Based on a review of this drug by the National Academy of Sciences–National Research Council and/or other information, FDA has classified the indications as follows: "possibly" effective: For use as adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis.
[1][2] Clinical studies have been performed on different combinations of belladonna alkaloids and phenobarbital over the last 70 years.
A small assessment of sustained release of 0.4 mg belladonna alkaloids and ~60 mg phenobarbital (1 grain) was performed in patients with functional GI disorders (i.e., gastric hyperacidity, dyspepsia, pyrosis, gas pains and epigastric distress.
Hock also examined the effect of 0.25 mg belladonna alkaloids and 50 mg phenobarbital sustained release formulation in 82 clinical practice patients with various gastrointestinal disturbances including “functional distress” over 27 months.
One of the earliest randomized double-blind clinical trials of belladonna alkaloids + phenobarbital was in 1959 by Lichstein et al.[5] The study involved 75 patients with unstable bowel (whose symptoms are typical or similar to a current diagnosis of IBS) to investigate the combination therapy of an anticholinergic with the addition of phenobarbital against placebo over 15 months.
The intent-to-treat population of 204 IBS patients was evaluated for pain (cramping), nighttime and daytime pain severity, bowel movement frequency, and with a clinician global evaluation of improvement in response to treatment.
Females taking Donnatal® tablets were 4 times more likely to experience weeks free of daytime pain compared to phenobarbital alone and twice as likely to experience weeks free of nighttime pain compared to belladonna alkaloids.
Only the phenobarbital group demonstrated a significant change in pain type compared to belladonna alkaloids at the end of the study with an approximate 48% response rate.
Males also showed a greater response for pain free-weeks on phenobarbital in comparison to Donnatal® tablets.
[16] These ANDAs, with the exception of the capsule formulation, are still in force today and the FDA has not changed the review status of Donnatal® as being conditionally approved for its indication.
Donnatal, although containing phenobarbital, is exempt from the Controlled Substances Act due to the belladonna alkaloids present in the formulation.