Of course it is possible to make a fixed timetable with breakdowns turned on.
As long as it's not a "Normal" breakdowns setting - I can't imagine playing with this setting, it's terrible. More than once I have had a situation that the vehicle broke down even just after leaving the workshop!
This screenshot is from 2015, when the last time (by accident) I played with this setting. Version of the game 1.5.X, but it probably works the same now.
Reduced breakdowns are ok.
Maybe they are not realistic, especially the fact that the vehicle travels with passengers for inspection during the course between stations. Probably everyone who traveled by rail has such experiences, right?
As a curiosity: On the Polish-Belarusian border (general on the old soviet union border), trains enter workshops, passengers stay in the carriages, and during this time the chassis of the entire train is replaced... This is not a joke. This is happening! The reason is that the track gauge has changed. Currently, a special mechanism is being introduced or has been introduced, but previously it was similar to OTTD.
Anyway reduced brakedowns can be an interesting challenge, especially with more complex networks.
General, the basic rule I follow is the service at least every 100-120 days. The distance between the workshops is not important, but the travel time. During this time, the risk of brakedown is minimal and thanks to this I practically never have any failures - it is an unknown problem for me. The second, equally important rule is the lack of train / vehicle driver will - the service is to take place where I want, and not where blind fate will decide. Services are either specified in the timetable or are imposed by the way the routes are built. Another important thing is to exclude the possibility of going for a periodic inspection by self - it is enough to extend this time to the maximum in the company settings (the condition is your own, scheduled workshops at appropriate intervals).
Most basic solutions
It is possible to create a workshop layout that can handle any traffic volume. Sometimes you have to use a waypoint, sometimes pre-signaling devices are enough. Creating an efficient machine can sometimes be an interesting challenge.
Sometimes, unusual signaling possibilities can be discovered...
When it comes to the timetable, despite the fact that breakdowns are extremely rare for me, I always give some extra time for unexpected situations. However, I don't extend the time of each trip or stop, only those at the ends of the route, even by 10-15 days. Sometimes I also use a different method and leave one or two sections at both ends of the route without a set time, but this requires the creation of special buffers (for example, a station with a single platform where the train doesn't load or unload, but only waits for a certain amount of time.) that ensure the appropriate spacing between vehicles.