Chemical Imbalance and Depression: Cause or Effect?
A couple of months ago, Dr. Jonathan Leo contacted me about an article he had published that asks a very important question on the relationship that we (including myself) have come to take for granted: chemical balance and depression.
The journal article is called, “The Media and the Chemical Imbalance Theory of Depression.” It is a follow up to another article published in an open source scientific journal (PLoS Medicine) about the serotonin theory of depression.
The following is an excerpt of my response to Dr. Leo about his article.
Dear Jonathan,
I’ve read your paper and find your premise intriguing. Even though I’ve been trained as a scientist and also have experienced depression as a patient, I can honestly say that I’ve never questioned the semantics used around depression, as your paper questions. (Before I continue, I’ll also declare a potential conflict of interest since I used to work in the pharma industry and currently provide consulting services to biopharma companies in the area of medical affairs.)
I’m saying this without citing any sources or references, but rather based on personal experience of having received both pharmacological agents and psychological (cognitive) intervention. While I do think there is some sort of a “chemical imbalance” that occurs in a condition such as depression, I don’t believe that serotonin alone (or even in conjunction with an array of neurotransmitters) can provide a simple enough answer to “cause” depression. …Thus your demand to distinguish between “causative” vs. “correlative” is extremely important to address.
I also believe that depression is not a chemical problem alone, nor is it a sociological problem alone (i.e. “lack of willpower” or “oversensitive individual”), but a complex condition that may very well include genetic predisposition, chemical pathways, sociological context, and a person’s emotional make-up (which obviously can hardly be adequately objectively quantified to be scientifically examined). It is unlike certain cancers where a genetic defect leading to lack of a tumor suppressor protein then leads an individual to develop a cancer.
One of the “benefits” of the unproven chemical imbalance hypothesis has been an encouragement of those to seek treatment who otherwise may never have sought help for depression. However, this also goes to the other extreme, to the point where doctors are too quick to prescribe an antidepressant because they wanted to see the next patient and make their per diem “patient quotas” and break even financially as practicing doctors. Hence the overprescribed society we live in today.
Dr. Leo is now working on a paper about ghost writing and has edited a book called, Rethinking ADHD
I’m interested to what you think about Dr. Leo’s research, and questioning the “chemical imbalance (causative) theory” of depression.
Originally published on February 2, 2008
Acomplia Linked to Depression and Anxiety Risk
Acomplia (rimonabant, manufactured by Sanofi-Aventis) is an anti-obesity drug that was supposed to be a big hit in the U.S. However, earlier this year, U.S. FDA decided not to approve the drug here in the states because the drug was found to increase suicidal thoughts and depression. Acomplia is, however, approved and available in Europe. This week, medical journal The Lancet published a review of clinical trials involving Acomplia to look at the safety and efficacy of this drug.
According to the review analysis (a meta analysis) of 4 past clinical trials involving a total of over 4100 patients, Acomplia did reduce more weight after 1 year of treatment than placebo. However, patients taking Acomplia were more than twice as likely as patients taking placebo to stop treatment because of depression. More anxiety was also seen in the Acomplia treatment group than in placebo. Even though patients with a history or risk of depressive mood were excluded from clinical trials, the observation that depression and anxiety still arose when Acomplia was taken suggests that the drug increases the risk of depression of anxiety. The study researchers suggest that doctors should monitor patients taking Acomplia for these serious psychiatric side effects. Also reported by Reuters.
The Lancet 2007; 370:1706-1713
DOI:10.1016/S0140-6736(07)61721-8Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials
Robin Christensen MSc a, Pernelle Kruse Kristensen BSc a b, Else Marie Bartels DSc c, Prof Henning Bliddal MD a and Prof Arne Astrup MD email address b Corresponding Author
Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant.
Methods
We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo.Findings
Patients given rimonabant had a 4·7 kg (95% CI 4·1–5·3 kg; p<0·0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1·4; p=0·0007; number needed to harm=25 individuals [95% CI 17–58]), and 1·4 times more serious adverse events (OR=1·4; p=0·03; number needed to harm=59 [27–830]). Patients given rimonabant were 2·5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2·5; p=0·01; number needed to harm=49 [19–316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3·0; p=0·03; number needed to harm=166 [47–3716]).Interpretation
Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events—ie, depressed mood disorders and anxiety—despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.Affiliations
a. The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Frederiksberg, Denmark
b. The Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark
c. Copenhagen University Library, Copenhagen, Denmark
Breast Cancer Drug in Bipolar Mania Suggests Novel Therapy Options
Reuters reported on a study by the National Institute of Mental Health that showed breast cancer drug tamoxifen may have an effect on the “manic” symptoms of bipolar disorder. The researchers used tamoxifen because of its effect on protein kinase C (PKC), an enzyme that has many effects on cells, including brain cells. PKC may be overactive in bipolar mania. The study was published in the September 2007 issue of the medical journal, Bipolar Disorders.
My major concern about this study is that it is extremely small: only 16 patients. These 16 patients were then given either tamoxifen or placebo for 3 weeks, and 10 out of the 16 patients had reduced mania symptoms compared with placebo. According to the study, effects were observable within 5 days. According to Reuters, tamoxifen is “too dangerous” of a drug for use in bipolar disorder, and this study is meant to encourage the search for bipolar disorder drugs that target PKC. One of the study investigators believes that targeting PKC may allow for faster effects of antimania drugs.
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