Concerns have been accumulating on the widespread use of all the
current classes of antidepressants.
This is reflected in the recently published North American based
treatment guidelines (Grunze et al. 2002; Hirschfeld et al., 2002);
including those of the APA (Sachs, et al., 2000). These
recommendations have voiced considerable limitations and a
conservative attitude to their use, recommending use be restricted
to severe bipolar depressions (Goodwin and Jamison, 1990; Murray and
Lopez, 1996; Bostwick and Pankratz, 2000). The recommendations go on to
suggest that if antidepressants are used they should be withdrawn as
early as possible; thus we are now seeing a shift away from both the
use of the current classes of antidepressants and recommendations
for their long-term use since they are associated with the following
The risk for induced mania.
There is now established a considerable risk of antidepressant
induced manic switching and/or rapid cycling. This is seen in both
short term and long term exposures. For example with selective
reuptake inhibitors (SRIs) clinical samples demonstrate length of
switch that are not minimal, that is 15 to 27%. The authors of a
number of review articles on this topic suggest that the real rates
are around 40% for tricyclic antidepressants and 20% with new
SRI antidepressants. Substance abuse has been shown to be a major
predictor of antidepressant-induced mania.
The risk of suicide in bipolar depressed patients.
This risk is in and of itself a significant issue of concern. An
analysis of SRIs and other novel antidepressants submitted to the
FDA totaling nearly 20 thousand cases showed that there was no
significant difference in completed or attempted suicides between
patients on antidepressants and placebo treated groups. Simply
stated, it appears that antidepressants as a group have not been
shown to adequately reduce suicide rates. However, the data on
lithium is in contrast to this with a very well established finding
of its prophylactic effects against suicidality in a variety of
Antidepressant efficiency in treating bipolar depression.
Prophylactic studies with antidepressants are not robust in the
treatment of depressive episodes in bipolar disorders. Again, in
contrast, the evidence of efficiency in treating bipolar depression
with mood stabilizers is much higher (e.g., lithium and