the 3 ORs were not adjusted for confounders. We hypothesized that the association between schizophrenia and smoking is so strong that it can be detected in populations with limited access to smoking after carefully controlling for confounders. Of the three Colombian studies, one included 73 schizophrenia patients (DSM-IV schizophrenia or schizoaffective disorder) and 111 patients with mood disorders (DSM-IV bipolar or major depressive disorders). The current study matched each of these patients with 2 controls from the general population and performed more sophisticated statistical analyses. Prevalences of current smoking were 26% for schizophrenia patients and 10% for their matched controls (adjusted Mantel-Haenszel OR=3.1, 95% CI, 1.4-6.8), and 7% for patients with mood disorders and 12% for their matched controls (adjusted Mantel-Haenszel OR=0.62; CI, 0.28-1.4). The previously observed lack of association between schizophrenia and current smoking was due to lack of control of important confounding variables because of the absence of a control group. This re-analysis, which used a careful matching that controlled for confounders, suggests that the association between schizophrenia and smoking behaviors can stand in populations with low monetary income and low smoking rates. This study also suggests that the association between severe mood disorders (bipolar and major depression) and smoking is not as strong as that observed between schizophrenia and smoking, and may not be observable in countries where people have limited economic resources.

Adult↗

Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders.

Disturbances in dopaminergic systems have been implicated in the etiology of mood disorders. Although genetic factors also play an important role, no major gene has been identified. We conducted an association study using the dopamine D2, D3 and D4 receptor, and transporter gene polymorphisms, comparing 101 mood-disorder patients (52 bipolar and 49 unipolar) and 100 controls. Our results suggest that there is a significant association between the dopamine D4 receptor gene and mood disorders, especially major depression, but no association between the other polymorphisms and mood disorders. Further investigations are needed to clarify the clinical significance of this association in the pathophysiology of mood disorders.

Adult↗

Prevalence of mood disorders and utility of the PRIME-MD in patients undergoing radiation therapy.

PURPOSE: To validate a short, structured interview procedure that allows practicing oncologists to quickly and reliably identify mood disorders in their patients, and to estimate the prevalence and types of mood disorders in a radiation therapy patient setting, noting relationships between mood disorders and patient characteristics. METHODS: Consecutive, eligible adult patients from the practices of two radiation oncologists were administered the Primary Care Evaluation of Mental Disorders (PRIME-MD) by the treating physician. A subset of these patients was also evaluated with the SCID, administered by trained mental health care personnel. Agreement between the two instruments was examined using the kappa statistic. Prevalence of mood disorders was determined from the PRIME-MD. The significance of relationships between patient characteristics and mood disorders was examined by chi-square and ANOVA analysis, and subsequently by multivariate logistic regression analysis. RESULTS: One hundred twenty-two patients were studied. Fifty-three of these were administered the SCID. Agreement between the two instruments was very good (kappa = 0.70). A diagnosis of a depressive or anxiety disorder by the PRIME-MD was made in 59 of the 122 patients (48%, 95% confidence interval = 39%, 58%). Multivariate analysis showed that a diagnosis of a depressive mood disorder was significantly related to pain intensity and prior history of depression. CONCLUSION: We have demonstrated the validity and feasibility of the PRIME-MD administered by oncologists in making diagnoses of mood disorders. The prevalence of mood disorders in our set of patients undergoing a course of RT was nearly 50%. Future studies should describe the natural history of these disorders, and determine optimal intervention strategies.

Adult↗

Case study: nefazodone for juvenile mood disorders.

OBJECTIVE: Despite the increasing recognition of juvenile mood disorders, few medications have been shown to be effective. Nefazodone is a novel antidepressant that remains untested in children. Seven cases are described, including four with bipolar depression, in which nefazodone was used for depression. METHOD: The authors systematically studied the response to nefazodone used naturalistically in seven treatment-refractory and very comorbid children and adolescents (mean age +/- SD, 12.4 + 3.1) with a juvenile mood disorder that was diagnosed clinically and confirmed by structured psychiatric interview. Response to treatment was evaluated retrospectively by an independent rater using the Clinical Global Impression (CGI) of severity and improvement of depression. RESULTS: Children and adolescents received nefazodone for 13 (+/-8) weeks at a mean daily dose of 357 +/- 151 mg (3.4 mg/kg). Fifty-six percent of children and adolescents previously unresponsive to multiple medication trials manifested much to very much improvement as measured by the CGI. Two of four children with bipolar depression responded well to treatment, whereas the other two had mild manic activation. Overall, nefazodone was well tolerated, with adverse effects reported in only three subjects. CONCLUSION: Nefazodone appears to be a well-tolerated compound that may provide a treatment option for juveniles with mood disorders. Further controlled trials are warranted.

Adolescent↗

Antipsychotics in the treatment of mood disorders and risk of tardive dyskinesia.

Psychosis occurs commonly in patients with mood disorders and has traditionally been treated with typical antipsychotics. Exposure to typical antipsychotics poses a risk for the emergence of tardive dyskinesia. Atypical antipsychotics may have advantages over typical agents in the treatment of patients with mood disorders complicated by psychotic features. The studies of typical and atypical antipsychotics in the treatment of mood disorders were reviewed. Similarly, studies regarding the risk of tardive dyskinesia from typical and atypical agents in patients with mood disorders were surveyed. Typical and atypical antipsychotics appear to be comparably effective in the treatment of acute mania. Limited data regarding these medications in psychotic depression are available. Advantages of atypical antipsychotics include, for most agents, minimal extrapyramidal and prolactin effects, inherent thymoleptic activity, and lower rates of tardive dyskinesia. Atypical antipsychotics appear to have a number of advantages over typical agents in the treatment of patients with psychotic mood disorders.

Acute Disease↗

Genetics of affective (mood) disorders.

The enormous public health importance of mood disorders, when considered alongside their substantial heritabilities, has stimulated much work, predominantly in bipolar disorder but increasingly in unipolar depression, aimed at identifying susceptibility genes using both positional and functional molecular genetic approaches. Several regions of interest have emerged in linkage studies and, recently, evidence implicating specific genes has been reported; the best supported include BDNF and DAOA but further replications are required and phenotypic relationships and biological mechanisms need investigation. The complexity of psychiatric phenotypes is demonstrated by (a) the evidence accumulating for an overlap in genetic susceptibility across the traditional classification systems that divide disorders into schizophrenia and mood disorders, and (b) evidence suggestive of gene-environment interactions.

Bipolar Disorder↗

Screening for bipolar disorders using a French version of the Mood Disorder Questionnaire (MDQ).

BACKGROUND: Bipolar disorders remain much too often unrecognized and subsequently inappropriately treated. This paper presents the translation into French and validation of the MDQ, a screening instrument for bipolar spectrum disorders, in an adult psychiatric sample. Modifications of its criteria for a positive screening as well as its test-retest reliability are also addressed. METHODS: A sample of 96 patients, attending outpatient treatment programs and suffering from mood disorders, completed the MDQ before being interviewed according to the mood module of the structured clinical interview for DSM-IV (SCID). They completed the MDQ a second time 1 month later, in order to examine its stability over time. RESULTS: According to the SCID interview, 54 patients were suffering from bipolar disorder and 42 from unipolar disorder. Among the bipolar sample, the MDQ identified 74.1% of them, with higher sensitivity in bipolar I (90.3%) than bipolar II (52.4%) and 90.5% specificity. Lowering the level of impairment required for positive screening led to improved sensitivity for bipolar II patients (76.2%). The French MDQ demonstrated adequate internal consistency (Cronbach alpha=0.89). Its test-retest reliability proved to be satisfactory, with a kappa coefficient of 0.79. Similar stability over a 1-month interval was obtained for bipolar type I and type II (kappa=0.75 and 0.77, respectively). LIMITATIONS: Similarly to the American version, the French MDQ has lower sensitivity for bipolar II disorders. CONCLUSIONS: The performance of the French MDQ is comparable to the one reported in the original American study conducted with a similar patient population. In a psychiatric outpatient sample, the French MDQ proves to be a feasible and reliable screening instrument.

Adolescent↗

Prevalence, diagnosis, and pharmacological treatment of mood disorders in HIV disease.

Human immunodeficiency virus seropositive (HIV+) individuals are at a heightened risk of developing mood disorders and related syndromes. Over the past several decades, increased rates of mood disorders, including depression and mania, have been reported among HIV+ individuals. Because alterations in mood may impact on quality of life and perhaps reduce adherence to antiretroviral treatment regimens that are critical for preventing disease progression, recognition and effective treatment of mood disorders is essential. There are accumulating data showing that antidepressants and mood stabilizers, as well as other novel agents, might benefit HIV+ individuals suffering from a concomitant mood disturbance. This review highlights the relevant studies that have examined prevalence rates of mood disorders in HIV+ individuals, characteristics of HIV disease that influence the diagnosis and psychopharmacologic treatment of mood disorders, including complex interactions with antiretroviral medications, as well as the available evidence regarding the efficacy of agents used to treat depression and mania in the context of HIV disease.

Antidepressive Agents↗

Treatment of anxiety disorder in patients with mood disorders.

Symptoms compatible with a diagnosis of anxiety disorder frequently complicate the course of affective illness. Patients with depression may have panic attacks, phobias, severe social anxiety, obsessions, compulsions, and generalized anxiety. If the affective disorder is the primary condition, its treatment should be sufficient in most instances to relieve the concomitant anxiety symptoms. Thus, judicious choice of antidepressant therapy for treatment of major and atypical depression will usually resolve associated panic attacks, generalized anxiety, phobias, and compulsions. It must be recalled, however, that antidepressant therapy usually takes between 4 and 6 weeks to have full clinical effect; in the interim, anxiety symptoms may be the most troubling and disabling aspect of the illness. Therefore, using antianxiety agents in treating depressed patients who also have anxiety symptoms is often recommended while waiting for the antidepressant to work. Benzodiazepines are extremely useful for short-term treatment of most anxiety symptoms in depressed patients. The dose should be kept to the lowest possible to relieve symptoms, and the medication should be tapered and then discontinued once the underlying affective disturbance is relieved. Buspirone is also very effective in treating generalized anxiety disorder and may be used in conjunction with antidepressants of most classes. A wide range of behavioral and cognitive techniques may also help relieve anxiety symptoms in the depressed patient.

Antidepressive Agents↗