Individual factors associated with no or partial response include, among others, early age of onset, hopelessness, low psychosocial functioning, poor motivation toward treatment, or poor adherence (for factors associated with poor adherence, see Chapter 15). In the case of medication, this means incomplete adherence to the prescribed regime. When patients are treated with medications with shorter half-lives, such as sertraline, skipping dosages can result in withdrawal symptoms, which in turn can be associated with clinical deterioration and further nonadherence. With regard to psychotherapy, patients are required to practice and apply skills learned within the session. Other predictors of poor response include indicators of severity (high symptom ratings of depression, suicidal ideation, low functioning), chronicity (long duration), and complexity (e.g., presence of psychosis or comorbid conditions such as disruptive behavior disorders, anxiety, eating, and substance abuse disorders), personal identity issues (such as concern about same-sex attraction), and socioeconomic factors (e.g., poverty and poorer response to CBT23). Also, use of other medications (e.g., steroids, contraceptives, interferon, and/or retinoic acid) and medical illness such as hypothyroidism, anemia, mononucleosis, folate or B₁₂ deficiency and other chronic conditions can produce symptoms that overlap with the depressive symptoms or contribute to treatment nonresponse. Although relatively few studies have examined ethnicity and treatment response, there is some suggestion that IPT may have greater benefit in some domains than CBT for depressed Hispanic adolescents;24 conversely, response rates to CBT are better in Whites than in minority depressed youth.25 Hopelessness is
associated with both a poorer treatment response and dropout, at least in some psychotherapy trials.26,27 In addition, pharmacokinetic (e.g., absorption, rapid or slow metabolism, intolerance at adequate dosage) and pharmacogenetic (presence of certain polymorphisms, such as the less functional variant of the serotonin transporter) as well as medication side effects may contribute to poor response or poor adherence to antidepressant treatment.28

Among the first issues a clinician should consider when a patient is not responding to treatment is the possibility of misdiagnosis (e.g., bipolar-II versus unipolar depression) or that the patient has an unrecognized or untreated comorbid psychiatric or medical condition (e.g., anxiety, dysthymia, ADHD, eating, substance use, personality disorder, early-onset schizophrenia) or is using medications that are contributing to depressive symptomatology. Because most youth with a bipolar diathesis present in their first episode as major depression, one of the most problematic differential diagnosis is between unipolar and bipolar depression. 1, 2, 3,29 However, the presence of psychosis, a family history of bipolar disorder, or pharmacologically induced hypomania may help the clinician suspect the presence of bipolar instead of unipolar depression. 1, 2, 3 Also, the presence of recurrent periods of elation, euphoria, and agitation above and beyond what it is expected for the child’s age and cultural background may indicate the presence of bipolar disorder.

Clinicians should also consider that the pharmacotherapy or psychotherapy offered is not appropriate or that the length or dosage is inadequate for the specific child who is not responding to treatment. The presence of unrecognized medication side effects or ongoing exposure to chronic or severe life events (such as sexual abuse or ongoing family conflict) should be taken in consideration. Finally, the clinician may be an inadequate fit with the child, has poor motivation to help, or poor skills as a pharmacotherapist or psychotherapist.