Depressed people who respond strongly to placebos get the most help from antidepressants

The Fascinating Link Between Placebo and Antidepressants

brain-changes image
When the researchers gave depressed people a placebo and told them it might help their symptoms, they saw changes in brain chemistry (left) in patients who responded to the placebo pill, in the areas of the brain involved in emotional regulation. Those same brain changes were also observed in patients who responded to a real antidepressant (right). Image credit: University of Michigan

2015 Study Abstract

Importance
High placebo responses have been observed across a wide range of pathologies, severely impacting drug development.

Objective
To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD).

Design, Setting, and Participants
In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) were studied with positron emission tomography and the µ-opioid receptor–selective radiotracer [11C]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect.

Main Outcomes and Measures
Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of µ-opioid receptor binding.

Results
Higher baseline µ-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r = 0.48; P = .02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, were associated with increased placebo-induced µ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala (nucleus accumbens: r = 0.6; P < .001). Placebo-induced endogenous opioid release in these regions was associated with better antidepressant treatment response, predicting 43% of the variance in symptom improvement at the end of the antidepressant trial.

Conclusions and Relevance
These data demonstrate that placebo-induced activation of the µ-opioid system is implicated in the formation of placebo antidepressant effects in patients with MDD and also participate in antidepressant responses, conferring illness resiliency, during open administration.

Sources and more information
  • Placebo power: Depressed people who respond to fake drugs get the most help from real ones, medicalxpress, September 30, 2015.
  • The Fascinating Link Between Placebo and Antidepressants, time, Sept. 30, 2015.
  • Placebo power: Depressed people who respond to fake drugs get the most help from real ones, U-M study finds, University of Michigan, SEPTEMBER 30, 2015
  • Association Between Placebo-Activated Neural Systems and Antidepressant ResponsesNeurochemistry of Placebo Effects in Major Depression, JAMA Psychiatry, doi:10.1001/jamapsychiatry.2015.1335, September 30, 2015.

Morts sur ordonnance

Des substances aux effets secondaires sévères…

Documentaire, “Morts sur ordonnance” durée 52’, auteur-réalisateur Olivier Pighetti. Production Piments Pourpres Productions, avec la participation de France Télévisions, 2014.

Plus d’information
  • Anxiolytiques, antidépresseurs, somnifères et autres tranquillisants sauvent des vies, mais de nombreux experts parlent aussi de «bombes à retardement» : ils seraient à l’origine de vagues de suicides, de troubles de comportement graves, d’homicides et certains seraient plus addictifs que les drogues dures. Aux Etats-Unis, les procès intentés par les victimes ont coûté des milliards de dollars aux industries pharmaceutiques. Pourtant, ces médicaments restent un best-seller planétaire et, en tant que premier consommateur mondial, la France représente un véritable tiroir-caisse. Ce film montre la dangerosité potentielle de ces molécules et analyse comment l’industrie pharmaceutique a verrouillé le marché, avec un cynisme effrayant.
  • Regardez cette liste de vidéos sur l’industrie pharmaceutique sur notre chaîne YouTube.

Medicating normalness: saying “know” to drugs

Are we over-medicating ourselves and our children?
Video with Alan Cassels 5/6

Are we over-medicating ourselves and our children? Drug policy researcher Alan Cassels discusses the drug industry; the methods and practices on how they operate and he questions whether or not we need to take as many prescription drugs as we are lead to believe for that ‘quick fix’ in our lives.

More information

Medicating normalness: saying “know” to drugs

Are we over-medicating ourselves and our children?
Video with Alan Cassels 3/6

Are we over-medicating ourselves and our children? Drug policy researcher Alan Cassels discusses the drug industry; the methods and practices on how they operate and he questions whether or not we need to take as many prescription drugs as we are lead to believe for that ‘quick fix’ in our lives.

More information

Medicating normalness: saying “know” to drugs

Are we over-medicating ourselves and our children?
Video with Alan Cassels 2/6

Are we over-medicating ourselves and our children? Drug policy researcher Alan Cassels discusses the drug industry; the methods and practices on how they operate and he questions whether or not we need to take as many prescription drugs as we are lead to believe for that ‘quick fix’ in our lives.

More information

Antidepressant drugs use during pregnancy : Not safe

Who says antidepressants in pregnancy are safe?

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Prenatal exposure to antidepressant drugs was linked to ADHD In children in a 2014 study.

Four countries have done nine studies on the effects of antidepressants during pregnancy or breast feeding. They found that newer and older antidepressants can cause premature births, and increase the risk of cardiovascular interventions such as heart surgery in early childhood. In addition, newer antidepressants could also cause withdrawal symptoms, respiratory problems, and neurological problems.

Six counties have issued a total of 15 drug regulatory warnings on antidepressants causing severe problems for newborns. They warn of:

  • Newer antidepressants causing seizures,
  • Wellbutrin, Cipralex, Luvox, Remeron, Effexor and Zyban increasing the risk of a life-threatening lung condition in newborns,
  • Zoloft and Celexa causing withdrawal symptoms and increasing the risk of a life-threatening lung condition in newborns,
  • Paxil and Prozac causing withdrawal symptoms and increasing the risk of cardiovascular birth defects and a life-threatening lung condition in newborns

Read Antidepressant Drugs Are Not Safe During Pregnancy—No Matter What the Pharma Shills Say, by CCHR International, November 4, 2010.

In 2014, a study found that antidepressant use in pregnancy was associated with higher risk for ADHD in children, another found a link to ASD and developmental delays in boys  another found that pregnant mothers may be unknowingly predisposing their infants to type 2 diabetes and obesity later in life,.

Watch the video The Truth about Pills and Pregnancy.

Diethylstilbestrol Exposure in Utero and Depression in Women

Understanding the relation between in utero DES exposure and depression will provide insight to the potential adverse effects of BPA

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The 2010 study found that women who were exposed to DES in utero had a higher risk of depressive symptoms and use of antidepressants, and that this increase in risk extended into their middle age. Image via Hartwig HKD.

2010 Study Abstract

Diethylstilbestrol (DES) is an estrogenic endocrine disruptor with long-term health effects, possibly including depression, following exposure in utero. Understanding the relation between in utero DES exposure and depression will provide insight to the potential adverse effects of bisphenol A , a functionally similar and ubiquitous endocrine disruptor. The association between in utero DES exposure and depression was assessed among participants in the Nurses’ Health Study II who first reported their history of antidepressant use in 1993 and lifetime history of depressive symptoms in 2001. DES exposure was reported by 1,612 (2.2%) women. A history of depression at baseline was higher among women exposed to DES in utero compared with those not exposed (age-adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.26, 1.72) (P < 0.001). Incident depression (first use of antidepressants among women who also reported depressive symptoms) during follow-up (1995–2005) was reported by 19.7% of women exposed to DES and 15.9% unexposed (age-adjusted OR = 1.41, 95% CI: 1.22, 1.63) (P < 0.001). Adjustment for risk factors of depression and correlates of DES exposure moderately attenuated the association (multivariable-adjusted OR = 1.30, 95% CI: 1.13, 1.51) (P = 0.0004). These results suggest that the neurophysiologic effects of in utero exposure to DES could lead to an increased risk of depression in adult life. Further research should assess whether in utero exposure to bisphenol A has similar adverse effects..

Conclusion

In summary, we found that women who were exposed to DES in utero had a higher risk of depressive symptoms and use of antidepressants, and that this increase in risk extended into their middle age. Although the possibility that some women became depressed because of awareness of their exposure status cannot be ruled out, these results are consistent with the hypothesis that the physiologic effects of in utero exposure to DES lead to higher rates of depression during adult life. It remains to be established whether prenatal exposures to ubiquitous environmental chemicals that are structurally similar to DES and have similar estrogenic effects also increase the risk of depression.

Sources and Full Study
  • Diethylstilbestrol Exposure in Utero and Depression in Women, Am. J. Epidemiol. (2010) 171 (8): 876-882. doi: 10.1093/aje/kwq023, March 23, 2010.
More DES DiEthylStilbestrol Resources

Do anti-depressant medications work the way they are supposed to?

The science behind commonly used anti-depressants appears to be backwards

Mc Master University campus image
The science behind commonly used anti-depressants appears to be backwards says Mc Master University researchers

The science behind many anti-depressant medications appears to be backwards, say the authors of a paper that challenges the prevailing ideas about the nature of depression and some of the world’s most commonly prescribed medications.

We are taking people who are suffering from the most common forms of depression, and instead of helping them, it appears we are putting an obstacle in their path to recovery” said lead author Paul Andrews, assistant professor of Psychology, Neuroscience and Behaviour at McMaster University.

Sources and more information

  • The science behind commonly used anti-depressants appears to be backwards, McMaster University, February 17, 2015.
  • Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response, ScienceDirect, doi:10.1016/j.neubiorev.2015.01.018, 24 January 2015.

Your doctor or therapist has confirmed it: you have depression. Now what?

To Treat Depression : Drugs or Therapy?

Your doctor or therapist has confirmed it: you have depression. Now what?

…” Until recently, many experts thought that your clinician could literally pick any antidepressant or type of psychotherapy at random because, with a few clinical exceptions, there was little evidence to favor one treatment over another for a given patient.

In fact, I used to delight in tormenting the drug company representatives when they asked me how I picked an antidepressant. I would take a quarter out of my pocket, flip the coin and say I’d let chance decide because their drug was no better or worse than their competitors’. “…

  • continue reading To Treat Depression, Drugs or Therapy? nytimes, JANUARY 8, 2015.
  • more info via Toward a Neuroimaging Treatment Selection Biomarker for Major Depressive Disorder, JAMA Psychiatry, August 2013.

Almost half of all English population is now on prescription drugs

Half of women are taking an average of one prescription drug per week

prescription-drugs-taking
Drugs bust: half of women are taking an average of one prescription drug per week.

Almost half of the English population is taking prescription medication: 50% of women and 43% of men in England are now regularly taking prescription drugs (one in the last week), with more than a fifth taking at least three separate drugs at the same time. Neither contraceptives nor smoking cessation drugs were included. Prescription drug use rise with age, with 70% of those aged 75 or over taking at least three prescribed medicine.

According to the survey , commonly prescribed medications included:

  • cholesterol-lowering statins
  • medications used to treat high blood pressure
  • painkillers, including non-steroidal anti-inflammatory drugs
  • antidepressants: nearly one in five women on a low income areas are taking them.

Sources and more information

  • Use of prescribed medicines, hscic.gov, December 2014.
  • Half of women are taking drugs on prescription… and four in ten men are doing the same, DailyMail, 10 December 2014.
  • Nearly 50% take prescription drugs, bbc news health, 10 December 2014.
  • Spare us the moralising on prescription drugs. Many of us need themthe guardian, 11 December 2014.
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