Background: Athanasios Koukopoulos provided a radical model for understanding depressive
and manic conditions.
Objective: To review, explain, and analyze Koukopoulos’ concept of the primacy of mania, with special
attention to the role of antidepressants.
Method: A conceptual review of Koukopoulos’ writings and lectures on this topic is given.
Results: Koukopoulos held that depressive states are caused by manic states; the former do not occur
without the latter. The most common scenario of the inseparability of depressive and manic symptoms
occurs in mixed states, which we estimate to represent about one-half of all depressive episodes in all
patients (not just bipolar illness). In a review of the empirical evidence for this topic, we conclude that
empirical evidence exists to support the primary of mania thesis in almost 80% of depressed patients.
Since antidepressants worsen mania, they would be expected to worsen depression as well in this model.
We provide evidence that supports this view in most persons with depressive states.
Conclusion: Koukopoulos’ model of affective illness is one where manic states are the primary
pathology, and depressive conditions are a secondary consequence. Hence treatment of depression with
antidepressants would be less effective than treatment with mood stabilizers, since treating an effect is
less successful than treating its cause. This approach would reverse current assumptions in psychiatry.