title: Adverse drug reactions/interactions in maintenance therapy.
abstract: This paper begins with a brief review of the early onset, recidivism, and multiple consequences of recurrent major depressions. Increasing attention to these factors underscores the importance of long-term maintenance therapy. Successful maintenance rests on optimizing the risk:benefit profile for the patient. Literature is reviewed that the serotonin selective reuptake inhibitors exhibit a significantly lower discontinuation rate due to adverse events than do other conventional antidepressants. Adverse events clearly detract from patient compliance and, in turn, ultimately contribute to the risk of depressive recurrence. An overview of adverse events, in both short- and long-term anti-depressant trial experience is provided. In addition, extended pharmacotherapy carries an increased probability of concomitant drug therapy. Relevant drug:drug interaction issues are reviewed, including specific attention to those mediated by the hepatic isoenzyme cytochrome P450 IID6. Lastly, long-term clinical trial experience with fluoxetine relative to short- and long-term emergence of adverse events and adverse event experience following drug discontinuation is presented. Overall fluoxetine adverse events do not increase with chronic administration. When side effects occur, they typically emerge early in the course of acute treatment and wane in the face of continued treatment. Upon drug discontinuation, these events usually reverse at a much faster pace than the drug's half-life. In conclusion, the importance of maintenance therapy in recurrent major depression is increasingly recognized as a critical care issue. To optimize a therapeutic outcome, the clinician is challenged to maximize patient compliance through depression awareness education, regular follow-up, minimization of adverse drug events, and sensitivity to other intercurrent psychosocial events.
authors.affiliation: Department of Clinical Investigation and Regulatory Affairs (Psychopharmacology), Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN 46285.
authors.forename: G D
authors.initials: GD
authors.lastname: Tollefson
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003866:Depressive Disorder / Q000517:prevention & control* / Q000523:psychology / Q000628:therapy; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010349:Patient Compliance; D010353:Patient Education as Topic; D012008:Recurrence; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013405:Suicide / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System; D005473:Fluoxetine; D006899:Mixed Function Oxygenases; D017367:Selective Serotonin Reuptake Inhibitors