Many Unforeseen Drug-drug Interactions Possible By Following Clinical Guidelines


If doctors follow UK government guidelines, they may well seriously endanger patients who have both depression and any of a variety of other common diseases or conditions such as diabetes or hypertension, according to a study in BMJ. The problem, wrote the researchers, is that polypharmacy and drug-drug interactions are not accounted for in any of the guidelines.

A Scottish-led team of researchers examined UK government guidelines for the treatment of depression, diabetes, and heart failure, and the guidelines for the treatment of a variety of other diseases or conditions that people with any of those three conditions might also have. With respect to depression and accompanying conditions, they found 89 possible dangerous drug-drug interactions that the patients might experience.

“Despite widespread multimorbidity, clinical guidelines are largely written as though patients have a single condition and the cumulative impact of treatment recommendations from multiple clinical guidelines is not generally considered,” wrote the researchers. “In people with several conditions, simply application of recommendations from multiple single disease clinical guidelines can result in complex multiple drug regimens (polypharmacy) with the potential for implicitly harmful combinations of drugs.”

In the case of people taking drugs for depression who might also be taking recommended drugs for arthritis, pain, or other common ailments, possible side effects from the drug-drug interactions included cardiovascular problems, internal bleeding, kidney failure and central nervous system toxicity.

“One of the challenges for guideline developers is that the actual harms of many drug-drug and drug-disease interactions are poorly quantified, partly reflecting that whereas clinical trials produce high quality evidence about benefit, they are poorly suited to estimating harms, particularly in real world populations in which people are typically older, frailer, have more multiple illnesses and prescribed more drugs for other conditions than trial populations,” the authors concluded. “Research is needed to more systematically quantify these harms because understanding when harms outweigh benefits is critical for rational treatment decisions(.)”

Dumbreck, Siobhan, Angela Flynn, Moray Nairn, Martin Wilson, Shaun Treweek, Stewart W. Mercer, Phil Alderson, Alex Thompson, Katherine Payne, and Bruce Guthrie. “Drug-Disease and Drug-Drug Interactions: Systematic Examination of Recommendations in 12 UK National Clinical Guidelines.” BMJ 350 (March 11, 2015): h949. doi:10.1136/bmj.h949. (Full text)


  1. “Many Unforeseen Drug-drug Interactions Possible By Following Clinical Guidelines” is very true. And when one looks at the gold standard treatment for bipolar – combining mood stabilizers (like lithium) with antipsychotics / neuroleptics (like Seroquel) – one finds this:

    “GENERALLY AVOID: There is some concern that quetiapine may have additive cardiovascular effects in combination with other drugs that are known to prolong the QT interval of the electrocardiogram. In clinical trials, quetiapine was not associated with a persistent increase in QT intervals, and there was no statistically significant difference between quetiapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters including QT, QTc, and PR intervals. However, QT prolongation and torsade de pointes have been reported during postmarketing use in cases of quetiapine overdose and in patients with risk factors such as underlying illness or concomitant use of drugs known to cause electrolyte imbalance or increase QT interval. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

    And the antipsychotics can and do cause psychosis, especially when used in combination:

    “neuroleptics … may result in … the anticholinergic intoxication syndrome … Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.

    None of my psychiatrists seemed aware of this, so I do think it’s important all people be made aware of the fact that the antipsychotics, the gold standard of care for schizophrenia, are absolutely known to cause the schizophrenia symptoms.

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  2. Most likely one more reason why those labeled “seriously mentally ill” are dying 25 years before their peers.

    Most psychiatrists seem to practice without application of their knowledge of general medicine. And it sounds like their leaders support them in doing so, even when it’s killing off their clients.

    —- Steve

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  3. Here in the U.S., it reminds me of many years ago when I was abusing dramamine to try to deal with movement disorders, and wound up in the hospital because I could hardly move and my breathing was shallow. The first thing they put me on was benadryl, followed by haldol — one of the drugs that caused my movement disorders years earlier. Of course dramamine and benadryl are the EXACT same drugs, it’s just the way they are made that makes benadryl more potent. It’s the difference between a drug name ending in (diphen)hydrinate and one in (diphen)hydramine. So they gave me a drug I was already overdosing on, and in a more potent form. Not surprisingly, I had become delirious shortly after. I don’t go to hospitals anymore, unless I’m bleeding to death…

    When I was in the hospital for a Ulcerative Colitis flare-up recently, I struggled to get out without having to leave AMA, as just about everything they were doing was making me worse. They put me on corticosteroids to treat the inflammation, while putting me on antibiotics to treat a cdif infection, AT THE SAME TIME! Here I was, just some guy with the internet on his phone, telling them they’re supposed to treat the cdif infection FIRST, or otherwise ignore it until after the inflammation is down. Bah, just another dumb stupid patient who wont shut up, after all, they went to medical school… and how pathetic they are. Might as well be on welfare, at least then they wouldn’t be killing people. To make matters even WORSE, almost everything they allowed me to eat or drink had either carrageegan in it or were vegetables, those two things being what caused my flare-up in the first place.

    Needless to say, I wont go to the hospital ever again, for anything. I have no respect for doctors anymore, in any specialty. The education they receive is tainted and ultimately worthless. They’re the third leading cause of death in the developed world. They ought to hang their heads in shame, especially considering the money they are making.

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    • JefferyC,

      “The first thing they put me on was benadryl, followed by haldol.” Either you dealt with extraordinarily stupid doctors, or doctors who were intentionally trying to make you psychotic / delirious. Proof from

      “Agents with anticholinergic properties … sedating antihistamines …neuroleptics … may have additive effects when used in combination. Excessive parasympatholytic effects may result in … the anticholinergic intoxication syndrome … Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.”

      Why is it that the poor starving artists can medically explain how doctors create schizophrenia symptoms with their “gold standard” treatment, the neuroleptics / antipsychotics, for that supposed disease but the doctors can’t seem to confess that the antipsychotics cause psychosis?

      I know, it’s all about the money. It’s very profitable for the psychiatrists to create the “schizophrenia” symptoms, via the central symptoms of neuroleptic induced anticholinergic intoxication syndrome. But that is morally repugnant.

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    • Antibiotics for flu – the most common type of idiocy. But when you come with bacterial inflammation they refuse to give an anti-biotic because they “don’t like prescribing it”. Then they don’t even know that there are vaccines which prevent common bacterial infections of throat and upper respiratory track and you have to trick them into prescribing it to you.

      The biggest obstacle in talking to a doctor is to make him actually listen to you. Most of the time they have no clue but are too arrogant to admit it. And even if they would be capable of helping you they won’t bother to even think for 5 minutes about what can be causing your symptoms (or even to listen to the description). I’m so fed up with doctors – there are good ones but that’s a rare exception from a very miserable rule.

      And that’s just general medicine – psychiatry is not even in the same ballpark.

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  4. According to my medical records and, while dealing with psychiatrists, I was coerced and forced onto drug cocktails with:

    50 major drug interaction warnings
    80 moderate drug interaction warnings, and
    16 minor drug interaction warnings

    And this appalling maltreatment is considered “appropriate medical care” by a mainstream non-profit ELCA hospital in the USA today.

    Thanks for dying for my sins, Jesus. And shame on the US medical community.

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  5. “polypharmacy and drug-drug interactions are not accounted for in any of the guidelines”

    Surprise, surprise. But don’t worry – the good doctors don’t even follow the guidelines when prescribing one drug in isolation (like benzos only for short term use). If you want to stay healthy – stay away from the whole bunch or if you really need them double and triple check everything they say or do. Trust can kill you.

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    • Part of that has to due with the fact the doctors are being given so much misinformation by the drug companies, and their medical journals are filled with fraudulent and / or biased information.

      It’s weird, I may have found a decent new doctor, he’s taken the iatrogenic bipolar diagnosis off my medical records. But he’s one of those paternalistic doctors who expects you to trust him, and I can’t trust him, in part because of what I’ve been through, but mainly because I know the medical industry’s research is largely filled with misinformation. I’m quite certain he’s so brainwashed, he doesn’t understand this, however.

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