OBJECTIVE： To examine the efficacy and safety of short-term and long-term use of antidepres- sants in the treatment of bipolar disorder. DATA SOURCES： A literature search of randomized, double-blind, controlled tria...OBJECTIVE： To examine the efficacy and safety of short-term and long-term use of antidepres- sants in the treatment of bipolar disorder. DATA SOURCES： A literature search of randomized, double-blind, controlled trials published until December 2012 was performed using the PubMed, ISI Web of Science, Medline and Cochrane Central Register of Controlled Trials databases. The keywords ＂bipolar disorder, bipolar I disorder, bipolar II disorder, bipolar mania, bipolar depression, cyclothymia, mixed mania and depression, rapid cycling and bipolar disorder＂, AND ＂antidepressant agent, antidepressive agents second- generation, antidepressive agents tricyclic, monoamine oxidase inhibitor, noradrenaline uptake in- hibitor, serotonin uptake inhibitor, and tricyclic antidepressant agent＂ were used. The studies that were listed in the reference list of the published papers but were not retrieved in the above-mentioned databases were supplemented. STUDY SELECTION： Studies selected were double-blind randomized controlled trials assessing the efficacy and safety of antidepressants in patients with bipolar disorder. All participants were aged 18 years or older, and were diagnosed as having primary bipolar disorder. Antidepressants or antidepressants combined with mood stabilizers were used in experimental interventions. Placebos, mood stabilizers, antipsychotics and other antide pressants were used in the control interventions. Studies that were quasi-randomized studies, or used antidepressants in combination with antipsy- chotics in the experimental group were excluded. All analyses were conducted using Review Man- ager 5.1 provided by the Cochrane Collaboration.展开更多
In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for trea...In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for treating bipolar disorder. The main problem with the trials is that they were conducted mainly with outpatients, who on average were only moderately manic in the mania studies and only moderately depressed in the depression studies. The effectiveness of aripiprazole and cariprazine in treating moderate mania, most likely hypomania, and moderate depression, was far from encouraging. Aripiprazole produced just 7% greater reduction of mania symptoms than did placebo treatment, and just 1% greater reduction of depression symptoms than did placebo treatment when administered, as is common practice, with an SSRI or SNRI antidepressant. Cariprazine proved to be not much better because at the high dosage level of 3.0 mg/day to 12.0 mg/day, cariprazine produced only 9% greater reduction of mania symptoms than did placebo treatment, and at the typical low dosage of 1.5 to 3.0 mg/day produced just 4% greater reduction of depression symptoms than did placebo treatment. Moreover, as the pharmaceutical industry has long suspected, there is a massive placebo effect associated with these two drugs, especially for depression. These findings imply that government regulatory authorities’ approval of aripiprazole and cariprazine as mood stabilizers for treating bipolar disorder is dubious. Nevertheless, the possibility remains that the purported mood-stabilizing mechanism of these two medicines is activated only with patients presently experiencing severe mania or severe depression, a possibility that requires an in-hospital clinical trial or, at the very least, a longitudinal analysis of bipolar patients’ treatment records. Furthermore, an appendix to the present article demonstrates that the measures used in the trials, the Young Mania Rating Scale and the Montgomery-Asberg Depression Rating Scale, are deficient and that a briefer combination measure focusing only on the core symptoms of bipolar disorder should be used.展开更多
基金supported in part by the Key Projects of Science and Technology Research of the Department of Education in Henan Province,China,No.13A320869a special fund from Henan Health Science and Technology Innovation Talent Project,No.4173(2010-2015)
文摘OBJECTIVE： To examine the efficacy and safety of short-term and long-term use of antidepres- sants in the treatment of bipolar disorder. DATA SOURCES： A literature search of randomized, double-blind, controlled trials published until December 2012 was performed using the PubMed, ISI Web of Science, Medline and Cochrane Central Register of Controlled Trials databases. The keywords ＂bipolar disorder, bipolar I disorder, bipolar II disorder, bipolar mania, bipolar depression, cyclothymia, mixed mania and depression, rapid cycling and bipolar disorder＂, AND ＂antidepressant agent, antidepressive agents second- generation, antidepressive agents tricyclic, monoamine oxidase inhibitor, noradrenaline uptake in- hibitor, serotonin uptake inhibitor, and tricyclic antidepressant agent＂ were used. The studies that were listed in the reference list of the published papers but were not retrieved in the above-mentioned databases were supplemented. STUDY SELECTION： Studies selected were double-blind randomized controlled trials assessing the efficacy and safety of antidepressants in patients with bipolar disorder. All participants were aged 18 years or older, and were diagnosed as having primary bipolar disorder. Antidepressants or antidepressants combined with mood stabilizers were used in experimental interventions. Placebos, mood stabilizers, antipsychotics and other antide pressants were used in the control interventions. Studies that were quasi-randomized studies, or used antidepressants in combination with antipsy- chotics in the experimental group were excluded. All analyses were conducted using Review Man- ager 5.1 provided by the Cochrane Collaboration.
文摘In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for treating bipolar disorder. The main problem with the trials is that they were conducted mainly with outpatients, who on average were only moderately manic in the mania studies and only moderately depressed in the depression studies. The effectiveness of aripiprazole and cariprazine in treating moderate mania, most likely hypomania, and moderate depression, was far from encouraging. Aripiprazole produced just 7% greater reduction of mania symptoms than did placebo treatment, and just 1% greater reduction of depression symptoms than did placebo treatment when administered, as is common practice, with an SSRI or SNRI antidepressant. Cariprazine proved to be not much better because at the high dosage level of 3.0 mg/day to 12.0 mg/day, cariprazine produced only 9% greater reduction of mania symptoms than did placebo treatment, and at the typical low dosage of 1.5 to 3.0 mg/day produced just 4% greater reduction of depression symptoms than did placebo treatment. Moreover, as the pharmaceutical industry has long suspected, there is a massive placebo effect associated with these two drugs, especially for depression. These findings imply that government regulatory authorities’ approval of aripiprazole and cariprazine as mood stabilizers for treating bipolar disorder is dubious. Nevertheless, the possibility remains that the purported mood-stabilizing mechanism of these two medicines is activated only with patients presently experiencing severe mania or severe depression, a possibility that requires an in-hospital clinical trial or, at the very least, a longitudinal analysis of bipolar patients’ treatment records. Furthermore, an appendix to the present article demonstrates that the measures used in the trials, the Young Mania Rating Scale and the Montgomery-Asberg Depression Rating Scale, are deficient and that a briefer combination measure focusing only on the core symptoms of bipolar disorder should be used.
