| Objective:Bipolar disorder is a common type of psychiatric disorder.This study is to summarize evidence on the efficacy and safety of using adjunctive antidepressants in the treatment of acute bipolar depression and to investigate the use of antidepressant in patients with bipolar depression from Shanghai Mental Health Center.Methods:Part 1.Systematic reviewWe searched electronic databases and hand-searched unpublished trial data and studies in refences of included studies for Randomized controlled trials on adjunctive antidepressants for bipolar depression,included studies according to our registered protocol,extracted data,evaluated the risk of bias for each study and the level of quality for each outcome,and did a meta-analysis.Part 2.Retrospective studySamples for this study was collected from the medical archives of SMHC.We collected data from the archives of patients who were admitted to our hospital due to an episode of bipolar depression between the dates of 1/1/2000 to 12/31/2018.According to when the Chinese guidelines for the diagnosis and treatment for bipolar disorder was published,we divided the patients into 3 groups according to their date of admission.A total sample of 376 were analyzed.Cases were selected according to the criteria of our registered study protocol.We collected data on patient’s basic information,disease condition,treatment plans upon admission and discharge,as well as results related to treatment effect,including the frequency of hospitalization,length of hospitalization,and the occurrence of mood switch.Results:Part 1.Systematic review:19 studies met the criteria were included,with 1164 bipolar depressive patients using antidepressant in adjunction with mood stabilizer and 1423 patients using mood stabilizer and placebo.According to the criteria of overall bias by Risk of Bias Tool,2 studies were rated as of low risk of overall bias,7 studies of some concern and 10 studies of high risk.Adjunctive antidepressant showed no significant effect on improving response rate(RR=1.10,95%CI:0.98～1.23)or remission rate(RR=1.09,95%CI: 0.99～1.20),but it was of a small but significant impact on improving depressive symptoms(SMD=-0.13,95%CI:-0.24～-0.02).Meanwhile,adjunctive antidepressant was not associated with increased risk of mood switch(RR=0.97,95%CI: 0.68～1.39),the rate of patients having at least one adverse effect(RR=1.12,95%CI:0.96～1.31),or overall dropout rate(RR=0.98,95%CI: 0.87～1.12).Besides,adjunctive antidepressant was related to lower risk of dropout due to inefficacy(RR=1.21,95%CI:0.88～1.69).Subgroup analysis found that the efficacy of antidepressant was greater in antipsychotic trials than in mood stabilizer trials.In the subgroup using antipsychotics as a mood stabilizer,adjunctive antidepressants were significantly improving the response rate(RR=1.43,95%CI: 1.18～1.73,I2 = 0%).Using GRADE,we determined that the primary outcome of response rate has a low certainty level of evidence due to the overall bias of studies included,and the heterogeneity between included studies for this outcome.The outcome of score change in depressive symptom scales was rated as having high certainty of evidence,and other secondary outcomes were evaluated to have low or medium level of quality of evidence.Part 2.Retrospective study:1.We collected data from 376 patients in total,half of them were male.There were no statistical differences of age or gender among the 4 groups.2.Disease condition: Among the 3 groups,the difference in the number of different types of bipolar disorder and an increase in comorbidity among the inpatients over the years had statistical significance.3.Treatment plan: There is a significant decrease in the proportion of patients taking antidepressants and especially the proportion of patients using antidepressants as a monotherapy since the year 2008(p<0.05).There was a also a statistically significant number of patients who stopped using antidepressants,comparing their treatment plan upon admission and that of their discharge(p<0.05).Besides,there is an increase in the number of patients taking 2 or more than 2mood stabilizers,and a decrease in the use of benzodiazepines.Changes in the use of MECT,RTMS,and the different types of antidepressants and mood stabilizers was not statistically significant among the four groups.4.The present study used the stepwise logistic regression to investigate the associative factors of physicians’ decisions of using antidepressants in bipolar depression and the rate of mood switch.We found that old age,comorbidity,and a diagnosis of bipolar II disorder raises the chance of patients taking antidepressants during their acute episode of bipolar depression(p<0.05).Among the factors of age,gender,severity,diagnostic subtype,suicidal behavior,different types of antidepressants,using antidepressants along with a mood stabilizer and using antidepressants alone,only using antidepressants as a monotherapy is found to be a risk factor of mood switch(OR=3.53,95% CI = 1.37～9.09).Conclusions:Part 1.Systematic review1.Adjunctive use of antidepressants with mood stabilizers does not significantly increase the risk for mood switch,adverse effects or dropout.It reduces dropout rates due to inefficacy.2.Adjunctive use of antidepressants can cause a small but significant improvement on clinician-rated depression scale score compared with patients using mood stabilizers alone but does not significantly improve response rate or remission rate.3.Adjunctive antidepressants may have more effect on response rate when used together with antipsychotics,though more studies are needed to further give further proof on this evidence.Part 2.Retrospective study:1.The number of patients being prescribed an antidepressant as part of their treatment for acute bipolar depression decreased since the publication of the Chinese treatment for bipolar disorder guidelines in 2007.2.Using antidepressants as monotherapy is a significant risk factor of mood switch. |
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