Antidepressants Worsen Rapid Cycling in Bipolar Depression


SSRI antidepressant medications contribute to a significant worsening of emotional “rapid cycling” in patients diagnosed with bipolar disorder, according to a study published in the Journal of Affective Disorders. The authors described the study as the first-ever randomized clinical trial to test whether the finding from previous observational studies was true, and stated that the study clarified the “lack of safety” of antidepressants for some people with bipolar.

Involving psychiatric researchers from the University of Louisville, Tufts, Stanford and the University of Pennsylvania, the study described rapid cycling as a tendency among some patients with bipolar to have four or more episodes of mania or depression in a 12-month period. The researchers did a secondary analysis from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) with 68 people diagnosed with bipolar, including 18 identified rapid cyclers, who had already “achieved clinical recovery” for at least two months while taking both an antidepressant and a mood stabilizer. These people were then randomized into antidepressant continuation or discontinuation groups while their mood stabilizer was continued.

“(I)n all groups except the rapid cyclers maintained on antidepressants, distributions were skewed toward zero, meaning most patients had few if any depressive episodes,” the researchers wrote. “In the (rapid cyclers) group maintained on antidepressants, the distribution was normal, meaning most patients had 2-4 depressive episodes.”

“In this sample, long-term continuation of antidepressants was associated with more mood episodes in patients with rapid-cycling bipolar disorder, particularly with three-fold increased rate of depressive episodes in the first year of follow-up,” they stated. “These data represent the first randomized data with new generation antidepressants, and they confirm the only other randomized study, conducted with tricyclic antidepressants.”

The researchers conceded that their sample size was limited, but they said they attempted to compensate for that by using descriptive measurements — such as numbers of episodes — rather than relying on p-value estimates of effects.

Conversely, they noted that their sample consisted of “a selected population of patients who had responded to antidepressants for acute bipolar depression, without manic switch. Thus, this was an ‘enriched’ sample of antidepressant-responsive patients. Even so, there appeared to be worsening of depressive episodes over time in subjects with a history of rapid-cycling bipolar disorder… Further, all patients took baseline mood stabilizers, indicating that mood stabilizers were not protective against such antidepressant-related worsening of mood episodes in rapid-cycling bipolar disorder, at least in the depressive pole.”

They concluded: “Even with pre-selection for good antidepressant response and absence of acute mania related to antidepressants, and despite concurrent mood stabilizer treatment, a priori analysis of rapid cycling status predicted more depressive episode criteria in those who continued antidepressant treatment as opposed to discontinued antidepressant treatment. This decreased efficacy of antidepressants supports previous claims of limited clinical utility and lack of safety in long term treatment of (bipolar disorder) patients with (antidepressants).”

An analysis of the study is also available on Medscape Medical News.


El-Mallakh, Rif S., Paul A. Vöhringer, Michael M. Ostacher, Claudia F. Baldassano, Niki S. Holtzman, Elizabeth A. Whitham, Sairah B. Thommi, Frederick K. Goodwin, and S. Nassir Ghaemi. “Antidepressants Worsen Rapid-Cycling Course in Bipolar Depression: A STEP-BD Randomized Clinical Trial.” Journal of Affective Disorders 0, no. 0. Accessed June 29, 2015. doi:10.1016/j.jad.2015.04.054. (Abstract)

Discontinue Antidepressants in Rapid-Cycling Bipolar Disorder (Medscape Medical News, June 22, 2015) (Registration required)


  1. Yeah, whatever. I never had any mental illness till a mad psychiatrist put me on 375mg of dothiepin. I was damn 36……….. never had any mental health labels……….. Stupid me……I trusted a doctor…… I never drank, smoked, did illegal drugs, I was a virgin put on double recommended doseof dothiepin…. 8 weeks later? When manic, went nuts, he never said he had overdosed me and I had serotonin syndrome, he just said “nah dothiepin doesnt do that, you have underlying bypolar, uncovered by medication””””” I spent three weeks in hospital with the biggest migraine, I couldnt move………….. Off the stuff and quite fine, I stupidly went back to see this doctor……….. Why? I will never know, maybe nbecause my addicted sister was secretly in love with him and thought he was wonderful……… buggar!
    Bullshit,,,,,,,,,,,,,,,,, this man destroyed me, I am finally recovering, slowly, off his poisons… long story the rampant greenie will be my site.

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  2. I’m sorry Ang for the hell that horrible man put you through. I’m glad you are recovering.

    How psychiatrists get away with blaming the patient for drug reactions is beyond me. Its like whenever a drug makes a patient crazy these nutty doctors blame it as an “underlying condition brought out from the medication”. How can a sane or ethical person say that? That’s like pouring acid on the eyes and going blind and the doctor saying the blindness was already underlying and just uncovered by the acid. It’s crazy!

    Psychiatrists just hope to catch the next vulnerable person so they can convince them to try their “non-addicting” “anti”depressant drugs. Using phrases like “take weeks to work”, “correct chemical imbalances”, and “non-addicting”. They make these poisonous drugs sound like harmless vitamin supplements!

    Psychiatrists get paid to prescribe. Some make more money the more they prescribe and others are flat out paid (bribed) by pharmaceutical reps to push drugs onto patients.

    All these seemingly good “Mental Health Awareness” ads that I see here in the states is actually cleverly disguised ads funded by pharmaceutical companies. These companies know how easy it is to convince a healthy person they have a mental problem or aren’t as happy as they should be.

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  3. I can say that Doctors tried every kind of SSRI and other anti depressant with me .. They made me worse but during the years they tried them on me , They do not know if they work other then asking the patient “Do you feel better?” If you dont they up the dosage …Wow . So these thing can be making you worse but they will do what? Up the dosage . I got pretty bad sick . Almost killed myself and finally I was taken off the anti depressants , After years . I got better . I feel great these days and that was not until I got off the anti depressants . I take a klonipin if I have a panic attack and that works just fine . That medicine works and I have been living a happy life . Why all doctors think it is ok to prescribe Anti depressants for anxiety is beyond me . I have spoke to many many people who are on anti depressants for anxiety and panic attacks and they all say the same thing “either its not working , Not sure if they are working , or no , They do not work.” I hope this statement helps someone . Good luck there is hope!

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  4. They need to do something similar with people who haven’t taken them before and are NOT diagnosed with “bipolar.” This makes it sound as if you avoid them if you already have a “bipolar” diagnosis, and doesn’t acknowledge that this happens to people who have never had a manic episode in their lives.

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    • Absolutely, I think it’s 60% of “bipolar” patients today, are people who had the adverse effects of an antidepressant misdiagnosed (according to the DSM-IV-TR) as “bipolar.” And no doubt, because of this massive malpractice problem (especially among children in the US), the psychiatric industry thought it would be clever to change their DSM5 “bible” and make this completely iatrogenic pathway to “bipolar,” the now appropriate “standard of care.”

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      • By the way, this study does not seem to address the fact that the antipsychotics / neuroleptics are, in addition to the mood stabilizers, the current recommended treatment for ‘bipolar.’ And this is relevant because the neuroleptics and antidepressants prescribed together can result in anticholinergic toxidrome.

        “The symptoms of an anticholinergic toxidrome include blurred vision, coma, decreased bowel sounds, delirium, dry skin, fever, flushing, hallucinations, ileus, memory loss, mydriasis (dilated pupils), myoclonus, psychosis, seizures, and urinary retention. Complications include hypertension, hyperthermia, and tachycardia. Substances that may cause this toxidrome include the four “anti”s of antihistamines, antipsychotics, antidepressants, and antiparkinsonian drugs[3] as well as atropine, benztropine, datura, and scopolamine.”

        This might point out why so many who had the adverse effects of antidepressants misdiagnosed as bipolar are doing so poorly. The antidepressants and antipsychotics should not be used concurrently. It’d be nice if the psychiatric industry woke up to this reality.

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  5. Familiar tales.
    Long-term anti-depressant use (first tricyclics then SSRIs) – thanks to a psychiatrist who said I had an “incurable family disease” following a break-up with a boyfriend – caused me to do what Grace Jackson refers to as “flip” and have a manic episode.
    AHA! said the psychiatrist at the time! “A full expression of the family illness”!!
    So – lithium, along with the benzos.
    Wrecked my thyroid and almost wrecked me.
    Happy to report I’m drug-free (except for some red wine evenings) and psychiatrist-free, at long last.
    Having lost two family members (father and son) to the ministrations of psychiatry, I am grateful to be alive, despite the challenges of living with complicated grief.
    How these arrogant people get away with such practices is criminal, to me.

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  6. Wow, it took them this long to work that out? Anyone with a Bipolar Diagnosis could have told them years ago that antidepressants tend to trigger a rapid and extreme mood change in Bipolar Patients. If you have extreme mania, sooner or later you will have extreme depression/

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  7. I’m sure that’s going to cause all the good professionals to cease prescribing “anti-depressants” to “bipolar” patients, right? Just as they have stopped prescribing benzos for over 4 weeks or high doses of anti-psychotics for long periods of time. Or to elderly who can face early death on them. I’m certain that the good doctors will take that seriously…

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  8. The antidepressants and bipolar diagnosis link ought to be studied a lot more. I have a lot of experience with SSRIs (4 different ones). All of them cause a significant elevation in mood when I take them. I’ve experienced mania several times on SSRIs.

    Funnily enough, the antidepressant Mirtazapine (which is NOT an SSRI), doesn’t seem to cause the same sort of rapid mood change in me that the SSRIs do. But my psychiatrist tells me that Mirtazapine causes manias too in some people.

    It takes some time to figure out these pills. The first time I took an SSRI (sertraline), I had a prompt change in mood, and became very happy. I didn’t even realize that it was due to the drug. The same thing happened with Fluvoxamine (the “high” or mania). My friends also used to point out my shaking hands. Even I used to wonder why my hands were shaking. It took me quite some time to realise that these were SSRI induced tremors, and that every time I took them my body would have tremors and when I stopped they would go away.

    I take Mirtazapine these days, and I’m relatively new to it. Again, it takes time to figure out the effects of the drug on my body. I was told that the drug has a sedative effect, but I didn’t feel anything initially, because I was drinking alcohol (to cope with my tensions) along with the Mirtaz. I’ve barely had any alcohol for the last 8 months. Once I took the Mirtaz plain, the sedative effect was prompt and very clear. It indeed does have a strong sedative effect which reduces the longer you take it. I also found that it didn’t have the same rapid SSRI high (which I was desperate for at the time, due to my problems), and initially thought it’s probably not doing anything. But, I think it’s causing some vivid dreams when I take them (nothing nasty), so, it’s clearly doing something. I have to “experiment” with the drug on and off, if I want to find out what it’s doing precisely, but I don’t think I want to do that now. I have 7-8 years of experience with SSRIs, so I know their effects very well. Not so much with Mirtaz (in months).

    I hope I’m not buggered into taking SSRIs by any psychiatrist in the future. Nasty side effects. But certainly effective when in a deep depression or anxious state. But I can only stand them for like a month or 3 months max (along with a mood stabiliser, else mania is a major possibility). I’d rather die than take them for longer than that.

    My current psychiatrist is fine with me taking Mirtaz (which has no bad side effects like tremors) and he proactively says to avoid SSRIs. I’d like to keep it that way as much as possible.

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