Neuropsychological Tests Reveal Consequences of Polypharmacy

Neuropsychological assessments reveal the cognitive, occupational, and social impact of polypharmacy in psychiatry.

Gavin Crowell-Williamson
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A pair of Finnish researchers recently released a neuropsychological case report of a patient diagnosed with bipolar disorder who was treated with multiple psychiatric drugs. They conducted neuropsychological assessments before and two years after lithium and other drugs were discontinued. The testing monitored the patients’ cognitive impairments, visuomotor speed, visuoperceptual reasoning, and visual memory, among other measures.

“We presented a case of cognitive dysfunction that developed during long-term polypharmacy in a patient who had received a bipolar disorder diagnosis,” wrote the researchers.
“Our patient, a 41-year-old woman with a doctoral degree and a successful professional career, gradually became forgetful, visually distractible, and unable to function in her normal occupational and social roles after taking lithium for several months at a commonly used dosage, in combination with other psychiatric drugs she had taken as prescribed for years.”

It is relatively common for psychiatric patients to receive drugs from more than one class of medications. The practice of polypharmacy has sizably increased since the late ’90s and can lead to many adverse effects, including increased mortality. Combining multiple drugs brings an increased risk of cognitive side effects and iatrogenic neurological conditions.

The study authors contend that neuropsychological assessments can be useful for identifying cognitive deficits, identifying their etiology, and charting recovery. As it stands, this is something of a blind spot in existent research, making the identification of polypharmacy-induced iatrogenesis challenging for clinicians to identify. Research does demonstrate that non-severe cognitive deficits can improve following the discontinuation of lithium and that cognition can improve following the discontinuation of antipsychotics in general.

The patient described in this case report, identified as a 41-year-old woman named SN, was experiencing cognitive deficits following the initiation of lithium on top of other long-term psychiatric drug use — including citalopram, quetiapine, zopiclone, alprazolam, and levothyroxine. Her cognitive impairment was so severe that she could not function occupationally or socially.

To investigate, the researchers conducted two neuropsychological assessments, one immediately before and another, approximately two years after the discontinuation of psychiatric polypharmacy.

SN was a high-performing student who completed her PhD while working full-time. She was initially diagnosed with depressive neurosis, which was later changed to bipolar disorder despite no complaints of elevated mood or manic symptoms. She was never hospitalized for any indications of mania.

The original treatment plan was to substitute lithium for quetiapine, though SN continued to take both. 4-8 months following lithium initiation, she and her partner grew worried about her cognition, which was marked by issues with forgetfulness, concentration issues, visual attention, and the use of numbers. This severely impacted her work performance and necessitated a leave of absence from her job.

“A sudden decline in cognitive performance is a life-shattering tragedy for an active academic and a mother of two,” said SN. “When prescribed lithium, I wasn’t informed of any risks of developing cognitive problems, nor was there any follow up focused on these side effects.”

Following treatment for hypothyroidism, a common side effect of lithium, her cognitive problems remained. A neurological examination showed no neurological disease or gross cognitive impairment. An MRI showed normal findings, and lab tests showed normal liver and thyroid function.

Given this information, it seemed to be that the problems at hand resulted from one or several of her psychiatric drugs. Lithium was first tapered off, followed by her other psychiatric medications. She quickly regained energy but was plagued with restless legs and insomnia (for which she received melatonin), and her cognitive problems persisted. It took several weeks or months until she saw considerable improvement and had a cognitive ‘curtain of blur’ begin to lift.

During the neuropsychological assessments, SN had her general intellectual abilities, memory function, attention, executive function, motor function, visuoconstructive function, visual memory, and judgment of line orientation measured.

During her first assessment, her performance in several cognitive domains, including visuomotor abilities, perceptual reasoning, visual memory, and visuomotor processing, was severely impaired, which is suggestive of acquired and selective deficits.

By her second assessment, her visuomotor speed and perceptual reasoning, which had the highest degree of impairment, had vastly improved, as did her memory performance. She had, by the time of her second assessment, assumed her regular occupational and social roles again.

“SN’s cognitive difficulties emerged over a period of several months after lithium was initiated, strongly suggesting lithium as the likely primary etiological factor,” the authors concluded.
“This possibility is further supported by experimental evidence demonstrating that lithium impairs performance in several cognitive domains… our case shows that conditions of cognitive impairment involving lithium do not necessarily occur in the context of full-on intoxication. It is, however, an open question of whether SN’s condition was caused by lithium alone or by a combination of lithium and other drugs.”

This case provides evidence that psychiatric polypharmacy is associated with domain-specific cognitive dysfunction, and that further research on de-prescribing is warranted.

People diagnosed with Bipolar disorder, an oft-contested diagnosis, are often prescribed multiple drugs despite a lack of evidence for the effectiveness of this practice and significant evidence of adverse effects. Polypharmacy provides unnecessary risk for cognitive impairment and is something that should be monitored for patients undergoing lithium treatment.

SN was repeatedly clinically misinterpreted, was not informed of the risks of side effects, and did not know to associate her side effects with the medication she was taking, signaling inappropriate information from prescribers. Unfortunately, her case is not an outlier; the literature demonstrates that there have been other similar cases of cognitive impairment and misdiagnosis that have resolved following drug withdrawal.

Ultimately, this piece begs the question of why research is not being conducted regarding the long-term pharmacological impact of the discontinuation of psychiatric drugs.

 

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Valtonen, J., & Karrasch, M. (2020). Polypharmacy-induced cognitive dysfunction and discontinuation of psychotropic medication: a neuropsychological case report. Therapeutic Advances in Psychopharmacology (10). DOI: https://doi.org/10.1177/2045125320905734 (Link)

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Gavin Crowell-Williamson
MIA Research News Team: Gavin Crowell-Williamson is a Research Assistant at the University of Washington studying addiction-related suicide prevention. He is interested in researching how to provide opportunities for mental health care in communities that lack access, as well as understanding systemic factors that either facilitate or prevent getting help for mental health. He is currently pursuing a graduate degree in Community Development and Action from Vanderbilt University.

13 COMMENTS

  1. Is there some confusion in organizational management for the long and short term where applied research versus pure theoretical research is attempted? To identify who is the customer and then to honor a voice trying to communicate what might be problem when too often the nuanced side effects are not understood for the short and long term, I would think needs some calling out. Just pull up the Broad Institute and see how they work at generating large scale research in meta analysis while discouraging the customer’s voice at the table. Ironically, those who experience cancer and aids might have a better chance to have their voice be realized. So what is the difference between being human and being human? Amazing who chairs the organizations? The structure of monetizing knowledge production? Even if the brain is not technology!

  2. My cognitive skills were zilch on psychiatric drugs. My driving was scary because of impaired coordination and perception. So many times I wondered why my psychiatrist thought drugging me to oblivion was better? It’s a no brainer psychiatric drugs alter your perceptions and behavior, at least on this site. They also cause profound physical issues and this to needs to be addressed.

  3. “As it stands, this is something of a blind spot in existent research, making the identification of polypharmacy-induced iatrogenesis challenging for clinicians to identify.” All this polypharmacy induced harm of patients is by design. Just check out the “gold standard” drug cocktail recommendations, still on the Mayo Clinic’s website, for all the so called “bipolar diagnosed.”

    https://www.mayoclinic.org/diseases-conditions/bipolar-disorder/diagnosis-treatment/drc-20355961

    But none of this should be difficult for doctors to diagnose, since all doctors were taught in med school that both the antidepressants and antipsychotics can create psychosis and hallucinations, via anticholinergic toxidrome. But this toxidrome is, conveniently for the psychiatrists, missing from their DSM.

    https://en.wikipedia.org/wiki/Toxidrome

    The DSM-IV-TR used to warn about the impropriety of misdiagnosing the common adverse effects of the antidepressants as “bipolar,” although this common sense disclaimer was taken OUT of the DSM5 in 2013.

    “Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar I Disorder.”

    And Robert Whitaker did a great job pointing out both the antidepressant and ADHD drug induced etiology of America’s “iatrogenic childhood bipolar epidemic,” in his 2010 book “Anatomy of an Epidemic.” An iatrogenic etiologic “epidemic,” that is relevant to the adults who’ve been misdiagnosed as “bipolar,” as well.

    https://www.alternet.org/2010/04/are_prozac_and_other_psychiatric_drugs_causing_the_astonishing_rise_of_mental_illness_in_america/

    And the doctors were taught in med school that the antipsychotics/neuroleptics can create the negative symptoms of “schizophrenia” as well, via neuroleptic induced deficit syndrome. A syndrome, conveniently for the psychiatrists, which is also missing from their DSM.

    https://en.wikipedia.org/wiki/Neuroleptic-induced_deficit_syndrome

    So the psychiatrists, and the other doctors who recommend or require one speak to a psychiatrist, all have as their goal, intentionally harming people for profit. And all the complicit DSM “bible” thumping psychological, social worker, and therapist minion are just aiding and abetting in these intentional medical crimes against innocent humans, for profit.

    Especially since “Research does demonstrate that non-severe cognitive deficits can improve following the discontinuation of lithium and that cognition can improve following the discontinuation of antipsychotics in general.”

    “SN was repeatedly clinically misinterpreted,” so was I, to the extent that my entire life was eventually declared to be “a credible fictional story” by a highly deluded, child rape covering up, psychiatrist. She “was not informed of the risks of side effects,” nor was I, “and did not know to associate her side effects with the medication she was taking, signaling inappropriate information from prescribers.” I figured this out, but my concerns were blatantly and incessantly denied by prescribers.

    “Unfortunately, her case is not an outlier;” no, my story is similar, “the literature demonstrates that there have been other similar cases of cognitive impairment and misdiagnosis that have resolved following drug withdrawal.”

    According to my medical records, I was cognitively tested after (not prior) to being drugged, and I’d been judged as being cognitively impaired while neurotoxic poisoned. But shortly after being weaned off of the psych drugs, I missed only one on an IQ test. The future lawyer boss of mine who gave me that test, who’d taken that same test at the same time out of curiosity, missed five on the IQ portion.

    Absolutely, the psych drugs do cause cognitive damage, and research needs to be conducted into how to properly wean people off of the psychiatric drugs.

    As to, “why research is not being conducted regarding the long-term pharmacological impact of the discontinuation of psychiatric drugs.” It’s because it’s not profitable for the pharmaceutical industry, all those criminals who fund it, and those criminal doctors who profit from their systemic, iatrogenic illness creating, psychiatric crimes against humanity.

    And the “mental health” industry is killing 8 million people, every year, with their neurotoxic drugs, and their “invalid” DSM disorders.

    https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2013/transforming-diagnosis.shtml
    https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2015/mortality-and-mental-disorders.shtml

    That would amount to about 400,000,000 psychiatric murders over the past 50 years. I do so hope the impropriety of our modern day, ongoing, enormous in scope, psychiatric holocaust will make the mainstream news some day.

  4. If researchers are curious to know whether poly-pharmacy with psychoactive substances negatively impact cognition, let them try lithium, citalopram, quetiapine, zopiclone, alprazolam, and levothyroxine all together for a few months.

    I don’t see why this article would emphasizes lithium above the other drugs.

    • I hear you Berzerk. I have witnessed cognitive decline in all kinds of polypharmacy. Sometimes it’s the simple “pain prescription” of Cymbalta + Lyrica. Heck, Lyrica does a number all by itself, as do the neuroleptics and tranquilisers. Then there’s the “over time” problem, taking polypharmacy for 2 years. 5 years. 10 years. Watch the brain go away. I’ve seen this happen, too.

      I’m pleased to see this information getting out there – but – a single case study? This feels underwhelming for the magnitude of the problem.

  5. I would like to see Neuropsychological evaluations be apart of real independent trials for these meds and psychiatric treatments. We would see there is a serious, severe, and disturbing impact to the brains performance across the board for all of them. If real independent trials were performed in such a way and were used by regulators as criteria for treatment there is no way they would pass to the public, government officials would have to swallow that they are disabling their workforces. The same ones they are trying to accommodate with the treatments in the first place, because thats all they care about, just destroying the personal lives of everyone being treated by psychiatry is not enough.

    In my mind the independent objective measure of a persons performance is what shows best what is really happening. The subjective report of patients in trials managed by pharmaceutical companies tells us nothing of any value whatsoever.

  6. This study should not surprise anyone, except for those who like to keep their heads in the sand. Anyone with a modicum of experience in this area, first or second or third hand, knows that these drugs interfere with your thinking processes. The disturbing part is that this viewpoint would still be in any way controversial.

  7. And I was repeatedly warned of cognitive decline and “deterioration” if I failed to do exactly as my psychiatrist ordered. Counselors and case workers at the local Mental Illness Centers I dutifully attended. Support groups like NAMI. All the literature and TV shows…mainstream literature of course. All warned how dumb/crazy/helpless/dangerous I’d become unless I took my “meds” religiously.

    I pointed out how since starting my “therapeutic” doses of Haldol/Risperdol/Zoloft/Xanax/Celexa/Pick-your-neuropoison I could no longer take full time course loads at college or work full-time at my summer job or get by with less than 11 hours sleep. They would tell me it was all my “illness” which began at exactly the same time I sought “help” for social anxiety and had a horrible reaction to the SSRI. All entirely by coincidence. 😛 SMH

  8. Neuropsychological Tests Reveal Consequences of Polypharmacy.

    Like really!?? As if the consequences aren’t apparent and haven’t been for many years. I know many many people who have suffered from the conveyor belt type medication regime.
    ALL are suffering mental and physical decline or disability.

    I have recently discontinued (last 4 months) lithium, Prozac, tricyclic and Amphetamine with one to go.
    Driving to a place I frequented often ,I had to stop pull over and engage google maps to find my way .I was 2 kms from my destination .
    The destination was my home .
    I have lived there for 18 years.

    And to reflect on the impact Polypharmacy has had on my life . Well I look at it this way. My career, social life, family interaction and dignity are pretty well obliterated. But although the ramifications are real the consequences fade.

    Life on and after these “essential medications “leaves one with a sense of non existence in the past and unfortunately the future.
    It is very obvious the lady participating in the “Neuropsychological Tests”was affected by gross Polypharmacy. Unfortunately many victims live in denial of there own predicaments because they have been advised wrongly by there “expert medical providers” .

  9. Following 11 years of being labeled (“oft-contested”), 2 years of titration & withdrawal, & 4 of concerted self-care & self-rehab…my brain is firing on all twelve cylinders with what feels like a turbo-boost as if making up for lost time.
    I am relieved, delighted, & amazed.

    Were it not for the ‘pesky’ 19 seizures that littered the path to this moment…it would have been a perfect recovery.

    Apparently my price for a ticket out. Paid in full.

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