Use them relevantly
Discourse markers are only helpful if they are related to the attitude you are trying to establish. Otherwise, they sound out of place and might even get you opposite results!
If you are trying to express your sorrow over an event that happened in your life, you could say:
“When I was 5, unfortunately, I lost my grandmother, who was really close to me.”
But if you say:
“When I was 5, generally, I lost my grandmother, who was really close to me.“
you communicate a different message which has no meaning!
If the question is “what causes the air pollution in your city?”, You could say:
“Well, I think the excessive number of vehicles is the leading cause. I mean, it is not proportional considering the geographical position of my city, which is at the base of a mountain range.”
By using “well”, you stall the conversation intelligently to give yourself time to think and by using “I mean”, you clarify your response with more detailed information.
As you can see, discourse markers must be relevant to the logic and emotion of your statement.