Managing selective serotonin reuptake inhibitor-drug interactions in clinical practice

Combination drug therapy is common in psychiatry. It plays a role in the treatment of patients with multiple disorders, in the management of residual symptoms or resistant disease, and in the alleviation of unwanted effects of the primary drug. Coadministration of psychotropic drugs with medications for medical illnesses is becoming more common as well, because as many as half the patients with major depression require long term treatment, and because the number of patients who are elderly is increasing as the population ages. To safely manage multidrug regimens, the clinician must be knowledgeable about drug-drug interaction potential. Drug-drug interactions can produce a change in the pharmacological effect of a drug by altering activity at the site of action (a pharmacodynamic interaction), or by changing the plasma concentrations of a drug (a pharmacokinetic interaction), or both. Selective serotonin reuptake inhibitors (SSRIs) have the potential to impair the oxidative metabolism of several drugs, including tricyclic antidepressants and neuroleptics. However, the SSRIs highlight the maxim that overgeneralisation can be as detrimental to rational co-pharmacy as ignorance of interaction potential. The SSRIs differ in terms of which other drugs they affect, which patients are at risk, and to what extent the effect is clinically important. Clinicians must assess drug combinations on a case-by-case basis. Standard management practices of dose titration, monitoring plasma drug concentrations when the therapeutic index is narrow, and observing for adverse events minimise the clinical impact of potential drug-drug interactions.