Major depression is common, leading to marked suffering for patients and families and causing physical and mental disability, with a substantial economic burden. Although major depression is prevalent across different cultures and effective pharmacological and psychosocial interventions are available, low remission rates in clinical practice are discouraging. Poor outcomes are related to inadequate dose and duration of pharmacotherapy, poor treatment adherence, high dropout, and frequent as well as unnecessary medication changes. In addition, inconsistency of treatment strategies among clinicians is common. Even in current, guideline-driven practice, there are often wide variations in clinicians’ behaviors, resulting in practice bias rather than a tailored and individualized treatment algorithm.

So opens a new paper that has a large goal: trying to reduce that “wide variation” and improve patient care.

This week’s Reading: “Measurement-Based Care Versus Standard Care for Major Depression: A Randomized Controlled Trial With Blind Raters” by Tong Guo et al., just published online (and ahead of print) by The American Journal of Psychiatry.

Find the paper here:

http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2015.14050652

Here’s a quick summary: big study, big journal, and big implications for depression management (and, yes, your patients). In a head-to-head comparison, patients did better when depression management included an algorithm for medications rather than regular psychiatrist care.

This Reading will be the first part in a three-part series on depression.

This week: a look at better psychopharmacological management.

Next week: consideration of better treatment in the primary care setting.

Third Week: a look at the burden of illness on the patient and the psychiatrist.

(And this isn’t Mad Men Season 4. Miss a week and you aren’t lost.)

The Guo et al. paper is timely. While we can all agree that care has gotten much better in recent years with published guidelines, these guidelines (including CANMAT’s) aren’t very specific. As Dr. A. John Rush notes in an accompanying editorial: “Most clinical practice guidelines do not typically recommend specific tools, visit frequencies, dosage adjustment schedules, the routine measurement of side effects, or when to change treatments…”

And so I return to the point made in the opening paragraph from this paper. Wide variation. In speaking to clinicians over the years, I’m struck by the varied opinions about how to adjust and switch antidepressants – often based on little, except “hand-me-down” advice. Depression management in that way reminds me of the old joke of Jewish bride and her brisket recipe. The young bride prepares her husband’s favourite dinner, beef brisket. Her husband enjoys the meal but comments that his wife had cut off the brisket ends – the best part of the brisket. She responds by pointing out that it’s part of the family recipe, passed down from her grandmother. Weeks later, at a family event, she asks her grandmother why she cuts off the brisket ends. “Because I was poor and my pans are small.”

Is it possible to meaningfully come up with an algorithm for depression management? The idea isn’t new, and different studies have looked at just that (think STAR*D). But this study is unique in that it does a head-to-head comparison with regular psychiatric care.

Here’s what they did:

· Essentially, the study authors designed a randomized controlled trial, with assessors blind to protocol and treatment groups.

· Patients were recruited who were seeking psychiatric treatment from a Chinese hospital. They were outpatients, between 18 and 65, diagnosed with depression. Exclusion criteria included: bipolar, OCD, a lifetime history of drug or alcohol dependence.

· Patients were randomized into a standard treatment group and a measurement-based care group. They first were given a one-week washout period. In both groups, patients were treated with either mirtazapine (15 – 45 mg/day) or paroxetine (20 – 60 mg/day). Treatment and medication adjustments lasted for six months.

· Patients randomized into the standard treatment group where treated by psychiatrists who could decide on the antidepressant and the dosing, provided that they prescribed within the agreed upon dose range – obviously based on their perception of patient needs. Psychiatrists could switch the patients from one antidepressant to the other and they could prescribe benzodiazepines.

· Patients randomized to the measurement-based group were prescribed according to a schedule that included “starting dosages, dosage adjustment, and medication changes to minimize side effects, maximize safety, and optimize the therapeutic benefit for each patient.” Psychiatrists adjusted dosing, based on scales (the 16-item QID-SR and a side effect scale) administered at each patient visit.

· The primary outcome measure: the time to response and to remission, as measured by HAM-D scores. Raters assessed patients at 2, 4, 8, 12, and 24; raters were not involved in treatment.

Here’s what they found:

· Of 164 screened patients, 120 met study criteria and were randomly assigned to the standard treatment (59) or to the measurement-based care groups (61).

· Patients were predominately female (64%), married (78%), and had past episodes of depression (3.2). The measurement-based care group was a bit younger, but the other characteristics were similar.

· Discontinuation did not differ significantly between the measurement-based care and standard treatment groups (27.9% and 37.3%). Likewise, treatment adherence was similar (99.8% and 99.7%).

· People in the measurement-based group received higher dosages of antidepressants (at week 24, about 20% more).

· They tended to respond better than the standard treatment group (86.9% vs. 62.7%); they had a much higher remission rate (73.8% vs. 28.8%); their time to response to treatment was shorter (4.5 weeks vs. 8.1 weeks). !! See the figures below.

· The HAM-D scores decreased significantly in both groups, but the change was significantly larger in the measurement-based care group (p<0.001). !

· Adverse events occurred about equally in the two groups.

The study authors write:

To the best of our knowledge, this was the first randomized controlled trial with blind raters to systematically investigate the effect of measurement-based care, compared with standard treatment, on time to response and remission in patients with major depression, using identical medication options in the two groups in order to isolate the effect of measurement-based care.

More:

Our study demonstrated significantly higher response and remission rates at 6 months in the measurement-based care group compared with the standard treatment group, translating into numbers needed to treat of 5 and 3 for response and remission, respectively.

A few thoughts:

1. This is a good study – well designed and thoughtful.

2. The result is big. People in the measurement-based group didn’t do somewhat better than the people in the standard treatment group, they did much better. Consider: people in the measurement-based group responded or remitted about twice as fast as the standard treatment group. One explanation is that they were treated far more aggressively, with dosing pushed up faster. Yet, despite that aggressiveness, side effects, clinic visits, and attrition rates were similar between the two groups.

3. At the very least, this study result suggests that practice guidelines need to be better developed and more specific.

4. It’s possible to push further too: while more studies are needed, this paper certainly indicates that our usual approach is badly inferior to an approach involving scales and a clearly defined algorithm.

Reading of the Week. Every week I pick a reading — often an article or a paper — from the world of Psychiatry.