A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation

Context. Antiepileptic drugs (AEDs) are frequently used for their beneficial mood effects.Objective. We sought to determine if there was a quantifiable effect on mood of the vagus nerve stimulator (VNS) when used as an antiseizure treatment.Design. Mood was assessed before and 3 months after VNS implantation in adult epilepsy patients. A group of adult epilepsy patients on stable AED regimens were used as a comparison group. AED regimens were unchanged during the study. The change in mood scale scores across time was assessed by t test (intragroup) and two-factor repeated-measures ANOVA (intergroup).Setting. An epilepsy center in a university hospital was the setting.Subjects. Twenty consecutive adult epilepsy patients undergoing VNS implantation to improve seizure control and twenty adult seizure patients with no intervention were enrolled.Main outcome measures. The mood scales used were the Cornell Dysthymia Rating Scale (CDRS) and the Hamilton Depression (Ham-D), Hamilton Rating Scale for Anxiety (Ham-A), and Beck Depression Inventory (BDI) scales.Results. The VNS group showed a significant decrease in mood scale scores across time (t test CDRS P = 0.001, Ham-D P = 0.017, BDI P = 0.045), indicating a decrease in depressive symptoms. The Ham-A scores in the VNS group and the comparison group scores did not significantly change across time. There were no significant differences between groups across time, although the BDI approached significance at P = 0.07. The VNS group had a significant decrease in seizure frequency compared with the comparison group (P = 0.01). There was no difference in mood scales over time between the VNS treatment responders (defined by >50% decrease in seizure frequency) and nonresponders, suggesting dissociation between seizure frequency reduction and mood change.Conclusion. VNS treatment is associated with mood improvement as measured by multiple scales, but differences in mood scale scores over time between the VNS and a comparison group were not found.     

Oxcarbazepine improves mood in patients with epilepsy

This study prospectively examined whether continued add-on treatment with oxcarbazepine (OXC) is associated with quantitative improvement in mood and anxiety symptoms in adult patients with partial epilepsy. Depressive symptoms and anxiety were assessed by clinical interview using the Hamilton Depression Rating Scale (HDRS), the Cornell Dysthymia Rating Scale (CDRS), the Beck Depression Inventory (BDI), and the Hamilton Anxiety Rating Scale (HARS). Forty controls (patients with epilepsy treated with antiepileptic drugs other than OXC) and 40 OXC-treated patients were enrolled and completed the study. In our study, a significant improvement in affect, as measured by the CDRS, was demonstrated during the course of OXC treatment for 3 months. HDRS and BDI scores also declined in the OXC-treated group, but these decreases did not reach statistical significance. In addition, 28 of 40 OXC-treated subjects who were dysthymic by CDRS criteria on study entry (score > or =20) demonstrated affective improvement consistent with a treatment-related antidepressant effect (score <20). Although our results do not provide conclusive evidence supporting the specific use of OXC as an antidepressant, the significant decline in dysthymic symptoms in OXC-treated subjects compared with controls lends support to the hypothesis that OXC improves mood.     

Treatment of poststroke generalized anxiety disorder comorbid with poststroke depression: merged analysis of nortriptyline trials.

OBJECTIVE: The existence of anxiety disorders plays an important role in the prognosis and associated impairment among patients with poststroke depression. The authors examined the efficacy of nortriptyline treatment for patients with comorbid generalized anxiety disorder (GAD) and depression after stroke. METHODS: Data from three studies were merged to provide 27 patients with comorbid GAD and depression, who participated in double-blind treatment studies comparing nortriptyline (N=13) and placebo (N=14). Severity of anxiety was measured with the Hamilton Rating Scale for Anxiety (Ham-A), and severity of depression was measured with the Hamilton Rating Scale for Depression (Ham-D). Activities of daily living were assessed by use of the Johns Hopkins Functioning Inventory (JHFI). RESULTS: There were no significant differences between the nortriptyline and placebo groups in demographic characteristics, stroke type, and neurological findings. Patients receiving nortriptyline treatment showed significantly greater improvement on the Ham-A, Ham-D, and JHFI than patients receiving placebo. The anxiety symptoms showed earlier improvement than depressive symptoms in patients treated with nortriptyline. CONCLUSIONS: These findings suggest that poststroke GAD comorbid with poststroke depression may be effectively treated with nortriptyline, and data indicate the need for a trial specifically designed to examine treatment of anxiety disorder.     

Effects of depressive symptoms and anxiety on hemostatic responses to acute mental stress and recovery in the elderly

Depression and anxiety are prospectively associated with cardiac morbidity and mortality. Increased clotting diathesis may mediate this link. We hypothesized that there would be an association between mood and hemostatic changes that occur during and following recovery from acute mental stress. Forty-eight community-dwelling elderly subjects underwent a laboratory speech stressor task. Plasma von Willebrand factor (vWF), thrombin/antithrombin III (TAT) complexes, D-dimer, tissue-type plasminogen activator (t-PA), and type I plasminogen activator inhibitor (PAI-1) were measured at rest, after conclusion of the speech, and 14 min afterwards (recovery). Mood was assessed with the Hamilton Rating Scales for Depression (Ham-D) and Anxiety (Ham-A). Mental stress elicited a hypercoagulable state as evidenced by increases in TAT and D-dimer, and by a decrease in t-PA. Overall, hypercoagulability had increased after recovery. Ham-D scores and Ham-A scores correlated with increases in D-dimer over the testing interval (i.e. area under the curve). Ham-A (but not Ham-D) uniquely explained 8% and 17% of the variance in resting D-dimer and D-dimer area under the curve, respectively. The independent association of anxiety symptoms with resting and stress-induced fibrin formation (D-dimer) may be a mechanism linking mood with cardiovascular disease risk in the elderly.     

Gabapentin (Neurontin) as Add-on Therapy in Patients with Partial Seizures: A Double-Blind,Placebo-Controlled Study

Summary: A multicenter, double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add-on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12-week treatment phase (T) and the 12-week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200-mglday group provided doseresponse data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with ≥50% reduction in seizure frequency), and response ratio, where RRatio = (T B)/(T + B). Median PCH was–21.8% in the 900-mg/day group and ?17.8% in the 1,200-mg/day group as compared with ?0.3% in the placebo group. Responder rate was 22.9% in the 900-mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean Rratio was-0.136 in the 900-mg/day group and ?0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,20-mg/day than for the 900-mg/day group (RRatio =?0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900-mg/day group and in 64% in the 1,200-mg/day group as compared with 52% in patients receiving placebo as add-on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects. GBP is safe and effective in treating some patients with refractory partial seizures.     

Efficacy and Tolerance of Long-Term, High-Dose Gabapentin: Additional Observations

Summary: Gabapentin (GBP) has shown antiepileptic efficacy and good tolerance in clinical trials. Much remains to be learned about its clinical use. As a participating center in the US Gabapentin Study Group, we report observations that have practical implications for patient management. Twenty-three patients with intractable partial-onset seizures initiated open-label treatment after a blinded placebo-controlled add-on dose efficacy study. In the titration phase, GBP and concurrent antiepileptic drugs (AEDs) were adjusted to achieve optimal efficacy on maximally tolerated GBP doses. Nine patients had no significant improvement in seizure control and discontinued GBP. The remaining 14 patients were observed while treated long-term with stable-dose GBP and concurrent AEDs. Improvement was maintained as long as patients were followed: ≤4 years. The protocol-allowed upper dose limit, 2,400 mg/day, was well tolerated by 16 of 23 patients, indicating that higher doses may be tolerated. GBP discontinuation did not cause rebound increases in seizure frequency. The most common adverse events (AEs) (in 14 of 23) were similar to those induced by concurrent AEDs and responded to reduction of concurrent AEDs. Many patients reported positive psychostimulatory effects. These observations extend previous findings indicating that GBP is an effective and well-tolerated drug for treatment of partial-onset seizures.     

Gabapentin as Add-On Therapy in Children with Refractory Partial Seizures: A 12-Week, Multicentre, Double-Blind, Placebo-Controlled Study

PURPOSE: To evaluate the efficacy and safety of gabapentin (Neurontin; GBP) as add-on therapy for refractory partial seizures in paediatric patients aged 3-12 years. METHODS: After a 6-week baseline period, 247 patients (54 centres) entered a 12-week double-blind phase and were randomized to receive either GBP (t.i.d., titrated to 23-35 mg/kg/ day) or placebo. Seizure activity and type were recorded daily. Efficacy variables included Response Ratio (RRatio), responder rate, and percentage change in frequency (PCH) for all partial seizures; PCH and RRatio for individual types of partial seizures; and investigator and parent/guardian global assessments of seizure frequency and patient well-being. RESULTS: RRatio for all partial seizures was significantly lower (better) for GBP-treated patients (p = 0.0407). Responder rate favored GBP, but the difference between treatment groups was not statistically significant. Median PCH for all partial seizures for the GBP treatment group (-17.0%) was better than that for the placebo group (-6.5%). Median PCH for specific seizure types showed GBP to be most effective in controlling complex partial seizures (-35%) and secondarily generalized seizures (-28%) when compared with placebo (-12%, +13%, respectively). A greater percentage of GBP-treated patients exhibited improvement according to investigator and parent/guardian global assessments, with a statistically significant difference observed in the parent/guardian global assessment of seizure-frequency reduction (p = 0.046). Three GBP patients and one placebo patient were seizure free during the double-blind treatment period. GBP was well tolerated. CONCLUSIONS: GBP was effective and well tolerated as an add-on therapy for partial seizures in paediatric patients with previously drug-resistant seizures.     

A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders

Mantere O, Isometsä E, Ketokivi M, Kiviruusu O, Suominen K, Valtonen HM, Arvilommi P, Leppämäki S. A prospective latent analyses study of psychiatric comorbidity of DSM‐IV bipolar I and II disorders.
Bipolar Disord 2010: 12: 271–284. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood. Methods: In the Jorvi Bipolar Study (JoBS), 191 secondary‐care outpatients and inpatients with DSM‐IV bipolar I disorder (BD‐I) or bipolar II disorder (BD‐II) were evaluated with the Structured Clinical Interview for DSM‐IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD‐I, 79 BD‐II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM‐IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM‐IV‐based scales of substance use and eating disorders. Results: In the SEM, depression and anxiety exhibited strong cross‐sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16–0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15–0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001). Conclusions: Depression and anxiety covary strongly cross‐sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.     

Long-term safety and efficacy of gabapentin (neurontin) as add-on therapy in patients with refractory partial seizures

In an international, multicenter, open-label study, the long-term efficacy and safety of gabapentin (GBP, Neurontin) as add-on therapy were investigated in 203 patients with partial seizures refractory to standard antiepileptic drugs (AEDs). All patients enrolled in this study had experienced improved seizure control with GBP in one of four previous, short-term studies. Patients received mean GBP dosages of 1,283 to 2,220 mg/day for periods of ⩽1,894 days (mean, 385 days). For purposes of efficacy analyses, data were divided into 12-week treatment periods. During long-term treatment, the efficacy of GBP was shown to be maintained by several primary efficacy measures. In all of the 12-week treatment periods, the percentage of change in seizure frequency from baseline was equal to or less than −24%, responder rate was >35%, and response ratio ranged between −0.2 and −0.338. Results for secondary efficacy measures also indicated that efficacy was maintained. The favorable safety profile of GBP also was maintained during long-term treatment. Our results suggest that GBP is an effective, safe, and well-tolerated add-on treatment for long-term use in patients with partial seizures refractory to standard AEDs.     

Anxiety disorders,subsyndromic depressive episodes,and major depressive episodes: Do they differ on their impact on the quality of life of patients with epilepsy?

Aims of the study: To compare the impact of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on the quality of life of patients with epilepsy (PWEs), and to identify the variables predictive of poor quality of life. Methods: A psychiatric diagnosis according to DSM‐IV‐TR criteria was established in 188 consecutive PWEs with the MINI International Neuropsychiatric Interview. Patients also completed the Beck Depression Inventory‐II (BDI‐II), the Centers for Epidemiologic Studies‐Depression (CES‐D), and the Quality of Life in Epilepsy‐89 (QOLIE‐89). A diagnosis of SSDE was made in any patient with total scores of the BDI‐II >12 or CES‐D >16 in the absence of any DSM‐IV diagnosis of mood disorder according to the MINI. Results: Patients with SSDEs (n = 26) had a worse quality of life than asymptomatic patients (n = 103). This finding was also observed among patients with MDEs only (n = 10), anxiety disorders only (n = 21), or mixed MDEs/anxiety disorders (n = 28). Furthermore, having mixed SSDEs/anxiety disorders yielded a worse quality of life than having only SSDEs. Independent predictors of poor quality of life included having a psychiatric disorder and persistent epileptic seizures in the last 6 months. Conclusions: Although isolated mood and anxiety disorders, including SSDE, have a comparable negative impact on the quality of life of PWEs; the comorbid occurrence of mood and anxiety disorders yields a worse impact. In addition, seizure freedom in the previous 6 months predicts a better quality of life.     

Potential benefits of quetiapine in the treatment of substance dependence disorders

OBJECTIVE: Some antipsychotic medications prescribed for the treatment of psychoses, mood disorders or post-traumatic stress disorder in patients with coexisting substance dependence disorders (SDD) have reduced substance dependence. We studied the potential benefits of quetiapine in the treatment of SDD. METHODS: We conducted a retrospective chart review of data for 9 patients who were admitted to a 28-day residential rehabilitation program designed for individuals with SDD during a 3-month period from January 2003 through March 2003 and treated with quetiapine for nonpsychotic anxiety. These patients also met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for alcohol, cocaine and/or methamphetamine dependence and substance-induced anxiety disorder. The patients were assessed using the Hamilton-D Rating Scale for Depression (Ham-D), a 10-point Likert scale to measure alcohol or drug cravings, and random Breathalyzer and urine drug screens. RESULTS: Quetiapine was generally well tolerated. Only 1 of the 9 patients stopped taking the medication because of increased anxiety. Other patients reported improvement in sleep and anxiety. The mean decrease in Ham-D score at discharge for the responders was 18.5 (p < 0.005). The biggest decreases on the Ham-D occurred on the subscales of insomnia, agitation, somatic anxiety, psychologic anxiety, hypochondriasis and obsessional symptoms. The mean decrease in the Likert 10-point craving scale was 5.9 for the responders (p < 0.005). These patients' periodic Breathalyzer and urine test results suggested that they remained abstinent from alcohol and other drug use. CONCLUSION: Quetiapine was beneficial in the treatment of SDD in patients with nonpsychotic anxiety.     

双侧丘脑底核脑深部电刺激对PD患者焦虑症状的短期影响

目的探讨双侧丘脑底核脑深部电刺激(STN-DBS)对帕金森病(PD)患者焦虑症状及生活质量的短期影响。方法对上海交通大学附属瑞金医院功能神经外科中心自2017年8月至2019年8月行双侧STN-DBS治疗的39例PD患者,分别于术前、术后1个月和末次随访时进行贝克焦虑自评量表(BAI)、贝克抑郁自评量表(BDI)评分,于术前和术后末次随访时进行帕金森病患者生活质量问卷-8项(PDQ-8)评分,采用统计学方法分析各节点间评分的差异,以及评分改善程度间的相关性;并进一步依据术前BAI评分将患者分为无焦虑组(n=18)、轻度焦虑组(n=10)、中度焦虑组(n=8)和重度焦虑组(n=3),以进行亚组分析。结果(1)39例患者术后1个月及末次随访时的BAI评分[14(8,20)分、9(3,14)分]均明显低于术前[16(9,27)分],术后末次随访时的BDI评分[8(6,16)分]及PDQ-8评分[3(2,6)分]均明显低于术前[15(8,21)分、9(6,13)分],差异均有统计学意义(P<0.05)。(2)相关性分析显示,术后末次随访时的BAI评分较术前的改善程度与BDI评分的改善程度呈正相关关系(rs=0.722,P=0.000),也与术前BDI评分及术前PDQ-8评分呈负相关关系(rs=-0.714,P=0.000;rs=-0.378,P=0.018)。(3)亚组分析显示,轻度焦虑组和中度焦虑组患者中,术后末次随访时的BAI评分均明显低于术前,差异均有统计学意义(P<0.05);轻度焦虑组、中度焦虑组与重度焦虑组患者的术后末次随访时的BAI评分较术前的改善程度均明显高于无焦虑组,差异均有统计学意义(P<0.05)。结论双侧STN-DBS能在短期内显著改善PD患者的焦虑症状,提高其生活质量,提示STN参与了PD患者焦虑症状的神经机制。     

A double-blind, placebo-controlled trial of clonazepam in obsessive-compulsive disorder.

Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line pharmacological agents in treating obsessive-compulsive disorder (OCD). Appropriate treatment for OCD also involves cognitive behavioural therapy (CBT), including exposure and response prevention. As there is a time delay in seeing full therapeutic response, and not all patients tolerate SSRIs, there remains an unmet need for additional treatment approaches in OCD. In addition, most responders report only a partial reduction in symptoms. Clonazepam has demonstrated effectiveness in several preliminary reports in treating OCD. Twenty-seven patients with OCD were entered into a 10 week, double-blind, parallel design trial of clonazepam vs. placebo. Overall, only 3 out of 25 patients who had >/= 1 rating on clonazepam/placebo were judged to be treatment responders, by scoring a 1 (very much improved) or 2 (much improved) on the CGI improvement scale. Responders included 2 of 9 in the placebo group and 1 of 16 in the clonazepam group. No significant difference was found between clonazepam and placebo groups on responder/non responder status (Chi(2 )=1.39, df =1,24, p=0.238), nor on change in YBOCS, Ham-A, Ham-D or NIMH scales from beginning to last evaluation carried forward. These findings suggest that clonazepam is not effective as monotherapy in treating OCD. Its effectiveness in specific subgroups of OCD patients with co-morbid anxiety disorders or as an augmentation strategy added to SSRIs remains to be determined.     

Outcomes of Add-on Treatment with Lamotrigine in Partial Epilepsy

Summary: The need for new antiepileptic drugs (AEDs) and more sensitive methods of assessing their efficacy is well recognized. This study was designed to evaluate the efficacy and safety of lamotrigine (LTG), a potential new AED and to develop and test new outcome measures. A health-related quality of life (HRQL) model was developed which contains previously validated measures of anxiety, depression, happiness, overall mood, self-esteem, and mastery and a specifically designed seizure severity scale with patient- and caregiver-based components. This HRQL model was used in a randomized, placebo-controlled, double-blind, cross-over study of LTG in 81 patients with refractory partial seizures. Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy. The reduction in seizure frequency with LTG, relative to placebo, was 29.7% [95% confidence interval (CI) 17.8%, 39.9%] for total seizure count, 33.4% (95% CI 14.8%, 47.9%) for complex partial seizures (CPS) and 20.3% (95% CI 0.3%, 36.2%) for secondarily generalized tonic-clonic seizures (GTCS). However, although 41 patients elected to continue with LTG, only 11 experienced at least 50% reduction in total seizures, indicating that other factors influenced their decision. The score with LTG, relative to placebo, was significantly lower for the ictal (p = 0.017) and caregivers (p = 0.035) subscales of the seizure severity scale and significantly higher for happiness (p = 0.003) and mastery (p = 0.003). Simple correlation and multiple-regression analyses indicate that the effects on seizure frequency, seizure severity, and psychological variables appear to be independent of each other. This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity, mood, and perceived internal control. Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs.     

The use of lamotrigine, vigabatrin and gabapentin as add-on therapy in intractable epilepsy of childhood.

PURPOSE: Lamotrigine (LTG), vigabatrin (VGB) and gabapentin (GBP) are three anti-epileptic drugs (AEDs) used in the treatment of children with epilepsy for which long-term retention rates are not currently well known. This study examines the efficacy, long-term survival and adverse event profile of these three agents used as add-on therapy in children with refractory epilepsy over a 10-year period. METHODS: Three separate audits were conducted between February 1996 and September 2000. All children studied had epilepsy refractory to other AEDs. Efficacy was confirmed if a patient became seizure free or achieved >50% reduction in seizure frequency for 6 months or more after starting therapy. Adverse events and patient survival for each drug were recorded at the end of the study period. RESULTS: Between September 1990 and February 1996, 132 children received LTG, 80 VGB and 39 GBP. At the 10-year follow-up audit, 33% of the children on LTG had a sustained beneficial effect on their seizure frequency in contrast to 19% for VGB and 15% for GBP. No significant difference in efficacy was found in children with partial seizures. Children with epileptic encephalopathy (EE) including myoclonic-astatic epilepsy and Lennox-Gastaut Syndrome (LGS) achieved a more favorable response to LTG. The main reasons for drug withdrawal were lack of efficacy for VGB, apparent worsening of seizures for GBP and the development of a rash for LTG. CONCLUSIONS: Lamotrigine is a useful add-on therapy in treating children with epilepsy. It has a low adverse event profile and a sustained beneficial effect in children with intractable epilepsy.     

Personality disorders and response to medication treatment in panic disorder: a 1-year naturalistic study

OBJECTIVE: In this naturalistic and prospective study, personality was assessed in patients with panic disorder (PD), in order to evaluate whether personality features negatively influence the outcome of pharmacological treatment. METHOD: Before drug treatment, PD was diagnosed with the Structured Clinical Interview for DSM-IV disorders and personality was assessed with the Structured Interview for DSM-IV Personality Disorders. Moreover, all patients were evaluated with the SCL-90, the Ham-A and Ham-D. Then, patients were randomly treated with paroxetine (33.5+/-13.3 mg/day) or citalopram (34.7+/-15.2 mg/day) and were followed at monthly intervals for 1 year. Absence of full and limited-symptom attacks, anticipatory anxiety, phobic avoidance and depression for 3 months was used to establish remission. The effect of personality traits on each symptom domain was evaluated. RESULTS: Seventy-one patients completed the study. Remission rate was 76% for panic attacks and 46% for complete remission. When the effects of age, gender, age of onset and duration of PD, baseline SCL-90 phobic anxiety, Ham-A and Ham-D scores, Axis I comorbidity and the SIDP traits on remission were analyzed in a logistic regression, only borderline traits negatively influenced remission of panic attacks (OR=0.69; 95% CI=0.49-0.96; p=0.03), whereas the number of traits of each personality Cluster and the total number of SIDP traits did not affect the outcome of treatment. CONCLUSIONS: This study suggests that in PD patients, borderline features may negatively influence the response to monotherapy with SSRI drugs; therefore, other treatment strategies (i.e., combination of SSRI with psychotherapy) are needed to obtain remission in these patients.     

Symptoms of late-life depression: frequency and change during treatment.

OBJECTIVE: The authors determined the symptoms frequently present in older patients with major depression that showed the greatest change during treatment and that best correlated with an independent measure of improvement (the Clinical Global Impression scale [CGI]). METHODS: Subjects included 728 patients over the age of 60 years with major depression who were selected for entry into a clinical trial. Authors determined the frequency of symptoms on the 17-item Hamilton Rating Scale for Depression (Ham-D) and the effect size of symptom change during treatment. RESULTS: Nine symptoms were identified that were frequent, showed the greatest change during treatment, and best correlated with CGI. The items included depressed mood; loss of interest in work and activities; psychic anxiety; somatic symptoms, general (decreased energy); somatic anxiety; guilt; middle insomnia; late insomnia; and suicidal ideation. These nine items accounted for 92% of the variance in the 17-item Ham-D score, correlated with the CGI at a level similar to the 17-item Ham-D, and were at least as sensitive as the 17-item Ham-D for detecting drug-placebo differences. A comparison with five other similar approaches in non-geriatric samples suggested that the symptoms identified were relatively similar in both age-groups. CONCLUSIONS: Symptoms frequent in patients with late-life depression are similar to those in mixed-aged samples. Nine of the Ham-D items appear most useful for assessment of change during treatment.     

Seizure worsening with Topiramate amongst Indians with refractory epilepsy

In a prospective open label add-on study on 95 patients (age 1-63 years, mean 17.76 +/- 13.83 years) with seizures refractory to conventional antiepileptic drugs (AEDs) and other new AEDs, the addition of Topiramate (TPM) resulted in seizure worsening in 18 patients (19%) necessitating drug withdrawal over an average follow-up period of 4.94 +/- 1.69 months. Patients who had seizure worsening were older (P = 0.02), were more likely to have had a history of status epilepticus in the past (P = 0.03), were on three conventional AEDs (P = 0.027) or had tried one of the other new AEDs in the past with poor response (P = 0.04). Seven of 18 patients who had seizure worsening with TPM (7.4%) experienced initial seizure worsening, probably representing the subgroup with 'true' seizure worsening whilst 11 (11.6%) had initial improvement followed by 'apparent' seizure worsening. Initial seizure worsening was noted to be significantly more in females when compared with males who worsened after initial improvement (P = 0.05).     

Effect of lamotrigine on depressive symptoms in adult patients with epilepsy

In this investigation, the effects of lamotrigine versus placebo on depressive symptoms in patients with epilepsy were prospectively assessed. This investigation was a secondary analysis of a randomized, double-blind, placebo-controlled, parallel-group study in which adult patients received adjunctive lamotrigine (n=32) or placebo (n=38) for a 7-week dose escalation phase, followed by a 12-week maintenance phase, for primary generalized tonic-clonic (PGTC) seizures. Mood symptoms were assessed with the Beck Depression Inventory, second edition (BDI-II), the Profile of Mood States (POMS), and the Cornell Dysthymia Rating Scale-Self-Report (CDRS). Mean (SD) BDI-II scores at screening reflected mild depressive symptoms and were similar between groups (lamotrigine 18.3 (12.1), placebo 16.8 (12.0)). At the end of the maintenance phase, mean (SD) improvement from baseline was greater with lamotrigine than placebo with respect to BDI-II score (lamotrigine 8.9 (7.6), placebo 1.7 (8.5), P=0.01) and POMS total score (lamotrigine 32.0 (30.4), placebo 6.5 (32.3), P=0.03) and numerically greater with lamotrigine than placebo for CDRS score (lamotrigine 7.3 (7.8), placebo 4.1 (13.9), P=0.50). Among the subset of patients with at least mild depression (BDI-II score10), mean improvement from baseline was numerically, but not statistically significantly, greater with lamotrigine (11.5, n=13) than placebo (3.1, n=18) (P=0.054). Median percentage reductions in seizure frequency were significantly greater with lamotrigine than placebo during the escalation phase, the maintenance phase, and the escalation and maintenance phases combined for PGTC seizures and all generalized seizures. However, improvement in seizure frequency was not correlated with improvement in mood (r=0.1, P=ns). Compared with placebo, lamotrigine improved mood symptoms independently of seizure reduction in patients with generalized seizures. Lamotrigine may be useful in treating patients with epilepsy and comorbid depressive symptoms.     

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

OBJECTIVE: The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. METHODS: Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. RESULTS: Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. CONCLUSION: Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.