|
Abstract
|
OBJECTIVE: The burden of bipolar depression is greater than that of mania as reflected by the fact that patients spend more time in depressive phase (Fig. 1) and display greater impairment in social and family life and at work. Despite the substantial burden associated with bipolar depression, options for treatment are limited, and management represents a major clinical challenge. This study reviews current evidence regarding efficacy and safety of antidepressants and of alternative treatments for bipolar depression.
METHOD: A comprehensive review of the literature has been carried out using a computerized search of the relevant literature from MEDLINE for the period 1972-2006. Keywords used: bipolar disorder, unipolar major depression, rapid cycling, switch, antidepressant, anticonvulsant, antipsychotic, dopamine agonist, lithium and electroconvulsive therapy. Aim of the study is to answer the following questions: 1) do antidepressants work in acute bipolar depression?; 2) do antidepressants work in acute bipolar depression as well as they do in unipolar depression?; 3) what risks are related to short-term antidepressant treatment in bipolar depression?; 4) how effective are antidepressants in preventing depressive relapses?; 5) what is the risk of rapid cycling induction?; 6) how effective are the alternative treatments to antidepressants for bipolar depression? Results: Current limited evidence shows that antidepressants are effective in the short-term treatment of bipolar depression (Table 1) and that they may work in acute bipolar depression as well as they do in unipolar depression (Table II). There are indications, but no proof, of the efficacy of lithium or other mood stabilizers such as valproate, carbamazepine, gabapentin and topiramate. The only exception is lamotrigine, which is more effective than placebo. Olanzapine-fluoxetine combination and quetiapine are superior to placebo in the acute treatment of bipolar depression. Limited studies with dopamine agonists such as pramipexole and ropinirole show some promise; therefore, the potential role of this group of drugs, in depressed patients, requires further investigation. Electroconvulsive therapy remains an option for treatment-refractory patients and those intolerant to pharmacologic treatment, as well as patients at high risk of suicide. Retrospective and prospective studies show that extended antidepressant treatment (6 months or more) in combination with mood stabilizers may reduce the risk of depressive relapse (Table III). The major concerns regarding the use of antidepressants in bipolar depression are the risk of switch in (hypo)mania in the short-term, and the development of a rapid cycling course in the long-term (Table IV). Selective serotonine reuptake inhibitors, venlafaxine and bupropion are probably as effective as tricyclic antidepressants with a lower risk of inducing (hypo)mania switch. It is not clear if switch can be prevented by the combination of an antidepressant and a mood stabilizer, mostly lithium. Long-term studies demonstrate that lamotrigine is better than placebo and lithium in preventing depressive relapse. There is also some evidence that psychoeducation, cognitive-behavioural therapy and interpersonal therapy decrease the risk of relapse into depression.
CONCLUSIONS: Despite the considerable burden of bipolar depression, the literature on acute and long-term treatment of this phase of bipolar disorder is significantly limited. From current evidence, the most effective pharmacological treatment is that with antidepressants. Lamotrigine, atypical antipsychotics and dopamine agonists seem to be the more promising alternative treatments to antidepressants.
Language: it |