August 24, 2009

Antidepressants NOT Depression Associated with Obesity

There is a major contributor to the so-called "obesity epidemic" which never gets cited in the press--the antidepressant drugs which are the most frequently prescribed class of drugs in the pharmacopoeia.

Now a study that analyzes data from the Canadian National Population Health Survey (NPHS), a longitudinal study of a representative cohort of household residents in Canada, finds a strong correlation between the use of SSRIs, Effexor, and the development obesity. Lest you think that this is because depression makes people fat, this same study found no correlation between a history of a major depressive episode and the development of obesity.

It's the drugs, folks.

Here's the study:

Major Depression, Antidepressant Medication and the Risk of Obesity
Scott B. Patten et al. Psychother Psychosom 2009;78:182-186 (DOI: 10.1159/000209349) Vol. 78, No. 3, 2009

How widespread use of these antidepressant drugs is, is very hard to pin down. Anecdotally, it sometimes seems like everyone who has good health insurance is on them.

A report published in 2005 that analyzed Canadian data reported that " in five women (19%) in the province over the age of thirty received at least one prescription for SSRIs in the period between August 1, 2002 and July 30, 2003."

Canada's public health system controls access to prescriptions in the way the US system does not. The data for the US is 7 years old and at that time the CDC reported that 1 in 10 American Women were taking antidepressants which were the single most highly prescribed class of drugs in the US. That 2002 report also reported that antidepressant use had tripled over the previous decade, which makes it likely that antidepressant use has risen significantly in the 7 years since those statistics were analyzed.

The Canadian report also points out that
Prior to the introduction of SSRIs, depression was considered to affect only 100 people per million. Since the introduction of SSRIs, prevalence rates for depression are now considered to be in the range of 50,000 to 100,000 cases per million (a 500 to 1,000 fold increase).
One reason for this huge spike in prescriptions is, of course, the heavy marketing by pharmaceutical companies of these drugs--especially to family doctors not trained in psychiatry who are the doctors most likely to prescribe them.

It has long been known to psychiatrists that fully 1/3 of all people who experience episodes of depression recover naturally without any treatment. This is close to the rate of recovery experienced with the antidepressant drugs, however, the drug companies suppressed publication of the studies that would have made it evident that their drugs were often not any more effective than placebo.

You can read one study documenting the impact of drug company suppression of unfavorable research evidence HERE.

In addition, drug marketers deceptively promoted the factoid that that repeated episodes of depression are likely to lead to a form of permanent brain damage resulting in permanent depression. This is a twisted rendering of data that applies only to extremely severe depression of the kind that results in people being institutionalized because they cannot function at all. That kind of depression does not result from negative life experiences but appears to be a brain syndrome like schizophrenia. It is a very different kind of psychiatric condition from the bouts of sadness most people experience at some point of their lives when they suffer a serious loss or find themselves trapped in a situation, like a bad marriage or dead end career.

But this idea that one depressive episode, if not treated, will condemn a person to a life of worsening depression, has been used to scare family doctors into treating the normal periods of sadness characteristic of young people, who are facing the emotional challenges of growing up, as if they were medical emergencies.

People experiencing the normal struggles of adolescence and young adulthood are told that if they don't take the antidepressant drugs they'll end up permanently depressed. When they start feeling better after a month or two on the drugs--as they would without drugs--they are convinced that the drug saved them and are terrified to stop taking it.

Anyone who went through adolescence in the pre-antidepressant days knows it is not true that the periods of depression so common in early life invariably turn into severe psychiatric disease. Most of us grew out of the miseries of adolescence and have normal happy lives no matter how miserable we were when we broke up with our first serious boyfriend.

For many of us, depression was a signal that we needed to get help to learn why we made bad choices or to take the steps needed to get ourselves out of the dead end situations we had become trapped in. Sometimes therapists were helpful in giving us tools that made it possible to do this. Medicating the bad feelings away may prevented us taking those steps or making those changes which improved our lives and eliminated the causes of our depression.

But for the past decade any teen (or adult woman, for that matter) who experiences overwhelming sadness after breaking up with a boyfriend--or after failing to find an exciting career after earning a college degree in English--is very likely to be put on a powerful, mind altering SSRI drug that numbs their emotions--a drug, moreover, that can be extremely hard to stop since it causes withdrawal symptoms. Any teen with insurance, that is, since these drugs can be very costly.

And once people are, essentially, addicted to these mind-altering drugs, they do what all people who are dependent on mood-altering drugs do--defend their need to take the drugs very strongly and often with anger at any one who would take them away from them.

Because people who take these drugs have not learned that depression can be healed without drugs, and have not been taught the psychologically proven strategies that could help them cope with depressive episodes on their own, they are very frightened of what would happen if they stopped the drugs. Since the withdrawal symptoms when they do stop the drugs can be extremely unpleasant and long lasting, they may interpret this as proof that they need these drugs.

The common analogy--promoted heavily by the drug merchants, is that people with depression need SSRIs the way people with diabetes need insulin. This makes it sound like these drugs supply some essential, missing hormone.

In fact, this is completely untrue. The drugs don't supplement serotonin. It is not even clear if they actually raise serotonin levels long term. As the Canadian report point out, "there have been no studies that assess the effects of blocking serotonin over months or years. Most of the forty-two clinical trials for Prozac, Paxil, Zoloft, Celexa, Serzone and Effexor lasted only six weeks." Studies of other impacts of altering Serotonin levels in the gut suggest that long term use of SSRIs may actually lower Serotonin levels.

Some recent research suggests that these drugs actually work by remodeling the neurons in the hippocampus.You can read about what SSRIs really turn out to do, long term HERE.

Other drugs that affect Serotonin levels include Ritalin, Cocaine and Ecstasy. We know these drugs are addicting, but somehow the drug companies have been able to convince doctors that their mood-altering drugs are "habit forming" but not "addicting" though doctors also warn patients that it is dangerous to suddenly stop these drugs,just as it is with addicting drugs.

What all makes this relevant to diabetes is this: There has always been evidence that the SSRI drugs make people gain weight. Now this latest analysis of the Canadian health survey data makes it clear that the weight gain is almost certainly a side effect of the drugs, not of the depression that might have led to the prescription of the drug.

Obesity raises insulin resistance even in people with normal genes. For those of us who have the genes that lead to diabetes--genes that mean that even when we are thin our beta cells are barely keeping up with our insulin needs--the increase in insulin resistance obesity can push us into full fledged diabetes and by the time that diabetes is diagnosed, the high blood sugars we have lived with for years may have killed off so many of our beta cells we don't have a chance of regaining a normal blood sugar metabolism through weight loss.

Indeed, it is not irrational to wonder if the fact that these drugs are the single most frequently prescribed class of drugs in the US may have something to do with the development of the so-called "Obesity epidemic." SSRIs began to be prescribed in the late 80s. The "obesity epidemic" started catching the public's attention a decade later.

Yes, there are many other contributing factors to the obesity epidemic, including a huge growth in portion size. But when you mess with the brain chemistry involved in the pleasure response, one of the things you also do is mess with the in-built brain mechanisms that control satiety--the feeling that you've eaten enough.

A person with an intact brain satiety function is not likely to be able to eat a whole 10.5 ounce cinnamon roll at once. If they do, they will experience unpleasant emotional responses that are the body's way of teaching them that this is NOT something they should do again. Block those emotions, and they will do it again.

If you have become inadvertently addicted to mood altering drugs and believe that they are contributing to your weight problem and worsening your blood sugar control, you will probably need some help to get off them. A therapist who can help you deal with the emotions you will feel when you stop anesthetizing your feelings can be essential. A doctor who knows how to help you deal with the withdrawal symptoms in a way that does not involve putting you on another addictive drug is also essential.

Unfortunately, doctors have been prescribing antidepressants to pregnant women for the past decade too, which may have something to do with the concomitant epidemic of toddler obesity. How is it possible doctors have not considered the long term physiological consequences of exposing fetuses to a drug that remodels the neurons in their brain that control essential brain structures, while the brain is forming?

One reason is that few doctors have the time to read the research about the drugs they prescribe and so they don't understand what SSRIs really do, since they get all their information about these drugs from the drug company reps and the "education" the drug companies sponsor.

But thinking people cannot help but realize that thanks to aggressive drug company marketing a huge sector of the population--much of it young and female--and their babies--have been the subject of a decades long experiment to find out what it is that these drugs really do. The signal that is emerging out of the the very small amount of research NOT funded by the makers of these powerful, profitable drugs, is that they make people obese.

Note: In the comments that respond to this post, I'm asking you to limit your comments to discussion of the relationship between antidepressants, obesity and diabetes and the research connecting these topics. I am not going to make public the fervid and often hostile personal testimonials that are always provoked by any attempt to discuss the research that examines the true impact of these drugs. So don't waste your energy or mine posting them here.


Anonymous said...

Jenny, I really appreciate all of the research you do WRT SSRIs. I was not insulin resistant or at all overweight until I began taking them (I was, however, prone to hypoglycemia, so I suspect the genetic component was always there). I'm hoping the day will come soon when I can taper off - something I've done before, which always leads to me becoming 20 pounds lighter. Unfortunately, it also leads to me being prone to panic attacks, hence the drugs.

Courtney Ostaff said...

I think you could have a point about the link between SSRIs and obesity, although I think your link of "sedating emotions" and feedback from overeating is reaching a bit.

Note, also, that the authors of the study say that there "may" be a linkage between obesity and SSRIs, not that that SSRIs definitely cause weight gain.

However, I think that your vitriol of those who take SSRIs for depression risks alienating the very people who could benefit from your message.

In addition, I think that you either forget or do not realize that the SSRI alternatives -- MAOIs, TCAs, and benzodiazepines -- have serious side effects, such as easily fatal overdosing and serious drug interactions, not to mention major side effects.

If you were a medical professional, and you had a patient whose "depression significantly impairs his/her day-to-day functioning" and who may or may not be suicidal, which would you choose?

Even if an SSRI made your hypothetical patient gain weight, that would hardly outweigh the benefits of a medicine that has few to no drug interactions, that the patient can't suicide on, and has some flexibility in daily timing.

Further, I don't see what is so bad about changing behavior through growth of new neural pathways. That is, after all, what cognitive-behavioral therapy is based on, albeit with talk therapy rather than drugs. Unfortunately, talk therapy takes time to establish patient trust, something that is particularly difficult for depressed/anxious patients to do.

As for people not realizing that SSRIs work through neurogenesis, it's not exactly a secret. It's been noted in popular literature for nearly a decade. For example, the front page Discover article in June 2001:

water said...

DH seemed depressed.He was not interested in meds. He quit eating gluten. Major mood improvement, and borderline blood sugars are gone. I wonder if some of this depression is caused by gluten intolerance. Dring his gluten challenge, he quit dreaming. After he went GF, the dreams came back. Dreams and serotonin are connected. Gluten and serotonin can be connected through malnutrition:

"Malabsorption of important nutrients such as folic acid, vitamin B6 and amino acids, especially tryptophan, may lead to disturbances in CNS serotonin function associated with major depressive disorder and aggressive behavior."

Anna said...

SSRI samples are handed out like water in my healthcare network, especially if you are a woman entering middle age. But you can't get the thyroid hormones you really do need.

I took SSRI samples home twice after Primary Care Physician visits but couldn't bring myself to take them after I looked them up in the PDR. I just didn't think they were going to address the real issue - low thyroid function. I couldn't take something I didn't think would address the underlying issue and I sure as heck wasn't going to take something with strong withdrawal symptoms as an experiment. I'm not saying SSRSs aren't necessary for some people, but in my experience, the primary care docs too often use SSRIs like bandaids for conditions that are better treated in other ways.

I persisted and finally found better care for the hypothyroidism outside the HMO network. I never regretted tossing the SSRI samples in the trash.

ItsTheWooo said...

Jenny, you don't think it is possible that the increased prevalence of depression, like the increased prevalence of obesity and diabetes, are common symptoms of the same/similar underlying metabolic disturbance?

Your evidence suggests that it is only psychiatric drugs which increase the risk of obesity. I can also cite evidence which suggests that diabetes greatly increases the risk of depression and this has no relationship to either life circumstances (e.g. reacting to being diabetic) or drug use.

I am not using psychiatric drugs, however I do have recurrent type depressions of some sort, and I just intuitively KNOW that this is yet another symptom of my metabolic problems. My depressions have nothing to do with my life, I have been exorbitantly happy and miserably depressed when circumstances are rather static. Another reason I know my depressions are somehow related to my metabolic problem is the fact that my mother is also quite obese and has recurrent type depressions.
I have PCOS, and the rate of depression in PCOS so high that it is considered a diagnostic symptom. Even when the psychosocial effects of PCOS are taken into account, depression tendency is still elevated.

Think about this reasonably. Consider that the physiological systems which regulates energy use (mitochondria/insulin/blood sugar) is almost invariably discovered linked to systems which regulates mood. You would agree that the latter are more commonly damaged today... well then wouldn't the later possibly be affected?

The relationship between increased risk of diabetes with increased risk of depression is not limited to depression.
It is also shown that more severe psychiatric illnesses like schizophrenia and bipolar disorder are related to glucose metabolism/metabolic defects. Schizophrenics often show metabolic disturbance before they are put on drugs, for example. With bipolar disorder there is heaps of information regarding the etiology of defective/unstable brain energy production (similar to seizures). This causes psychiatric illness in the brain and diabetes/obesity in the body.

There are so many physiological mechanisms by which metabolic disease can cause psychiatric complications.

I mean, take inositol. Inositol is a b-vitamin, often deficient in hyperinsulinemics (diabetic type 2 and the obese). Inositol is necessary to make insulin receptors work, and it is also necessary to make serotonin receptors work. If you have chronic hyperinsulinemia, you will deplete inositol, you will worsen hyperinsulinemia and tend toward depression.

This is just ONE mechanism. There are many others, such as the hypocretin system (suppressed by cerebral hypoglycemia, this is responsible for keeping your brain "lit up", excited, interested), BDNF (suppressed by cerebral hypoglycemia as well), and numerous others I don't yet know of (and/or scientific understanding has yet to discover).

Anyway, I really think you need to reconsider your perspective on the relationship between depressive/psychiatric illnesses and metabolic disorders. As someone with this chronic problem, as well as metabolic issues, I feel they are both symptoms... and I am definitely sure that the increased rates in depression are a real phenomenon, just like the increase in obesity/diabetes. Just because you can't see depression when you look at a person doesn't mean it isn't there. No, not everyone with metabolic problems will get depression... but then, not everyone will get diabetes either. I don't have diabetes, but I do have hx/of severe obesity reactive hypoglycemia and PCOS (so I do have metabolic problems, just not the same sort as you).

Jenny said...

There is a growing body of research--the study cited in this post is only one--that show that depression does not correlate with diabetes when you take the depression drugs out of the equation.

These studies show that people with diabetes are no more likely to be depressed than any one else.

In your case, with PCOS you have a hormonal disturbance. Hormonal disturbances are known to cause strong mood changes. I am not convinced by the data that SSRIs are truly effective for this kind of mental problem.

Metformin and low carb drop testosterone levels, sometimes dramatically, and that will impact mood. There are other drugs that can impact on hormone levels too. And of course, people prone to hormonal issues need to be careful about hormone exposures and analyze where they may be increasing their hormone exposure.

Even flax oil can trigger depression in people sensitive to some female hormones. Removing it from the diet removes the problem.
Birth control pills are another huge problem for people with hormone sensitivity. Fortunately there are effective alternatives to them.

I agree it is very possible that the rise in hormone disrupters in our environment is causing some rise in depressive symptoms. But I question whether SSRIs are the best treatment for women's hormonal problems. Especially when they lead to sexual dysfunction and weight gain. There must be better treatments than mental numbing.

And the fact--and this is a fact, that the data does NOT show SSRIs to be more effective than cognitive (talk) therapy--something many people are not aware of--suggests to me that what is being treated with these drugs is not a physiological condition but more likely a response to the fragmented isolating quality of modern life.

Twittering is not the same as talking to someone, face to face, and too many people are spending too much time with the illusion of communication--via electronic devices, instead of in real full-fledged human interaction.

Anonymous said...

It's the dopamine IMO.

Used to be that TCA antidepressants hit all three relevant neurotransmitters (serotonin, norepinephrine and dopamine) to some degree, but they also hit histamine and cholinergic systems hence the side effects.

Paxil was most closely targetted on serotonin and most likely to produce weight gain. Prozac had more dopaminergic effect, Effexor more again, and Wellbutrin principally affected dopamine and norepinphrine with minimal serotonergic effect: these drugs were less likely to produce weight gain, and Wellbutrin often produced weight loss (I haven't kept up to fit newer drugs into this continuum)

A common happening is that SSRIs "poop out" over time (happened to me) due to long term dopamine reduction.

Paxil gave me hellish carb cravings. The weight gain went away on switching to Effexor (part of it was retained water, I was pissing three times as much as I drank for a few weeks)

IME there are a lot of interconnections between the endocrine system and neurotransmitters, getting a handle on my BG and insulin levels hugely improved the depression, which in my case was "Atypical" - physical symptoms not unrelated to hibernation, I'm currently on 1/6 the original venlafaxine dose with far fewer symptoms (vitamin D may also be implicated) and waiting to see if the decreasing daylength sets off SAD.

This all fits together in an evolutionary sense, a system designed to make us stuff our faces with carbs and then shut down for several months and live off the stored fat might have had an evolutionary advantage once, but factors in the modern world turn this system on permanently and leave it on.

Jenny said...

I have certainly noticed that Vitamin D (1000 IU a day) has a noticeable impact on my mood and that if I stop taking it in winter I feel a lot droopier.

I hestitate to recommend it for that use, because I have such strong and often idosyncratic responses to hormones, so I don't know how widespread that response is in others.

It's a harmless supplement and relatively cheap, and has other benefits for people with diabetes so it's well worth a try.

Some doctors recommend 2000 IU or even more. If you can get your levels checked, it can help you know how much you need.

Anonymous said...

It's yet another thing which seems to be in chronic shortage. Incredibly in Canada you are not permitted to get vitamin D levels checked. Elsewhere these guys do a mail-order test

ItsTheWooo said...

Yes trinkwasser I would agree - symptoms like hibernation (atypical depression) do make sense as being related to a metabolic disorder. I am also certain the increase in depression is a real phenomenon and it is related to the increase in obesity/diabetes. It is metabolic. Like you, my depression gets much better when I control my insulin.

Dopamine suppression is exactly why these serotonergic drugs make us fat. Dopamine is principally involved in:
1) fatty acid oxidation (if impaired this causes compensatory insulin resistance and weight gain)
2) suppressing insulin output from pancreas
3) suppressing appetite directly
4) spontaneous motor activity, energy production, motivation
5) altering thyroid hormone status (serotonin and dopamine exist on an axis; elevated serotonin tends to cause hypothyroid and suppresses TSH).

This is why SSRI drugs have the same/similar side effect profile of NEUROLEPTICS (antipsychotic drugs, dopamine blocking agents) and ANTIEMETICS (also tend to block dopamine).
From an SSRI you certainly can have the parkinsonian symptoms and tardive diskinesia even which is classically associated with antipsychotic (hard/direct dopamine blockers). Increased serotonin means blocked dopamine.

Fatigue and lack of motivation and sexual incompetence so common with serotonin drugs are mostly related to dopamine not working right.
Metabolic symptoms are also related to this as well. Serotonin ordinarily promotes glucose uptake and appetite suppression, but SSRIs mess up dopamine like antipsychotics and so has a similar effect on weight/energy/motivation/etc

Anonymous said...

Excellent points all! There used to be a fashion for adding Wellbutrin to Paxil as they worked synergystically and removed each other's side effects.

When I asked about this my GP recoiled with horror and told me dopaminergic drugs were illegal for a reason (at the time Wellbutrin was included but it is now available here as Zyban purely for smoking cessation).

I'm half convinced if amphetamine suplhate was available on the NHS I wouldn't be here now! I tried it once back in my hippy days and it made me feel so normal it was scary. It made me calm and relaxed and actually improved my sleep once the initial "rush" wore off, a typical ADD response. Would have been interesting to see what effect it had on my BG.

I was afraid of getting hooked and only ever tried it once more, with exactly the same results. My current combination of low dose venlafaxine, caffeine and nicotine causes a mere shadow of the effects. With strict BG and insulin control and currently vitamin D and a lot of saturated and Omega 3 fats I'm a lot nearer to functional both mentally and physically. The interractions are fiendish.

WRT depression, some research showed that while no one drug achieved significant improvements in more than 60% of subjects, over all meds and combinations something like 85% of patients showed improvement (if you threw in thyroid meds that would probably improve further). SSRIs were shown to be useful for many people short term but only a few long term, probably due to the dopamine downregulation.

Probably as with diabetes the best plan is to learn and avoid the stressors which express the genes, some of which may not appear to be related, like dietary/BG factors.