10 Factors That Influence Treatment Outcomes

Moderators are defined as baseline factors that can influence treatment outcomes. What follows are examples of moderators of pharmacotherapy outcome.

Baseline severity: More severely ill patients are less placebo-responsive; risk-benefit analyses often dictate the need for high-potency treatments (eg, clozapine, electroconvulsive therapy (ECT)) over side effect concerns

Race/ethnicity: Cytochrome P450 ultrarapid metabolizer genotypes are more common in Ethiopian blacks; Han-Chinese, Thai, or Malaysian individuals have an increased genetic risk (HLA-B*1502) for developing severe cutaneous reactions from carbamazepine.

Implications: Increased risk for suicide with antidepressants pertains to youth; increased mortality with second generation antipsychotics pertains to elderly patients with dementia related psychosis; tardive dyskinesia risk increases with both age and antipsychotic exposure duration; older adults with bipolar depression fare no better with lurasidone plus a mood stabilizer than with lurasidone alone.

Implications: Some drugs may work best in the first few episodes (eg, lithium).

Polarity proneness: Lithium and divalproex exert more potent antimanic than antidepressant effects; lamotrigine may be more useful in depression- than mania-prone patients.

Family history implications: Drug responsivity has not been well-demonstrated as a familial trait—except in the case of lithium.

Pharmacogenetics: Commercial pharmacogenetic testing can help to detect the roughly 6-10% of patients who may too slowly or quickly metabolize drugs that are cytochrome P450 substrates. That information mainly can help inform drug tolerability and safety for some patients.

Past treatment response implications: A personal history of an unequivocally favorable response to a particular agent is perhaps the highest grade of evidence to support use of that agent for the same clinical presentation—in that one particular patient.

For more on this topic, see Bespoke Psychopharmacology for Bipolar Disorder: An Individualized Patient Approach, on which this slideshow is based.