Category Archives: Medical Drugs

Low Serotonin and Depression Link Questioned

An article in New Scientist magazine, July 24th, 2010 by Linda Geddes, reported on the research of Christopher Lowry of the University of Boulder, Colorado.

Though the theory has never been proven, it has generally been thought that depression results from low levels in the brain of the neurotransmitter, serotonin.

The article outlines the central discovery of Lowry’s work that high levels of serotonin in people with depression as well as multiple type of serotonin releasing neurons in the brain is prompting a reassessment of the treatment of depression by simply increasing the neurotransmitter using SSRI antidepressants.


Though not mentioned this rethink likely calls into question the use of Tryptophan in complimentary/alternative medicine to boost serotonin in order to treat depression and other disorders presumed to involve low serotonin.

The true picture appears more complex (which seems to be the way it goes in the evolution of medical theory – especially in popular approaches of natural medicine) where multiple types of serotonin neurons are likely to be regulated in independent ways.

Jerry Kennard of Health Central reports Lowry as thinking it

 far more likely that there are subgroups of serotonin neurons that are overactive during depression, rather than under-active as many people have assumed. The piecing together of evidence started over three years ago when researchers at the Baker Heart Institute in Australia discovered up to four times the normal level of serotonin in the brains of people panic disorder. In depressed people not receiving treatment it was two times higher. Another interesting finding was that long-term use of SSRIs in people with depression and panic disorder actually seems to decrease serotonin levels – although it isn’t clear why.       


In a PLOS Medicine essay,  Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature, Jeffrey Lacasse and Jonathan Leo, cover the demise of the serotonin theory and the failure of the latest anti-depressant drugs to live up the media hype.

In subsequent years, there were numerous attempts to identify reproducible neurochemical alterations in the nervous systems of patients diagnosed with depression. For instance, researchers compared levels of serotonin metabolites in the cerebrospinal fluid of clinically depressed suicidal patients to controls, but the primary literature is mixed and plagued with methodological difficulties such as very small sample sizes and uncontrolled confounding variables…  Attempts were also made to induce depression by depleting serotonin levels, but these experiments reaped no consistent results [9]. Likewise, researchers found that huge increases in brain serotonin, arrived at by administering high-dose L-tryptophan, were ineffective at relieving depression [10].

Contemporary neuroscience research has failed to confirm any serotonergic lesion in any mental disorder, and has in fact provided significant counterevidence to the explanation of a simple neurotransmitter deficiency. Modern neuroscience has instead shown that the brain is vastly complex and poorly understood [11]. While neuroscience is a rapidly advancing field, to propose that researchers can objectively identify a “chemical imbalance” at the molecular level is not compatible with the extant science. In fact, there is no scientifically established ideal “chemical balance” of serotonin, let alone an identifiable pathological imbalance. To equate the impressive recent achievements of neuroscience with support for the serotonin hypothesis is a mistake.

With direct proof of serotonin deficiency in any mental disorder lacking, the claimed efficacy of SSRIs is often cited as indirect support for the serotonin hypothesis. Yet, this ex juvantibus line of reasoning (i.e., reasoning “backwards” to make assumptions about disease causation based on the response of the disease to a treatment) is logically problematic—the fact that aspirin cures headaches does not prove that headaches are due to low levels of aspirin in the brain. Serotonin researchers from the US National Institute of Mental Health Laboratory of Clinical Science clearly state, “[T]he demonstrated efficacy of selective serotonin reuptake inhibitors…cannot be used as primary evidence for serotonergic dysfunction in the pathophysiology of these disorders” [12].

Reasoning backwards, from SSRI efficacy to presumed serotonin deficiency, is thus highly contested. The validity of this reasoning becomes even more unlikely when one considers recent studies that even call into question the very efficacy of the SSRIs. Irving Kirsch and colleagues, using the Freedom of Information Act, gained access to all clinical trials of antidepressants submitted to the Food and Drug Administration (FDA) by the pharmaceutical companies for medication approval. When the published and unpublished trials were pooled, the placebo duplicated about 80% of the antidepressant response [13]; 57% of these pharmaceutical company–funded trials failed to show a statistically significant difference between antidepressant and inert placebo [14]. A recent Cochrane review suggests that these results are inflated as compared to trials that use an active placebo [15]. This modest efficacy and extremely high rate of placebo response are not seen in the treatment of well-studied imbalances such as insulin deficiency, and casts doubt on the serotonin hypothesis.

Also problematic for the serotonin hypothesis is the growing body of research comparing SSRIs to interventions that do not target serotonin specifically. For instance, a Cochrane systematic review found no major difference in efficacy between SSRIs and tricyclic antidepressants [16]. In addition, in randomized controlled trials, buproprion [17] and reboxetine [18] were just as effective as the SSRIs in the treatment of depression, yet neither affects serotonin to any significant degree. St. John’s Wort [19] and placebo [20] have outperformed SSRIs in recent randomized controlled trials. Exercise was found to be as effective as the SSRI sertraline in a randomized controlled trial [21].

Thomas Martin LAc.


Effectiveness of Depression Drugs Questioned

The discussion and links in this post are not meant to discourage anyone from listening to their healthcare provider or from taking medical drugs where deemed necessary. It does however serve to show how complex the mind/body is, how being informed and how conscientiousness and self-reliance are important no matter what treatment approach is followed

As to the much lauded effect of the best-selling antidepressant drugs turning out to be very little more than the depression alleviating effect of an inert placebo pill see Sharon Begley’s excellent expose from Newsweek

 …let me show you the studies on PubMed. It seems I am not alone in having moral qualms about blowing the whistle on antidepressants. That first analysis, in 1998, examined 38 manufacturer-sponsored studies involving just over 3,000 depressed patients. The authors, psychology researchers Irving Kirsch and Guy Sapirstein of the University of Connecticut, saw—as everyone else had—that patients did improve, often substantially, on SSRIs, tricyclics, and even MAO inhibitors, a class of antidepressants that dates from the 1950s. This improvement, demonstrated in scores of clinical trials, is the basis for the ubiquitous claim that antidepressants work. But when Kirsch compared the improvement in patients taking the drugs with the improvement in those taking dummy pills—clinical trials typically compare an experimental drug with a placebo—he saw that the difference was minuscule. Patients on a placebo improved about 75 percent as much as those on drugs. Put another way, three quarters of the benefit from antidepressants seems to be a placebo effect. “We wondered, what’s going on?” recalls Kirsch, who is now at the University of Hull in England. “These are supposed to be wonder drugs and have huge effects.”

The study’s impact? The number of Americans taking antidepressants doubled in a decade, from 13.3 million in 1996 to 27 million in 2005.

For more on this subject see my post here –


See also Harriet Fraad’s article in The Guardian

So-called miracle drugs like Prozac are taken by 11% of the population – and Prozac is only one of the 30 available antidepressants on the market. …

Anti-psychotics drugs alone net the pharmaceutical industry at least $14.6bn dollars a year. Psycho-pharmaceuticals are the most profitable sector of the industry, which makes it one of the most profitable business sectors in the world. Americans are less than 5% of the world’s population, yet they consume 66% of the world’s psychological medications.

Do these psycho pharmaceuticals work to restore mental health? Actually, the evidence is overwhelming that they fail. Antidepressants, the most popular psycho-pharmaceuticals, work no better than placebos. They work 25% of the time and stop working when the user stops taking them. In addition, they may actually harm patients in the long run. They disrupt brain neurotransmitters and may usurp the brain’s organic soothing functions.

Until quite recently there used to be a fairly clear demarcation between reactive sadness and major depression that is sustained and apparently without cause – a distinction going back as far as the ancient Greeks. In past years however this distinction has been confused and normal sadness that most people experience from time to time has been increasingly medicalized into a treatable disorder and actively marketed as such.

Here Gordon Parker in the British Medical Journal, discusses this increasing medicalization of sadness.

Also on the over-diagnosis of depression from the Guardian


Andrew Weil’s Integrative approach to improving Mood

See Andrew Weil’s (who has experienced bouts of depression life-long) book Spontaneous Happiness on the wholistic approach to emotional wellbeing. Weil also recommends acupuncture, exercise and meditation for this mood condition.

Exercise Improves Depression

The following study demonstrated exercise to be  equal to Zoloft in improving depression in older adults at 4 months of intervention.


Thomas Martin LAc