Treatment-Resistant Depression Case 1: Level 1

Jane is a 29 yo female who presents to your clinic stating she feels tired and down for over 6 wks. Her PHQ-2 is positive for both questions and her PHQ-9 score is 16. She denies SI/HI. She is interested in treatments for depression, andsays she keeps seeing commercials for Cymbalta. She wonders if that would be a good first choice…

  1. What is the best screening tool for depression?
  1. How do you make the diagnosis of depression?
  1. List at least FIVE alternative diagnoses for Jane other than unipolar major depression.
  1. How would you treat Jane? Show your evidence!
  1. Many instruments have been developed for depression screening. Although the USPSTF found little evidence that one is superior, the most practical tool for the clinical setting should be used.

Positive results on a screening test should trigger full diagnostic interviews that use standard diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). Ultrashort screening instruments, such as the Patient Health Questionnaire (PHQ)-2 may rule out, but not definitively diagnose, depression. However, the PHQ-2, which asks two simple questions about mood and anhedonia, has strengths. It is as effective as longer screening instruments, such as the Beck Depression Inventory or Zung Depression Scale. The PHQ-2 has been found to be up to 97 percent sensitive and 67 percent specific in adults, with a 38 percent positive predictive value and 93 percent negative predictive value. It is reported to have a 74 percent sensitivity and 75 percent specificity in adolescents. The PHQ-9 is one of the most common instruments used for depression screening. Although it can be used on its own as a screening test or to monitor treatment, it is increasingly administered for confirmation of a positive PHQ-2 result. The PHQ-9 is valid, takes two to five minutes to complete, and has demonstrated 61 percent sensitivity and 94 percent specificity for mood disorders in adults, and 89.5 percent sensitivity and 77.5 percent specificity in adolescents.

  1. a. Bipolar disorder

b. Substance abuse

c. OCP’s

d. Anemia

e. Hypothyroidism

f. Malignancy

g. Migraine

h. Medications/supplements

  1. See attached figures for assistance and/or

For initial treatment of depression, the effectiveness of antidepressant medication is comparable between classes; therefore, selection of a particular antidepressant should largely be based on the side effect profile of the drug, any history of response in the patient or a family member, and cost of the medication.

Evidence regarding psychotherapy and pharmacotherapy has recently been enhanced by results from the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, a seven-year randomized controlled trial (RCT) that evaluated medication switching and augmentation in 3,671 outpatients with unipolar depression. Citalopram (Celexa) was the initial treatment (20mg daily, titrated to 60mg daily if needed). Three additional levels of treatment were included, based on response. Each treatment level was sustained for at least 12 weeks (if the drug was tolerated) before response was determined.

The STAR*D trial found that patients who received CBT after failing to respond to citalopram (with or without continued citalopram) had similar rates of response (i.e., at least 50% improvements in symptoms compared with baseline) and remission (i.e., resolution of symptoms) as those who received other medication regimens. Patients who received CBT alone (rather than in conjunction with citalopram) achieved remission less rapidly, but they also had fewer adverse effects than those who were switched to other medications.

A systematic review identified 16 RCTs of treatment resistant depression, all of which were considered too small to detect an important clinical response. (Br J Psychiatry 2002)

The STAR*D trial significantly expanded the evidence base for pharmacotherapy of treatment-resistant unipolar major depression. Remission rates after the first level of treatment were 37%; after the second level, 31%; after the third level, 14 percent; and after the fourth level, 13 percent. The cumulative remission rate was 67%. In general, patients who required more treatment steps had higher relapse rates. Ultimately, fewer than one half of patients achieved sustained remission, even after all four treatment levels.

There were significant differences between only three treatment strategies tested in the STAR*D trial. Augmentation of citalopram with bupropion resulted in slightly improved response rates and fewer adverse effects compared with buspirone (Buspar), but no difference in remission rates. Augmentation of the level 2 treatment with T3 resulted in fewer adverse effects than augmentation with lithium, but there was no difference in effectiveness. Venlafaxine plus mirtazapineresulted in slightly improved response rates and fewer adverse effects compared with tranylcypromine (Parnate). Beyond these findings, the STAR*D trial did not find that any of the studied treatments are better than another. Other evidence suggests that augmentation of second-generation antidepressants or TCAs with pindolol, lithium, or methylphenidate (Ritalin) is not effective for treatment resistant depression.