Clinical outcomes after local field conformal reirradiation of patients with retropharyngeal nodal metastasis.

BACKGROUND: The purpose of this study was to present our experience with retropharyngeal node reirradiation using highly conformal radiotherapy (RT). METHODS: A retrospective screen of 2504 consecutively irradiated patients with head and neck malignancies between 2005 and 2015 identified 19 patients who underwent reirradiation for retropharyngeal node metastasis. Clinical and toxicity outcomes were assessed in these patients. RESULTS: Thirteen patients (68%) had squamous cell carcinoma. Eleven patients (58%) received conventionally fractionated intensity-modulated radiotherapy (IMRT) or proton therapy, and 8 patients (42%) received single-fractionated or hypofractionated stereotactic RT. Fourteen patients (74%) received chemotherapy. Median follow-up was 14.7 months. The 1-year local control, locoregional control, overall survival, and progression-free survival rates were 100%, 94%, 92%, and 92%, respectively. Three patients (16%) experienced acute grade 3 toxicity and occurred in those treated with IMRT. There was no late grade ≥3 toxicity. CONCLUSION: Retropharyngeal node reirradiation with conformal therapy is well tolerated and associated with excellent short-term disease control.

The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode.

OBJECTIVE: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC) in pediatric subjects suffering from bipolar I disorder. METHOD: Medically healthy youths aged 10-17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200-1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs) and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS). RESULTS: A total of 60 children (ages 10-12) and 97 adolescents (ages 13-17), with an overall average age of 13.4 years (standard deviation [SD] 2.0 years) received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days), with 66 (42%) completing the entire study. At end of study participation (end point), the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2) at baseline to a mean of 13.8 (SD 9.4) (P<0.0001) at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6), white blood cell count decreased (n=5), nausea (n=3), and vomiting (n=3). No deaths were reported. The most commonly reported AEs were headache (n=41), somnolence (n=30), nausea (n=22), dizziness (n=21), and fatigue (n=19). CONCLUSIONS: Open-label administration of ERC might be a safe and effective intervention in this subject population. More definitive studies are warranted.

STX209 (arbaclofen) for autism spectrum disorders: an 8-week open-label study.

STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified, and a score ≥17 on the Aberrant Behavior Checklist (ABC)-Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted.

Parent-reported executive function behaviors and clinician ratings of attention-deficit/hyperactivity disorder symptoms in children treated with lisdexamfetamine dimesylate.

OBJECTIVE: The purpose of this article was to describe the relationships between parent-rated executive function (EF) and clinician-rated attention-deficit/hyperactivity disorder (ADHD) symptoms before and after lisdexamfetamine dimesylate (LDX) treatment in children with and without EF deficit. METHODS: In post-hoc analyses of children with ADHD who participated in a 7 week open-label, dose-optimized (LDX 20-70 mg/day) trial, ADHD Rating Scale-IV (ADHD-RS-IV) change scores were compared (using two-sample t tests) between youth with and without clinically significant EF impairment at baseline. Clinically significant impairment was defined as parent-rated Behavior Rating Inventory of EF (BRIEF) Global Executive Composite (GEC) t scores ≥65. Relationships between baseline and endpoint BRIEF and ADHD-RS-IV scores were examined using Pearson correlations and generalized effect linear model. Safety assessment included treatment-emergent adverse events (TEAEs). RESULTS: At baseline, 265/315 participants (84.1%) had a clinically significant BRIEF score. Their mean (SD) ADHD-RS-IV total score at baseline was 42.1 (6.64) for those with, and 36.5 (6.67) for those without, clinically significant BRIEF. At endpoint, ADHD-RS-IV total and subscale scores were significantly improved (p<0.0001) for both those with and those without clinically significant baseline BRIEF scores. Moderately strong, positive Pearson correlations were observed between BRIEF and ADHD-RS-IV total and subscale scores. In the generalized effect linear model, ADHD-RS-IV change scores were significantly correlated with endpoint BRIEF scores (r(2)=0.35, ß=0.73, p<0.0001). In the subgroup without clinically significant BRIEF t scores at endpoint, parents and clinicians rated 90% and 95%, respectively, as improved. In the subgroup with clinically significant BRIEF t scores at endpoint, parents and clinicians rated 69% and 78%, respectively, as improved. TEAEs were experienced by 269/318 (84.9%) participants; most (82.7%) experienced events mild to moderate in intensity. A total of 12/318 (4.1%) participants discontinued because of TEAEs. CONCLUSION: Clinically significant impairment of EF behaviors in children with ADHD was associated with more severe ADHD symptoms. LDX therapy improved ADHD symptom severity, and at endpoint, fewer participants displayed impairment of EF behaviors (versus baseline). The parent-rated BRIEF may describe clinically important EF behaviors not assessed by the 18-item ADHD-RS-IV.

L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode.

OBJECTIVE: Evaluate the efficacy of L-methylfolate in combination with SSRI or SNRI compared to SSRI or SNRI monotherapy in a major depressive episode. DESIGN: A retrospective analysis of L-methylfolate plus SSRI/SNRI at treatment initiation (n=95) and SSRI/SNRI monotherapy (n=147) from patient charts. SETTING: Outpatient, private psychiatric clinic/practice. PARTICIPANTS: Adults 18 to 70 with major depressive episode (single or recurrent). MEASUREMENTS: Clinical Global Impressions-Severity (CGI-S) and safety/tolerability measures. RESULTS: Major improvement (CGI-S reduced by ≥2 points) was experienced by 18.5 percent of L-methylfolate plus SSRI/SNRI patients (CGI-S=4-5) compared to 7.04 percent of SSRI/SNRI monotherapy (p=0.01) patients at 60 days. Forty percent of L-methylfolate plus SSRI/SNRI patients with greater functional impairment (CGI-S=5) experienced major improvement compared to 16.3 percent of SSRI/SNRI monotherapy patients (p=0.02). Median times to major improvement were 177 days for L-methylfolate plus SSRI/SNRI patients and 231 days for SSRI/SNRI monotherapy patients (p=0.03). Median time to major improvement for L-methylfolate plus SSRI/SNRI patients with greater functional impairment (CGI-S=5) was 85 days and 150 days for SSRI/SNRI monotherapy patients (p=0.018). There were no significant differences between groups in adverse events. Discontinuation due to adverse events was 17.9 percent in L-methylfolate plus SSRI/SNRI patients compared to 34 percent in the SSRI/SNRI monotherapy patients over duration of the study (p=0.0078). CONCLUSION: L-methylfolate plus antidepressant at treatment onset was more effective in improving depressive symptoms and function measured by CGI-S scores within 60 days than antidepressant monotherapy, led to major symptomatic improvement more rapidly than SSRI/SNRI monotherapy, and was better tolerated.

Effectiveness, safety, and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: an open-label, dose-optimization study.

OBJECTIVE: The aim of this study was to assess the effectiveness and safety of lisdexamfetamine dimesylate (LDX) in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: This was a 7-week, open-label study evaluating 20, 30, 40, 50, 60, or 70 mg/day LDX in 318 children aged 6-12 years with ADHD. The ADHD Rating Scale IV (ADHD-RS-IV) was the primary efficacy assessment. Secondary measures included the Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), and Behavior Rating Inventory of Executive Function (BRIEF). Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms. RESULTS: At end point, mean (standard deviation [SD]) improvement from baseline in ADHD-RS-IV total score was 28.6 (10.9) (p < 0.0001). Most subjects (89.9%) were rated "improved" (i.e., CGI-I 1 or 2). Improvements from baseline were observed in the EESC total and subscale scores (p < or = 0.0002). LDX treatment resulted in significant improvement on the Global Executive Composite, Behavioral Regulation, and Metacognition indices of the BRIEF (p < 0.0001). TEAEs (incidences > or =10%) were decreased appetite, decreased weight, irritability, insomnia, headache, upper abdominal pain, and initial insomnia. CONCLUSIONS: LDX was effective and generally well tolerated with a safety profile consistent with long-acting stimulant use. There was overall improvement in ADHD symptoms and executive function measures and no worsening of emotional expression measures. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00500071.

Safety and effectiveness of coadministration of guanfacine extended release and psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to evaluate the safety and effectiveness of guanfacine extended release (GXR) administered concomitantly with psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and suboptimal response to a psychostimulant alone. DESIGN AND METHODS: This was a multicenter, open-label, 9-week, dose-escalation study of 75 subjects with ADHD treated with methylphenidate (MPH) or amphetamine (AMP) alone for at least 1 month, yet with suboptimal control of ADHD symptoms. Sixty-three subjects (84.0%) completed the study. Patients received GXR in addition to their psychostimulant. Starting with 1 mg/day, GXR was increased weekly to the highest tolerated dose (1, 2, 3, or 4 mg/day), which was maintained through week 6. GXR was then titrated downward in 1-mg weekly decrements from week 7 through week 9. Psychostimulant treatment regimens were continued until at least week 7. MAIN OUTCOME MEASURES: Safety assessments included adverse events (AEs), vital signs, physical examination, clinical laboratory tests, the Pediatric Daytime Sleepiness Scale, and the Pittsburgh Side Effects Rating Scale. Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV), the Conners' Parent Rating Scale-Revised Short Form, Clinical Global Impressions, Parent Global Assessment, and Child Health Questionnaire-Parent Form. RESULTS: The most common treatment-related AEs were upper abdominal pain (25.3%), fatigue (24.0%), irritability (22.7%), headache (20.0%), and somnolence (18.7%). Most AEs were mild to moderate in severity. Investigator-rated AEs due to blood pressure decreases, heart rate, or electrocardiogram findings were infrequent. Mean changes from baseline (psychostimulant monotherapy just prior to receiving GXR) to end point in ADHD-RS-IV total score were statistically significant overall: -16.1 (p < 0.0001). Significant improvement in both subscales of the ADHD-RS-IV was observed. Improvement of symptoms was observed in a majority of subjects. CONCLUSION: Coadministration of GXR and MPH or AMP was generally safe and associated with statistically significant and clinically meaningful ADHD symptom improvement in children and adolescents.

Impact of drug tolerability on the selection of antidepressant treatment in patients with major depressive disorder.

Despite significant progress in the development of antidepressant therapies, tolerability remains an important factor associated with the selection of appropriate antidepressant treatment. Side effects commonly reported by depressed patients taking antidepressants include weight gain, sexual dysfunction, and gastrointestinal effects.Tolerability issues associated with antidepressants can negatively impact treatment outcomes for patients with major depressive disorder. In addition, a drug's tolerability profile substantially influences a physician's choice of specific antidepressant therapy, Despite the availability of many antidepressants, empirical clinical evidence to guide physicians in making the best choice is limited and not always clear.Thus, it is key for clinicians to understand the short- and long-term outcomes and side effect profiles of the available antidepressants.

Effect of lisdexamfetamine dimesylate on parent-rated measures in children aged 6 to 12 years with attention-deficit/hyperactivity disorder: a secondary analysis.

UNLABELLED: To evaluate the efficacy of lisdexamfetamine dimesylate (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD), using the Conners' Parent Rating Scale, Revised Short Version (CPRS-R:S) and its subscales. METHODS: This was a secondary post hoc analysis of data from a placebo-controlled, double-blind, parallel-group, forced dose-escalation trial. Boys and girls aged 6 to 12 years with a primary diagnosis of ADHD were randomly assigned to LDX (30, 50, or 70 mg/d) or placebo. Improvement on the CPRS-R:S and its subscales (ADHD Index, hyperactivity, oppositional, and cognition) at 10:00 AM, 2:00 PM, and 6:00 PM was analyzed. Safety assessments included the identification of adverse events and were conducted throughout the study. RESULTS: Of the 290 patients randomized, 285 were included in the intent-to-treat population. Parents noted significant improvements at all 3 assessment times on the CPRS-R:S total score and for the CPRS-R:S ADHD Index, hyperactivity, and cognition subscales, regardless of the subject baseline disease severity. For the CPRS-R:S oppositional subscale, significant improvement was noted at 10:00 AM and 2:00 PM (P < 0.01), and overall, significant improvement occurred in subjects who were more severely ill at baseline. The tolerability of LDX was comparable to that of other stimulants. CONCLUSION: Once-daily treatment with LDX was associated with significant improvement in parent-rated assessments of ADHD-related behavior throughout the day at approximately 10:00 AM, 2:00 PM, and 6:00 PM. Lisdexamfetamine dimesylate was effective and well tolerated in this study population of children aged 6 to 12 years with ADHD.

Bipolar II disorder: current and future treatment options.

BACKGROUND: Bipolar II (BPII) disorder is a significant public health problem in the United States, and there is a dearth of studies of effective treatment modalities to deal with the recurrent major depressive episodes that accompany the disorder. This review attempts to summarize available data on agents useful in treating patients with the disease. METHODS: English language controlled clinical trials involving BPII patients obtained from an extensive Medline search were critically reviewed. RESULTS: Agents that have potential utility in the treatment of BPII are profiled, based on their efficacy in bipolar I (BPI) or unipolar depression. CONCLUSIONS: The most efficacious agents are likely those with bimodal stabilizing properties, such as lithium, carbamazepine, and quetiapine. In fact, on the strength of favorable efficacy data obtained in patients with major depressive symptoms accompanying bipolar disorder, quetiapine recently became the first agent to be indicated by the FDA for monotherapeutic use in the treatment of bipolar depression, including BPII depression. Aside from the aforementioned agents, lamotrigine also shows promise in the treatment of BPII.

Carbamazepine extended-release capsules: a retrospective review of its use in children and adolescents.

BACKGROUND: Bipolar disorder occurs in 1% of children and adolescents, but few clinical trials address treatment of this population. This retrospective chart review evaluated the long-term safety and tolerability of carbamazepine extended-release capsules (CBZ-ERC) (Shire, Wayne, PA, USA) in 300 children and adolescent patients who had been treated for bipolar disorder in a private psychiatric practice. METHODS: Data were collected from the medical records of all young and adolescent (4-17 years old) patients who met the DSM-IV criteria for a diagnosis of bipolar disorder type I, type II, or bipolar not otherwise specified who had been treated with CBZ-ERC either as add-on or monotherapy between October 1998 and November 2003 at Red Oak Psychiatry Associates, Houston, TX. The severity of illness was assessed using the Clinical Global Impression-Severity scale, and improvement was measured by the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: A response, defined as a CGI-I score of or=5) at CBZ-ERC initiation. Treatment was well tolerated, with the most common adverse events being somnolence (9.7%), nausea (6.3%), dizziness (5.0%), and rash (4.3%). CONCLUSIONS: Carbamazepine extended-release capsules appear safe and efficacious for the treatment of bipolar disorders in children and adolescent patients.

Carbamazepine extended-release capsules use in bipolar disorder: efficacy and safety in adult patients.

BACKGROUND: Safety, tolerability, and efficacy of carbamazepine (CBZ) have been demonstrated in numerous studies over the last three decades. Until recently, CBZ studies largely involved immediate-release formulations, while long-term studies have been few in number. The recent development of beaded CBZ extended-release capsules (CBZ-ERC) (Shire, Wayne, PA, USA) provides a new formulation with potential advantages in safety, tolerability, and efficacy over earlier formulations. METHODS: The present study assesses these parameters in patients of various bipolar subtypes (mixed/manic, bipolar I depression, and bipolar II), in a single-site private practice setting. Data were obtained from the charts of 300 patients>or=18 years old who met DSM-IV criteria for bipolar disorder. Clinical response to CBZ-ERC therapy was defined as a score of or=4 in those subjects who had previously achieved clinical response. RESULTS: Clinical response occurred in 73% of patients, leading to a mean CGI-I score of 2.5 (SD=1.2). Relapse was seen in 33% of responders. Most common adverse events were somnolence, dizziness, and nausea. A high level of treatment response and a low relapse rate were observed in long-term treatment with CBZ-ERC in adults with bipolar disorder. The limited number and nature of the adverse events observed during the course of this study provide evidence of the safety and tolerability of CBZ-ERC. CONCLUSIONS: Carbamazepine extended-release capsules appear safe and efficacious for the treatment of bipolar disorder. Controlled studies are warranted to further establish the safety, tolerability, and efficacy of CBZ-ERC for treatment of adult bipolar patients.

Outcomes and length of treatment with carbamazepine extended-release capsules in bipolar disorder.

BACKGROUND: This analysis was a retrospective chart review evaluating the relationship between outcomes and length of treatment with carbamazepine extended-release capsules (CBZ-ERC) (Shire, Wayne, PA, USA) in bipolar disorder. METHODS: The medical records of adult patients (>or=18 years) meeting DSM-IV criteria for bipolar disorder who were treated with CBZ-ERC for 30 days or less, 31 to 180 days, and more than 180 days were reviewed in this study. RESULTS: There were significant differences in mean Clinical Global Impression-Improvement (CGI-I) scores at the best office visit among the three treatment groups. The mean CGI-I scores for the 31- to 180-day (2.3+/-1.1) and >180-day (1.8+/-1.0) groups were significantly lower than the mean score for the 180-day group was significantly lower than that of the 31- to 180-day group (p=0.0027). Significantly fewer patients in the 31- to 180-day (5.4%; p=0.0039) and >180-day groups reported nausea (4.8%; p=0.034) when compared to the <30 day group. CONCLUSIONS: The results of this study indicate that future controlled studies are warranted to further explore the safety and efficacy of CBZ-ERC as a long-term therapy for bipolar disorder.

Safety of carbamazepine extended-release capsules in bipolar disorder polypharmacy.

BACKGROUND: This analysis is a retrospective chart review evaluating the safety of carbamazepine (CBZ) extended-release capsules (CBZ-ERC) (Shire, Wayne, PA, USA) when used in combination with other agents as part of a polypharmacy regimen in the treatment of patients with bipolar disorder. The safety of CBZ-ERC was determined by comparing the adverse event profiles of patients on monotherapy versus those of patients on polytherapy. METHODS: The medical records of 300 adult patients (aged 18-70) treated in a private practice setting with CBZ (monotherapy or polytherapy) who met the DSM-IV criteria for bipolar disorder were examined. RESULTS: We found that patients taking CBZ-ERC together with other agents (antipsychotics, antiepileptics, selective serotonin reuptake inhibitors and other antidepressants, anxiolytics, lithium, and attention-deficit/hyperactivity disorder medications) were no more likely to report gastrointestinal, nervous system, or cutaneous adverse events than patients on CBZ-ERC monotherapy. CONCLUSIONS: These real-world data suggest that the occurrence of adverse events may not differ significantly between patients on CBZ-ERC monotherapy and those on polytherapy with multiple other agents.

Predictors of response to carbamazepine extended-release capsules treatment in bipolar disorder.

BACKGROUND: Predictors of response to psychoactive drugs are valuable in providing practical guidance and in optimizing a treatment regimen. Here we used linear regression analysis to identify treatment-specific predictors of response to therapy with beaded extended-release carbamazepine capsules (CBZ-ERC) (Shire, Wayne, PA, USA) in 600 outpatients with bipolar disorder. METHODS: Data were obtained from medical charts of subjects who received CBZ-ERC in a private practice setting. Illness severity and improvement were assessed using the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales. RESULTS: We found that increasing baseline CGI-S scores correlated with lower CGI-I scores (R2=0.01, p=0.009); that is, the higher the baseline CGI-S score, the greater the expected degree of improvement. There was also a correlation between increasing CBZ-ERC dose and improvement in CGI-I scores (R2=0.02; p=0.0004). Moreover, we found that increasing carbamazepine (CBZ) blood concentration correlated with decreases in CGI-I scores (R2=0.12; p=0.025), and that there was a correlation between higher total daily CBZ-ERC dose in mg/kg of body weight and decreases in CGI-I scores (R2=0.01; p=0.038). CONCLUSIONS: These findings suggest that bipolar patients with more severe baseline symptoms, on higher CBZ-ERC doses, and with higher CBZ blood levels were more likely to respond to CBZ-ERC treatment.

Safety and efficacy of carbamazepine extended-release capsules in patients with bipolar disorder: QD vs BID.

BACKGROUND: Adherence to prescribed pharmacotherapy is an important factor in the success of a selected treatment regimen. Because the dosing frequency of a particular medication can affect adherence rates, this important aspect of treatment must be taken into account. This report presents results from a retrospective assessment of the charts of 23 patients who received once-daily (qd) carbamazepine extended-release capsules (CBZ-ERC) (Shire, Wayne, PA, USA) for the treatment of bipolar disorder. METHODS: The assessment compared qd dosing of CBZ-ERC with twice-daily (bid) dosing by matching the charts of the 23 study subjects to those of 23 similar control patients who had been taking CBZ-ERC dosed bid. RESULTS: In this study, no significant difference was observed in Clinical Global Impression-Improvement (CGI-I) scores between the qd and bid groups. In addition, the percentage of responders (those whose CGI-I score were

A retrospective analysis of changing from alternative agents to carbamazepine extended-release capsules in bipolar disorder.

BACKGROUND: Patients with bipolar disorder do not respond to the same therapy in the same way. This potentially necessitates the trial of various treatment modalities in a patient until the illness can be successfully controlled. METHODS: Medical histories from 187 patients were reviewed to obtain information on efficacy when patients were switched from their initial drug therapy-immediate-release (IR) or extended-release (ER) carbamazepine (CBZ) tablets, valproic acid, lamotrigine, lithium, olanzapine, and oxcarbazepine-to beaded CBZ extended-release capsules (CBZ-ERC) (Shire, Wayne, PA, USA). Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were used to assess severity of illness, and response and relapse rates, respectively. RESULTS: The overall response rate was 79.7%. The greatest percentage of responders to CBZ-ERC treatment was seen in patients originally on lithium (90.5%), followed by those initially treated with oxcarbazepine (84.8%), olanzapine (81.5%), lamotrigine (77.8%), valproic acid (75.4%), and IR or ER CBZ tablets (74.2%). The overall relapse rate was 38.2%. Patients on lithium had the highest relapse rate (52.6%), followed by those on olanzapine (50.0%), valproic acid (34.9%), IR or ER CBZ tablets (34.8%), oxcarbazepine (32.1%), and lamotrigine (28.6%). Adverse events were minimal, with nausea, dizziness, and somnolence being the most frequent. CONCLUSIONS: The encouraging treatment response and adverse event profile observed in this retrospective analysis suggest that CBZ-ERC is an efficacious agent for the treatment of patients with bipolar disorder switched from other psychotropic agents.

Efficacy and safety of lamotrigine for adults with bipolar disorder in a private practice setting.

INTRODUCTION: Lamotrigine is approved by the Food and Drug Administration for maintenance therapy in patients with bipolar I disorder. However, several studies of acute-phase and maintenance treatment support the efficacy of lamotrigine for bipolar I and bipolar II disorders. This chart review was performed to assess the efficacy and safety of lamotrigine in the treatment of bipolar disorder in a private psychiatric practice setting and to investigate differences in response among patients with different diagnostic subtypes of bipolar disorder. METHODS: The charts of 587 adult outpatients with a primary diagnosis of bipolar disorder who received treatment with lamotrigine in a private practice setting between July 1998 and May 2004 were reviewed retrospectively. Treatment response was assessed with the Clinical Global Impression-Improvement scale and was defined as achievement of a score of <2. RESULTS: Three hundred forty-nine patients (59.5%) responded to lamotrigine. Response rates were comparable among patients with bipolar I disorder, bipolar II disorder, bipolar disorder not otherwise specified, and among patients with bipolar I disorder who presented with depressive, manic, or mixed episodes. Nonserious rash (12.8%) and headache (2.9%) were the most frequently reported adverse events. CONCLUSION: These results suggest that lamotrigine is effective and well-tolerated in the treatment of bipolar disorder across the spectrum of subtypes of the illness.

Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder.

BACKGROUND: This analysis describes the effects of bipolar I disorder on self-reported neurocognitive measures and remediation of these deficits with lamotrigine therapy. METHOD: Data were derived from 2 clinical trials designed to assess the efficacy of lamotrigine as maintenance therapy for recently manic (N = 349) or depressed (N = 966) patients (DSM-IV criteria). During the 8- to 16-week open stabilization phase, patients received lamotrigine as monotherapy or as adjunctive therapy (target dose = 200 mg/day, minimum dose = 100 mg/day) while other psychotropic drugs were discontinued. The Medical Outcomes Study Cognitive Scale (MOS-Cog) and the AB-Neurological Assessment Scale (AB-NAS) were used to measure cognitive functioning at baseline and at the end of the open-label phase. To examine the relationship between depressive and manic symptomatology, initiation of lamotrigine, and cognitive functioning, correlational analyses and analyses of covariance were conducted. RESULTS: Bipolar patients in both trials had significant cognitive impairment; however, it was much greater in index episode depressed bipolar patients compared with index episode manic patients. In both studies, substitution of lamotrigine for other psychotropic medications significantly improved the mean scores from baseline to the end of the open-label phase on the MOS-Cog and the AB-NAS (p < .0001). Among patients who took lamotrigine as monotherapy, the mean MOS-Cog score also improved significantly versus baseline (+32.2, or 81%, for depressed patients, p < .0001; and +19.9, or 35%, for manic patients, p < .0001). Mean AB-NAS scores (-19.7, or -55%, for depressed patients, p < .0001; and -7.2, or -32%, for manic patients, p = .0062) showed similar improvement. Cognitive impairment was significantly correlated with depression symptom severity based on Hamilton Rating Scale for Depression scores (p < .0001). After controlling for change in mood, age, gender, baseline score, duration of illness, and duration of use of other psychotropics, a significant improvement in cognition was observed during the open-label phase when lamotrigine was used as monotherapy/adjunctive therapy. CONCLUSION: Treatment with lamotrigine as monotherapy and as adjunctive therapy was associated with improved cognitive functioning and reduced neurocognitive side effects, regardless of index mood polarity.