Open adjunctive ziprasidone associated with weight loss in obese and overweight bipolar disorder patients

Objective

To assess effectiveness and tolerability of open adjunctive ziprasidone for weight loss in obese/overweight patients with bipolar disorders (BD) in diverse mood states, taking weight gain-implicated psychotropic medications.

Method

22 obese and three overweight BD patients (20 female; 10 BD-I, 14 BD-II, 1 BD-NOS) with mean ± SD baseline body mass index (BMI) of 31.8 ± 2.5 kg/m² received ZIP (mean final dose 190 ± 92 mg/day) for mean of 79.2 ± 23.2 days. Weight was assessed at six weekly and three biweekly visits. Subjects entered the study in diverse mood states. At baseline, 21 were taking second-generation antipsychotics, 7 lithium, and 1 valproate, which could be reduced/discontinued at investigators’ discretion.

Results

Weight and BMI decreased from baseline to endpoint by 4.5 ± 3.4 kg and 1.6 ± 1.2 kg/m², respectively, at weekly rates of 0.37 kg and 0.13 kg/m², respectively (all p < 0.00001). 48% of patients had at least 5% weight loss. Obesity rate decreased from 88% to 35% (p < 0.0001). Waist circumference decreased 1.6 inches (p = 0.0001). Overall, mood did not change. Patients with at least moderate baseline mood symptoms experienced significant mood improvement, despite 72% patients decreasing/discontinuing weight gain-implicated psychotropic medications. Seven patients discontinued ZIP early: 3 for weight loss inefficacy, and 1 each for viral gastroenteritis, loss of consciousness, pneumonia with hypomania, and lost to follow up.

Conclusion

Open adjunctive ziprasidone may be effective for weight loss in obese/overweight BD patients taking weight gain-implicated psychotropic medications. These preliminary data should be considered with caution due to the open uncontrolled design, small sample size, and brief duration.     

The impact of zonisamide on weight. A clinical study in 103 patients with epilepsy

Objective – To investigate the impact of zonisamide (ZNS) on body weight in patients with epilepsy. Methods – A retrospective chart analysis of weight changes after initiation of ZNS (103 patients; 54 female; age 17–68 years). For 31 patients follow‐up data after ZNS‐withdrawal were available. Patients were categorized according to body‐mass‐index (BMI) <20, 20–25, and >25 kg/m². Results – Body weight before ZNS was 78.6 ± 16.0 kg (range 45–120 kg), BMI 26.5 ± 5.2 kg/m² (range17.6–41.3 kg/m²). Within 13 ± 7.2 months of treatment, mean body weight decreased by ?3.7% ± 9.1%, showing high interindividual variability (?36% to +32%). Weight loss >5% was documented in 35%, weight gain >5% in 14% of patients. Weight loss was more prominent in patients being overweight prior to treatment onset. At the end of follow‐up, patients with overweight had decreased by number. Weight changes under ZNS were not correlated to ZNS daily dosage. Following discontinuation of ZNS treatment weight loss proved to be reversible. Conclusion – Zonisamide reduced weight in 35% of patients, especially in patients with overweight prior to treatment. Weight loss is reversible following discontinuation of treatment with ZNS.     

Long-term effectiveness of quetiapine in bipolar disorder in a clinical setting

Objective

To assess quetiapine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Methods

We naturalistically administered open quetiapine to outpatients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results

96 patients (36 BD I, 50 BD II, 9 BD NOS, 1 Schizoaffective Bipolar Type, mean ± SD age 42.3 ± 13.8 years, 66.7% female) received quetiapine, combined with an average of 2.5 (in 66.7% of patients at least 2) other psychotropic medications and 0.9 non-psychotropic medications, started most often during depressive symptoms (53.1%) or euthymia (37.5%). Mean quetiapine duration and final dose were 385 days and 196 mg/day (50.0% of patients took ≤75 mg/day). Quetiapine was discontinued in 38.5% of trials, after on average 307 days, most often (in 19.8%) due to CNS adverse effects (primarily sedation). In 38.5% of trials quetiapine was continued on average 328 days with no subsequent psychotropic added. In 22.9% quetiapine was continued on average 613 days, but had subsequent psychotropic added after on average 113 days, most often for depressive symptoms. In 67 trials started at Stanford, quetiapine tended to primarily maintain euthymia and relieve depressive symptoms. In 29 trials started prior to Stanford, continuing quetiapine tended to primarily maintain euthymia and relieve mood elevation symptoms. Aside from sedation, quetiapine was generally well tolerated.

Conclusions

In bipolar disorder outpatients quetiapine had a moderate (38.5%, with 385-day mean duration) discontinuation rate, and commonly did not require subsequent additional pharmacotherapy, suggesting effectiveness in a clinical setting.     

Weight gain and metabolic effects of mood stabilizers and antipsychotics in pediatric bipolar disorder: a systematic review and pooled analysis of short-term trials

OBJECTIVE: To review weight and metabolic effects of mood-stabilizing treatments in pediatric bipolar disorder. METHOD: Systematic PubMed/Medline search of studies reporting on change in weight and/or glucose/lipid values with mood-stabilizing drugs in at least nine pediatric patients with bipolar disorder. RESULTS: Nineteen studies, including 24 medication trials in 684 patients (mean age, 12.3 +/- 2.9 years) were included. Youngsters received lithium, antiepileptics, or their combinations (n = 459), or second-generation antipsychotics, alone or combined with lithium or divalproex (n = 225), for 4 to 48 (mean, 15.4 +/- 12.7) weeks. Weight increase was significant/clinically relevant in 18 (75.0%) trials. Weight loss was significant with topiramate (2 studies, 38 subjects) and present with aripiprazole (1 study, 14 subjects). In trials lasting < or =12 weeks, weight gain was greater with second-generation antipsychotics plus mood stabilizers (5.5 +/- 1.8 kg) compared to mood-stabilizer monotherapy (1.2 +/- 1.9 kg, p <.05, Cohen's d = 2.33) or mood-stabilizer cotreatment (2.1 +/- 1.3 kg, p <.05, Cohen's d = 2.17), but not compared to antipsychotic monotherapy (3.4 +/- 1.3 kg, p >.05, Cohen's d = 1.34). Nonfasting glucose/lipid changes were nonsignificant in two second-generation antipsychotic trials (n = 61, 8.9%). CONCLUSIONS: Data are sparse regarding body composition effects and lacking for fasting metabolic effects of mood stabilizers in pediatric bipolar disorder. Combining antipsychotics with mood stabilizers seems to lead to greater weight gain than treatment with one or two mood stabilizers.     

Venlafaxine treatment of binge-eating disorder associated with obesity: a series of 35 patients

BACKGROUND: Binge-eating disorder is a newly recognized eating disorder characterized by recurrent episodes of binge eating without extreme weight loss behaviors. It commonly co-occurs with overweight and obesity. To preliminarily explore the effectiveness and tolerability of venlafaxine in binge-eating disorder, we retrospectively reviewed the response of 35 consecutive overweight or obese outpatients with binge-eating disorder presenting at the University of Cincinnati Physicians Weight Management Program, Cincinnati, Ohio, to clinical treatment with venlafaxine. METHOD: The medical charts of 35 consecutive outpatients with binge-eating disorder (DSM-IV criteria) and overweight (body mass index [BMI] = 25.0-29.9) or obesity (BMI > or = 30.0) who received clinical treatment with venlafaxine at a weight management program were reviewed. Response of binge-eating disorder symptoms was assessed by weekly binge frequency (the number of binges reported by the patient the week before the clinic appointment), the Clinical Global Impressions-Severity of Illness (CGI-S) scale, and categorical response (no response, mild, moderate, marked, or remission). Weight, BMI, waist circumference, comorbid Axis I diagnoses, vital signs, and side effects also were collected. RESULTS: Twenty-nine patients (83%) received venlafaxine as monotherapy and 6 (17%) received the drug adjunctively for a median of 120 days (range, 28-300 days). The mean +/- SD venlafaxine treatment dose was 222 +/- 63 mg/day (range, 75-300 mg/day). In the 33 patients who were actively binge eating at the time venlafaxine was begun, weekly binge frequency, severity of binge-eating and mood symptoms as measured by the CGI-S scale, weight, BMI, waist circumference, and diastolic blood pressure all showed statistically significant decreases over time (p < .05). Of these 33 patients, 29 (88%) displayed a moderate (50% reduction) or better response of binge-eating episodes. Fifteen (43%) of the 35 patients lost 5% or more of their baseline weight. In general, venlafaxine was well tolerated, with dry mouth, sexual dysfunction, insomnia, and nausea being the most frequently reported side effects. Sustained increases in blood pressure seen in 6 patients (17%) were considered clinically insignificant. No patients discontinued the drug. CONCLUSION: Venlafaxine may be an effective treatment for binge-eating disorder associated with overweight or obesity. Controlled studies of venlafaxine in binge-eating disorder appear warranted.     

A 24-week, randomized, controlled trial of adjunctive sibutramine versus topiramate in the treatment of weight gain in overweight or obese patients with bipolar disorders

OBJECTIVES: Patients with bipolar disorder (BD) have an increased risk of obesity as well as psychotropic-associated weight gain. The objective of this study was to compare sibutramine and topiramate as adjunctive treatments for psychotropic-associated weight gain in overweight or obese outpatients with BD. METHODS: In this 24-week, open-label, flexible-dose, comparison trial, 46 outpatients with bipolar disorders who had a body mass index (BMI) > or =30 kg/m(2), or > or =27 kg/m(2) with obesity-related comorbidities, and psychotropic-associated weight gain were randomly assigned to receive sibutramine (n = 18; 5-15 mg/day) or topiramate (n = 28; 25-600 mg/day). The primary outcome measure was weight loss. Secondary measures included changes in BMI, percent body weight loss, and mood symptoms. RESULTS: Patients randomized either to sibutramine or topiramate lost comparable amounts of weight (4.1 +/- 5.7 and 2.8 +/- 3.5 kg, respectively) and displayed similar rates of weight loss (0.85 and 0.82 kg/week, respectively). However, only four (22%) patients receiving sibutramine and six (21%) patients receiving topiramate completed the 24-week trial. In addition, the attrition patterns for the two drugs were different, with patients discontinuing topiramate doing so early in treatment and patients discontinuing sibutramine doing so throughout treatment. Also, higher ratings of manic and depressive symptoms significantly increased risk for early topiramate discontinuation compared to that for sibutramine. CONCLUSIONS: Adjunctive sibutramine and topiramate may have comparable weight loss effects in overweight or obese bipolar patients with psychotropic-associated weight gain, but are each associated with similarly high discontinuation rates. In addition, they may have different attrition profiles. Compared to sibutramine, discontinuation of topiramate may be more likely to occur early in treatment and may be more dependent upon manic and depressive symptoms.     

Current irritability robustly related to current and prior anxiety in bipolar disorder

BackgroundAlthough current irritability and current/prior anxiety have been associated in unipolar depression, these relationships are less well understood in bipolar disorder (BD). We investigated relationships between current irritability and current/prior anxiety as well as other current emotions and BD illness characteristics.MethodsOutpatients referred to the Stanford Bipolar Disorders Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Prevalence and clinical correlates of current irritability and current/prior anxiety and other illness characteristics were examined.ResultsAmong 497 BD outpatients (239 Type I, 258 Type II; 58.1% female; mean ± SD age 35.6 ± 13.1 years), 301 (60.6%) had baseline current irritability. Patients with versus without current irritability had significantly higher rates of current anxiety (77.1% versus 42.9%, p < 0.0001) and history of anxiety disorder (73.1% versus 52.6%, p < 0.0001). Current irritability was more robustly related to current anxiety than to current anhedonia, sadness, or euphoria (all p < 0.001), and current irritability-current anxiety associations persisted across current predominant mood states. Current irritability was more robustly related to past anxiety than to all other assessed illness characteristics, including 1° family history of mood disorder, history of alcohol/substance use disorder, bipolar subtype, and current syndromal/subsyndromal depression (all p < 0.05).LimitationsLimited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample.ConclusionsIn BD, current irritability was robustly related to current/prior anxiety. Further studies are warranted to assess longitudinal clinical implications of relationships between irritability and anxiety in BD.     

Attention-deficit hyperactivity disorder -- bipolar comorbidity in children and adolescents

OBJECTIVE: A substantial portion of juvenile bipolar disorder (BD) has a comorbid attention-deficit hyperactivity disorder (ADHD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. METHODS: Ninety-eight refereed patients (mean age 13.7 +/- 3.0 years) with a diagnosis of BD by the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime version (K-SADS-PL) were followed for 6 months. RESULTS: Thirty-seven BD patients (37.8%) presented a lifetime diagnosis of comorbid ADHD. The mean age of onset of ADHD was 3.7 +/- 1.1 years, and the mean age of onset of BD was 10.0 +/- 3.2 years. Bipolar subjects with comorbid ADHD were predominantly male, younger, and had an earlier onset of BD (8.1 +/- 2.8 versus 11.1 +/- 2.9 years). Bipolar-ADHD patients presented more frequently a chronic rather than an episodic course of BD, with an irritable rather than an elated mood. They showed higher rates of oppositional defiant disorder/conduct disorder, lower rates of panic disorder, and less frequently received antidepressant medications. Finally, ADHD comorbidity was associated with a greater psychosocial impairment. CONCLUSIONS: ADHD comorbidity is frequent in juvenile BD and can influence age of onset, phenomenology, comorbidity, and course of BD. A timely diagnosis should improve our efforts regarding the outcome of these subjects.     

Differential prevalence and demographic and clinical correlates of second-generation antipsychotic use in bipolar I versus bipolar II disorder

AimsTo assess second-generation antipsychotic (SGA) use, demographics, and clinical correlates in patients with bipolar I disorder (BDI) versus bipolar II disorder (BDII).MethodsStanford Bipolar Disorder (BD) Clinic outpatients enrolled during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Current SGA use, demographics, and clinical correlates were assessed for BDI versus BDII.ResultsAmong 503 BD outpatients, in BDI versus BDII, SGA use was more than twice as common (44.0% versus 21.2%), and doses were approximately twice as high. BDI patients taking (N = 107) versus not taking (N = 136) SGAs less often had current full time employment and college degree; and more often had lifetime psychiatric hospitalization, current depression, and current complex pharmacotherapy, and had a higher mean current Clinical Global Impression for Bipolar Version Overall Severity score, and these persisted significantly after covarying for employment and education. Prior psychiatric hospitalization was the most robust correlate of SGA use in BDI patients. In contrast, these demographic and clinical correlates of SGA use were not statistically significant among patients with BDII, although BDII (but not BDI) patients taking (N = 55) versus not taking (N = 205) SGAs were more likely to have current mood stabilizer use (67.3% versus 51.7%).LimitationsAmerican tertiary bipolar disorder clinic referral sample, cross-sectional design.ConclusionsCurrent SGA use was robustly associated with prior psychiatric hospitalization in BDI and to a more limited extent with current mood stabilizer use in BDII. SGA use associations with other unfavorable illness characteristics in BDI were less robust.     

APOE-epsilon4 is associated with weight loss in women with AD: a population-based study

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.     

Low serum leptin level is associated with zonisamide-induced weight loss in overweight female epilepsy patients

Because iatrogenic obesity may hinder medication compliance, it would be a reasonable approach to consider antiepileptic drugs (AEDs) that promote weight loss in overweight patients. We performed an open-label, observational study to assess the effects of zonisamide on weight in overweight female epilepsy patients. In particular, we studied how the basal serum leptin level is related to changes in the weight of these patients. We recruited female epilepsy patients with basal body mass index 25 or more. Laboratory findings including serum leptin level were measured and zonisamide was administered as a monotherapy at a dose of 200 to 400mg/day. Six months later, we measured changes in the body weight. Thirty-seven female epilepsy patients enrolled in the study, and 23 of them completed the treatment. Weight loss after zonisamide treatment was correlated with initial body weight (p=0.020), follow-up weight (p=0.010), and basal serum leptin level (p=0.008), but was not correlated with patients' age, results of lipid profile, and dosage of zonisamide. The correlation of the serum leptin level with weight loss was still significant after the effect of the initial weight was adjusted (p=0.042). Our study shows that low serum leptin level is associated with weight loss in overweight female epilepsy patients. This result may be beneficial for selecting AEDs and provide clues for the pathophysiology of zonisamide-induced weight loss.     

Open-label adjunctive zonisamide in the treatment of bipolar disorders: a prospective trial

BACKGROUND: The response of 62 outpatients with DSM-IV bipolar disorders to open-label adjunctive zonisamide was evaluated in a prospective 8-week acute trial, followed by a 48-week continuation trial, conducted from June 2001 through May 2002. METHOD: During the acute trial, response to zonisamide was assessed weekly for the first 4 weeks and every 2 weeks for the second 4 weeks with the Clinical Global Impressions scale modified for bipolar illness (CGI-BP), the Young Mania Rating Scale (YMRS), and the Inventory for Depressive Symptomatology (IDS). During the continuation trial, patients were assessed with these scales every 4 weeks. Patients' weights and side effects were also evaluated. Outcome measures were analyzed with repeated-measures analyses of variance. RESULTS: Patients with manic symptoms at study entry (N = 34) displayed significant reductions in CGI-BP-Mania Severity and YMRS scores in the acute and continuation (N = 19) trials (p values < .0001 and < .001, respectively). Patients with depressive symptoms at study entry (N = 22) showed significant decreases in CGI-BP-Depression Severity and IDS scores in the acute trial (p values < .001 and < .05, respectively), but only 9 patients entered the continuation trial. Among these 9 patients, maintenance of anti-depressant response was mostly maintained. Initially euthymic patients (N = 6) showed no change in any rating scale scores acutely, but 2 of 4 patients who entered the continuation trial developed depressive symptoms. The 62 patients as a group showed significant weight loss in both trials (p values < .001). However, 20 patients (32%) discontinued zonisamide for worsening mood symptoms. CONCLUSION: Adjunctive zonisamide was associated with beneficial effects on mood and body weight in some patients with bipolar disorders, but was also associated with a high discontinuation rate due to worsening mood symptoms. Double-blind, placebo-controlled studies are necessary to determine zonisamide's thymoleptic properties, if any, in bipolar disorders.     

Developmental differences according to age at onset in juvenile bipolar disorder

BACKGROUND: This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. METHODS: A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. RESULTS: Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. CONCLUSIONS: Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.     

Long-term maintenance of weight loss in patients with severe mental illness through a behavioural treatment programme in the UK

OBJECTIVE: Obesity is common among people with severe mental illness (SMI). We report our experience from the first 4 years of The Cromwell House weight management clinic. METHOD: Ninety-three patients with SMI aged 43.7 +/- 1.2 years referred themselves to this clinic. The patients were seen in weekly group sessions that involved weight measurement, discussion and education. RESULTS: Mean baseline weight was 89.5 +/- 1.8 kg [body mass index (BMI) 32.3 +/- 0.5 kg/m(2)]. Twenty-three per cent dropped out within the first 8 weeks. There was progressive statistically significant reduction in mean weight and BMI throughout the duration of monitoring with no suggestion of a plateau. The mean final weight loss was 6.2 +/- 0.6 kg. Weight loss was correlated only with the number of sessions attended (r = 0.53, P < 0.0001). CONCLUSION: Long-term weight management of obese and overweight patients with severe forms of mental illness was possible through the provision of simple lifestyle advice within the group setting.     

Effectiveness of lamotrigine in bipolar disorder in a clinical setting

Objective

To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Method

Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results

One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean ± SD age 42.2 ± 14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1 ± 1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434 ± 444 days, and mean final dose was 236 ± 132 mg/day without valproate, and 169 ± 137 mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255 ± 242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264 ± 375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674 ± 479 days, but had subsequent psychotropic added at 146 ± 150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.

Conclusion

In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.     

Zonisamide produces weight loss in psychotropic drug-treated psychiatric outpatients

This study examined the long-term effectiveness and tolerability of zonisamide for weight control in psychiatric outpatients using various psychotropic medications. We conducted a systematic chart review of 82 psychiatric outpatients with unwanted weight gain after the introduction of psychotropic drugs between January 2008 and September 2009 at Korea University Ansan Hospital. The primary outcome measure was the effect of zonisamide on body mass index (BMI). Additional outcome measures included safety and tolerability as assessed by the clinical global impression-severity of illness scale (CGI-S) and discontinuation rate. The mean final dose of zonisamide was 124.6 ± 53.4 mg/day and ranged from 50 mg/day to 300 mg/day. The mean BMI reduction was 0.8 ± 1.7 kg/m² and ranged from − 2.9 kg/m² to 4.7 kg/m² (p < 0.001). We also observed a significant reduction in CGI-S scores from the baseline (3.8 ± 0.9) to the endpoint (3.3 ± 0.8; p < 0.001). Twelve patients (14.6%) discontinued their zonisamide treatment due to its side effects. Patients treated with zonisamide showed significant weight loss. Furthermore, its treatment was generally safe and well tolerated with few negative effects on patients' overall psychiatric symptoms. Additional research is required to confirm these results and to investigate whether patients have rebound weight gains after discontinuing zonisamide.     

Clinical implications of DSM-IV subtyping of bipolar disorders in referred children and adolescents

OBJECTIVE: According to DSM-IV, bipolar disorders (BDs) include four subtypes, BD I, BD II, cyclothymic disorder, and BD not otherwise specified (NOS). We explore the clinical implications of this subtyping in a naturalistic sample of referred youths with BD I, BD II, and BD-NOS. METHOD: The sample consisted of 217 patients, 135 males and 82 females, ages between 8 and 18 years (mean age, 13.6 +/- 2.9 years), diagnosed according to historical information, prolonged observations, and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version). The location of the study was the Stella Maris Scientific Institute of Child Neurology and Psychiatry of Pisa (Italy). RESULTS: Seventy-eight patients (35.9%) had BD I, 97 (44.7%) had BD II, and 42 (19.4%) had BD-NOS. Patients with BD I presented more frequently psychotic symptoms and elated rather than irritable mood. Patients with BD II were less severely impaired, presented more frequently depression as the intake affective episode, and had the highest comorbidity with anxiety disorders. Patients with BD-NOS presented an earlier onset of the disorder, a chronic rather than episodic course, an irritable rather than an elated mood, and a more frequent comorbidity with attention-deficit/hyperactivity disorder and oppositional defiant disorder. CONCLUSIONS: DSM-IV categorization of BD may have meaningful implications in youths, but needs to be detailed further.     

Circulating leptin levels and weight loss in Alzheimer's disease patients

Weight loss is common in Alzheimer's disease (AD) and is predictive of mortality. Leptin, an adipocyte-derived peptide hormone is implicated in the regulation of satiety and energy expenditure. It acts on the hypothalamus to suppress appetite and increase energy expenditure. We undertook this study to determine if inappropriately elevated leptin levels play a role in AD-associated weight loss. Serum leptin levels of 8 patients in each of the following groups were determined: (1) AD, body mass index (BMI) >25; (2) AD, BMI <20; (3) non-Alzheimer's (vascular) dementia (VaD), BMI >25, and (4) VaD, BMI <20. Mean serum leptin levels were significantly lower in below-appropriate-weight patients (both AD and VaD) than in appropriate-weight controls. Below-appropriate-weight AD patients had a significantly lower mean serum leptin concentration than appropriate-weight VaD controls. Weight loss is a feature of AD. Inappropriately elevated leptin levels do not appear to be implicated. Indeed, we have shown that the afferent limb of the leptin feedback loop is intact in below-appropriate-weight AD patients and suggest hypothalamic dysfunction may underlie this feature.     

A relative resistance of T cells to dexamethasone in bipolar disorder

OBJECTIVE: A relative resistance of immune cells to steroids has been established in patients with major depression (MD). In this study, we investigated the in vitro responsiveness of T cells to dexamethasone (DEX) of patients with bipolar disorder (BD). METHODS: T cells of outpatients with DSM-IV BD (n = 54) and of healthy control subjects (HC; n = 29) were isolated, cultured and stimulated with phytohemagglutinin (PHA) for 72 h. The suppressive effect of graded concentrations of DEX (5 x 10(-9)-10(-5) M) on PHA-induced CD25 (IL-2R) expression was measured by fluorescence-activated cell sorting (FACS) analysis. Data were correlated to the T-cell activation status in the peripheral blood of the same patients and to their diagnosis, current mood state, ultradian cycling pattern and current use of medication, including lithium. RESULTS: T cells of patients with BD were less sensitive to DEX-induced suppressive effects as compared with T cells of HC. These data were particularly evident at 10(-7) M DEX (mean % suppression +/- SEM BD: 18.9% +/- 3.5 versus HC: 35.8% +/- 4.7, p = 0.001). We found no correlations of this relative in vitro DEX resistance of T cells neither with the previously mentioned clinical characteristics nor with the actual activation status of the T cells in the BD patients. CONCLUSION: A relative T-cell resistance to steroids, as has been observed in MD previously, may be a trait phenomenon of BD, independent of mood state.