A 6-month, multicenter, open-label evaluation of beaded, extended-release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes

BACKGROUND: Carbamazepine is frequently used for treating bipolar disorder, but few large trials have assessed its efficacy in preventing relapse. We evaluated open-label monotherapy with beaded extended-release carbamazepine capsules (ERC-CBZ; SPD417) as continuation and short-term maintenance therapy in bipolar disorder patients with manic and mixed episodes. METHOD: A 6-month, open-label study enrolled 92 patients with DSM-IV bipolar disorder (most recent episode: 67% [N = 62] mixed, 33% [N = 30] manic) who had participated in 2 previous 3-week, double-blind, placebo-controlled studies. Subjects received beaded ERC-CBZ (200-1600 mg/day), titrated at investigators' discretion to a final mean dose of 938 mg/day and serum carbamazepine concentration of 6.6 microg/mL. The primary efficacy measure was time to relapse, and secondary efficacy measures included Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and Hamilton Rating Scale for Depression (HAM-D) scores. Data were gathered from January 2000 to January 2002. RESULTS: Of 77 patients analyzed in the intent-to-treat population, 11 (14.3%) relapsed. Fifty-three patients (68.8%) discontinued early, including 18 (23.4%) due to adverse events. Observed mean time to relapse was 61.1 days, while estimated mean time to relapse based on the Kaplan-Meier model was 141.8 days. Improvements on the YMRS, CGI, and HAM-D from the beginning of prior double-blind treatment were maintained. The most common adverse events were headache, dizziness, and rash. No significant weight gain was noted. CONCLUSION: We noted a low relapse rate with beaded ERC-CBZ in this 6-month trial. Adverse events were generally mild to moderate and were typical of those associated with carbamazepine. Controlled studies are warranted to further explore the efficacy of beaded ERC-CBZ in preventing relapse in bipolar disorder.     

Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Although carbamazepine has long been used for the treatment of acute mania, only recently was its efficacy confirmed in a large, multicenter, parallel-group, placebo-controlled, randomized trial. In the present study, we further evaluated the efficacy and safety of monotherapy with beaded, extended-release carbamazepine capsules (ERC-CBZ) in patients with bipolar I disorder experiencing manic or mixed episodes. METHOD: Hospitalized bipolar I disorder (DSM-IV criteria) patients (N = 239) with manic or mixed episodes were randomly assigned on a double-blind basis to receive ERC-CBZ or placebo for 3 weeks, following a single-blind placebo lead-in. Treatment with ERC-CBZ was initiated at 200 mg twice daily, and investigators were encouraged to increase doses, as necessary and tolerated, by 200 mg/day up to 1600 mg/day. Efficacy was assessed weekly with the Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and Hamilton Rating Scale for Depression. The study was conducted from July 23, 2002, to April 1, 2003. RESULTS: 144 patients (60.3%) completed the study, with a significant number of placebo patients discontinuing due to lack of efficacy (p < .001). Extended-release carbamazepine treatment was associated with significant improvements in mean YMRS total and CGI total scores, using last-observation-carried-forward analyses, beginning at day 7 (p < .05). Adverse events occurring more frequently in the ERC-CBZ-treated group included dizziness (39.3%), somnolence (30.3%), and nausea (23.8%) [corrected] Patients taking ERC-CBZ experienced a significant increase in total cholesterol, composed of increases in both high-density and low-density lipoproteins. CONCLUSION: Extended-release carbamazepine monotherapy had significantly greater efficacy compared with placebo in the treatment of acute mania in this large, randomized, double-blind, placebo-controlled trial.     

A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder

OBJECTIVE: To investigate the safety and efficacy of aripiprazole in preventing relapse of a mood episode in recently manic- or mixed-episode patients with bipolar I disorder stabilized on aripiprazole. METHOD: This randomized, double-blind, parallel-group, placebo-controlled, multicenter study enrolled patients from 76 centers in 3 countries (Argentina, Mexico, United States) from March 2000 to June 2003. Bipolar I disorder (DSM-IV) patients who had recently been hospitalized and treated for a manic or mixed episode entered an open-label stabilization phase (aripiprazole monotherapy: 15 or 30 mg/day, 6-18 weeks). After meeting stabilization criteria (Young Mania Rating Scale score of < or = 10 and Montgomery-Asberg Depression Rating Scale score of < or = 13 for 6 consecutive weeks), 161 patients were randomly assigned to aripiprazole or placebo for the 26-week, double-blind phase. The primary endpoint was time to relapse for a manic, mixed, or depressive episode (defined by discontinuation caused by lack of efficacy). RESULTS: Aripiprazole was superior to placebo in delaying the time to relapse (p = .020). Aripiprazole-treated patients had significantly fewer relapses (25%) than placebo patients (43%; p = .013). Aripiprazole was superior to placebo in delaying the time to manic relapse (p = .01); however, no significant differences were observed in time to depressive relapse (p = .68). Weight gain (> or = 7% increase) occurred in 7 (13%) aripiprazole-treated and 0 placebo-treated patients. Adverse events (> or = 5% incidence and twice that of placebo) reported by aripiprazole-treated patients were akathisia, pain in the extremities, tremor, and vaginitis. CONCLUSIONS: Aripiprazole, 15 or 30 mg/day, was superior to placebo in maintaining efficacy in patients with bipolar I disorder with a recent manic or mixed episode who were stabilized and maintained on aripiprazole treatment for 6 weeks, as shown by a longer time to relapse.     

A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder

OBJECTIVE: To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder. METHOD: In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002. RESULTS: More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events. CONCLUSIONS: Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated.     

A randomized, double-blind, placebo-controlled, trial of lamotrigine therapy in bipolar disorder, depressed or mixed phase and cocaine dependence

Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1-10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.     

A placebo-controlled,double-blind study of the efficacy and safety of aripiprazole for the treatment of acute manic or mixed episodes in Asian patients with bipolar I disorder (the AMAZE study)

Objectives. To investigate the efficacy and safety of aripiprazole in Asian patients with manic or mixed episodes associated with bipolar I disorder. Methods. Subjects were randomised to aripiprazole (24 mg/day; reduced to 12 mg/day if needed for tolerability; n = 128) or placebo (n = 130) for 3 weeks in this multicentre, double-blind study. The primary efficacy measure was mean change from baseline in Young Mania Rating Scale (YMRS) Total score. Results. A total of 136 patients (aripiprazole 56.3%; placebo 49.2%) completed the study. The majority of patients (92.6%) received aripiprazole 24 mg/day. Aripiprazole produced statistically significant mean improvements in YMRS Total scores compared with placebo from Day 4 through to Week 3 (–11.3 vs. –5.3; P < 0.001). The most common adverse events (>?15% of patients; aripiprazole vs. placebo) were akathisia (22.0 vs. 5.6%) and insomnia (16.3 vs. 9.6%). Aripiprazole treatment resulted in no significant difference from placebo in change in mean body weight from baseline (–0.4 vs. –0.7 kg; P = 0.231). Aripiprazole was not associated with an elevated serum prolactin level. Conclusions. Aripiprazole had significantly greater efficacy than placebo for the treatment of acute manic or mixed episodes associated with bipolar I disorder in Asian patients. Treatment was generally safe and well tolerated.     

Adjunctive herbal medicine with carbamazepine for bipolar disorders: A double-blind, randomized, placebo-controlled study

Chinese herbal medicines possess the therapeutic potential for mood disorders. This double-blind, randomized, placebo-controlled study was designed to evaluate the efficacy and side effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as an adjunct to carbamazepine (CBZ) in patients with bipolar disorders. One hundred and twenty-four bipolar depressed and 111 manic patients were randomized to treatment with CBZ alone, CBZ plus FEWP, or equivalent placebo for 12 weeks. CBZ was initiated at 300mg/day and FEWP was given at a fixed dose of 36g/day. Efficacy measures included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale , Young Mania Rating Scale, Bech-Rafaelsen Mania Scale, and Clinical Global Impression-Severity (CGI-S). CBZ monotherapy produced significantly greater improvement on manic measures at week 2 through endpoint and CGI-S of depression at endpoint compared to placebo. CBZ monotherapy also yielded significantly higher clinical response rates than placebo on bipolar depression (63.8% vs. 34.8%, p=0.044) and mania (87.8% vs. 57.1%, p=0.012). Compared to CBZ monotherapy, adjunctive FEWP with CBZ resulted in significantly better outcomes on the three measures of depression at week 4 and week 8 and significantly greater clinical response rate in depressed subjects (84.8% vs. 63.8%, p=0.032), but failed to produce significantly greater improvement on manic measures and the response rate in manic subjects. There was a lesser incidence of dizziness and fatigue in the combination therapy compared to CBZ monotherapy. These results suggest that adjunctive FEWP has additive beneficial effects in bipolar patients, particularly for those in depressive phase.     

Once-daily extended-release levetiracetam as adjunctive treatment of partial-onset seizures in patients with epilepsy: A double-blind, randomized, placebo-controlled trial

Purpose:   Double-blind randomized trial to assess efficacy and tolerability of once-daily extended-release levetiracetam (LEV XR) tablets (2 × 500 mg) as add-on therapy in patients (12–70 years old) with partial-onset seizures (POS) refractory to one to three antiepileptic drugs.
Methods:   After an 8-week prospective baseline-period, eligible patients were randomized (1:1) to once-daily LEV XR 1,000 mg/day or placebo for 12 weeks. Evaluations included changes from baseline in POS-frequency/week, responders (≥50% reduction in POS-frequency/week), seizure-freedom, adverse events, laboratory tests, physical and neurologic examinations, vital signs, body-weight, and 12-lead electrocardiogram.
Results:   Of 188 patients screened, 158 were randomized (intention-to-treat population): LEV XR (n = 79) or placebo (n = 79). Seventy-one (89.9%) LEV XR and 72 (91.1%) placebo patients completed the trial. Median POS-frequency/week reduction was 46.1% on LEV XR and 33.4% on placebo. Estimated reduction with LEV XR over placebo was 14.4% (p   =   0.038). Thirty-four (43%) LEV XR and 23 (29.1%) placebo patients experienced ≥50% reduction in POS-frequency/week. Eight (10.1%) patients receiving LEV XR and one (1.3%) receiving placebo were free of POS during the 12-week treatment period. Forty-one (53.2%) LEV XR and 43 (54.4%) placebo patients reported ≥1 adverse event. Adverse events reported with an incidence >5% and seen more often with LEV XR than with placebo were somnolence, influenza, irritability, nasopharyngitis, dizziness, and nausea .
Discussion:   Once-daily LEV XR 1,000 mg was effective and well-tolerated as adjunct therapy in patients with POS. Ten percent of patients randomized to LEV XR experienced freedom from POS. These results support the clinical value of this new LEV XR formulation.     

碳酸锂单用与合并阿立哌唑治疗双相障碍I型躁狂发作患者的随机对照研究

目的:探讨碳酸锂单用及合并阿立哌唑治疗双相障碍I型躁狂发作患者的疗效和安全性。方法:86例门诊双相障碍I型躁狂发作患者被随机分为联合组(碳酸锂+阿立哌唑治疗)和单药组(碳酸锂单药治疗),疗程8周。分别在治疗前、治疗2、4、8周进行杨氏躁狂量表(YMRS)和汉密顿抑郁量表(HAMD)-17项评定,采用治疗中出现的症状量表(TESS)评定不良反应。结果:治疗前两组YMRS评分差异无统计学意义;治疗2、4、8周后联合组YMRS减分值明显高于对照组(P0.05或P0.01);治疗前后两组HAMD均7分;两组TESS评分差异无统计学意义。结论:碳酸锂联合阿立哌唑治疗双相障碍I型躁狂发作较单用碳酸锂起效快,症状改善更明显,且未见不良反应明显增加。     

Differential efficacy of olanzapine and lithium in preventing manic or mixed recurrence in patients with bipolar I disorder based on number of previous manic or mixed episodes

INTRODUCTION: Bipolar disorder outcome worsens as number of manic episodes increases, suggesting that prevention of recurrent episodes early during the disorder could improve patient prognosis. We investigated treatment efficacy in prevention of mood episodes in patients subgrouped by number of prior manic episodes. METHOD: This study was a post hoc analysis of data from a multicenter, double-blind, 12-month clinical trial of relapse/recurrence in 431 initially euthymic patients with at least 2 prior manic/ mixed episodes and a DSM-IV diagnosis of bipolar I disorder randomly assigned to olanzapine (5-20 mg/day) or lithium (serum concentration 0.6 to 1.2 mEq/L). Data were collected between August 1999 and June 2002. Patients were subcategorized by illness stage according to number of prior manic/mixed episodes-early stage: 2 prior episodes (N = 53, lithium; N = 48, olanzapine), intermediate stage: 3 to 5 prior episodes (N = 80, lithium; N = 98, olanzapine), and later stage: more than 5 prior episodes (N = 81, lithium; N = 71, olanzapine)-and were evaluated for rates of relapse/recurrence. RESULTS: There were significant effects for treatment (p < .001) and illness stage (p = .006) but no significant interaction (p = .107) on rate of manic/mixed relapse/recurrence. Rates of manic/ mixed relapse/recurrence for olanzapine versus lithium were 2.1% versus 26.4% (p = .008), 13.3% versus 23.8% (p = .073), and 23.9% versus 33.3% (p = .204) for early-, intermediate-, and later-stage groups, respectively. There was no significant effect for treatment (p = .096) or illness stage (p = .731) for depressive relapse/recurrence. CONCLUSIONS: Early-stage (but not intermediate-or later-stage) patients had a significantly lower rate of relapse/recurrence of manic/mixed episodes with olanzapine compared to lithium. Thus, olanzapine maintenance therapy may be particularly effective early in the course of bipolar illness.     

Aripiprazole in combination with lamotrigine for the long-term treatment of patients with bipolar I disorder (manic or mixed): a randomized, multicenter, double-blind study (CN138-392)

Carlson BX, Ketter TA, Sun W, Timko K, McQuade RD, Sanchez R, Vester‐Blokland E, Marcus R. Aripiprazole in combination with lamotrigine for the long‐term treatment of patients with bipolar I disorder (manic or mixed): a randomized, multicenter, double‐blind study (CN138‐392). Bipolar Disord 2012: 14: 41–53. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: To evaluate the efficacy and safety of aripiprazole (ARI) plus lamotrigine (LTG) compared with placebo (PBO) plus LTG, for long‐term treatment in bipolar I disorder patients with a recent manic/mixed episode. Methods: After a 9–24 week stabilization phase receiving single‐blind ARI (10–30 mg/day) plus open‐label LTG (100 or 200 mg/day), patients maintaining stability (Young Mania Rating Scale/Montgomery–Åsberg Depression Rating Scale total scores ≤ 12) with ARI + LTG for eight consecutive weeks were randomized to continue on double‐blind ARI + LTG or to receive PBO + LTG, after removing ARI from ARI + LTG treatment, and followed up for 52 weeks. The primary outcome measure was time from randomization to relapse into a manic/mixed episode. Results: A total of 787 patients entered the stabilization phase, and 351 were randomized to ARI + LTG (n = 178) or PBO + LTG (n = 173). ARI + LTG yielded a numerically longer time to manic/mixed relapse than PBO + LTG, but it was not statistically significant [hazard ratio (HR) = 0.55; 95% confidence interval (CI): 0.30–1.03; p = 0.058]. The estimated relapse rates at Week 52 were 11% for ARI + LTG and 23% for PBO + LTG, yielding a number needed‐to‐treat of nine (95% CI: 5–121). The three most common adverse events were akathisia [10.8%, 6.1% for ARI + LTG and PBO + LTG, respectively; number needed‐to‐harm (NNH) = 22], insomnia (7.4%, 11.5%), and anxiety (7.4%, 3.6%). Mean weight change was 0.43 kg and ?1.81 kg, respectively (last observation carried forward, p = 0.001). Rates of ≥ 7% weight gain with ARI + LTG and PBO + LTG were 11.9% and 3.5%, respectively (NNH = 12). Conclusions: ARI + LTG delayed the time to manic/mixed relapse but did not reach statistical significance. Safety and tolerability results revealed no unexpected adverse events for ARI combination with LTG.     

A double-blind,randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes

BACKGROUND: Evidence of the antidepressant efficacy of lamotrigine is increasing, although there are no placebo-controlled trials of lamotrigine augmentation in depression. The aim of this study was to assess if augmentation with lamotrigine was superior to placebo in patients who were receiving fluoxetine for resistant major depressive episodes. METHOD: Twenty-three patients who had experienced at least 1 major depressive episode that was resistant to at least 1 prior trial of antidepressant therapy were selected. These patients were treated with fluoxetine, 20 mg/day, and concomitantly randomly assigned to receive either lamotrigine (N = 13) or placebo (N = 10) for 6 weeks. The dose of lamotrigine was titrated upward from 25 mg/day to 100 mg/day. Patients suffering from bipolar II disorder (N = 8) or from major depressive disorder (N = 15) (DSM-IV criteria) were enrolled, resulting in heterogeneity of the sample. The primary outcome measure was Hamilton Rating Scale for Depression score. Data were collected from 2000-2001. RESULTS: Lamotrigine was statistically superior to placebo on the Clinical Global Impressions scale at endpoint, both in absolute terms (mean +/- SD Clinical Global Impressions-Severity of Illness scores: lamotrigine, 2.15 +/- 1.28; placebo, 3.40 +/- 1.17; p =.0308) and using a responder analysis, with response defined as a Clinical Global Impressions-Improvement score of 2 or less (lamotrigine, 84.62% [N = 11]; placebo, 30.00% [N = 3]; p =.013). The effect of lamotrigine on Clinical Global Impressions scale scores was seen in both major depressive disorder and bipolar II disorder. Lamotrigine, however, failed to separate statistically from placebo on the Hamilton Rating Scale for Depression and Montgomery-Asberg Depression Rating Scale. This failure to differentiate on a primary outcome measure is essentially a negative study result. This result is most likely an artifact of the small sample size used and the resultant limited power of the study. CONCLUSION: The results of this trial add to the literature suggesting potential efficacy of the antidepressant profile of lamotrigine. In addition, this study points to a possible role of lamotrigine as an augmentation agent in depression.     

A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive gabapentin for bipolar disorder

OBJECTIVE: To conduct the first randomized, controlled trial assessing the prophylactic efficacy of gabapentin in bipolar disorder. METHOD: We conducted a 1-year, double-blind, randomized, comparative, placebo-controlled, parallel-group, multicenter study. As this was a pure prophylactic trial, only euthymic bipolar I and II patients (DSM-IV) were randomly assigned in a 1:1 ratio to gabapentin (N = 13) or placebo (N = 12) added to the current treatment (lithium, valproate, carbamazepine, or any combination but not antipsychotics or antidepressants). Subjects participated in the study for 12 months. The primary efficacy parameter was the Clinical Global Impressions scale for Bipolar Illness, Modified (CGI-BP-M), which was assessed at all visits. Other assessments were the Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index (PSQI), and the systematic collection of reported adverse events. Data were collected from May 1999 to February 2004. RESULTS: The change from baseline to month 12 in mean CGI-BP-M scores between groups was statistically significant (p = .0046). Mean score change from baseline to endpoint in the gabapentin group was -2.1, and the mean score change in the placebo group was -0.6. No emerging manic or depressive symptoms were seen in either group as measured with the YMRS, HAM-D, HAM-A, and PSQI. In the PSQI-6 subscale (use of sleeping medication), the mean score change at month 12 in the gabapentin group was 0.9, and the mean score change in the placebo group was 0.05 (p = .0267). Overall, gabapentin was well tolerated. CONCLUSION: This small, randomized clinical trial comparing the prophylactic efficacy of adjunctive gabapentin to placebo suggests that, despite lack of acute efficacy, treatment with gabapentin might provide some benefit on the long-term outcome of bipolar disorder.     

A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder

BACKGROUND: Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials. This double-blind, placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder. METHODS: After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued, patients were randomized to lamotrigine (100-400 mg daily), lithium (0.8-1.1 mEq/L), or placebo as double-blind maintenance treatment for as long as 18 months. RESULTS: Of 349 patients who met screening criteria and entered the open-label phase, 175 met stabilization criteria and were randomized to double-blind maintenance treatment (lamotrigine, 59 patients; lithium, 46 patients; and placebo, 70 patients). Both lamotrigine and lithium were superior to placebo at prolonging the time to intervention for any mood episode (lamotrigine vs placebo, P =.02; lithium vs placebo, P =.006). Lamotrigine was superior to placebo at prolonging the time to a depressive episode (P =.02). Lithium was superior to placebo at prolonging the time to a manic, hypomanic, or mixed episode (P =.006). The most common adverse event reported for lamotrigine was headache. CONCLUSIONS: Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode. The results indicate that lamotrigine is an effective, well-tolerated maintenance treatment for bipolar disorder, particularly for prophylaxis of depression.     

A randomized, double-blind, placebo-controlled clinical trial of acamprosate in alcohol-dependent individuals with bipolar disorder: a preliminary report

Tolliver BK, DeSantis SM, Brown DG, Prisciandaro JJ, Brady KT. A randomized, double‐blind, placebo‐controlled clinical trial of acamprosate in alcohol‐dependent individuals with bipolar disorder: a preliminary report. Bipolar Disord 2012: 14: 54–63. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Background: Alcohol use disorders commonly co‐occur with bipolar disorder and are associated with a more severe course of bipolar illness, yet treatment research in this important clinical population is scarce. The current study assessed the effects of acamprosate on alcohol use and mood symptoms in subjects with co‐occurring bipolar disorder and active alcohol dependence. Methods: Thirty‐three adults meeting criteria for bipolar I or bipolar II disorder and current alcohol dependence were randomized to receive add‐on acamprosate (1998 mg/day) or placebo while concurrently maintained on mood stabilizing medications. Participants were assessed weekly for frequency and quantity of alcohol consumption and general clinical severity for eight weeks. Depressive symptoms, manic symptoms, and alcohol craving were assessed biweekly. Biomarkers of alcohol use were assessed at study baseline and endpoint. Results: Of the 33 subjects randomized, 23 (69.7%) completed all active phase visits. Over the trial as a whole, no statistically significant treatment differences were detected in drinking outcomes. Post‐hoc analysis revealed lower Clinical Global Impression scores of substance use severity in acamprosate‐treated participants in weeks 7–8 of the trial. No significant differences in depressive symptoms, manic symptoms, or adverse events were observed between groups. Conclusions: Acamprosate was well‐tolerated, with no worsening of depressive or manic symptoms, and appeared to confer some clinical benefit in study completers in the last two weeks of the trial. Larger studies of longer duration are required to fully explore the utility of acamprosate in this population.