Correction to: Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder.

In the original version of this article unfortunately two tables have been missing. By mistake they have been published as Supplementary Material. We apologize for any inconvenience caused. The original article has been corrected.

Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder.

OBJECTIVE: To present up-to-date information and recommendations on the management of body weight changes during the use of antiepileptic mood stabilizers in bipolar disorder to help clinicians and patients make well-informed, practical decisions. DATA SOURCES: Umbrella review. Systematic reviews and meta-analyses on the prevention, treatment, and monitoring of body weight changes as a side effect of the mood stabilizers valproate, lamotrigine, topiramate, and carbamazepine were identified in Embase (2010-2015, no language restrictions). STUDY SELECTION: The search yielded 18 relevant publications on antiepileptic mood stabilizers and weight changes in bipolar disorder. DATA EXTRACTION: Relevant scientific evidence was abstracted and put into a clinical perspective by a multidisciplinary expert panel of clinicians with expertise in the treatment of bipolar disorders across all age groups and a patient representative. RESULTS: Valproate has been proven to be associated with weight gain in up to 50% of its users, and can be detected 2-3 months after initiation. Carbamazepine has been proven to have a low risk of weight gain. Lamotrigine and topiramate are associated with weight loss. Other option for this sentence = Weigth gain has been proven to be associated with valproate use in up to 50% of its users, and can be detected within 2-3 months after initiation. CONCLUSION: Each antiepileptic mood stabilizer has specific effects on body weight and accordingly requires a discrete education, prevention, monitoring, and treatment strategy. Clinicians are recommended to adopt an active, anticipatory approach, educating patients about weight change as an important side effect in order to come to informed shared decisions about the most suitable mood stabilizer.

Long-term outcome of bipolar depressed patients receiving lamotrigine as add-on to lithium with the possibility of the addition of paroxetine in nonresponders: a randomized, placebo-controlled trial with a novel design.

OBJECTIVE: In two previous manuscripts, we described the efficacy of lamotrigine versus placebo as add-on to lithium (followed by the addition of paroxetine in nonresponders) in the short-term treatment of bipolar depression. In this paper we describe the long-term (68 weeks) outcome of that study. METHODS: A total of 124 bipolar depressed patients receiving lithium were randomized to addition of lamotrigine or placebo. After eight weeks, paroxetine was added to nonresponders for another eight weeks. Responders continued medication and were followed for up to 68 weeks or until a relapse or recurrence of a depressive or manic episode. RESULTS: After eight weeks, the addition of lamotrigine to lithium was significantly more efficacious than addition of placebo, while after addition of paroxetine in nonresponders both groups further improved with no significant difference between groups at week 16. During follow-up the efficacy of lamotrigine was maintained: time to relapse or recurrence was longer for the lamotrigine group [median time 10.0 months (confidence interval: 1.1-18.8)] versus the placebo group [3.5 months (confidence interval: 0.7-7.0)]. CONCLUSION: In patients with bipolar depression, despite continued use of lithium, addition of lamotrigine revealed a continued benefit compared to placebo throughout the entire study.

The perspectives of patients with lithium-induced end-stage renal disease.

BACKGROUND: Lithium is the treatment of choice for patients suffering from bipolar disorder (BD) but prolonged use induces renal dysfunction in at least 20% of patient. Intensive monitoring of kidney functioning helps to reveal early decline in renal failure. This study investigates the views and experiences of BD patients who have developed end-stage renal disease and were receiving renal replacement therapy. RESULTS: The patients overall reported not to have been offered alternative treatment options at the start of lithium therapy or when renal functions deteriorated. All indicated to have lacked sound information and dialogue in accordance with shared decision making. Kidney monitoring was inadequate in many cases and decision making rushed. CONCLUSIONS: Retrospectively, the treatment and monitoring of lithium and the information process were inadequate in many cases. We give suggestions on how to inform patients taking lithium for their BD timely and adequately on the course of renal function loss in the various stages of their treatment.

Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients.

BACKGROUND: Alternatives to lithium for prophylactic treatment of patients with bipolar affective disorders are increasingly being advocated. However, trials comparing lithium with alternatives are scarce and often biased. METHOD: We studied 94 patients with at least 2 episodes of bipolar disorder (DSM-III-R) during the previous 3 years who were in remission at entry into the study. Treatment with lithium or carbamazepine had not exceeded a total of 6 months during their lifetime. Patients were randomly assigned to carbamazepine or lithium at entry into the 2-year double-blind study or during the acute index episode previous to entry into the study. No concurrent antipsychotics or antidepressants were allowed. RESULTS: On lithium treatment, 12/44 patients developed an episode, compared with 21/50 on carbamazepine treatment. Episodes on lithium treatment occurred almost exclusively during the first 3 months of the trial. Carbamazepine carried a constant risk of an episode of about 40% per year. Efficacy of lithium was superior to that of carbamazepine in patients with a (hypo)manic index episode that had not been treated with study drug during the index episode (p <.01) and also in patients with prior hypomanic but no manic episodes (p <.05). The proportion of patients who dropped out was slightly higher among those taking lithium (16/44) compared with those taking carbamazepine (13/50), resulting in 16/44 patients (36%) on lithium treatment completing the 2 years with no episode, compared with 16/50 (32%) on carbamazepine treatment. CONCLUSION: Lithium appears to be superior in prophylactic efficacy to carbamazepine in bipolar patients not previously treated with mood stabilizers. Our results should reinforce efforts to put and maintain such patients on treatment with lithium.

[Autoimmune limbic encephalitis: importance of early diagnosis and treatment]. / Auto-immune limbische encefalitis: belang van tijdige diagnostiek en behandeling.

BACKGROUND: Autoimmune limbic encephalitis is a rare disorder, characterised by the subacute onset of seizures, short-term memory loss, and psychiatric and behavioural symptoms. Initially, it was recognised as a paraneoplastic disorder, but recently a subgroup of patients without systemic cancer was identified. This type of limbic encephalitis is associated with voltage-gated potassium channel (VGKC) or N-methyl-D-aspartate receptor (NMDAR) antibodies. CASE DESCRIPTION: We describe a 69-year-old man with anti-VGKC limbic encephalitis suffering from generalised tonic-clonic seizures, severe insomnia, increasing memory deficits, visual hallucinations and depression. We also describe a 22-year-old woman, suffering from complex partial seizures and dysphasia, and displaying inappropriate behaviour. She was diagnosed with anti-NMDAR limbic encephalitis. Both showed marked improvement after starting prednisone and intravenous immunoglobulin therapy. CONCLUSION: These case descriptions emphasise the importance of timely recognition of autoimmune limbic encephalitis in order to rule out malignancy and to quickly initiate treatment. This potentially life-threatening disease responds well to immunomodulatory therapy.

Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy. This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression. METHOD: Outpatients (N = 124) aged 18 years and older with a DSM-IV bipolar I or II disorder and a major depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS] score > or = 18 and Clinical Global Impressions-Bipolar Version [CGI-BP] severity of depression score > or = 4) while receiving lithium treatment (0.6-1.2 mmol/L) were randomly assigned to 8 weeks of double-blind treatment with lamotrigine (titrated to 200 mg/d) or placebo. The primary outcome measure was mean change from baseline in total score on the MADRS at week 8. Secondary outcome measures were response (defined as a reduction of > or = 50% on the MADRS and/or change of depression score on the CGI-BP of "much improved" or "very much improved" compared to baseline) and switch to mania or hypomania (defined as a CGI-BP severity of mania score of at least mildly ill at any visit). Patients were included in the study between August 2002 (Spain started in October 2003) and May 2005. RESULTS: Endpoint mean change from baseline MADRS total score was -15.38 (SE = 1.32) points for lamotrigine and -11.03 (SE = 1.36) points for placebo (t = -2.29, df = 104, p = .024). Significantly more patients responded to lamotrigine than to placebo on the MADRS (51.6% vs. 31.7%, p = .030), but not on the CGI-BP change of depression (64.1% vs. 49.2%, p = .105). Switch to mania or hypomania occurred in 5 patients (7.8%) receiving lamotrigine and 2 patients (3.3%) receiving placebo (p = .441). CONCLUSION: Lamotrigine was found effective and safe as add-on treatment to lithium in the acute treatment of bipolar depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00224510.

Self-reported psychopathological symptoms and quality of life in outpatients with bipolar disorder.

PURPOSE: Patients with bipolar disorder in a euthymic mood state can suffer from subsyndromal or residual symptoms of depression or hypomania. This study was undertaken to gain insight into the broader spectrum of psychopathological symptoms and quality of life. DESIGN AND METHODS: Participants (n = 157) completed the Symptoms Checklist-90, the World Health Organization Quality of Life Assessment Instrument-Bref, and a questionnaire addressing demographic and clinical characteristics. FINDINGS: Outpatients with bipolar disorder reported fewer symptoms of psychopathology than psychiatric outpatients in general, but relative to the general population, a significantly lower quality of life was reported. The number of symptoms showed consistently negative correlations with the quality of life. PRACTICE IMPLICATIONS: The results of this study urge nurses to not settle for treatment response in terms of reduced manic or depressive episodes, but instead to strive for full remission of all symptoms.