Antidepressants Associated with Increased Risk for Manic Symptoms

Justin Karter
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An analysis of medical records in the UK reveals that the use of certain antidepressants for depression is linked to a heightened risk for mania and bipolar disorder. The research, published this week in BMJ Open, found the strongest effect for serotonin reuptake inhibitors (SSRIs) and the antidepressant venlafaxine.

bmj-open“We have demonstrated an association between antidepressant therapy and subsequent mania/bipolar disorder using a large data set of clinical data that is prospectively recorded and representative of everyday clinical practice in secondary mental health care,” the researchers, led by Dr. Rashmi Patel from King’s College London, concluded.

Previous studies have established that some people who are diagnosed with clinical depression and given antidepressants go on to develop mania, hypomania, and other symptoms associated with bipolar disorder. It remains unclear, however, whether these symptoms are caused by the antidepressant treatment or if the drugs trigger the onset of symptoms that would have emerged later on their own.

As clinical studies show that people diagnosed with bipolar disorder more often present to physicians when they are in a depressed state, rather than a manic state, and that depressive symptoms are more common than manic symptoms, it is also possible that some patients are treated for depression without recognition of existing manic symptoms. Also, patients treated for depression that later develop mania are more likely to have a family history of bipolar disorder than those who do not develop mania.

While past studies have examined the connection between antidepressants and manic symptoms in randomized control trial settings, Patel and his team of researchers tested the hypothesis that antidepressant exposure is associated with an increased risk for subsequent bipolar diagnosis in a “real world” sample. They examined the anonymized health care records of more than 21,000 adults diagnosed with major depression in London between 2006 and 2013.

The analysis showed that of the 21,000 adults being treated for depression in the study, 994 were subsequently diagnosed with mania or bipolar disorder during the follow-up period. All of the antidepressants, including SSRIs, mirtazapine, venlafaxine, and tricyclics (TCAs), were associated with an increased risk for a subsequent mania/bipolar diagnosis.

SSRIs and venlafaxine were associated with the greatest risk. These drugs were associated with a 34-35% increased risk of being diagnosed with bipolar disorder and/or mania.

The researchers stress that because this is an observational study, no firm conclusions can be drawn about cause and effect. The study is also limited by the researcher’s inability to control for risk factors for manic/bipolar symptoms, like family history.

“However, regardless of underlying diagnosis or aetiology, the association of antidepressant therapy with mania demonstrated in the present and previous studies highlights the importance of considering whether an individual who presents with depression could be at high risk of future episodes of mania.”

In the accompanying videocast below, the researchers highlight that the study is important because it uses a large clinical data set obtained from a real-world healthcare setting and shows that antidepressants are both widely prescribed and associated with an increased risk of developing mania.

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Patel R, Reiss P, Shetty H, et al. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study. BMJ Open 2015;5:e008341.doi:10.1136/bmjopen-2015-008341 (Full Text)

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21 COMMENTS

  1. Here’s the party-line bullshit straight from the young psychiatrist in the video clip:

    “Antidepressants are a safe and effective treatment for depression… antidepressants continue to be a safe and effective treatment for depression and anxiety disorders.”

    Come on… There’s a reason that warning labels are on antidepressants noting that they are linked to suicide risk. And even more important, Kirsch’s studies show that for most people labeled with depression – those with so-called mild to moderate depression – that antidepressants have no clinically significant effect in how the people feel relative to placebo. So, not very effective at all for most people, beyond the belief effect.

    Presumably this young guy is simply ignorant about the data on antidepressants revealed by writers like Kirch, Moncrieff, Whitaker, etc. He was probably brainwashed in medical school. It’s sad because in the interactions with the clients he seemed like a nice, decent guy who wants to help.

    As for mania being a valid illness, it isn’t. Mania is a behavior that people can have different degrees of at different times, not an illness with a cut-off that can be reliably measured. So you’d want to see a pattern of such quasi-experimental studies before interpreting anything from the trend, since the diagnosis of mania is not a real diagnosis and in one sense does not exist as a condition separable from “normality”. This applies even to extreme manic behaviors, which are simply many degrees further up the chain from mildly hypomanic or excited behaviors, and not at all evidence of a brain illness. Phil Hickey writes well about this.

    Here’s an alternate developmental view of “bipolar disorder”:

    From the psychoanalytic-viewpoint bipolarity is part of the normal personality development. The little child divides and in fact needs to divide his experiences and the events into good and bad ones, as he does with the things and people around him. The good experiences are to start with often grossly idealized and the bad ones grossly demonized depending on how bad and frustrating they have been for the child. This is called the paranoid-schizoid position. Gradually the vide gap between these blissful omnipotent states of extreme happiness on the other had the paranoid dread of facing annihilation and death (falling into a death, dissolving into nothingness, or the like) melt into a new slightly more mature type of bipolarity that is manic triumph and narcissistic self idealization on one hand and deep depression that is feelings of total worthlessness and inadequacy or the like. The changes happen over many years gradually little by little. Then this continues to transform and become more moderate and realistic when the person begins to realize that he is both good and bad at the same time and there is an eternal balance, no-one is totally good or totally bad resulting in normal balanced life where the amplitude between swings between the extreme states diminish and integration to normal maturity ushers in. (The New Dictionary of Kleinian Thought (2011) General editor: Elisabeth Spillius. by Elizabeth Bott Spillius, Jane Milton, Penelope Garvey, Cyril Couve and Deborah Steiner. Routledge, London and New York. )

    In this viewpoint bipolar mental states represent a developmental arrest within the early ego position located between “schizophrenia” and more evolved states of splitting that are mislabeled “personality disorders”. Manic activity can also be understood as a defense against guilt, depression, or grief.

    Here is a chart showing the relative developmental position of bipolar states relative to schizophrenias and personality disorders (sorry to use these inaccurate words) –

    https://bpdtransformation.files.wordpress.com/2015/03/cam00157update2.png

  4. Bipolar spectrum extends from 1.4 to 6.o.0.25 is depression,0.5 is hypomania,mania,1,5 is hypomania without depression,2.5 is cyclothymic with depression,3.0 is depression with AD induced hypomania,3.5 is bipolar disorder due to substance abuse,4.0 is depression with hyperthymic temperament,5.0 is depression with mixed hypomania,6.0 is bipolar in the setting of dementia.
    These psychiatrists are a confused lot trying to appease the govt and the pharma company.Theses drugs do not respect the classification.For ease of treatment they add a mood stabilizer along with an anti depressant.Trying to diagnose a bipolar from this spectrum is like searching for a needle in a hay-stack.More over the unipolar depression has also been included into the bipolar spectrum.Such a classification may benefit the pharma company,which treats LABELS as against PATIENTS.Genetic theory too,does not have any role in psychiatric disorders.They are all multifactorial causes.This genetic theory in psychiatry is a big witch hunting to dismantle the public health care system in psychiatry,by the pharma company.To do this they invent such theories.No genes have been found which encodes for any psychiatric illness.
    Kindly check out the conflict of interests.

  5. Which drug is a mood stabilizer? Anti epileptic drugs usually.Psychiatrists usually add this to their prescription to prevent any anti-depressant poop out.The rationale is that antidepressants are activating agents and mood stabilizers does the opposite.A patient who is in depression and also has suicidal ideas,when he gets activated upon starting antidepressants,he will commit that act because the antidepressant action takes time to set in,before which his motor activities are stimulated to carry out the suicidal mission.
    The psychiatrists have to come out with a patient-centric classification rather than a pharma centered classification of illness.And it should be devoid of labeling patients.
    Is there anything wrong?If so where? The classification,the drugs,the practical difficulties in diagnosing using such a complicated classification,secondary medical illness which presents with psychiatric illnesses,compliance,consuming more SSRI’s can lead to extreme hyperactivity and reckless behaviour due to serotonin syndrome.

  6. Eloquently presented tautology. This moves Pharma Marketing Masquerading as Medicine from pseudo-science to science fiction.
    Wasn’t the recent, truly scientific re-analysis of Study 329 also a BMJ publication? (September 2015.) “Neither Effective nor Safe.”

    Once again, no mention of unrecognised AKATHISIA as the real cause of the lethal and quality of life destroying – ( i.e. the rest of a foreshortened) – life, via mis-diagnosed iatrogenic “pseudo-bipolar.”

    This is clearly the banned “A -word” of “academic psychiatry”, primary care prescribing, and the whole toxic enterprise of the psychiatry – pharma industry. When a cursory reference to AKATHISIA is made, it is “downgraded” to an “inner restlessness.” The intensity of OVERWHELMING AGITATION and PHYSICAL, ACUTE PSYCHOLOGIC and BEHAVIOURAL changes – following, introduction or withdrawal of, change of, and – or, increased dose of SSRI, is a presentation of utmost, dramatic intensity.

    Once witnessed and correctly diagnosed, never forgotten.
    AKATHISIA is a diagnosis that saves life and prevents the tragedy of iatrogenic multifocal brain, endocrine, integumentary, and metabolic systemic injury via the assumption that SSRI induced AKATHISIA is a mandatory, permanent indication for the “Oppenheimer” prescription drugs marketed as
    “anti-psychotic” + “mood stabiliser”.

    “For I am become death, the destroyer of worlds.”

  7. Check out what he says between :35 seconds and :50 seconds, and note the nervous swallow. It’s something about the drugs causing symptoms of elevated mood and mania … As part of a bipolar disorder. No, it was “People who take antidepressants can also develop…” Which locates the problem in the patient: the first resort of a bad doctor. It works so well they don’t need a backup method.

  8. What about accounting for the people who no longer experience episodes of mania after they discontinue antidepressants and have not experienced mania before they took the antidepressants? Is this only considered anecdotal evidence?
    Why does he appear to be totally ignorant of the effect of Cytochrome P450 metabolism on drug response, interactions, and adverse effects?
    What is the money trail to this research project?

    • This study is a damp dishrag. Even the title refuses to say anything. Why the question mark?Throughout, they talk about “mania/bipolar.” What is that? Mania is a state with signs and symptoms, or a sign/symptom. Bipolar is an adjective usually associated with ‘disorder.’ So what do the drugs cause? A symptom/state, or a lifelong disorder?

      “Nothing. It is only a correlation.”

      Oh, Okay.

      What happens is…if you go manic, and had never been manic before….it doesn’t matter. You will be stuffed with Abilify or Seroquel, which too often leads to akathisia which no doctor has ever heard of, take a leave of absence, and then its Lamictal or Topamax, the side effects do you in, switch to Lithium, lose your boy- or girlfriend, add an ssri, gain 40 lbs, start drinking, gain 20 lbs, quit the ssri, hit the emergency room and have a seizure and a head injury, cry for six weeks, add an snri, kick holes in the walls, increase snri dose, emergency room, drop snri, file for disability, add Wellbutrin, quit drinking, lose 70 pounds, quit try to get a loan mod, talk constantly and stop bathing, add Geodon, get cataplexy, cant read a web page without passing out, all under the watchful eye of an MD. Finally clue in, stop all drugs, enter the nastiest pit in Hades aka post-psychotropic dysphoria and dysthymia and anhedonia and neuralgia and Breggin’s Chronic Brain Impairment for two years solid while the bank starts to take your house, which is a drag because you haven’t been outside for 7 months, get scammed by foreclosure lawyers, find Mad in America and Rxisk.org, etc., call malpractice attorneys “we don’t handle those cases,” file for bankruptcy, lose disability because you’re not being “treated” for anything…I think that’s it, except crashing your car a few times and posting bizarre stuff on Facebook and Twitter, losing friends and ex-co-workers and credibility and thus job prospects.

      Imagine all that and not finding Mad in America or Rxisk.org. THAT would suck.

  9. Look to history BEFORE the drugs. Manic depression was rare and episodic. People would have perhaps, 1 episode of mania in their lives, and/or one or two episodes of depression. Yes, they looked for help for the depression more often. So why the change? Did people manage the `illness’ better? Did they suffer in silence? Or is the huge increase not because more are `coming out’ or being diagnosed, but because more are being created? Manic depression has always been with us so massive (5 fold +) increases are unlikely to happen over the 40 years that just happens to coincide with the introduction of drugs.
    If a physical condition that was at a baseline level for millenia, for example, stomach ulcers, or asthma, increased 5 fold over a period of 40 years, investigations would be aimed at finding out `what changed ‘? For manic depression, drugs changed!

  10. I’m not saying manic depression/bipolar doesn’t exist but we still have to account for the huge increase SINCE the drugs. The evolution of a well documented illness severetenough to seriously disrupt people’s lives, so pretty obvious to all, does not usually escalate without something changing. Environmental toxins, smoking, medical poisoning (e.g. mercury for what ails you), were all deemed benign if not good for you until proven otherwise. It would be very interesting to see if the incidence of bipolar/manic depression DECREASES in a population where SSRIs are removed as an option. It might be possible to take a population of depressed people who have never received drugs e.g. Peter Breggin’s, or some other non-prescriber’s patients, and check the incidence of bipolar in them. It might at least be a pointer to further investigation. The chronicity of `real’ manic depression is another change. On the drugs there seems to be no return to `normal’ between episodes in many cases. Take them away and let’s see. There is also the situation when the person who stops the SSRIs and all other drugs, never has another episode. Of course the criteria is used here in that only one episode of mania is required for a diagnosis and in many cases before the drugs this was the case anyway. But again it would be a pointer. No drugs, no mania.

  11. Another issue is that many people diagnoses with bipolar actually embrace it. First it takes responsibility from them, `It’s not my/my parents/my upbringing’s fault, it’s in my genes.’ Second, there’s a support community, always helpful even if they do perpetuate a myth. Third, there is a certain kudos, club mentality, because some extraordinary historical figures, particularly artists, musicians and authors have been identified as bipolar, e.g. van Gogh, Virginia Woolfe, Lord Byron etc. Many of these retro diagnoses are questionable but what the Hell, people can identify and maybe feel proud to have it, and if it makes people feel better and keep taking the drugs, so be it. What these claims DON’T say is that these greats achieved what they did IN SPITE of their condition, and the the vast majority of high achievers did NOT have any clear cut mental problems. Fourth, for many people it makes some sort of sense to have a label to explain the chaos in your life. Fifth. it’s easier, and cheaper to take pills for life than have to find a therapist, few and far between, if you want to use a psychiatrist, and pay for maybe a couple of years of talking that has no guarantees and could be difficult.
    So just being a bit miserable is nowhere near as glamorous as joining Stephen Fry, Ernest Hemingway, Carrie Fisher and Vincent van Gogh et al as a bipolar sufferer. That the pills your doctor will give you for the condition the pills she gave you, has given you, that will rob you of joy for life, may not be an issue.

    • Another thing about those “famous people with bipolar” is that till very recently none of them were drugged out of their gourds. Virginia Woolf might not have been able to write or Van Gogh paint. They still would probably have killed themselves, but at least they wouldn’t have “died with their rights on.” That’s what counts after all. Dying with your rights off is perfectly acceptable!

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