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Depression Research Update: November 2016

Depression Research Update: November 2016

  • Three new studies examine placebo responses to antidepressants, the effect of SSRIs on sleep in the elderly, and the best time of day for psychotherapy sessions.[1-3] Scroll through the slides for the latest findings and take-home messages. View the information in PDF format.

  • Study 1. No Rise in Placebo Responses With Antidepressants
    1. Average Placebo Response Rates in Antidepressant Trials Have Been Stable for More Than 25 Years: Previous studies showed that placebo response rates in antidepressant trials have been increasing since the 1970s, but these studies have methodological problems. A recent systematic review included 252 double-blind, randomized, placebo-controlled trials of first- and second-generation antidepressants for acute treatment of major depression in adults. The results show that average placebo response rates in antidepressant trials have remained constant, in the range between 35% and 40%.[1] Link to study.

  • Clinical implications for Study 1: The continuing placebo response to antidepressants identifies a need for non-drug strategies to boost clinical responses.

  • Study 2. SSRIs Affect REM Sleep in the Elderly
    2. SSRIs May Disrupt REM Sleep in Elderly Patients, Leading to Neurodegeneration: Antidepressants significantly affect sleep architecture in the elderly by increasing sleep latency and decreasing REM sleep duration. A review of 10 studies of patients age 50 or older with REM sleep disorders who took antidepressants found that REM sleep behavioral disorders may be an early sign of neurodegeneration. Antidepressants, particularly SSRIs, can put elderly patients at risk for neurodegenerative diseases.[2] Link.

  • Clinical implications for Study 2: Consider screening elderly patients for neurodegenerative signs and symptoms before prescribing an antidepressant.

  • Study 3. Early-Day Psychotherapy for Panic Disorder
    3. Morning Psychotherapy Sessions Are More Helpful Than Later-Day Sessions: Patients appear to make more progress toward overcoming anxiety, fears, and phobias when therapy sessions are scheduled in the morning. A recent study included 24 patients with panic disorder and agoraphobia who received 3 weekly exposure sessions. Early-day sessions were associated with superior therapeutic gains, as well as higher pre-exposure cortisol levels. This suggests that cortisol mediates the effect of time of day on therapeutic outcomes.[3] Link to study.

  • Take-home message for Study 3: Early-day extinction-based therapy yields better outcomes than later-day sessions, partly because of the enhancing effect of higher cortisol levels.

View the information in PDF format.

1. Furukawa TA, Cipriani A, Atkinson LZ, et al. Placebo response rates in antidepressant trials: a systematic review of published and unpublished double-blind randomised controlled studies. Lancet Psychiatry. 2016 Oct 7. pii: S2215-0366(16)30307-8. doi: 10.1016/S2215-0366(16)30307-8.
2. Tahir MA, et al. Effect of antidepressants on REM sleep in the elderly population: a literature review. Presented at: Institute of Psychiatric Services (IPS): The Mental Health Services 2016 Conference; October 7, 2016; Washington, DC. Abstract 14.
3. Meuret AE, Rosenfield D, Bhaskara L, et al. Timing matters: Endogenous cortisol mediates benefits from early-day psychotherapy. Psychoneuroendocrinology. 2016;74:197-202.


Thumbs up to George, you hit the nail right on the head! Either the assumption of blame for the ND is a wild leap of logic, or he's leaving out something very important.

Susanna @

The effects of anti depressants in suppressing REM sleep has been studies for decades and the degree of suppression is associated with the effectiveness in lifting mood. Depression generally is associated with increased time spent in REM sleep. The fact that sleep disorders may be an indicator of a neurodegenerative disorder can't really be blamed on something given to manage the sleep disorder.

George @

In many comments about: 'placebo response rates', the basic fact that placebo is actually an active therapy is missed, just attending an office triggers, for example, the 'transfert' phenomenon, and anything prescribed, including placebo, elicits responses and noticeable changes in the brain and disease process of the patient who consulted.
The best attitude wouldn't be perhaps: 'searching for new non-drug tactics', the strategy is always achieving cure or relievement, but considering what caused this 30-40% 'subjective improvement' with placebo, or the adequacy of the diagnostic label, as the disease that never gets a good therapy is the undiagnosed or misdiagnosed condition.
Is biology, e.g, infectious, metabolic diseases, always considered enough in the work-up of 'psychiatric' patients?
I have the hunch that Neurology and Psychiatry will soon reunite, and not only because 'Entwurf einer Psychologie fuer Neurologen', by S Freud...

Jose @

The high placebo rate can be attributed to two factors;

1. Under the rubric Major Depressive Disorder are more than one illness.
Not all will respond to current psychopharmalogical agents used without any discrimination among them.This will include those for whom anti depressants will not be at all effective.

2. Unless regulations have changed since my days an IRB chairman,the FDA requires that new antidepressants first be tested against placebo. Therefore, severely depressed patients, who are most likely to respond to medication cannot be included in these clinical trials.

Therefore,no surprise. We exclude those most likely to respond to an effective drug and include those least likely to do so.

Don Kornfeld

donald @

You are talking about Phase I of a clinical trial in which the med is compared against a placebo in a normal (not diagnosed as depressed) random population to determine what adverse effects or side-effects the proposed med has. Only in later Phases of a clinical trial are the med and the placebo tried on study participants diagnosed as depressed. My impression is that antidepressants of all kinds are not significantly better than placebo, as shown in completed clinical trials.

George @

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