Unipolar depression (or major depressive disorder), which means that the person has never had a manic, hypomanic, or mixed (blend of depression and mania) episode, looks much the same as the depression associated with bipolar disorder. Studies trying to tease out subtle differences between the two have yielded little that is definitive. In bipolar depression people are likely to sleep more, rather than less. Also, psychosis is more common in bipolar depression. People with bipolar depression are more likely to have a family history of bipolar disorder. They also appear to have an earlier onset of symptoms and a greater number of depressive episodes. Unipolar depression has a higher incidence of insomnia, somatic (physical) complaints, and sadness.
Next, most treatments for depression have been studied only in unipolar depression. There have not been the same number of systematic controlled trials of antidepressants in the depression associated with bipolar disorder, although they are often used in the treatment of bipolar depression, an area of some controversy that will be discussed later.
One notable exception is that the antipsychotic medication Quetiapine (Seroquel) recently received FDA approval for the treatment of bipolar depression, as did the combination pill of Olanzapine/Fluoxetine (Symbyax), the first medications to have this specific indication.
So the jury is still out on this question. From a clinical perspective, one of the reasons there is such a high miss rate on the diagnosis of bipolar disorder is that unipolar depression and bipolar depression look similar. Without reports of a manic or mixed episode, it can be hard to identify bipolar as such. If indeed these are two distinct entities, it would be wonderful to have some reliable way to differentiate between them.