Behavioral Toxicity Revisited: Iatrogenic Comorbidity in Psychiatric Evaluation and Treatment

In 1968 Di Mascio and Shader provided a conceptual framework for behavioral toxicity of psychotropic drugs (i.e., the pharmacological actions of a drug that, within the dose range in which it has been found to possess clinical utility, may produce alterations in mood, perceptual, cognitive and psychomotor functions, that limit the capacity of the individual or constitute a hazard to his/her well-being). A drug effect such as sedation or motor stimulation may be considered adverse for one patient, and yet therapeutic and desired for another patient; within the same patient it may be of value at one stage of his/her illness and adverse at a later stage. The concept of behavioral toxicity encompasses adverse events that may be limited to the period of drug administration and/or persist long after their discontinuation. These latter phenomena can be subsumed under the rubric of iatrogenic comorbidity. Behavioral toxicity may ensue with any type of medical drug. Examples related to antidepressant drug use (onset of suicidality and aggression, switching from unipolar to bipolar course, withdrawal phenomena upon discontinuation, post-withdrawal persistent disorders) are discussed. Consideration of potential vulnerability to adverse events including behavioral toxicity should be placed in the context of the benefits treatment may entail.