Reasons for a failure to respond to antidepressant therapy:
(1) underdiagnosis (failure to appreciate the severity of the depression, resulting in underdosing of medication)
(2) overdiagnosis of depression (treating a mood disorder that is not true depression)
(3) depression caused or worsened by an underlying physical disorder
(4) depression caused or worsened by a concurrent medication
(5) inadequate dose of antidepressant
(6) inadequate duration of therapy
(7) poor adherence
(8) drug interaction decreasing the effectiveness of the antidepressant
(9) genetic polymorphism reducing response (serotonin transporter protein "s" allele)
(10) comorbid substance abuse
(11) comorbid personality disorder
(12) history of physical, sexual or emotional abuse
(13) insufficient level of concurrent psychotherapy, cognitive behavioral therapy or alternative support therapy
(14) concurrent neurologic disease causing decreased response to antidepressants (dementia, vascular depression, other)
Additional reasons:
(1) individual variation in response to the antidepressant (one works while another does not)
(2) concurrent event that worsens the depression (loss of job, divorce, etc.)
