Can Benadryl worsen depression or cause irritability? I have depression and anxiety and I’m on Wellbutrin. I have terrible allergies and struggle with hives. I generally take Allegra or Claritin but sometimes I have to take Benadryl. When I take it I not only feel drugged out and exhausted the next day but I’ve noticed I’m very emotional irritable and depressed to the point I’m on the verge of tears. Anyone know if this is normal or have dealt with this?