Comparative plasma levels of doxepin and desipramine in the elderly

Although tricyclic antidepressants remain a principal mode of treatment of depression in the elderly, concomitant medical illness in this subgroup creates particular concern regarding the safety of these drugs. Doxepin has gained favour for use in the geriatric population due to claims of low cardiovascular side effects. This perceived safety has been questioned, however, since few investigators have actually reviewed plasma levels. A recent finding of interest revealed that two patients on 150 mg of doxepin daily with assured compliance had undetectable levels of doxepin or desmethyldoxepin in their plasma. A prospective study was consequently undertaken to compare oral doses and plasma levels of doxepin with desipramine as a standard reference compound. Data was collected for 19 females (12 on doxepin, seven on desipramine) and 12 males (five on doxepin, seven on desipramine) with a mean age of 76. Eight patients on doxepin showed undetectable plasma levels as compared with none on desipramine. This is a highly significant difference. Although the therapeutic plasma range for doxepin remains controversial, it is unlikely that patients can respond to levels of zero. The authors recommend routine monitoring of doxepin levels in the elderly and question poor bioavailability or absorption of this tricyclic antidepressant in some patients.