Lithium and Suicide: What Does the Evidence Show?

Joanna Moncrieff, MD
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There appears to be increasing acceptance of the idea that lithium prevents suicide, and even that it can reduce mortality rates. For a toxic drug that makes most people feel rather depressed, this seems curious. I did wonder whether it might be having this effect on suicide by sapping people of the will to act, but the proposed effect on mortality seems completely inexplicable. A closer look at the evidence, however, suggests the idea is simply not justified.

When I looked into the claims about lithium and sucide for my book The Myth of the Chemical Cure, the evidence consisted of follow-up studies of people on long-term lithium; people attending lithium clinics or other mental health services where they would be having their lithium levels monitored and their moods checked. So firstly, these people represent an especially compliant group, and we know that people who are compliant with any therapy, including placebo, generally have better outcomes than those who are not. The large Women’s Health Initiative trial of hormone replacement therapy, for example, showed that adherence to placebo was associated with lower risks of hip fracture, myocardial infarction, death from cancer and death from any cause.

People who follow their lithium regime religiously are, in general, not likely to be the people who are chaotic, impulsive, desperate and most likely to commit suicide. In fact, one study showed just this. People who were highly compliant with lithium had a five times lower risk of suicidal acts than those who were judged to be ‘poorly adherent’ with it. Secondly, because even small overdoses of lithium can produce dangerously toxic blood levels, people who are thought to be at a high risk of committing suicide are usually not prescribed it. If they are, it is with a strong warning about the toxicity of the drug, and close monitoring by mental health service staff – both of which may, in themselves, help to stabilise someone regardless of the lithium.

More recent cohort studies showing reduced suicide and mortality in people on lithium are likely to be what we call ‘confounded’ by these same issues. People who show suicidal tendencies are less likely to be given lithium and the same applies to people with medical conditions. Not only does lithium cause direct damage to organs like the kidneys and thyroid, it interacts with many drugs commonly prescribed for physical health problems. These interactions can lead to dangerously raised lithium levels. Hence any decent clinician is naturally cautious about starting lithium in anyone who is physically sick or taking other sorts of medication.

In order to control for these factors, we really need evidence from randomised controlled trials, where lithium is compared with no treatment, or a placebo, in a similar population. Suicide is thankfully a rare event, however, and it is even more rare in trials, which usually screen and exclude anyone who is thought to be a high suicide risk. Two meta-analyses have therefore combined data from randomised controlled trials to look at suicide rates.

So what does the trial evidence suggest? Unfortunately, as I pointed out in my last blog, most trials of lithium are not trials of starting lithium, but trials of stopping lithium. They consist of a comparison between people who have been taken off lithium (or other medication) and put on placebo and people who have continued to take it. There is some evidence from cohort studies that suicide risk may be increased following lithium discontinuation, although this could also be an artefact, since people may stop, or be taken off their lithium, if they become suicidal. Nevertheless, comparing the effects of continuing on lithium with the effects of stopping it is clearly not the same as establishing the prophylactic effects of starting lithium in terms of suicide as well as relapse.

Bearing this in mind, let’s look at the results of the meta-analyses of randomised trials. One of the meta-analyses combined studies of different drugs used for bipolar disorder and asked whether the suicide rate was increased in people randomised to placebo compared to those taking an active drug of some sort. The analysis included four studies of bipolar relapse prevention, all of which lasted at least a year, and three of which included a lithium-treated group. Combined, the studies included 943 patients on active drugs, of which 258 were on lithium, and 418 patients on placebo. There were two suicides in these trials during the experimental comparison phase, and a further one three weeks after it finished. All involved patients taking active drugs rather than placebo. There were ten suicide attempts, eight in patients on active compounds, and two in patients randomised to placebo.

Unfortunately results are not presented according to the different active agents used, so we don’t know if any of the suicides occurred in patients randomised to take lithium. However, the suicide rate in placebo-treated patients in these studies was zero.

So it is curious that the meta-analysis that focuses solely on lithium includes so little data from placebo-controlled trials. In fact it does not include a single placebo-controlled trial in which the placebo suicide rate is zero. Reading the paper again, I found that this is because the authors ‘excluded trials with no events in any treatment arm as uninformative’. This decision is totally unsound, however, as it reduces the denominator (the total number of participants) and thereby makes the events included appear more common than they actually were. How this passed the British Medical Journal’s referees is beyond me. This must be why well-known studies, such as the comparison between lithium, valproate and placebo and the two placebo-controlled studies of lithium and lamotrigine were not included in the analysis of suicides. I assume this means there were no suicides in these studies.

So the meta-analysis of suicide rates included only four placebo-controlled trials. There were 6 suicides in these studies, which all occurred among the 241 participants allocated to placebo and there were no suicides in the 244 participants on lithium. Thus the proportion of suicides in people on placebo as presented in the meta-analysis was 2.5%, and the proportion in the lithium group was 0%, a difference that is small, but not negligible. But if the studies in which there were no suicides had been included, the number of participants would have been much larger and the proportion of suicides in the placebo group much smaller. For example, if you add the valproate and lamotrigine trials, the total number of placebo treated patients reaches 524 and the proportion of suicides is then 1.1%. If you add in the large study of quetiapine, lithium and placebo (this study was included in the analysis of suicide attempts, but not completed suicides), then the total number of placebo-treated subjects is then 928, and the proportion of suicides in placebo-treated patients is only 0.6%.

Of the six suicides that occurred in the placebo-controlled studies of lithium, three occurred in one study. This study, conducted in Germany and published in 2008, is worth taking a more detailed look at. Unlike most of the other trials included in the meta-analysis, it is not a discontinuation study. The study explicitly set out to test whether or not lithium is effective in preventing suicide and attempted suicide. It involved randomising people with a variety of diagnoses, who had just made a suicide attempt, to have lithium or placebo. The authors don’t tell us whether any of the participants had been on lithium prior to the study, but I guess it would have been few, since most participants were diagnosed with depression, personality disorder and substance misuse rather than bipolar disorder. Other drugs people were taking were not stopped. The researchers found it difficult to recruit people to the study, and difficult to sustain lithium treatment. Importantly they say they did not maintain the double blind design in cases of  ‘insufficient drug compliance’.

It is not clear exactly what this means, but it seems to suggest that people in the lithium group were unblinded in order to maintain what the researchers deemed to be adequate lithium blood levels. They don’t tell us how many people they broke the blind for in this way, but it is possible that it included a large proportion of the lithium group, since the average blood lithium level were frequently lower than the levels specified in the protocol, especially in the early months of the study. So these unblinded patients on lithium were aware they were taking a dangerous drug, and would have had extra visits and blood tests. Now, there is considerable evidence from trials conducted with people with depression that increased visits can improve outcome. So it is plausible that the extra attention received by unblinded lithium-treated participants in the German study prevented some suicides.

There were three suicides in the placebo group in this trial (incidentally far fewer than was predicted, which may indicate the placebo effect of being in a trial of a potentially toxic drug, with regular monitoring), and none in the lithium group. The difference was borderline statistically significant when analysed by the time to event technique (p=0.05). However, regardless of the statistics, the number of events is small, and as explained above, the conditions of treatment were not comparable across the groups because of the unblinding. There was also no difference in suicide attempts, with 7 occurring in each group.

A similar study was conducted recently in Italy in people diagnosed with ‘major depression’ who had just committed an act of deliberate self-harm. It was not blinded, and no placebo was used. Again, it proved difficult to recruit to the study. In the end 29 people were randomised to start lithium, and 27 to ‘usual care’. There was one suicide in the lithium group, and five suicide attempts. In the placebo group there were no suicides, but seven suicide attempts.

So there is the evidence on lithium and suicide. The meta-analysis that has been accepted as demonstrating that lithium prevents suicide spuriously inflated the suicide rate on placebo by excluding studies in which no suicides occurred. The only double blind, prospective study designed to test whether lithium reduces suicide in people at high risk, ended up unblinding many of its participants, and in any case suicidal events were low in both groups.

The fact that studies of suicide prevention have been so difficult to recruit to, suggests patients may have more sense than researchers in this field!

23 COMMENTS

  1. It was my investigation of lithium in the late 1970s and early 1980s that was a key to my recovery (termed a “spontaneous remission”) from eight years of “chronic mental illness”, which I came to realize was actually iatrogenic disease.

    My first contact with lithium was in the US Submarine Force in 1968. Lithium hydroxide, LiOH, was used in extreme emergencies to absorb the CO2 which built up in the boat’s atmosphere from re-breathing when no fresh air was available. Sealed gallon cans of the highly irritating powder were opened and the substance was spread on the vinyl flash covers on the bunks. There it turned to a moist, mushy lithium carbonate LiCO and water H20 as it reacted with CO2. The oxygen, O2, was replenished from on-board tanks. This was a very dangerous procedure and we were well informed about the toxicity of the lithium hydroxide. On more modern submarines, and in the developing space craft, the LiOH was contained in a filtered CO2 “scrubber” machine and never came in contact with the crews.

    When I later became involved with “mental health care” and was prescribed lithium carbonate, I repeatedly mentioned my previous exposure to my doctors who were not the least interested. One even wrote in the record that “Mr. Subvet is under the delusion that his bunk was covered with lithium pills when he was on a submarine.”
    Every time I reported for an appointment at the VA Hospital I was asked “Were you exposed to Agent Orange?” and I would reply “Not that I know of, but I was exposed to other toxic chemicals. Do you want to know what they were?” The response was always the same. “No, I am only supposed to ask about Agent Orange.”

    Fortunately, I had worked in the nuke weapons field. Lithium is an important hydrogen bomb element. Friends and co-workers who knew more chemistry than either I or my doctors warned me of the folly of taking it internally as a “medication”. My own research turned up some interesting lithium trivia. Lithium is atomic number 7, and lithia was an ingredient in the “UnCola” soft drink 7-UP until it was removed by order of the FDA in the late 1950s. In the 1970s, the sole source of the important defence element was The Lithium Corporation of America. It was a check from that corporation that paid for the burglary of the Democratic National Committee at the Watergate Hotel.

  2. subvet416, what you have reported about lithium and your experiences with lithium was interesting and alarming. I was lithium on and off since 1992 until this year. I became concerned about lithium; when I kept seeing ads on television and then the lithium batteries in the local drugstore. I don’t know hardly anything about chemistry; as I am chemistry drop-out from college; yet I thought to myself; why I am ingesting something each day that is similar to a chemical in batteries. Lately, I have heard the air companies have been various lithium batteries from airplanes as they can cause dangerous fires. I heard we use these batteries in our computers and smartphones. A lithium battery is most likely allowing me to type this post. When, I started to take lithium, they told me it was just a salt and not to be a salt-restrictive diet and drink sports drinks. On lithium or not; the only thing that leads me to thoughts that may be of a suicidal nature is when someone abuses me, threatens me, criticizes me unmercifully, causes me unneeded false shame and guilt just for being me and being my unique, free-spirited, creative, poetic, optimistic, etc. self. What frees me from these thoughts is my faith and belief in God and my acceptance as Jesus Christ as my personal savior. Jesus loves me for being my special, unique me; even if some in my world discount me and seek to make me feel bad for me; being me.
    My question; who would ever have thought that the same similar ingredient used in batteries and nuclear weapons could be good for you and be used against the false disease of “bi-polar ” disorder or whatever? Whose mind is more messed up? Please tell me.

    • Rebel,
      I have mentioned in other posts how potassium bromide, KBr, was the drug of choice prior to the introduction of lithium carbonate, LiCO, but that bromine is a toxin which outweighed the benefits of the potassium (which is essential). Then came lithium carbonate, which can cause a potassium deficiency in those who take it. To treat the potassium deficiency potassium chloride KCl was often prescribed, but this also requires regular blood level testing because chlorine is extremely toxic. Potassium supplementation (chelated potassium) without side effects has been available for many years, but it is safe, available without a prescription, unpatentable and medical doctors have little incentive to investigate its use or to prescribe it.

      A favourite of yours, a man who once walked the Earth with knowledge far ahead of his fellow men once asked “What if the salt should loose its flavour? It is good for nothing but to be thrown in the trash.” He knew what most of the learned scientists and alchemists of his time did not know, that salt was not a pure element, but rather a compound of sodium and chlorine. If the salt molecule is split, loosing its flavour, sodium which immediately bursts into flame, and chlorine gas, a deadly poison, are released. Neither sodium or chlorine had any use in the ancient world.

      A visionary of the twentieth century, Mr. George I. Gurdjieff, was fond of saying “The Great Knowledge is more material than materialism.” and he mentions an esoteric “Chemistry of the Octaves.” One of my nuke buddies saw a Gurdjieff book at my home and suggested that if I was interested in such a chemistry I should obtain books by Walter Russell, especially “Atomic Suicide?”
      http://www.philosophy.org

      Now one of my favourites is Dan Winter, an American who studied both Gurdjieff and Russell and who himself was diagnosed with “mental illness” and eventually forced to leave the Country.
      http://www.goldenmean.info Winter’s experience may have been the inspiration for the story line of Pi-The Movie, 1998. https://www.youtube.com/watch?v=6_CtgelI6xU&list=PLE7F91BB8C872A152

    • Misdiagnosis of the common symptoms of Wellbtrin withdrawal is what led to my DSM-IV-TR “bipolar” misdiagnosis, too. My personal experience with lithium, in combination with Seroquel, is it caused me to get “voices” in my head. Then I was coresed into taking almost all the “new wonder drugs,” all of which made me ungodly ill (actually via something known as anticholinergic toxidrome, according to my medical research).

      I was finally slowly weaned off all the drugs, lithium being the last, the evil “voices” went away. But six months later I suffered from a drug withdrawal induced super sensitivity manic “psychosis” / awakening to my dreams. In my case, it was a cool story about a collective unconscious, but I understand for many their psychoses can be very frightening.

      I had never been suicidal, however, nor depressed, I was just dealing with a medical / religious cover up of the abuse of my child and a “bad fix” on a broken bone. As my subsequent ethical pastor called it, “the dirty little secret of the two original educated professions.” The Wellbutrin had been fraudulently prescribed to me initially as a “safe smoking cessation med.”

      I hope you are able to wean from the lithium, drudro8. Beware of the fact that if you go off the lithium you may become manic or psychotic, however. None of my doctors had forewarned me of this medically known reality, and it was, of course, misdiagnosed as a return of the “bipolar.”

      But, I did escape, and have been drug free for many years now, so I’m certain you could get off the toxic lithium, too. Best of luck, and if you do try to get off the lithium, set up people to try to help you, forewarn them of the possibility of a manic psychosis, and try to avoid hospitization as much as possible.

      • Similar experience. Diagnosed with depression. I was on Effexor. Then the ‘kindling effect’. Then mood swings. Then bipolar diagnosis. Then lithium. Then kidney disease. Then forced off lithium. Then intensive trauma therapy. No more depression. No more mood swings. No more need for psychiatric medications. No more need for psychiatry. (Gotta love that) 🙂

  3. Almost anyone has more sense than researchers in this field.

    As Joanna initially suggested, an alternate view on these studies is that lithium dulls down people’s feelings and “saps them of the will” to commit suicide.

    In this regard, when measuring well-being, quality of life, and connection with feelings, a group with more suicides could actually be doing better as a whole compared to a group with less suicides. Not being on lithium could give more people a chance to face difficult feelings. This might result in a few more suicides, but also in many more people feeling more alive, related, and functional over the long term.

    Of course, meaningful quality of life factors are hardly ever measured in these cold, ascetic reports. Where are the people in these studies?

    And as always, it should be noted that bipolar is a meaningless wastebasket label with no biomarkers, no validity, and no reliability. In that regard all the studies cited in this article are spurious. In order to discuss others’ “research”, Moncrieff talks about bipolar disorder as if it were a reliable illness, but I doubt she even believes that.

    • Bipolar is not a reliable diagnosis. That’s the problem. Research on bipolar is sketchy and slippery and serves to reinforce the “mood stabilization’, “it’s all genetic”, “it’s all in your head”, “you need this medication else you’ll never get better” doomsday “create a pharmaceutical drug dependency” paradigm.

      Love your comment: “Almost anyone has more sense than researchers in this field”. Research isn’t done for the purposes of making sense, is it? It is done in order to legitimate particular kinds of treatment interventions: psychiatric medications. There seems to be tons of money to support whatever research idea they come up with. I do a “forehead slap” every time I read this crappy research that just serves to reinforce psychiatry’s own self serving perspective.

      Also the comment” “Not being on lithium could give more people a chance to face difficult feelings.” This is also true in the way the Dr. Peter Breggin makes clear in his writing. However, many people prefer to be drugged, prefer to live in a mind numbing semi dissociative state rather than having to face the truth of their lives and their past.

      Of course, the cost of healthcare would be exorbitant if individuals were given full permission to face those difficult feelings by working it through in a therapeutic setting, Doing deep therapeutic work requires more than a psychiatric medication and ten to twelve sessions of CBT and some yoga. The state of the mental health system in England is the greatest challenge in furthering trauma informed care. When British citizens are begging for access to psychiatric services, when the services are just not there because of lack of resources, where is the will to provide meaningful and sustainable healing for individual’s pain and suffering?

    • “:As Joanna initially suggested, an alternate view on these studies is that lithium dulls down people’s feelings and “saps them of the will” to commit suicide”

      Lithium affected me this way the first month of taking it. After that I had proper mood swings, but not crazy highs and crippling lows. It has been 2 years now. Lithium is a wonder substance!

    • Yes. Lithium is very good at numbing the brain, numbing emotions, disconnecting you from ‘life’, your sense of yourself and creativity. I think it can be ‘life saving’, but at what cost to the human spirit? There are other ways to achieve a life worthy living. a life that is not defined by a existential ‘being unto death’ and ‘looking forward to the experience’ kind of GOTH/EMO – death = freedom. There are other possibilities. There are other ways to live in the world that do not require the intervention (or imposition) of mind altering substances that enable us to numb our pain while also let us live a zombie like existence. That was my experience, anyways, for what it’s worth. A lithium free existence is so much worth living.

      • Please. What evidence do you have for your statement? How long did you take Lithium and what were the blood concentration. In my first month taking lithium, i had very little emotion but this loosened up after a few months. I am creative as I have ever been without the crippling lows.

  4. Like I said in the previous article on this subject, I still find it hard to tell if lithium isn’t benefical to the human body as a mineral.

    I know there have been tests on worms and it’s increased their lifespan for instance.

    http://biomedgerontology.oxfordjournals.org/content/early/2014/01/03/gerona.glt210.full

    ETC. From what i’ve read some say it’s neuroprotective or increases grey matter, some say it just increases water content or something.

    Either way, from what I see, yep it does seem pretty stupid to take a whopping dose of lithium carbonate. More data on it though would be good to find.

  5. Rather than focusing on “Lithium and Suicide: What Does the Evidence Show?”, the focus should be, “Why the heck are people put on lithium (a toxic substance) in the first place? Lithium numbed my brain. Lithium numbed the trauma. Lithium dosage was increased from 900 to 1200 to 1500 to 1800 mg. per day, and still the depression broke through. I did not have bipolar disorder. I had a trauma history that was not acknowledged by my psychiatrist. And it is not acknowledged by you, Dr. Moncrieff. Nor have I seen the word, TRAUMA, mentioned in any of the other limited readings I have done of your work.

    As much as I respect your work on exposing the dangers and limitations of psychiatric medications, and your general critical position towards psychiatry, I do not believe you take your critique far enough. Until Mad in America and other writers that represent what I consder to be the “Mental Health Intelligensia” wake up to the reality of trauma and its all ubiqitous manifestations through various DSM diagnoses (whether it be ADHD, Bipolar, Borderline Personality Disorder, Depression, Schizophrenia), your work will not have much impact on psychiatry as it is currently practiced.

    Calling the ’emperor’ on the fact that he has no clothes on, might make him feel embarassed for a short while, but believe me, his ‘ego’ is big enough. He’ll just find another suit to wear. The latest article by Dr. Richard Friedman, head of psychiatry, expressed the typical arrogance of American psychiatrists who present themselves as concillitory when, in fact, they have mastered political posturing in its finest form.

    http://www.nytimes.com/2015/07/19/opinion/psychiatrys-identity-crisis.html

    There is nothing revolutionary about his thoughts. Nothing that acknolwedges trauma. Nothing that suggests any interest in providing meaningful treatment that would faciliate healing other than psychotherapy which in the form of CBT doesn’t exactly have a great track record either. None of what he proposes is conducive to healing trauma or is consistent with the latest findings in neuroscience (which he claims to LOVE – but I would say, more accurately LOVES to HATE because to fully embrace the findings would require him to rethink his work on clinical depression and its etiology).

    The reason I mention Friedman’s piece is because it was noted by you on Twitter as a newsworthy item, and I think it is very telling of your perspective when it comes to mental health reform and the role in which you believe psychiatry should play. What does he suggest as a prescription for what ails the psychiatry field today? More research money devoted to studying psychotherapy. This is complete and utter nonsense to anyone who possesses a trauma informed understanding.

    I was disappointment by what I felt I sensed was an alignment of your sentiment with his views. I cannot help but see everything that you profess is worthy of study (e.g. – the rate of suicide and lithium use) through my own trauma informed lens. From my perspective, it’s a non issue.

    As far as suicide goes, I would say that most people that commit suicide are in immense psychic pain. The more relevant question in my mind is where does that pain originate? A) Is it genetic? B) Is it drug induced? C) Or is it trauma or childhood abuse/neglecy related? I would say ‘C’ is the correct answer in more cases than we would care to acknowledge.

    In my case, I do not think that lithium prevented me from committing suicide (although anyone with the amount of trauma I endured from childhood would have most likely already killed themselves. I chalk up my survival to resiliency!) Lithium did cause me to acquire kidney disease. It did cause me to have thyorid issues. Thank you for acknowledging its limitations, Dr. Moncrieff! I will need to have my blood levels checked and have to see a doctor every year for the rest of my life. I also have the constant worry in the back of my head that one day, I might need to go on dialysis and could experience an early death. It could be viewed as being analagous to being on death row. The date of your impending death has not been determined, but it’s something you cannot help but focus some attention.

    I’d like to see the scope of the discourse about psychaitry expanded. Let’s talk about misdiagnosis and overdiagnosis of bipolar disorder. Let’s talk about borderline personality disorder as it relates to attachment disorders and childhood trauma. Let’s leverage your immense knowledge about the limitations of psychiatric drugs to create some meaningful and long lasting mental health reform.

    I think the problem lies less in the fact that people are given lithium, rather the problem is with the associated diagnosis ‘bipolar’ which is something psychiatrists love to diagnose because it conveniently circumvents the issue of trauma and the need to talk about it in the treatment setting. The “mood stabilization” discourse is reaffirmed and remains unquestioned and unchallenged. The patient bows the authority of the psychiatrist as “all knowing” authority, and the lies and denial of trauma continues as patient/doctor play a game of collusion.

    Trauma may continue to be ignored by some academicians, but trauma survivors know the truth. And we will not be silenced despite our lack of academic credentials and affiliations.

    • Look, I was prescribed as Bipolar 2 at the age of 50. Everything made sense for me after that diagnosis. Two years later I have been doing great by just taking Lithium. For some people it works really well and best of all you are not beholden to a pharmaceutical company.

  6. After being diagnosed with bipolar, my psych said “lithium is our preferred treatment…..” I suggested he could take as much as he liked as I considered I was not a good candidate for it and thank you but no.” Valproate has really helped my bipolar symptoms, that and psychological treatment for my extreme anxiety….. The man had never lived an “ordinary” day in his life, from private school to uni to med school……no idea about the challenges of the average persons life, what could be considered normal or what kind of lifestyle would make lithium a reasonable drug to take. Glad that as crazy as I felt, and probably was, I did my research and had a good GP who knew me and listened.

  7. Hello everybody i was sent to prison for
    selling marijuana then due to manic symptoms I’ve been forced into a psychiatric center against my will where they have been poisoning my body and mind for about 5 months. in the beginning they were giving me lithium, valproate and olanzapine (an antipsichotic) and benzodiazepine for sleep. now i only take two “mood stabilizers” valproate and lithium but this is theyre effect on me: depression, sadness, slow reaction time, slow thought processing, no will to act or do anything, loss of creativity, loss of previous religious interest, loss of confidence, negative thinking. when i wasnt on drugs i was way happier lithium kills you it sucks i feel like i am not alive anymore i cant wait for this bad dream to be all over. the worst part my family is all against me and they think drugs are the cure for my mental problems and they wont allow me to be drug free i feel like theres no way out