Are SSRIs responsible for precipitating suicidal ideation in teenagers with 'subsyndromal' bipolar affective disorder who have been misdiagnosed with unipolar depression?

Concerns have recently been raised about a possible link between suicidal ideation and the use of SSRIs in teenagers diagnosed with unipolar depression, such that the USA FDA and UK CSM have issued warnings regarding the use of SSRIs in adolescents with depression. We investigated this phenomenon first by recognizing that the initial presentation of unipolar and bipolar depression may only differ in subtle ways and with the result being that a significant number of patients are misdiagnosed at the expense of patient outcomes. This is especially pertinent as patients with bipolar disorder have increased lifetime rates of suicide as compared with those patients with unipolar depression. The normal developmental trajectory of bipolar disorder often involves recurrent depressive episodes in early adolescence before the development of hypomanic/manic episodes. Therefore, a misdiagnosis of bipolar disorder as unipolar depression in teenagers could explain the failure of SSRIs to adequately treat depressive episodes. A suboptimal response to SSRIs and so a lack of control of the depression is a risk factor for suicide. One reason for this suboptimal response is the markedly different neurotransmission involved in bipolar depression as compared to the neurotransmitter systems operated on by SSRIs. In bipolar disorder, dopamine is the principal neurotransmitter disrupted and we marshal structural, pharmacological and biochemical evidence to support this claim. One important strand of evidence involves polymorphisms in D1 and D2 dopamine receptors being implicated in the pathogenesis of bipolar affective disorder. Serotonin neurotransmission is affected by SSRIs, however the role of serotonin in bipolar disorder is much more ambiguous. The conclusion we arrive at is that the link between suicidality and SSRI use in adolescents diagnosed with unipolar depression may in fact be due to inappropriate treatment of misdiagnosed bipolar disorder that has yet to manifest with hypomanic/manic symptoms.