Comorbidity of mental disorders and substance use: a brief guide for the primary care clinician
1.2 Drug interactions
In these guidelines, the quality of scientific evidence supporting statements concerning drug interactions is indicated by different indications of 'level of evidence'.
As it is unethical to conduct RCTs of drug interaction in clinical populations, it is not possible to base levels of evidence on clinical RCTs. As a result, the following 'level of evidence' statements have been formulated.
xxx Definite - Multiple case reports or controlled pharmacological studies have confirmed interactions of the combination of these drugs.
Caution: if these drugs are administered in combination with one another, interactions will occur. Alternative treatment should be sought if appropriate. Should it be necessary to combine these drugs, patients should be monitored and doses adjusted as needed to prevent adverse events.
xx Likely - Case reports indicate that interactions have occured in a clinical situation.
Alternatives should be offered where appropriate. If the combination is to be administered, the individual should be monitored to confirm interactions and adjust treatments if necessary.
x Theoretical - Based on pharmacokinetic and pharmacodynamic properties of the drugs, there is a theoretical possibility that they may interact to cause a different effect if the drugs were administered individually OR in vitro, or animal studies suggest that there may be an interaction.
Individuals taking these combinations of drugs should be monitored.