Long-term antidepressant use is tied to an increased risk of adverse outcomes, including cardiovascular disease (CVD), cerebrovascular disease (CV), coronary heart disease (CHD), and all-cause mortality, new research suggests.

Investigators drew on 10-year data from the UK Biobank on over 220,000 adults and compared the risk of developing adverse health outcomes among those taking antidepressants with the risk among those who were not taking antidepressants.

After adjusting for preexisting risk factors, they found that 10-year antidepressant use was associated with a twofold higher risk of CHD, an almost twofold higher risk of CVD as well as CVD mortality, a higher risk of CV, and more than double the risk of all-cause mortality.

On the other hand, at 10 years, antidepressant use was associated with a 23% lower risk of developing hypertension and a 32% lower risk of diabetes.

The main culprits were mirtazapine, venlafaxine, duloxetine, and trazodone, although selective serotonin reuptake inhibitors (SSRIs) were also tied to increased risk.

"Our message for clinicians is that prescribing of antidepressions in the long- term may not be harm-free [and] we hope that this study will help doctors and patients have more informed conversations when they weigh up the potential risks and benefits of treatments for depression," study investigator Narinder Bansal, MD, honorary research fellow, Centre for Academic Health and Centre for Academic Primary Care, University of Bristol, United Kingdom, said in a news release.

"Regardless of whether the drugs are the underlying cause of these problems, our findings emphasize the importance of proactive cardiovascular monitoring and prevention in patients who have depression and are on antidepressants, given that both have been associated with higher risks," she added.

The study was published online September 13 in the British Journal of Psychiatry Open.

Monitoring of CVD Risk "Critical"
Antidepressants are among the most widely prescribed drugs; 70 million prescriptions were dispensed in 2018 alone, representing a doubling of prescriptions for these agents in a decade, the investigators note. "This striking rise in prescribing is attributed to long-term treatment rather than an increased incidence of depression."

Most trials that have assessed antidepressant efficacy have been "poorly suited to examining adverse outcomes." One reason for this is that many of the trials are short-term studies. Since depression is "strongly associated" with CVD risk factors, "careful assessment of the long-term cardiometabolic effects of antidepressant treatment is critical."

Moreover, information about "a wide range of prospectively measured confounders...is needed to provide robust estimates of the risks associated with long-term antidepressant use," the authors note.

The researchers examined the association between antidepressant use and four cardiometabolic morbidity outcomes ― diabetes, hypertension,

CV, and CHD. In addition, they assessed two mortality outcomes ― CVD mortality and all-cause mortality. Participants were divided into cohorts on the basis of outcome of interest.

The dataset contains detailed information on socioeconomic status, demographics, anthropometric, behavioral, and biochemical risk factors, disability, and health status and is linked to datasets of primary care records and deaths.

The study included 222,121 participants whose data had been linked to primary care records during 2018 (median age of participants, 56–57 years). About half were women, and 96% were of White ethnicity.

Participants were excluded if they had been prescribed antidepressants ≤12 months before baseline, if they had previously been diagnosed for the outcome of interest, if they had been previously prescribed psychotropic drugs, if they used cardiometabolic drugs at baseline, or if they had undergone treatment with antidepressant polytherapy.

Potential confounders included age, gender, body mass index, waist/hip ratio, smoking and alcohol intake status, physical activity, parental history of outcome, biochemical and hematologic biomarkers, socioeconomic status, and long-term illness, disability, or infirmity.

Mechanism Unclear
By the end of the 5- and 10-year follow-up periods, an average of 8% and 6% of participants in each cohort, respectively, had been prescribed an antidepressant. SSRIs constituted the most commonly prescribed class (80% – 82%), and citalopram was the most commonly prescribed SSRI (46% – 47%). Mirtazapine was the most frequently prescribed non-SSRI antidepressant (44% – 46%).

At 5 years, any antidepressant use was associated with an increased risk for diabetes, CHD, and all-cause mortality, but the findings were attenuated after further adjustment for confounders. In fact, SSRIs were associated with a reduced risk of diabetes at 5 years (hazard ratio

---

, 0.64; 95% CI, 0.49 – 0.83).

At 10 years, SSRIs were associated with an increased risk of CV, CVD mortality, and all-cause mortality; non-SSRIs were associated with an increased risk of CHD, CVD, and all-cause mortality.

Antidepressant class Risk (95% CI)
SSRIs CV: 1.34 (1.02 – 1.77)
CVD mortality: 1.87 (1.38 – 2.53)
All-cause mortality: 1.73 (1.48 – 2.03)
Other antidepressants CHD: 1.99 (1.31 – 3.01)
CVD: 1.86 (1.10 – 3.15)
All-cause mortality: 2.20 (1.71 – 2.84)


On the other hand, SSRIs were associated with a decrease in risk of diabetes and hypertension at 10 years (HR, 0.68; 95% CI, 0.53 – .87; and HR, 0.77; 95% CI, 0.66 – 0.89, respectively).

"While we have taken into account a wide range of pre-existing risk factors for cardiovascular disease, including those that are linked to depression such as excess weight, smoking, and low physical activity, it is difficult to fully control for the effects of depression in this kind of study, partly because there is considerable variability in the recording of depression severity in primary care," said Bansal.

"This is important because many people taking antidepressants such as mirtazapine, venlafaxine, duloxetine and trazodone may have a more severe depression. This makes it difficult to fully separate the effects of the depression from the effects of medication," she added.

Further research "is needed to assess whether the associations we have seen are genuinely due to the drugs; and, if so, why this might be," she added.



Cite this: Long-term Antidepressant Use Tied to an Increase in CVD, Mortality Risk - Medscape - Oct 06, 2022.

Commenting for Medscape Medical News, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Canada, and head of the Mood Disorders Psychopharmacology Unit, discussed the strengths and weaknesses of the study.

The UK Biobank is a "well-described, well-phenotyped dataset of good quality," said McIntyre, chairperson and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study. Another strength is the "impressive number of variables the database contains, which enabled the authors to go much deeper into the topics."

A "significant limitation" is the confounding that is inherent to the disorder itself — "people with depression have a much higher intrinsic risk of CVD, CV, and cardiovascular mortality," McIntyre noted.

The researchers did not adjust for trauma or childhood maltreatment, "which are the biggest risk factors for both depression and CVD; and drug and alcohol misuse were also not accounted for."

Additionally, "to determine whether something is an association or potentially causative, it must satisfy the Bradford-Hill criteria," said McIntyre. "Since we're moving more toward using these big databases and because we depend on them to give us long-term perspectives, we would want to see coherent, compelling Bradford-Hill criteria regarding causation. If you don't have any, that's fine, too, but then it's important to make clear that there is no clear causative line, just an association."

link: https://www.medscape.com/viewarticle/981951#vp_3



I think the takeaway from this study is that these drugs are not innoucuous and should only be prescribed after careful evaluation, not some checklist in the office. The number of Americans taking these drugs is astronomical.

quote:

Originally posted by ZSMICHAEL:
The number of Americans taking these drugs is astronomical.

I am in no position to judge the validity of anyone's taking antidepressants, but whenever I see the numbers it does seem strange. How did people cope a century or more ago when, I would argue, there was a lot more in most people's lives to be depressed about?
(That's not a claim that people don't suffer from depression, but a question about coping without drugs.)

The current estimate is 13 percent of the population takes these drugs. The word is slowly getting out that SSRIs are not very effective either and that people experience withdrawal when they stop.

quote:

Originally posted by sigfreund:

quote:

Originally posted by ZSMICHAEL:
The number of Americans taking these drugs is astronomical.

I am in no position to judge the validity of anyone's taking antidepressants, but whenever I see the numbers it does seem strange. How did people cope a century or more ago when, I would argue, there was a lot more in most people's lives to be depressed about?
(That's not a claim that people don't suffer from depression, but a question about coping without drugs.)

The amount of suicidal/mental health calls I go on a week now equates to the amount I would go on in 6 months when I started this job 17 years ago.
However the amount of actual suicide calls I go on per year has not really changed.

quote:

The amount of suicidal/mental health calls I go on a week now equates to the amount I would go on in 6 months when I started this job 17 years ago.
However the amount of actual suicide calls I go on per year has not really changed.

^^^^^^^^^^^^
Could you clarify? Are you speaking of completed suicides has remained steady?

quote:

Originally posted by sigfreund:

quote:

Originally posted by ZSMICHAEL:
The number of Americans taking these drugs is astronomical.

I am in no position to judge the validity of anyone's taking antidepressants, but whenever I see the numbers it does seem strange. How did people cope a century or more ago when, I would argue, there was a lot more in most people's lives to be depressed about?
(That's not a claim that people don't suffer from depression, but a question about coping without drugs.)

I would offer that many men spent more time drinking and beating their wives, children, and girlfriends to relieve their depression. Acting out was less spoken about or acknowledged. Also religion was often seen as a refuge for victims

quote:

Originally posted by Black92LX:
The amount of suicidal/mental health calls I go on a week now equates to the amount I would go on in 6 months when I started this job 17 years ago.
However the amount of actual suicide calls I go on per year has not really changed.

My last exposure is 15 years old, but I would say it is consistent with my experience starting in early 80s

As time went on and it became more acceptable to call for help, the number of calls went up. This resulted in more folks entering the system and lead to more people being on medication. I should add that many folks on anti-depressants don't want to be and many of our calls were the result of stopping their meds and and then acting out.

Over the years, I'd actually seen the number of actual attempted suicide calls go down as folks found other ways to call attention to themselves

I'm glad that you posted this. I had a recent visit with a new neurologist, who prescribed Cymbalta (duloxetine) for the nerve pain in my feet due to Guillain Barré.

She said that this med had dual uses: nerve pain, and anti-depressant.

I have not started taking it yet, and after reading this article, I think that I'll forego it.

quote:

Originally posted by ZSMICHAEL:
The current estimate is 13 percent of the population takes these drugs. The word is slowly getting out that SSRIs are not very effective either and that people experience withdrawal when they stop.

What realistic alternatives would you suggest for these folks?

A thorough evaluation to properly diagnose. Thyroid problems are one possibiity. Effective psychotherpy, whether it is CBT, interpersonal psychotherapy etc. has been around since the 1940s. I am not speaking of psychoanalysis but problem oriented therapy. Insurance typically will cover with a small copay. No CV risk there.
People forget that the first SSRI, Prozac did not come on the market until 1987.

Benzos aka Valium came earlier in 1963 and half of the American housewives were taking it. The Stones called it "Mother'little helper." It has dropped in popularity due to its addictive nature.

quote:

Originally posted by ZSMICHAEL:

quote:

The amount of suicidal/mental health calls I go on a week now equates to the amount I would go on in 6 months when I started this job 17 years ago.
However the amount of actual suicide calls I go on per year has not really changed.

^^^^^^^^^^^^
Could you clarify? Are you speaking of completed suicides has remained steady?

That is correct. However, there may be a caveat as I go to so many more overdose deaths than I used to, that without a note there is no telling whether it was intentional or not. So a number of these overdoses actually could be suicides but are not chalked up as that because there was no note left.

quote:

Originally posted by 9mmepiphany:

quote:

Originally posted by sigfreund:

quote:

Originally posted by ZSMICHAEL:
The number of Americans taking these drugs is astronomical.

I am in no position to judge the validity of anyone's taking antidepressants, but whenever I see the numbers it does seem strange. How did people cope a century or more ago when, I would argue, there was a lot more in most people's lives to be depressed about?
(That's not a claim that people don't suffer from depression, but a question about coping without drugs.)

I would offer that many men spent more time drinking and beating their wives, children, and girlfriends to relieve their depression. Acting out was less spoken about or acknowledged. Also religion was often seen as a refuge for victims

I’d argue that the number for all of those is up as well. There is certainly no shortage there. I’d also add that far more females are beating their men now than before as well. Not to mention the same sex partners.

I have my thoughts and theories on most of these things after being involved in the aftermath of many of these day in and day out. Not to mention the same places and people day in and day out.


I worry about this very much as it is in no way going to get any better anytime soon.

quote:

I worry about this very much as it is in no way going to get any better anytime soon.

^^^^^^^^^^^^^^^^
Thanks for the reply. Once someone has tried to kill themselves the chances of another attempt increase. Women try more than men but are less successful primarily due to the method chosen.

Providing acessible effective psychotherapy would help. Giving a vet with PTSD some pills and telling him to return in three months is not treatment.

quote:

Originally posted by ZSMICHAEL:
Providing acessible effective psychotherapy would help. Giving a vet with PTSD some pills and telling him to return in three months is not treatment.

Lots of money in prescribing these pills and it's a easy and lazy thing to do and most people will quickly accept that the answer is in the pill. Spend ten minutes in front of a tv and count the number of commercials for drugs you see. Than listen to the number and kind of side effects they have to disclose about them. Here's a happy pill for you're depression. Then the very next commercial is Oh, you are now having involuntary body movements from taking that pill here's a pill that will stop that. And so on and so on. The Marlboro man had nothing on these guys.

God I hate the bastardization of my native tongue.

The mortality rate for all known life forms is 100%.

quote:

Originally posted by ZSMICHAEL:
The word is slowly getting out that SSRIs are not very effective either and that people experience withdrawal when they stop.

I'm sure I've told this story, here, before: One of my prior docs, to address what she felt to be a mild case of depression, gave me a "starter pack" for one-or-another antidepressant. Upon day two or three I experienced a very odd, very disquieting visual anomaly. The next morning it happened, again, only worse. (Temporary tunnel vision.)

I did some research on the drug. (ISTR it was an SSRI.) This was not an uncommon initial side-effect, but, it was written, usually goes away. In the process I found you couldn't just stop taking these things. That it could take months to wean yourself off of them.

Called the doc and told her no way was I going to take this drug.

(I solved my problem on my own. First with St. John's Wort. Ultimately with regular exercise and a little introspection.)

I think that was my first clue that I should question everything my doctor told me--and be particularly wary of any pharmaceutical they wanted to prescribe.

One of my wife's friends became depressed after her husband passed away. Eventually her doctor put her on an antidepressant. She's still depressed and her health began declining precipitously after she started taking that stuff. My wife's been trying to tell her that stuff is killing her. But her doctor says she should take it, so...

quote:

She's still depressed and her health began declining precipitously after she started taking that stuff. My wife's been trying to tell her that stuff is killing her. But her doctor says she should take it, so...

^^^^^^^^^^^^^^^^^^^
Sad. I have heard this many times. Just saw a TV ad this morning for Rexulti. If your SSRI is not working take this drug to add to your progress. It does quickly mention it can cause Tardive Dyskenisia a permanent disabling neurological condition. Of course there is now a drug for TD as they like to call it.

Perhaps I could find it myself, but is there a difference between antidepressants and antianxiety drugs like Lexapro?
(I can’t follow all the abbreviations that are used in describing certain medications.)

quote:

Originally posted by ZSMICHAEL:
Sad. I have heard this many times. Just saw a TV ad this morning for Rexulti. If your SSRI is not working take this drug to add to your progress. It does quickly mention it can cause Tardive Dyskenisia a permanent disabling neurological condition. Of course there is now a drug for TD as they like to call it.

This is exactly what's happening to my wife's friend.

Doc put her on the anti-depressant. There were side-effects. Doc put her on another med to combat those. That drug induced new side-effects. Yup: Yet Another Drug.

All the while her health's continued to decline and she's remained depressed.

My mother, whose only health issue I recall was arthritis, and she was seriously overweight--so likely high BP and cholesterol, as well (?), ended-up on a whole pharmacy's worth of prescriptions. She kept 'em on the bottom shelf of a kitchen cabinet. When over there, one day, I opened said cabinet, went "Geez, mom, what the hell's all this?!?!" "Well," she explained, "this one is for <this>. This one is to counteract the side-effects of <that>. This other one is to counteract..." and so-on and so-on.

"Ma, there's something wrong with this picture." But, like my wife's friend, she was "The doctor says..."

With the introduction of Taurine to my supplements I'm now on zero prescription meds. Just the way I like it.