Researchers Push Back Against Recommendation to Combine Antidepressants for Suicide Prevention

Researchers challenge the recommendation of starting two antidepressants simultaneously to increase preventative effects against suicide.


Psychologist Michael P. Hengartner from Zurich University and Austrian psychologist Martin Plöderl from Paracelsus Medical University Salzburg respond to the recommendation to prescribe two antidepressants simultaneously when aiming to prevent suicide, calling the suggestion “dangerous.” Hengartner and Plöderl, whose research focuses on suicide prevention, challenge the recommendation, which was made in another article by Horgan and Malhi.

“In sum, there is a growing body of evidence from meta-analyses of randomized controlled trials and from representative real-world pharmacoepidemiologic studies that newer generation antidepressants may increase the suicide risk, while there still is a lack of consistent evidence whether combining antidepressants is an effective strategy to reduce depression symptoms,”  Hengartner and Plöderl write.

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Horgan and Malhi’s recommendations are explicit within the article titled, “Intensive Suicide Prevention: Provide Intensive Contact and Start 2 Antidepressants.” published in the Australian and New Zealand Journal of Psychiatry. Hengartner and Plöderl support the former recommendation of intensive contact as an effective approach to suicidality but were “truly amazed” by the latter, they explain in their recently published commentary.

Horgan and Malhi wrote, “we cannot predict which single antidepressant will work, with the delay endangering life, so presumably, the use of two antidepressants increases the statistical chances of response and survival.” They go on to make the analogy of using two antibiotics or two anti-asthma medications for life-threatening physical illnesses to argue for starting treatment for high-risk suicidal patients with two antidepressants. However, Hengartner and Plöderl point out that “no single meta-analysis conducted thus far found a significantly lower suicide risk in antidepressant groups relative to placebo recipients.”

Horgan and Malhi also suggest potential effective antidepressant combinations. For instance, they recommend the combination of venlafaxine and mirtazapine based on the results of the  STAR*D trial. Hengartner and Plöderl, however, raise alarms about the mix, noting that “exactly these two drugs appear to convey the largest suicide risk in a dose-dependent manner according to a real-world analysis of a representative primary care database.”

The original article by Horgan and Malhi cites just one trial supporting antidepressant co-medication, and the study spans only 6-weeks and includes only 105 participants. The response points out that they neglected to examine a much larger study of 665 participants that reported: “combined medications are no more effective than monotherapy both at 12-week and at 7-month follow-up.”

Hengartner and Plöderl conclude:

“We contend that the recommendations of Horgan and Malhi (2018) to start two antidepressants to prevent suicide is at best empirically unsubstantiated and at worst conflicting with the literature and thus potentially dangerous.”



Hengartner, M. P., & Plöderl, M. (2019). Starting two antidepressants to prevent suicide: A potentially dangerous recommendation? Australian & New Zealand Journal of Psychiatry, 53(1), 82–83. (Link)


  1. In general, combining the antidepressants is unwise, since the antidepressants are anticholinergic drugs. And all doctors are taught in med school that too much of any of the anticholinergic drugs can result in anticholinergic intoxication syndrome. The “central nervous system-depressant effects may … be additively or synergistically increased when these [anticholinergic] agents are combined.” These “Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.”

    I agree, “the recommendations of Horgan and Malhi (2018) to start two antidepressants to prevent suicide is at best empirically unsubstantiated and at worst conflicting with the literature and thus potentially dangerous.”

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  2. This is the most shockingly ignorant suggestion from the field of psychiatry I’ve seen in quite a long time.

    How many people have to die from antidepressant induced suicide before the industry stops its doubling down on the same old failed “treatments”?

    They know the drugs don’t work. They know polypharnacy with multiple classes of drugs don’t work. They’re literally grasping at straws and to do it in the name of suicide prevention is disgusting. People will die from this.

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    • Oh, the drugs work all right, they just don’t have any affect on “depression”. They numb you to your feelings and emotions, they ruin your sex life, they make you into a zombie, they make many people consider suicide or homicide and the list of the things they do goes on and on. But they don’t help people with “depression”.

      This is why we need to get rid of the medical specialty of psychiatry. All it does it come up with new ways to destroy peoples’ lives. Name one thing positive that psychiatry does for people in distress, name one thing.

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    • My thoughts exactly. Psychiatry has nothing else to offer than their magic pills and when I looked at the original article to find out what is meant by “intensive contact” the authors were quick to point out that is not for every psychiatrist (?), how stressful it is for psychiatrists to care for people in crisis and that many are traumatised by this kind of work. And they make the astonishing suggestion that psychiatrist and suicidal patient should have daily consultations. At $450 an hour in Australia who can afford that, but it is all about the patient, right?

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        • Isn’t that why they went into the field of psychiatry in the first place????? All they want to do is spend fifteen minutes doing “med” checks and then shove the person out of their office so that they can run another person in for the same purpose. I’ve met only two psychiatrists in my entire life who were willing to sit down and listen to people and then embrace the struggle to find some good answers to the person’s issues, rather than prescribe the convenient pills. And I’ve dealt with quite a few psychiatrists in the past fifteen years, both as a “patient” and as a co-worker (although most of them do not accept me as on an equal par with them as a staff person).

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  3. “no single meta-analysis conducted thus far found a significantly lower suicide risk in antidepressant groups relative to placebo recipients.”

    Nice understatement. In fact, a meta-analysis by Healy and Whitaker (2003) shows that antidepressants multiply the risk of suicide by 5 compared with placebo.

    Giving antidepressants to suicidal people is like giving opioids to people with respiratory depression “to prevent them from suffering too much from the choking sensation”.

    Healy, D., Whitaker, C. (2003). Antidepressants and suicide: risk-benefit conundrums (html) Psychiatry Neurosci 2003; 28 (5)

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  4. Another thing: can we really suspect the honest mistake of authors Horgan and Malhi, to recommend a practice as directly and explicitly contrary to the survival of patients?

    What should be the reaction of the scientific community and society in general, in the face of doctors who would recommend the combination of two opioids to treat respiratory depression?

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  5. I just don’t get how anyone with any sense of responsibility can prescribe a drug to someone in crisis when that drug has a black box warning about deepening your crisis and making you more suicidal. But psychiatry has never failed to disappoint us with yet another “model of care” and firmly establishing themselves as nothing more than sales agents for drug companies

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  6. I know I am late, but I’ll jump in here…

    remember, Szasz and others have pointed out the -religious- nature of psychiatry. Our 21st century witch doctors dole out ineffective, dangerous drugs to the sinners/witches/penitents/slaves because that is their #1 ritual at this point. Facts do not phase faith, especially faith that is bolstered by society as a whole, the current economic structure, and even the legal system.

    Mental Health, Inc. -is- a religion. I think the industry has morphed into a modern death cult, and has proven to be an extremely wasteful, expensive cult, at that. Szasz points out that abolishing psychiatry will lead to greater clarity of thought. I agree, wholeheartedly. Personally, I think the psychiatrists should be retrained in useful forms of real medicine (or retire and fade into obscurity), and the talking “professionals” should be given vocational training, so they can do something practical, useful. Many counselors/low level enforcers do not make enough per year to qualify as truly middle-middle class (in the US…), anyway, so..

    why not train them to be plumbers, HVAC people, skilled factory laborers? They might earn more income and -contribute to society-. Meanwhile…

    the survivors and dependents of Mental Health, Inc. should be compensated and provided with the freedom and resources to “de-program.” 🙂

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  7. When you see the number of members on that are poly-drugged and miserable, trying to come off their cocktails, you KNOW adding more doesn’t work! When it is discovered that two antidepressants still isn’t working, now you’ve got two to come off of, no easy fete. Of course, a bunch of other drugs will be added along the way, z-pills, anti-anxiety, antipsychotics, to treat all the side effects of the previous meds, and then add another antidepressant to deal with the depression caused by all the other drugs. The Medi-Go-Round, as they say. But look at all the money Big Pharma is making in the meantime!

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  8. When I badly fractured my ankle a couple of years ago during a sh*tstorm of bad luck events, I wound up in the orthopedic ward of the local hospital following surgery to repair my ankle. I live alone in a 3rd floor apartment, I have no family or close friends, and I knew I was facing a terrible situation when I was discharged of how to get in and out of my apartment and how to care for myself and my cat. As it turned out it was several months before I could even put weight on the foot. I was right to be worried. I started having suicidal thoughts and confided this to one of the nurses on the orthopedic ward. Huge mistake! After that I needed a “sitter” in my room at all times. One of the sitters pinched me. I screamed. The staff came running in and threatened me with restraints. They said I was acting like a child. The rest of the time I spent in the orthopedic ward most of the nurses mocked and yelled at me. One said to another, “I heard when she came in she had bedbugs” right in front of me.
    From that ward I was sent to a rehab facility. Because I’d admitted to feeling suicidal at the hospital, the rehab psychiatrist came to see me after I’d been transferred there. Her solution was to prescribe Wellbutrin. I told her I’d been on Wellbutrin in the past, that it hadn’t worked and had made me very agitated. She just said “that was then, this is now” and went on prescribing it. I was already taking Zoloft. The Wellbutrin was an addition.
    After less than 2 weeks at the rehab I was sent home because Medicare wouldn’t pay for more days there. I was discharged in a wheelchair and when I got home I had to crawl up three flights of stairs to get in my apartment. For the next month or so – until I was able to put weight on the foot – that’s how I got around…by crawling. It’s what I had been afraid of and was one of the reasons I had suicidal thoughts at the hospital. This psychiatrist who I saw only once for 5 minutes thought she was actually doing something constructive by prescribing Wellbutrin; either that or she didn’t care at all, knew the whole thing was a charade. I stopped the Wellbutrin as soon as I was discharged. The idiocy.

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