PHQ-9

Table 3. PHQ-9

1. Over the past 2 weeks, how often have you been bothered by any of the following problems?
	Not at all (0)	Several days (1)	More than half the days (2)	Nearly every day (3)
a. Little interest or pleasure in doing things
b. Feeling down, depressed, or hopeless
c. Trouble falling/staying asleep, sleeping too much
d. Feeling tired or having little energy
e. Poor appetite or overeating
f. Feeling bad about yourself -- or that you are a failure or have let yourself or your family down
g. Trouble concentrating on things, such as reading the newspaper or watching television
h. Moving or speaking so slowly that other people could have noticed. Or the opposite -- being so fidgety or restless that you have been moving around a lot more than usual
i. Thoughts that you would be better off dead or of hurting yourself in some way
2. If you checked off any problem on this questionnaire so far, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?
	Not difficult at all	Somewhat difficult	Very difficult	Extremely difficult

Table 4. Interpretation of PHQ-9 Results

Score/ Symptom Level	Treatment
0-4 No depression	Consider other diagnoses
5-9 Minimal	▪ Consider other diagnoses ▪ If diagnosis is depression, watchful waiting is appropriate initial management
10-14 Mild	▪ Consider watchful waiting ▪ If active treatment is needed, medication or psychotherapy is equally effective; consider function score in choosing treatment
15-19 Moderate	▪ Active treatment with medication or psychotherapy is recommended ▪ Medication or psychotherapy is equally effective
20-27 Severe	▪ Medication treatment is recommended ▪For many people, psychotherapy is useful as an additional treatment ▪ People with severe symptoms often benefit from consultation with a psychiatrist

Data from Kroenke K, Spitzer R. Psychiatr Ann. 2002;32:509-521.

A number of combinations have some benefit in selected patients, including:

• Lithium augmentation at stage 3 of STAR*D resulted in remissions in 15.9%.^[84] Lithium in combination with SSRIs and TCAs also has been effective in placebo-controlled studies, most involving small numbers of subjects. Such treatment requires monitoring of lithium levels, because there is a small difference between therapeutic and toxic levels.^[85]
• Thyroid hormone, and particularly triiodothyronine, has been studied for augmentation with the TCAs. In the STAR*D study, at step 3, augmentation with triiodothyronine led to a remission rate of 24.7%.^[84] Placebo-controlled studies have involved small numbers of subjects and have had mixed results.^[86]
• A heterocyclic-SSRI combination in 1 small study produced more rapid treatment onset and increased the likelihood of remission.^[87] In the study, a combination of fluoxetine and desipramine (a norepinephrine reuptake inhibitor) was more effective in achieving remission than either drug used as monotherapy: 53.8% for the combination, compared with 7.1% and 0%, respectively. However, such combinations can produce the serotonin syndrome, which is potentially life-threatening, and the dose of the heterocyclic must be adjusted using blood levels because SSRIs increase TCA levels through CYP-450 isoenzyme interactions (eg, fluoxetine increases the levels of desipramine 3- to 4-fold).^[88] Consequently, this augmentation strategy should rarely be considered in primary care.
• Mirtazapine has recently been evaluated in combination therapy with an SSRI (fluoxetine), an SNRI (venlafaxine), or bupropion.^[89] The investigators found that all 3 combinations were more effective than fluoxetine alone in achieving remission (52%, 58%, 46%, respectively, compared with 25%). In patients who responded, double-blind discontinuation resulted in relapse in about 40%. Of note, treatment was initiated with these combinations, rather than mirtazapine being used as an augmenting agent in those not initially responding.
• Methylfolate and folate have been used to augment SSRIs, resulting in increased rates of remission, particularly in women.^[90] The degree to which the response is due to folate deficiency, and whether methylfolate is of greater benefit due to its increased ability to cross the blood-brain barrier, are subject to further research.
• Antidepressants and hypnotics have been used together, with early improvement not only in sleep measures, but also in rates of depression remission.^[91]
• Stimulant drugs have been used as augmentation of heterocyclics or SSRIs.^[92] Of note, in individuals with comorbid medical illness, amphetamine stimulants should be used with caution, particularly if cardiac disease is potentially present.

Clinical and Pharmacologic Strategies to Achieve Remission in Depression