The use of antidepressants in the treatment of bipolar disorder remains controversial. Some studies and treatment guidelines suggest that antidepressant treatment for bipolar disorder may have the potential to increase the manic switch, while others recommend short-term antidepressant treatment and early discontinuation.
A recent study by Dr. Yingli Zhang and co-workers from Mental Health Institute of Central South University in China involved new large-sample double-blind randomized controlled trials, excluded open-label design studies, and supplemented studies involving homogeneous patients. Suicidality firstly served as an important outcome, strict inclusion criteria included limitation to double-blind randomized controlled studies and interventional treatment without use of antipsychotics to make the study results more objective and convincing. The results from this study do not support that antidepressants are more effective in the treatment of bipolar disorder. Antidepressants are not superior to placebo and other medication in short-term, and long-term use of antidepressants cannot achieve higher response and remission rates of bipolar disorder. These findings, published in the Neural Regeneration Research (Vol. 8, No. 31, 2013), guide future clinical studies and provide evidence for preparing treatment strategy for bipolar disorder.
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Research Highlights
(1) The use of antidepressants in the treatment of bipolar disorder remains controversial. To the best of our knowledge, there have been no meta-analysis papers of randomized, double-blind, controlled trials and the therapeutic effects and safety of long-term antidepressants in the treatment of bipolar disorder were not evaluated.
(2) The study involved new large-sample double-blind randomized controlled trials, excluded open-label design studies, and supplemented studies involving homogeneous patients. Strict inclusion criteria included limitation to double-blind randomized controlled studies and interventional treatment without use of antipsychotics to make the study results more objective and convincing.
(3) The present results do not support that antidepressants are more effective in the treatment of bipolar disorder. Antidepressants are not superior to placebo and other medication in short-term, and long-term use of antidepressants cannot achieve higher response and remission rates of bipolar disorder. These findings guide future clinical studies and provide evidence for preparing treatment strategy for bipolar disorder.
Article: ” Antidepressants for bipolar disorder: a meta-analysis of randomized, double-blind, controlled trials ” by Yingli Zhang, Huan Yang, Shichang Yang, Wei Liang, Ping Dai, Changhong Wang, Yalin Zhang ( Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China; Psychological Counseling Center, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, Henan Province, China; Department of Psychology, Xinxiang Medical University, Xinxiang 453000, Henan Province, China; Department of Clinical Psychology, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, Henan Province, China; Sichuan University Library, Chengdu 610041, Sichuan Province, China)
Zhang YL, Yang H, Liang W, Dai P, Wang CH, Yang SC, Zhang YL. Antidepressants for bipolar disorder: a meta-analysis of randomized, double-blind, controlled trials. Neural Regen Res. 2013;8(31):2962-2974.
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Bipolar disorder is a major psychotic disorder characterized by a chronic and highly recurrent course. Bipolar disorder is associated with a high rate of morbidity, disability, and comorbid anxiety and drug abuse, and has a major effect on social and occupational development. The average onset age of bipolar disorder is between 20 and 40 years, while the lifetime prevalence ranges from 0.5% to 1.5%, with equal occurrence in women and men. Because of its early onset and chronicity, bipolar disorder is one of the top thirty causes of worldwide disability.
Bipolar disorder is characterized by periods of mania, depression and mixed episodes. Most patients experience multiple episodes, with each lasting 3 -6 months.
In the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), bipolar disorder has been subcategorized into bipolar I and bipolar II disorders. Current data indicate that bipolar II disorder is more prevalent than bipolar I. Despite mania being the hallmark of bipolar disorder, depression is the most important quantitative aspect of the illness and the one associated with higher levels of impaired social functioning and suicidality.
Over the last half-century, the management of bipolar disorder has been centered on manic phase treatment, and a great deal of research attention has been received regarding bipolar disorder treatment during this period.
While mood stabilizers, especially lithium, are the first choice in the treatment of bipolar disorder, their efficacy in treating depression is suboptimal. Studies have suggested that lithium reduces the rates of manic relapse and depressive relapse by about 40% and 25%, respectively.
Although there is some evidence that atypical antipsychotics are effective in the treatment of bipolar depression, the resulting adverse effects, such as weight gain, prolactin elevation, hyperglycemia, hyperlipidemia, and extrapyramidal symptoms, have become troublesome issues. Meanwhile, little progress has been made on reducing the length of depressive episodes in bipolar disorder for the last 20 years. It has been shown that pharmacological management of bipolar depression is an exceptionally difficult task. Appropriate treatments for bipolar depression remain controversial. Avoiding antide pressant use has usually been proposed by clinical guide lines, considering the potential risk for switching to mania or rapid cycling during the treatment, while mood stabilizers (e.g., lithium, divalproex, and lamotrigine) as first line treatment drugs for bipolar disorder have been recommended. However, recent reports have shown that short-term second-generation antidepressant treatment is effective for the treatment of bipolar disorder, and that second-generation antidepressant monotherapy might be associated with a relatively low manic switch rate.
Meanwhile, the use of mood stabilizers for acute episodes of depression, either alone or in combination with an antidepressant, has generally been recommended by treatment guidelines published over the past 5 to 10 years.
Some studies and treatment guidelines suggest that antidepressant treatment for bipolar disorder may have the potential to increase the manic switch, while others recommend short-term antidepressant treatment and early discontinuation. However, many of these are based on a single or several randomized controlled groups, rather than all high-quality randomized controlled trials presently. When most guidelines extrapolate from studies of patients taking tricyclic antidepressants (TCAs), the guidelines of bipolar depression with antidepressants are not informed by a rich evidence base and remain controversial. Meanwhile, little attention has been received for long-term antidepressant therapy of bipolar disorder.
Contact: Meng Zhao
eic@nrren.org
86-138-049-98773
Neural Regeneration Research
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Antidepressants for bipolar disorder
A meta-analysis of randomized, double-blind, controlled trials
Yingli Zhang, Huan Yang, Shichang Yang, Wei Liang, Ping Dai, Changhong Wang, Yalin Zhang
doi:10.3969/j.issn.1673-5374.2013.31.009