There are three primary hypotheses presented to potentially explain the cause, if it exists (note: there is no concrete evidence to support or refute any of these potential mechanisms).

1. The first hypothesis is that as one's depression improves, a person experiences more energy, less apathy, and is better able to make decisions. If a patient were to remain suicidal during this shift, the risk of suicide would increase. There has been evidence that suicidal ideas and behaviors are highest in the first month of medication treatment.

2. A second hypothesis is concerning the side effects of antidepressants. These mostly include activation, agitation, impulsivity, and disinhibition. These characteristics, especially early on in treatment, may increase the risk of considering suicide.

3. The third hypothesis states that antidepressants have been found occasionally to precipitate manic episodes, especially with a family history of bipolar disorder. Those with bipolar disorder experience an increased risk of suicide.