Antidepressants are useful in the treatment of bipolar disorders

Using antidepressant drugs in Bipolar Depression (BD) has not been adequately considered or explored. This matter is indeed an area of ambiguity which should to be clarified as soon as possible due to the following facts concerning bipolar disorder:

• It is repetitive and progresses relatively slowly
• It tends to become chronic
• It involves a high risk of suicide
• It causes more disability than the other variations of the disease (1).

Treatment manuals, expert views and practices do not fully agree with each other on the issue of whether or not it is appropriate to use antidepressant (AD) drugs to treat BD. There are also differences in the manuals of various countries although they have similar approaches. Americans and Canadians, in particular, strictly oppose the use of ADs in BD. They generally recommend using mood stabilizers (MSs) in treating less severe depressions, using ADs alongside these drugs only in severe depressions and discontinuing ADs as soon as possible. In Germany and some other countries, there is a long and firm tradition of using ADs as a first line treatment (2). Despite different approaches, it is a fact that the decision to use antidepressant drugs in BD is not easy.

The difficulty might stem from a number of reasons including:

• Studies supporting the effectiveness of ADs in BD are few in number and they are not sufficient to approve the use of ADs in this area.
• Although the issue has not been supported by placebo-controlled studies, there is a common belief that ADs cause manic transitions and rapid cycles (3).
The matters of debate that may clarify this issue can be summarized as follows (2):

• Transition to mania and rapid cycling are significant phenomena in Bipolar Disorder (BD). • The issue of suicide is, in fact, of minimal importance in BD.
• The efficacy of antidepressants in BD has not been supported by satisfactory evidence.
• MSs having an AD effect in BD has been supported by satisfactory evidence.

Here are some brief answers to the matters of debate:

• Like ADs, MSs have also not been officially approved in the treatment of BD. It is worthwhile to discuss the new generation antipsychotics (NGAPs) which have been approved in this context.
• The data on manic transition and rapid cycling are problematic for the use of tricyclics to a certain extent; the data obtained from modern antidepressants have largely removed this issue from being a special problem area. There are also other alternatives to diminish the risk (4).
• The antidepressant effect is directed towards the syndrome, thus these drugs are also effective in BD, but there are no noteworthy positive data on this issue for MSs other than a slight benefit obtained from Lithium.
• The issues of suicide and chronicity cause a greater risk than all other issues in terms of contribution to a bad result for BD.
In view of these and similar benefit/risk comparisons, we can conclude that it is reasonable and necessary to use ADs as a single agent or in combination with MSs or NGAPs in the treatment of BD. This approach is already commonly applied in practice.

References:

1. Gijsman HJ, Geddes JR, Rendell JM, Nolen WA, Goodwinn GM: Antidepressant for bipolar depression: A systematic review of randomized, controlled trials. Am J Psychiatry 2004;161:1537-1547.
2. Möller HJ, Grunze H: Have some guidelines fort he treatment of acute bipolar depression gone too far in the restriction of antidepressants? Eur Arch Psychiatry Clin Neurosci 2000;250:57-68.
3. Sachs SG, Nierenberg AA, Calabrese JR, Ketter TA, Marangeli LB, Milowitz DJ, Miyahara MS, Bauer MS: Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Eng J Med 2007;356:1711-1722.
4. Ghaemi SN, Rosenquist KJ, Ko YJ, Baldassano CF, Kontos NJ, Baldessarini RJ: Antidepressant treatment in bipolar versus unipolar depression. Am J Psychiatry2004;161:163-165.