Lithium has been an intriguing treatment option in psychiatry for over a century. While seemingly just a simple elemental compound, it has powerful treatment effects for both depression and bipolar disorder. Lithium is still one of few drugs that have been proven to reduce the risk of suicidality and prevention for depressive symptoms, and it may have utility in illnesses beyond affective disorders in recent years[2,3]. Practically, as a primary agent or as an adjunct, lithium continues to claim a rightful place in the treatment for adjunctive for depression[17,18,19,20,21,22].In China,many studies have proven that lithium carbonate combination with antidepressant is more effective than that monotherapy by antidepressant in management of depression,especially in irritability,compulsive behavior[17-22].
The certain number of depressive patients switch to mania or exciting status during treatment by antidepressant,of which could be diagnosed by criteria of bipolar disorder in DSM-5[26 ].But this is not successful therapeutic plan for patient duo to switch,because it induce the mania ahead.So avoiding switch to mania is important part of therapeutic plan,whereas the patients is unipolar or bipolar depression.In general ,four status indicate the patients come into switch.First is mania or hypomania.Second is primary rapid cycle become acceleration,Third is obvious and serious behavior of irritability,compulsive,agitated behavior to have to change manege methods during treatment,Fourth is antidepressant induced chronic irritability(AICD). These all indicate the patients switch to mania,which suggest that the therapeutic plan should be changed.
To recognize the risk of switch was one of prevention methods before treatment[8,9].And therapeutic drug was also very important. In Cox proportional hazard analyses, both antidepressant monotherapy and polytherapy exhibited higher risk of manic switch than their alternatives (antidepressant monotherapy vs. SGA monotherapy, hazard ratio [HR]=2.87 [95% CI: 1.10-7.49].So establishing of correct management program is necessary.The add on mood stabilizer,such as lithium carbonate maybe one important methods in treatment of patients with depressive episode if possible.
This meta-analysis found switch rate of lithium carbonate group was 8.26%(21/254), switch rate of antidepressant group was 25.09%( 64/255) in unibipolar patients, which was very different in switch rate(OR=0.25 ,95% CI: 0.15–0.43).The switch rate in experimental group was significantly lower than in that in control group (Z=4.96,P<0.0001). But the funnel plot analysis of study about switch rate show asymmetric due to a gap,which indicate there maybe a bias of publication.Whereas the Egger`s publication bias test(P=0.16) and Begg`s publication bias test(P=0.62) all show the there not were publication bias. This suggest lithium carbonate do decrease the switch rate induced by antidepressant during treatment for patients with episode of depression.
It was known to all that different depression and different antidepressant were accompanied different switch rate[7,8,9].So the subgroup analysis was made. The result also show lithium carbonate can decreased the switch rate both in patients with unipolar depression and bipolar depression, although bipolar disorder have higher switch rate than that in unipolar disorder[28,29].The result also show lithium carbonate can decreased the switch rate both in patients treated with TCA and SSRI, although switch rate related to TCA was higher than that related to SSRI[29,30]. These all means that lithium carbonate reduce switch rate regardless of the type of antidepressant and the type of depressive episode.
The switch-inducing potential of antidepressants is unclear, although tricyclic antidepressants, which confer higher risk of switching than other classes of antidepressants, with higher NE function in CNS, are a possible exception. Converging evidence suggests that certain pharmacologic and nonpharmacologic interventions with very different mechanisms of action, such as sleep deprivation, exogenous corticosteroids, and dopaminergic agonists, can trigger mood episode switches in patients with bipolar disorder or soft bipolar disorder. But lithium carbonate may displace Na+ from the allosteric Na+-binding sites in neurotransmitter transporters and G-protein coupled receptors (GPCRs),which can stabilize the unsettle of mood.
This study had several limitations. Firstly, the sample size of this meta-analysis was relatively small. Only 9 studies and 695 subjects were involved. Secondly, collecting data style may influence the result of investigation, for example,different criteria of switch can get different detection rate of switch. so it was very import to establish a diagnostic criteria for switch associated with antidepressant.Thirdly, not all the studies had blind observation. .These factors are partly responsible for the source of pool rate of switch associated with antidepressant, also affect us to see the real significance and risk of switch.